Radioactive emission detector equipped with a position tracking system and utilization thereof with medical systems and in medical procedures

Abstract
A system for calculating a position of a radioactivity emitting source in a system-of-coordinates, the system comprising (a) a radioactive emission detector; (b) a position tracking system being connected to and/or communicating with the radioactive emission detector; and (c) a data processor being designed and configured for receiving data inputs from the position tracking system and from the radioactive emission detector and for calculating the position of the radioactivity emitting source in the system-of-coordinates.
Description
FIELD AND BACKGROUND OF THE INVENTION

The present invention relates to a radioactive emission detector equipped with a position tracking system. More particularly, the present invention relates to the functional integration of a radioactive emission detector equipped with a position tracking system as above with medical imaging modalities and/or with guided minimally-invasive surgical instruments. The present invention is therefore useful for calculating the position of a concentrated radiopharmaceutical in the body in positional context of imaged portions of the body, which information can be used, for example, for performing an efficient minimally invasive surgical procedure. The present invention further relates to a surgical instrument equipped with a position tracking system and a radioactive emission detector for fine in situ localization during resection and/or biopsy procedures, which surgical instrument is operated in concert with other aspects of the invention.


The use of minimally invasive surgical techniques has dramatically affected the methods and outcomes of surgical procedures. Physically cutting through tissue and organs to visually expose surgical sites in conventional “open surgical” procedures causes tremendous blunt trauma and blood loss. Exposure of internal tissues and organs in this manner also dramatically increases the risk of infection. Trauma, blood loss, and infection all combine to extend recovery times, increase the rate of complications, and require a more intensive care and monitoring regiment. The result of such open surgical procedures is more pain and suffering, higher procedural costs, and greater risk of adverse outcomes.


In sharp contrast, minimally invasive surgical procedures cause little blunt trauma or blood loss and minimize the risk of infection by maintaining the body's natural barriers to infection substantially intact. Minimally invasive surgical procedures result in faster recovery and cause fewer complications than conventional, open, surgical procedures. Minimally invasive surgical procedures, such as laparoscopic, endoscopic, or cystoscopic surgeries, have replaced more invasive surgical procedures in all areas of surgical medicine. Due to technological advancements in areas such as fiber optics, micro-tool fabrication, imaging and material science, the physician performing the operation has easier-to-operate and more cost effective tools for use in minimally invasive procedures. However, there still exist a host of technical hurdles that limit the efficacy and increase the difficulty of minimally invasive procedures, some of which were overcome by the development of sophisticated imaging techniques. As is further detailed below the present invention offers a yet further advantage in this respect.


Radionuclide imaging is one of the most important applications of radioactivity in medicine. The purpose of radionuclide imaging is to obtain a distribution image of a radioactively labeled substance, e.g., a radiopharmaceutical, within the body following administration thereof to a patient. Examples of radiopharmaceuticals include monoclonal antibodies or other agents, e.g., fibrinogen or fluorodeoxyglucose, tagged with a radioactive isotope, e.g., 99Mtechnetium, 67gallium, 201thallium, 111indium, 123iodine, 125iodine and 18fluorine, which may be administered orally or intravenously. The radiopharmaceuticals are designed to concentrate in the area of a tumor, and the uptake of such radiopharmaceuticals in the active part of a tumor, or other pathologies such as an inflammation, is higher and more rapid than in the tissue that neighbors the tumor. Thereafter, a radiation emission detector, typically an invasive detector or a gamma camera (see below), is employed for locating the position of the active area. Another application is the detection of blood clots with radiopharmaceuticals such as ACUTECT from Nycomed Amersham for the detection of newly formed thrombosis in veins, or clots in arteries of the heart or brain, in an emergency or operating room. Yet other applications include radioimaging of myocardial infarct using agents such as radioactive anti-myosin antibodies, radioimaging specific cell types using radioactively tagged molecules (also known as molecular imaging), etc.


The distribution image of the radiopharmaceutical in and around a tumor, or another body structure, is obtained by recording the radioactive emission of the radiopharmaceutical with an external radiation detector placed at different locations outside the patient. The usual preferred emission for such applications is that of gamma rays, which emission is in the energy range of approximately 20-511 KeV. When the probe is placed in contact with the tissue, beta radiation and positrons may also be detected.


The first attempts at radionuclide “imaging” were in the late 1940's. An array of radiation detectors was positioned mechanically on a matrix of measuring points around the head of a patient. Alternatively, a single detector was positioned mechanically for separate measurements at each point on the matrix.


A significant advance occurred in the early 1950's with the introduction of the rectilinear scanner by Ben Cassen. With this instrument, the detector was scanned mechanically in a predetermined pattern over the area of interest.


The first gamma camera capable of recording all points of the image at one time was described by Hal Anger in 1953. Anger used a detector comprised of a NaI(Tl) screen and a sheet of X-ray film. In the late 1950's, Anger replaced the film screen with a photomultiplier tube assembly. The Anger camera is described in Hal O. Anger, “Radioisotope camera in Hine G J”, Instrumentation in Nuclear Medicine, New York, Academic Press 1967, chapter 19. U.S. Pat. No. 2,776,377 to Anger, issued in 1957, also describes such a radiation detector assembly.


U.S. Pat. No. 4,959,547 to Carroll et al. describes a probe used to map or provide imaging of radiation within a patient. The probe comprises a radiation detector and an adjustment mechanism for adjusting the solid angle through which radiation may pass to the detector, the solid angle being continuously variable. The probe is constructed so that the only radiation reaching the detector is that which is within the solid angle. By adjusting the solid angle from a maximum to a minimum while moving the probe adjacent the source of radiation and sensing the detected radiation, one is able to locate the probe at the source of radiation. The probe can be used to determine the location of the radioactivity and to provide a point-by-point image of the radiation source or data for mapping the same.


U.S. Pat. No. 5,246,005 to Carroll et al. describes a radiation detector or probe, which uses statistically valid signals to detect radiation signals from tissue. The output of a radiation detector is a series of pulses, which are counted for a predetermined amount of time. At least two count ranges are defined by circuitry in the apparatus and the count range which includes the input count is determined. For each count range, an audible signal is produced which is audibly discriminable from the audible signal produced for every other count range. The mean values of each count range are chosen to be statistically different, e.g., 1, 2, or 3 standard deviations, from the mean of adjacent lower or higher count ranges. The parameters of the audible signal, such as frequency, voice, repetition rate, and/or intensity are changed for each count range to provide a signal which is discriminable from the signals of any other count range.


U.S. Pat. No. 5,475,219 to Olson describes a system for detecting photon emissions wherein a detector serves to derive electrical parameter signals having amplitudes corresponding with the detected energy of the photon emissions and other signal generating events. Two comparator networks employed within an energy window, which define a function to develop an output, L, when an event-based signal amplitude is equal to or above a threshold value, and to develop an output, H, when such signal amplitude additionally extends above an upper limit. Improved reliability and accuracy is achieved with a discriminator circuit which, in response to these outputs L and H, derives an event output upon the occurrence of an output L in the absence of an output H. This discriminator circuit is an asynchronous, sequential, fundamental mode discriminator circuit with three stable states.


U.S. Pat. Nos. 5,694,933 and 6,135,955 to Madden et al. describe a system and method for diagnostic testing of a structure within a patient's body that has been provided with a radioactive imaging agent, e.g., a radiotracer, to cause the structure to produce gamma rays, associated characteristic x rays, and a continuum of Compton-scattered photons. The system includes a radiation receiving device, e.g., a hand-held probe or camera, an associated signal processor, and an analyzer. The radiation receiving device is arranged to be located adjacent the body and the structure for receiving gamma rays and characteristic X-rays emitted from the structure and for providing a processed electrical signal representative thereof. The processed electrical signal includes a first portion representing the characteristic X-rays received and a second portion representing the gamma rays received. The signal processor removes the signal corresponding to the Compton-scattered photons from the electrical signal in the region of the full-energy gamma ray and the characteristic X-ray. The analyzer is arranged to selectively use the X-ray portion of the processed signal to provide near-field information about the structure, to selectively use both the X-ray and the gamma-ray portions of the processed signal to provide near-field and far-field information about the structure, and to selectively use the gamma-ray portion of the processed signal to provide extended field information about the structure.


U.S. Pat. No. 5,732,704 to Thurston et al. describes a method for identifying a sentinel lymph node located within a grouping of regional nodes at a lymph drainage basin associated with neoplastic tissue wherein a radiopharmaceutical is injected at the situs of the neoplastic tissue. This radiopharmaceutical migrates along a lymph duct towards the drainage basin containing the sentinel node. A hand-held probe with a forwardly disposed radiation detector crystal is maneuvered along the duct while the clinician observes a graphical readout of count rate amplitudes to determine when the probe is aligned with the duct. The region containing the sentinel node is identified when the count rate at the probe substantially increases. Following surgical incision, the probe is maneuvered utilizing a sound output in connection with actuation of the probe to establish increasing count rate thresholds followed by incremental movements until the threshold is not reached and no sound cue is given to the surgeon. At this point of the maneuvering of the probe, the probe detector will be in adjacency with the sentinel node, which then may be removed.


U.S. Pat. No. 5,857,463 to Thurston et al. describes further apparatus for tracking a radiopharmaceutical present within the lymph duct and for locating the sentinel node within which the radiopharmaceutical has concentrated. A smaller, straight, hand-held probe is employed carrying two hand actuable switches. For tracking procedures, the probe is moved in an undulatory manner, wherein the location of the radiopharmaceutical-containing duct is determined by observing a graphics readout. When the region of the sentinel node is approached, a switch on the probe device is actuated by the surgeon to carry out a sequence of squelching operations until a small node locating region is defined.


U.S. Pat. No. 5,916,167 to Kramer et al. and U.S. Pat. No. 5,987,350 to Thurston describe surgical probes wherein a heat-sterilizable and reusable detector component is combined with a disposable handle and cable assembly. The reusable detector component incorporates a detector crystal and associated mountings along with preamplifier components.


U.S. Pat. No. 5,928,150 to Call describes a system for detecting emissions from a radiopharmaceutical injected within a lymph duct wherein a hand-held probe is utilized. When employed to locate sentinel lymph nodes, supplementary features are provided including a function for treating validated photon event pulses to determine count rate level signals. The system includes a function for count-rate based ranging as well as an adjustable thresholding feature. A post-threshold amplification circuit develops full-scale aural and visual outputs.


U.S. Pat. Nos. 5,932,879 and 6,076,009 to Raylman et al. describe an intraoperative system for preferentially detecting beta radiation over gamma radiation emitted from a radiopharmaceutical. The system has ion-implanted silicon charged-particle detectors for generating signals in response to received beta particles. A preamplifier is located in proximity to the detector filters and amplifies the signal. The probe is coupled to a processing unit for amplifying and filtering the signal.


U.S. Pat. No. 6,144,876 to Bouton describes a system for detecting and locating sources of radiation, with particular applicability to interoperative lymphatic mapping (ILM) procedures. The scanning probe employed with the system performs with both an audible as well as a visual perceptive output. A desirable stability is achieved in the readouts from the system through a signal processing approach which establishes a floating or dynamic window analysis of validated photon event counts. This floating window is defined between an upper edge and a lower edge. The values of these window edges vary during the analysis in response to compiled count sum values. In general, the upper and lower edges are spaced apart a value corresponding with about four standard deviations.


To compute these count sums, counts are collected over successive short scan intervals of 50 milliseconds and the count segments resulting therefrom are located in a succession of bins within a circular buffer memory. The count sum is generated as the sum of the memory segment count values of a certain number of the bins or segments of memory. Alteration of the floating window occurs when the count sum either exceeds its upper edge or falls below its lower edge. A reported mean, computed with respect to the window edge that is crossed, is developed for each scan interval which, in turn, is utilized to derive a mean count rate signal. The resulting perceptive output exhibits a desirable stability, particularly under conditions wherein the probe detector is in a direct confrontational geometry with a radiation source.


U.S. Pat. No. 5,846,513 teaches a system for detecting and destroying living tumor tissue within the body of a living being. The system is arranged to be used with a tumor localizing radiopharmaceutical. The system includes a percutaneously insertable radiation detecting probe, an associated analyzer, and a percutaneously insertable tumor removing instrument, e.g., a resectoscope. The radiation detecting probe includes a needle unit having a radiation sensor component therein and a handle to which the needle unit is releasably mounted. The needle is arranged to be inserted through a small percutaneous portal into the patient's body and is movable to various positions within the suspected tumor to detect the presence of radiation indicative of cancerous tissue. The probe can then be removed and the tumor removing instrument inserted through the portal to destroy and/or remove the cancerous tissue. The instrument not only destroys the tagged tissue, but also removes it from the body of the being so that it can be assayed for radiation to confirm that the removed tissue is cancerous and not healthy tissue. A collimator may be used with the probe to establish the probe's field of view.


The main limitation of the system is that once the body is penetrated, scanning capabilities are limited to a translational movement along the line of penetration.


An effective collimator for gamma radiation must be several mm in thickness and therefore an effective collimator for high energy gamma radiation cannot be engaged with a fine surgical instrument such as a surgical needle. On the other hand, beta radiation is absorbed mainly due to its chemical reactivity after passage of about 0.2-3 mm through biological tissue. Thus, the system described in U.S. Pat. No. 5,846,513 cannot efficiently employ high energy gamma detection because directionality will to a great extent be lost and it also cannot efficiently employ beta radiation because too high proximity to the radioactive source is required, whereas body tissue limits the degree of maneuvering the instrument.


The manipulation of soft tissue organs requires visualization (imaging) techniques such as computerized tomography (CT), fluoroscopy (X-ray fluoroscopy), magnetic resonance imaging (MRI), optical endoscopy, mammography or ultrasound which distinguish the borders and shapes of soft tissue organs or masses. Over the years, medical imaging has become a vital part in the early detection, diagnosis and treatment of cancer and other diseases. In some cases medical imaging is the first step in preventing the spread of cancer through early detection and in many cases medical imaging makes it possible to cure or eliminate the cancer altogether via subsequent treatment.


An evaluation of the presence or absence of tumor metastasis or invasion has been a major determinant for the achievement of an effective treatment for cancer patients. Studies have determined that about 30% of patients with essentially newly diagnosed tumor will exhibit clinically detectable metastasis. Of the remaining 70% of such patients who are deemed “clinically free” of metastasis, about one-half are curable by local tumor therapy alone. However, some of these metastasis or even early stage primary tumors do not show with the imaging tools described above. Moreover often enough the most important part of a tumor to be removed for biopsy or surgically removed is the active, i.e., growing part, whereas using only conventional imaging cannot distinguish this specific part of a tumor from other parts thereof and/or adjacent non affected tissue.


A common practice in order to locate this active part is to mark it with radioactivity tagged materials generally known as radiopharmaceuticals, which are administered orally or intravenously and which tend to concentrate in such areas, as the uptake of such radiopharmaceuticals in the active part of a tumor is higher and more rapid than in the neighboring tumor tissue. Thereafter, a radiation emission detector, typically an invasive detector, is employed for locating the position of the active area.


Medical imaging is often used to build computer models which allow doctors to, for example, guide exact radiation in the treatment of cancer, and to design minimally-invasive or open surgical procedures. Moreover, imaging modalities are also used to guide surgeons to the target area inside the patient's body, in the operation room during the surgical procedure. Such procedures may include, for example, biopsies, inserting a localized radiation source for direct treatment of a cancerous lesion, known as brachytherapy (so as to prevent radiation damage to tissues near the lesion), injecting a chemotherapy agent into the cancerous site or removing a cancerous or other lesions.


The aim of all such procedures is to pin-point the target area as precisely as possible in order to get the most precise biopsy results, preferably from the most active part of a tumor, or to remove such a tumor in its entirety on the one hand with minimal damage to the surrounding, non affected tissues, on the other hand.


However, in the current state of the prior art this goal is yet to be achieved, as most of the common imaging modalities such as fluoroscopy, CT, MRI, mammography or ultrasound demonstrate the position and appearance of the entire lesion with anatomical modifications that the lesion causes to its surrounding tissue, without differentiating between the non-active mass from the physiologically active part thereof.


On the other hand, prior art radiation emission detectors and/or biopsy probes, while being suitable for identifying the location of the radiation site, they leave something to be desired from the standpoint of facilitating the removal or other destruction of the detected cancerous tissue with minimum invasion of the patient.


The combination of modalities, as is offered by the present invention, can reduce the margin of error in positioning such tumors. In addition, the possibility of demonstrating the position of the active part of a tumor superimposed on a scan from an imaging modality that shows the organ or tumor, coupled with the possibility to follow a surgical tool in reference to the afflicted area during a surgical procedure will allow for a more precise and controlled surgical procedures to take place, minimizing the aforementioned problems.


The present invention addresses these and other issues which are further elaborated hereinbelow, and offers the physicians and patients more reliable targeting, that in turn will result in less invasive and less destructive surgical procedures and less cases of mistaken diagnosis.


SUMMARY OF THE INVENTION

According to one aspect of the present invention there is provided a system for calculating a position of a radioactivity emitting source in a system-of-coordinates, the system comprising (a) a radioactive emission detector; (b) a position tracking system being connected to and/or communicating with the radioactive emission detector; and (c) a data processor being designed and configured for receiving data inputs from the position tracking system and from the radioactive emission detector and for calculating the position of the radioactivity emitting source in the system-of-coordinates.


According to another aspect of the present invention there is provided a system for calculating a position of a radioactivity emitting source in a system-of-coordinates, the system comprising (a) at least two radioactive emission detectors; (b) a position tracking system being connected to and/or communicating with at least two radioactive emission detectors; and (c) a data processor being designed and configured for receiving data inputs from the position tracking system and from the at least two radioactive emission detectors and for calculating the position of the radioactivity emitting source in the system-of-coordinates.


According to still another aspect of the present invention there is provided a method for defining a position of a radioactivity emitting source in a system-of-coordinates, the method comprising the steps of (a) providing a radioactive emission detector being connected to or communicating with a position tracking system; and (b) monitoring radioactivity being emitted from the radioactivity emitting source, while at the same time, monitoring the position of the radioactive emission detector in the system-of-coordinates thereby defining the position of the radioactivity emitting source in the system-of-coordinates.


According to yet another aspect of the present invention there is provided a method for defining a position of a radioactivity emitting source in a system-of-coordinates, the method comprising the steps of (a) providing at least one radioactive emission detector being connected to or communicating with a position tracking system; and (b) monitoring radioactivity being emitted from the radioactivity emitting source, while at the same time, monitoring the position of the at least one radioactive emission detector in the system-of-coordinates, thereby defining the position of the radioactivity emitting source in the system-of-coordinates.


According to yet another aspect of the present invention there is provided a system for calculating a position of a radioactivity emitting source in a first system-of-coordinates and further of projecting the position of the radioactivity emitting source onto a second system-of-coordinates, the system comprising (a) a radioactive emission detector; (b) a position tracking system being connected to and/or communicating with the radioactive detector; and (c) a data processor being designed and configured for (i) receiving data inputs from the position tracking system and from the radioactive emission detector; (ii) calculating the position of the radioactivity emitting source in the first system-of-coordinates; and (iii) projecting the position of the radioactivity emitting source onto the second system-of-coordinates.


According to still another aspect of the present invention there is provided a system for calculating a position of a radioactivity emitting source in a first system-of-coordinates and further of projecting the position of the radioactivity emitting source onto a second system-of-coordinates, the system comprising (a) at least two radioactive emission detectors; (b) a position tracking system being connected to and/or communicating with the at least two radioactive emission detectors; and (c) a data processor being designed and configured for (i) receiving data inputs from the position tracking system and from the at least two radioactive emission detectors; (ii) calculating the position of the radioactivity emitting source in the first system-of-coordinates; and (iii) projecting the position of the radioactivity emitting source onto the second system-of-coordinates.


According to still another aspect of the present invention there is provided a method for calculating a position of a radioactivity emitting source in a first system-of-coordinates and for projecting the position of the radioactivity emitting source onto a second system-of-coordinates, the method comprising the steps of (a) providing a radioactive emission detector being connected to or communicating with a position tracking system; and (b) monitoring radioactivity being emitted from the radioactivity emitting source, while at the same time, monitoring the position of the radioactive emission detector in the first system-of-coordinates, thereby defining the position of the radioactivity emitting source in the first system-of-coordinates and projecting the position of the radioactivity emitting source onto the second system-of-coordinates.


According to an additional aspect of the present invention there is provided a method for calculating a position of a radioactivity emitting source in a first system-of-coordinates and for projecting the position of the radioactivity emitting source onto a second system-of-coordinates, the method comprising the steps of (a) providing at least one radioactive emission detector being connected to or communicating with a position tracking system; and (b) monitoring radioactivity being emitted from the radioactivity emitting source, while at the same time, monitoring the position of the at least one radioactive emission detector in the first system-of-coordinates, thereby defining the position of the radioactivity emitting source in the first system-of-coordinates and projecting the position of the radioactivity emitting source onto the second system-of-coordinates.


According to yet an additional aspect of the present invention there is provided a system for calculating a position of a body component and a position of a radiopharmaceutical uptaking portion of the body component within a subject, the system comprising (a) a two-dimensional (projectional or cross-sectional) or a three-dimensional (consecutive cross-sectional) imaging modality being connected to and/or communicating with a first position tracking system for calculating the position of the body component in a first system-of-coordinates; (b) a radioactive emission detector being connected to and/or communicating with a second position tracking system for tracking a position of the radiopharmaceutical uptaking portion of the body component in a second system-of-coordinates; and (c) at least one data processor being designed and configured for receiving data inputs from the three-dimensional imaging modality, the first position tracking system, the radioactive emission detector and the second position tracking system and calculating the position of the body component and the position of the radiopharmaceutical uptaking portion of the body component in a common system-of-coordinates.


According to yet an additional aspect of the present invention there is provided a method for calculating a position of a body component and a position of a radiopharmaceutical uptaking portion of the body component within a subject, the method comprising the steps of (a) providing a two-dimensional or a three-dimensional imaging modality being connected to and/or communicating with a first position tracking system and calculating the position of the body component in a first system-of-coordinates; (b) providing a radioactive emission detector being connected to and/or communicating with a second position tracking system and tracking a position of the radiopharmaceutical uptaking portion of the body component in a second system-of-coordinates; and (c) receiving data inputs from the three-dimensional imaging modality, the first position tracking system, the radioactive emission detector and the second position tracking system and calculating the position of the body component and the position of the radiopharmaceutical uptaking portion of the body component in a common system-of-coordinates.


According to still an additional aspect of the present invention there is provided a system for performing an intrabody surgical procedure on a radiopharmaceutical uptaking portion of a body component within a subject, the system comprising (a) a radioactive emission detector being connected to and/or communicating with a first position tracking system for tracking a position of the radiopharmaceutical uptaking portion of the body component in a first system-of-coordinates; (b) a surgical instrument being connected to and/or communicating with a second position tracking system for tracking a position of the surgical instrument in a second system-of-coordinates; and (c) at least one data processor being designed and configured for receiving data inputs from the first position tracking system, the radioactive emission detector and the second position tracking system and for calculating the position of the surgical instrument and the radiopharmaceutical uptaking portion of the body component in a common system-of-coordinates.


According to a further aspect of the present invention there is provided a method for performing an intrabody surgical procedure on a radiopharmaceutical uptaking portion of a body component within a subject, the method comprising the steps of (a) providing a radioactive emission detector being connected to and/or communicating with a first position tracking system and tracking a position of the radiopharmaceutical uptaking portion of the body component in a first system-of-coordinates; (b) providing a surgical instrument being connected to and/or communicating with a second position tracking system and tracking a position of the surgical instrument in a second system-of-coordinates while performing the intrabody surgical procedure; and (c) receiving data inputs from the first position tracking system, the radioactive emission detector and the second position tracking system and calculating the position of the surgical instrument and the radiopharmaceutical uptaking portion of the body component in a common system-of-coordinates while performing the intrabody surgical procedure.


According to further features in preferred embodiments of the invention described below, the second system-of-coordinates serves as the common system-of-coordinates and therefore the position of the radiopharmaceutical uptaking portion of the body component in the first system-of-coordinates is projected onto the second system-of-coordinates.


According to still further features in the described preferred embodiments the first system-of-coordinates serves as the common system-of-coordinates and therefore the position of the surgical instrument in the second system-of-coordinates is projected onto the first system-of-coordinates.


According to still further features in the described preferred embodiments the second system-of-coordinates, the first system-of-coordinates and the common system-of-coordinates are a single system-of-coordinates.


According to still further features in the described preferred embodiments the first system-of-coordinates, the second system-of-coordinates and the common system-of-coordinates are each a separate system-of-coordinates and therefore the position of the surgical instrument in the second system-of-coordinates and the position of the radiopharmaceutical uptaking portion of the body component in the first system-of-coordinates are both projected onto the common system-of-coordinates.


According to still further features in the described preferred embodiments the first position tracking system and the second position tracking system are a single position tracking system.


According to still further features in the described preferred embodiments an image presentation device serves for visual co-presentation of the position of the surgical instrument and the radiopharmaceutical uptaking portion of the body component.


According to still further features in the described preferred embodiments the radioactive emission detector is selected from the group consisting of a narrow angle radioactive emission detector, a wide angle radioactive emission detector, a plurality of individual narrow angle radiation emission detectors and a spatially sensitive radioactivity detector, such as a gamma camera employed in nuclear imaging.


According to still further features in the described preferred embodiments the first and the second position tracking systems may include, but are not limited to, any combination of an articulated arm position tracking system, an accelerometers based position tracking system, a potentiometers based position tracking system, a sound wave based position tracking system, a radio frequency based position tracking system, a magnetic field based position tracking system and an optical (e.g., optical encoder) based position tracking system.


According to still further features in the described preferred embodiments the surgical instrument may include, but is not limited to, any combination of laser probe, cardiac catheter, angioplasty catheter, endoscopic probe, biopsy needle, ultrasonic probe, fiber optic scopes, aspiration tubes, laparoscopy probe, thermal probe and suction/irrigation probe.


According to still further features in the described preferred embodiments the radiopharmaceutical may include, but is not limited to, 131I, 67Ga (which may be administered as Ga-citrate), 99MTc methoxyisobutyl isonitrile, 201TlCl, 18F-fluorodeeoxyglucose, 125I-fibrinogen and 111In-octreotide, to name a few.


According to still further features in the described preferred embodiments the two- or three-dimensional imaging modality is connected to and/or communicating with a third position tracking system and is used for calculating the position of a body component in a third system-of-coordinates.


According to still further features in the described preferred embodiments data inputs are received from the two- or three-dimensional imaging modality and the third position tracking system and are used for calculating the position of the surgical instrument and the position of the radiopharmaceutical uptaking portion of a body component and the position of the body component in a common system-of-coordinates.


According to still further features in the described preferred embodiments the first position tracking system, the second position tracking system and the third position tracking system are a single position tracking system.


According to still further features in the described preferred embodiments the position of the surgical instrument, the radiopharmaceutical uptaking portion of the body component and the body component are co-represented by a visual presentation device.


According to still further features in the described preferred embodiments each of the first, the second and the third position tracking system is independently selected from the group consisting of an articulated arm position tracking system, an accelerometers based position tracking system, a sound wave based position tracking system, a radio frequency based position tracking system, a magnetic field based position tracking system and an optical based position tracking system.


According to still further features in the described preferred embodiments the second system-of-coordinates serves as the common system-of-coordinates and therefore the position of the radiopharmaceutical uptaking portion of the body component in the first system-of-coordinates and the position of the body component in the third system-of-coordinates are projected onto the second system-of-coordinates.


According to still further features in the described preferred embodiments the first system-of-coordinates serves as the common system-of-coordinates and therefore the position of the surgical instrument in the second system-of-coordinates and the position of the body component in the third system-of-coordinates are projected onto the first system-of-coordinates.


According to still further features in the described preferred embodiments the third system-of-coordinates serves as the common system-of-coordinates and therefore the position of the surgical instrument in the second system-of-coordinates and the position of the radiopharmaceutical uptaking portion of the body component in the first system-of-coordinates are projected onto the third system-of-coordinates.


According to still further features in the described preferred embodiments the second system-of-coordinates, the first system-of-coordinates, the third system-of-coordinates and the common system-of-coordinates are a single system-of-coordinates.


According to still further features in the described preferred embodiments the second system-of-coordinates, the first system-of-coordinates, the third system-of-coordinates and the common system-of-coordinates are each a separate system-of-coordinates and therefore the position of the surgical instrument in the second system-of-coordinates and the position of the radiopharmaceutical uptaking portion of the body component in the first system-of-coordinates and the position of the body component in the third system-of-coordinates are all projected onto the common system-of-coordinates.


According to another aspect of the present invention there is provided a system for generating a two- or three-dimensional image of a radioactivity emitting source in a body, the system comprising (a) a radioactive emission detector; (b) a position tracking system being connected to and/or communicating with the radioactive emission detector; and (c) a data processor being designed and configured for receiving data inputs from the position tracking system and from the radioactive emission detector and for generating the two- or three-dimensional image of the radioactivity emitting source.


According to still another aspect of the present invention there is provided a method of generating a two- or three-dimensional image of a radioactivity emitting source in a body, the system comprising (a) scanning the body with a radioactive emission detector; (b) using a position tracking system being connected to and/or communicating with the radioactive emission detector for determining a position in a two- or three-dimensional system of coordinates of the radioactive emission detector; and (c) data processing inputs from the position tracking system and from the radioactive emission detector for generating the two- or three-dimensional image of the radioactivity emitting source.


According to still another aspect of the present invention there is provided a system for performing an intrabody surgical procedure on a radiopharmaceutical uptaking portion of a body component within a subject, the system comprising a surgical instrument being connected to and/or communicating with a position tracking system for tracking a position of the surgical instrument in a system-of-coordinates, the surgical instrument including a radioactive emission detector coupled thereto for monitoring the radiopharmaceutical in situ. Preferably, radioactive emission detector is sensitive to beta radiation and/or positron radiation. Optionally it is sensitive to low energy (10-30 KeV) or gamma radiation. The surgical instrument preferably includes a tissue resecting mechanism and/or a tissue sampling mechanism, such as an aspiration mechanism.


According to an additional aspect of the present invention there is provided a system for calculating a position of a radioactivity emitting source in a system-of-coordinates, the system comprising (a) a surgical instrument designed and constructed for invading a body of a subject, the surgical instrument including a radioactive emission detector connected thereto or integrated therein; (b) a position tracking system being connected to and/or communicating with the surgical instrument; and (c) a data processor being designed and configured for receiving data inputs from the position tracking system and from the radioactive emission detector and for calculating the position of the radioactivity emitting source in the system-of-coordinates.


According to yet an additional aspect of the present invention there is provided a system for calculating a position of a radioactivity emitting source in a first system-of-coordinates and further of projecting the position of the radioactivity emitting source onto a second system-of-coordinates, the system comprising (a) a surgical instrument designed and constructed for invading a body of a subject, the surgical instrument including a radioactive emission detector connected thereto or integrated therein; (b) a position tracking system being connected to and/or communicating with the surgical instrument; and (c) a data processor being designed and configured for (i) receiving data inputs from the position tracking system and from the radioactive emission detector; (ii) calculating the position of the radioactivity emitting source in the first system-of-coordinates; (iii) calculating the position of the surgical instrument in the first system-of-coordinates; and (iii) projecting the position of the radioactivity emitting source and of the surgical instrument onto the second system-of-coordinates.


According to still an additional aspect of the present invention there is provided a method for calculating a position of a radioactivity emitting source in a first system-of-coordinates and for projecting the position of the radioactivity emitting source onto a second system-of-coordinates, the method comprising the steps of (a) providing a surgical instrument designed and constructed for invading a body of a subject, the surgical instrument including a radioactive emission detector connected thereto or integrated therein, the surgical instrument being connected to or communicating with a position tracking system; and (b) monitoring radioactivity being emitted from the radioactivity emitting source, while at the same time, monitoring the position of the radioactive emission detector in the first system-of-coordinates, thereby defining the positions of the radioactivity emitting source and of the surgical instrument in the first system-of-coordinates and projecting the position of the radioactivity emitting source onto the second system-of-coordinates.


According to a further aspect of the present invention there is provided a system for calculating a position of a body component and a position of a radiopharmaceutical uptaking portion of the body component within a subject, the system comprising (a) a two- or three-dimensional imaging modality being connected to and/or communicating with a first position tracking system for calculating the position of the body component in a first system-of-coordinates; (b) a surgical instrument designed and constructed for invading the body, the surgical instrument including a radioactive emission detector connected thereto or integrated therein, the surgical instrument being connected to and/or communicating with a second position tracking system for tracking a position of the radiopharmaceutical uptaking portion of the body component in a second system-of-coordinates; and (c) at least one data processor being designed and configured for receiving data inputs from the three-dimensional imaging modality, the first position tracking system, the radioactive emission detector and the second position tracking system and calculating the position of the body component, the position of the radiopharmaceutical uptaking portion of the body component and the position of the surgical instrument in a common system-of-coordinates.


According to yet a further aspect of the present invention there is provided a method for calculating a position of a body component and a position of a radiopharmaceutical uptaking portion of the body component within a subject, the method comprising the steps of (a) providing a two- or three-dimensional imaging modality being connected to and/or communicating with a first position tracking system and calculating the position of the body component in a first system-of-coordinates; (b) providing a surgical instrument designed and constructed for invading the body, the surgical instrument including a radioactive emission detector connected thereto or integrated therein, the surgical instrument being connected to and/or communicating with a second position tracking system for tracking a position of the radiopharmaceutical uptaking portion of the body component in a second system-of-coordinates; and (c) receiving data inputs from the two- or three-dimensional imaging modality, the first position tracking system, the radioactive emission detector and the second position tracking system and calculating the position of the body component, the position of the surgical instrument and the position of the radiopharmaceutical uptaking portion of the body component in a common system-of-coordinates.


The present invention seeks to improve and expand upon generation of one, two- or three-dimensional images of radioactivity emitting sources. Specifically, the present invention seeks to provide an improved method and system for imaging and guiding a diagnostic or therapeutic instrument towards a target region inside the patient's body, particularly by means of a nuclear radiation detector with a position tracking system.


In one aspect of the invention, a radiation probe is housed in a collimator and attached to a position tracking system. As the probe moves in two- or three-dimensional space about the patient being examined, data is collected and an image of the radiation patterns emanating from within the patient are mapped. One advantage of a two- or three-dimensional scan is that higher safety and accuracy are achieved through a greater number of directional searches and in turn a better localization of the radiation source.


The invention enables mapping radiation source regions and surrounding uncertainty regions. One way of accomplishing this is by means of a feedback system that employs statistical analysis to determine the bounds of an uncertainty region, and which guides medical personnel to conduct additional scans in these uncertainty regions to improve accuracy, reduce error, and hence minimize the bounds of the uncertainty regions.


The present invention successfully addresses the shortcomings of the presently known configurations by providing a radioactive emission detector per se and/or integrated in a surgical instrument connected to or communicating with a position tracking system and the use thereof in a variety of systems and methods used for medical imaging and/or medical procedures.


The present invention has many other applications in the direction of therapeutics, such as, but not limited to, implanting brachytherapy seeds, ultrasound microwave radio-frequency cryotherapy and localized radiation ablations.


Implementation of the methods and systems of the present invention involves performing or completing selected tasks or steps manually, automatically, or a combination thereof. Moreover, according to actual instrumentation and equipment of preferred embodiments of the methods and systems of the present invention, several selected steps could be implemented by hardware or by software on any operating system of any firmware or a combination thereof. For example, as hardware, selected steps of the invention could be implemented as a chip a circuit. As software, selected steps of the invention could be implemented as a plurality of software instructions being executed by a computer using any suitable algorithms. In any case, selected steps of the method and system of the invention could be described as being performed by a data processor, such as a computing platform for executing a plurality of instructions.





BRIEF DESCRIPTION OF THE DRAWINGS

The invention is herein described, by way of example only, with reference to the accompanying drawings. With specific reference now to the drawings in detail, it is stressed that the particulars shown are by way of example and purposes of illustrative discussion of the preferred embodiments of the present invention only, and are presented in the cause of providing what is believed to be the most useful and readily understood description of the principles and conceptual aspects of the invention. In this regard, no attempt is made to show structural details of the invention in more detail than is necessary for a fundamental understanding of the invention, the description taken with the drawings making apparent to those skilled in the art how the several forms of the invention may be embodied in practice.


In the drawings:



FIG. 1 is a black box diagram of a system according to the teachings of the present invention;



FIG. 2 is a perspective view of an articulated arm which serves as a position tracking system shown carrying a radioactive emission detector in accordance with the teachings of the present invention;



FIG. 3 is a schematic depiction of a radioactive emission detector carrying a pair of three coaxially aligned accelerometers which serve as a position tracking system in accordance with the teachings of the present invention;



FIG. 4 is a schematic presentation of a radioactive emission detector communicating with yet another type of a position tracking system in accordance with the teachings of the present invention;



FIG. 5 is a simplified cross-sectional view of a narrow or wide angle radioactive emission detector used to implement an embodiment of the present invention;



FIG. 6 is a presentation of a scanning protocol which can be effected with the detector of FIG. 5;



FIG. 7 is a simplified cross-sectional view of a spatially sensitive radioactive emission detector, e.g., a gamma camera, used to implement another embodiment of the present invention;



FIG. 8 is a presentation of a scanning protocol which can be effected with the detector of FIG. 7;



FIG. 9 demonstrates a system in accordance with the teachings of the present invention which employs four position tracking systems for co-tracking the positions of a patient, a radioactive emission detector, an imaging modality and a surgical instrument;



FIG. 10 demonstrates the use of a pair of radiation emission detectors connected therebetween via a connector, preferably a flexible connector or a flexible connection to the connector according to the present invention;



FIG. 11 is a schematic diagram of a surgical instrument and accompanying system elements according to the teachings of the present invention;



FIG. 12 is a simplified pictorial illustration of an imaging system constructed and operative in accordance with a preferred embodiment of the present invention, including a radiation probe and position sensor, position tracking system, medical imaging system and coordinate registration system;



FIG. 13 is a simplified pictorial illustration of a single dimension image formation with a nuclear radiation probe attached to a position tracking system of the system of FIG. 12, in accordance with a preferred embodiment of the present invention;



FIG. 14 is a simplified pictorial plot of detecting a radiation point source with the nuclear radiation probe of the system of FIG. 12, without further processing, in accordance with a preferred embodiment of the present invention;



FIG. 15 is a simplified flow chart of an averaging algorithm used in the imaging system of FIG. 12, in accordance with a preferred embodiment of the present invention;



FIG. 16 is a simplified pictorial plot of detecting a radiation point source with the nuclear radiation probe of the system of FIG. 12, with averaging processing, in accordance with a preferred embodiment of the present invention;



FIGS. 17 and 18 are simplified pictorial illustrations of hot cross and hot bar phantom images, respectively, of images produced by a gamma radiation probe of the system of FIG. 12;



FIG. 19 is a simplified flow chart of a minimizing algorithm used in the imaging system of FIG. 12, in accordance with a preferred embodiment of the present invention;



FIG. 20 is a simplified pictorial plot of detecting a radiation point source with the nuclear radiation probe of the system of FIG. 12, with minimizing processing, in accordance with a preferred embodiment of the present invention;



FIG. 21 is a simplified pictorial illustration of an image reconstruction system constructed and operative in accordance with a preferred embodiment of the present invention, which produces a combined image made up of medical images, the position of the peak radiation location and the location of a therapeutic instrument;



FIG. 22 is a simplified flow chart of a radiation map reconstruction algorithm, in accordance with a preferred embodiment of the present invention;



FIGS. 23A and 23B are illustrations of radiolabeled patterns observed in images produced by the system of the invention and by a conventional gamma camera, respectively, of an autonomous adenoma of a thyroid;



FIGS. 24A and 24B are illustrations of radiolabeled patterns observed in images produced by the system of the invention and by a conventional gamma camera, respectively, of suspected Paget's disease of a humerus;



FIGS. 25A and 25B are illustrations of radiolabeled patterns observed in images produced by the system of the invention and by a conventional gamma camera, respectively, of chronic osteomyelitis; and



FIGS. 26A and 26B are illustrations of radiolabeled patterns observed in images produced by the system of the invention and by a conventional gamma camera, respectively, of skeletal metastasis from medulloblastoma.



FIGS. 27A-G demonstrate the operation of an algorithm provided by the present invention for estimating the distribution of radiation sources in a control volume.





DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention is of a radioactive emission detector equipped with a position tracking system which can be functionally integrated with medical two- or three-dimensional imaging modalities and/or with guided minimally-invasive or other surgical tools. The present invention can be used for calculating the position of a concentrated radiopharmaceutical in the body in positional context of imaged portions of the body, which information can be used, for example, for performing an efficient and highly accurate minimally invasive surgical procedure.


The principles and operation of the present invention may be better understood with reference to the drawings and accompanying descriptions.


Before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not limited in its application to the details of construction and the arrangement of the components set forth in the following description or illustrated in the drawings. The invention is capable of other embodiments or of being practiced or carried out in various ways. Also, it is to be understood that the phraseology and terminology employed herein is for the purpose of description and should not be regarded as limiting.


The use of radioactive materials to tag physiologically active tissue within the body of a patient, for determining the tissue's localization and demarcation by radioactive emission detectors has been disclosed in the medical literature for at least forty years. Significant developments in the localization and demarcation of tissue bearing radioactive isotope tags for diagnostic and/or therapeutic purposes have occurred since that time. In fact, it is now becoming an established practice in the diagnosis and/or treatment of certain diseases, e.g., cancer, blood clots, myocardial infarct and abscesses, to introduce monoclonal antibodies or other agents, e.g., fibrinogen, fluorodeoxyglucose labeled with a radioactive isotope (e.g., 99MTechnetium, 67Gallium, 201Thallium, 111Indium, 123Iodine, 18Fluorine and 125Iodine) into the body of the patient. Such radiopharmaceuticals tend to localize in particular tissue or cell type, whereas uptake or binding of the specific radiopharmaceutical is increased in more “physiologically active” tissue such as the active core of a cancerous tissue, so that the radiation emitted following nuclear disintegrations of the isotope can be detected by a radiation detector to better allocate the active portion of a tumor. Such radiation may be, for example, α, β, β+ and/or γ radiation.


In another type of applications radioactive substances are used to determine the level of flow of blood in blood vessels and the level of perfusion thereof into a tissue, e.g., coronary flow and myocardial perfusion.


Referring now to the drawings, FIG. 1 illustrates a system for calculating a position of a radioactivity emitting source in a system-of-coordinates, in accordance with the teachings of the present invention, which system is referred to hereinbelow as system 20.


System 20 includes a radioactivity emission detector 22. System 20 according to the present invention further includes a position tracking system 24. System 24 is connected to and/or communicating with radioactive emission detector 22 so as to monitor the position of detector 22 in a two- or three-dimensional space defined by a system-of-coordinates 28 in two, three or more, say four, five or preferably six degrees-of-freedom (x, y, z, ρ, θ and φ). System 20 further includes a data processor 26. Data processor 26 is designed and configured for receiving data inputs from position tracking system 24 and from radioactive emission detector 22 and, as is further detailed below, for calculating the position of the radioactivity emitting source in system-of-coordinates 28. The phrases “system-of-coordinates” and “three-dimensional space” are used herein interchangeably. As shown in FIG. 10, a pair (or more) of detectors 22 connected therebetween via a physical connector, each of detectors 22 is position tracked, can be used for calculating the position of the radioactivity emitting source in system-of-coordinates 28. If more than a single detector 22 is used, detectors 22 are preferably connected there between via a connector 29. Connector 29 is preferably flexible. In the alternative, the connections of detectors 22 to connector 29 provide the required flexibility.


Position tracking systems per se are well known in the art and may use any one of a plurality of approaches for the determination of position in a two- or three-dimensional space as is defined by a system-of-coordinates in two, three and up to six degrees-of-freedom. Some position tracking systems employ movable physical connections and appropriate movement monitoring devices (e.g., potentiometers) to keep track of positional changes. Thus, such systems, once zeroed, keep track of position changes to thereby determine actual positions at all times. One example for such a position tracking system is an articulated arm.



FIG. 2 shows an articulated arm 30 which includes six arm members 32 and a base 34, which can therefore provide positional data in six degrees-of-freedom. Monitoring positional changes may be effected in any one of several different ways. For example, providing each arm member 32 with, e.g., potentiometers or optical encoders 38 used to monitor the angle between adjacent arm members 32, to thereby monitor the angular change of each such arm member with respect to adjacent arm members, so as to determine the position in space of radioactive emission detector 22, which is physically connected to articulated arm 30.


As is shown in FIG. 3 other position tracking systems can be attached directly to radioactive emission detector 22 in order to monitor its position in space. An example of such a position tracking system is an assortment of three triaxially (e.g., co-orthogonally) oriented accelerometers 36 which may be used to monitor the positional changes of radioactive emission detector 22 with respect to a space. A pair of such assortments, as is specifically shown in FIG. 3, can be used to determine the position of detector 22 in six-degrees of freedom.


As is shown in FIGS. 4 and 10, other position tracking systems re-determine a position irrespective of previous positions, to keep track of positional changes. Such systems typically employ an array of receivers/transmitters 40 which are spread in known positions in a three-dimensional space and transmitter(s)/receiver(s) 42, respectively, which are in physical connection with the object whose position being monitored. Time based triangulation and/or phase shift triangulation are used in such cases to periodically determine the position of the monitored object, radioactive emission detector 22 in this case. Examples of such a position tracking systems employed in a variety of contexts using acoustic (e.g., ultrasound) electromagnetic radiation (e.g., infrared, radio frequency) or magnetic field and optical decoding are disclosed in, for example, U.S. Pat. Nos. 5,412,619; 6,083,170; 6,063,022; 5,954,665; 5,840,025; 5,718,241; 5,713,946; 5,694,945; 5,568,809; 5,546,951; 5,480,422 and 5,391,199, which are incorporated by reference as if fully set forth herein.


Radioactive emission detectors are well known in the art and may use any one of a number of approaches for the determination of the amount of radioactive emission emanating from an object or portion thereof. Depending on the type of radiation, such detectors typically include substances which when interacting with radioactive decay emitted particles emit either electrons or photons in a level which is proportional over a wide linear range of operation to the level of radiation impinging thereon. The emission of electrons or photons is measurable and therefore serves to quantitatively determine radiation levels. Solid-state detectors in the form of N-type, P-type, PIN-type pixellated or unpixellated include, for example, Ge, Si, CdTe, CdZnTe, CdSe, CdZnSe, HgI2, TlBrI, GaAs, InI, GaSe, Diamond, TlBr, PbI2, InP, ZnTe, HgBrI, a-Si, a-Se, BP, GaP, CdS, SiC, AlSb, PbO, BiI3 and ZnSe detectors. Gas (e.g., CO2 CH4) filled detectors include ionization chamber detectors, proportional chamber detectors and geiger chamber detectors. Scintillation detectors include organic scintillators crystals and liquids, such as C14H10, C14H12, C10H8, etc., Plastics, NE102A, NE104, NE 110, Pilot U and inorganic scintillators, such as NaI, CsI, BGO, LSO, YSO, BaF, ZnS, ZnO, CaWO4 and CdWO4. Also known are scintillation fiber detectors. Scintillator coupling include photomultiplier tube (PMT) of the following types: side-on type, head-on type, hemispherical type, position sensitive type, icrochannel plate-photomultiplier (MCP-PMTs) and electron multipliers, or photodiodes (and photodiodes arrays), such as Si photodiodes, Si PIN photodiodes, Si APD, GaAs(P) photodiodes, GaP and CCD.



FIG. 5 shows a narrow angle or wide angle radioactive emission detector 22′. Narrow or wide angle radioactive emission detector 22′ includes a narrow slit (collimator) so as to allow only radiation arriving from a predetermined angular direction (e.g., 1°-280°-wide angle, preferably 1°-80°-narrow angle) to enter the detector. Narrow or wide angle radioactive emission detectors especially suitable for the configuration shown in FIG. 10 are manufactured, for example, by Neoprobe, Dublin, Ohio (www.neoprobe.com), USA, Nuclear Fields, USA (www.nufi.com) IntraMedical Imaging, Los Angeles, Calif., USA (www.gammaprobe.com).


As is shown in FIG. 6, such a detector is typically used to measure radioactivity, point by point, by scanning over the surface of a radioactive object from a plurality of directions and distances. In the example shown, scans from four different directions are employed. It will be appreciated that if sufficient radioactivity records are collected from different angles and distances, and the orientation and position in space of detector 22′ is simultaneously monitored and recorded during such scans, a three-dimensional model of a radioactive region can be reconstituted and its position in space determined. If two or more detectors are co-employed, as shown in the configuration of FIG. 10, the results may be collected faster.



FIG. 7 shows another example of a radioactive emission detector, a spatially sensitive (pixelated) radioactive emission detector 22″ (such as a gamma camera). Detector 22″, in effect, includes an array of multitude narrow angle detector units 23. Such an arrangement is used in accordance with the teachings of the present invention to reduce the amount of measurements and angles necessary to acquire sufficient data so as to reconstitute a three-dimensional model of the radioactive object. Examples of spatially sensitive radioactive emission detectors employed in a variety of contexts are disclosed in, for example, U.S. Pat. Nos. 4,019,057; 4,550,250; 4,831,262; and 5,521,373; which are incorporated by reference as if set forth herein. An additional example is the COMPTON detector (http://www.ucl.ac.uk/MedPhys/posters/giulia/giulia.htm). FIG. 8 shows a scan optionally made by spatially sensitive radioactive emission detector 22″ (such as a gamma camera).


A radioactive emmission detector of particular advantages for use in context of the present invention is the Compton gamma probe, since, in the Compton gamma probe, spatial resolution is independent of sensitivity and it appears possible to exceed the noise equivalent sensitivity of collimated imaging systems especially for systems with high spatial resolution. The Compton probe is a novel type of gamma-probe that makes use of the kinematics of Compton scattering to construct a source image without the aid of mechanical collimators. Compton imaging telescopes were first built in the 1970s for astronomical observations [V. Schoenfelder et al., Astrophysical Journal 217 (1977) 306]. The first medical imaging laboratory instrument was proposed in the early 1980s [M. Singh, Med. Phys. 10 (1983) 421]. The potential advantages of the Compton gamma probe include higher efficiency, 3-D imaging without detector motion, and more compact and lightweight system. In the Compton gamma probe, high-energy gamma rays are scattered from a first detector layer (or detectors array) into a second detector layer array. For each gamma, the deposited energy is measured in both detectors. Using a line drawn between these two detectors, the Compton scattering equation can be solved to determine the cone of possible direction about this axis on which the gamma ray must have entered the first detector. The intersection of cones from many events is then developed to locate gamma ray sources in the probe's field-of-view. Obviously only coincident events are considered, and the more accurately their energy can be determined, the less uncertainty there is in the spatial angle of the arrival cone. The probe's electronic system is combining coincidence measurements across many detectors and detectors layers with a very good energy resolution. The choice of the geometry and the material of the first layer detector plays a major role in the system imaging capability and depends on (i) material efficiency of single Compton events, in relation to other interactions; (ii) detector energy resolution; and (iii) detector position resolution. In particular, the overall angular resolution results from the combination of two components, related to the energy resolution and to the pixel volume of the detector.


Thus, as now afforded by the present invention, connecting a radioactive emission detector to a position tracking system, permits simultaneous radioactivity detecting and position tracking at the same time. This enables the accurate calculation of the shape, size and contour of the radiating object and its precise position in a three-dimensional space.


The present invention thus provides a method for defining a position of a radioactivity emitting source in a system-of-coordinates. The method is effected by (a) providing a radioactive emission detector which is connected to or communicating with a position tracking system; and (b) monitoring radioactivity emitted from the radioactivity emitting source, while at the same time, monitoring the position of radioactive emission detector in the system-of-coordinates, thereby defining the position of the radioactivity emitting source in the system-of-coordinates.


It will be appreciated by one of skills in the art that the model produced by system 20 is projectable onto any of the other systems-of-coordinates, or alternatively, the system-of-coordinates defined by position tracking system 24 may be shared by other position tracking systems, as is further detailed hereinbelow, such that no such projection is required.


Thus, as is further shown in FIG. 1, system 20 of the present invention can be used for calculating a position of a radioactivity emitting source in a first system-of-coordinates 28 and further for projecting the position of the radioactivity emitting source onto a second system-of-coordinates 28′. The system includes radioactive emission detector 22, position tracking system 24 which is connected to and/or communicating with radioactive emission detector 22, and data processor 26 which is designed and configured for (i) receiving data inputs from position tracking system 24 and from radioactive emission detector 22; (ii) calculating the position of the radioactivity emitting source in the first system-of-coordinates; and (iii) projecting the position of the radioactivity emitting source onto the second system-of-coordinates.


A method for calculating a position of a radioactivity emitting source in a first system-of-coordinates and for projecting the position of the radioactivity emitting source onto a second system-of-coordinates is also offered by the present invention. This method is effected by (a) providing a radioactive emission detector being connected to or communicating with a position tracking system; and (b) monitoring radioactivity being emitted from the radioactivity emitting source, while at the same time, monitoring the position of the radioactive emission detector in the first system-of-coordinates, thereby defining the position of the radioactivity emitting source in the first system-of-coordinates and projecting the position of the radioactivity emitting source onto the second system-of-coordinates.


It will be appreciated that the combination of a radioactive emission detector and a position tracking system connected thereto and/or communicating therewith allows a suitable data processor to generate a two- or three-dimensional image of the radioactivity emitting source. An algorithm can be used to calculate image intensity based on, for example, a probability function which averages radiation counts and generates an image in which the shorter the time interval between radioactive counts, the brighter the image and vise versa, while down-compensating when a location is re-scanned. A free-hand scanning with a directional detector can be employed for this purpose.


In one embodiment, when scanning a body area with the detector, the detector is made to follow a three-dimensional surface which defines the body curvature and in effect is used also as a position tracking pointer. This information can be used to define the position of the radioactive source with respect to the outer surface of the body, so as to create a three-dimensional map of both the radioactive source and of the body curvature. This approach can also be undertaken in open surgeries, such as open chest surgeries so as to provide the surgeon in real time with information concerning the functionality of a tissue.


The radioactive emission detector which can be used in context of the present invention can be a beta emission detector, a gamma emission detector, a positron emission detector or any combination thereof. A detector that is sensitive to both beta (and/or positron) and gamma emission can be used to improve localization by sensing for example gamma emission distant from the source and sensing beta or positrons emission closer to the source. A beta detector is dedicated for the detection of either electrons from sources such as 131Iodine, or positrons from sources such as 18Fluorine. A gamma detector can be designed as a single energy detector or as a detector that can distinguish between different types of energies, using the light intensity in the scintillator as a relative measure of the gamma energy. Also, the detector can be designed to utilize coincidence detection by using detectors facing one another (180 degrees) with the examined organ or tissue in-between. The radiation detector can have different collimators with different diameters. A large bore will be used for high sensitivity with lower resolution while a small bore collimator will have higher resolution at the expense of lower sensitivity.


Another possibility is to have a the collimator moving or rotating with the opening eccentric so that a different solid angle is exposed to the incoming photons at any one time, thus gathering the photons from overlapping volumes at different time intervals. The rest of the image processing is similar if the probe moves or if the collimator eccentric opening moves.


System 20 of the present invention can be used in concert with other medical devices, such as, but not limited to, any one of a variety of imaging modalities and/or surgical instruments.


Imaging modalities are well known in the art, the main modalities that serve for two-(projectional or cross sectional) or three-(consecutive cross sectional) dimensional imaging are a fluoroscope, a computerized tomography scanner, a magnetic resonance imager an ultrasound imager and an optical camera.


Medical images taken of the human body are typically acquired or displayed in three main orientations (i) coronal orientation: in a cross section (plane), for example, across the shoulders, dividing the body into front and back halves; (ii) sagittal orientation: in a cross section (plane), for example, down the middle, dividing the body into left and right halves; and (iii) axial orientation: in a cross section (plane), perpendicular to the long axis of the body, dividing the body into upper and lower halves. Oblique views can also be acquired and displayed.


Various types of X-ray imaging are central to diagnosis of many types of cancer. Conventional X-ray imaging has evolved over the past 100 years, but the basic principal is still the same as in 1895, when first introduced. An X-ray source is turned on and X-rays are radiated through the body part of interest and onto a film cassette positioned under or behind the body part. The energy and wavelength of the X-rays allows them to pass through the body part and create the image of the internal structures like bones. As the X-rays pass through the hand, for instance, they are attenuated by the different density tissues they encounter. Bone attenuates a great deal more of the X-rays than the soft tissue surrounding it because of its grater density. It is these differences in absorption and the corresponding varying exposure level of the film that creates the images. In fact, X-ray imaging results in a projection of the integrated density of column-voxels defined by the X-rays as they pass through the body.


Fluoroscopy is a method based on the principals of film X-ray that is useful for detecting disorders and tumors in the upper gastro-intestinal (GI) system (for example, the stomach and intestines). Fluoroscopic imaging yields a moving X-ray picture. The physician can watch the screen and see an image of the patient's body (for example the beating heart). Fluoroscopic technology improved greatly with the addition of television cameras and fluoroscopic “image intensifiers”. Today, many conventional X-ray systems have the ability to switch back and forth between the radiographic and fluoroscopic modes. The latest X-ray systems have the ability to acquire the radiograph or fluoroscopic movie using digital acquisition.


Computed Tomography (CT) is based on the X-ray principal, where the film is replaced by a detector that measures the X-ray profile. Inside the covers of the CT scanner is a rotating frame which has an X-ray tube mounted on one side and the detector mounted on the opposite side. A fan beam of X-ray is created as the rotating frame spins the X-ray tube and detector around the patient. Each time the X-ray tube and detector make a 360° rotation, an image or “slice” has been acquired. This “slice” is collimated to a thickness between 1 mm and 10 mm using lead shutters in front of the X-ray tube and X-ray detector.


As the X-ray tube and detector make this 360° rotation, the detector takes numerous profiles of the attenuated X-ray beam. Typically, in one 360° lap, about 1,000 profiles are sampled. Each profile is subdivided spatially by the detectors and fed into about 700 individual channels. Each profile is then backwards reconstructed (or “back projected”) by a dedicated computer into a two-dimensional image of the “slice” that was scanned.


The CT gantry and table have multiple microprocessors that control the rotation of the gantry, movement of the table (up/down and in/out), tilting of the gantry for angled images, and other functions such as turning the X-ray beam on an off. The CT contains a slip ring that allows electric power to be transferred from a stationary power source onto the continuously rotating gantry. The innovation of the power slip ring has created a renaissance in CT called spiral or helical scanning. These spiral CT scanners can now image entire anatomic regions like the lungs in a quick 20 to 30 second breath hold. Instead of acquiring a stack of individual slices which may be misaligned due to slight patient motion or breathing (and lung/abdomen motion) in between each slice acquisition, spiral CT acquires a volume of data with the patient anatomy all in one position. This volume data set can then be computer-reconstructed to provide three-dimensional models such as of complex blood vessels like the renal arteries or aorta. Spiral CT allows the acquisition of CT data that is perfectly suited for three-dimensional reconstruction.


MR Imaging is superior to CT in detecting soft tissue lesions such as tumors as it has excellent contrast resolution, meaning it can show subtle soft-tissue changes with exceptional clarity. Thus, MR is often the method of choice for diagnosing tumors and for searching for metastases. MR uses magnetic energy and radio waves to create single or consecutive cross-sectional images or “slices” of the human body. The main component of most MR systems is a large tube shaped or cylindrical magnet. Also, there are MR systems with a C-shaped magnet or other type of open designs. The strength of the MR systems magnetic field is measured in metric units called “Tesla”. Most of the cylindrical magnets have a strength between 0.5 and 1.5 Tesla and most of the open or C-shaped magnets have a magnetic strength between 0.01 and 0.35 Tesla.


Inside the MR system a magnetic field is created. Each total MR examination typically is comprised of a series of 2 to 6 sequences. An “MR sequence” is an acquisition of data that yields a specific image orientation and a specific type of image appearance or “contrast”. During the examination, a radio signal is turned on and off, and subsequently the energy which is absorbed by different atoms in the body is echoed or reflected back out of the body. These echoes are continuously measured by “gradient coils” that are switched on and off to measure the MR signal reflecting back. In the rotating frame of reference, the net magnetization vector rotate from a longitudinal position a distance proportional to the time length of the radio frequency pulse. After a certain length of time, the net magnetization vector rotates 90 degrees and lies in the transverse or x-y plane. It is in this position that the net magnetization can be detected on MRI. The angle that the net magnetization vector rotates is commonly called the ‘flip’ or ‘tip’ angle. At angles greater than or less than 90 degrees there will still be a small component of the magnetization that will be in the x-y plane, and therefore be detected. Radio frequency coils are the “antenna” of the MRI system that broadcasts the RF signal to the patient and/or receives the return signal. RF coils can be receive-only, in which case the body coil is used as a transmitter; or transmit and receive (transceiver). Surface coils are the simplest design of coil. They are simply a loop of wire, either circular or rectangular, that is placed over the region of interest.


A digital computer reconstructs these echoes into images of the body. A benefit of MRI is that it can easily acquire direct views of the body in almost any orientation, while CT scanners typically acquire cross-sectional images perpendicular or nearly perpendicular to the long body axis.


Ultrasound imaging is a versatile scanning technique that uses sound waves to create images of organs or anatomical structures in order to make a diagnosis. The ultrasound process involves placing a small device called a transducer, against the skin of the patient near the region of interest, for example, against the back to image the kidneys. The ultrasound transducer combines functions of emitting and receiving sound. This transducer produces a stream of inaudible, high frequency sound waves which penetrate into the body and echo off the organs inside. The transducer detects sound waves as they echo back from the internal structures and contours of the organs. Different tissues reflect these sound waves differently, causing a signature which can be measured and transformed into an image. These waves are received by the ultrasound machine and turned into live pictures with the use of computers and reconstruction software.


Ultrasound scanning has many uses, including: diagnosis of disease and structural abnormalities, helping to conduct other diagnostic procedures, such as needle biopsies etc.


There are limitations to some ultrasound techniques: good images may not be obtained in every case, and the scan may not produce as precise results as some other diagnostic imaging procedures. In addition, scan results may be affected by physical abnormalities, chronic disease, excessive movement, or incorrect transducer placement.


Both two-(cross sectional) and three-(consecutive cross-sectional) ultrasound imaging techniques are available nowadays. Worth mentioning is the Dopler three-dimensional ultrasound imaging.


In many cases imaging modalities either inherently include (e.g., fluoroscope, CT, MRI) and/or are integrated with position-tracking-systems, which enable the use of such systems to reconstruct three-dimensional image models and provide their position in a three-dimensional space.


It will be appreciated that, similar to the vision system, also an optical camera can be used to generate three-dimensional imagery date according to the present invention by imaging a body from a plurality (at least two) directions. This type of imaging is especially applicable in open chest surgeries or other open surgeries. Software for calculating a three-dimensional image from a pair of stereoscopic images is well known in the art.


Thus, as used herein and in the claims section that follows, the phrase “three-dimensional imaging modality” refers to any type of imaging equipment which includes software and hardware for generating a three-dimensional image. Such an equipment can generate a three-dimensional image by imaging successive cross-sections of a body, e.g., as if viewed from a single direction. Alternatively, such an equipment can generate a three-dimensional image by imaging a body from different angles or directions (typically two angles) and thereafter combining the data into a three-dimensional image.


Surgical instruments are also well known in the art and may use any one of a plurality of configurations in order to perform minimally-invasive surgical procedures. Examples include laser probes, cardiac and angioplastic catheters, endoscopic probes, biopsy needles, aspiration tubes or needles, resecting devices, ultrasonic probes, fiber optic scopes, laparoscopy probes, thermal probes and suction/irrigation probes. Examples of such surgical instruments employed in a variety of medical contexts are disclosed in, for example, U.S. Pat. Nos. 6,083,170; 6,063,022; 5,954,665; 5,840,025; 5,718,241; 5,713,946; 5,694,945; 5,568,809; 5,546,951; 5,480,422 5,391,199, 5,800,414; 5,843,017; 6,086,554; 5,766,234; 5,868,739; 5,911,719; 5,993,408; 6,007,497; 6,021,341; 6,066,151; 6,071,281; 6,083,166 and 5,746,738, which are incorporated by reference as if fully set forth herein.


For some applications, examples of which are provided in the list of patents above, surgical instruments are integrated with position-tracking-systems, which enable to monitor the position of such instruments while placed in and guided through the body of a treated patient.


According to a preferred embodiment of the present invention, the surgical instrument is equipped with an additional radioactive emission detector attached thereto or placed therein. This additional detector is used, according to preferred embodiments of the invention, to fine tune the location of radioactive emission from within the body, and in closer proximity to the radioactive source. Since the surgical tool is preferably connected to or communicating with a position-tracking system, the position of the additional detector can be monitored and its readouts used to fine tune the position of the radioactive source within the body. Thus, according to this aspect of the present invention, at least one extracorporeal detector and an intracorporeal detector are used in concert to determine the position of a radioactive source in the body in highest precision. The extracorporeal detector provides the general position of the source and is used for directing the surgical instrument thereto, whereas the intracorporeal detector is used for reassuring prior to application of treatment or retrieval of biopsy that indeed the source was correctly targeted at the highest precision.


While according to a presently preferred embodiment of the invention two detectors, one extracorporeal and one intracorporeal, are employed as described above, for some applications a single intracorporeal detector may be employed, which detector is attached to or integrated with a surgical instrument whose position is tracked.


The use of intracorporeal and extracorporeal detectors calls for careful choice of the radioactive isotope employed with the radiopharmaceutical. While the extracorporeal detector can be constructed with a suitable collimator for handling strong radiation, such as gamma radiation, the intracorporeal detector is miniature by nature and is limited in design and construction by the construction of the surgical instrument with which it is employed. Since collimators for high energy (80-511 KeV) gamma radiation are robust in nature, they are not readily engageable with miniature detectors. Electron (beta) and positron radiation are characterized by: (i) they highly absorbed by biological tissue as they are of lower energy and higher chemical reactivity; and (ii) they are readily collimated and focused by thin metal collimators. It is also possible to use low energy gamma radiation (10-30 KeV) for intracorporal applications since the collimation of these gamma photons can be achieved with thin layers of Tantalum or Tungsten. As such, the radio pharmaceutical of choice is selected to emit both gamma and beta and/or positron radiation, whereas the extracorporeal detector is set to detect the high energy gamma radiation, whereas the intracorporeal detector is set to detect the low energy gamma, beta and/or positron radiation. Isotopes that emit both high energy gamma and/or low energy gamma, beta and/or positron radiation and which can be used per se or as a part of a compound as radiopharmaceuticals include, without limitation, 18F, 111In and 123I in radiopharmaceuticals, such as, but not limited to, 2-[18F]fluoro-2-deoxy-D-glucose (18FDG), 111In-Pentetreotide ([111In-DTPA-DPhe1]-octreotide), L-3-[123I]-Iodo-alpha methyl-tyrosine (IMT), O-(2-[18F]fluoroethyl)-L-tyrosine (L-[18F]FET), 111In-Capromab Pendetide (CYT-356, Prostascint) and 111In-Satumomab Pendetide (Oncoscint).



FIG. 11 illustrates a system in accordance with this aspect of the present invention. A surgical instrument 100 is shown connected to a resection/aspiration control element 102 as well known in the art. Surgical instrument 100 includes a radioactive emission detector 104, which has a collimator 106 for collimating low energy gamma, beta and/or positron radiation. In some embodiments, as indicated by arrow 108, detector 104 may be translated within instrument 100. A position tracking system having one element thereof 110 attached to instrument 100 and another element thereof 112 at a fixed location serves to monitor the position of instrument 100 at all times in two, three and up to six degrees of freedom. Radioactive emission detector 104 communicates with a counter 114 for counting low energy gamma, beta and/or positron radiation. All the data is communicated to, and processed by, a processor 116. The 2D or 3D data may be projected and displayed along with 2D or 3D imaging data derived from an imaging modality using a shared presentation device as described elsewhere herein. A real or virtual image of the surgical instrument itself may also be co-displayed. Examples of commercially available radiation emission detectors that can fit inside, for example, a biopsy needle include scintillating plastic optical fibers like S101 and S104, manufactured by PPLASTIFO or an optical fiber communicating with a scintillator (either detector paint or scintillation crystal) at the fiber edge. The level of detected radiation can be reported visually or by an audio signal, as is well known in the art.


Thus, a surgical instrument equipped with a radiation emission detector and which is connected to and/or communicating with a position tracking system forms one embodiment of this aspect of the present invention. Such a design acting in concert with either conventional imaging modalities and/or extracorporeal radiation emission detectors form other embodiments of this aspect of the invention. In all cases, a surgical instrument equipped with a radiation emission detector and which is connected to and/or communicating with a position tracking system serves for in situ fine tuning of a radioactive source in the body.


It will be appreciated that in some minimally-invasive procedures even the position of the patient him or herself is monitored via a position tracking system, using, for example, electronic or physical fiducial markers attached at certain locations to the patient's body.


Thus, as is further detailed hereinbelow, by projecting the three-dimensional data and positions received from any of the above mentioned devices into a common system of coordinates, or alternatively, employing a common position tracking system for all of these devices, one can integrate the data into a far superior and comprehensive presentation.


An example to this desired outcome is shown in FIG. 9. In the embodiment shown, four independent position tracking systems 50, 52, 54 and 56 are used to track the positions of a patient 58, an imaging modality 60, a radioactive emission detector 62 and a surgical instrument 64 in four independent systems-of-coordinates 66, 68, 70 and 72, respectively. If the patient is still, no tracking of the patient's position is required.


It will be appreciated that any subset or all of the position tracking systems employed may be integrated into one or more common position tracking systems, and/or that any subset or all of the position tracking systems employed may share one or more systems-of-coordinates, and further that any positional data obtained by any of the position tracking systems described in any of the systems-of coordinates may be projected to any other system of coordinates or to an independent (fifth) system of coordinates 74. In one preferred embodiment, applicable for applications at the torso of the patient, the system of coordinates is a dynamic system of coordinates which takes into account the chest breathing movements of the patient during the procedure.


As indicated at 76, the raw data collected by detector 62 is recorded and, as indicated at 78, the position and the radioactive data records are used to generate a three-dimensional model of a radiopharmaceutical uptaking portion of a body component of the patient.


Similarly, as indicated at 80, the imagery data collected by imaging modality 60 is recorded and the position and the imagery data records are used to generate a three-dimensional model of the imaged body component of the patient.


All the data collected is then fed into a data processor 82 which processes the data and, as indicated at 84, generates a combined or superimposed presentation of the radioactive data and the imagery data, which is in positional context with patient 58 and surgical instrument 64.


Instrument 64, which by itself can be presented in context of the combined presentation, may then be used to perform the procedure most accurately. Processor 82 may be a single entity or may include a plurality of data processing stations which directly communicate with, or even integral to, any one or more of the devices described.


The present invention provides a major advantage over prior art designs because it positionally integrates data pertaining to a body portion as retrieved by two independent imaging techniques, conventional imaging and radioactive imaging, to thereby provide a surgeon with the ability the fine point the portion of the body to be sampled or treated.


It will be appreciated that subsets of the devices described in FIG. 9 may be used as stand-alone systems. For example, a combination of detector 62 with its position-tracking system and instrument 64 with its position-tracking-system may in some instances be sufficient to perform intrabody procedures. For mere diagnostic purposes, without biopsy, a combination of detector 62 position-tracking-system and modality 60 position-tracking-system are sufficient.


Reference is now made to FIG. 12, which illustrates an imaging system 202 constructed and operative in accordance with a preferred embodiment of the present invention. Imaging system 200 preferably includes a radiation probe 202, such as the narrow angle radioactive emission detector 22′ described hereinabove with reference to FIGS. 5 and 10.


A position sensor 204 is provided for sensing the position of radiation probe 202. Position sensor 204 may be physically attached to radiation probe 202, or may be distanced therefrom. Position sensor 204 transmits the sensed position data to a position tracking system 206. Position tracking system 206 may be a system like position tracking system 24, described hereinabove with reference to FIG. 1, and position sensor 204 may be any kind of sensor applicable for such position tracking systems.


Another method which can be used to locate the source of radiation emission is by using a small hand held gamma camera 205 (such as the DigiRad 2020tc Imager TM, 9350 Trade Place, San Diego, Calif. 92126-6334, USA), attached to position sensor 204.


Position tracking system 206 enables radiation probe 202 to freely scan back and forth in two- or three-dimensions over the area of interest of the patient, preferably incrementing a short distance between each scan pass. Position tracking system 206 tracks the position of radiation probe 202 with respect to a position tracking coordinate system, such as Xp, Yp and Zp, with an origin Op.


Imaging system 200 also includes a medical imaging system 208, such as, but not limited to, computed or computerized tomography (CT), magnetic resonance imaging (MRI), ultrasound imaging, positron emission tomography (PET) and single photon emission computed tomography (SPECT), for example. Medical imaging system 208 provides images of a patient 209 with respect to a medical imaging coordinate system, such as Xm, Ym and Zm, with an origin Om.


Imaging system 200 also includes a coordinate registration system 210, such as that described in U.S. patent application Ser. No. 09/610,490, the disclosure of which is incorporated herein by reference. Coordinate registration system 210 is adapted to register the coordinates of the position tracking coordinate system with those of the medical imaging coordinate system.


Position tracking system 206, medical imaging system 208 and coordinate registration system 210 are preferably in wired or wireless communication with a processing unit 212 (also referred to as a data processor 212).


In operation of imaging system 200, after administration of a radiopharmaceutical to patient 209, a clinician/physician/surgeon (not shown) may move or scan radiation probe 202 about a target area under examination. A physiological activity map of the target area is obtained by measuring the radiation count rate with radiation probe 202, and by correlating the count rate with the count rate direction with position tracking system 206, which follows the motion of the moving or scanning radiation probe 202.


Reference is now made to FIG. 13 which illustrates image formation with radiation probe 202, in accordance with a preferred embodiment of the present invention. For the purposes of simplicity, the example shown in FIG. 13 is for a single dimension image formation, but it is readily understood that the same principles hold true for any other dimensional image formation.


In one example of carrying out the invention, radiation probe 202 may be a gamma ray detector probe that comprises a collimator 211 and radiation detector 213. Gamma rays are projected through the probe collimator 211 onto radiation detector 213, which produces electronic signals in accordance with the radiation detected. Radiation probe 202 sends pulses to a probe counter 215 which may include a pulse height analyzer circuit (not shown). The pulse height analyzer circuit analyzes the electronic signals produced by radiation detector 213. If the electronic signals are within a selected energy window, the level of radiation, i.e., number of radiation counts, is counted by probe counter 215.


Examples of suitable radiation detectors include a solid state detector (SSD) (CdZnTe, CdTe, HgI, Si, Ge, and the like), a scintillation detector (NaI(Tl), LSO, GSO, CsI, CaF, and the like), a gas detector, or a scintillating fiber detector (S101, S104, and the like), for example.


The position sensor 204 associated with the radiation probe 202 senses the position of radiation probe 202, and position tracking system 206 calculates and monitors the motion of radiation probe 202 with respect to the position tracking coordinate system. The motion is calculated and monitored in two, three and up to six dimensions—the linear directions of the X, Y and Z axes as well as rotations about the X, Y and Z axes (i.e., rotational angles ρ, θ and φ, respectively).


Examples of suitable position tracking systems include a measurement mechanical arm (FaroArm, http://www.faro.com/products/faroarm.asp), optical tracking systems (Northern Digital Inc., Ontario, Canada NDI-POLARIS passive or active systems), magnetic tracking systems (NDI-AURORA), infrared tracking systems (E-PEN system, http://www.e-pen.com), and ultrasonic tracking systems (E-PEN system), for example.


Processing unit 212 combines the radiation probe count rate from probe counter 215 together with the positional information from position tracking system 206, and uses an imaging software algorithm 217 to form a two-dimensional or three-dimensional radiotracer-spread image of the target area inside the patient's body. The spatial probe positions together with the spatial count rates may be stored in memory or displayed on a computer monitor 214 as a pattern of marks corresponding to the spatial and count rate position.


An example of such a pattern is shown in FIG. 14, which illustrates a single-dimensional, unprocessed simulation of a radiation point source 218 (FIG. 13), 30 mm deep inside the human body, detected by using a 10 mm nuclear radiation probe 202 coupled to position tracking system 206. The graph of FIG. 14 indicates to a physician that there is a peak count rate of about 500 in the probe position of about 50 mm.


In one embodiment of the invention, the imaging software algorithm 217 employs an averaging process to refine the curve of FIG. 14. This averaging process will now be described with reference to FIG. 15.


Probe counter 215 feeds probe count rate information N(Xc, Yc, Zc, ρ, θ, φ) to processing unit 212 (step 301). Position sensor 204 feeds probe position information (Xc, Yc, Zc, ρ, θ, φ) to processing unit 212 (step 302). Probe parameters (such as its physical size, dx, dy, dz) are also input into processing unit 212 (step 303).


Processing unit 212 then finds all the voxels (i.e., volume pixels) that represent the probe volume in the processing unit memory (step 304), i.e., Xc+dx, Yc+dy, Zc+dz. Processing unit 212 calculates the number of times that the calculation process has been done in each voxel from the beginning of the image formation (step 305), i.e., M(Xc+dx, Yc+dy, Zc+dz). Processing unit 212 then calculates the new average count rate values in each voxel (step 306), in accordance with the formula:










N


(


Xc
+
dx

,

Yc
+
dy

,

Zc
+
dz


)


=



[


N


(


Xc
+
dx

,

Yc
+
dy

,

Zc
+
dz


)


+












N


(

Xc
,
Yc
,
Zc
,
ρ
,
θ
,
φ

)


]

/









[


M


(


Xc
+
dx

,

Yc
+
dy

,

Zc
+
dz


)


+
1

]








Processing unit 212 then corrects the display image that represents the perceived voxels at N(Xc+dx, Yc+dy, Zc+dz) (step 307). The algorithm then repeats itself for the next probe position (step 308).


The resulting graph of the averaging algorithm of FIG. 15, as applied to the example of FIG. 14, is shown in FIG. 16.



FIGS. 17 and 18 respectively show examples of a hot cross phantom image and a hot 4.77 mm bar phantom image, produced by a gamma radiation probe coupled with position tracking system 206 and the averaging algorithm of FIG. 15. The probe images were made by using a probe, EG&G Ortec NaI(Tl) model 905-1 (thickness=1″, diameter=1″) connected to a ScintiPack model 296. The position tracking system used was the Ascension miniBIRD, commercially available from Ascension Technology Corporation, P.O. Box 527, Burlington, Vt. 05402 USA (http://www.ascension-tech.com/graphic.htm). The magnetic tracking and location systems of Ascension Technology Corporation use DC magnetic fields to overcome blocking and distortion from nearby conductive metals. Signals pass through the human body without attenuation.


In another embodiment of the invention, the imaging software algorithm 217 may employ a minimizing process to refine the curve of FIG. 14 as is now described with reference to FIG. 19.


Probe counter 215 feeds probe count rate information N(Xc, Yc, Zc, ρ, θ, φ) to processing unit 212 (step 401). Position sensor 204 feeds probe position information (Xc, Yc, Zc, ρ, θ, φ) to processing unit 212 (step 402). Probe parameters (such as its physical size, dx, dy, dz) are also input into processing unit 212 (step 403).


Processing unit 212 then finds all the voxels that represent the probe volume in the processing unit memory (step 404), i.e., Xc+dx, Yc+dy, Zc+dz. From the voxels that represent the probe volume in the processing unit memory, processing unit 212 finds those that have a higher count rate value N(Xc+dx, Yc+dy, Zc+dz) than the inputted probe count rate N(Xc, Yc, Zc, ρ, θ, φ) (step 405). Processing unit 212 then changes the higher count rate voxels to that of inputted probe count rate N(Xc, Yc, Zc, ρ, θ, φ) (step 406), and corrects the display image at the higher count rate voxels N(Xc+dx, Yc+dy, Zc+dz) (step 407). The algorithm then repeats itself for the next probe position (step 408).


The resulting graph of the minimizing algorithm of FIG. 19, as applied to the example of FIG. 14, is shown in FIG. 20.


Another algorithm is provided by the invention for estimating the distribution of radiation sources in a control volume, and is described with reference to FIGS. 27A-27G. In this algorithm, it is assumed that the radiation sources comprise dot sources that radiate uniformly in all directions, and that the radiation sources are localized and smoothly distributed in a bounded volume.


Reference is now made to FIGS. 27A and 27B, which illustrate a radiation sensor 600, preferably generally shaped as a tube collimator. Radiation quanta 602 are registered by the radiation sensor 600, as described hereinabove, thereby providing the average number of quanta per unit time. The radiation sensor 600 may be moved around a volume of interest 604. The position of the sensor 600 and its direction (as well as the position of the investigated volume 604) are assumed to be known at any given moment (FIG. 27A).


The tube collimator is preferably provided with a plane circular detector 606 of radiation quanta. The quanta detector 606 is preferably disposed on a rear end 608 of the tube and radiation quanta can reach the detector 606 only through an open front end 610 of the tube (FIG. 27B)


Reference is now made to FIG. 27C, which illustrates a system of coordinates (x, y, z) with the origin O in the center of the radiation sensor 600, the (x, y) plane being the plane of the detector, and the z axis being in the center of the collimator tube. The geometry parameters of the collimator tube—height h and radius ρ—are known.


From the rotational symmetry of the tube, it is clear that having a radiation source Q=Q(x, y, z) with the total intensity I uniformly radiating in all directions, the portion of the intensity registered by the quanta detector 606 of the radiation sensor 600 is determined only by the distance r from Q to the axis of the collimator (axis z) and the distance z from Q to the (x, y) plane. In other words, there is a function Φ(r, z), which is defined only by the collimator parameters ρ and h (corresponding expressions from ρ, h, r and z may be easily written in explicit form), such that the intensity of the radiation spot Q=Q(x, y, z)=Q(r, z) registered by detector 606 is proportional to Φ(r, z) and to the total intensity I of the radiation spot.


Reference is now made to FIG. 27D. It follows from the foregoing discussion, that if instead of one radiation spot there is some radiation distribution I(Q)=I(Q(r, z)) in a volume V, then the radiation intensity, registered by radiation sensor 600, is proportional (with some constant not depending on the radiation distribution and the sensor position) to the following integral:











V




I


(

Q


(

r
,
z

)


)




Φ


(

r
,
z

)









Q






(
1
)







An algorithm for estimating the intensity distribution I(Q) from the values obtained in the measurement scheme of Equation (1) is now discussed. For the sake of simplicity, the first case is discussed with reference to FIG. 27E for a two-dimensional problem, wherein intensities I(Q) are distributed in some 2-dimensional plane. The 3D problem is a direct generalization of the corresponding 2D problem, as is explained hereinbelow.


As seen in FIG. 27E, the radiation sources are distributed in a rectangular region V in a plane. Two systems of coordinates are considered. The first one is the sensor coordinate system (x, y, z) corresponding to the sensor 600. The second one is the radiation source coordinate system (u, v, w) corresponding to the radiation sources plane (u, v).


It is assumed that at each discrete time increment, the position of the origin of (x, y, z) system and the direction of the z-axis unit vector in (u, v, w) coordinates are known. In other words, the position and direction of the moving sensor in the (u, v, w) coordinate system is known, and the (u, v, w) coordinate system is assumed to be motionless.


The radiation sources are considered to be distributed in accordance with the distribution function I(Q)) in some bounded, given rectangle V on the plane (u, v). I(Q)=I(u, v) is the unknown and sought-for radiation (or radiation intensity) distribution function defined in V.


To regularize the problem of estimation of the radiation distribution function I(Q), the function I(Q) will be considered to be given from some finite dimensional space H of functions defined in V. In other words, the function I(Q) itself will not be estimated but rather some finite dimensional approximation of the distribution I(Q).


The simplest approach to finite dimensional approximation is to subdivide the rectangle V into sets of equal rectangular cells and consider the space H of step-functions corresponding to this subdivision (i.e., the space of functions that are constant in the cells of subdivision), as shown in FIG. 27F.


If the subdivision of rectangle V into small rectangles is sufficiently fine, then this step-function approximation is good enough for the estimation of radiation distribution I(Q).


Let each side of rectangle V be divided into n equal parts (FIG. 27F). Then m=n2 is the dimension of the space H of step-functions on the corresponding subdivision.


The space H is naturally isomorphic to the m-dimensional space of n×n matrixes (with its natural scalar product <•, •>).


Let I=(Iij)i,j=1, . . . , n be the unknown element of H that it is desired to estimate. Suppose that element I is measured on K functionals {Φk}k=1 . . . K of the form of the integral (1):

<I,Φk>=Σi,j=1 . . . nIijΦij(k)  (2)

where Φk=(Φij(k))i,j=1, . . . , n, k=1, . . . , K (after approximation of function I(Q) by the corresponding step-function, the integral (1) is transformed to the sum (2)).


Functionals Φk, k=1, . . . , K, correspond to K discrete positions of the sensor (FIG. 27E). Knowing the explicit expressions for functions Φ(r, z) from (1) and knowing for each time moment k, the position of the sensor relative to inspection region V, one can calculate all matrixes Φk=(Φij(k))i, j=1, . . . , n, k=1, . . . , K.


Accordingly the following scheme of measurements are obtained:

ψk=<I,Φk>+εk,k=1, . . . ,K.  (3)


Here ψk are results of measurements of the unknown element I of the space H, and εk are random errors (εk—independent random variables, Εεk=0, k=1, . . . , K).


Let M:H→H the operator in the space H of the form:

M=Σk=1 . . . KΦk{circle around (×)}Φk.  (4)


Then the best non-biased linear estimate Î of the element I is given by the formula:

Î=M−1Ψ,  (5)

where M−1:H→H the inverse operator to the operator M of the form (4), and

Ψ=Σk=1 . . . KψkΦk,  (6)

(where ψk are the results of measurements of the form (3)).


One problem of using estimates (5) (besides computational problems if the dimension m of the space H is very large) is that the operator M: H→H of the form (3) is “bad invertable”. In other words, the estimation problem is “ill-posed”. It means that having a noise εk in the measurements scheme (3), even if the noise is small, may sometimes result in a very large estimation error dist(I, Î).


This means that the estimation problem requires additional regularization. This is a general problem of solving a large set of linear equations. There are several methods for solving such equations. Below is described one of the known methods for solving such equations but numerous other methods are also possible, theses include gradient decent methods such as in (http://www-visl.technion.ac.il/1999/99-03/www/) and other methods that are generally known in the art. Further, it is possible to improve the image reconstruction by taking into account the correlation between measurements as they are done with substantial overlap. Also, in the following description, a regular step function is assumed for the representation of the pixels or voxels, other basis may be used such as wavelet basis, gaussian basis, etc., which may be better suited for some applications.


To obtain regularized estimate ÎR instead of the estimate Î, the eigenvector decomposition of the operator M may be used:


Let φ1, φ2, . . . , φm be eigenvectors of operator M:H→H corresponding to eigenvalues λ1≧λ2≧ . . . ≧λm≧0.


Let R be some natural number, 1<R<m (R is the “regularization parameter”). Let H(R) be the subspace of the space H spanned by the first R eigenvectors φ1, . . . , φR.

H(R)=sp{φk}k=1 . . . R  (7)


Let P(R):H→H(R) be the orthogonal projection on subspace H(R).


The regularized estimate ÎR may be obtained as follows:

Let Φk(R)=P(R)Φk,k=, . . . ,K.
Ψ(R)k=1 . . . KψkΦk(R),  (8)


M(R):H(R)→H(R) the operator of the form:

M(R)k=1 . . . KΦk(R){circle around (×)}Φk(R)  (9)

(operator M(R) is the restriction of the operator M of the form (4). to the subspace H(R) of the form (7)),

then Î(R)=(M(R))−1Ψ(R).  (10)


When the regularization parameter R is properly chosen (so that the eigenvalue λR is not too small), then the estimate (10) becomes stable.


There are several possible approaches to choosing the parameter R. One approach is to leave R as a “program parameter” and to obtain the reasonable value “in experiment”. Another approach is to choose some “optimal” value. This is possible if the covariation operators of the random noise εk in (3) are known, and information about the element I of the space H is known a priori.


The subdivision into a large number of equal rectangles has the disadvantage of making the dimension of the space H too big (especially in the 3D case). If each side of rectangle V is subdivided into n equal parts, then the dimension of the space H will be n2 and the dimension of the matrices used in solving the corresponding estimation equations would be n2×n2=n4 (in the 3D case, n3×n3=n6). It is clear that for large n, this situation may cause serious memory and computation time.


In accordance with a preferred embodiment of the present invention, an irregular subdivision of the rectangle V is used. This irregular approach may significantly decrease the dimension of the problem and facilitate computer calculations.


More specifically, a drawback of the regular subdivision of the investigated region V, discussed hereinabove, is that a lot of cells that actually have no signal may be taken into account (FIG. 27F). It would be much better to have small cells only in regions with high signal and have big cells in regions with low signal.


Reference is now made to FIG. 27G, which illustrates an advantageous irregular cell subdivision, in accordance with a preferred embodiment of the present invention.


In a first stage, regular subdivisions are made in “large” cells, and measurements and estimations are made as described hereinabove. In this manner, the intensity distribution is estimated in the large cells.


In a second stage, the large cells, which have an intensity larger than some threshold, are subdivided into 4 equal subcells (or 8 subcells in the 3D case). A suitable threshold may be obtained by taking the average intensity (of all large cells) minus two (or three) sigmas (standard deviation), for example. Measurements and estimations are made in these subdivisions as described hereinabove.


The act of subdivision and subsequent measurements and estimations are continued until a desired accuracy is reached at some smaller level of subdivision, typically defined by the computational and memory capabilities of the computer being used.


The 3D problem may be treated in the same way as the 2D case, the only difference being that instead of rectangle V, there is a parallelepiped V (FIG. 27D). Accordingly, the cells in each subdivision are also parallelepipeds.


The algorithms described hereinabove may be used for a variety of imaging systems. For example, the algorithms may be used with single radiation detector probe, an array of radiation detector probes, large gamma cameras of various design, such as multi head cameras, general purpose cameras, and automatic white balance (AWB) scanners. The algorithms are suitable for SPECT and planar imaging, and may be used for all types of isotopes of with any type of photon energy.


From the foregoing discussion, the skilled artisan will appreciate that the algorithms described hereinabove may be used to predict the location of the radiation source and the uncertainty region (based on the system measurement errors) in the vicinity of the radiation source. The algorithms also guide the user to perform additional measurements to minimize the uncertainty region according to the requirements of the system operator.


The algorithms thus comprise a feedback system that employs analysis to determine the bounds of an uncertainty region about the radiation source, and which guides medical personnel to conduct additional scans in these uncertainty regions to improve accuracy, reduce error, and hence minimize the bounds of the uncertainty regions.


Continuous sampling with radiation probe 202 may provide localization of a tumor and a physiological radiation activity map of the tumor region. Higher safety and accuracy are gained by a greater number of scans.


Reference is now made to FIG. 21 which illustrates an image reconstruction system 450, constructed and operative in accordance with a preferred embodiment of the present invention. Image reconstruction system 450 produces a combined image 451 made up of the images coming from the medical imaging system 208 with the position of the peak radiation location (and its uncertainty area) from processing unit 212, together with the location of a therapeutic instrument 452, such as a biopsy needle. The combined image 451 allows the physician to better assess the relative position of therapeutic instrument 452 in relation to the anatomical image (from medical imaging system 208) and the position of the radioactive area as inferred by the radiation detection algorithm.


Reference is now made to FIG. 22 which illustrates a flow chart of a radiation map reconstruction algorithm, in accordance with a preferred embodiment of the present invention.


Deconvolution methods are often used in image processing procedures. Examples of such deconvolution methods are described in U.S. Pat. No. 6,166,853 to Sapia et al., the disclosure of which is incorporated herein by reference. (However, it is appreciated that these are just examples and the present invention is not limited to the deconvolution methods mentioned in U.S. Pat. No. 6,166,853)


In typical image acquisition, light (or other electromagnetic wave energy) passes through a finite aperture to an image plane. The acquired image is a result of a convolution of the source object's light with the aperture of the imaging system. A system transfer-function may be generally obtained directly by taking the Fourier transform of the aperture. As is known in the art, the blurring effects due to convolution generally exist in two-dimensions only, i.e., the x-y planes. A point-spread-function (PSF) is an expression used to describe the convolutional blurring in two-dimensions. The PSF physically results from imaging a point source. The Fourier transform of the PSF is the system transfer-function, which is obtained by convolving the system transfer-function with a Dirac-delta function. A point source is the physical equivalent of a Dirac-delta function, and, in the frequency domain, the Dirac-delta function is a unity operator across the spectrum. Therefore, the Fourier transform of the PSF should be the Fourier transform of the aperture. However, the PSF contains noise and blurring due to other effects such as aberrations.


The PSF contribution to the overall blurriness may be diminished or eliminated by deconvolution.


Referring to FIG. 22, in the case of the present invention, the transfer function of the radiation detector may be determined by taking the Fourier transform of the aperture of the detector, and taking into account the noise and blurring due to other effects such as aberrations (step 500). An example of a transfer function may be a normal distribution. Using known mathematical techniques, the deconvolution of the transfer function may be determined (step 502).


The count readings of each spatial location of the detector constitute the sum of radiation counts from all the voxels (or pixels in the case of two-dimensional maps, the term “voxel” being used herein to include both pixels and voxels) within the detector's field of view. At least one voxel, or preferably each such voxel, may be assigned a count value based on the deconvolution of the unique transfer function of the radiation detector in use (step 504). An additional mathematical procedure may treat the various values that each voxel receives due to the multiple readings from viewpoints of different detectors (step 506). This treatment may constitute for example a simple algebraic average, minimum value or reciprocal of averaged reciprocals in order to produce a single value of readings in each voxel. The deconvolution is then used to reconstruct the voxels of the radiation map with diminished or no blurriness (step 508).


The algorithms described herein are applicable not only to the analysis of readings obtained using a directional radioactivity detector, rather they also apply for spatially sensitive (pixelated) radioactivity detectors. In this case, the readings of each pixel are algorithmically treated as described herein like for a directional radioactivity detector. The motivation behind using a spatially sensitive detector is to save on measurement time by receiving readings from a multitude of directions in parallel. This, in essence, creates a number of overlapping low resolution images which can then be processed to form a high resolution image. In addition, the spatially sensitive detector can be scanned to improve even further the resolution using the algorithms described hereinabove.


Thus, the same algorithms that apply for a directional detector apply for the spatially sensitive detector, only now instead of one radiation reading at each position, a large set of desecrate positions are processed in parallel. Each pixel can be seen as a separate detector with an angle of acceptance dictated by the geometry of a segmented collimator employed thereby. Each of the pixels occupies a different position in space and hence can be seen as a new position of a single directional probe by the algorithm described herein. It is also possible, like with the directional detector, to scan the whole set of pixels by scanning the spatially sensitive detector and to acquire a new set of data points from the new position. Once obtaining a low resolution image from each of the pixels of the spatially sensitive detector, a super resolution algorithm can be employed to generate an image of higher resolution. Suitable super resolution algorithms are described in, for example, J. Acoust. Soc. Am., Vol. 77, No. 2, February 1985 Pages 567-572; Yokota and Sato, IEEE Trans. Acoust. Speech Signal Process. (April 1984); Yokota and Sato, Acoustical Imaging (Plenum, New York, 1982, Vol. 12; H. Shekarforoush and R. Chellappa, “Data-Driven Multi-channel Super-resolution with Application to Video Sequences”, Journal of Optical Society of America-A, vol. 16, no. 3, pp. 481-492, 1999; H. Shekarforoush, J. Zerubia and M. Berthod, “Extension of Phase Correlation to Sub-pixel Registration”, IEEE Trans. Image Processing, to appear; P. Cheeseman, B. Kanefsky, R. Kruft, J. Stutz, and R. Hanson, “Super-Resolved Surface Reconstruction From Multiple Images,” NASA Technical Report FIA-94-12, December, 1994; A. M. Tekalp, M. K. Ozkan, and M. I. Sezan, “High-Resolution Image Reconstruction for Lower-Resolution Image Sequences and Space-Varying Image Restoration,” IEEE International Conference on Acoustics, Speech, and Signal Processing (San Francisco, Calif.), pp. III-169-172, Mar. 23-26, 1992, http://www-visl.technion.ac.il/1999/99-03/www/, which are incorporated herein by reference.


EXPERIMENTAL RESULTS

In a series of clinical experiments, some of the basic concepts of the invention have been tested on patients who were pre-injected with a suitable radiopharmaceutical for their particular pathology. Two-dimensional color-coded maps have been constructed based on a scan of a pre-determined lesion area by a hand-held radiation detector with a magnetic position-tracking system. The resulting maps, which represented the radiation count level, were compared to images of conventional gamma camera. The list of radiopharmaceuticals tested includes 18FDG, 99MTc-MDP, 99MTc sodium pertechnetate, 99MTc erythrocytes. Similar radiolabeled patterns were observed in the images produced by the system of the invention and in the images produced by a conventional gamma camera in the following pathologies:



FIGS. 23A and 23B illustrate radiolabeled patterns observed in images produced by the system of the invention and by a conventional gamma camera, respectively, of an autonomous adenoma of a thyroid of a 58 year-old male.



FIGS. 24A and 24B illustrate radiolabeled patterns observed in images produced by the system of the invention and by a conventional gamma camera, respectively, of suspected Paget's disease of a humerus in an 89 year-old female.



FIGS. 25A and 25B illustrate radiolabeled patterns observed in images produced by the system of the invention and by a conventional gamma camera, respectively, of chronic osteomyelitis in a 19 year-old female.



FIGS. 26A and 26B illustrate radiolabeled patterns observed in images produced by the system of the invention and by a conventional gamma camera, respectively, of skeletal metastasis from medulloblastoma in an 18 year-old male.


The following provides a list of known procedures which can take advantage of the system and method of the present invention:


In cancer diagnosis the system and method of the present invention can find uses for screening for cancer and/or directing invasive diagnosis (biopsies) either from outside the body or by way of endoscopic approach. Examples include, but are not limited to, lung cancer biopsy, breast cancer biopsy, prostate cancer biopsy, cervical cancer biopsy, liver cancer biopsy, lymph node cancer biopsy, thyroid cancer biopsy, brain cancer biopsy, bone cancer biopsy, colon cancer biopsy, gastro intestine cancer endoscopy and biopsy, endoscopic screening for vaginal cancer, endoscopic screening for prostate cancer (by way of the rectum), endoscopic screening for ovarian cancer (by way of the vagina), endoscopic screening for cervical cancer (by way of the vagina), endoscopic screening for bladder cancer (by way of the urinary track), endoscopic screening for bile cancer (by way of the gastrointestinal track), screening for lung cancer, screening for breast cancer, screening for melanoma, screening for brain cancer, screening for lymph cancer, screening for kidney cancer, screening for gastro intestinal cancer (from the outside).


In the special case of MRI, the radiation detector can be combined and packaged together with a small RF coil for the transmission and reception or reception only of the MRI signals in a rectal probe configuration for prostate diagnosis and treatment or any other close confinement position such as the vagina, airways, the uper portion of the gastrointestinal track, etc)


Procedures known as directing localized treatment of cancer can also benefit from the system and method of the present invention. Examples include, but are not limited to, intra tumoral chemotherapy, intra tumoral brachytherapy, intra tumoral cryogenic ablation, intra tumoral radio frequency ablation, intra tumoral ultrasound ablation, and intra tumoral laser ablation, in cases of, for example, lung cancer, breast cancer, prostate cancer, cervical cancer, liver cancer, lymph cancer, thyroid cancer, brain cancer, bone cancer, colon cancer (by way of endoscopy through the rectum), gastric cancer (by way of endoscopy through the thorax), thoracic cancer, small intestine cancer (by way of endoscopy through the rectum or, by way of endoscopy through the thorax), bladder cancer, kidney cancer, vaginal cancer and ovarian cancer.


In interventional cardiology the following procedures can take advantage of the present invention wherein the method and system can be used to assess tissue perfusion, tissue viability and blood flow intra operatively during PTCA procedure (balloon alone or in conjunction with the placement of a stent), in cases of cardiogenic shock to asses damage to the heart, following myocardial infarct to asses damage to the heart, in assessing heart failure condition tissue in terms of tissue viability and tissue perfusion, in intra vascular tissue viability and perfusion assessment prior to CABG operation.


The radioactivity detector can be mounted on a catheter that is entered through the blood vessels to the heart to evaluate ischemia from within the heart in order to guide ablation probes or another type of treatment to the appropriate location within the heart. Another application which may benefit from the present invention is the localization of blood clots. For example, a radioactivity detector as described herein can be used to asses and differentiate between new clots and old clots. Thus, for example, the radioactivity detector can be placed on a very small caliber wire such as a guide wire that is used during PTCA in order to image intrabloodvessel clots. Intrabloodvessel clots can be searched for in the aortic arc as clots therein are responsible for about 75% of stroke cases.


Using the method and system of the present invention to assess tissue perfusion, tissue viability and blood flow intra operatively can also be employed in the following: during CABG operation to asses tissue viability, to mark infarct areas, during CABG operations to asses the success of the re vascularization.


The present invention has many other applications in the direction of therapeutics, such as, but not limited to, implanting brachytherapy seeds, ultrasound microwave radio-frequency cryotherapy and localized radiation ablations.


It will be appreciated that many other procedures may also take advantage of the present invention.


It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination.


Although the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims. All publications in printed or electronic form, patents and patent applications mentioned in this specification are herein incorporated in their entirety by reference into the specification, to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated herein by reference. In addition, citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present invention.

Claims
  • 1. A system for calculating a position of a radioactivity emitting source distributed in a system-of-coordinates, the system comprising: (a) a first radioactive emission detector configured for detecting a radioactively emitting source;(b) a surface contour circuit configured for obtaining a contour of a surface associated with said radioactively emitting source, by one or more of (i) receiving raw data from said detector, and generating a surface contour from said raw data; (ii) receiving a surface contour from a 3D imager; and (iii) receiving data related to said detector representing a three dimensional surface which defines a body curvature followed by said detector;(c) a position tracking system being connected to and/or communicating with said radioactive emission detector; and(d) a data processor being designed and configured for receiving and processing data inputs from said position tracking system, from said surface contour circuit and from said first radioactive emission detector and for calculating the distribution of said radioactivity emitting source in the system-of-coordinates using said inputs from said position tracking system, from said surface contour circuit and from said first radioactive emission detector.
  • 2. The system of claim 1, wherein said radioactivity emitting source is selected from the group consisting of a radiopharmaceutically labeled benign tumor, a radiopharmaceutically labeled malignant tumor, a radiopharmaceutically labeled vascular clot, radiopharmaceutically labeled inflammation related components, a radiopharmaceutically labeled abscess and a radiopharmaceutically labeled vascular abnormality.
  • 3. The system of claim 1, wherein said first radioactive emission detector is selected from the group consisting of a narrow angle radioactive emission detector, a wide angle radiation emission detector, a plurality of individual narrow angle radiation emission detectors and a spatially sensitive radioactivity detector.
  • 4. The system of claim 1, wherein said position tracking system is selected from the group consisting of an articulated arm position tracking system, an accelerometer based position tracking system, a potentiometer based position tracking system, a sound wave based position tracking system, a radio frequency based position tracking system, a magnetic field based position tracking system and an optical based position tracking system.
  • 5. The system of claim 1, wherein said data processor is adapted to combine a radiation detector count rate from said radioactive emission detector together with positional information from said position tracking system, and is adapted to form a radiotracer-spread image of a target area including therein said radioactivity emitting source.
  • 6. The system of claim 5, further comprising a memory adapted to store therein said positional information together with said count rate.
  • 7. The system of claim 5, further comprising a display adapted to display thereon said positional information together with said count rate as a pattern of marks corresponding to said positional information and said count rate.
  • 8. The system of claim 5, wherein said data processor is adapted to refine said count rate and said positional information.
  • 9. The system of claim 8, wherein said system-of-coordinates comprises mutually perpendicular linear axes X, Y and Z, and rotations about the X, Y and Z axes, ρ, θ and φ, respectively, and wherein in the system-of-coordinates, said positional information of said detector is defined as (Xc, Yc, Zc, ρ, θ, φ),said detector count rate is defined as N(Xc, Yc, Zc, ρ, θ, φ), anda physical size of said detector is defined as (dx, dy, dz); andfurther, wherein said data processor is adapted to average said count rate and said positional information by finding all volume pixels, called voxels, that represent the detector volume, defined as Xc+dx, Yc+dy, Zc+dz,determining M(Xc+dx, Yc+dy, Zc+dz) which represents the number of times that said count rate and said positional information have been calculated in each voxel, and,calculating average count rate values in each voxel in accordance with: N(Xc+dx, Yc+dy, Zc+dz)=[N(Xc+dx, Yc+dy, Zc+dz)+N(Xc, Yc, Zc, ρ, θ, φ)]/[M(Xc+dx, Yc+dy, Zc+dz)+1].
  • 10. The system of claim 8, wherein said system-of-coordinates comprises mutually perpendicular linear axes X, Y and Z, and rotations about the X, Y and Z axes, ρ, θ and φ, respectively, and wherein in the system-of-coordinates, said positional information of said detector is defined as (Xc, Yc, Zc, ρ, θ, φ), said detector count rate is defined as N(Xc, Yc, Zc, ρ, θ, φ), and a physical size of said detector is defined as (dr, dy, dz); and further, wherein said data processor is adapted to minimize said count rate and said positional information by finding all volume pixels, called voxels, that represent the detector volume, defined as Xc+dx, Yc+dy, Zc+dz, finding those voxels that have a higher count rate value N(Xc+dx, Yc+dy, Zc+dz) than said detector count rate N(Xc, Yc, Zc, ρ, θ, φ) which was input, and changing the higher count rate voxels to that of the inputted detector count rate N(Xc, Yc, Zc, ρ, θ, φ).
  • 11. The system of claim 1, wherein said first radioactive emission detector comprises a collimator having an eccentric opening.
  • 12. The system of claim 1, wherein said first radioactive emission detector comprises a narrow slit collimator configured to allow passage of radiation arriving from a predetermined angular direction.
  • 13. The system of claim 12, wherein said predetermined angular direction is between 1° and 280°.
  • 14. The system of claim 12, wherein said predetermined angular direction is between 1° and 80°.
  • 15. The system of claim 1, wherein said first radioactive emission detector comprises a Compton gamma probe.
  • 16. The system of claim 1, wherein said first radioactive emission detector is configured for receiving at least two collimators; a first collimator having a first bore diameter and a second collimator having a second bore diameter.
  • 17. The system of claim 1, wherein said data processor is designed and configured for calculating the position of said radioactivity emitting source with respect to a surface contour provided by said surface contour circuit.
  • 18. The system of claim 1, wherein said surface contour associated with said radioactively emitting source comprises a contour of at least one of: an internal organ;an anatomical structure; andan external body surface.
  • 19. The system of claim 18, wherein said surface contour circuit, comprises said first radioactive emission detector.
  • 20. The system of claim 18, wherein said surface contour circuit comprises an ultrasound transducer.
  • 21. The system of claim 20, wherein said ultrasound transducer uses at least one of: a) two, cross sectional;b) three, consecutive cross-sectional; andc) three-dimensional,ultrasound imaging techniques.
  • 22. The system of claim 18, wherein said surface 3D imager comprises at least one of: a fluoroscope;a Computed tomographic X-ray (CT); anda Magnetic resonance imaging (MRI).
  • 23. The system of claim 22, wherein said surface contour circuit provides an image of said surface using at least one imaging technique of: i) successive cross-section images from a single direction;ii) successive imaging from two different angles; andiii) successive imaging from three different angles.
  • 24. The system of claim 23, wherein said surface contour circuit provides at least one reconstructed three-dimensional image model.
  • 25. The system of claim 24, wherein said reconstructed three-dimensional image model provides positional information in a three-dimensional space.
  • 26. The system of claim 18, wherein said surface contour associated with said radioactively emitting source comprises a contour of an internal organ.
  • 27. The system of claim 18, wherein said surface contour associated with said radioactively emitting source comprises a contour of an anatomical structure.
  • 28. The system of claim 18, wherein said surface contour associated with said radioactively emitting source comprises a contour of an external body surface.
  • 29. The system of claim 1, wherein said calculating the position of said radioactivity emitting source comprises calculating a single value reading of a voxel value.
  • 30. The system of claim 29, wherein said calculating a single value is applied to each voxel value.
  • 31. The system of claim 30, wherein said calculating comprises using at least one of: an algebraic average;a minimum value; anda reciprocal of averaged reciprocals.
  • 32. The system of claim 30, wherein said calculating is deconvoluted.
  • 33. The system of claim 32, wherein said deconvolution is used to reconstruct the voxels in a radiation map of said radioactivity emitting source.
  • 34. The system of claim 1, wherein said position tracking system is configured to track the position of said radioactive emission detector: on the x, y and z axes; andin rotational angles ρ, θ and φ.
  • 35. The system of claim 1, including a display that communicates with said data processor and provides a visual representation of said surface contour and a volume containing said radioactivity emitting source.
  • 36. The system of claim 35, wherein said surface contour is projected into a first set of coordinates and said volume containing said radioactivity emitting source is projected into a second set of coordinates.
  • 37. The system of claim 36, wherein said data processor is designed and configured for projecting a first array and a second array into a common array comprising a common system-of-coordinates on said display, said first array comprising one of: said first set of coordinates; andsaid second set of coordinates,
  • 38. The system of claim 37, wherein said first array is used as a feedback system to reduce uncertainty regions in said second array.
  • 39. The system of claim 38, wherein said radioactive emission detector is operatively associated with an articulated arm positioning system and said tracking system communicates with said articulated arm positioning system.
  • 40. The system of claim 39, wherein at least one of: said articulated arm positioning system; andsaid tracking system,
  • 41. The system of claim 38, wherein said first radioactive emission detector comprises two flexibly connected mobile radioactive emission detectors and said position tracking system in communication with said two flexibly connected radioactive emission detectors.
  • 42. The system of claim 41, wherein said position tracking system is designed and configured to track the position of said two flexibly connected mobile radioactive emission detectors: on the x, y and z axes; andin rotational angles ρ, θ and φ.
  • 43. The system of claim 38, wherein said first radioactive emission detector is configured to be contained within a catheter.
  • 44. The system of claim 43, wherein said catheter is configured to explore tissue from the group comprising a radiopharmaceutically labeled benign tumor, a radiopharmaceutically labeled malignant tumor, radiopharmaceutically labeled abscess, a radiopharmaceutically labeled vascular clot, radiopharmaceutically labeled inflammation related components, a radiopharmaceutically labeled stenotic vessel, a radiopharmaceutically labeled ischemic tissue and a radiopharmaceutically labeled infarcted tissue.
  • 45. The system of claim 43, wherein said first radioactive emission detector is configured to be detect a radiopharmaceutically labeled vascular clot in a manner that allows substantially accurate determination of the age of said vascular clot.
  • 46. The system of claim 38, wherein said first radioactive emission detector is configured to pass along a guide wire and detect radiopharmaceutically labeled ischemic tissue.
  • 47. The system of claim 46, wherein said system is configured to display said ischemic tissue in a mariner that allows substantially accurate determination of the extent of ischemia in said radiopharmaceutically labeled ischemic tissue.
  • 48. The system of claim 38, wherein said a volume containing said radioactivity emitting source comprises a dynamically moving volume and said data processor is designed and configured for calculating the position of said radioactivity emitting source with respect to said dynamically moving volume.
  • 49. The system of claim 48, wherein movement of said dynamically moving volume is associated with at least one of: respiratory movement;cardiac movement; anddigestive track peristaltic movement.
  • 50. The system of claim 38, wherein said radioactive emission detector is in operative association with a therapeutic instrument configured to administer a therapy to a volume containing said radioactivity emitting source.
  • 51. The system of claim 50, wherein said therapeutic instrument is from the group comprising a biopsy needle; tissue ablation head, laser probe, cardiac catheter, angioplastic catheter, endoscopic probe, ultrasonic probe, fiber optic scope, aspiration tube, laparoscopy probe, thermal probe and suction/irrigation probe.
  • 52. The system of claim 51, wherein said therapeutic instrument is configured to administer a therapy to a tissue from the group of tissues comprising a radiopharmaceutically labeled benign tumor, a radiopharmaceutically labeled malignant tumor, a radiopharmaceutically labeled atheroma, and radiopharmaceutically labeled stenotic tissue.
  • 53. The system of claim 50, wherein said therapeutic instrument includes at least one of: a tissue resecting mechanism;a tissue sampling mechanism; andan aspiration mechanism.
  • 54. The system of claim 50, wherein said position tracking system communicates with said therapeutic instrument.
  • 55. The system of claim 54, wherein said position of said therapeutic instrument is projected into a third set of coordinates.
  • 56. The system of claim 55, wherein said data processor is designed and configured for projecting a first array and a second array into a common array comprising a common system-of-coordinates on said display, said first array comprising one of: said first set of coordinates;said second, set of coordinates; andsaid third set of coordinates,
  • 57. The system of claim 56, wherein said first array is usable as a feedback system to reduce to reduce uncertainty regions in said second array.
  • 58. The system of claim 57, wherein said system is configured to display said surface contour and said volume containing said radioactivity emitting source in a manner that allows substantially precise manipulation of said therapeutic instrument in administering said therapyto said volume.
  • 59. The system of claim 57, wherein said system is configured to display said surface contour and said volume containing said radioactivity emitting source in a manner that allows substantially precise manipulation of said therapeutic instrument in administering said therapy to said volume.
  • 60. The system of claim 57, wherein said first radioactive emission detector is configured for detecting at least two of: i) gamma emission;ii) beta emission; andiii) positron emission.
  • 61. The system of claim 60, wherein said first radioactive emission detector is configured for detecting said gamma emission and said beta emission.
  • 62. The system of claim 60, wherein said first radioactive emission detector is configured for detecting said gamma emission that is associated with said beta emission.
  • 63. The system of claim 60, wherein said first radioactive emission detector is configured for detecting said gamma emission and said positron emission.
  • 64. The system of claim 60, wherein said first radioactive emission detector is configured for detecting said beta emission and said positron emission.
  • 65. The system of claim 60, wherein said first radioactive emission detector is configured for detecting a radiopharmaceutical selected from the group consisting 131I, 67Ga, 99mTc methoxyisobutyl isonitrile, 201TlCl, 18F-fluorodeoxyglucose, 125I-fibrinogen and 111In-octreotide.
  • 66. The system of claim 55, including a second radioactive emission detector configured for additionally receiving data from said volume.
  • 67. The system of claim 66, wherein said position tracking system communicates with said second radioactive emission detector.
  • 68. The system of claim 67, wherein said radioactive emissions from said second radioactive emission detector is projected into a fourth set of coordinates.
  • 69. The system of claim 68, wherein said data processor is designed and configured for projecting a first array and a second array into a common array comprising a common system-of-coordinates on said display, said first array comprising between one and three coordinate sets comprising: said first set of coordinates;said second set of coordinates;said third set of coordinates, andsaid fourth set of coordinates,
  • 70. The system of claim 69, wherein said first array is used as a feedback system to reduce to reduce uncertainty regions in said second array.
  • 71. The system of claim 1, wherein said data processor is designed and configured for setting up a scan of said source with parameters selected so that said scan is focused on said source, in response to said data inputs.
  • 72. A system according to claim 1, wherein said contour of a spatial surface associated with said radioactively emitting source comprises a contour of an internal organ.
  • 73. A method for defining a position of a radioactivity emitting source distributed in a body, in a system-of-coordinates, the method comprising the steps of: (a) scanning the body with a radioactive emission detector being connected to or communicating with a position tracking system;(b) obtaining information associated with a contour of a surface associated with said radioactively emitting source, by one or more of (i) receiving raw data from said detector and generating a surface contour from said raw data, (ii) receiving a surface contour from a 3D imager, and (iii) receiving data related to said detector representing a three dimensional surface which defines a body curvature followed by said detector; and(c) monitoring radioactivity being emitted from the radioactivity emitting source using said contour information, while at the same time, monitoring the position of said radioactive emission detector in the system-of-coordinates, and calculating the position of the radioactivity emitting source in the system-of-coordinates based on said monitoring radioactivity and position.
  • 74. The method for claim 73, wherein the radioactivity emitting source is selected from the group consisting of a radiopharmaceutically labeled benign tumor, a radiopharmaceutically labeled malignant tumor, a radiopharmaceutically labeled vascular clot, radiaphamaceutically labeled inflammation related components, a radiopharmaceutically labeled abscess and a radiopharmaceutically labeled vascular abnormality.
  • 75. The method for claim 73, wherein said radioactive emission detector is selected from the group consisting, of a narrow angle radioactive emission detector, a wide angle radiation emission detector, a plurality of individual narrow angle radiation emission detectors and a spatially sensitive radioactivity detector.
  • 76. The method for claim 73, wherein said position tracking system is selected from the group consisting of an articulated arm position tracking system, an accelerometers based position tracking system, a potentiometers based position tracking system, a sound wave based position tracking system, a radio frequency based position tracking system, a magnetic field based position tracking system and an optical based position tracking system.
  • 77. The method of claim 73, further comprising combining a radiation detector count rate from said radioactive emission detector together with positional information from said position tracking system, and forming a radiotracer-spread image of a target area including therein said radioactivity emitting source.
  • 78. The method of claim 77, further comprising storing said positional information together with said count rate in a memory.
  • 79. The method of claim 77, further comprising displaying said positional information together with said count rate as a pattern of marks corresponding to said positional information and said count rate.
  • 80. The method of claim 77, further comprising refining said count rate and said positional information.
  • 81. The method of claim 80, wherein said system-of-coordinates comprises mutually perpendicular linear axes X, Y and Z, and rotations about the X, Y and Z axes, ρ, θ and φ, respectively, and wherein in the system-of-coordinates, said positional information of said detector is defined as (Xc, Yc, Zc, ρ, θ, φ),said detector count rate is defined as N(Xc, Yc, Zc, ρ, θ, φ), anda physical size of said detector is defined as (dx, dy, dx); andfurther, wherein said refining comprises finding all volume pixels, called voxels, that represent the detector volume, defined as Xc+dx, Yc+dy, Zc+dz,determining M(Xc+dx, Yc+dy, Zc+dz) which represents the number of times that said count rate and said positional information have been calculated in each voxel, andcalculating average count rate values in each voxel in accordance with N(Xc+dx, Yc+dy, Zc+dz)+[N(Xc+dx, Yc+dy, Zc+dz)+N(Xc, Yc, Zc, ρ, θ, φ)]/[(Xc+dx, Yc+dy, Zc+dz)+1].
  • 82. The method of claim 80, wherein said system-of-coordinates comprises mutually perpendicular linear axes X, Y and Z, and rotations about the X, Y and Z axes, ρ, θ and φ, respectively, and wherein in the system-of-coordinates, said positional information of said detector is defined as (Xc, Yc, Zc, ρ, θ, φ), said detector count rate is defined as N(Xc, Yc, Zc, ρ, θ, φ), and a physical size of said detector is defined as (dx, dy, d); and further, wherein said refining comprises finding all volume pixels, called voxels, that represent the detector volume, defined as Xc+dx, Yc+dy, Zc+dz, finding those voxels that have a higher count rate value N(Xc+dx, Yc+dy, Zc+dz) than said detector count rate N(Xc, Yc, Zc, ρ, θ, φ) which was input, and changing the higher count rate voxels to that of the inputted detector count rate N(Xc, Yc, Zc, ρ, θ, φ).
  • 83. The method of claim 73, comprising: reconstructing an image of said source; andrepeating said providing and said monitoring based on said image, to more specifically obtain radiation signals from said source.
  • 84. A method according to claim 73, further comprising: (d) moving said radioactive emission detector in response to said monitoring.
  • 85. A method according to claim 84, further comprising: (e) obtaining information associated with a portion of said contour after said (d).
  • 86. A method according to claim 73, further comprising: (d) moving said radioactive emission detector in response to said obtaining information associated with a contour of a physical surface associated with said radioactively emitting source.
  • 87. A method according to claim 86, wherein said contour of a physical surface comprises a contour of an internal organ.
  • 88. A system for calculating a position of a radioactivity emitting source in a first system-of-coordinates and further of projecting the position of the radioactivity emitting source onto a second system-of-coordinates, the system comprising: (a) a radioactive emission detector;(b) a surface contour circuit configured for obtaining information associated with a contour of a surface associated with said radioactively emitting source, by one or more of (1) receiving raw data from said detector and generating a surface contour from said raw data, (ii) receiving a surface contour from a 3D imager, and (iii) receiving data related to said detector representing a three dimensional surface which defines a body curvature followed by said detector;(c) a position tracking system being connected to and/or communicating with said radioactive emission detector; and(d) a data processor being configured for: (i) receiving data inputs from said position tracking system, from said contour input and from said radioactive emission detector;(ii) calculating the position of the radioactivity emitting source in the first system-of-coordinates using said received data inputs; and(iii) projecting the position of the radioactivity emitting source onto the second system-of-coordinates.
  • 89. The system of claim 88, wherein the radioactivity emitting source is selected from the group consisting of a radiopharmaceutically labeled benign tumor, a radiopharmaceutically labeled malignant tumor, a radiopharmaceutically labeled vascular clot, radiopharmaceutically labeled inflammation related components, a radiopharmaceutically labeled abscess and a radiopharmaceutically labeled vascular abnormality.
  • 90. The system of claim 88, wherein said radioactive emission detector is selected from the group consisting of a narrow angle radioactive emission detector, a wide angle radiation emission detector, a plurality of individual narrow angle radiation emission detectors and a spatially sensitive radioactivity detector.
  • 91. The system of claim 88, wherein said position tracking system is selected from the group consisting of an articulated arm position tracking system, an accelerometers based position tracking system, a potentiometers based position tracking system, a sound wave based position tracking system, a radio frequency based position tracking system, a magnetic field based position tracking system and an optical based position tracking system.
  • 92. The system of claim 88, wherein said data processor is adapted to combine a radiation detector count rate from said radioactive emission detector together with positional information from said position tracking system, and is adapted to form a radiotracer-spread image of a target area including therein said radioactivity emitting source.
  • 93. The system of claim 92, further comprising a memory adapted to store therein said positional information together with said count rate.
  • 94. The system of claim 92, further comprising a display adapted to display thereon said positional information together with said count rate as a pattern of marks corresponding to said positional information and said count rate.
  • 95. The system of claim 92, wherein said data processor is adapted to refine said count rate and said positional information.
  • 96. The system of claim 95, wherein said system-of-coordinates comprises mutually perpendicular linear axes X, Y and Z, and rotations about the X, Y and Z axes, ρ, θ and φ, respectively, and wherein in the system-of-coordinates, said positional information of said detector is defined as (Xc, Yc, Zc, ρ, θ, φ), said detector count rate is defined as N(Xc, Yc, Zc, ρ, θ, φ), and a physical size of said detector is defined as (dx, dy, dz); and further, wherein said data processor is adapted to average said count rate and said positional information by finding all volume pixels, called voxels, that represent the detector volume, defined as Xc+dx, Yc+dy, Zc+dz, determining M(Xc+dx, Yc+dy, Zc+dz) which represents the number of times that said count rate and said positional information have been calculated in each voxel, and calculating average count rate values in each voxel in accordance with N(Xc+dx, Yc+dy, Zc+dz)=[N(Xc+dx, Yc+dy, Zc+dz)+N(Xc, Yc, Zcúρ, θ, φ)]/[M(Xc+dx, Yc+dy, Zc+dz)+1].
  • 97. The system of claim 95, wherein said system-of-coordinates comprises mutually perpendicular linear axes X, Y and Z, and rotations about the X, Y and Z axes, ρ, θ and φ, respectively, and wherein in the system-of-coordinates, said positional information of said detector is defined as (Xc, Yc, Zc, ρ, θ, φ), said detector count rate is defined as N(Xc, Yc, Zc, ρ, θ, φ), and a physical size of said detector is defined as (dx, dy, dz); and further, wherein said data processor is adapted to minimize said count rate and said positional information by finding all volume pixels, called voxels, that represent the detector volume, defined as Xc+dx, Yc+dy, Zc+dz, finding those voxels that have a higher count rate value N(Xc+dx, Yc+dy, Zc+dz) than said detector count rate N(Xc, Yc, Zc, ρ, θ, φ) which was input, and changing the higher count rate voxels to that of the inputted detector count rate N(Xc, Yc, Zc, ρ, θ, φ).
  • 98. A system according to claim 88, wherein said contour of a physical surface associated with said radioactively emitting source comprises a contour of an internal organ.
  • 99. A method for calculating a position of a radioactivity emitting source distributed in a body, in a first system-of-coordinates and for projecting the position of the radioactivity emitting source onto a second system-of-coordinates, the method comprising the steps of: (a) scanning the body with a radioactive emission detector being connected to or communicating with a position tracking system (b) obtaining information associated with a contour of a surface associated with said radioactively emitting source, said information obtained by one or more of (i) receiving raw data from said detector and generating a surface contour from said raw data, (ii) receiving a surface contour from a 3D imager, and (iii) receiving data related to said detector representing a three dimensional surface which defines a body curvature followed by said detector; and(c) monitoring radioactivity being emitted from the radioactivity emitting source using said contour, while at the same time, monitoring the position of said radioactive emission detector in the first system-of-coordinates, calculating the position of the radioactivity emitting source in the first system-of-coordinates based on said monitoring radioactivity and position, and projecting the position of the radioactivity emitting source onto the second system-of-coordinates.
  • 100. The method for claim 99, wherein the radioactivity emitting source is selected from the group consisting of a radiopharmaceutically labeled benign tumor, a radiopharmaceutically labeled malignant tumor, a radiopharmaceutically labeled vascular clot, radiopharmaceutically labeled inflammation related components, a radiopharmaceutically labeled abscess and a radiopharmaceutically labeled vascular abnormality.
  • 101. The method for claim 99, wherein said radioactive emission detector is selected from the group consisting of a narrow angle radioactive emission detector, a wide angle radiation emission detector, a plurality of individual narrow angle radiation emission detectors and a spatially sensitive radioactivity detector.
  • 102. The method, for claim 99, wherein said position tracking system is selected from the group consisting of an articulated arm position tracking system, an accelerometers based position tracking system, a potentiometers based position tracking system, a sound wave based position tracking system, a radio frequency based position tracking system, a magnetic field based position tracking system and an optical based position tracking system.
  • 103. A method according to claim 99, further comprising: (d) moving said radioactive emission detector in response to said monitoring.
  • 104. A method according to claim 103, further comprising: (e) obtaining information associated with a portion of said contour after said (d).
  • 105. A method according to claim 99, further comprising: (d) moving said radioactive emission detector in response to said obtaining information associated with a contour of a physical surface associated with said radioactively emitting source.
  • 106. A method according to claim 105, wherein said contour of a physical surface comprises a contour of an internal organ.
  • 107. A system for generating a two- or three-dimensional image of a radioactivity emitting source distributed in a body, the system comprising: (a) a radioactive emission detector;(b) a surface contour circuit configured for obtaining information associated with a contour of a surface associated with said radioactively emitting source, by one or more of (i) receiving raw data from said detector and generating a surface contour from said raw data, (ii) receiving a surface contour from a 3D imager, and (iii) receiving data related to said detector representing a three dimensional surface which defines a body curvature followed by said detector;(c) a position tracking system being connected to and/or communicating with said radioactive emission detector; and(d) a data processor being configured for receiving data inputs from said position tracking system, from said surface contour circuit and from said radioactive emission detector and for generating the two- or three-dimensional image of the radioactivity emitting source using said received inputs.
  • 108. The system of claim 107, wherein said data processor is adapted to combine a radiation detector count rate from said radioactive emission detector together with positional information from said position tracking system, and is adapted to form a radiotracer-spread image of a target area including therein said radioactivity emitting source.
  • 109. The system of claim 108, further comprising a memory adapted to store therein said positional information together with said count rate.
  • 110. The system of claim 108, further comprising a display adapted to display thereon said positional information together with said count rate as a pattern of marks corresponding to said positional information and said count rate.
  • 111. The system of claim 108, wherein said data processor is adapted to refine said count rate and said positional information.
  • 112. The system of claim 111, wherein said system-of-coordinates comprises mutually perpendicular linear axes X, Y and Z, and rotations about the X, Y and Z axes, ρ, θ and φ, respectively, and wherein in the system-of-coordinates, said positional information of said detector is defined (Xc, Yc, Zc, ρ, θ, φ), said detector count rate is defined as N(Xc, Yc, Zc, ρ, θ, φ), and a physical size of said detector is defined as (dx, dy, dz); and further, wherein said data processor is adapted to average said count rate and said positional information by finding all volume pixels, called voxels, that represent the detector volume, defined as Xc+dx, Yc+dy, Zc+dz, determining M(Xc+dx, Yc+dy, Zc+dz) which represents the number of times that said count rate and said positional information have been calculated in each voxel, and calculating average count rate values in each voxel in accordance with N(Xc+dx, Yc+dy, Zc+dz)=[N(Xc+dx, Yc+dy, Zc+dz)+N(Xc, Yc, Zc, ρ, θ, φ)]/[(Xc+dx, Yc+dy, Zc+dz)+1].
  • 113. The system of claim 111, wherein said system-of-coordinates comprises mutually perpendicular linear axes X, Y and Z, and rotations about the X, Y and Z axes, ρ, θ and φ, respectively, and wherein in the system-of-coordinates, said positional information of said detector is defined as (Xc, Yc, Zc, ρ, θ, φ), said detector count rate is defined as N(Xc, Yc, Zc, ρ, θ, φ), and a physical size of said detector is defined as (dx, dy, dz); and further, wherein said data processor is adapted to minimize said count rate and said positional information by finding all volume pixels, called voxels, that represent the detector volume, defined as Xc+dx, Yc+dy, Zc+dz, finding those voxels that have a higher count rate value N(Xc+dx, Yc+dy, Zc+dz) than said detector count rate N(Xc, Yc, Zc, ρ, θ, φ) which was input, and changing the higher count rate voxels to that of the inputted detector count rate N(Xc, Yc, Zc, ρ, θ, φ).
  • 114. A system according to claim 107, wherein said contour of a physical surface associated with said radioactively emitting source comprises a contour of an internal organ.
  • 115. A method of generating a two- or three-dimensional image of a radioactivity emitting source distributed in a body, the system comprising: (a) scanning the body with a radioactive emission detector;(b) obtaining information associated with a contour of a surface associated with said radioactively emitting source, said information obtained by one or more of (i) receiving raw data from said detector and extracting generating a surface contour from said raw data, (ii) receiving a surface contour from a all imager, and (iii) receiving data related to said detector representing a three dimensional surface which defines a body curvature followed by said detector;(c) using a position tracking system being connected to and/or communicating with said radioactive emission detector for calculating a position in a three-dimensional system of coordinates of said radioactive emission detector; and(d) data processing inputs from said position tracking system, from said contour circuit and from said radioactive emission detector for generating the two- or three-dimensional image of the radioactivity emitting source.
  • 116. The method of claim 115, further comprising combining a radiation detector count rate from said radioactive emission detector together with positional information said position tracking system, and forming a radiotracer-spread image of a target area including therein said radioactivity emitting source.
  • 117. The method of claim 116, further comprising storing said positional information together with said count rate in a memory.
  • 118. The method of claim 116, further comprising displaying said positional information together with said count rate as a pattern of marks corresponding to said positional information and said count rate.
  • 119. The method of claim 116, further comprising refining said count rate and said positional information.
  • 120. The method of claim 119, wherein said system-of-coordinates comprises mutually perpendicular linear axes X, Y and Z, and rotations about the X, Y and Z axes, ρ, θ and φ, respectively, and wherein in the system-of-coordinates, said positional information of said detector is defined as (Xc, Yc, Zc, ρ, θ, φ),said detector count rate is defined as N(Xc, Yc, Zc, ρ, θ, φ), anda physical size of said detector is defined as (dr, dy, dz); andfurther, wherein said refining comprises finding all volume pixels, called voxels, that represent the detector volume, defined as Xc+dx, YC+dy, Zc+dz,determining M(Xc+dx, Yc+dy, Zc+dz) which represents the number of times that said count rate and said positional information have been calculated in each voxel, andcalculating average count rate values in each voxel in accordance with N(Xc+dx, Yc+dy, Zc+dz)=[N(Xc+dx, Yc+dy, Zc+dz)+N(Xc, Yc, Zc, ρ, θ, φ)]/[M(Xc+dx, Yc+dy, Zc+dz)+1].
  • 121. The method of claim 119, wherein said system-of-coordinates comprises mutually perpendicular linear axes X, Y and Z, and rotations about the X, Y and Z axes, ρ, θ and φ, respectively, and wherein in the system-of-coordinates, said positional information of said detector is defined as (Xc, Yc, Zc, ρ, θ, φ), said detector count rate is defined as N(Xc, Yc, Zc, ρ, θ, φ), and a physical size of said detector is defined as (dx, dy, dz); and further, wherein said refining comprises finding all volume pixels, called voxels, that represent the detector volume, defined as Xc+dx, Yc+dy, Zc+dz, finding those voxels that have a higher crate value N(Xc+dx, Yc+dy, Zc+dz) than said detector count rate N(Xc, Yc, Zc, ρ, θ, φ) which was input, and changing the higher count rate voxels to that of the inputted detector count rate N(Xc, Yc, Zc, ρ, θ, φ).
  • 122. A method according to claim 115, further comprising: (e) moving said radioactive emission detector in response to said data processing.
  • 123. A method according to claim 122, further comprising: (f) obtaining information associated with a portion of said contour after said (e).
  • 124. A method according to claim 115, further comprising: (e) moving said radioactive emission detector in response to said obtaining information associated with a contour of a physical surface associated with said radioactively emitting source.
  • 125. A method according to claim 124, wherein said contour of a physical surface comprises a contour of an internal organ.
  • 126. A system for calculating a position of a radioactivity emitting source in a first system-of-coordinates and further of projecting the position of the radioactivity emitting source onto a second system-of-coordinates, the system comprising: (a) at least two radioactive emission detectors;(b) a surface contour circuit configured for obtaining information associated with a contour of a surface associated with said radioactively emitting source, by one or more of (i) receiving raw data from at least one of said detectors and generating a surface contour from said raw data, (ii) receiving a surface contour from a 3D imager, and (iii) receiving data related to said at least one detector representing a three dimensional surface which defines a body curvature followed by said at least one detector;(c) a position tracking system being connected to and/or communicating with said at least two radioactive emission detectors; and(d) a data processor being configured for: (i) receiving data inputs from said position tracking system, from said contour circuit and from said at least two radioactive emission detectors;(ii) calculating the position of the radioactivity emitting source in the first system-of-coordinates using said received inputs; and(iii) projecting the position of the radioactivity emitting source onto the second system-of-coordinates.
  • 127. The system of claim 126, wherein said at least two radioactive emission detectors are physically connected therebetween via a flexible connector.
  • 128. The system of claim 126, wherein said data processor is adapted to combine a radiation detector count rate from said at least two radioactive emission detectors together with positional information from said position tracking system, and is adapted to form a radiotracer-spread image of a target area including therein said radioactivity emitting source.
  • 129. The system of claim 128, further comprising a memory adapted to store therein said positional information together with said count rate.
  • 130. The system of claim 128, further comprising a display adapted to display thereon said positional information together with said count rate as a pattern of marks corresponding to said positional information and said count rate.
  • 131. The system of claim 128, wherein said data processor is adapted to refine said count rate and said positional information.
  • 132. The system of claim 131, wherein said system-of-coordinates comprises mutually perpendicular linear axes X, Y and Z, and rotations about the X, Y and Z axes, ρ, θ and φ, respectively, and wherein in the system-of-coordinates, said positional information of at least one of said at least two detectors is defined as (Xc, Yc, Zc, ρ, θ, φ), said detector count rate is defined as N(Xc, Yc, Zc, ρ, θ, φ), and a physical size of said at least one of said at least two detectors is defined as (dx, dy, dz); and further, wherein said data processor is adapted to average said count rate and said positional information by finding all volume pixels, called voxels, that represent the detector volume, defined as Xc+dx, Yc+dy, Zc+dz, determining M(Xc+dx, Yc+dy, Zc+dz) which represents the number of times that said count rate and said positional information have been calculated in each voxel, and calculating average count rate values in each voxel in accordance with N(Xc+dx, Yc+dy, Zc+dz)=[N(Xc+dx, Yc+dy, Zc+dz)+N(Xc, Yc, Ze, ρ, θ, φ)]/[M(Xc+dx, Yc+dy, Zc+dz)+1].
  • 133. The system of claim 131, wherein said system-of-coordinates comprises mutually perpendicular linear axes X, Y and Z, and rotations about the X, Y and Z axes, ρ, θ and φ, respectively, and wherein in the system-of-coordinates, said positional information of at least one of said at least two detectors is defined as (Xc, Yc, Zc, ρ, θ, φ), said detector count rate is defined as N(Xc, Yc, Zc, ρ, θ, φ), and a physical size of said at least one of said at least two detectors is defined as (dx, dy, dz); and further, wherein said data processor is adapted to minimize said count rate and said positional information by finding all volume pixels, called voxels, that represent the detector volume, defined as Xc+dx, Yc+dy, Zc+dz, finding those voxels that have a higher count rate value Xc+dx, Yc+dy, Zc+dz) than said detector count rate N(Xc, Yc, Zc, ρ, θ, φ) which was input, and changing the higher count rate voxels to that of the inputted detector count rate N(Xc, Yc, Zc, ρ, θ, φ).
  • 134. A system according to claim 126, wherein said contour of a physical surface associated with said radioactively emitting source comprises a contour of an internal organ.
  • 135. A method for calculating a position of a radioactivity emitting source distributed in a body, in a first system-of-coordinates and for projecting the position of the radioactivity emitting source onto a second system-of-coordinates, the method comprising the steps of: (a) scanning the body with at least one radioactive emission detector being connected to or communicating with a position tracking system;(b) obtaining information associated with a contour of a surface associated with said radioactively emitting source, said information obtained by one or more of (i) receiving raw data from said detector and generating a surface contour from said raw data, (ii) receiving a surface contour from a 3D imager, and (iii) receiving data related to said detector representing a three dimensional surface which defines a body curvature followed by said detector; and(c) monitoring radioactivity being emitted from the radioactivity emitting source using said contour, while at the same time, monitoring the position of said at least one radioactive emission detector in the first system-of-coordinates, and calculating the position of the radioactivity emitting source in the first system-of-coordinates based on said monitoring radioactivity and position, and projecting the position of the radioactivity emitting source onto a second system-of-coordinates.
  • 136. The method of claim 135, further comprising combining a radiation detector count rate from said at least one radioactive emission detector together with positional information from said position tracking system, and forming a radiotracer-spread image of a target area including therein said radioactivity emitting source.
  • 137. The method of claim 136, further comprising storing said positional information together with said count rate in a memory.
  • 138. The method of claim 136, further comprising displaying said positional information together with said count rate as a pattern of marks corresponding to said positional information and said count rate.
  • 139. The method of claim 136, further comprising refining said count rate and said positional information.
  • 140. The method of claim 139, wherein said system-of-coordinates comprises mutually perpendicular linear axes X, Y and Z, and rotations about the X, Y and Z axes, ρ, θ and φ, respectively, and wherein in the system-of-coordinates, said positional information of said at least one detector is defined as (Xc, Yc, Zc, ρ, θ, φ),said detector count rate is defined as N(Xc, Yc, Zc, ρ, θ, φ), anda physical size of said at least one detector is defined as (dx, dy, dz); andfurther, wherein said refining comprises finding all volume pixels, called voxels, that represent the detector volume, defined as Xc+dx, Yc+dy, Zc+dz,determining M(Xc+dx, Yc+dy, Zc+dz) which represents the number of times that said count rate and said positional information have been calculated in each voxel, and,calculating average count rate values in each voxel in accordance with N(Xc+dx, Yc+dy, Zc+dz)=[N(Xc+dx, Yc+dy, Zc+dz)+N(Xc, Yc, Zc, ρ, θ, φ)]/[M(Xc+dx, Yc+dy, Zc+dz)+1].
  • 141. The method of claim 139, wherein said system-of-coordinates comprises mutually perpendicular linear axes X, Y and Z, and rotations about the X, Y and Z axes, ρ, θ and φ, respectively, and wherein in the system-of-coordinates, said positional information of said at least one detector is defined as (Xc, Yc, Zc, ρ, θ, φ), said detector count rate is defined as N(Xc, Yc, Zc, ρ, θ, φ), and a physical size of said at least one detector is defined as (dx, dy, dz); and further, wherein said refining comprises finding all volume pixels, called voxels, that represent the detector volume, defined as Xc+dx, Yc+dy, Zc+dz, finding those voxels that have a higher count rate value N(Xc+dx, Yc+dy, Zc-dz) than said detector count rate N(Xc, Yc, Zc, ρ, θ, φ) which was input, and changing the higher count rate voxels to that of the inputted detector count rate N(Xc, Yc, Zc, ρ, θ, φ).
  • 142. A method according to claim 135, further comprising: (d) moving said radioactive emission detector in response to said monitoring.
  • 143. A method according to claim 142, further comprising: (e) obtaining information associated with a portion of said contour after said (d).
  • 144. A method according to claim 135, further comprising: (d) moving said radioactive emission detector in response to said obtaining information associated with a contour of a physical surface associated with said radioactively emitting source.
  • 145. A method according to claim 144, wherein said contour of a physical surface comprises a contour of an internal organ.
  • 146. A method for radiation map reconstruction, the method comprising: (a) determining a transfer function of a radiation detector;(b) determining a deconvolution of said transfer function;(c) obtaining information associated with a contour of a surface associated with a radioactively emitting source distributed in a body, said information obtained by one or more of (i) receiving raw data from said detector and generating a surface contour from said raw data, (ii) receiving a surface contour from a 3D imager, and (iii) receiving data related to said detector representing a three dimensional surface which defines a body curvature followed by said detector;(d) assigning a count value based on said deconvolution to at least one voxel within a field of view of said radiation detector; and(e) using said deconvolution and said contour to reconstruct said at least one voxel.
  • 147. The method of claim 146, wherein said using said deconvolution comprises at least diminishing blurriness of said at least one voxel.
  • 148. The method of claim 146, further comprising mathematically treating multiple readings from viewpoints of different detectors that said at least one voxel receives.
  • 149. The method of claim 148, wherein said mathematically treating comprises determining a value used in place of a single value of reading in said at least one voxel.
  • 150. The method of claim 149, wherein said determining a value comprises determining at least one of an algebraic average, a minimum value, and a reciprocal of averaged reciprocals of readings in said at least one voxel.
  • 151. A system for calculating a position of a body component and a position of a radiopharmaceutical uptaking portion distributed in the body component within a subject, the system comprising: (a) a two-dimensional imager being connected to and/or communicating with a first position tracking system for calculating the position of the body component in a first system-of-coordinates;(b) a surface contour circuit configured for obtaining information associated with a contour of a surface associated with said radioactively emitting source;a radioactive emission detector being connected to and/or communicating with a second position system for tracking a position of the radiopharmaceutical uptaking portion of the body component in a second system-of-coordinates; and(d) at least one data processor being configured for receiving data inputs from said two-dimensional imager, said first position tracking system, said contour circuit and said radioactive emission detector and said second position tracking system and calculating the position of the body component and the position of the radiopharmaceutical uptaking portion of the body component in a common system-of-coordinates using said received inputs, wherein the surface contour circuit is configured to obtain said contour by one or more of (i) receiving raw data from said detector and generating a surface contour from said raw data, (ii) receiving a surface contour from a 3D imager, and (iii) receiving data related to said detector representing a three dimensional surface which defines a body curvature followed by said detector.
  • 152. A system according to claim 151, wherein said contour of a physical surface associated with said radioactively emitting source comprises a contour of an internal organ.
  • 153. A method for calculating a position of a body component and a position of a radiopharmaceutical uptaking portion distributed in the body component within a subject, the method comprising the steps of: (a) scanning the body with a two-dimensional imager being connected to and/or communicating with a first position tracking system and calculating the position of the body component in a first system-of-coordinates;(b) obtaining information associated with a contour of a physical surface associated with said radioactively emitting source;(c) providing a radioactive emission detector being connected to and/or communicating with a second position tracking system and tracking a position of the radiopharmaceutical uptaking portion of the body component in a second system-of-coordinates; and(d) receiving data inputs from said two-dimensional imager, said first position tracking system, said contour circuit, said radioactive emission detector and said second position tracking system and calculating the position of the body component and the position of the radiopharmaceutical uptaking portion of the body component in a common system-of-coordinates using said received inputs, wherein said information associated with a contour of a physical surface is obtained by one or more of (i) receiving raw data from said detector and generating a surface contour from said raw data, (ii) receiving a surface contour from a 3D imager, and (iii) receiving data related to said detector representing a three dimensional surface which defines a body curvature followed by said detector.
  • 154. A method according to claim 153, further comprising: (e) moving said radioactive emission detector in response to said calculating.
  • 155. A method according to claim 154, further comprising: (f) obtaining information associated with a portion of said contour after said (e).
  • 156. A system for calculating a position of a radioactivity emitting source distributed in a system-of-coordinates, the system comprising: (a) a first radioactive emission detector configured for detecting a radioactively emitting source;(b) a surface contour circuit configured for obtaining a contour of a surface associated with said radioactively emitting source, by one or more of (i) receiving raw data from said detector and generating a surface contour from said raw data, (ii) receiving a surface contour from a 3D imager, and (iii) receiving data related to said detector representing a three dimensional surface which defines a body curvature followed by said detector;(c) a position tracking system being connected to and/or communicating with said radioactive emission detector; and(d) a data processor being designed and configured for receiving and processing data inputs from said position tracking system, from said surface contour circuit and from said first radioactive emission detector and for calculating the position of said radioactivity emitting source in the system-of-coordinates using said inputs from said position tracking system, from said surface contour circuit and from said first radioactive emission detector,wherein said surface contour associated with said radioactively emitting source comprises a contour of at least one of: an internal organ;an anatomical, structure; andan external body surface.
  • 157. A method according to claim 153, further comprising: (e) moving said radioactive emission detector in response to said obtaining information associated with a contour of a physical surface associated with said radioactively emitting source.
  • 158. A method according to claim 157, wherein said contour of a physical surface comprises a contour of an internal organ.
RELATED APPLICATIONS

This application is a National Phase of PCT Patent Application No. PCT/IL01/00638 having International filing date of Jul. 11, 2001, which claims the benefit of priority under 35 USC §119(e) of U.S. Provisional Patent Application No. 60/286,044 filed on Apr. 25, 2001. PCT Patent Application No. PCT/IL01/00638 is also a Continuation-in-Part (CIP) of U.S. patent application Ser. No. 09/727,464 filed on Dec. 4, 2000, now U.S. Pat. No. 7,826,889, which is a Continuation-in-Part (CIP) of U.S. patent application Ser. No. 09/714,164 filed on Nov. 17, 2000, now abandoned, which is a Continuation-in-Part (CIP) of U.S. patent application Ser. No. 09/641,973 filed on Aug. 21, 2000, now U.S. Pat. No. 8,489,176.

PCT Information
Filing Document Filing Date Country Kind 371c Date
PCT/IL01/00638 7/11/2001 WO 00 2/4/2003
Publishing Document Publishing Date Country Kind
WO02/16965 2/28/2002 WO A
US Referenced Citations (731)
Number Name Date Kind
630611 Knapp et al. Aug 1899 A
2776377 Anger Jan 1957 A
3340866 Nöller Sep 1967 A
3446965 Ogier et al. May 1969 A
3535085 Shumate et al. Oct 1970 A
3684887 Hugonin Aug 1972 A
3690309 Pluzhnikov et al. Sep 1972 A
3719183 Schwartz Mar 1973 A
3739279 Hollis Jun 1973 A
3971362 Pope et al. Jul 1976 A
3978337 Nickles et al. Aug 1976 A
3988585 O'Neill et al. Oct 1976 A
4000502 Butler et al. Dec 1976 A
4015592 Bradley-Moore Apr 1977 A
4055765 Gerber et al. Oct 1977 A
4061919 Miller et al. Dec 1977 A
4095107 Genna et al. Jun 1978 A
4165462 Macovski et al. Aug 1979 A
4181856 Bone Jan 1980 A
4278077 Mizumoto Jul 1981 A
4289969 Cooperstein et al. Sep 1981 A
4291708 Frei et al. Sep 1981 A
4296785 Vitello et al. Oct 1981 A
4302675 Wake et al. Nov 1981 A
4364377 Smith Dec 1982 A
4383327 Kruger May 1983 A
4476381 Rubin Oct 1984 A
4503331 Kovacs, Jr. et al. Mar 1985 A
4521688 Yin Jun 1985 A
H12 Bennett et al. Jan 1986 H
4580054 Shimoni Apr 1986 A
4595014 Barrett et al. Jun 1986 A
4674107 Urban et al. Jun 1987 A
4679142 Lee Jul 1987 A
4689041 Corday et al. Aug 1987 A
4689621 Kleinberg Aug 1987 A
4709382 Sones Nov 1987 A
4710624 Alvarez et al. Dec 1987 A
4731536 Rische et al. Mar 1988 A
4773430 Porath Sep 1988 A
4782840 Martin, Jr. et al. Nov 1988 A
4791934 Brunnett Dec 1988 A
4801803 Denen et al. Jan 1989 A
4828841 Porter et al. May 1989 A
4834112 Machek et al. May 1989 A
4844067 Ikada et al. Jul 1989 A
4844076 Lesho et al. Jul 1989 A
4853546 Abe et al. Aug 1989 A
4854324 Hirschman et al. Aug 1989 A
4854330 Evans, III et al. Aug 1989 A
4893013 Denen et al. Jan 1990 A
4893322 Hellmick et al. Jan 1990 A
4919146 Rhinehart et al. Apr 1990 A
4924486 Weber et al. May 1990 A
4928250 Greenberg et al. May 1990 A
4929832 Ledley May 1990 A
4938230 Machek et al. Jul 1990 A
4951653 Fry et al. Aug 1990 A
4959547 Carroll et al. Sep 1990 A
4970391 Uber, III Nov 1990 A
4995396 Inaba et al. Feb 1991 A
5014708 Hayashi et al. May 1991 A
5018182 Cowan et al. May 1991 A
5032729 Charpak Jul 1991 A
5033998 Corday et al. Jul 1991 A
5039863 Matsuno et al. Aug 1991 A
5042056 Hellmick et al. Aug 1991 A
5070877 Mohiuddin et al. Dec 1991 A
5070878 Denen Dec 1991 A
5088492 Takayama et al. Feb 1992 A
5115137 Andersson-Engels et al. May 1992 A
5119818 Carroll et al. Jun 1992 A
5132542 Bassalleck et al. Jul 1992 A
5145163 Cowan et al. Sep 1992 A
5151598 Denen Sep 1992 A
5170055 Carroll et al. Dec 1992 A
5170439 Zeng et al. Dec 1992 A
5170789 Narayan Dec 1992 A
5196796 Misic et al. Mar 1993 A
5210421 Gullberg et al. May 1993 A
5243988 Sieben et al. Sep 1993 A
5246005 Carroll et al. Sep 1993 A
5249124 DeVito Sep 1993 A
5252830 Weinberg Oct 1993 A
5254101 Trombley, III Oct 1993 A
5258717 Misic et al. Nov 1993 A
5263077 Cowan et al. Nov 1993 A
5279607 Schentag et al. Jan 1994 A
5284147 Hanaoka et al. Feb 1994 A
5299253 Wessels Mar 1994 A
5304165 Haber et al. Apr 1994 A
5307808 Dumoulin et al. May 1994 A
5307814 Kressel et al. May 1994 A
5309959 Shaw et al. May 1994 A
5317506 Coutre et al. May 1994 A
5317619 Hellmick et al. May 1994 A
5323006 Thompson et al. Jun 1994 A
5329976 Haber et al. Jul 1994 A
5334141 Carr et al. Aug 1994 A
5349190 Hines et al. Sep 1994 A
5355087 Claiborne et al. Oct 1994 A
5365069 Eisen et al. Nov 1994 A
5365928 Rhinehart et al. Nov 1994 A
5367552 Peschmann Nov 1994 A
5377681 Drane Jan 1995 A
5381791 Qian Jan 1995 A
5383456 Arnold et al. Jan 1995 A
5383858 Reilly et al. Jan 1995 A
5386446 Fujimoto et al. Jan 1995 A
5387409 Nunn et al. Feb 1995 A
5391877 Marks Feb 1995 A
5395366 D'Andrea et al. Mar 1995 A
5399868 Jones et al. Mar 1995 A
5404293 Weng et al. Apr 1995 A
5415181 Hofgrefe et al. May 1995 A
5431161 Ryals et al. Jul 1995 A
5435302 Lenkinski et al. Jul 1995 A
5436458 Tran et al. Jul 1995 A
5441050 Thurston et al. Aug 1995 A
5448073 Jeanguillaume Sep 1995 A
5451232 Rhinehart et al. Sep 1995 A
5472403 Cornacchia et al. Dec 1995 A
5475219 Olson Dec 1995 A
5475232 Powers et al. Dec 1995 A
5476095 Schnall et al. Dec 1995 A
5479969 Hardie et al. Jan 1996 A
5481115 Hsieh et al. Jan 1996 A
5484384 Fearnot Jan 1996 A
5489782 Wernikoff Feb 1996 A
5493595 Schoolman Feb 1996 A
5493805 Penuela et al. Feb 1996 A
5494036 Uber, III et al. Feb 1996 A
5501674 Trombley, III et al. Mar 1996 A
5517120 Misik et al. May 1996 A
5519221 Weinberg May 1996 A
5519222 Besett May 1996 A
5519931 Reich May 1996 A
5520182 Leighton et al. May 1996 A
5520653 Reilly et al. May 1996 A
5521506 Misic et al. May 1996 A
5536945 Reich Jul 1996 A
5545899 Tran et al. Aug 1996 A
5559335 Zeng et al. Sep 1996 A
5565684 Gullberg et al. Oct 1996 A
5569181 Heilman et al. Oct 1996 A
5572132 Pulyer et al. Nov 1996 A
5572999 Funda et al. Nov 1996 A
5579766 Gray Dec 1996 A
5580541 Wells et al. Dec 1996 A
5585637 Bertelsen et al. Dec 1996 A
5587585 Eisen et al. Dec 1996 A
5591143 Trombley, III et al. Jan 1997 A
5600145 Plummer Feb 1997 A
5604531 Iddan et al. Feb 1997 A
5610520 Misic Mar 1997 A
5617858 Taverna et al. Apr 1997 A
5629524 Stettner et al. May 1997 A
5635717 Popescu Jun 1997 A
5657759 Essen-Moller Aug 1997 A
5672877 Liebig et al. Sep 1997 A
5677539 Apotovsky et al. Oct 1997 A
5682888 Olson et al. Nov 1997 A
5687542 Lawecki et al. Nov 1997 A
5690691 Chen et al. Nov 1997 A
5692640 Caulfield et al. Dec 1997 A
5694933 Madden et al. Dec 1997 A
5695500 Taylor et al. Dec 1997 A
5716595 Goldenberg Feb 1998 A
5727554 Kalend et al. Mar 1998 A
5729129 Acker Mar 1998 A
5732704 Thurston et al. Mar 1998 A
5739508 Uber, III Apr 1998 A
5741232 Reilly et al. Apr 1998 A
5742060 Ashburn Apr 1998 A
5744805 Raylman et al. Apr 1998 A
5757006 De Vito et al. May 1998 A
5779675 Reilly et al. Jul 1998 A
5780855 Pare et al. Jul 1998 A
5781442 Engleson et al. Jul 1998 A
5784432 Kurtz et al. Jul 1998 A
5786597 Lingren et al. Jul 1998 A
5795333 Reilly et al. Aug 1998 A
5799111 Guissin Aug 1998 A
5800355 Hasegawa Sep 1998 A
5803914 Ryals et al. Sep 1998 A
5806519 Evans, III et al. Sep 1998 A
5808203 Nolan, Jr. et al. Sep 1998 A
5810742 Pearlman Sep 1998 A
5811814 Leone et al. Sep 1998 A
5813985 Carroll Sep 1998 A
5818050 Dilmanian et al. Oct 1998 A
5821541 Tuemer Oct 1998 A
5825031 Wong et al. Oct 1998 A
5827219 Uber, III et al. Oct 1998 A
5828073 Zhu et al. Oct 1998 A
5833603 Kovacs et al. Nov 1998 A
5838009 Plummer et al. Nov 1998 A
5840026 Uber, III et al. Nov 1998 A
5841141 Gullberg et al. Nov 1998 A
5842977 Lesho et al. Dec 1998 A
5843037 Uber, III Dec 1998 A
5846513 Carroll et al. Dec 1998 A
5847396 Lingren et al. Dec 1998 A
5857463 Thurston et al. Jan 1999 A
5871013 Wainer et al. Feb 1999 A
5873861 Hitchins et al. Feb 1999 A
5880475 Oka et al. Mar 1999 A
5882338 Gray Mar 1999 A
5884457 Ortiz et al. Mar 1999 A
5885216 Evans, III et al. Mar 1999 A
5891030 Johnson et al. Apr 1999 A
5893397 Peterson et al. Apr 1999 A
5899885 Reilly et al. May 1999 A
5900533 Chou May 1999 A
5903008 Li May 1999 A
5910112 Judd et al. Jun 1999 A
5911252 Cassel Jun 1999 A
5916167 Kramer et al. Jun 1999 A
5916197 Reilly et al. Jun 1999 A
5920054 Uber, III Jul 1999 A
5927351 Zhu et al. Jul 1999 A
5928150 Call Jul 1999 A
5932879 Raylman et al. Aug 1999 A
5938639 Reilly et al. Aug 1999 A
5939724 Eisen et al. Aug 1999 A
5944190 Edelen Aug 1999 A
5944694 Hitchins et al. Aug 1999 A
5947935 Rhinehart et al. Sep 1999 A
5953884 Lawecki et al. Sep 1999 A
5954668 Uber, III et al. Sep 1999 A
5961457 Raylman et al. Oct 1999 A
5967983 Ashburn Oct 1999 A
5973598 Beigel Oct 1999 A
5974165 Giger et al. Oct 1999 A
5984860 Shan Nov 1999 A
5987350 Thurston Nov 1999 A
5993378 Lemelson Nov 1999 A
5997502 Reilly et al. Dec 1999 A
6002134 Lingren Dec 1999 A
6002480 Izatt et al. Dec 1999 A
6017330 Hitchins et al. Jan 2000 A
6019745 Gray Feb 2000 A
6021341 Scibilia et al. Feb 2000 A
6037595 Lingren Mar 2000 A
6040697 Misic Mar 2000 A
6042565 Hirschman et al. Mar 2000 A
RE36648 Uber, III et al. Apr 2000 E
6046454 Lingren et al. Apr 2000 A
6048334 Hirschman et al. Apr 2000 A
6052618 Dahlke et al. Apr 2000 A
6055450 Ashburn Apr 2000 A
6055452 Pearlman Apr 2000 A
RE36693 Reich May 2000 E
6063052 Uber et al. May 2000 A
D426891 Beale et al. Jun 2000 S
D426892 Beale et al. Jun 2000 S
6072177 McCroskey et al. Jun 2000 A
6076009 Raylman et al. Jun 2000 A
6080984 Friesenhahn Jun 2000 A
D428491 Beale et al. Jul 2000 S
6082366 Andra et al. Jul 2000 A
6090064 Reilly et al. Jul 2000 A
6091070 Lingren et al. Jul 2000 A
6096011 Trombley, III et al. Aug 2000 A
6107102 Ferrari Aug 2000 A
6115635 Bourgeois Sep 2000 A
6129670 Burdette et al. Oct 2000 A
6132372 Essen-Moller Oct 2000 A
6135955 Madden et al. Oct 2000 A
6135968 Brounstein Oct 2000 A
6137109 Hayes Oct 2000 A
6145277 Lawecki et al. Nov 2000 A
6147352 Ashburn Nov 2000 A
6147353 Gagnon et al. Nov 2000 A
6148229 Morris, Sr. et al. Nov 2000 A
6149627 Uber, III Nov 2000 A
6155485 Coughlin et al. Dec 2000 A
6160398 Walsh Dec 2000 A
6162198 Coffey et al. Dec 2000 A
6172362 Lingren et al. Jan 2001 B1
6173201 Front Jan 2001 B1
6184530 Hines et al. Feb 2001 B1
6189195 Reilly et al. Feb 2001 B1
6194715 Lingren et al. Feb 2001 B1
6194726 Pi et al. Feb 2001 B1
6197000 Reilly et al. Mar 2001 B1
6202923 Boyer et al. Mar 2001 B1
6205347 Morgan et al. Mar 2001 B1
6212423 Krakovitz Apr 2001 B1
6223065 Misic et al. Apr 2001 B1
6224577 Dedola et al. May 2001 B1
6226350 Hsieh May 2001 B1
6229145 Weinberg May 2001 B1
6232605 Soluri et al. May 2001 B1
6233304 Hu et al. May 2001 B1
6236050 Tumer May 2001 B1
6236878 Taylor et al. May 2001 B1
6236880 Raylman et al. May 2001 B1
6239438 Schubert May 2001 B1
6240312 Alfano et al. May 2001 B1
6241708 Reilly et al. Jun 2001 B1
6242743 DeVito et al. Jun 2001 B1
6242744 Soluri et al. Jun 2001 B1
6242745 Berlad et al. Jun 2001 B1
6246901 Benaron Jun 2001 B1
6252924 Davantes et al. Jun 2001 B1
6258576 Richards-Kortum et al. Jul 2001 B1
6259095 Bouton et al. Jul 2001 B1
6261562 Xu et al. Jul 2001 B1
6263229 Atalar et al. Jul 2001 B1
6269340 Ford et al. Jul 2001 B1
6270463 Morris, Sr. et al. Aug 2001 B1
6271524 Wainer et al. Aug 2001 B1
6271525 Majewski et al. Aug 2001 B1
6280704 Schutt et al. Aug 2001 B1
6281505 Hines et al. Aug 2001 B1
6308097 Pearlman Oct 2001 B1
6310968 Hawkins et al. Oct 2001 B1
6315981 Unger Nov 2001 B1
6317623 Griffiths et al. Nov 2001 B1
6317648 Sleep et al. Nov 2001 B1
6318630 Coughlin et al. Nov 2001 B1
6322535 Hitchins et al. Nov 2001 B1
6323648 Belt et al. Nov 2001 B1
6324418 Crowley et al. Nov 2001 B1
RE37487 Reilly et al. Dec 2001 E
D452737 Nolan, Jr. et al. Jan 2002 S
6336913 Spohn et al. Jan 2002 B1
6339652 Hawkins et al. Jan 2002 B1
6339718 Zatezalo et al. Jan 2002 B1
6344745 Reisker et al. Feb 2002 B1
6346706 Rogers et al. Feb 2002 B1
6346886 de la Huerga Feb 2002 B1
RE37602 Uber, III et al. Mar 2002 E
6353227 Boxen Mar 2002 B1
6356081 Misic Mar 2002 B1
6368331 Front et al. Apr 2002 B1
6371938 Reilly et al. Apr 2002 B1
6375624 Uber, III et al. Apr 2002 B1
6377838 Iwanczyk et al. Apr 2002 B1
6381349 Zeng et al. Apr 2002 B1
6385483 Uber, III et al. May 2002 B1
6388244 Gagnon May 2002 B1
6388258 Berlad et al. May 2002 B1
6392235 Barrett et al. May 2002 B1
6396273 Misic May 2002 B2
6397098 Uber, III et al. May 2002 B1
6399951 Paulus et al. Jun 2002 B1
6402717 Reilly et al. Jun 2002 B1
6402718 Reilly et al. Jun 2002 B1
6407391 Mastrippolito et al. Jun 2002 B1
6408204 Hirschman Jun 2002 B1
6409987 Cardin et al. Jun 2002 B1
6415046 Kerut, Sr. Jul 2002 B1
6420711 Tuemer Jul 2002 B2
6425174 Reich Jul 2002 B1
6426917 Tabanou et al. Jul 2002 B1
6429431 Wilk Aug 2002 B1
6431175 Penner et al. Aug 2002 B1
6432089 Kakimi et al. Aug 2002 B1
6438401 Cheng et al. Aug 2002 B1
6439444 Shields, II Aug 2002 B1
6440107 Trombley, III et al. Aug 2002 B1
6442418 Evans, III et al. Aug 2002 B1
6448560 Tumer Sep 2002 B1
6453199 Kobozev Sep 2002 B1
6459925 Nields et al. Oct 2002 B1
6459931 Hirschman Oct 2002 B1
6468261 Small et al. Oct 2002 B1
6469306 Van Dulmen et al. Oct 2002 B1
6471674 Emig et al. Oct 2002 B1
6480732 Tanaka et al. Nov 2002 B1
6484051 Daniel Nov 2002 B1
6488661 Spohn et al. Dec 2002 B1
6490476 Townsend et al. Dec 2002 B1
6504157 Juhi Jan 2003 B2
6504178 Carlson et al. Jan 2003 B2
6504899 Pugachev et al. Jan 2003 B2
6506155 Sluis Jan 2003 B2
6510336 Daghighian et al. Jan 2003 B1
6512374 Misic et al. Jan 2003 B1
6516213 Nevo Feb 2003 B1
6519569 White et al. Feb 2003 B1
6520930 Critchlow et al. Feb 2003 B2
6522945 Sleep et al. Feb 2003 B2
6525320 Juni Feb 2003 B1
6525321 Juni Feb 2003 B2
6541763 Lingren et al. Apr 2003 B2
6545280 Weinberg Apr 2003 B2
6549646 Yeh et al. Apr 2003 B1
6560354 Maurer, Jr. et al. May 2003 B1
6562008 Reilly et al. May 2003 B1
6563942 Takeo et al. May 2003 B2
6565502 Bede et al. May 2003 B1
6567687 Front et al. May 2003 B2
6575930 Trombley, III et al. Jun 2003 B1
6576918 Fu et al. Jun 2003 B1
6583420 Nelson et al. Jun 2003 B1
6584348 Glukhovsky Jun 2003 B2
6585700 Trocki et al. Jul 2003 B1
6587710 Wainer Jul 2003 B1
6589158 Winkler Jul 2003 B2
6591127 McKinnon Jul 2003 B1
6592520 Peszynski et al. Jul 2003 B1
6602488 Daghighian Aug 2003 B1
6607301 Glukhovsky et al. Aug 2003 B1
6611141 Schulz et al. Aug 2003 B1
6614453 Suri et al. Sep 2003 B1
6620134 Trombley, III et al. Sep 2003 B1
6627893 Zeng et al. Sep 2003 B1
6628983 Gagnon Sep 2003 B1
6628984 Weinberg Sep 2003 B2
6630735 Carlson et al. Oct 2003 B1
6631284 Nutt et al. Oct 2003 B2
6632216 Houzego et al. Oct 2003 B2
6633658 Dabney et al. Oct 2003 B1
6638752 Contag et al. Oct 2003 B2
6643537 Zatezalo et al. Nov 2003 B1
6643538 Majewski et al. Nov 2003 B1
6652489 Trocki et al. Nov 2003 B2
6657200 Nygard et al. Dec 2003 B2
6662036 Cosman Dec 2003 B2
6664542 Ye et al. Dec 2003 B2
6670258 Carlson et al. Dec 2003 B2
6671563 Engelson et al. Dec 2003 B1
6673033 Sciulli et al. Jan 2004 B1
6674834 Acharya et al. Jan 2004 B1
6676634 Spohn et al. Jan 2004 B1
6677182 Carlson Jan 2004 B2
6677755 Belt et al. Jan 2004 B2
6680750 Tournier et al. Jan 2004 B1
6694172 Gagnon et al. Feb 2004 B1
6697660 Robinson Feb 2004 B1
6699219 Emig et al. Mar 2004 B2
6704592 Reynolds et al. Mar 2004 B1
6713766 Garrard et al. Mar 2004 B2
6714012 Belt et al. Mar 2004 B2
6714013 Misic Mar 2004 B2
6716195 Nolan, Jr. et al. Apr 2004 B2
6722499 Reich Apr 2004 B2
6723988 Wainer Apr 2004 B1
6726657 Dedig et al. Apr 2004 B1
6728583 Hallett Apr 2004 B2
6731971 Evans, III et al. May 2004 B2
6731989 Engleson et al. May 2004 B2
6733477 Cowan et al. May 2004 B2
6733478 Reilly et al. May 2004 B2
6734416 Carlson et al. May 2004 B2
6734430 Soluri et al. May 2004 B2
6737652 Lanza et al. May 2004 B2
6737866 Belt et al. May 2004 B2
6740882 Weinberg et al. May 2004 B2
6743202 Hirschman et al. Jun 2004 B2
6743205 Nolan, Jr. et al. Jun 2004 B2
6747454 Belt Jun 2004 B2
6748259 Benaron et al. Jun 2004 B1
6751500 Hirschman et al. Jun 2004 B2
6765981 Heumann Jul 2004 B2
6766048 Launay et al. Jul 2004 B1
6771802 Patt et al. Aug 2004 B1
6774358 Hamill et al. Aug 2004 B2
6776977 Liu Aug 2004 B2
6787777 Gagnon et al. Sep 2004 B1
6788758 De Villiers Sep 2004 B2
6798206 Misic Sep 2004 B2
6808513 Reilly et al. Oct 2004 B2
6809321 Rempel Oct 2004 B2
6813868 Baldwin et al. Nov 2004 B2
6821013 Reilly et al. Nov 2004 B2
6822237 Inoue et al. Nov 2004 B2
6833705 Misic Dec 2004 B2
6838672 Wagenaar et al. Jan 2005 B2
6841782 Balan et al. Jan 2005 B1
6843357 Bybee et al. Jan 2005 B2
6851615 Jones Feb 2005 B2
6866654 Callan et al. Mar 2005 B2
6870175 Dell et al. Mar 2005 B2
6881043 Barak Apr 2005 B2
6888351 Belt et al. May 2005 B2
6889074 Uber, III et al. May 2005 B2
6897658 Belt et al. May 2005 B2
6906330 Blevis et al. Jun 2005 B2
D507832 Yanniello et al. Jul 2005 S
6915170 Engleson et al. Jul 2005 B2
6915823 Osborne et al. Jul 2005 B2
6917828 Fukuda Jul 2005 B2
6921384 Reilly et al. Jul 2005 B2
6935560 Andreasson et al. Aug 2005 B2
6936030 Pavlik et al. Aug 2005 B1
6937750 Natanzon et al. Aug 2005 B2
6939302 Griffiths et al. Sep 2005 B2
6940070 Tumer Sep 2005 B2
6943355 Shwartz et al. Sep 2005 B2
6957522 Baldwin et al. Oct 2005 B2
6958053 Reilly Oct 2005 B1
6963770 Scarantino et al. Nov 2005 B2
6970735 Uber, III et al. Nov 2005 B2
6972001 Emig et al. Dec 2005 B2
6974443 Reilly et al. Dec 2005 B2
6976349 Baldwin et al. Dec 2005 B2
6984222 Hitchins et al. Jan 2006 B1
6985870 Martucci et al. Jan 2006 B2
6988981 Hamazaki Jan 2006 B2
6994249 Peterka et al. Feb 2006 B2
7009183 Wainer et al. Mar 2006 B2
7011814 Suddarth et al. Mar 2006 B2
7012430 Misic Mar 2006 B2
7017622 Osborne et al. Mar 2006 B2
7018363 Cowan et al. Mar 2006 B2
7019783 Kindem et al. Mar 2006 B2
7025757 Reilly et al. Apr 2006 B2
7026623 Oaknin et al. Apr 2006 B2
7043063 Noble et al. May 2006 B1
7102138 Belvis et al. Sep 2006 B2
7103204 Celler et al. Sep 2006 B1
7127026 Amemiya et al. Oct 2006 B2
7142634 Engler et al. Nov 2006 B2
7145986 Wear et al. Dec 2006 B2
7147372 Nelson et al. Dec 2006 B2
7164130 Welsh et al. Jan 2007 B2
7176466 Rousso et al. Feb 2007 B2
7187790 Sabol et al. Mar 2007 B2
7217953 Carlson May 2007 B2
7256386 Carlson et al. Aug 2007 B2
7291841 Nelson et al. Nov 2007 B2
7327822 Sauer et al. Feb 2008 B2
7359535 Salla et al. Apr 2008 B2
7373197 Daighighian et al. May 2008 B2
7394923 Zou et al. Jul 2008 B2
7444010 De Man Oct 2008 B2
7468513 Charron et al. Dec 2008 B2
7470896 Pawlak et al. Dec 2008 B2
7490085 Walker et al. Feb 2009 B2
7495225 Hefetz et al. Feb 2009 B2
7502499 Grady Mar 2009 B2
7570732 Stanton et al. Aug 2009 B2
7592597 Hefetz et al. Sep 2009 B2
7620444 Le et al. Nov 2009 B2
7627084 Jabri et al. Dec 2009 B2
7652259 Kimchy et al. Jan 2010 B2
7671331 Hefetz Mar 2010 B2
7671340 Uribe et al. Mar 2010 B2
7672491 Krishnan et al. Mar 2010 B2
7680240 Manjeshwar et al. Mar 2010 B2
7705316 Rousso et al. Apr 2010 B2
7826889 David et al. Nov 2010 B2
7831024 Metzler et al. Nov 2010 B2
7872235 Rousso et al. Jan 2011 B2
7894650 Weng et al. Feb 2011 B2
7968851 Rousso et al. Jun 2011 B2
8013308 Guerin et al. Sep 2011 B2
8055329 Kimchy et al. Nov 2011 B2
8111886 Rousso et al. Feb 2012 B2
8158951 Bal et al. Apr 2012 B2
8163661 Akiyoshi et al. Apr 2012 B2
8204500 Weintraub et al. Jun 2012 B2
8338788 Zilberstein et al. Dec 2012 B2
8440168 Yang et al. May 2013 B2
20010016029 Tumer Aug 2001 A1
20010020131 Kawagishi et al. Sep 2001 A1
20010035902 Iddan et al. Nov 2001 A1
20010049608 Hochman Dec 2001 A1
20020072784 Sheppard et al. Jun 2002 A1
20020085748 Baumberg Jul 2002 A1
20020087101 Barrick et al. Jul 2002 A1
20020099295 Gil et al. Jul 2002 A1
20020099310 Kimchy et al. Jul 2002 A1
20020099334 Hanson et al. Jul 2002 A1
20020103429 DeCharms Aug 2002 A1
20020103431 Toker et al. Aug 2002 A1
20020145114 Inoue et al. Oct 2002 A1
20020148970 Wong et al. Oct 2002 A1
20020165491 Reilly Nov 2002 A1
20020168094 Kaushikkar et al. Nov 2002 A1
20020168317 Daighighian et al. Nov 2002 A1
20020172405 Schultz Nov 2002 A1
20020179843 Tanaka et al. Dec 2002 A1
20020183645 Nachaliel Dec 2002 A1
20020188197 Bishop et al. Dec 2002 A1
20020198738 Osborne Dec 2002 A1
20030001098 Stoddart et al. Jan 2003 A1
20030001837 Baumberg Jan 2003 A1
20030006376 Tumer Jan 2003 A1
20030013950 Rollo et al. Jan 2003 A1
20030013966 Barnes et al. Jan 2003 A1
20030038240 Weinberg Feb 2003 A1
20030055685 Cobb et al. Mar 2003 A1
20030063787 Natanzon et al. Apr 2003 A1
20030071219 Motomura et al. Apr 2003 A1
20030081716 Tumer May 2003 A1
20030135388 Martucci et al. Jul 2003 A1
20030136912 Juni Jul 2003 A1
20030144322 Kozikowski et al. Jul 2003 A1
20030158481 Stotzka et al. Aug 2003 A1
20030183226 Brand et al. Oct 2003 A1
20030189174 Tanaka et al. Oct 2003 A1
20030191430 D'Andrea et al. Oct 2003 A1
20030202629 Dunham et al. Oct 2003 A1
20030208117 Shwartz et al. Nov 2003 A1
20030215122 Tanaka Nov 2003 A1
20030215124 Li Nov 2003 A1
20030216631 Bloch et al. Nov 2003 A1
20030219149 Vailaya et al. Nov 2003 A1
20040003001 Shimura Jan 2004 A1
20040010397 Barbour et al. Jan 2004 A1
20040015075 Kimchy et al. Jan 2004 A1
20040021065 Weber Feb 2004 A1
20040044282 Mixon et al. Mar 2004 A1
20040051368 Caputo et al. Mar 2004 A1
20040054248 Kimchy et al. Mar 2004 A1
20040054278 Kimchy et al. Mar 2004 A1
20040065838 Tumer Apr 2004 A1
20040075058 Blevis et al. Apr 2004 A1
20040081623 Eriksen et al. Apr 2004 A1
20040082918 Evans et al. Apr 2004 A1
20040084340 Morelle et al. May 2004 A1
20040086437 Jackson et al. May 2004 A1
20040101176 Mendonca et al. May 2004 A1
20040101177 Zahlmann et al. May 2004 A1
20040116807 Amrami et al. Jun 2004 A1
20040120557 Sabol Jun 2004 A1
20040122311 Cosman Jun 2004 A1
20040125918 Shanmugaval et al. Jul 2004 A1
20040138557 Le et al. Jul 2004 A1
20040153128 Suresh et al. Aug 2004 A1
20040162492 Kobayashi Aug 2004 A1
20040171924 Mire et al. Sep 2004 A1
20040183022 Weinberg Sep 2004 A1
20040184644 Leichter et al. Sep 2004 A1
20040193453 Butterfield et al. Sep 2004 A1
20040195512 Crosetto Oct 2004 A1
20040204646 Nagler et al. Oct 2004 A1
20040205343 Forth et al. Oct 2004 A1
20040210126 Hajaj et al. Oct 2004 A1
20040238743 Gravrand et al. Dec 2004 A1
20040251419 Nelson et al. Dec 2004 A1
20040253177 Elmaleh et al. Dec 2004 A1
20040263865 Pawlak et al. Dec 2004 A1
20050001170 Juni Jan 2005 A1
20050006589 Young et al. Jan 2005 A1
20050020898 Vosniak et al. Jan 2005 A1
20050020915 Bellardinelli et al. Jan 2005 A1
20050023474 Persyk et al. Feb 2005 A1
20050029277 Tachibana Feb 2005 A1
20050033157 Klein et al. Feb 2005 A1
20050055174 David et al. Mar 2005 A1
20050056788 Juni Mar 2005 A1
20050074402 Cagnolini et al. Apr 2005 A1
20050107698 Powers et al. May 2005 A1
20050107914 Engleson et al. May 2005 A1
20050108044 Koster May 2005 A1
20050113945 Engleson et al. May 2005 A1
20050121505 Metz et al. Jun 2005 A1
20050131270 Weil et al. Jun 2005 A1
20050145797 Oaknin et al. Jul 2005 A1
20050148869 Masuda Jul 2005 A1
20050149350 Kerr et al. Jul 2005 A1
20050156115 Kobayashi et al. Jul 2005 A1
20050173643 Tumer Aug 2005 A1
20050187465 Motomura et al. Aug 2005 A1
20050198800 Reich Sep 2005 A1
20050203389 Williams Sep 2005 A1
20050205792 Rousso et al. Sep 2005 A1
20050205796 Bryman Sep 2005 A1
20050207526 Altman Sep 2005 A1
20050211909 Smith Sep 2005 A1
20050215889 Patterson, II Sep 2005 A1
20050234424 Besing et al. Oct 2005 A1
20050247893 Fu et al. Nov 2005 A1
20050253073 Joram et al. Nov 2005 A1
20050261936 Silverbrook et al. Nov 2005 A1
20050261937 Silverbrook et al. Nov 2005 A1
20050261938 Silverbrook et al. Nov 2005 A1
20050266074 Zilberstein et al. Dec 2005 A1
20050277833 Williams, Jr. Dec 2005 A1
20050277911 Stewart et al. Dec 2005 A1
20050278066 Graves et al. Dec 2005 A1
20050288869 Kroll et al. Dec 2005 A1
20060000983 Charron et al. Jan 2006 A1
20060033028 Juni Feb 2006 A1
20060036157 Tumer Feb 2006 A1
20060072799 McLain Apr 2006 A1
20060074290 Chen et al. Apr 2006 A1
20060104519 Stoeckel et al. May 2006 A1
20060109950 Arenson et al. May 2006 A1
20060122503 Burbank et al. Jun 2006 A1
20060145081 Hawman Jul 2006 A1
20060160157 Zuckerman Jul 2006 A1
20060188136 Ritt et al. Aug 2006 A1
20060214097 Wang et al. Sep 2006 A1
20060237652 Kimchy et al. Oct 2006 A1
20060257012 Kaufman et al. Nov 2006 A1
20070081700 Blumenfeld et al. Apr 2007 A1
20070116170 De Man et al. May 2007 A1
20070133852 Collins et al. Jun 2007 A1
20070156047 Nagler et al. Jul 2007 A1
20070166227 Liu et al. Jul 2007 A1
20070166277 Liu et al. Jul 2007 A1
20070189436 Goto et al. Aug 2007 A1
20070194241 Rousso et al. Aug 2007 A1
20070265230 Rousso et al. Nov 2007 A1
20080029704 Hefetz et al. Feb 2008 A1
20080033291 Rousso et al. Feb 2008 A1
20080036882 Uemura et al. Feb 2008 A1
20080039721 Shai et al. Feb 2008 A1
20080042067 Rousso et al. Feb 2008 A1
20080128626 Rousso et al. Jun 2008 A1
20080137938 Zahniser Jun 2008 A1
20080230705 Rousso et al. Sep 2008 A1
20080237482 Shahar et al. Oct 2008 A1
20080260228 Dichterman et al. Oct 2008 A1
20080260580 Helle et al. Oct 2008 A1
20080260637 Dickman Oct 2008 A1
20080277591 Shahar et al. Nov 2008 A1
20090001273 Hawman Jan 2009 A1
20090018412 Schmitt Jan 2009 A1
20090078875 Rousso et al. Mar 2009 A1
20090112086 Melman Apr 2009 A1
20090152471 Rousso et al. Jun 2009 A1
20090190807 Rousso et al. Jul 2009 A1
20090201291 Ziv et al. Aug 2009 A1
20090236532 Frach et al. Sep 2009 A1
20100006770 Balakin Jan 2010 A1
20100021378 Rousso et al. Jan 2010 A1
20100102242 Burr et al. Apr 2010 A1
20100202664 Busch et al. Aug 2010 A1
20100245354 Rousso et al. Sep 2010 A1
20120248320 Wangerin et al. Oct 2012 A1
20120326034 Sachs et al. Dec 2012 A1
20130114792 Zilberstein et al. May 2013 A1
20130308749 Zilberstein et al. Nov 2013 A1
Foreign Referenced Citations (65)
Number Date Country
1516429 Dec 1969 DE
19814199 Jul 1999 DE
19815362 Oct 1999 DE
0273257 Jul 1988 EP
0525954 Feb 1993 EP
0526970 Feb 1993 EP
0543626 May 1993 EP
0592093 Apr 1994 EP
0697193 Feb 1996 EP
0813692 Dec 1997 EP
0887661 Dec 1998 EP
1237013 Sep 2002 EP
2031142 Apr 1980 GB
59-141084 Aug 1984 JP
61-026879 Feb 1986 JP
01-324568 Jun 1986 JP
03-121549 May 1991 JP
04-151120 May 1992 JP
6-109848 Apr 1994 JP
06-109848 Apr 1994 JP
07-059763 Mar 1995 JP
07-141523 Jun 1995 JP
08-292268 Nov 1996 JP
10-260258 Sep 1998 JP
11-072564 Mar 1999 JP
WO 9200402 Sep 1992 WO
WO 9816852 Apr 1998 WO
9903003 Jan 1999 WO
WO 9903003 Jan 1999 WO
WO 9930610 Jun 1999 WO
WO 9939650 Aug 1999 WO
WO 0010034 Feb 2000 WO
WO 0031522 Feb 2000 WO
WO 0022975 Apr 2000 WO
WO 0025268 May 2000 WO
WO 0018294 Jun 2000 WO
WO 0038197 Jun 2000 WO
WO 0189384 Nov 2001 WO
WO 0258531 Jan 2002 WO
WO 0216965 Feb 2002 WO
WO 02075357 Sep 2002 WO
WO 03073938 Sep 2003 WO
WO 03086170 Oct 2003 WO
WO 2004004787 Jan 2004 WO
WO 2004032151 Apr 2004 WO
WO 2004042546 May 2004 WO
WO 2004113951 Dec 2004 WO
WO 2005002971 Jan 2005 WO
WO 2005059592 Jun 2005 WO
WO 2005059840 Jun 2005 WO
WO 2005067383 Jul 2005 WO
WO 2005104939 Nov 2005 WO
WO 2005118659 Dec 2005 WO
WO 2005119025 Dec 2005 WO
WO 2006042077 Apr 2006 WO
WO 2006051531 May 2006 WO
WO 2006054296 May 2006 WO
WO 2006075333 Jul 2006 WO
WO 2006129301 Dec 2006 WO
WO 2007010534 Jan 2007 WO
WO 2007010537 Jan 2007 WO
WO 2007054935 May 2007 WO
WO 2007074467 Jul 2007 WO
WO 2008010227 Jan 2008 WO
WO 2008075362 Jun 2008 WO
Non-Patent Literature Citations (407)
Entry
Bloch et al. Application of Computerized Tomography to Radiation Therapy and Surgical Planning. Proceedings of the IEEE. 71(3): p. 351-355. Mar. 1983.
Charland et al (The use of deconvolution and total least squares in recovering a radiation detector line spread funct'on. Med Phys. 25(2)152-160. Feb 1998.
Garcia et al. “Accuracy of Dynamic SPECT Acquisition for Tc-99m Teboroxime Myocardial Perfusion Imaging: Preliminary Results”, American College of Cardiology, 51st Annual Scientific Session, Atlanta, Georgia, USA, 8 P., 2002.
Hassan et al. “A Radiotelemetry Pill for the Measurement of Ionising Radiation Using a Mercuric Iodide Detector”, Phys. Med. Biol., 23(2): 302-308, 1978.
Zhang et al. “An Innovative High Efficiency and High Resolution Probe for Prostate Imaging”, The Journal of Nuclear Medicine, 68: 18, 2000. Abstract.
Quartuccio et al, “Computer Assisted Collimation Gamma Camera: A New Approach to Imaging Contaminated Tissues”, Radiation Protection Dosimetry, 89(3-4):343-348, 2000.
Bromiley et al. “Attenuation Correction in PET Using Consistency Conditions and a Three-Dimensional Template”, IEEE Transactions on Nuclear Science, 48(4): 1371-1377, 2001. p. 1376, col. 2, § 2.
Hayakawa et al. “A PET-MRI Registration Technique for PET Studies of the Rat Brain”, Nuclear Medicine & Biology, 27: 121-125, 2000. p. 121, col. 1.
Lavallée et al. “Building a Hybrid Patient's Model for Augmented Reality in Surgery: A Registration Problem”, Computing in Biological Medicine, 25(2): 149-164, 1995. p. 149-150.
Kojima et al. “Quantitative Planar Imaging Method for Measurement of Renal Activity by Using a Conjugate-Emission Image and Transmission Data”, Medical Physics, 27(3): 608-615, 2000. p. 608.
Pardridge et al. “Tracer Kinetic Model of Blood-Brain Barrier Transport of Plasma Protein-Bound Ligands”, Journal of Clinical Investigation, 74: 745-752, 1984.
Reutter et al. “Direct Least Squares Estimation of Spatiotemporal Distributions From Dynamic SPECT Projections Using a Spatial Segmentation and Temporal B-Splines”, IEEE Transactions on Medical Imaging, 19(5): 434-450, 2000.
Huesman et al. “Kinetic Parameter Estimation From SPECT Cone-Beam Projection Measurements”, Physics in Medicine and Biology, 43(4): 973-982, 1998.
Reutter et al. “Kinetic Parameter Estimation From Attenuated SPECT Projection Measurements”, IEEE Transactions on Nuclear Science, 45(6): 3007-3013, 1998.
Jeanguillaume et al. “From the Whole-Body Counting to Imaging: The Computer Aided Collimation Gamma Camera Project (CACAO)”, Radiation Projection Dosimetry 89(3-4): 349-352, 2000.
Quartuccia et al. “Computer Assisted Collimation Gama Camera: A New Approach to Imaging Contaminated Tissues”, Radiation Projection Dosimetry 89(3-4): 343-348, 2000.
Piperno et al. “Breast Cancer Screening by Impedance Measurements”, Frontiers Med. Biol. Engng., 2(2): 11-17, 1990.
Rajshekhar “Continuous Impedence Monitoring During CT-Guided Stereotactic Surgery: Relative Value in Cystic and Solid Lesions”, British Journal of Neurosurgery, 6: 439-444, 1992.
Jessup “Tumor Markers—Prognostic and Therapeutic Implications for Colorectal Carcinoma”, Surgical Oncology, 7: 139-151, 1998.
Corstens et al. “Nuclear Medicine's Role in Infection and Inflamation”, The Lancet, 354: 765-770, 1999.
Mori et al. “Overexpression of Matrix Metalloproteinase-7mRNA in Human Colon Carcinomas”, Cancer, 75: 1516-1519, 1995.
Erbil et al. “Use and Limitations of Serum Total and Lipid-Bound Sialic Acid Concentrations as Markers for Colorectal Cancer”, Cancer, 55: 404-409, 1985.
Molinolo et al. “Enhanced Tumor Binding Using Immunohistochemical Analyses by Second Generation Anti-Tumor-Associated Glycoprotein 72 Monoclonal Antibodies versus Monoclonal Antibody B72.3 in Human Tissue”, Cancer Research, 50: 1291-1298, 1990.
Day et al. “Localization of Radioiodinated Rat Fibrogen in Transplanted Rat Tumors”, J. Nat. Cancer Inst., 23: 799-812, 1959.
Aoi et al. “Absolute Quantitation of Regional Myocardial Blood Flow of Rats Using Dynamic Pinhole SPECT”, IEEE Nuclear Science Symposium and Medical Imaging Conference Record, 3: 1780-1783, 2002. Abstract, Figs.
Hoffman et al. “Intraoperative Probes and Imaging Probes”, European Journal of Nuclear Medicine, 26(8): 913-935, 1999.
International Search Report May 24, 2007 From the International Searching Authority of the Patent Cooperation Treaty Re.: Application No. PCT/IL05/00575.
Official Action Dated Dec. 2, 2007 From the Israeli Patent Office Re.: Application No. 158442.
Official Action Dated Jul. 12, 2007 From the Re.: U.S Appl. No. 10/616,301.
Official Action Dated Feb. 15, 2008 From the Re.: U.S. Appl. No. 10/343,792.
Official Action Dated Mar. 15, 2004 From the Re.: U.S. Appl. No. 09/725,316.
Official Action Dated Jul. 17, 2007 From the Israeli Patent Office Re.: Application No. 154323.
Official Action Dated Jan. 7, 2009 From the Re.: U.S. Appl. No. 10/616,307.
Summons to Attend Oral Proceedings Pursuant to Rule 115(1) EPC Dated Jan. 16, 2009 From the European Patent Office Re.: Application No. 03810570.6.
Supplementary Partial European Search Report Dated Sep. 4, 2007 From the European Patent Office Re.: Application No. 0 2716285.8.
Supplementary Partial European Search Report Dated Nov. 20, 2007 From the European Patent Office Re.: Application No. 02716285.8.
Kinahan et al. “Attenuation Correction for a Combined 3D PET/CT Scanner”, Medical Physics, 25(10): 2046-2053, Oct. 1998.
Takahashi et al. “Attenuation Correction of Myocardial SPECT Images With X-Ray CT: Effects of Registration Errors Between X-Ray CT and SPECT”, Annals of Nuclear Medicine, 16(6): 431-435, Sep. 2002.
Yu et al. “Using Correlated CT Images in Compensation for Attenuation in PET Image Reconstruction”, Proceedings of the SPIE, Applications of Optical Engineering: Proceedings of OE/Midwest '90, 1396: 56-58, 1991.
Zaidi et al. “Magenetic Resonance Imaging-Guided Attenuation and Scatter Corrections in Three-Dimensional Brain Positron Emission Tomography”, Medical Physics, 30(5): 937-948, May 2003.
Zaidi et al. “MRI-Guided Attenuation Correction in 3D Brain PET”, Neuroimage Human Brain Mapping 2002 Meeting, 16(2): Abstract 504, Jun. 2002.
Official Action Dated May 13, 2009 From the Re.: U.S. Appl. No. 11/798,017.
Official Action Dated May 14, 2009 From the Re.: U.S. Appl. No. 11/656,548.
Response Dated Mar. 13, 2008 to Official Action of Dec. 13, 2007 From the Re.: U.S. Appl. No. 10/616,301.
Response Dated Mar. 15, 2007 to Official Action of Dec. 15, 2006 From the Re.: U.S. Appl. No. 10/616,301.
Response Dated Sep. 22, 2008 to Official Action of Jun. 25, 2008 From Re.: U.S. Appl. No. 10/616,301.
Response Dated Oct. 31, 2007 to Official Action of Jul. 12, 2007 From the Re.: U.S. Appl. No. 10/616,301.
Second International Search Report Dated Jun. 1, 2009 From the International Searching Authority Re.: Application No. PCT/IL07/00918.
Second Written Opinion Dated Jun. 1, 2009 From the International Searching Authority Re.: Application No. PCT/IL07/00918.
Official Action Dated Jul. 12, 2007 From the Re.: U.S. Appl. No. 10/616,301.
Invitation to Pay Additional Fees.
Invitation to pay additional fees dated Apr. 18, 2007.
Official Action Dated Apr. 15, 2008 From the Re.: U.S. Appl. No. 09/727,464.
Official Action Dated Dec. 23, 2008 From the Re.: U.S. Appl. No. 09/727,464.
International Preliminary Report on Patentability Dated Apr. 16, 2009 From the International Bureau of WIPO Re.: Application No. PCT/IL2007/000918.
International Preliminary Report on Patentability Dated Jun. 21, 2007 From the International Bureau of WIPO Re.: Application No. PCT/IL2005/000575.
International Preliminary Report on Patentability Dated Jan. 22, 2009 From the International Bureau of WIPO Re.: Application No. PCT/IL2006/000834.
International Preliminary Report on Patentability Dated Jan. 22, 2009 From the International Bureau of WIPO Re.: Application No. PCT/IL2006/001511.
International Preliminary Report on Patentability Dated May 22, 2007 From the International Preliminary Examining Authority Re.: Application No. PCT/IL06/00059.
International Preliminary Report on Patentability Dated May 22, 2008 From the International Bureau of WIPO Re.: Application No. PCT/IL2006/001291.
International Preliminary Report on Patentability Dated May 24, 2007 From the International Bureau of WIPO Re.: Application No. PCT/IL2005/001173.
International Preliminary Report on Patentability Dated Apr. 26, 2007 From the International Bureau of WIPO Re.: Application No. PCT/IL2005/000394.
International Preliminary Report on Patentability Dated Jan. 31, 2008 From the International Bureau of WIPO Re.: Application No. PCT/IL2006/000840.
International Search Report Dated Oct. 15, 2008 From the International Searching Authority Re.: Application No. PCT/IL07/00918.
Invitation to Pay Additional Fees Dated Jul. 10, 2008 From the International Searching Authority Re.: Application No. PCT/IL06/01511.
Invitation to Pay Additional Fees Dated Feb. 15, 2007 From the International Searching Authority Re.: Application No. PCT/IL05/00575.
Official Action Dated Nov. 26, 2008 From the Re.: U.S. Appl. No. 10/240,239.
Official Action Dated Apr. 29, 2009 From the Re.: U.S. Appl. No. 11/980,690.
Response Dated Aug. 14, 2008 to Official Action of Apr. 15, 2008 From the Re.: U.S. Appl. No. 09/727,464.
Response Dated Nov. 25, 2005 to Office Action of May 13, 2005 From the Patent Office of the People's Rebublic of Chine Re.: Application No. 1817689.5.
Response to the International Search Report and the Written Opinion of Oct. 10, 2006 From the International Searching Authority Re.: Application No. PCT/IL06/00059.
Translation of Office Action Dated May 13, 2005 From the Patent Office of the People's Republic of China Re.: Application No. 01817689.5.
Written Opinion Dated Oct. 15, 2008 From the International Searching Authority Re.: Application No. PCT/IL07/00918.
Communication Pursuant to Article 94(3) EPC Dated Jul. 22, 2009 From the European Patent Office Re.: Application No. 06809851.6.
Notice of Allowance Dated Jul. 16, 2009 From the Re.: U.S. Appl. No. 12/084,559.
Official Action Dated Jul. 7, 2009 From the Re.: U.S. Appl. No. 10/533,568.
Official Action Dated Jul. 15, 2009 From the Re.: U.S. Appl. No. 10/616,301.
Official Action Dated Jul. 20, 2009 From the Re.: U.S. Appl. No. 11/980,617.
Ogawa et al. “Ultra High Resoultion Pinhole SPECT”, IEEE Nuclear Science Symposium, 2: 1600-1604, 1998.
Pellegrini et al. “Design of Compact Pinhole SPECT System Based on Flat Panel PMT”, IEEE Nuclear Science Symposium Conference Record, 3: 1828-1832, 2003.
Wu et al. “ECG-Gated Pinhole SPECT in Mice With Millimeter Spatial Resolution”, IEEE Transactions on Nuclear Science, 47(3): 1218-1221, Jun. 2000.
Notice of Allowance Dated Jul. 22, 2010 From the Re.: U.S. Appl. No. 11/794,799.
Response Dated Aug. 16, 2010 to Communication Pursuant to Article 94(3) EPC of Apr. 16, 2010 From the European Patent Office Re. U.S. Appl. No. 01951883.6.
Supplemental Response Under 37 C.F.R. § 1.125 Dated Aug. 12, 2010 to Telephonic Interview of Aug. 6, 2010 From the US Patent and Trademark Office Re. U.S. Appl. No. 11/980,617.
Official Action Dated Oct. 26, 2011 From the Re.: U.S. Appl. No. 10/836,223.
Official Action Dated Oct. 27, 2011 From the Re.: U.S. Appl. No. 11/656,548.
Supplemental Notice of Allowability Dated Oct. 24, 2011 From the Re.: U.S. Appl. No. 11/607,075.
Response Dated Sep. 1, 2011 to Communication Pursuant to Article 94(3) EPC of Mar. 2, 2011 From the European Patent Office Re.: Application No. 06756259.5.
Response Dated Aug. 29, 2011 to Official Action of Apr. 27, 2011 From the Re.: U.S. Appl. No. 10/836,223.
Response Dated Oct. 14, 2011 to Supplementary European Search Report and the European Search Opinion of Mar. 16, 2011 From the European Patent Office Re. Application No. 05803689.8.
Notice of Allowance Dated Oct. 11, 2011 From the Re. U.S. Appl. No. 11/988,926.
Response Dated Oct. 14, 2011 to Communication Pursuant to Rules 70(2) and 70a(2) EPC of Apr. 4, 2011 From the European Patent Office Re. Application No. 05803689.8.
Restriction Official Action Dated Nov. 8, 2011 From the Re. U.S. Appl. No. 12/309,479.
Amendment After Allowance Under 37 CFR 1.312 Dated Sep. 13, 2010 to Notice of Allowance of Jul. 22, 2010 From the Re.: U.S. Appl. No. 11/794,799.
Appeal Brief Dated Jan. 19, 2010 to Notice of Appeal of Nov. 16, 2009 From the Re.: U.S. Appl. No. 10/616,301.
Communication Pursuant to Article 93(3) EPC Dated Mar. 8, 2010 From the European Patent Office Re.: Application No. 06832278.3.
Communication Pursuant to Article 94(3) EPC Dated Mar. 2, 2011 From the European Patent Office Re.: Application No. 06756259.5.
Communication Pursuant to Article 94(3) EPC Dated Mar. 8, 2010 From the European Patent Office Re.: Application No. 06832278.3.
Communication Pursuant to Article 94(3) EPC Dated May 12, 2010 From the European Patent Office Re.: Application No. 06809851.6.
Communication Pursuant to Article 94(3) EPC Dated Apr. 16, 2010 From the European Patent Office Re. Application No. 01951883.6.
Communication Pursuant to Article 94(3) EPC Dated Oct. 21, 2009 From the European Patent Office Re.: Application No. 02716285.8.
Communication Pursuant to Article 96(2) EPC Dated Jun. 19, 2006 From the European Patent Office Re.: Application No. 03810570.6.
Communication Pursuant to Article 96(2) EPC Dated Aug. 30, 2007 From the European Patent Office Re.: Application No. 03810570.6.
Communication Pursuant to Rules 70(2) and 70a(2) EPC Dated Apr. 4, 2011 From the European Patent Office Re. Application No. 05803689.8.
Communication Relating to the Results of the Partial International Search Dated Apr. 18, 2007 From the International Searching Authority of the Patent Cooperation Treaty Re.: Application No. PCT/IL2006/001291.
Communication Relating to the Results of the Partial International Search Dated May 21, 2008 From the International Searching Authority of the Patent Cooperation Treaty Re.: Application No. PCT/IL2007/001588.
International Search Report Dated Oct. 10, 2006 From the International Searching Authority of the Patent Cooperation Treaty Re.: Application No. PCT/IL06/00059.
International Search Report Dated Jul. 11, 2008 From the International Searching Authority of the Patent Cooperation Treaty Re.: Application No. PCT/IL06/01511.
International Search Report Dated Jul. 25, 2008 From the International Searching Authority of the Patent Cooperation Treaty Re.: Application No. PCT/IL2007/001588.
International Search Report Dated Feb. 1, 2006 From the International Searching Authority of the Patent Cooperation Treaty Re.: Application No. PCT/IL05/00048.
International Search Report Dated Jul. 1, 2008 From the International Searching Authority of the Patent Cooperation Treaty Re.: Application No. PCT/IL06/00834.
International Search Report Dated Nov. 1, 2007 From the International Searching Authority of the Patent Cooperation Treaty Re.: Application No. PCT/IL06/00840.
International Search Report Dated Jul. 2, 2007 From the International Searching Authority of the Patent Cooperation Treaty Re.: Application No. PCT/IL2006/001291.
International Search Report Dated Aug. 3, 2006 From the International Searching Authority of the Patent Cooperation Treaty Re.: Application No. PCT/IL05/001173.
International Search Report Dated May 11, 2006 From the International Searching Authority of the Patent Cooperation Treaty Re.: Application No. PCT/IL05/001215.
International Search Report Dated Sep. 11, 2002 From the International Searching Authority of the Patent Cooperation Treaty Re.: Application No. PCT/IL01/00638.
International Search Report Dated Sep. 12, 2002 From the International Searching Authority of the Patent Cooperation Treaty Re: Application No. PCT/IL02/00057.
International Search Report Dated Mar. 18, 2004 From the International Searching Authority of the Patent Cooperation Treaty Re.: Application No. PCT/IL03/00917.
International Search Report Dated Mar. 23, 2006 From the International Searching Authority of the Patent Cooperation Treaty Re.: Application No. PCT/IL05/00572.
International Search Report Dated May 24, 2007 From the International Searching Authority of the Patent Cooperation Treaty Re.: Application No. PCT/IL05/00575.
International Search Report Dated Mar. 26, 2007 From the International Searching Authority of the Patent Cooperation Treaty Re.: Application No. PCT/IL05/00394.
Interview Summary Dated Mar. 25, 2011 From the Re.: U.S. Appl. No. 10/836,223.
Interview Summary Dated May 31, 2011 From the Re. Application No. 10/616,301.
Notice of Allowance Dated May 5, 2011 From the Re.: U.S. Appl. No. 10/240,239.
Notice of Allowance Dated May 6, 2011 From the Re. U.S. Appl. No. 11/980,617.
Notice of Allowance Dated Nov. 15, 2010 From the Re. U.S. Appl. No. 10/616,301.
Notice of Allowance Dated Dec. 17, 2010 From the Re. U.S. Appl. No. 11/980,617.
Notice of Allowance Dated Sep. 17, 2009 From the Re.: No. 10/533,568. Suppl. IDS VIII in 25855.
Notice of Allowance Dated Feb. 23, 2011 From the Re.: U.S. Appl. No. 11/980,690.
Notice of Allowance Dated Jun. 23, 2011 From the Re.: U.S. Appl. No. 10/616,301.
Notice of Allowance Dated Nov. 23, 2009 From the Re.: U.S. Appl. No. 12/084,559.
Notice of Allowance Dated Aug. 25, 2010 From the Re. U.S. Appl. No. 11/980,617.
Notice of Allowance Dated Jun. 30, 2010 From the Re.: U.S. Appl. No. 09/727,464.
Notice of Appeal Dated Nov. 16, 2009 to Official Action of Jul. 15, 2009 From the Re.: U.S. Appl. No. 10/616,301.
Notice of Non-Compliant Amendment Dated Feb. 14, 2011 From the Re.: U.S. Appl. No. 10/616,307.
Office Action Dated Dec. 2, 2007 From the Israeli Patent Office Re.: Application No. 158442.
Office Action Dated Jan. 2, 2006 From the Israeli Patent Office Re.: Application No. 154323.
Office Action Dated Sep. 4, 2007 From the Israeli Patent Office Re.: Application No. 157007.
Office Action Dated Jul. 17, 2007 From the Israeli Patent Office Re.: Application No. 154323.
Official Action Dated Jun. 1, 2006 From the Re.: U.S. Appl. No. 10/686,536.
Official Action Dated Mar. 1, 2010 From the Re.: U.S. Appl. No. 11/794,799.
Official Action Dated Nov. 1, 2010 From the Re.: U.S. Appl. No. 11/980,690.
Official Action Dated Sep. 1, 2009 From the Re.: U.S. Appl. No. 11/794,799.
Official Action Dated Jul. 2, 2004 From the Re.: U.S. Appl. No. 09/641,973.
Official Action Dated Mar. 2, 2010 From the Re.: U.S. Appl. No. 10/836,223.
Official Action Dated Mar. 2, 2010 From the Re.: U.S. Appl. No. 11/980,617.
Official Action Dated Aug. 3, 2010 From the Re.: U.S. Appl. No. 11/980,690.
Official Action Dated May 3, 2007 From the Re.: U.S. Appl. No. 10/240,239.
Official Action Dated Sep. 4, 2008 From the Re.: U.S. Appl. No. 10/533,568.
Official Action Dated Sep. 5, 2002 From the Re.: U.S. Appl. No. 12/084,559.
Official Action Dated Oct. 7, 2008 From the Re.: U.S. Appl. No. 10/616,301.
Official Action Dated Apr. 8, 2010 From the Re.: U.S. Appl. No. 11/980,690.
Official Action Dated Dec. 8, 2009 From the Re.: U.S. Appl. No. 11/132,320.
Official Action Dated Dec. 8, 2010 From the Re.: U.S. Appl. No. 09/641,973.
Official Action Dated Dec. 8, 2010 From the Re.: U.S. Appl. No. 11/980,690.
Official Action Dated Jan. 8, 2010 From the Re.: U.S. Appl. No. 11/656,548.
Official Action Dated Apr. 9, 2010 From the Re.: U.S. Appl. No. 11/798,017.
Official Action Dated Aug. 10, 2007 From the Re.: U.S. Appl. No. 10/836,223.
Official Action Dated Nov. 10, 2010 From the Re.: U.S. Appl. No. 10/616,307.
Official Action Dated Nov. 10, 2010 From the Re.: U.S. Appl. No. 10/836,223.
Official Action Dated Aug. 11, 2009 From the Re.: U.S. Appl. No. 09/641,973.
Official Action Dated Mar. 11, 2010 From the Re.: U.S. Appl. No. 11/607,075.
Official Action Dated Dec. 13, 2007 From the Re.: U.S. Appl. No. 10/616,301.
Official Action Dated Apr. 15, 2008 From the Re.: U.S. Appl. No. 09/641,973.
Official Action Dated Dec. 15, 2006 From the Re.: U.S. Appl. No. 10/616,301.
Official Action Dated Jul. 15, 2008 From the Re.: U.S. Appl. No. 09/641,973.
Official Action Dated Mar. 15, 2004 From the Re.: U.S. Appl. No. 09/765,316.
Official Action Dated Sep. 15, 2009 From the Re.: U.S. Appl. No. 10/616,307.
Official Action Dated Sep. 15, 2009 From the Re.: U.S. Appl. No. 10/836,223.
Official Action Dated Sep. 16, 2009 From the Re.: U.S. Appl. No. 09/727,464.
Official Action Dated Jan. 17, 2006 From the Re.: U.S. Appl. No. 11/034,007.
Official Action Dated Mar. 19, 2010 From the Re.: U.S. Appl. No. 10/240,239.
Official Action Dated Apr. 20, 2006 From the Re.: U.S. Appl. No. 10/240,239.
Official Action Dated Apr. 20, 2011 From the Re.: U.S. Appl. No. 11/798,017.
Official Action Dated Mar. 21, 2008 From the Re.: U.S. Appl. No. 10/533,568.
Official Action Dated Sep. 21, 2009 From the Re.: U.S. Appl. No. 11/798,017.
Official Action Dated Feb. 23, 2010 From the Re.: U.S. Appl. No. 09/641,973.
Official Action Dated Jun. 23, 2006 From the Re.: U.S. Appl. No. 09/727,464.
Official Action Dated May 23, 2011 From the Re. U.S. Appl. No. 11/667,793.
Official Action Dated May 23, 2011 From the Re.: U.S. Appl. No. 10/616,307.
Official Action Dated May 23, 2011 From the Re.: U.S. Appl. No. 11/980,690.
Official Action Dated Nov. 23, 2010 From the Re.: U.S. Appl. No. 11/656,548.
Official Action Dated Jun. 25, 2008 From the Re.: U.S. Appl. No. 10/616,301.
Official Action Dated Sep. 25, 2006 From the Re.: U.S. Appl. No. 10/616,301.
Official Action Dated Apr. 27, 2011 From the Re.: U.S. Appl. No. 10/836,223.
Official Action Dated Jul. 27, 2010 From the Re.: U.S. Appl. No. 10/616,307.
Official Action Dated Apr. 28, 2010 From the Re.: U.S. Appl. No. 10/616,301.
Official Action Dated Aug. 28, 2009 From the Re.: U.S. Appl. No. 10/240,239.
Official Action Dated Dec. 28, 2010 From the Re.: U.S. Appl. No. 11/607,075.
Official Action Dated Jan. 28, 2011 From the Re.: U.S. Appl. No. 09/641,973.
Official Action Dated Oct. 30, 2009 From the Re.: U.S. Appl. No. 11/980,690.
Official Action Dated Sep. 30, 2008 From the Re.: U.S. Appl. No. 10/616,301.
Official Action Dated Sep. 30, 2010 From the Re.: U.S. Appl. No. 11/798,017.
Official Action Dated Jan. 31, 2011 From the Re. U.S. Appl. No. 11/667,793.
Response Dated Jul. 1, 2010 to Official Action of Mar. 2, 2010 From the Re.: U.S. Appl. No. 11/980,617.
Response Dated Jun. 1, 2010 to Official Action of Mar. 1, 2010 From the Re.: U.S. Appl. No. 11/794,799.
Response Dated Sep. 1, 2010 to Official Action of Aug. 3, 2010 From the Re.: U.S. Appl. No. 11/980,690.
Response Dated Mar. 3, 2011 to Notice of Non-Compliant Amendment of Feb. 14, 2011 From the Re.: U.S. Appl. No. 10/616,307.
Response Dated Apr. 5, 2011 to Official Action of Nov. 10, 2010 From the Re.: U.S. Appl. No. 10/836,223.
Response Dated Oct. 5, 2010 to Official Action of Jul. 19, 2010 From the Re.: U.S. Appl. No. 11/656,548.
Response Dated Apr. 7, 2009 to Official Action of Oct. 7, 2008 From the Re.: U.S. Appl. No. 10/616,301.
Response Dated Jul. 8, 2010 to Communication Pursuant to Article 94(3) EPC of Mar. 8, 2010 From the European Patent Office Re.: Application No. 06832278.3.
Response Dated Mar. 8, 2011 to Official Action of Dec. 8, 2010 From the Re.: U.S. Appl. No. 11/980,690.
Response Dated Sep. 8, 2010 to Communication Pursuant to Article 94(3) EPC Dated May 12, 2010 From the European Patent Office Re.: Application No. 06809851.6.
Response Dated Dec. 10, 2009 to Official Action of Aug. 11, 2009 From the Re.: U.S. Appl. No. 09/641,973.
Response Dated Feb. 10, 2011 to Notice of Allowance of Nov. 15, 2010 From the Re. U.S. Appl. No. 10/616,301.
Response Dated Feb. 10, 2011 to Official Action of Nov. 10, 2010 From the Re.: U.S. Appl. No. 10/616,307.
Response Dated May 10, 2010 to Official Action of Apr. 8, 2010 From the Re.: U.S. Appl. No. 11/980,690.
Response Dated May 10, 2010 to Official Action of Jan. 8, 2010 From the Re.: U.S. Appl. No. 11/656,548.
Response Dated May 11, 2010 to Official Action of Mar. 11, 2010 From the Re.: U.S. Appl. No. 11/607,075.
Response Dated Oct. 12, 2009 to Notice of Allowance of Jul. 16, 2009 From the Re.: U.S. Appl. No. 12/084,559.
Response Dated Jan. 14, 2010 to Official Action of Sep. 15, 2009 From the Re.: U.S. Appl. No. 10/616,307.
Response Dated Jan. 14, 2010 to Official Action of Sep. 15, 2009 From the Re.: U.S. Appl. No. 10/836,223.
Response Dated Oct. 14, 2009 to Official Action of May 14, 2009 From the Re.: U.S. Appl. No. 11/656,548.
Response Dated Dec. 15, 2010 to Official Action of Jul. 19, 2010 From the Re.: U.S. Appl. No. 11/656,548.
Response Dated Nov. 18, 2010 to Official Action of Jul. 19, 2010 From the Re.: U.S. Appl. No. 11/607,075.
Response Dated Jan. 21, 2010 to Official Action of Sep. 21, 2009 From the Re.: U.S. Appl. No. 11/798,017.
Response Dated Feb. 22, 2010 to Communication Pursuant to Article 94(3) EPC of Oct. 21, 2009 From the European Patent Office Re.: Application No. 02716285.8.
Response Dated Mar. 24, 2011 to Official Action of Dec. 8, 2010 From the Re.: U.S. Appl. No. 09/641,973.
Response Dated Aug. 25, 2010 to Official Action of Jul. 27, 2010 From the Re.: U.S. Appl. No. 10/616,307.
Response Dated Jul. 26, 2010 to Official Action of Apr. 28, 2010 From the Re.: U.S. Appl. No. 10/616,301.
Response Dated May 26, 2010 to Official Action of Mar. 19, 2010 From the Re.: U.S. Appl. No. 10/240,239.
Response Dated Jan. 27, 2011 to Official Action of Nov. 1, 2010 From the Re.: U.S. Appl. No. 12/728,383.
Response Dated Dec. 28, 2009 to Official Action of Aug. 28, 2009 From the Re.: U.S. Appl. No. 10/240,239.
Response Dated Dec. 30, 2009 to Official Action of Sep. 1, 2009 From the Re.: U.S. Appl. No. 11/794,799.
Response Dated Dec. 30, 2009 to Official Action of Oct. 30, 2009 From the Re.: U.S. Appl. No. 11/980,690.
Response Dated Jan. 31, 2011 to Official Action of Sep. 30, 2010 From the Re.: U.S. Appl. No. 11/798,017.
Response Dated Mar. 31, 2011 to Official Action of Jan. 31, 2011 From the Re. U.S. Appl. No. 11/667,793.
Response to the International Search Report and the Written Opinion of Oct. 10, 2006 From the International Searching Authority Re.: Appliction No. PCT/IL06/00059.
Supplemental Response After Interview Dated Aug. 4, 2010 to Official Action of Mar. 2, 2010 From the Re.: U.S. Appl. No. 11/980,617.
Supplementary European Search Report and the European Search Opinion Dated Mar. 16, 2011 From the European Patent Office Re. Application No. 05803689.8.
Supplementary European Search Report Dated Dec. 12, 2005 From the European Patent Office Re.: Application No. 03810570.6.
Supplementary Partial European Search Report and the European Search Opinion Dated Dec. 15, 2009 From the European Patent Office Re.: Application No. 06832278.3.
Supplementary Partial European Search Report and the European Search Opinion Dated Oct. 16, 2009 From the European Patent Office Re.: Application No. 06756259.5.
Supplementary Partial European Search Report Dated Nov. 11, 2008 From the European Patent Office Re.: Application No. 01951883.6.
Written Opinion Dated Feb. 1, 2006 From the International Searching Authority of the Patent Cooperation Treaty Re.: Application No. PCT/IL05/00048.
Written Opinion Dated Jul. 1, 2008 From the International Searching Authority of the Patent Cooperation Treaty Re.: Application No. PCT/IL06/00834.
Written Opinion Dated Jul. 2, 2007 From the International Searching Authority of the Patent Cooperation Treaty Re.: Application No. PCT/IL2006/001291.
Written Opinion Dated Aug. 3, 2006 From the International Searching Authority of the Patent Cooperation Treaty Re.: Application No. PCT/IL05/001173.
Written Opinion Dated Oct. 10, 2006 From the International Searching Authority of the Patent Cooperation Treaty Re.: Application No. PCT/IL06/00059.
Written Opinion Dated Mar. 23, 2006 From the International Searching Authority of the Patent Cooperation Treaty Re.: Application No. PCT/IL05/00572.
Written Opinion Dated May 24, 2007 From the International Searching Authority of the Patent Cooperation Treaty Re.: Application No. PCT/IL05/00575.
Written Opinion Dated Jul. 25, 2008 From the International Searching Authority of the Patent Cooperation Treaty Re.: Application No. PCT/IL05/001173.
Written Opinion Dated Mar. 26, 2007 From the International Searching Authority of the Patent Cooperation Treaty Re.: Application No. PCT/IL05/00394.
Beekman et al. “Efficient Fully 3-D Iterative SPECT Reconstruction With Monte Carlo-Based Scatter Compensation”, IEEE Transactions on Medical Imaging, 21(8): 867-877, Aug. 2002.
Bloch et al. “Application of Computerized Tomography to Radiation Therapy and Surgical Planning”, Proceedings of the IEEE, 71(3): 351-355, Mar. 1983.
Bromiley et al. “Attenuation Correction in PET Using Consistency Conditions and a Three-Dimensional Template”, IEEE Transactions on Nuclear Science, XP002352920, 48(4): 1371-1377, 2001. p. 1376, col. 2, § 2.
Brown et al. “Method for Segmenting Chest CT Image Data Using an Anatomical Model: Preliminary Results”, IEEE Transactions on Medical Imaging, 16(6): 828-839, Dec. 1997.
Chengazi et al. “Imaging Prostate Cancer With Technetium-99m-7E11-05.3 (CYT-351)”, Journal of Nuclear Medicine, 38: 675-682, 1997.
Corstens et al. “Nuclear Medicine's Role in Infection and Inflammation”, The Lancet, 354: 765-770, 1999.
Day et al. “Localization of Radioiodinated Rat Fibrogen in Transplanted Rat Tumors”, Journal of the National Cancer Institute, 23(4): 799-812, 1959.
Del Guerra et al. “An Integrated PET-SPECT Small Animal Imager: Preliminary Results”, Nuclear Science Symposium, IEEE Records, 1: 541-544, 1999.
Gilland et al. “A 3D Model of Non-Uniform Attenuation and Detector Response for Efficient Iterative Reconstruction in SPECT”, Physics in Medicine and Biology, XP002558623, 39(3): 547-561, Mar. 1994. p. 549-550, Section 2.3 ‘Active Voxel Reconstruction’, p. 551, Lines 4-8.
Gilland et al. “Simultaneous Reconstruction and Motion Estimation for Gated Cardiac ECT”, IEEE Transactions on Nuclear Science, XP011077797, 49(5): 2344-2349, Oct. 1, 2002. p. 2344, Section ‘Introduction’, First §.
Gugnin et al “Radiocapsule for Recording the Ionizing Radiation in the Gastrointestinal Tract”, UDC 615. 417:616.34-005.1-073.916-71 (All-Union Scientific-Research Institute of medical Instrument Design, Moscow. Translated from Meditsinskaya Tekhnika, 1:21-25, Jan.-Feb. 1972).
Hassan et al. “A Radiotelemetry Pill for the Measurement of Ionising Radiation Using a Mercuric Iodide Detector”, Physics in Medicine and Biology, 23(2): 302-308, 1978.
Herrmann et al. “Mitochondrial Proteome: Altered Cytochtrome C Oxidase Subunit Levels in Prostate Cancer”, Proteomics, XP002625778, 3(9): 1801-1810, Sep. 2003.
Kadrmas et al. “Static Versus Dynamic Teboroxime Myocardial Perfusion SPECT in Canines”, IEEE Transactions on Nuclear Science, 47(3): 1112-1117, Jun. 2000.
Krieg et al. “Mitochondrial Proteome: Cancer-Altered Metabolism Associated With Cytochrome C Oxidase Subunit Level Variation”, Proteomics, XP002625779, 4(9): 2789-2795, Sep. 2004.
Lavall?e et al. “Building a Hybrid Patient's Model for Augmented Reality in Surgery: A Registration Problem”, Computing in Biological Medicine, 25(2): 149-164, 1995.
Li et al. “A HOTLink/Networked PC Data Acquisition and Image Reconstruction System for a High Resolution Whole-Body PET With Respiratory or ECG-Gated Performance”, IEEE Nuclear Sience Symposium and Medical Imaging Conference, Norfolk, VA, USA, Nov. 10-16, 2002, XP010663724, 2: 1135-1139, Nov. 10, 2002. p. 1137, First col. 2nd §.
Lin et al. “Improved Sensor Pills for Physiological Monitoring”, NASA Technical Brief, JPL New Technology Report, NPO-20652, 25(2), 2000.
Mao et al. “Human Prostatic Carcinoma: An Electron Microscope Study”, Cancer Research, XP002625777, 26(5): 955-973, May 1966.
McJilton et al. “Protein Kinase C? Interacts With Bax and Promotes Survival of Human Prostate Cancer Cells”, Oncogene, 22; 7958-7968, 2003.
Mettler et al. “Legal Requirements and Radiation Safety”, Essentials of Nuclear Medicine Imaging, 2nd Ed., Chap.13: 323-331, 1985.
Moore et al. “Quantitative Multi-Detector Emission Computerized Tomography Using Iterative Attenuation Compensation”, Journal of Nuclear Medicine, XP002549083, 23(8): 706-714, Aug. 1982. Abstract, p. 707, Section ‘The Multi-Detector Scanner’, First §.
Pluim et al. “Image Registration by Maximization of Combined Mutual Information and Gradient Information”, IEEE Transactions on Medical Imaging, 19(8): 1-6, 2000.
Qi et al. “Resolution and Noise Properties of MAP Reconstruction for Fully 3-D PET”, IEEE Transactions on Medical Imaging, XP002549082, 19(5): 493-506, May 2000. p. 493, col. 2, Lines 10-21, p. 495, col. 1, Last §.
Stoddart et al. “New Multi-Dimensional Reconstructions for the 12-Detector, Scanned Focal Point, Single-Photon Tomograph”, Physics in Medicine and Biology, XP020021960, 37(3): 579-586, Mar. 1, 1992. p. 582, § 2-p. 585, § 1.
Storey et al. “Tc-99m Sestamibi Uptake in Metastatic Prostate Carcinoma”, Clinical Nuclear Medicine, XP009145398, 25(2): 133-134, Feb. 2000.
Wilson et al. “Non-Stationary Noise Characteristics for SPECT Images”, Proceedings of the Nuclear Science Symposium and Medical Imaging Conference, Santa Fe, CA, USA, Nov. 2-9, 1991, XP010058168, p. 1736-1740, Nov. 2, 1991. p. 1736, col. 2, Lines 4-6.
Xu et al. “Quantitative Expression Profile of Androgen-Regulated Genes in Prostate Cancer Cells and Identification of Prostate-Specific Genes”, International Journal of Cancer, 92: 322-328, 2001.
Official Action Dated Jun. 28, 2011 From the Re. U.S. Appl. No. 11/628,074.
Examination Report Dated Jun. 22, 2011 From the Government of India, Patent Office, Intellectual Property Building Re. Application No. 2963/CHENP/2006.
Official Action Dated Mar. 9, 2011 From the Re.: U.S. Appl. No. 10/616,301.
Response Dated Jun. 7, 2011 to Official Action of Mar. 9, 2011 From the Re.: U.S. Appl. No. 10/616,301.
Response Dated Jun. 28, 2011 to Official Action of Dec. 28, 2010 From the Re.: U.S. Appl. No. 11/607,075.
Communication Pursuant to Article 94(3) EPC Dated Sep. 22, 2011 From the European Patent Office Re. Application No. 06756258.7.
Notice of Allowance Dated Sep. 16, 2011 From the Re.: U.S. Appl. No. 11/607,075.
Official Action Dated Sep. 12, 2011 From the Re. U.S. Appl. No. 11/980,653.
Official Action Dated Sep. 12, 2011 From the Re. U.S. Appl. No. 12/087,150.
Official Action Dated Sep. 13, 2011 From the Re. U.S. Appl. No. 11/976,852.
Response Dated Sep. 12, 2011 to Official Action of Jul. 11, 2011 From the Re.: U.S. Appl. No. 11/980,683.
Response Dated Sep. 20, 2011 to Official Action of Apr. 20, 2011 From the Re.: U.S. Appl. No. 11/798,017.
Ellestad “Stress Testing: Principles and Practice”, XP008143015, 5th Edition, p. 432, Jan. 1, 2003.
Gilland et al. “Long Focal Length, Asymmetric Fan Beam Collimation for Transmission Acquisition With a Triple Camera SPECT System”, IEEE Transactions on Nuclear Science, XP011087666, 44(3): 1191-1196, Jun. 1, 1997.
Meyers et al. “Age, Perfusion Test Results and Dipyridamole Reaction”, Radiologic Technology, XP008142909, 73(5): 409-414, May 1, 2002.
Zhang et al. “Potential of a Compton Camera for High Performance Scintimammography”, Physics in Medicine and Biology, XP020024019, 49(4): 617-638, Feb. 21, 2004.
Official Action Dated Jul. 12, 2011 From the Re.: U.S. Appl. No. 09/641,973.
Official Action Dated Jul. 11, 2011 From the Re.: U.S. Appl. No. 11/980,683.
Official Action Dated Mar. 6, 2012 From the Re. U.S. Appl. No. 12/792,856.
Restriction Official Action Dated Mar. 9, 2012 From the Re. U.S. Appl. No. 11/976,852.
Office Action Dated Jul. 17, 2007 From the Israeli Patent Office Re.: Application No. 154323 and Its Translation Into English.
Official Action Dated Apr. 16, 2012 From the Re.: U.S. Appl. No. 10/836,223.
Restriction Official Action Dated Apr. 13, 2012 From the Re. U.S. Appl. No. 11/989,223.
Response Dated Nov. 14, 2011 to Official Action of Sep. 12, 2011 From the Re. U.S. Appl. No. 12/087,150.
Response Dated Oct. 24, 2011 to Official Action of May 23, 2011 From the Re. U.S. Appl. No. 11/667,793.
Restriction Official Action Dated Nov. 15, 2011 From the Re. U.S. Appl. No. 11/980,683.
Response Dated Dec. 8, 2011 to Restriction Official Action of Nov. 8, 2011 From the Re. U.S. Appl. No. 12/309,479.
Notice of Panel Decision From Pre-Appeal Brief Review Dated Feb. 29, 2012 From the Re.: U.S. Appl. No. 10/836,223.
Official Action Dated Mar. 1, 2012 From the Re.: U.S. Appl. No. 10/616,307.
Official Action Dated Feb. 28, 2012 From the Re.: U.S. Appl. No. 09/641,973.
Official Action Dated Jul. 30, 2012 From the Re.: U.S. Appl. No. 11/980,683.
Bowsher et al. “Treatment of Compton Scattering in Maximum-Likelihood, Expectation-Maximization Reconstructions of SPECT Images”, Journal of Nuclear Medicine, 32(6): 1285-1291, 1991.
Official Action Dated Dec. 20, 2011 From the Re. U.S. Appl. No. 12/309,479.
Response Dated Nov. 13, 2011 to Official Action of Sep. 12, 2011 From the Re. U.S. Appl. No. 11/980,653.
Response Dated Dec. 29, 2011 to Office Action of Jul. 17, 2007 From the Israeli Patent Office Re.: Application No. 154323.
Berman et al. “Dual-Isotope Myocardial Perfusion SPECT With Rest Thallium-201 and Stress Tc-99m Sestamibi”, Cardiology Clinics, 12(2): 261-270, May 1994.
DeGrado et al. “Topics in Integrated Systems Physiology. Tracer Kinetic Modeling in Nuclear Cardiology”, Journal of Nuclear Cardiology, 7: 686-700, 2000.
Links “Advances in SPECT and PET Imaging”, Annals in Nuclear Medical Science, 13(2): 107-120, Jun. 2000.
Communication Pursuant to Article 94(3) EPC Dated Nov. 18, 2011 From the European Patent Office Re. Application No. 05803689.8.
Response Dated Nov. 14, 2011 to Official Action of Jul. 12, 2011 From the Re.: U.S. Appl. No. 09/641,973.
Response Dated Nov. 23, 2011 to Official Action of May 23, 2011 From the Re.: U.S. Appl. No. 10/616,307.
Response Dated Nov. 23, 2011 to Official Action of May 23, 2011 From the Re.: U.S. Appl. No. 11/980,690.
Response Dated Nov. 29, 2011 to Official Action of Jun. 28, 2011 From the Re. U.S. Appl. No. 11/628,074.
Notice of Allowance Dated Feb. 2, 2012 From the Re. U.S. Appl. No. 11/628,074.
Official Action Dated Jan. 19, 2012 From the Re. U.S. Appl. No. 11/667,793.
Official Action Dated Jan. 23, 2012 From the Re. U.S. Appl. No. 12/087,150.
Jin et al. “Reconstruction of Cardiac-Gated Dynamic SPECT Images”, IEEE International Conference on Image Processing 2005, ICIP 2005, Sep. 11-14, 2005, 3: 1-4, 2005.
Toennies et al. “Scatter Segmentation in Dynamic SPECT Images Using Principal Component Analysis”, Progress in Biomedical Optics and Imaging, 4(23): 507-516, 2003.
Applicant-Initiated Interview Summary Dated Jan. 28, 2013 From the Re.: U.S. Appl. No. 11/798,017.
Official Action Dated Feb. 7, 2013 From the Re. U.S. Appl. No. 11/980,653.
Communication Under Rule 71(3) EPC Dated Feb. 26, 2013 From the European Patent Office Re. Application No. 06756259.5.
Official Action Dated Feb. 22, 2013 From the Re.: U.S. Appl. No. 10/616,307.
Advisory Action Before the Filing of an Appeal Brief Dated Feb. 26, 2013 From the U.S. Appl. No. 11/989,223.
Notice of Allowance Dated Feb. 27, 2013 From the Re. U.S. Appl. No. 12/514,785.
Official Action Dated Nov. 30, 2012 From the Re. U.S. Appl. No. 11/989,223.
Applicant-Initiated Interview Summary Dated May 1, 2013 From the Re. U.S. Appl. No. 11/980,653.
Advisory Action before the Filing of an Appeal Brief Dated May 21, 2013 From the Re. U.S. Appl. No. 11/980,653.
Applicant-Initiated Interview Summary Dated May 9, 2013 From the Re. U.S. Appl. No. 12/448,473.
Communication Pursuant to Article 94(3) Epc Dated 12 Nov. 2012 From the European Patent Office Re. Application No. 06756258.7.
Communication Pursuant to Article 94(3) Epc Dated 17 Sep. 2012 From the European Patent Office Re. Application No. 06832278.3.
Communication Pursuant to Article 94(3) Epc Dated 26 Oct. 2012 From the European Patent Office Re. Application No. 05803689.8.
Notice of Allowance Dated 15 Nov. 2012 From the Re.: Application No. 11/980,683.
Notice of Allowance Dated 26 Oct. 2012 From the Re. Application No. 12/514,785.
Notice of Allowance Dated 28 Sep. 2012 From the Re. Application No. 12/792,856.
Official Action Dated 02 Aug. 2012 From the Re. Application No. 12/087,150.
Official Action Dated 10 Oct. 2012 From the No. 11/798,017.
Official Action Dated 11 Oct. 2012 From the Re. Application No. 11/976,852.
Official Action Dated 30 Nov. 2012 From the Re. Application No. 12/514,785.
Official Action Dated 31 Aug. 2012 From the Re. Application No. 11/980,653.
Restriction Official Action Dated 16 Aug. 2012 From the Re. Application No. 12/448,473.
Summons to Attend Oral Proceedings Pursuant to Rule 115(1) EPC Dated Nov. 29, 2012 From the European Patent Office Re. Application No. 06756259.5.
Supplementary European Search Report and the European Search Opinion Dated Nov. 13, 2012 From the European Patent Office Re. Application No. 06728347.3.
Brzymialkiewicz et al. “Evaluation of Fully 3-D Emission Mammotomography With a Compact Cadmium Zinc Telluride Detector”, IEEE Transactions on Medical Imaging, 24(7): 868-877, Jul. 2005.
Cancer Medicine “Radiolabeled Monoclonal Antibodies. Historical Perspective”, Cancer Medicine, 5th Ed., Sec.16: Principles of Biotherapeutics, Chap.65: Monoclonal Serotherapy, 2000.
Handrick et al. “Evaluation of Binning Strategies for Tissue Classification in Computed Tomography Images”, Medical Imaging 2006: Image Processing, Proceedings of the SPIE, 6144: 1476-1486, 2006.
Jan et al. “Preliminary Results From the AROPET”, IEEE Nuclear Science Symposium Conference Record, Nov. 4-10, 2001, 3: 1607-1610, 2001.
Lange et al. “EM Reconstruction Algorithms for Emission and Transmission Tomography”, Journal of Computer Assisted Tomography, 8(2): 306-316, Apr. 1984.
Ohno et al. “Selection of Optimum Projection Angles in Three Dimensional Myocardial SPECTA”, IEEE Nuclear Science Symposium Conference Record 2001, 4: 2166-2169, 2001.
Ohrvall et al. “Intraoperative Gamma Detection Reveals Abdominal EndocrineTumors More Efficiently Than Somatostatin Receptor Scintigraphy”, 6th Conference on Radioimmunodetection and Radioimmunotherapy of Cancer, Cancer, 80: 2490-2494, 1997.
Ouyang et al. “Incorporation of Correlated Structural Images in PET Image Reconstruction”, IEEE Transactions of Medical Imaging, 13(4): 627-640, Dec. 1994.
Rockmore et al. “A Maximum Likelihood Approach to Emission Image Reconstruction From Projections”, IEEE Transactions on Nuclear Science, 23(4): 1428-1432, Aug. 1976.
Seret et al. “Intrinsic Uniformity Requirements for Pinhole SPECT”, Journal of Nuclear Medicine Technology, 34(1): 43-47, Mar. 2006.
Shepp et al. “Maximum Likelihood Reconstruction for Emission Tomography”, IEEE Transactions on Medical Imaging, MI-1: 113-122, Oct. 1982.
Sitek et al. “Reconstruction of Dynamic Renal Tomographic Data Acquired by Slow Rotation”, The Journal of Nuclear Medicine, 42(11): 1704-1712, Nov. 2001.
Smither “High Resolution Medical Imaging System for 3-D Imaging of Radioactive Sources With 1 mm FWHM Spatial Resolution”, Proceedings of the SPIE, Medical Imaging 2003: Physics of Medical Imaging, 5030: 1052-1060, Jun. 9, 2003.
Solanki “The Use of Automation in Radiopharmacy”, Hospital Pharmacist, 7(4): 94-98, Apr. 2000.
Thorndyke et al. “Reducing Respiratory Motion Artifacts in Positron Emission Tomography Through Retrospective Stacking”, Medical Physics, 33(7): 2632-2641, Jul. 2006.
Tornai et al. “A 3D Gantry Single Photon Emission Tomograph With Hemispherical Coverage for Dedicated Breast Imaging”, Nuclear Instruments & Methods in Physics Research, Section A, 497: 157-167, 2003.
Weldon et al. “Quantification of Inflammatory Bowel Disease Activity Using Technetium-99m HMPAO Labelled Leucocyte Single Photon Emission Computerised Tomography (SPECT)”, Gut, 36: 243-250, 1995.
Advisory Action Before the Filing of an Appeal Brief Dated Feb. 26, 2013 From the Re. U.S. Appl. No. 12/514,785.
Notice of Allowance Dated Feb. 21, 2013 From the Re. U.S. Appl. No. 11/798,017.
Notice of Allowance Dated Mar. 14, 2013 From the Re.: U.S. Appl. No. 11/798,017.
Official Action Dated Mar. 11, 2013 From the Re. U.S. Appl. No. 13/345,719.
Studen “Compton Camera With Position-Sensitive Silicon Detectors”, Doctoral Thesis, University of Ljubljana, Faculty of Mathematics and Physics, 36 P.
Advisory Action Before the Filing of an Appeal Brief Dated Feb. 26, 2013 From the Re. U.S. Appl. No. 11/989,223.
Notice of Allowance Dated Jun. 21, 2013 From the Re. U.S. Appl. No. 11/980,653.
Notice of Allowance Dated Jun. 14, 2013 From the Re. U.S. Appl. No. 10/616,307.
Official Action Dated Jun. 12, 2013 From the Re. U.S. Appl. No. 12/087,150.
Bacharach et al. “Attenuation Correction in Cardiac Positron Emission Tomography and Single-Photon Emission Computed Tomography”, Journal of Nucelar Cardiology, 2(3): 246-255, 1995.
Uni Magdeburg “Attenuation Map”, University of Magdeburg, Germany, Retrieved From the Internet, Archived on Jul. 31, 2002.
Zaidi et al. “Determination of the Attenuation Map in Emission Tomography”, Journal of Nuclear Medicine, 44(2): 291-315, 2003.
Official Action Dated Dec. 19, 2012 From the Re. U.S. Appl. No. 12/448,473.
Notice of Allowance Dated Dec. 26, 2012 From the Re.: U.S. Appl. No. 11/980,690.
Communication Pursuant to Article 94(3) EPC Dated Sep. 16, 2013 From the European Patent Office Re.: Application No. 06832278.3.
Notice of Allowance Dated Jul. 19, 2013 From the Re. U.S. Appl. No. 11/989,223.
Notice of Allowance Dated Aug. 20, 2013 From the Re. U.S. Appl. No. 11/932,872.
Notice of Allowance Dated Jul. 25, 2013 From the Re. U.S. Appl. No. 13/345,719.
Official Action Dated Aug. 5, 2013 From the Re. U.S. Appl. No. 12/309,479.
Official Action Dated Sep. 5, 2013 From the Re. U.S. Appl. No. 13/947,198.
Official Action Dated Aug. 14, 2013 From the Re. U.S. Appl. No. 12/448,473.
Official Action Dated Jul. 31, 2013 From the Re. U.S. Appl. No. 11/667,793.
Supplemental Notice of Allowability Dated Aug. 20, 2013 From the Re. U.S. Appl. No. 11/980,653.
Berman et al. “D-SPECT: A Novel Camera for High Speed Quantitative Molecular Imaging: Initial Clinical Results”, The Journal of Nuclear Medicine, 47(Suppl.1): 131P, 2006.
Berman et al. “Myocardial Perfusion Imaging With Technetium-99m-Sestamibi: Comparative Analysis of Available Imaging Protocols”, The Journal of Nuclear Medicine, 35: 681-688, 1994.
Borges-Neto ct al. “Perfusion and Function at Rest and Treadmill Exercise Using Technetium-99m-Sestamibi: Comparison of One- and Two-Day Protocols in Normal Volunteers”, the Journal of Nuclear Medicine, 31(7): 1128-1132, Jul. 1990.
Kwok et al. “Feasability of Simultaneous Dual-Isotope Myocardial Perfusion Acquisition Using a Lower Dose of Sestamibi”, European Journal of Nuclear Medicine, 24(3): 281-285, Mar. 1997.
Patton et al. “D-SPECT: A New Solid State Camera for High Speed Molecular Imaging”, The Journal of Nuclear Medicine, 47(Suppl.1): 189P, 2006.
Notice of Allowance Dated Jul. 15, 2013 From the Re. U.S. Appl. No. 11/932,987.
Official Action Dated Jul. 5, 2013 From the Re.: U.S. Appl. No. 11/656,548.
Communication Pursuant to Article 94(3) EPC Dated Nov. 25, 2013 From the European Patent Office Re. Application No. 06756258.7.
Notice of Allowance Dated Dec. 17, 2013 From the Re. U.S. Appl. No. 13/913,804.
Official Action Dated Nov 15, 2013 From the Re. U.S. Appl. No. 13/345,773.
Official Action Dated Dec. 16, 2013 From the Re. U.S. Appl. No. 12/087,150.
Official Action Dated Feb. 10, 2014 From the Re. U.S. Appl. No. 11/667,793.
Official Action Dated Jul. 19, 2010 From the Re.: U.S. Appl. No. 11/607,075.
Official Action Dated Jul. 19, 2010 From the Re.: U.S. Appl. No. 11/656,548.
Response Dated Jul. 1, 2010 to Official Action of Mar. 2, 2010 From the Re.: U.S. Appl. No. 10/836,223.
Response Dated Jul. 8, 2010 to Official Action of Apr. 9, 2010 From the Re.: U.S. Appl. No. 11/798,017.
Response Dated Jun. 23, 2010 to Official Action of Feb. 23, 2010 From the Re.: U.S. Appl. No. 09/641,973.
Applicant-Initiated Interview Summary Dated Jan. 29, 2014 From the Re. U.S. Appl. No. 13/345,773.
Applicant-Initiated Interview Summary Dated Mar. 20, 2014 From Re. U.S. Appl. No. 12/087,150.
Communication Pursuant to Article 94(3) EPC Dated May 8, 2014 From the European Patent Office Re. Application No. 05803689.8.
Official Action Dated Apr. 11, 2014 From Re. U.S. Appl. No. 12/309,479.
Official Action Dated May 13, 2014 From Re. U.S. Appl. No. 12/448,473.
Sharir et al. “D-SPECT: High Speed Myocardial Perfusion Imaging: A Comparison With Dual Detector Anger Camera (A-SPECT)”, The Journal of Nuclear Medicine, 48(Suppl.2): 51P, # 169, 2007.
Related Publications (1)
Number Date Country
20040015075 A1 Jan 2004 US
Provisional Applications (1)
Number Date Country
60286044 Apr 2001 US
Continuation in Parts (3)
Number Date Country
Parent 09727464 Dec 2000 US
Child 10343792 US
Parent 09714164 Nov 2000 US
Child 09727464 US
Parent 09641973 Aug 2000 US
Child 09714164 US