The present invention relates to a radioactive emission probe equipped with a position tracking system. More particularly, the present invention relates to the functional integration of a radioactive emission probe 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 probe 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 extent of complications, and require a more intensive care and monitoring regimen. 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 further advantages 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 comprising 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 GJ”, 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 distrainable 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 graphic 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 threshold 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, with minimal damage to the surrounding, non affected tissues.
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.
Furthermore, prior art radiation emission detectors and (or) biopsy probes, while being suitable for identifying the location of the radiation site, leave something to be desired from the standpoint of facilitating the removal or other destruction of the detected cancerous tissue, with minimal trauma.
The combination of modalities, as is offered by the present invention, can reduce the margin of error in locating 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, which in turn will result in less invasive and less destructive surgical procedures and fewer cases of mistaken diagnoses.
The present invention successfully addresses the shortcomings of the presently known configurations by providing a radioactive emission probe in communication with a position tracking system and the use thereof in a variety of systems and methods of medical imaging and procedures. Specifically, wide aperture collimation—deconvolution algorithms are provided, for obtaining a high-efficiency, high resolution image of a radioactivity emitting source, by scanning the radioactivity emitting source with a probe of a wide-aperture collimator, and at the same time, monitoring the position of the radioactive emission probe, at very fine time intervals, to obtain the equivalence of fine-aperture collimation. The blurring effect of the wide aperture is then corrected mathematically. Furthermore, an imaging method by depth calculations is provided, based on the attenuation of photons of different energies, which are emitted from the same source, coupled with position monitoring.
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.
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:
The present invention relates to a radioactive emission probe in communication with a position tracking system and the use thereof in a variety of systems and methods of medical imaging and procedures. Specifically, wide-aperture collimation—deconvolution algorithms are provided, for obtaining a high-efficiency, high resolution image of a radioactivity emitting source, by scanning the radioactivity emitting source with a probe of a wide-aperture collimator, and at the same time, monitoring the position of the radioactive emission probe, at very fine time intervals, to obtain the equivalence of fine-aperture collimation. The blurring effect of the wide aperture is then corrected mathematically. Furthermore, an imaging method by depth calculations is provided, based on the attenuation of photons of different energies, which are emitted from the same source, coupled with position monitoring.
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.
Functional imaging, or 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 probes has been disclosed in the medical literature for at least forty years. Functional imaging shows the metabolic activity of body tissue, since dying or damaged body tissue absorbs radiopharmaceuticals at a different rate from a healthy tissue. The functional image may be used for example, to study cardiac rhythm, or respiratory rhythm. However, a functional image may not show structural, or anatomic details.
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,
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 probe 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 probe 22 and, as is further detailed below, for constructing the image of the radioactivity emitting source in system-of-coordinates 28. As shown in
It will be appreciated that system 20 of radioactivity emission detector 22 and position tracking system 24 is inherently different from known SPECT and PET imaging systems, as well as from other imaging systems such as X-ray, Mammography, CT, and MRI, since the motion of detector 22 of the present invention is not limited to a predetermined track or tracks, with a respect to an immovable gantry. Rather, detector 22 of the present invention is adapted for a variable-course motion, which may be for example, free-hand scanning, variable-course motion on a linkage system, motion within a body lumen, endoscopic motion through a trocar valve, or another form of variable-course motion.
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.
As is shown in
As is shown in
Radioactive emission probes 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 scintillator crystals and liquids, such as C14H10, C14H12, C10H8, etc., Plastics, NE102A, NE104, NE110, Pilot U and inorganic scintillator crystals, 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.
As is shown in
A radioactive emission 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 probe 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 system-of-coordinates.
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 probe which is in communication 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 probe in the system-of-coordinates, thereby defining the image 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
A method for calculating a position of a radioactivity emitting source in a first system-of-coordinates and for projecting the image 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 probe being in communication 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 probe in the first system-of-coordinates, thereby defining the image of the radioactivity emitting source in the first system-of-coordinates and projecting the image of the radioactivity emitting source onto the second system-of-coordinates.
It will be appreciated that the combination of a radioactive emission probe 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 probe, 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.
Structural imaging modalities, which provide anatomic, or structural maps of the body, 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 planer X-ray imager, a fluoroscope, a computerized tomography scanner, a magnetic resonance imager an ultrasound imager, an impedance 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 gastrointestinal (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 Doppler 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 system-of-coordinates.
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 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.
In accordance with the present invention, a structural imaging probe, for example, an ultrasound probe, may be combined with a position tracking system, in a manner analogous to System 20 of radioactivity emission detector 22 and position tracking system 24 (
Additionally, a structural imaging probe, for example, an ultrasound probe, may be combined with system 20 of radioactivity emission detector 22 and position tracking system 24 (
Furthermore, the structural imaging modality may have an additional, dedicated position tracking system, or share position tracking system 24 of radioactivity emission detector 22.
Position tracking may also be accomplished by using imaging information from the structural imaging system. This may be accomplished by tracking relative changes from one image to another to determine relative motion.
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, laparoscopic prob s, thermal probes and suction/irrigation probes. Examples of such surgical instruments employed in a variety of medical cont xts 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 probe 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 in communication 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 intracorporeal 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-D-Phe1]-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).
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
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 uptake 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 he 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.
Additionally or alternatively, a structural imaging probe, for example, an ultrasound probe, or another structural probe, as known, may be incorporated with the surgical instrument.
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
Reference is now made to
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
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 2020 tc Imager™, 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 commonly owned, now abandoned, U.S. patent application No. 09/610,490, entitled, “method for registering coordinate systems,” 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
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).
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), infared 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
In one embodiment of the invention, the imaging software algorithm 217 employs an averaging process to refine the curve of
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:
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
In another embodiment of the invention, the imaging software algorithm 217 may employ a minimizing process to refine the curve of
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
Reference is now made to
In accordance with preferred embodiments of the present invention, image acquisition and reconstruction algorithms are provided, based on image acquisition with wide-aperture collimation and image reconstruction, which includes deconvolution. The overall algorithms are herethereto referred to as wide-aperture collimation—deconvolution algorithms.
In essence, the wide-aperture collimation—deconvolution algorithms enable one to obtain a high-efficiency, high resolution image of a radioactivity emitting source, by scanning the radioactivity emitting source with a probe of a wide-aperture collimator, and at the same time, monitoring the position of the radioactive emission probe, at very fine time intervals, to obtain the equivalence of fine-aperture collimation. The blurring effect of the wide aperture is then corrected mathematically.
The wide-aperture collimation—deconvolution algorithms are described hereinbelow, in conjunction with
It will be appreciated that the wide-apeture collimation—deconvolution algorithms of the present invention apply also to systems on fixed gantries, such as gamma camera and SPECT.
Referring further to the drawings,
Consider a single-pixel, wide-bore-collimator probe 707, seen in
By contrast, as seen in
Yet, there are disadvantages to wide-bore-collimator probe 707:
With regard to the first point, the generation of an image, as wide-bore-collimator probe 707 is moved in space, while its position and angular orientation are accurately tracked, at very short time intervals, for example, of about 100 or 200 ms, or any other short time interval, a one-, two-, or three-dimensional image of counting rate as a function of position can be obtained, by data processing.
More specifically, knowing the position and orientation of probe 707 at each time interval and the photon count rate at that position and orientation can be used to reconstruct the radiation density of an unknown object, even in three dimensions.
With regard to the second point, the blurring effect of the wide-angle aperture, while it is known that the information is blurred, or convolved, by the wide-aperture collimator, a deconvolution process may be used to obtain dependable results. Moreover, the convolving function for a wide aperture depends only on the geometry of the collimator and may be expressed as a set of linear equations that can be readily solved.
Thus, in accordance with the present invention, a wide-bore collimator probe, having a position tracking system, operating at very short time intervals, and connected to a data processor for wide-aperture collimation—deconvolution algorithms, can be used for the construction of an image of radiation density in one-, two-, or three-dimensions, with high degree of accuracy.
It will be appreciated that similar analyses may be employed for wide aperture probes having non-circular collimators. For example, the wide-aperture probe may have a rectangular collimator of a single cell or of a coarse grid of cells. Additionally, the collimator may be a wide-angle collimator. A corresponding deconvolution function may be used by the data processor.
Reference is now made to
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 (
Reference is now made to
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 □(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 □(r, z) and to the total intensity I of the radiation spot.
Reference is now made to
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
As seen in
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
If the subdivision of rectangle V into small rectangles is sufficiently fine, then this step-function approximation is good enough for th estimation of radiation distribution I(Q).
Let each side of rectangle V be divided into n equal parts (
The space H is naturally isomorphic to the m-dimensional space of n×n matrixes (with its natural scalar product <•,•>).
Let I=(Ii j)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 . . . n IijΦij(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 (
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, Eεk=0 ,k=1, . . . , K).
Let M: H→H the operator in the space H of the form:
M=Σk=1 . . . KΦk{circle around (X)}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 invertible”. 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≧ . . . ≧λm24 0.
Let R be some natural number, I<R<m (R is the “regularization parameter” ). Let H(R) be the subspace of the space H spanned by the first R eigenvectors φl, . . . , 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=1, . . . , K.
Ψ(R)=Σk=1 . . . K ΨkΦk(R), (8)
M(R): H(R)→H(R) the operator of the form:
M(R)=Σk=1 . . . K Φk(R){circle around (X)}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 δk in (3) are known, and information about the element I of the space H is known a priori.
The subdivision of rectangle V 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 (
Reference is now made to
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 (
In accordance with the present invention, the wide-aperture collimation—deconvolution 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 designs, 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.
Other deconvolution methods are known and 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)
Reference is now made to
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-imensions. 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.
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 (pixellated) 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, R. 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.
Referring further to the drawings,
As seen in
Handheld probe 700 includes a radiation detector 706, mounted onto a housing 702, wherein the various electronic components (not shown) are contained. Housing 702 is preferably formed of a rigid, lightweight plastic, a composite, or the like, and includes a handle 704, for easy maneuvering of probe 700.
A control unit 710, which may be mounted on housing 702, may include basic control knobs, such as “stop”, “start”, and “pause.” Additionally or alternatively, control unit 710 may be a computer unit, such as a microcomputer or the like, having processing and memory units, contained within housing unit 702. Additionally, control unit 710 may include a display screen 718, mounted on housing unit 702, for displaying information such as gamma counts, gamma energies, device position, and the like. Display screen 718 may be interactive, for control and display. Control unit 710 may further include a data unit 720, for receiving a diskette, a minidisk, or the like. Preferably, data unit 720 is a read and write unit. An eject button 722 may be included with data unit 720.
A cable 724 may provide signal communication between handheld probe 700 and a main-data-collection-and-analysis-system 726, such as a PC computer or a server. Additionally or alternatively, signal communication with main-data-collection-and-analysis-system 726 may be wireless, for example, by radio frequency or infrared waves. Alternatively, hand-held probe 700 may be a stand-alone unit, operative with built-in computer unit 710. Additionally, data may be transferred to and from main-data-collection-and-analysis-system 726 via a diskette or a minidisk, from data unit 720.
A preferably rechargeable battery 716 may be attached to housing unit 702. Additionally or alternatively, a cable 712 may be used to provide power communication between handheld probe 700 and the grid (not shown), or between handheld probe 700 and main-data-collection-and-analysis-system 726.
Positioning device 714 is preferably a Navigation sensor, for determination of six coordinates X, Y and Z axes and rotational angles ρ,θ and φ, as shown in
As seen in
Additionally, as seen in
Alternatively, as seen in
As seen in
Preferably, radiation detector 706 is equipped with a positive contact array, for forming contact with each pixel 703, and a common negative contact. Preferably, each pixel 703 is connected to a preamplifier.
Preferably, radiation detector 706 is a single module array, for example, of 4×4, or of 16×16 pixels, of room temperature CdZnTe, obtained, for example, from IMARAD IMAGING SYSTEMS LTD., of Rehovot, ISRAEL, 76124, www.imarad.com.
Room temperature solid-state CdZnTe (CZT) is among the more promising nuclear detectors currently available. It has a better count-rate capability than other detectors on the market, and its pixilated structure provides intrinsic spatial resolution. Furthermore, because of the direct conversion of the gamma photon to charge-carriers, energy resolution is enhanced and there is better rejection of scatter events and improved contrast.
In accordance with the present invention, the detector may be optimized, in accordance with the teaching of “Electron lifetime determination in semiconductor gamma detector arrays,” bttp://urila.tripod.com/hecht.htm, “GdTe and CdZnTe Crystal Growth and Production of Gamma Radiation Detectors,” http://members.tripod.com/˜urila/crystal.htm, and “Driving Energy Resolution to the Noise Limit in Semiconductor Gamma Detector Arrays,” Poster presented at NSS2000 Conference, Lyon France, 15-20 Oct. 2000, http://urila.tripod.com/NSS.htm, all by Uri Lachish, of Guma Science, P.O.Box 2104, Rehovot 76120, Israel, urila@internet-zahav.net, all of whose disclosures are incorporated herein by reference.
Accordingly, radiation detector 706 may be a monolithic CdZnTe crystal, doped with a trivalent donor, such as indium. Alternatively, aluminum may be used as the trivalent donor. When a trivalent dopant, such as indium, replaces a bivalent cadmium atom within the crystal lattice, the extra electron falls into a deep trap, leaving behind an ionized shallow donor. The addition of more donors shifts the Fermi level from below the trapping band to somewhere within it. An optimal donor concentration is achieved when nearly all the deep traps become occupied and the Fermi level shifts to just above the deep trapping band.
Optimal spectral resolution may be achieved by adjusting the gamma charge collection time (i.e., the shape time) with respect to the electron transition time from contact to contact. Gamma photons are absorbed at different depth within the detector where they generate the electrons. As a result, these electrons travel a different distance to the counter electrode and therefore produce a different external signal for each gamma absorption event. By making the shape time shorter than the electron transition time, from contact to contact, these external signals become more or less equal leading to a dramatic improvement in resolution.
Furthermore, for a multi-pixel detector, the electrons move from the point of photon absorption towards the positive contact of a specific pixel. The holes, which arc far slower, move towards the negative contact, and their signal contribution is distributed over a number of pixels. By adjusting the gamma charge collection time (i.e., the shape time) with respect to the electron transition time from contact to contact, the detector circuit collects only the electrons' contribution to the signal, and the spectral response is not deteriorated by the charge of the holes.
For an optimal detector, crystal electrical resistively may be, for example, about 5×108 ohm cm. The bias voltage may be, for example, −200 volts. The shape time may be, for example, 0.5×10−6 sec. It will be appreciated that other values, which may be larger or smaller are also possible.
In accordance with a preferred embodiment of the present invention, control unit 710 includes data acquisition and control components, which further include a very small, single-module Detector Carrier Board (DCB). The DCB preferably includes a temperature control system, having a temperature sensor, a desired temperature setting, and a heat removal system, preferably operative by peltier cooling. Preferably, the DCB further includes a High Voltage (HV) power supply, a HV setting, a HV and dark current output-sensing, and power regulators, preferably having a range of about ±2V, a XAIM_MBAIS current driver, and noise filtering components.
Preferably, data acquisition and control components are based on Application Specific Integrated Circuit (ASIC) architecture for the control, calibration, and readout. ASIC data acquisition and control includes calibration of ASIC data, I/V conversion, amplification and shaping. Data identification includes threshold discrimination (i.e., noise rejection) and energy windows discrimination, wherein there may be one or several energy windows per radionuclide. Preferably, there are up to four energy windows per radionuclide, but it will be appreciated that another number is also possible.
Data acquisition relates to counting events per pixel, per energy window, for an acquisition period, which may be very short, for example, about 100 msec, in a continuous mode. It will be appreciated that larger or smaller counting periods arc also possible.
The events per pixel 703, per energy window, is synchronized with signals from positioning device 714, preferably via a DIO card, either within control unit 710, or main-data collection-and-analysis-system 726, or both. Additionally, initialization information, including Digital to Analog Convertor (DAC) information, may be stored in software of main-data-collection-and-analysis-system 726 or within control system 710.
Preferably, an Integrated Drive Electronics (IDE) system provides the electronic interface.
Referring further to the drawings,
An energy spectrum for each pixel 703 of radiation detector 706 is obtained in a classical fashion. Radiation detector 706 is irradiated by a flood source of a known photon energy, for example, 24 KeV, and for each pixel 703, such as 703(1), 703(2), 703(3) . . . 703(n), a summation of counts as a function of voltage is obtained, during a finite time interval. The location of the energy peak, corresponding to the peak photon energy, for example, 24 KeV is bounded, by an upper level (UL) and a lower level (LL) for that pixel 703(n), forming an energy window for the specific pixel. Only photons which fall within the bounded energy window for each pixel are counted, to exclude Compton scattering and pair production. A multi-energy source may be used, and several energy windows may be bounded for each pixel
After the energy windows, representing specific energy peaks, are determined for each pixel, they are stored in a memory unit.
During acquisition, each collimator cell 705(n) is operative as a single pixel. Thus, the sensitivity correction factor has to be at a collimator-cell level, rather than at a pixel-level.
To calculate the sensitivity correction factor, an average counts per cell 705, is obtained as:
During acquisition, the sum of counts within the bounded windows of all pixels in cell 705(n) is multiplied by the correction factor for that cell 705(n) to obtain a sensitivity corrected count rate.
Referring further to the drawings,
Referring further to the drawings,
As seen in
A uniform radiation field, formed of a sheet source (not shown), was placed directly behind the bar phantom 750, and bar phantom 750 was scanned with probe 700.
Probe 700 of the present embodiment comprised an eV Pen-type CdZnTe solid state detector with collimator diameter D, of 5 mm, and collimator length, L2 of 30 mm. The CdZnTe detector was attached to a charge sensitive preamp probe and connected to a Digital and analog V-target alpha system PC cards. The probe energy window calibration was performed at the beginning of the test by using EG&G Ortec Maestro 2K Tramp ISA Spectra Processing connected to the analog and the digital V-target alpha system cards. The probe position information was provided by MicroScribe-6DLX arm manufactured by Immersion Corporation. Acquisition time was 6 minutes.
Referring further to the drawings,
As seen in Table 1, there is a clear advantage to the probe of the present invention.
Good energy resolution of the detector is important for precise identification and separation of γ rays, for radionuclide identification and for scatter rejection. A major advantage of CdZnTe detector is better energy resolution, for example than that of the Nai(Tl) detector.
Referring further to the drawings,
Referring further to the drawings,
As seen in
As seen in
As seen in
Referring further to the drawings,
The transmitted intensity of a monochromatic gamma-ray bean of photon energy F, and intensity I0 crossing an absorbing layer, such as a tissue layer, of a depth d, is a function of the photons energy E, the layer thickness d, and the total linear attenuation coefficient as a function of energy, μtotal, of the material constituting the layer. The transmitted intensity is given by:
I(E)=I0(E)exp(−μtotal(E)d) (Eq-1)
The linear attenuation coefficient is expressed in cm−1 and is obtained by multiplying the cross section (in cm2/gr) with the absorbing medium density. The total linear attenuation coefficient accounts for absorption due to all the relevant interaction mechanisms: photoelectric effect, Compton scattering, and pair production.
The layer thickness d, which is the depth of the radiation source, can be measured using a radionuclide that emits two or more photon energies, since attenuation is a function of the photon energy.
For photons of different energies, originating from a same source, and having the same half-life, we get:
R=e
{μ(E
)−μ(E
)}d
ln(R)={μ(E2)−μ(E1)}d (Eq-6)
The source depth, d, can be calculated as:
The linear attenuation coefficients for specific energies are calculated from the photon mass attenuation and energy absorption coefficients table.
The ratio I0(E1)/I0(E2) for a known isotope or isotopes is calculated from an isotope table and the ratio I(E1)/I(E2) is measured at the inspected object edges.
Additionally, X-ray information, for example, mammography may be used, for more material linear attenuation coefficient, since X-ray imaging provides information about the material density.
For example, we may consider a lesion inside a soft tissue, such as a breast, at a distance d that holds an isotope of 123I, which emits two main photons, as follows:
E1=27 keV with 86.5%; and
E2=159 keV with 83.4%.
The soft tissue density is 0.8 g/cu3.
The linear attenuation coefficients for E1 and E2 are calculated from J. H Hubbell, “Photon Mass Attenuation and Energy—absorption Coefficients from 1 keV to 20 MeV”, Int. J. Appl. Radiat. Isat. Vol. 33. pp. 1269 to 1290, 1982, as follows:
μ(E1)=0.474 cm/g→μ(E1)=0.474 cm/g·0.8 g/cm3=0.38 1/cm
μ(E2)=0.1489 cm/g→μ(E2)=0.1489 cm/g·0.8 g/cm3=0.119 1/cm
The measured ratio between I(E1) to I(E2) on the attenuating soft tissue edge is 0.6153.
Using Eq-7, one gets that the lesion depth is: d=2 cm.
Alternatively, if the measured ration between I(E1) to I(E2) is 0.473 the extracted lesion depth is: d=3 cm.
It will be appreciated that when two or more isotopes used for obtaining the different photons, corrections for their respective half-lives may be required.
It will be appreciated that by calculating the depth of a radiation source at each position, one may obtain a radiation source depth map, in effect, a three-dimensional image of the radiation source. This information may be superimposed on the radiation source image, as produced by other methods of the present invention, as an independent check of the other methods. For example, a radiation source image produced by the wide-aperture collimation—deconvolution algorithms may be superimposed on a radiation source image produced by depth calculations of based on the attenuation of photons of different energies.
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:
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 syste m 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 assess 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 assess 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 blood-vessel clots. Blood-vessel 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.
This is a continuation-in-part of U.S. patent application Ser. No. 10/343,792, filed on Jul. 11, 2001, which is a National Phase application of PCT/IL01/00638, filed on Jul. 11, 2001, which is a continuation-in-part of U.S. patent application Ser. No. 09/727,464 filed Dec. 4, 2000, which is a continuation-in-part of U.S. patent application Ser. No. 09/714,164, filed Nov. 17, 2000, which is a continuation-in-part of U.S. patent application Ser. No. 09/641,973, filed Aug. 21, 2000. Additionally, this application is filed concurrently with co-pending application “INGESTIBLE PILL,” whose disclosure is incorporated herein by reference, and both applications derive priority from U.S. Provisional application No. 60/394,936, filed on Jul. 11, 2002.
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 |
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 et al. | 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 | Hogrefe 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 | Misic 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 |
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 | Tümer | 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 |
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 |
6194725 | Colsher 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 |
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 et al. | 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 et al. | 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 |
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 |
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 et al. | Jan 2004 | B2 |
6677755 | Belt et al. | Jan 2004 | B2 |
6680750 | Tournier et al. | Jan 2004 | B1 |
6694172 | Gagnon et al. | 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 |
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 |
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 |
7672491 | Krishnan et al. | Mar 2010 | B2 |
7680240 | Manjeshwar et al. | Mar 2010 | B2 |
7705316 | Rousso et al. | Apr 2010 | B2 |
7734331 | Dhawale et al. | Jun 2010 | B2 |
7826889 | David et al. | Nov 2010 | B2 |
7831024 | Metzler et al. | Nov 2010 | B2 |
7835927 | Schlotterbeck 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 |
8204500 | Weintraub et al. | Jun 2012 | B2 |
8338788 | Zilberstein et al. | Dec 2012 | 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 |
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 |
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 | Shanmugavel et al. | Jul 2004 | A1 |
20040138557 | Le et al. | Jul 2004 | A1 |
20040143449 | Behrenbruch 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 |
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 | Joung et al. | Jan 2005 | A1 |
20050020898 | Vosniak et al. | Jan 2005 | A1 |
20050020915 | Belardinelli et al. | Jan 2005 | A1 |
20050023474 | Persyk et al. | Feb 2005 | A1 |
20050029277 | Tachibana | Feb 2005 | A1 |
20050033157 | Klein et al. | Feb 2005 | A1 |
20050049487 | Johnson et al. | Mar 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 |
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 |
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 |
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 |
20070166297 | 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 |
20100121184 | Dhawale et al. | May 2010 | A1 |
20100140483 | Rousso et al. | Jun 2010 | A1 |
20100202664 | Busch et al. | Aug 2010 | A1 |
20100245354 | Rousso et al. | Sep 2010 | A1 |
20120172699 | Nagler et al. | Jul 2012 | A1 |
20120248320 | Wangerin et al. | Oct 2012 | A1 |
20120326034 | Sachs et al. | Dec 2012 | A1 |
20130114792 | Zilberstein et al. | May 2013 | A1 |
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 |
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 |
Entry |
---|
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. |
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. |
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. |
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 Inflammation”, 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. |
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. |
Hoffman et al. “Intraoperative Probes and Imaging Probes”, European Journal of Nuclear Medicine, 26(8): 913-935, 1999. |
Zhang et al. “An Innovative High Efficiency and High Resolution Probe for Prostate Imaging”, The Journal of Nuclear Medicine, 68: 18, 2000. Abstract. |
Jeanguillaume et al, “From the Whole-Body Counting to Imaging: The Computert Aided Collimation Gamma Camera Project (CACAO)”, Radiation Projection Dosimetry, 89(3-4):349-352, 2000. |
Quartuccia et al, “Computer Assisted Collimation Gamma Camera: A New Approach to Imaging Contaminated Tissues”, Radiation Projection Dosimetry, 89(3-4):343-348, 2000. |
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 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 Jul. 11, 2008 From the International Searching Authority of the Patent Cooperation Treaty Re.: Application No. PCT/IL06/01511. |
International Search Report May 24, 2007 From the International Searching Authority of the Patent Cooperation Treaty Re.: Application No. PCT/IL05/00575. |
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. 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 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 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 Mar. 26, 2007 From the International Searching Authority of the Patent Cooperation Treaty Re.: Application No. PCT/IL05/00394. |
Official Action Dated Jun. 1, 2006 From the United States Patent and Trademark Office Re.: U.S. Appl. No. 10/686,536. |
Official Action Dated Dec. 2, 2007 From the Israeli Patent Office Re.: Application No. 158442. |
Official Action Dated May 3, 2007 From the United States Patent and Trademark Office Re.: U.S. Appl. No. 10/240,239. |
Official Action Dated Sep. 4, 2008 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/533,568. |
Official Action Dated Sep. 5, 2002 From the United States Patent and Trademark Office Re.: U.S. Appl. No. 12/084,559. |
Official Action Dated Oct. 7, 2008 From the US Patent Office Re.: U.S. Appl. No. 10/616,301. |
Official Action Dated Aug. 10, 2007 From the United States Patent and Trademark Office Re.: U.S. Appl. No. 10/836,223. |
Official Action Dated Jul. 12, 2007 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/616,301. |
Official Action Dated Dec. 13, 2007 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/616,301. |
Official Action Dated Dec. 15, 2006 From the US Patent Office Re.: U.S. Appl. No. 10/616,301. |
Official Action Dated Apr. 15, 2008 From the United States Patent and Trademark Office Re.: U.S. Appl. No. 09/641,973. |
Official Action Dated Feb. 15, 2008 From the United States Patent and Trademark Office Re.: U.S. Appl. No. 10/343,792. |
Official Action Dated Jul. 15, 2008 From the United States Patent and Trademark Office Re.: U.S. Appl. No. 09/641,973. |
Official Action Dated Mar. 15, 2004 From the United States Patent and Trademark Office Re.: U.S. Appl. No. 09/725,316. |
Official Action Dated Jan. 17, 2006 From the United States Patent and Trademark Office Re.: U.S. Appl. No. 11/034,007. |
Official Action Dated Jul. 17, 2007 From the Israeli Patent Office Re.: Application No. 154323. |
Official Action Dated Apr. 20, 2006 From the United States Patent and Trademark Office Re.: U.S. Appl. No. 10/240,239. |
Official Action Dated Mar. 21, 2008 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/533,568. |
Official Action Dated Jun. 23, 2006 From the United States Patent and Trademark Office Re.: U.S. Appl. No. 09/727,464. |
Official Action Dated Jun. 25, 2008 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/616,301. |
Official Action Dated Sep. 25, 2006 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/616,301. |
Official Action Dated Sep. 30, 2008 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/616,301. |
Supplementary European Search Report Dated Dec. 12, 2005 From the European Patent Office Re.: Application No. 03810570.6. |
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 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. |
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). |
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. |
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. |
Final OA dated Jul. 12, 2007. |
Invitation to Pay Additional Fees. |
Invitation to pay additional fees dated Apr. 18, 2007. |
OA dated Sep. 4, 2008. |
OA of Jun. 1, 2006. |
OA of Aug. 10, 2007. |
OA of Jan. 17, 2006. |
OA of Jun. 19, 2006. |
OA of Dec. 2, 2007. |
OA of Jan. 7, 2009. |
Official Action Dated May 3, 2007 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/240,239. |
Official Action Dated Oct. 7, 2008 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/616,301. |
Official Action Dated Apr. 15, 2008 From the US Patent and Trademark Office Re.: U.S. Appl. No. 09/727,464. |
Official Action Dated Dec. 15, 2006 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/616,301. |
Official Action Dated Feb. 15, 2008 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/343,792. |
Official Action Dated Jul. 15, 2008 From the US Patent and Trademark Office Re.: U.S. Appl. No. 09/641,973. |
Official Action Dated Apr. 20, 2006 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/240,239. |
Official Action Dated Dec. 23, 2008 From the US Patent and Trademark Office Re.: U.S. Appl. No. 09/727,464. |
Official Action Dated Jun. 23, 2006 From the US Patent and Trademark Office 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 Sep. 12, 2002 from the International Searching Authority of the Patent Cooperation Treaty Re: Application No. PCT/IL02/00057. |
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 US Patent and Trademark Office Re.: U.S. Appl. No. 10/240,239. |
Official Action Dated Apr. 29, 2009 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/980,690. |
Response Dated Aug. 14, 2008 to Official Action of Apr. 15, 2008 From the US Patent and Trademark Office 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 Republic of China 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.: Appliction 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. |
Official Action Dated Apr. 8, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/980,690. |
Official Action Dated Apr. 28, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/616,301. |
Response Dated May 10, 2010 to Official Action of Apr. 8, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/980,690. |
Response Dated May 10, 2010 to Official Action of Jan. 8, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/656,548. |
Communication Pursuant to Article 94(3) EPC Dated Oct. 21, 2009 From the European Patent Office Re.: Application No. 02716285.8. |
Notice of Allowance Dated Sep. 17, 2009 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/533,568. |
Official Action Dated Sep. 1, 2009 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/794,799. |
Official Action Dated Jul. 2, 2004 From the US Patent and Trademark Office Re.: U.S. Appl. No. 09/641,973. |
Official Action Dated Sep. 2, 2009 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/343,792. |
Official Action Dated Aug. 11, 2009 From the US Patent and Trademark Office Re.: U.S. Appl. No. 09/641,973. |
Official Action Dated Sep. 15, 2009 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/616,307. |
Official Action Dated Sep. 15, 2009 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/836,223. |
Official Action Dated Sep. 16, 2009 From the US Patent and Trademark Office Re.: U.S. Appl. No. 09/727,464. |
Official Action Dated Sep. 21, 2009 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/798,017. |
Official Action Dated Aug. 28, 2009 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/240,239. |
Official Action Dated Oct. 30, 2009 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/980,690. |
Response Dated Dec. 10, 2009 to Official Action of Aug. 11, 2009 From the US Patent and Trademark Office Re.: U.S. Appl. No. 09/641,973. |
Response Dated Oct. 12, 2009 to Notice of Allowance of Jul. 16, 2009 From the US Patent and Trademark Office Re.: U.S. Appl. No. 12/084,559. |
Response Dated Oct. 14, 2009 to Official Action of May 14, 2009 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/656,548. |
Supplementary Partial European Search Report and the European Search Opinion Dated Oct. 16, 2009 From the European Patent Office Re.: Application No. 06756259.5. |
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 §. |
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, co1. 2, Lines 10-21, p. 495, co1. 1, Last §. |
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, co1. 2, Lines 4-6. |
Appeal Brief Dated Jan. 19, 2010 to Notice of Appeal of Nov. 16, 2009 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/616,301. |
Notice of Allowance Dated Nov. 23, 2009 From the US Patent and Trademark Office Re.: U.S. Appl. No. 12/084,559. |
Notice of Appeal and Pre-Appeal Brief Dated Jan. 4, 2010 to Official Action of Sep. 2, 2009 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/343,792. |
Official Action Dated Mar. 1, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/794,799. |
Official Action Dated Mar. 2, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/836,223. |
Official Action Dated Mar. 2, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/980,617. |
Official Action Dated Dec. 8, 2009 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/132,320. |
Official Action Dated Jan. 8, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/656,548. |
Official Action Dated Mar. 11, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/607,075. |
Official Action Dated Feb. 23, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 09/641,973. |
Response Dated Jan. 14, 2010 to Official Action of Sep. 15, 2009 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/836,223. |
Response Dated Jan. 21, 2010 to Official Action of Sep. 21, 2009 From the US Patent and Trademark Office 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 Dec. 28, 2009 to Official Action of Aug. 28, 2009 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/240,239. |
Response Dated Dec. 30, 2009 to Official Action of Sep. 1, 2009 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/794,799. |
Response Dated Dec. 30, 2009 to Official Action of Oct. 30, 2009 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/980,690. |
Supplementary Partial European Search Report and the European Search Opinion Dated Dec. 15, 2009 From the European Patent Office Re.: Application No. 06832278.3. |
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 §. |
Kadrmas et al. “Static Versus Dynamic Teboroxime Myocardial Perfusion SPECT in Canines”, IEEE Transactions on Nuclear Science, 47(3): 1112-1117, Jun. 2000. |
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 §. |
Written Opinion Dated Aug. 3, 2006 From the International Searching Authority of the Patent Cooperation Treaty Re.: Application No. CT/IL05/001173. |
Notice of Appeal Dated Nov. 16, 2009 to Official Action of Jul. 15, 2009 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/616,301. |
International Search Report Dated Oct. 10, 2006 From the International Searching Authority of the Patent Cooperation Treaty Re.: Application No. PCT/IL06/00059. |
Rajshekhar, “Continuous Impedence Monitoring During CT-Guided Stereotactic Surgery: Relative Value in Cystic and Solid Lesions”, British Journal of Neurosurgery, 6: 439-444, 1992. |
Official Action Dated Apr. 9, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/798,017. |
Communication Pursuant to Article 94(3) EPC Dated Mar. 8, 2010 From the European Patent Office Re.: Application No. 06832278.3. |
Official Action Dated Mar. 19, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/240,239. |
Response Dated Jun. 3, 2010 to Notice of Appeal and Pre-Appeal Brief of Jan. 4, 2010 to Official Action of Sep. 2, 2009 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/343,792. |
Communication Pursuant to Article 93(3) EPC Dated Mar. 8, 2010 From the European Patent Office Re.: Application No. 06832278.3. |
Written Opinion Dated Aug. 3, 2006 From the International Searching Authority of the Patent Cooperation Treaty Re.: Application No. PCT/IL05/001173. |
Response Dated May 11, 2010 to Official Action of Mar. 11, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/607,075. |
Response Dated May 26, 2010 to Official Action of Mar. 19, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/240,239. |
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 Jul. 22, 2009 From the European Patent Office Re.: Application No. 06809851.6. |
Notice of Allowance Dated Jul. 16, 2009 From the US Patent and Trademark Office Re.: U.S. Appl. No. 12/084,559. |
Official Action Dated Jul. 7, 2009 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/533,568. |
Official Action Dated May 13, 2009 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/798,017. |
Official Action Dated May 14, 2009 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/656,548. |
Official Action Dated Jul. 15, 2009 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/616,301. |
Official Action Dated Dec. 16, 2008 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/343,792. |
Official Action Dated Jul. 20, 2009 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/980,617. |
Response Dated Mar. 13, 2008 to Official Action of Dec. 13, 2007 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/616,301. |
Response Dated Mar. 15, 2007 to Official Action of Dec. 15, 2006 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/616,301. |
Response Dated Sep. 22, 2008 to Official Action of Jun. 25, 2008 From US Patent and Trademark Office Re.: U.S. Appl. No. 10/616,301. |
Response Dated Oct. 31, 2007 to Official Action of Jul. 12, 2007 From the US Patent and Trademark Office 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. |
Bloch et al. “Application of Computerized Tomography to Radiation Therapy and Surgical Planning”, Proceedings of the IEEE, 71(3): 351-355, Mar. 1983. |
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. |
Amendment After Allowance Under 37 CFR 1.312 Dated Sep. 13, 2010 to Notice of Allowance of Jul. 22, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/794,799. |
Response Dated Jul. 1, 2010 to Official Action of Mar. 2, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/980,617. |
Response Dated Jun. 1, 2010 to Official Action of Mar. 1, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/794,799. |
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 Jul. 26, 2010 to Official Action of Apr. 28, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/616,301. |
Notice of Allowance Dated Jun. 30, 2010 From the United States Patent and Trademark Office Re.: U.S. Appl. No. 09/727,464. |
Official Action Dated Aug. 3, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/980,690. |
Supplemental Response After Interview Dated Aug. 4, 2010 to Official Action of Mar. 2, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/980,617. |
Notice of Allowance Dated Jul. 22, 2010 From the US Patent and Trademark Office 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. Application 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. |
Communication Pursuant to Article 94(3) EPC Dated May 12, 2010 From the European Patent Office Re.: Application No. 06809851.6. |
Notice of Allowance Dated Aug. 25, 2010 From the US Patent and Trademark Office Re. U.S. Appl. No. 11/980,617. |
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. |
Official Action Dated Dec. 8, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/980,690. |
Official Action Dated Nov. 10, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/836,223. |
Official Action Dated Nov. 23, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/656,548. |
Response Dated Nov. 18, 2010 to Official Action of Jul. 19, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/607,075. |
Official Action Dated Jan. 28, 2011 From the US Patent and Trademark Office Re.: U.S. Appl. No. 09/641,973. |
Response Dated Jan. 27, 2011 to Official Action of Nov. 1, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/980,690. |
Response Dated Jan. 31, 2011 to Official Action of Sep. 30, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/798,017. |
Response Dated Mar. 8, 2011 to Official Action of Dec. 8, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/980,690. |
Notice of Allowance Dated Feb. 23, 2011 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/980,690. |
Communication Pursuant to Rules 70(2) and 70a(2) EPC Dated Apr. 4, 2011 From the European Patent Office Re. Application No. 05803689.8. |
Response Dated Mar. 31, 2011 to Official Action of Jan. 31, 2011 From the US Patent and Trademark Office Re. U.S. Appl. No. 11/667,793. |
Official Action Dated Sep. 30, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/798,017. |
Response Dated Oct. 5, 2010 to Official Action of Jul. 19, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/656,548. |
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. |
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. |
Del Guerra et al. “An Integrated PET-SPECT Small Animal Imager: Preliminary Results”, Nuclear Science Symposium, IEEE Records, 1: 541-544, 1999. |
Office Action Dated Dec. 2, 2007 From the Israeli Patent Office Re.: Application No. 158442. |
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. |
Response dated Sep. 1, 2010 to Official Action of Aug. 3, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/980,690. |
Interview Summary Dated Mar. 25, 2011 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/836,223. |
Mao et al. “Human Prostatic Carcinoma: An Electron Microscope Study”, Cancer Research, XP002625777, 26(5): 955-973, May 1966. |
Storey et al. “Tc-99m Sestamibi Uptake in Metastatic Prostate Carcinoma”, Clinical Nuclear Medicine, XP009145398, 25(2): 133-134, Feb. 2000. |
Response Dated Apr. 5, 2011 to Official Action of Nov. 10, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/836,223. |
Supplementary European Search Report and the European Search Opinion Dated Mar. 16, 2011 From the European Patent Office Re. Application No. 05803689.8. |
Herrmann et al. “Mitochondrial Proteome: Altered Cytochtrome C Oxidase Subunit Levels in Prostate Cancer”, Proteomics, XP002625778, 3(9): 1801-1810, Sep. 2003. |
Krieg et al. “Mitochondrial Proteome: Cancer-Altered Metabolism Associated With Cytochrome C Oxidase Subunit Level Variation”, Proteomics, XP002625779, 4(9): 2789-2795, Sep. 2004. |
Communication Pursuant to Article 94(3) EPC Dated Mar. 2, 2011 From the European Patent Office Re.: Application No. 06756259.5. |
International Search Report Dated May 24, 2007 From the International Searching Authority of the Patent Cooperation Treaty Re.: Application No. PCT/IL05/00575. |
Notice of Allowance Dated Nov. 15, 2010 From the US Patent and Trademark Office Re. U.S. Appl. No. 10/616,301. |
Notice of Non-Compliant Amendment Dated Feb. 14, 2011 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/616,307. |
Office Action Dated Jan. 2, 2006 From the Israeli Patent Office Re.: Application No. 154323. |
Official Action Dated Jun. 1, 2006 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/686,536. |
Official Action Dated Sep. 5, 2002 From the US Patent and Trademark Office Re.: U.S. Appl. No. 12/084,559. |
Official Action Dated Jan. 7, 2009 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/616,307. |
Official Action Dated Aug. 10, 2007 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/836,223. |
Official Action Dated Apr. 15, 2008 From the US Patent and Trademark Office Re.: U.S. Appl. No. 09/641,973. |
Official Action Dated Mar. 15, 2004 From the US Patent and Trademark Office Re.: U.S. Appl. No. 09/765,316. |
Official Action Dated Mar. 15, 2011 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/343,792. |
Response Dated Feb. 10, 2011 to Notice of Allowance of Nov. 15, 2010 From the US Patent and Trademark Office Re. U.S. Appl. No. 10/616,301. |
Response Dated Mar. 24, 2011 to Official Action of Dec. 8, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 09/641,973. |
Response Dated Jan. 27, 2011 to Official Action of Nov. 1, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 12/728,383. |
Written Opinion Dated Jul. 2, 2007 From the International Searching Authority of the Patent Cooperation Treaty Re.: Application No. PCT/IL2006/001291. |
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, co1. 2, § 2. |
Day et al. “Localization of Radioiodinated Rat Fibrogen in Transplanted Rat Tumors”, Journal of the National Cancer Institute, 23(4): 799-812, 1959. |
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. |
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. & RSNA 2000 Infosystem, 87th Scientific Assembly and Annual Meeting, Chicago, Illinois, 2000. |
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. |
Lin et al. “Improved Sensor Pills for Physiological Monitoring”, NASA Technical Brief, JPL New Technology Report, NPO-20652, 25(2), 2000. |
Mettler et al. “Legal Requirements and Radiation Safety”, Essentials of Nuclear Medicine Imaging, 2nd Ed., Chap.13: 323-331, 1985. |
Quartuccia et al. “Computer Assisted Collimation Gama Camera: A New Approach to Imaging Contaminated Tissues”, Radiation Projection Dosimetry, 89(3-4): 343-348, 2000. |
Notice of Allowance Dated Dec. 17, 2010 From the US Patent and Trademark Office Re. U.S. Appl. No. 11/980,617. |
Official Action Dated Dec. 8, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 09/641,973. |
Official Action Dated Dec. 28, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/607,075. |
Response Dated Dec. 15, 2010 to Official Action of Jul. 19, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/656,548. |
Official Action Dated Jan. 31, 2011 From the US Patent and Trademark Office Re. U.S. Appl. No. 11/667,793. |
Response Dated Dec. 8, 2011 to Restriction Official Action of Nov. 8, 2011 From the US Patent and Trademark Office Re. U.S. Appl. No. 12/309,479. |
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 US Patent and Trademark Office Re.: U.S. Appl. No. 09/641,973. |
Response Dated Nov. 23, 2011 to Official Action of May 23, 2011 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/980,690. |
Response Dated Nov. 28, 2011 to Official Action of Jun. 28, 2011 From the US Patent and Trademark Office Re. U.S. Appl. No. 11/628,074. |
Official Action Dated Oct. 7, 2011 From the US Patent and Trademark Office Re. U.S. Appl. No. 11/750,057. |
Official Action Dated Oct. 7, 2011 From the US Patent and Trademark Office Re. U.S. Appl. No. 11/932,872. |
Interview Summary Dated May 31, 2011 From the US Patent and Trademark Office Re. U.S. Appl. No. 10/616,301. |
Notice of Allowance Dated May 5,2011 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/240,239. |
Notice of Allowance Dated May 6, 2011 From the US Patent and Trademark Office Re. U.S. Appl. No. 11/980,617. |
Official Action Dated Apr. 20, 2011 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/798,017. |
Official Action Dated May 23, 2011 From the US Patent and Trademark Office Re. U.S. Appl. No. 11/667,793. |
Official Action Dated May 23, 2011 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/980,690. |
Official Action Dated Apr. 27, 2011 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/836,223. |
McJilton et al. “Protein Kinase C? Interacts With Bax and Promotes Survival of Human Prostate Cancer Cells”, Oncogene, 22; 7958-7968, 2003. |
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. |
Notice of Allowance Dated Jun. 23, 2011 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/616,301. |
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 US Patent and Trademark Office Re.: U.S. Appl. No. 11/607,075. |
Official Action Dated Jul. 11, 2011 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/980,683. |
Official Action Dated Jul. 12, 2011 From the US Patent and Trademark Office Re.: U.S. Appl. No. 09/641,973. |
Official Action Dated Sep. 12, 2011 From the US Patent and Trademark Office Re. U.S. Appl. No. 11/980,653. |
Official Action Dated Sep. 12, 2011 From the US Patent and Trademark Office Re. U.S. Appl. No. 12/087,150. |
Official Action Dated Sep. 13, 2011 From the US Patent and Trademark Office Re. U.S. Appl. No. 11/976,852. |
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 Sep. 12, 2011 to Official Action of Jul. 11, 2011 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/980,683. |
Response Dated Jul. 14, 2011 to Official Action of Mar. 15, 2011 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/343,792. |
Response Dated Sep. 20, 2011 to Official Action of Apr. 20, 2011 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/798,017. |
Response Dated Aug. 29, 2011 to Official Action of Apr. 27, 2011 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/836,223. |
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. |
Notice of Allowance Dated Oct. 11, 2011 From the US Patent and Trademark Office Re. U.S. Appl. No. 11/988,926. |
Official Action Dated Oct. 26, 2011 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/836,223. |
Official Action Dated Oct. 27, 2011 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/656,548. |
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. |
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. |
Restriction Official Action Dated Nov. 8, 2011 From the US Patent and Trademark Office Re. U.S. Appl. No. 12/309,479. |
Supplemental Notice of Allowability Dated Oct. 24, 2011 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/607,075. |
Response Dated Nov. 14, 2011 to Official Action of Sep. 12, 2011 From the US Patent and Trademark Office Re. U.S. Appl. No. 12/087,150. |
Response Dated Oct. 24, 2011 to Official Action of May 23, 2011 From the US Patent and Trademark Office Re. U.S. Appl. No. 11/667,793. |
Restriction Official Action Dated Nov. 15, 2011 From the US Patent and Trademark Office Re. U.S. Appl. No. 11/980,683. |
Official Action Dated Dec. 15, 2011 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/343,792. |
Official Action Dated Dec. 20, 2011 From the US Patent and Trademark Office Re. U.S. Appl. No. 12/309,479. |
Response Dated Nov. 13, 2011 to Official Action of Sep. 12, 2011 From the US Patent and Trademark Office 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. |
Notice of Allowance Dated Oct. 26, 2012 From the US Patent and Trademark Office Re. U.S. Appl. No. 12/514,785. |
Official Action Dated Nov. 30, 2012 From the US Patent and Trademark Office Re. U.S. Appl. No. 12/514,785. |
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. |
Jan et al. “Preliminary Results From the AROPET”, IEEE Nuclear Science Symposium Conference Record, Nov. 4-10, 2001, 3: 1607-1610, 2001. |
Ohno et al. “Selection of Optimum Projection Angles in Three Dimensional Myocardial SPECT”, IEEE Nuclear Science Symposium Conference Record 2001, 4: 2166-2169, 2001. |
Seret et al. “Intrinsic Uniformity Requirements for Pinhole SPECT”, Journal of Nuclear Medicine Technology, 34(1): 43-47, Mar. 2006. |
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. |
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. |
Official Action Dated Dec. 19, 2012 From the US Patent and Trademark Office Re. U.S. Appl. No. 12/448,473. |
Notice of Allowance Dated Dec. 26, 2012 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/980,690. |
Official Action Dated Dec. 28, 2012 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/343,792. |
Charland et al. “The Use of Deconvolution and Total Least Squares in Recovering a Radiation Detector Linc Spread Function”, Medical Physics, 25(2): 152-160, Feb. 1998. Abstract Only! |
Notice of Panel Decision From Pre-Appeal Brief Review Dated Feb. 29, 2012 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/836,223. |
Official Action Dated Mar. 6, 2012 From the US Patent and Trademark Office Re. U.S. Appl. No. 12/792,856. |
Official Action Dated Apr. 16, 2012 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/836,223. |
Official Action Dated Feb. 28, 2012 From the US Patent and Trademark Office Re.: U.S. Appl. No. 09/641,973. |
Restriction Official Action Dated Mar. 9, 2012 From the US Patent and Trademark Office Re. U.S. Appl. No. 11/976,852. |
Restriction Official Action Dated Apr. 13, 2012 From the US Patent and Trademark Office Re. U.S. Appl. No. 11/989,223. |
Advisory Action Before the filing of an Appeal Brief Dated Jul. 12, 2012 From the US Patent and Trademark Office Re. U.S. Appl. No. 11/667,793. |
Official Action Dated May 18, 2012 From the US Patent and Trademark Office Re. U.S. Appl. No. 12/514,785. |
Official Action Dated Apr. 19, 2012 From the US Patent and Trademark Office Rc. U.S. Appl. No. 11/750,057. |
Official Action Dated Apr. 23, 2012 From the US Patent and Trademark Office Re. U.S. Appl. No. 11/932,987. |
Examination Report Dated Jun. 22, 2011 From the Government of India, Patent Office, Intellectual Property Building Re. Application No. 2963/CHENP/2006. |
International Search Report Dated Jul. 2, 2007 From the International Searching Authority Re. Application No. PCT/IL2006/001291. |
Notice of Allowance Dated Feb. 23, 2011 From the US Patent and Trademark Office Re.: U.S. Appl. No. 12/728,383. |
Official Action Dated Nov. 1, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 12/728,383. |
Official Action Dated Mar. 9, 2011 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/616,301. |
Official Action Dated Apr. 19, 2012 From the US Patent and Trademark Office Re. U.S. Appl. No. 11/750,057. |
Official Action Dated Jun. 28, 2011 From the US Patent and Trademark Office Re. U.S. Appl. No. 11/628,074. |
Official Action Dated Jul. 30, 2012 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/980,683. |
Response Dated Apr. 7, 2009 to Official Action of Oct. 7, 2008 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/616,301. |
Response Dated Jun. 7, 2011 to Official Action of Mar. 9, 2011 From the US Patent and Trademark Office Re.: U.S. Appl. No. 10/616,301. |
Response Dated Jun. 28, 2011 to Official Action of Dec. 28, 2010 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/607,075. |
Berman et al. “Dual-Isotope Myocardial Perfusion SPECT With Rest Thallium-201 and Stress Tc-99m Sestamibi”, Nuclear Cardiology, 12(2): 261-270, May 1994. |
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. |
Chengazi et al. “Imaging Prostate Cancer With Technetium-99m-7E11-C5.3 (CYT-351)”, Journal of Nuclear Medicine, 38: 675-682, 1997. |
Official Action Dated Aug. 2, 2012 From the US Patent and Trademark Office Re. U.S. Appl. No. 12/087,150. |
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. |
Thorndyke et al. “Reducing Respiratory Motion Artifacts in Positron Emission Tomography Through Retrospective Stacking”, Medical Physics, 33(7): 2632-2641, Jul. 2006. |
Restriction Official Action Dated Aug. 16, 2012 From the US Patent and Trademark Office Re. U.S. Appl. No. 12/448,473. |
Official Action Dated Aug. 31, 2012 From the US Patent and Trademark Office Re. U.S. Appl. No. 11/980,653. |
Communication Pursuant to Article 94(3) EPC Dated Sep. 17, 2012 From the European Patent Office Re. Application No. 06832278.3. |
Ouyang et al. “Incorporation of Correlated Structural Images in PET Image Reconstruction”, IEEE Transactions of Medical Imaging, 13(4): 627-640, Dec. 1994. |
Cancer Medicine “Radiolabeled Monoclonal Antibodies. Historical Perspective”, Cancer Medicine, 5th Ed., Sec.16: Principles of Biotherapeutics, Chap.65: Monoclonal Serotherapy, 2000. |
Lange et al. “EM Reconstruction Algorithms for Emission and Transmission Tomography”, Journal of Computer Assisted Tomography, 8(2): 306-316, Apr. 1984. |
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. |
Rockmore et al. “A Maximum Likelihood Approach to Emission Image Reconstruction From Projections”, IEEE Transactions on Nuclear Science, 23(4): 1428-1432, Aug. 1976. |
Shepp el 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. |
Solanski “The Use of Automation in Radiopharmacy”, Hospital Pharmacist, 7(4): 94-98, Apr. 2000. |
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. |
Official Action Dated Oct. 11, 2012 From the US Patent and Trademark Office Re. U.S. Appl. No. 11/976,852. |
Official Action Dated Oct. 10, 2012 From the US Patent and Trademark Office Re. U.S. Appl. No. 11/798,017. |
Communication Pursuant to Article 94(3) EPC Dated Oct. 26, 2012 From the European Patent Office Re. Application No. 05803689.8. |
Communication Pursuant to Article 94(3) EPC Dated Nov. 12, 2012 From the European Patent Office Re. Application No. 06756258.7. |
Notice of Allowance Dated Nov. 15, 2012 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/980,683. |
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. |
Applicant-Initiated Interview Summary Dated Jan. 28, 2013 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/798,017. |
Official Action Dated Feb. 7, 2013 From the US Patent and Trademark Office Re. U.S. Appl. No. 11/980,653. |
Advisory Action Before the Filing of an Appeal Brief Dated Feb. 26, 2013 From the US Patent and Trademark Office Re. U.S. Appl. No. 12/514,785. |
Notice of Allowance Dated Feb. 21, 2013 From the US Patent and Trademark Office Re. U.S. Appl. No. 11/798,017. |
Notice of Allowance Dated Feb. 2, 2012 From the US Patent and Trademark Office Re. U.S. Appl. No. 11/628,074. |
Official Action Dated Jan. 19, 2012 From the US Patent and Trademark Office Re. U.S. Appl. No. 11/667,793. |
Official Action Dated Jan. 23, 2012 From the US Patent and Trademark Office 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. |
Advisory Action Before the Filing of an Appeal Brief Dated Feb. 26, 2013 From the US Patent and Trademark Office Re. U.S. Appl. No. 11/989,223. |
Official Action Dated Nov. 30, 2012 From the US Patent and Trademark Office Re. U.S. Appl. No. 11/989,223. |
Notice of Allowance Dated Mar. 14, 2013 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/798,017. |
Official Action Dated Mar. 11, 2013 From the US Patent and Trademark Office 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. |
Applicant-Initiated Interview Summary Dated May 1, 2013 From the US Patent and Trademark Office Re. U.S. Appl. No. 10/343,792. |
Applicant-Initiated Interview Summary Dated May 1, 2013 From the US Patent and Trademark Office Re. U.S. Appl. No. 11/980,653. |
Advisory Action before the Filing of an Appeal Brief Dated May 21, 2013 From the US Patent and Trademark Office Re. U.S. Appl. No. 11/980,653. |
Applicant-Initiated Interview Summary Dated May 9, 2013 From the US Patent and Trademark Office Re. U.S. Appl. No. 12/448,473. |
Communication Pursuant to Article 94(3) EPC Dated Sep. 23, 2011 From the European Patent Office Re.: Application No. 06832278.3. |
Written Opinion Dated Nov. 1, 2007 from the International Searching Authority of the Patent Cooperation Treaty Re.: Application No. PCT/IL06/00840. |
Written Opinion Dated Jul. 11, 2008 from the International Searching Authority of the Patent Cooperation Treaty Re.: Application No. PCT/IL06/01511. |
Communication Under Rule 71(3) EPC Dated Feb. 26, 2013 From the European Patent Office Re. Application No. 06756259.5. |
Notice of Allowance Dated Jun. 21, 2013 From the US Patent and Trademark Office Re. U.S. Appl. No. 11/980,653. |
Notice of Allowance Dated Jul. 15, 2013 From the US Patent and Trademark Office Re. U.S. Appl. No. 11/932,987. |
Notice of Allowance Dated Jul. 19, 2013 From the US Patent and Trademark Office Re. U.S. Appl. No. 11/989,223. |
Notice of Allowance Dated Jul. 25, 2013 From the US Patent and Trademark Office Re. U.S. Appl. No. 13/345,719. |
Official Action Dated Aug. 5, 2013 From the US Patent and Trademark Office Re. U.S. Appl. No. 12/309,479. |
Official Action Dated Jul. 5, 2013 From the US Patent and Trademark Office Re.: U.S. Appl. No. 11/656,548. |
Official Action Dated Jun. 12, 2013 From the US Patent and Trademark Office Re. U.S. Appl. No. 12/087,150. |
Official Action Dated Aug. 14, 2013 From the US Patent and Trademark Office Re. U.S. Appl. No. 12/448,473. |
Official Action Dated Jul. 30, 2013 From the US Patent and Trademark Office Re. U.S. Appl. No. 10/343,792. |
Official Action Dated Jul. 31, 2013 From the US Patent and Trademark Office Re. U.S. Appl. No. 11/667,793. |
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. |
Berman et al. “D-SPECT: A Novel Camera for High Speed Quantitative Molecular Imaging: Initial Clinical Results”, The Journal of Nuclear Medicine, 47(Supp1.1): 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 et 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. |
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. |
Number | Date | Country | |
---|---|---|---|
20040054248 A1 | Mar 2004 | US |
Number | Date | Country | |
---|---|---|---|
60394936 | Jul 2002 | US |
Number | Date | Country | |
---|---|---|---|
Parent | 10343792 | US | |
Child | 10616307 | US | |
Parent | 09727464 | Dec 2000 | US |
Child | 10343792 | US | |
Parent | 09714164 | Nov 2000 | US |
Child | 09727464 | US | |
Parent | 09641973 | Aug 2000 | US |
Child | 09714164 | US |