Patent Grant
8620046
The present invention relates to nuclear imaging and more particularly, to systems, methods, and probes for radioactive-emission-measurement optimization to specific body structures, possibly together with structural imaging, for example, by x-rays, ultrasound, or MRI.
Radioactive-emission imaging relies on the fact that in general, pathologies, such as malignant tumors, malfunctioning organs, and inflammations, display a level of activity different from that of healthy tissue. Thus, radiopharmaceutical, which circulate in the blood stream, are picked up by the active pathologies to a different extent than by the surrounding healthy tissue; in consequence, the pathologies are operative as radioactive-emission sources and may be detected by radioactive-emission imaging.
The pathological feature may appear as a concentrated source of high radiation, or a hot region, as may be associated with a tumor, or as a region of low-level to radiation, which is nonetheless above the background level, as may be associated with carcinoma. Additionally, a reversed situation is possible. Dead tissue has practically no pick up of radiopharmaceuticals, and is thus operative as a region of little radiation, or a cold region, below the background level.
Thus radiopharmaceuticals may be used for identifying active pathologies as well as dead tissue, and the image that is constructed is generally termed, a functional image.
The mechanism of localization of a radiopharmaceutical in a particular organ of interest depends on various processes in the organ of interest, such as antigen-antibody reactions, physical trapping of particles, receptor site binding, removal of intentionally damaged cells from circulation, and transport of a chemical species across a cell membrane and into the cell by a normally operative metabolic process. A summary of the mechanisms of localization by radiopharmaceuticals is described in http://www.lunis.luc.edu/nucmed/tutorial/radpharm/i.htm. For example:
1. Active transport involves the use of a normally operative metabolic pathway in the body, for moving a radiopharmaceutical across a cell membrane and into the cell. An example of a radiopharmaceutical that may be used for active transport is I131 in the form of NaI, for thyroid imaging.
2. Phagocytosis involves physical entrapment of colloidal particles by Kupffer cells in the RE System. An example of a radiopharmaceutical that may be used for phagocytosis is Tc99m in the form of sulfur colloid, for liver and spleen imaging.
3. Capillary blockage involves intentional microembolization of a capillary bed with particles. An example of a radiopharmaceutical that may be used for capillary blockage is Tc99m in the form of MAA, for pulmonary perfusion imaging.
4. Cell sequestration involves injection of damaged RBC's to produce a spleen scan with no visualization of the liver. An example of a radiopharmaceutical that may be used for cell sequestration is heat damaged autologous Tc99m RBC's.
5. Simple or exchange diffusion involves a mechanism whereby a radiotracer diffuses across cell membranes and then binds or attaches itself to a cell component. An example of a radiopharmaceutical that may be used for simple or exchange diffusion is F18, in the form of NaF, for bone imaging.
6. Compartmental Localization involves placement of a radiotracer in a fluid space and imaging of that fluid space. Examples of radiopharmaceuticals that may be used for compartmental localization are Tc99m HAS, for MUGA's, In111 DTPA, for cistemograms, and Xe133 gas for pulmonary perfusion.
7. Chemisorption involves surface binding of radiopharmaceutical to a solid structure. An example of a radiopharmaceutical that may be used for chemisorption is In111 platelets bound to a surface of an active thrombus.
8. Antigen or antibody reaction involves uptake at tumor site due to specific binding of radiolabeled antibody to surface antigens on tumors. Examples of radiopharmaceuticals that may be used for antigen or antibody reaction are In111 Oncoscint, for the localization of recurrent ovarian or colorectal carcinoma, or In111 ProstaScint for the localization or recurrent cancer.
9. Receptor binding involves the binding of a radiopharmaceutical to high-affinity receptor sites. An example of a radiopharmaceutical that may be used for receptor binding is In111 octreotide, for localization of neuroendocrine and other tumors based on binding of a somatostatin analog to receptor sites in tumors.
Examples of other radiopharmaceuticals include the following:
1. anti-CEA, a monoclonal antibody fragment, which targets CEA—produced and shed by colorectal carcinoma cells—and may be labeled by Tc99m or by other radioisotopes, for example, iodine isotopes (Jessup J M, 1998, Tumor markers—prognostic and therapeutic implications for colorectal carcinoma, Surgical Oncology; 7: 139-151);
2. In111-Satumomab Pendetide (Oncoscint®), designed to target TAG-72, a mucin-like glycoprotein, expressed in human colorectal, gastric, ovarian, breast and lung cancers, but rarely in healthy human adult tissues (Molinolo A; Simpson J F; et al., 1990, 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 Res., 50(4): 1291-8);
3. Lipid-Associated Sialic Acid (LASA), a tumor antigen, used for colorectal carcinoma, with a similar sensitivity as anti-CEA monoclonal antibody fragment but a greater specificity for differentiating between benign and malignant lesions (Ebril K M, Jones J D, Klee G G, 1985, Use and limitations of serum total and lipid-bound sialic acid concentrations as markers for colorectal cancer, Cancer; 55:404-409);
4. Matrix Metaloproteinase-7 (MMP-7), a proteins enzyme, believed to be involved in tumor invasion and metastasis (Mori M, Barnard G F et al., 1995, Overexpression of matrix metalloproteinase-7 mRNA in human colon carcinoma, Cancer; 75: 1516-1519);
5. Ga67 citrate, used for detection of chronic inflammation (Mettler F A, and Guiberteau M J, Eds., 1998, Inflammation and infection imaging, Essentials of nuclear medicine, Fourth edition, Pgs: 387-403);
6. Nonspecific-polyclonal immunoglobulin G (IgG), which may be labeled with both In111 or Tc99m, and which has a potential to localize nonbacterial infections (Mettler F A, and Guiberteau M J, ibid);
7. Radio-labeled leukocytes, such as such as In111 oxine leukocytes and Tc99m HMPAO leukocytes, which are attracted to sites of inflammation, where they are activated by local chemotactic factors and pass through the endothelium into the soft tissue (Mettler F A, and Guiberteau M J, ibid; Corstens F H; van der Meer J W, 1999, Nuclear medicine's role in infection and inflammation, Lancet; 354 (9180): 765-70); and
8. Tc99m bound to Sodium Pertechnetate, which is picked up by red blood cells, and may be used for identifying blood vessels and vital organs, such as the liver and the kidneys, in order to guide a surgical instrument without their penetration.
The particular choice of a radionuclide for labeling antibodies depends upon the chemistry of the labeling procedure and the isotope nuclear properties, such as, the number of gamma rays emitted, their respective energies, the emission of other particles, such as beta or positrons, the isotope half-life, and the existence of different isotopes of identical chemistry but different half-lives (e.g., I131 and I133). The usual preferred emission for medical applications is that of gamma rays, with an energy range of approximately 11-511 KeV. However, beta and positron radiation may also be detected.
The detector may be a room temperature, solid-state CdZnTe (CZT) detector, configured as a single-pixel or a multi-pixel detector, obtained, for example, from eV Products, a division of II-VI Corporation, Saxonburg Pa., 16056, or from IMARAD IMAGING SYSTEMS LTD., of Rehovot, ISRAEL, 76124, www.imarad.com, or from another source. Alternatively, another solid-state detector such as CdTe, HgI, Si, Ge, or the like, or a scintillation detector (such as NaI(Tl), LSO, GSO, CsI, CaF, or the like, or a combination of a scintillation detector and a photomultiplier, to form an Anger camera, or another detector as known, may be used.
As seen in
As seen in
The collimator's geometry, and specifically, the ratio of D/L, provides the detecting unit 12 with a collection solid angle δ analogous to a viewing solid angle of an optical camera. The collection solid angle δ limits the radioactive-emission detection to substantially only that radioactive emission, which impinges on the detector 91 after passing through a “corridor” of the collimator 96 (although in practice, some high-energy gamma rays may penetrate the collimator's walls). With no collimator, the collection angle δ, is essentially a solid angle of 4π steradians.
Thus, the collimator's geometry affects both the detection efficiency and the image resolution, which are defined as follows:
Naturally, it is desired to optimize both the detection efficiency and the image resolution. Yet, they are inversely related to each other. The detection efficiency increases with increasing collimator's collection angle, and the image resolution decreases with increasing collimator's collection angle.
In other words, while a wide-aperture, single-pixel detecting unit, such as that of
Commonly owned US Applications 20040015075 and 20040054248 and commonly owned PCT publication WO2004/042546, all of whose disclosures are incorporated herein by reference, describe systems and methods for scanning a radioactive-emission source with a radioactive-emission-measuring probe of a wide-aperture collimator, and at the same time, monitoring the position of the radioactive-emission-measuring probe, at very fine time intervals, to obtain the equivalence of fine-aperture collimation. In consequence, high-efficiency, high-resolution images of a radioactivity emitting source are obtained.
A system according to US Applications 20040015075 and 20040054248 and PCT publication WO2004/042546 is seen in
Images according to this concept are illustrated in
An example of a suitable position-tracking device 124 is miniBird™, which is a magnetic tracking and location system commercially available from Ascension Technology Corporation, P.O. Box 527, Burlington, Vt. 05402 USA (http://www.ascension-tech.com/graphic.htm). The miniBird™ measures the real-time position and orientation (in six degrees of freedom) of one or more miniaturized sensors, so as to accurately track the spatial location of probes, instruments, and other devices. The dimensions of miniBird™ 124 are 18 mm×8 mm×8 mm for the Model 800 and 10 mm×5 mm×5 mm the Model 500. Alternatively, an optical tracking device, of Northern Digital Inc., Ontario, Canada NDI-POLARIS, which provides passive or active systems, a magnetic tracking device of NDI-AURORA, an infrared tracking device of E-PEN system, http://www.e-pen.com, or an ultrasonic tracking device of E-PEN system may be used. Additionally or alternatively, the position-tracking device may be an articulated-arm position-tracking device, an accelerometer-based position-tracking device, a potentiometer-based position-tracking device, or a radio-frequency-based position-tracking device.
Commonly owned US application 20040054248 and commonly owned PCT to publication WO2004/042546 further disclose various extracorporeal and intracorporeal systems 120, of radioactive-emission-measuring probes 122, of relatively wide apertures, associated with position-tracking devices 124. Examples of extracorporeal and intracorporeal radioactive-emission-measuring probes of this type, operative with position-tracking devices, are seen in
The acquisition of both a functional image of the body, such as a radioactive-emission image, and a structural image, such as an ultrasound, an x-ray, or an MRI image, and their co-registration on a single frame of reference, is disclosed by commonly owned U.S. Pat. No. 6,173,201 to Front, whose disclosure is incorporated herein by reference, as well as by M. W. Vannier and D. E. Gayou, “Automated registration of multimodality images”, Radiology, vol. 169 pp. 860-861 (1988); J. A. Correia, “Registration of nuclear medicine images, J. Nucl. Med., vol. 31 pp. 1227-1229 (1990); J-C Liehn, A. Loboguerrero, C. Perault and L. Demange, “superposition of computed tomography and single photon emission tomography immunoscinigraphic images in the pelvis: validation in patients with colorectal or ovarian carcinoma recurrence”, Eur. J. Nucl. Med., vol. 19 pp. 186-194 (1992); F. Thomas et al., “Description of a prototype emission transmission computed tomography imaging system”, J. Nucl. Med., vol. 33 pp. 1881-1887 (1992); D. A. Weber and M. Ivanovic, “Correlative image registration”, Sem. Nucl. Med., vol. 24 pp. 311-323 (1994); and Hasegawa et al., U.S. Pat. No. 5,376,795.
In essence, several images may be acquired and co-registered to the same frame of reference, as follows:
In this manner, a physician may locate the pathological feature in reference to the blood vessels, vital organs, and the bones.
Additionally, correlation may be used to guide a minimally invasive surgical instrument to the pathological feature, while avoiding the blood vessels, vital organs, and bones. The minimally invasive surgical instrument may be a biopsy needle, a wire, for hot resection, a knife for cold resection, an instrument of focused energy, to produce ablation, for example, by ultrasound, or by laser, an instrument for cryosurgery, an instrument for croyetherapy, or an instrument for bractherapy, wherein seeds of a radioactive metal are planted close to a tumor, for operating as a radioactive source near the tumor.
Commonly owned PCT publication WO2004/042546 further discloses that the surgical instrument may be visible on at least one of the images, for example, on the structural image, to enable the physician to see the instrument, the pathological feature, and the surrounding anatomy on the display 129 (
Commonly owned U.S. Pat. No. 6,173,201 discloses a method of stereotactic therapy, wherein a frame, which includes at least three markers, visible on a structural image, is rigidly secured to a patient. The structural image of a region inside the patient's body, which includes a pathological feature and the markers, is acquired. A functional image of the pathological feature is then acquired and co-registered with the structural image, to correlate the images to the same frame of reference. A stereotactic guide is rigidly attached to the frame and is used to guide a surgical instrument, such as a biopsy needle or a brachytherapy needle, to the pathological feature, with reference to the co-registered images.
Commonly owned PCT publication WO2004/042546 further disclosures the use of a structural image, such as of ultrasound or MRI, for information about tissue attenuation. The information may then be used to correct the radioactive-emission measurements.
Nuclear imaging for coronary artery disease is also known. For example, U.S. Pat. No. 6,597,940, to Bishop, et al, relates to screening patients for an early stage of coronary artery disease. According to this method, a patient is screened based on the time-activity curve for a radioactive tracer passing through a left ventricle region of the patient's body. According to another aspect of the invention, an array of gamma particle detectors is employed to obtain data for a region of interest that is larger than and encompasses a left ventricle region of the patient's body. An analysis of the data identifies the subset of the region of interest that corresponds to the left ventricle region. According to a further aspect of the present invention, a second technique is employed to locate the left ventricle region. A still further aspect of the present invention relates to obtaining images of a patient's heart using a high temporal resolution gamma camera.
Additionally, U.S. Pat. No. 6,671,541, to Bishop et al. relates to a cardiovascular imaging and functional analysis system and method, wherein a dedicated fast, sensitive, compact and economical imaging gamma camera system that is especially suited for heart imaging and functional analysis is employed. The cardiovascular imaging and functional analysis system of the present invention can be used as a dedicated nuclear cardiology small field of view imaging camera. The disclosed cardiovascular imaging system and method has the advantages of being able to image physiology, while offering an inexpensive and portable hardware, unlike MRI, CT, and echocardiography systems. The cardiovascular imaging system of the invention employs a basic modular design suitable for cardiac imaging with one of several radionucleide tracers. The detector can be positioned in close proximity to the chest and heart from several different projections, making it possible rapidly to accumulate data for first-pass analysis, positron imaging, quantitative stress perfusion, and multi-gated equilibrium pooled blood (MUGA) tests. In a preferred embodiment, the Cardiovascular Non-Invasive Screening Probe system can perform a novel diagnostic screening test for potential victims of coronary artery disease. The system provides a rapid, inexpensive preliminary indication of coronary occlusive disease by measuring the activity of emitted particles from an injected bolus of radioactive tracer. Ratios of this activity with the time progression of the injected bolus of radioactive tracer are used to perform diagnosis of the coronary patency (artery disease).
The present invention successfully addresses the shortcomings of the presently known configurations by providing systems, methods, and probes for functional imaging by radioactive-emission-measurements, specific to body structures, such as the prostate, the esophagus, the cervix, the uterus, the ovaries, the heart, the breast, the brain, and the whole body, and other body structures. The nuclear imaging may be performed alone, or together with structural imaging, for example, by x-rays, ultrasound, or MRI. Preferably, the radioactive-emission-measuring probes include detectors, which are adapted for individual motions with respect to the probe housings, to generate views from different orientations and to change their view orientations. These motions are optimized with respect to functional information gained about the body structure, by identifying preferred sets of views for measurements, based on models of the body structures and information theoretic measures. A second iteration, for identifying preferred sets of views for measurements of a portion of a body structure, based on models of a location of a pathology that has been identified, makes it possible, in effect, to zoom in on a suspected pathology. The systems are preprogrammed to provide these motions automatically.
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. In case of conflict, the patent specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.
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 for 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 of systems, methods, and probes for functional imaging by radioactive-emission-measurements, specific to body structures, such as the prostate, the esophagus, the cervix, the uterus, the ovaries, the heart, the breast, the brain, and the whole body, and other body structures. The nuclear imaging may be performed alone, or together with structural imaging, for example, by x-rays, ultrasound, or MRI. Preferably, the radioactive-emission-measuring probes include detectors, which are adapted for individual motions with respect to the probe housings, to generate views from different orientations and to change their view orientations. These motions are optimized with respect to functional information gained about the body structure, by identifying preferred sets of views for measurements, based on models of the body structures and information theoretic measures. A second iteration, for identifying preferred sets of views for measurements of a portion of a body structure, based on models of a location of a pathology that has been identified, makes it possible, in effect, to zoom in on a suspected pathology. The systems are preprogrammed to provide these motions automatically.
The principles and operation of the radioactive-emission-measuring systems, probes and methods, according to embodiments 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.
Referring now to the drawings,
We thus consider the following problem: how can we best identify an optimal and permissible set of views for radioactive-emission measurements of the region of interest 200, for reconstructing a three-dimensional image of it?
In accordance with embodiments of the present invention, our approach is delineated in
It will be appreciated that the model 250 of the region of interest 200 may be based on general medical information of the body structure 215 and common pathological features associated with it. Additionally, the model may be based on information related to a specific patient, such as age, sex, weight, and body type. Furthermore, a structural image, such as by ultrasound or MRI, may be used for providing information about the size and location of the body structure 215 in relation to the body section 230, for generating the model 250.
Referring further to the drawings,
Seen in
A view may thus be defined as a group of nonzero probabilities of detecting a radioactive emission associated with all the voxels that form a sector S (
A view is dependent on the following viewing parameters:
Location and Orientation Parameters:
A location and an orientation in a six-dimensional space, P1(x1; y1; z1; ω1; θ1; σ1), with respect to the origin P0(x0; y0; z0; ω0; θ0; σ0) of the volume U, in which the detecting unit 12 is positioned;
Detecting-Unit Parameters:
Attenuation properties of all the voxels within the sector S, as they affect the probabilities that radioactive emissions from a specific voxel within the sector S will reach the detector, wherein different voxels within the sector S may have different attenuation properties, since several types of tissue may be involved;
Radiopharmaceutical Parameters:
The half life t1/2, of the radiopharmaceutical, the types of radioactive emission, whether gamma or beta, and the energies of the radioactive emission affect the probability of detection; and
Time Parameters:
Given that T0 is the time of administrating the radiopharmaceutical, the time T1 since administration, and the duration of the measurement ΔT1, affect the number of emissions that occur during the radioactive-emission measurement.
Some of these viewing parameters are fixed for a particular situation. Specifically, the tissue attenuation parameters are given. Additionally, the time T1 since administration of the radiopharmaceutical is generally governed by the blood pool radioactivity, since it is generally necessary to wait until the blood pool radioactivity dies out for low-level detection to be possible. For the remaining viewing parameters, optimization may be carried out.
The remaining viewing parameters may be divided into two categories:
Referring further to the drawings,
In
In
In each of these cases, it is desired that a reconstructed three-dimensional radioactive-emission image of the region of interest 200 be obtained, at a predetermined quality. This is achieved by predefining an optimal set of radioactive-emission measurement views, tailored to the specific organ 215 and optimized with respect to the information gained, regarding the body structure 215.
Referring further to the drawings,
The model of the body structure is based on anatomical knowledge regarding its size, shape, and weight. In fact different models may be provided, for example, for to different ages, sexes, weights, and body types, such as heavy-built, medium-built, or small-built. In accordance with a first embodiment, the body structure is modeled assuming no radioactive emission throughout its volume. In accordance with other embodiments, the body structure may be modeled with one or more modeled organ targets, simulating different pathological features. Specifically, the modeled organ targets may be hot regions, of a radioactive-emission intensity, higher than the background level, regions of low-level radioactive-emission intensity, which is nonetheless above the background level, and cold regions, of a radioactive-emission intensity, lower than the background level. These may be distributed in accordance with medical records, which teach of sites within the body structure that may be more susceptible to certain pathologies.
Similarly, the model of anatomical constraints, which limit accessibility to the body structure, is based on anatomical knowledge, and different models may be provided, for example, for different ages, sexes, weights, and body types.
The collection of views may be obtained by several methods. It may be calculated analytically, for the modeled body, based on the view parameters. Additionally or alternatively, computer simulations of the modeled body and the view parameters may provide the collection of views. Additionally or alternatively, measurements may be performed, using a point source and a detecting unit of appropriate parameters, at different locations and orientations of the detecting unit, so as to simulate the desired geometries.
It will be appreciated that a combination of these may be used. For example, the measurements may be performed in air, but corrected analytically or by computer simulations, for tissue attenuation.
Referring further to the drawings,
The modeled organ targets may be termed emittance models. In general, an emittance model is based on a particular radiopharmaceutical, which fixes both the rate of emission and the change in the rate of emission with time, determining the difference between the modeled organ target and the background level, as a function of time. To study the effect of different radiopharmaceuticals on the views, one may provide different emittance models, based on different radiopharmaceuticals and different elapsed times from their administration.
The choice of an optimal set of views from among a collection of views, such as any of those illustrated in
A brief description of the information theoretic measures, upon which the scoring function may be based, is as follows:
Uniformity:
The information theoretic measure of uniformity requires that the probability of detecting a radioactive emission from each voxel, by one of the views, be substantially equal for all the voxels, that is, substantially uniform for all the voxels.
This is illustrated in conjunction with
Separability:
The information theoretic measure of separability rates resolution, or the ability of a set of views to distinguish between a pair of close models of the body structure, each having substantially identical dimensions, so as to define substantially identical volumes U, but with a slightly different distribution of modeled organ targets.
Consider for example, a pair of models of substantially identical volumes, as follows: The model of
An optimal set of views, from the standpoint of separability, is that which will best distinguish between HS of
Additionally, consider the model of
Scores, in terms of separability, may be given to all the paring combinations, that is the models of
It will be appreciated that where more than one modeled organ target may be included in the volume U.
It will be further appreciated that a set of views may be selected so as to provide high resolution for portions of the volume U, known to be susceptible to pathologies, and low resolution for portions of the volume U, known to be generally free of pathological features.
Reliability:
The information theoretic measure of reliability rates repeatability in measurement, so that repeated reconstructions are not substantially different. Reliability may be scored with respect to a single model of a body structure, having a specific distribution of modeled organ targets, for example, any one of the models of to
A Weighted Combination:
A weighted combination of several information theoretic measures may also be used. For example, a plurality of models may be provided, all having substantially identical dimensions and volumes, as follows:
Identical sets of views may be applied to all the models of the volume U, and each view may be scored in terms of uniformity, separability, and reliability. An optimal set of views may be selected based on a summation of the three scores, or based on a weighted average of the three scores.
The Greedy Construction
Some approaches for selecting an optimal set are based on determining a required quality of reconstruction, and finding a set of views that meets that requirement. Others are based on fixing the size for the set (i.e., the number of views in the set) and maximize the quality of the reconstruction for the given set size. Still other approaches define both a desired size for the set and a desired quality of to reconstruction and search for a set of the desired size, which meets the desired quality of reconstruction.
However, given a desired size for a set of views and a desired quality of reconstruction, while it may be possible to search through all possible sets of the desired size, scoring each, in order to identify the set that meets the desired quality, such a task may be monumental. For example, where the collection of views includes several thousand views, and a set size of 100 is desired, rating each combination of 100 views would be computationally impractical.
An alternative approach is the Greedy Construction. When applying the Greedy construction, an information theoretic measure is chosen, for example, separability, and an initial set of a minimal number of views is defined. The set is gradually built up, so that with every addition, a view is picked so as to maximize the chosen information theoretic measure of the set.
This may be illustrated in conjunction with
It will be appreciated that other scoring functions, as known, may similarly be used.
Performing Measurements
The power of the method of the present invention, of predefining a set of views based on a model of a body structure, using an information theoretic measure, so as to optimize the functional information from the views of the corresponding body structure, in vivo, becomes apparent when compared with the prior art alternatives. The prior art relies on obtaining random views, in vivo, or views dictated by anatomical constraints, with no rigorous approach to the manner by which they are chosen.
The method of the present invention, of predefining a set of views, based on a model of a body structure, using an information theoretic measure, so as to optimize the functional information from the views of the corresponding body structure, in vivo, is further illustrated hereinbelow, in conjunction with
Referring further to the drawings,
It will be appreciated that the region of interest 200 may include an organ, such as a heart or a pancreas, a gland, such as a thyroid gland or a lymph gland, blood vessels, for example, the coronary artery or the pulmonary artery, a portion of an organ, such as an aorta or a left atrium of a heart, a bone, a ligament, a joint, a section of the body, such as a chest or an abdomen, or a whole body.
A still more powerful approach may be achieved by taking the method of the present invention through second and third iterations, so as to zoom in on suspected pathological features that are identified. Specifically, when a suspected pathological feature is identified, a second, inner region of interest, limited to the region of the pathological feature and its surrounding anatomical structure, can be identified and modeled. An optimal pathology set of views, specifically for the second, inner region of interest, may be predefined, based on information theoretic measures, as before. This is illustrated hereinbelow, in conjunction with
Referring further to the drawings,
Referring further to the drawings,
It will be appreciated that the model of the suspected pathological feature may be provided responsive to a patient's complaint, a physician's examination, or based on input from another imaging system, for example, x-rays, CT, MRI, ultrasound, and gamma scanning, for example, with a hand-held gamma camera, rather then based on the findings of the first set of measurements, of the step 356, hereinabove.
Design of a Radioactive-Emission-Measuring Probe
While the embodiments described in conjunction with
Thus, the embodiments described hereinbelow, in conjunction with
Referring further to the drawings,
According to the present example, the probe 226 has two detecting units 222A and 222B whose collimators are arranged in parallel. The two detecting units 222A and 222B are adapted for motion in the directions of ±x, within the probe 226, as shown by arrows 224 and 228, so as to provide coverage of a plane within the bodies U1 U2 and U3, in parallel sectors. Upon reaching the end of the travel in the +x direction, as shown by the arrow 224, the two detecting units 222A and 222B may be rotated in the direction of ω, as shown by an arrow 217, and return in the −x direction of the arrow 228. In this manner, complete coverage of the whole body is provided. A representative collection of views of the probe 226 may be defined as a set of views of the bodies U1, U2, and U3, taken at predetermined increments of Δx and Δω.
Intuitively, a set formed of parallel sectors may score poorly in terms of uniformity since radioactive emissions from voxels closer to the detecting unit have higher probabilities of being detected than radioactive emissions from voxels far from the detecting unit. Additionally, a set formed of parallel sectors may score poorly in terms of separability, since it cannot distinguish between two models, which only differ in the depth of a pathological feature, along the z-axis.
The probe 220 has the two detecting units 222A and 222B, arranged to sweep a plane within the volume U2, in a windshield-wiper-like manner, along ±θ, as illustrated by arrows 216 and 218. When sweeping along ±θ is completed, the detecting units 222A and 222B rotate a few degrees along ω, as illustrated by the arrow 217, and sweeping along ±θ is repeated in the new orientation. In this manner, coverage of the whole volume U2 is performed, from two locations and a large plurality of orientations. A representative collection of views of the probe 220 may be defined as a set of views of the volume U2, taken at predetermined increments of Δθ and Δω.
The significance of the present embodiment, is as follows:
A score may be applied to this set, based on the information theoretic measure of reliability.
It will be appreciated that similarly, the probe 220 may be arranged for measuring the radioactive-emission-density distribution of the volume U1 (
Intuitively, the set of representative collection of views of the present example is likely to score more highly in terms of separability than that of the probe 226 of
In
Intuitively, the set of representative collection of views of the present example is likely to score more highly in terms of all three information theoretic measures, than those of the probe of
In this manner, the information theoretic measures may be used for scoring representative collections of views of suggested probe designs, and an optimal probe design may be chosen based on this score, as described hereinbelow, in conjunction with
Referring further to the drawings,
In this manner, a comparison of the quality of the data that may be produced by each probe design can be made. This analysis is important at the probe-design stage, in order to eliminate situations where views which are anatomically possible and which are desired from the standpoint of information theoretic measures, are unattainable because of probe design limitations. For example, the probe 190 of
Additionally, when selecting a probe design, it is generally desired to consider secondary issues, such as the rate of data collection, the cost of the probe, the complexity of the design, for example, in terms of the number of motors and motion-transfer systems, and the like.
The rate of data collection is important both because it may be associated with patient discomfort and because it affects the number of patients that may be examined in a period of time. Where data collection with one probe design may take an hour and with another probe design it may take 10 minutes, the design of the faster probe is highly advantageous. Complexity and cost are important because they affect the accessibility of the general public to the probe.
Thus, a design scoring function may be provided, for rating each probe design with a design score, based on any one or a combination of the secondary issues. The design scoring function may be used for selecting a probe design from several that have been found acceptable in terms of the quality of the data, by the method 370 of
Referring further to the drawings,
It will be appreciated other manners of combining the scoring function, which rates information, and the design scoring function, which rates secondary issues, are possible. For example, a combined scoring function, which takes both into account, may be used.
As will be shown, hereinbelow, in conjunction with
Referring further to the drawings,
The views that are obtained by the present example may be used both as:
Referring further to the drawings,
As seen in
As seen in
As seen in
A series of coronal, sagital, and transverse images were taken, by a state of the art gamma camera and by the probe of the present invention. A total of 2,500 counts were obtained, for which the state of the art camera required 9 minutes, and the probe of the present invention required 1 minute.
As seen on
Reference is now made to the following examples of radioactive-emission-measuring probes and probe systems, for the comparative study taught in conjunction with
Referring further to the drawings,
It will be appreciated that a combination of these may be used. For example, the block 90 may include wide-angle collimators at the periphery and normal collimators of 90-degrees at the center.
As seen in
The distal view 111 of the collimator grid is seen in
Two optional proximal views 109 of the photomultipliers 103 are seen in
Referring further to the drawings,
As a consequence, a spiral trace 48 is formed, for example, on an inner surface of a body lumen 232, as seen in
Preferably, the motions of the detecting unit 12 are contained within the housing 20, so that the external surface of the probe 10 remains stationary. The external surface of the probe may be formed of a carbon fiber, a plastic, or another material, which is substantially transparent to nuclear radiation.
Referring further to the drawings,
As a consequence, a plurality of spiral traces 49 is formed, for example, on an inner surface of a body lumen, as seen in
Preferably, the motions of the block 90 are contained within the housing 20, so that the external surface of the probe 10 remains stationary, wherein the external surface of the probe is substantially transparent to nuclear radiation.
Referring further to the drawings,
For understanding the motion of the probe 10 of the present example, it is desirable to define a cylindrical coordinate system of a longitudinal axis, x, and a radius r, wherein the motion around the longitudinal axis, x, is denoted by ω, while the motion around the radius r is denoted by φ.
The single block 90 has a motion with respect to the housing 20, which is performed in steps, as follows:
As a consequence, a plurality of broken line traces 59 are formed, as seen in
Preferably, the motions of the block 90 are contained within the housing 20, so that the external surface of the probe 10 remains stationary, wherein the external surface of the probe is substantially transparent to nuclear radiation.
Referring further to the drawings,
Additionally, a rotational motion of the housing 20, around the x-axis in the direction of ω, an amount Δω, to a new measuring position along ω, is provided, after each step of the oscillatory motion, as shown in
The resultant traces are the plurality of broken line traces 59, as seen in
In essence, the probe 10 of
In accordance with the present example,
Preferably, the motions of the blocks 90 are contained within the housing 20, so that the external surface of the probe 10 remains stationary, wherein the external surface of the probe is substantially transparent to nuclear radiation.
In particular, as seen in
The operational manner of the probe 10 of
It will be appreciated that the single detecting units 12 may be used in place of the single blocks 90.
Referring further to the drawings,
Additionally, a rotational motion of each of the blocks 90 around the x-axis, in the direction of ω, an amount Δω, to a new measuring position along ω, is provided, after each step of the oscillatory motion, as shown in
This is unlike
The resultant traces are the plurality of broken line traces 59, as seen in
In accordance with the present example,
Preferably, the motions of the blocks 90 are contained within the housing 20, so that the external surface of the probe 10 remains stationary, wherein the external surface of the probe is substantially transparent to nuclear radiation.
It will be appreciated that the detecting units 12 may be used in place of the blocks 90.
Referring further to the drawings,
The plurality of assemblies 92 are preferably arranged in parallel, and their rotational motions, around the x-axis, may be synchronized in an antipodal manner, so as to be diametrically opposed to each other, as shown in
Thus, the resultant traces are a large plurality of the broken line traces 66 and 68, as seen in
In essence, the probe 95 of
In accordance with the present example,
The operational manner of the probe 95 is described in conjunction with
Preferably, the motions of the blocks 90 and of the assemblies 92 are contained within the housing 20, so that the external surface of the probe 95 remains stationary, wherein the external surface of the probe 95 is substantially transparent to nuclear radiation.
It will be appreciated that probe 95 may include a plurality of assemblies 92, which are not parallel to each other. For example, the assemblies 92 may be at right angles to each other, or at some other angle.
It will be appreciated that the assemblies 92 may include the detecting units 12 rather then the blocks 90.
Having designed a radioactive-emission-measuring probe capable of obtaining a collection of views, and having predefined a set of views, which is optimal for a body structure, based on its model, the task of performing measurements, selectively at the predefined set of views, would be quite impossible if it were to be performed manually. Generally, between several hundreds and several thousands of views are taken, and manually tuning each to a predetermined location, orientation, and possibly also duration would be impractical. Therefore, the probe and method of the present invention are operative with an overall system, in which computer controlled motion providers govern the motions of the detecting units or of the overall probe. The computer may be any one of a personal computer, a laptop, a palmtop, or another computer, adapted for communication with the probe, or a microcomputer, built into the probe. Additionally, a combination of a microcomputer, built into the probe, and an external computer such as a personal computer, a laptop, a palmtop, or the like, may be used.
Preferably, before measurements are performed, personal details are fed into the computer, and the models of the body structure and anatomical constraints are adapted to these details. The personal details may include age, sex, weight, body type, and the like.
Referring further to the drawings,
As seen in
Preferably, the controller 404 registers the location and orientation of each of the detecting unit 12 as it moves. Additionally or alternatively, a position-tracking device may be associated with each of the detecting units 12.
Preferably, a position-tracking device 418 is associated with the probe 10 as a whole, for registering its position with respect to the body, for example, with respect to the body structure 215 (
A power supply 410 powers the probe 10. Alternatively, power may be supplied from the grid.
Preferably, a transceiver 402, or a transmitter 402, reports the measurements to an external computer. Alternatively, a cable may be used. Alternatively, the controller 404 includes a microcomputer, or the like, and performs the data analysis.
Additionally, the transceiver 402 may be adapted to receive input data relating to the personal details of the patient, such as the age, sex, weight, body type, and the like, in order to adjust the model of the body structure, hence the locations and orientations of the predefined, optimal set of views, to the particular patient.
Furthermore, the transceiver 402 may be adapted to receive input data from an ultrasound imager, for providing information such as location, size of the body structure and the like, by ultrasound imaging, in order to adjust the model of the body structure, hence the locations and orientations of the predefined, optimal set of views, to the particular patient.
Preferably, the motion of the one or several motion providers 76 relates to motion of the detecting units 12 with respect to the probe housing 20, for example, as to taught in conjunction with
Alternatively or additionally, the motion of the one or several motion providers 76 may relate to motion of the probe housing as a whole, with respect to the body structure 215 (
It will be appreciated that the controller 404, while being part of the system 400, need not part of the actual probe 10. Rather it may be an external computer, communicating with the probe 10 either by cables or via a transceiver.
As seen in
As seen in
It will be appreciated that the multiple motions may be provided to the detecting units 12, rather then to the blocks 90.
It will be appreciated that a tertiary motion provider may also be used and that many arrangements for providing the motions are possible, and known.
As seen in
In the example of
Reference is now made to the following examples of radioactive-emission-measuring probes and probe systems, for specific applications.
Referring further to the drawings,
As seen in
It will be appreciated that the first and second scoring functions may be based on any one of or a combination of the information theoretic measures of uniformity, separability, and reliability. It will be further appreciated that the first and second scoring functions need not be the same.
The significance of the present embodiment, is as follows:
It is important to point out that during the operation of the probe 10, the external surface of the intracorporeal portion 82 (
Referring further to the drawings,
Referring further to the drawings,
As seen in
Referring further to the drawings,
The control unit of the extracorporeal portion 610 may include control buttons 612 and possibly a display screen 614, and may provide connections with a computer station. It may receive power from a grid or be battery operated. The control unit of the extracorporeal portion 610 may further include a computer or a microcomputer. It will be appreciated that the control unit may be incorporated with the intracorporeal section 630, and operated remotely.
The intracorporeal portion 630 defines a cylindrical coordinate system of x;r, wherein x is the longitudinal axis. The plurality of blocks 90 along the length of the intracorporeal portion 630 is housed in an inner housing 21 (
Each of the blocks 90 is adapted for the windshield-wiper like oscillatory motion, around the radius r, as denoted by the arrows 50. The oscillatory motions may be synchronized in an antipodal manner, so as to be diametrically opposed to each other, as shown hereinabove in
Additionally, the inner housing 21 is adapted for rotational motion around the x-axis, in the direction of ω, wherein after each step of oscillatory motion at a certain orientation of ω, the inner housing rotates by a step to a new orientation of ω, and the oscillatory motion is repeated.
As a consequence, a plurality of broken line traces 59 are formed, in the body section 230, as seen in
Preferably, the controller or the computer registers the locations and orientations of each detecting unit or block and correlates the measurements with the corresponding positions and orientations.
A position-tracking device 635 may also be used, for providing information regarding the position of the probe 600 relative to a known reference. For example, if a structural scan, or another scan by another imager has been made, the position-tracking device 635 may be used to register the previous scan with the measurements of the probe 600.
It will be appreciated that the probe 600 may include detecting units 12 rather then blocks 90.
Preferably, the housing 20 remains stationary and is substantially transparent to nuclear radiation, formed, for example, of a hydrocarbon material.
The intracorporeal portion 630 may further include dedicated electronics 634 and motion providers 636, such as miniature motors and motion transfer systems, as known.
It will be appreciated that a single distal detecting unit may be employed in place of the distal block 90A.
It will be appreciated that the probes 600 of the present invention may also be moved manually, both linearly, into the body lumen and rotationally, around its longitudinal axis, preferably while the position-tracking device 635 (
It will be appreciated that a probe with a single block or a single detecting unit may also be used.
Referring further to the drawings,
The control unit 610 may include control buttons 612 and possibly a display screen 614, and may provide connections with a computer station. It may receive power from a grid or be battery operated. The control unit 610 may further include a computer or a microcomputer.
The intracorporeal portion 630 is constructed essentially as the probe 10 of
Thus, the intracorporeal section 630 defines a cylindrical coordinate system of x;r, wherein x is the longitudinal axis. The plurality of blocks 90 along the intracorporeal portion 630 is housed in an inner housing 21.
Each of the blocks 90 is adapted for the windshield-wiper like oscillatory motion, around the radius r, as denoted by the arrows 50. The oscillatory motions may be synchronized in an antipodal manner, so as to be diametrically opposed to each other, as shown hereinabove in
Additionally, the inner housing 21 is adapted for rotational motion around the x-axis, in the direction of ω, wherein after each step of oscillatory motion at a certain orientation of ω, the inner housing rotates by a step to a new orientation of ω, and the oscillatory motion is repeated.
As a consequence, a plurality of broken line traces 59 are formed, in the body section 230, as seen in
Preferably, the controller or the computer registers the locations and orientations of each detecting unit or block and correlates the measurements with the corresponding positions and orientations.
A position-tracking device 635 may also be used, for providing information regarding the position of the probe relative to a known reference.
It will be appreciated that the probe 600 may include detecting units 12 rather then blocks 90, for example, as taught in conjunction with
Preferably, the housing 20 remains stationary, and has an external surface, which is substantially transparent to nuclear radiation.
A ball bearing 632 may be used at the connecting point with the cable 620, to enable the rotational motion.
The intracorporeal section 630 may further include dedicated electronics 634 and motion providers 636, such as miniature motors and motion transfer systems, as known. Alternatively, the motion may be transferred via the cable 620.
The radioactive-emission measuring probe 600 for the esophagus (
The probe system of the present invention allows imaging of internal organs from a close proximity. Additionally, it is particularly advantageous for overweight people and for women with large breasts, for whom extracorporeal imaging, for example, extracorporeal cardiac imaging by nuclear emission measurements, is ineffective, because of losses in the tissue.
For cardiac imaging, the radiopharmaceuticals associated with the probe of
Referring further to the drawings,
Similarly,
Referring further to the drawings,
As seen in
It will be appreciated that another chair or a bed may be used rather than the chair 520. Alternatively, the patient may be standing.
The probe assembly 530 defines an internal frame of reference 80, while each assembly 92 has a reference cylindrical coordinate system of x;r, with rotation around x denoted by ω and rotation around r denoted by φ, wherein the oscillatory motion about r is denoted by the arrow 50.
Preferably, the motion of the probe assembly 530 corresponds to that described hereinabove, in conjunction with
The plurality of blocks 90 is adapted for the windshield-wiper like oscillatory motion, around the radius r, as denoted by the arrow 50. The oscillatory motions may be synchronized in an antipodal manner, so as to be diametrically opposed to each other, as shown hereinabove in
Furthermore, the plurality of assemblies 92 are preferably arranged in parallel, and their rotational motions, around the x-axis, in the direction of to, may also be synchronized in an antipodal manner, so as to be diametrically opposed to each other, as shown hereinabove, in
Thus, the resultant traces are a large plurality of the broken line traces 59, as seen hereinabove, in conjunction with
In accordance with the present example,
The operational manner of the probe 530 is described hereinbelow in conjunction with
Preferably, the motions of the blocks 90 and of the assemblies 92 are contained within the housing 20, so that the external surface of the probe assembly 530 remains stationary, wherein the external surface of the probe assembly 530 is substantially transparent to nuclear radiation. Alternatively, the housing may be open on the side facing the patient.
It will be appreciated that the oscillatory motions need not be synchronized in an antipodal manner. Rather, the blocks 90 may move together, or independently. It will be appreciated that an odd number of blocks 90 is also possible.
It will be appreciated that probe 530 may include a plurality of assemblies 92, which are not parallel to each other. For example, the assemblies 92 may be at right angles to each other, or at some other angle. It will be appreciated that the assemblies 92 may include detecting units 12 rather then blocks 90, for example, as in the probe 10 of
Thus the assembly 92 includes a row of at least two blocks 90, each adapted of oscillatory motion about r. The blocks 90 are arranged within the inner housing 21.
A motor 88 and a shaft 85 form the motion provider 76, while a secondary motor 86 and a secondary shaft 84 form the secondary motion provider 78, for the oscillatory motion about r. A plurality of motion transfer systems 74, for example to gear systems, equal in number to the number of blocks 90, transfer the motion of the secondary motion provider 78 to the blocks 90. The motion transfer systems 74, of gears, make it possible to provide the row of blocks 90 with any one of parallel oscillatory motion, antipodal oscillatory motion, or independent motion, depending on the gear systems associated with each block 90. It will be appreciated that other motion transfer systems, as known, may be used.
It will be appreciated that detecting units 12 may be used in place of blocks 90.
In accordance with the present example, adjacent blocks 90A and 90B may move in an antipodal manner and adjacent blocks 90C and 90D may move in an antipodal manner, while adjacent blocks 90B and 90C may move in parallel. It will be appreciated that many other arrangements are similarly possible. For example, all the pairing combinations of the blocks 90 may move in an antipodal manner, all the blocks 90 may move in parallel, or the blocks 90 may move independently. It will be appreciated that an odd number of blocks 90 may be used in the assembly 92.
The dimensions, which are provided in
In
In
A similar observation is made by
Again, it will be appreciated that many other arrangements are similarly possible. For example, all the pairing combinations of the blocks 90 may move in an antipodal manner, all the blocks 90 may move in parallel, or the blocks 90 may move independently. It will be appreciated that an odd number of blocks 90 may be used in the assembly 92.
Preferably, the radiopharmaceuticals associated with the probe of
It will be appreciated that cardiac imaging, in accordance with embodiments of the present invention relates to the imaging of the whole heart, or to a portion of the heart, or to blood vessels near the heart, for example, the coronary artery.
Referring further to the drawings,
The dual imaging system 700 includes a three-dimensional structural imager 720, preferably, on a structural-imager gantry 722, and a radioactive-emission measuring probe 730, preferably, on a probe gantry 732. A patient 750 may lie on a bed 740, which is adapted for motion into the radioactive-emission measuring probe 730 and the three-dimensional structural imager 720, on a bed gantry 742.
A control unit 710 controls the operation of the dual system 700, including the three-dimensional structural imager 720, the radioactive-emission measuring probe 730, and the bed 740. The control unit 710 may also analyze the data.
Alternatively, two control units may be used, one for controlling the three-dimensional structural imager 720 and another for controlling the radioactive-emission measuring probe 730. It will be appreciated that the control system of the radioactive-emission measuring probe 730 generally controls the order of the to operation of the dual system 700, wherein the radioactive-emission measuring may be performed before or after the structural imaging.
It will be further appreciated that the radioactive-emission measuring probe 730 may be configured as an add-on system, adapted for operating with an existing structural imager. It may be supplied with a dedicated software, for example, in a CD format, or with its own control unit, which is preferably adapted for communication with the structural imager control unit.
The three-dimensional structural imager 720 may be, for example, a CT or an MRI, which defines a frame of reference, wherein the radioactive-emission measuring probe 730 is co-registered to the frame of reference.
In this manner, co-registration of functional and structural images is possible. Additionally, the structural image may be used for providing tissue information for attenuation correction of the functional image, resulting in a more accurate functional image.
The radioactive-emission measuring probe 730 may be constructed as one arc 730A, preferably adapted for viewing a full width of a body from a single position of the probe 730. Alternatively, the radioactive-emission measuring probe 730 may be constructed as two arcs 730A and 730B, which are adapted for viewing a full circumference of a body, from a single position of the probe 730. It will be appreciated that the probe 730 may have other geometries, for example, a circle, an ellipse, a polygon, a plurality of arcs forming a circle, or a plurality of sections, forming a polygon, or other shapes.
Preferably, where the probe 730 is adapted for viewing a full circumference of a patient, from a single position, the bed 740 is formed as a stretcher, with a sheet 744, which is substantially transparent to radioactive emission, for example, of a hydrocarbon material.
Preferably, the gantry 732 of the probe 730 is adapted for vertical motion, as described by the arrows 734, so as to bring the probe 730 closer to the patient 750.
Additionally, the gantry 722 of the three-dimensional structural imager 720 may be adapted for rotation, as described by an arrow 724.
The bed 740 is preferably adapted for motion into and out of the probe 730 and the three-dimensional structural imager 720.
Preferably, the rate of imaging by the three-dimensional structural imager 720 and by the radioactive-emission measuring probe is substantially the same, to the bed moves into the two imagers at a constant speed.
It will be appreciated that the body structure that may be imaged may be an organ, such as a heart or a pancreas, a gland, such as a thyroid gland or a lymph gland, blood vessels, for example, the coronary artery or the pulmonary artery, a portion of an organ, such as an aorta or a left atrium of a heart, a bone, a ligament, a joint, a section of the body, such as a chest or an abdomen, or a whole body.
Preferably, the radiopharmaceuticals associated with the probe of the present invention be any one of the following:
1. anti-CEA, a monoclonal antibody fragment, which targets CEA—produced and shed by colorectal carcinoma cells—and may be labeled by Tc99m or by other radioisotopes, for example, iodine isotopes (Jessup J M, 1998, Tumor markers—prognostic and therapeutic implications for colorectal carcinoma, Surgical Oncology; 7: 139-151);
2. In111-Satumomab Pendetide (Oncoscint®), designed to target TAG-72, a mucin-like glycoprotein, expressed in human colorectal, gastric, ovarian, breast and lung cancers, but rarely in healthy human adult tissues (Molinolo A; Simpson J F; et al., 1990, 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 Res., 50(4): 1291-8);
3. Lipid-Associated Sialic Acid (LASA), a tumor antigen, used for colorectal carcinoma, with a similar sensitivity as anti-CEA monoclonal antibody fragment but a greater specificity for differentiating between benign and malignant lesions (Ebril K M, Jones J D, Klee G G, 1985, Use and limitations of serum total and lipid-bound sialic acid concentrations as markers for colorectal cancer, Cancer; 55:404-409);
4. Matrix Metaloproteinase-7 (MMP-7), a proteins enzyme, believed to be involved in tumor invasion and metastasis (Mori M, Barnard G F et al., 1995, Overexpression of matrix metalloproteinase-7 mRNA in human colon carcinoma, Cancer; 75: 1516-1519);
5. Ga67 citrate, used for detection of chronic inflammation (Mettler F A, and Guiberteau M J, Eds., 1998, Inflammation and infection imaging, Essentials of nuclear medicine, Fourth edition, Pgs: 387-403);
6. Nonspecific-polyclonal immunoglobulin G (IgG), which may be labeled with both In111 or Tc99m, and which has a potential to localize nonbacterial infections (Mettler F A, and Guiberteau M J, ibid);
7. Radio-labeled leukocytes, such as such as In111 oxine leukocytes and Tc99m HMPAO leukocytes, which are attracted to sites of inflammation, where they are activated by local chemotactic factors and pass through the endothelium into the soft tissue (Mettler F A, and Guiberteau M J, ibid; Corstens F H; van der Meer J W, 1999, Nuclear medicine's role in infection and inflammation, Lancet; 354 (9180): 765-70); and
8. Tc99m bound to Sodium Pertechnetate, which is picked up by red blood cells, and may be used for identifying blood vessels and vital organs, such as the liver and the kidneys, in order to guide a surgical instrument without their penetration.
It will be appreciated that other agents may be used.
The probe 730 defines an internal frame of reference 80, while each assembly 92 has a reference cylindrical coordinate system of x;r, with rotation around x denoted by ω and rotation around r denoted by φ, wherein the oscillatory motion about r is denoted by the arrow 50.
Preferably, the motions of the assemblies 92 and the blocks 90 correspond to those described hereinabove, in conjunction with
The plurality of blocks 90 is adapted for the windshield-wiper like oscillatory motion, around the radius r, as denoted by the arrow 50. The oscillatory motions may be synchronized in an antipodal manner, so as to be diametrically opposed to each other, as shown hereinabove in
Furthermore, the plurality of assemblies 92 are preferably arranged in parallel, and their rotational motions, around the x-axis, in the direction of ω, may also be synchronized in an antipodal manner, so as to be diametrically opposed to each other, as shown hereinabove, in
Thus, the resultant traces are a large plurality of the broken line traces 59, as seen hereinabove, in conjunction with
In accordance with the present example,
The operational manner of the probe 730 is described hereinbelow in conjunction with
Preferably, the motions of the blocks 90 and of the assemblies 92 are contained within the housing 20, so that the housing 20 of the probe 730 remains stationary, wherein the external surface of the probe 730 is substantially transparent to nuclear radiation. Alternatively, the housing may be open on the side facing the patient.
It will be appreciated that the oscillatory motions need not be synchronized in an antipodal manner. Rather, the blocks 90 may move together, or independently. It will be appreciated that an odd number of blocks 90 is also possible.
It will be appreciated that the probe 730 may include a plurality of assemblies 92, which are not parallel to each other. For example, the assemblies 92 may be at right angles to each other, or at some other angle. It will be appreciated that the assemblies 92 may include detecting units 12 rather then blocks 90, for example, as in the probe 10 of
Thus the assembly 92 includes a row of at least two blocks 90, each adapted of oscillatory motion about r. The blocks 90 are arranged within the inner housing 21.
A motor 88 and a shaft 85 form the motion provider 76, while a secondary motor 86 and a secondary shaft 84 form the secondary motion provider 78, for the oscillatory motion about r. A plurality of motion transfer systems 74, for example gear systems, equal in number to the number of blocks 90, transfer the motion of the secondary motion provider 78 to the blocks 90. The motion transfer systems 74, of gears, make it possible to provide the row of blocks 90 with any one of parallel oscillatory motion, antipodal oscillatory motion, or independent motion, depending on the gear systems associated with each block 90. It will be appreciated that other motion transfer systems, as known, may be used.
It will be appreciated that detecting units 12 may be used in place of blocks 90.
In accordance with the present example, adjacent blocks 90A and 90B may move in an antipodal manner and adjacent blocks 90C and 90D may move in an antipodal manner, while adjacent blocks 90B and 90C may move in parallel. It will be appreciated that many other arrangements are similarly possible. For example, all the pairing combinations of the blocks 90 may move in an antipodal manner, all the blocks 90 may move in parallel, or the blocks 90 may move independently. It will be appreciated that an odd number of blocks 90 may be used in the assembly 92.
It will be appreciated that many other probes and probe systems may be considered and the examples here are provided merely to illustrate the many types of combinations that may be examined, in choosing and scoring a probe design, both in terms of information and in terms of secondary considerations, such as rate of data collection, cost, and complexity of the design.
Brain cancer is the leading cause of cancer-related death in patients younger than age 35, and in the United States, the annual incidence of brain cancer generally is 15-20 cases per 100,000 people.
There are two types of brain tumors: primary brain tumors that originate in the brain and metastatic (secondary) brain tumors that originate from cancer cells that have migrated from other parts of the body.
Approximately 17,000 people in the United States are diagnosed with primary cancer each year; nearly 13,000 die of the disease. Amongst children, the annual incidence of primary brain cancer is about 3 per 100,000.
Primary Brain Tumors are generally named according to the type of cells or the part of the brain in which they begin. The most common are gliomas, which begin in glial cells, and of which there are several types, as follows:
Astrocytoma, a tumor which arises from star-shaped glial cells called astrocytes, and which in adults, most often arises in the cerebrum, whereas in children, it occurs in the brain stem, the cerebrum, and the cerebellum.
Brain stem glioma, a tumor that occurs in the lowest part of the brain, and is diagnosed in young children as well as in middle-aged adults.
Ependymoma, a tumor, most common in middle-aged adults, which arises from cells that line the ventricles or the central canal of the spinal cord and which occurs in children and young adults.
Oligodendroglioma, a rare tumor, which arises from cells that make the fatty substance that covers and protects nerves and usually occurs in the cerebrum, grows slowly and generally does not spread into surrounding brain tissue.
Some types of brain tumors do not begin in glial cells. The most common of these are:
Medulloblastoma, also called a primitive neuroectodermal tumor, a tumor which usually arises in the cerebellum and is the most common brain tumor in children.
Meningioma, which arises in the meninges and usually grows slowly.
Schwannoma, also called an acoustic neuroma, and occurring most often in adults, it is a tumor that arises from a Schwann cell, of the cells that line the nerve that controls balance and hearing, in the inner ear.
Craniopharyngioma, a tumor which grows at the base of the brain, near the pituitary gland, and most often occurs in children.
Germ cell tumor of the brain, a tumor which arises from a germ cell, generally, in people younger than 30, the most common type of which is a germinoma.
Pineal region tumor, a rare brain tumor, which arises in or near the pineal gland, located between the cerebrum and the cerebellum.
Certain inherited diseases are associated with brain tumors, for example, Multiple endocrine neoplasia type 1 (pituitary adenoma), Neurofibromatosis type 2 (brain and spinal cord tumors), Retinoblastoma (malignant retinal glioma), Tuberous sclerosis (primary brain tumors), and Von Hippel-Lindau disease (retinal tumor, CNS tumors). Furthermore, genetic mutations and deletions of tumor suppressor genes (i.e., genes that suppress the development of malignant cells) increase the risk for some types of brain cancer.
Additionally, exposure to vinyl chloride is an environmental risk factor for brain cancer. Vinyl chloride is a carcinogen, used in the manufacturing of plastic products such as pipes, wire coatings, furniture, car parts, and house wares, and is present in tobacco smoke. Manufacturing and chemical plants may release vinyl chloride into the air or water, and it may leak into the environment as a result of improper disposal. People who work in these plants or live in close proximity to them have an increased risk for brain cancer.
Secondary brain cancer occurs in 20-30% of patients with metastatic disease and its incidence increases with age. In the United States, about 100,000 cases of secondary brain cancer are diagnosed each year. Patients with a history of melanoma, lung, breast, colon, or kidney cancer are at risk for secondary brain cancer.
Brain tumors can obstruct the flow of cerebrospinal fluid (CSF), which results in the accumulation of CSF (hydrocephalus) and increased intracranial pressure (IICP). Nausea, vomiting, and headaches are common symptoms. They can damage vital neurological pathways and invade and compress brain tissue. Symptoms usually develop over time and their characteristics depend on the location and size of the tumor.
The first step in diagnosing brain cancer involves evaluating symptoms and taking a medical history. If there is any indication that there may be a brain tumor, various tests are done to confirm the diagnosis, including a complete neurological examination, imaging tests, and biopsy.
Referring now to the drawings,
a cerebellum 802, which is the part of the brain below the back of the cerebrum. it regulates balance, posture, movement, and muscle coordination;
a corpus callosum 804, which is a large bundle of nerve fibers that connect the left and right cerebral hemispheres;
a frontal lobe of the cerebrum 806, which is the top, front regions of each of the cerebral hemispheres, and is used for reasoning, emotions, judgment, and voluntary movement;
a medulla oblongata 808, which is the lowest section of the brainstem (at the top end of the spinal cord) and controls automatic functions including heartbeat, breathing, and the like;
a occipital lobe of the cerebrum 810, which is the region at the back of each cerebral hemisphere, at the back of the head, and contains the centers of vision and reading ability;
a parietal lobe of the cerebrum 812, which is the middle lobe of each cerebral hemisphere between the frontal and occipital lobes, located at the upper rear of the head, and which contains important sensory centers;
a pituitary gland 814, which is a gland attached to the base of the brain that secretes hormones, and is located between the pons and the corpus callosum;
pons 816, which is the part of the brainstem that joins the hemispheres of the cerebellum and connects the cerebrum with the cerebellum, located just above the medulla oblongata;
a spinal cord 818, which is a thick bundle of nerve fibers that runs from the base of the brain to the hip area, through the spine (vertebrae);
a temporal lobe of the cerebrum 820, which is the region at the lower side of each cerebral hemisphere, located at the sides of the head and containing centers of hearing and memory.
The brain 215 may include a pathological feature 213, termed herein an organ target 213. A region of interest (ROI) 200 may be defined so as to encompass the brain 215 and the pathological feature 213.
As seen in
Referring further to the drawings,
As seen in
In I: The region of interest 200, associated with the organ 215, such as the brain 215, is defined for the body section 230.
Referring further to the drawings,
Preferably, radioactive-emission-measuring probe 850 for the brain is shaped as a helmet 860, adapted for wearing on a head 862. The helmet 860 is preferably mounted on a gantry 870, which may be adjustable in the directions of arrows 872, 874 and 876, for adapting to individual heights and comfort.
Alternatively, no gantry is used, and the helmet 860 may be worn directly on the head 862, for example, like a motorcycle helmet.
A chair 880 may be provided for the comfort of the patient.
Preferably, the radioactive-emission-measuring probe 850 for the brain is operable with a control unit 890, which may be a desktop computer, a laptop, or the to like. The control unit 890 is preferably used both for controlling the motions of the detecting units 12, blocks 90 and assemblies 92 of the radioactive-emission-measuring probe 850 for the brain and for analyzing the data.
It will be appreciated that the radioactive-emission-measuring probe 850 for the brain may be supplied merely as the probe helmet 860 and a data storage device, such as a CD 892, a disk 892, or the like, containing the appropriate software, for operation with an existing computer, at the site.
It will be appreciated that the radioactive-emission-measuring probe 850 for the brain may be operable with a structural imager, as taught by commonly owned PCT publication WO2004/042546, whose disclosure is incorporated herein by reference. The structural imager may be a handheld ultrasound imager, possibly with a position-tracking device, a 3-D imager such as an ultrasound imager, a CT imager, or an MRI imager, as known. The data provided by the structural imager may be used for any one or a combination of the following:
Referring further to the drawings
Preferably, the proximal side of the housing 864 with respect to the head 862 (
Alternatively, as seen in
The assembly 92 and the block 90, in accordance with a preferred embodiment of the present invention are described in
Thus the assembly 92 includes a row of at least two blocks 90, each adapted of oscillatory motion about r. The blocks 90 are arranged within the inner housing 21.
A motor 88 and a shaft 85 form the motion provider 76, while a secondary motor 86 and a secondary shaft 84 form the secondary motion provider 78, for the to oscillatory motion about r. A plurality of motion transfer systems 74, for example gear systems, equal in number to the number of blocks 90, transfer the motion of the secondary motion provider 78 to the blocks 90. The motion transfer systems 74, of gears, make it possible to provide the row of blocks 90 with any one of parallel oscillatory motion, antipodal oscillatory motion, or independent motion, depending on the gear systems associated with each block 90. It will be appreciated that other motion transfer systems, as known, may be used.
It will be appreciated that detecting units 12 may be used in place of blocks 90.
In accordance with the present example, adjacent blocks 90A and 90B may move in an antipodal manner and adjacent blocks 90C and 90D may move in an antipodal manner, while adjacent blocks 90B and 90C may move in parallel. It will be appreciated that many other arrangements are similarly possible. For example, all the pairing combinations of the blocks 90 may move in an antipodal manner, all the blocks 90 may move in parallel, or the blocks 90 may move independently. It will be appreciated that an odd number of blocks 90 may be used in the assembly 92.
It will be appreciated that imaging, in accordance with embodiments of the present invention relates to the imaging of the whole brain, or to a portion of the brain, or to blood vessels near the brain, for example, the coronary artery.
Preferably, the radiopharmaceuticals associated with the probe of the present invention may be Tc99m-d, 1-hexamethyl propylene amine oxime (1-HMPAO) commercially known as Ceretec by GE-Amersham, or 99mTc-ECD, commercially known as Neurolite, and made by Bristol Myers Squibb.
The present invention applies to the two types of brain tumors: primary brain tumors, which originate in the brain and metastatic (secondary) brain tumors that originate from cancer cells that have migrated from other parts of the body.
Additionally, the primary brain tumors may be gliomas, which begin in glial cells, and of which there are several types, as follows:
Astrocytoma, a tumor which arises from star-shaped glial cells called astrocytes, and which in adults, most often arises in the cerebrum, whereas in children, it occurs in the brain stem, the cerebrum, and the cerebellum.
Brain stem glioma, a tumor that occurs in the lowest part of the brain, and is to diagnosed in young children as well as in middle-aged adults.
Ependymoma, a tumor, most common in middle-aged adults, which arises from cells that line the ventricles or the central canal of the spinal cord and which occurs in children and young adults.
Oligodendroglioma, a rare tumor, which arises from cells that make the fatty substance that covers and protects nerves and usually occurs in the cerebrum, grows slowly and generally does not spread into surrounding brain tissue.
Additionally or alternatively, the present invention applies to other types of brain tumors, which do not begin in glial cells. The most common of these are:
Medulloblastoma, also called a primitive neuroectodermal tumor, a tumor which usually arises in the cerebellum and is the most common brain tumor in children.
Meningioma, which arises in the meninges and usually grows slowly.
Schwannoma, also called an acoustic neuroma, and occurring most often in adults, it is a tumor that arises from a Schwann cell, of the cells that line the nerve that controls balance and hearing, in the inner ear.
Craniopharyngioma, a tumor which grows at the base of the brain, near the pituitary gland, and most often occurs in children.
Germ cell tumor of the brain, a tumor which arises from a germ cell, generally, in people younger than 30, the most common type of which is a germinoma.
Pineal region tumor, a rare brain tumor, which arises in or near the pineal gland, located between the cerebrum and the cerebellum.
Additionally or alternatively, the present invention applies to tumors associated with certain inherited diseases, for example, Multiple endocrine neoplasia type 1 (pituitary adenoma), Neurofibromatosis type 2 (brain and spinal cord tumors), Retinoblastoma (malignant retinal glioma), Tuberous sclerosis (primary brain tumors), and Von Hippel-Lindau disease (retinal tumor, CNS tumors), and genetic mutations and deletions of tumor suppressor genes (i.e., genes that suppress the development of malignant cells), which increase the risk for some types of brain cancer.
Additionally or alternatively, the present invention applies to tumors associated with exposure to vinyl chloride.
Additionally or alternatively, the present invention applies to secondary brain cancer, for example, originating from the lungs, the breasts, or other parts of the body.
It will be appreciated that the present invention further applies to other types brain tumors, which may be malignant or benign, blood clots in the brain, and other brain pathologies. It will be appreciated that many other probes and probe systems may be considered and the examples here are provided merely to illustrate the many types of combinations that may be examined, in choosing and scoring a probe design, both in terms of information and in terms of secondary considerations, such as rate of data collection, cost, and complexity of the design.
As seen in
Alternatively,
Thus, as seen in
Mammography is currently the most effective method of screening for breast cancer, for the detection of early non-palpable tumors. In essence, it involves compressing the breast between two plates, a support plate and a compression plate, and passing x-rays through the compressed breast. The compression is desirous both in order to spread the breast fatty tissue thin, to reduce its attenuation, and in order to fix the breast tissue, with respect to a frame of reference, so that the x-ray image may be correlated with a surgical tool frame of reference, such as a biopsy needle frame of reference, for guiding the surgical tool to a suspected location on the x-ray image, without the breast tissue moving between the taking of the x-ray image and the guiding of the surgical tool.
Often stereotactic mammography is applied, meaning that the x-ray head is rotated with respect to the plates, so as to provide at least two views of the fixed breast, compressed between the plates, from at least two angles, for stereo imaging.
In general, each breast is imaged separately, generally, both in a vertical direction and from the side (laterally), preferably, stereotactically. In other words, generally, at least four views of each breast are taken, two vertically and two laterally.
A surgical instrument, for example, a biopsy needle, or an ablation device, such as a cryosurgery device, an ultrasound ablation device, a knife, or a laser ablation device, may be built onto the mammograph, its frame of reference correlated with that of the x-ray image.
An x-ray tube 905 is preferably arranged so as to move within a track 907, for obtaining x-ray images of the compressed breast 909 from at least two views, so as to obtain stereotactic viewing, for depth evaluation. A film 901 is preferably arranged under the breast 909, for example, under the support plate 902, for registering the x-ray image.
Additionally, the mammograph 900 is preferably adapted for rotation, as illustrated by an arrow 908, for compressing a breast from at least two orientations, for example vertically and laterally.
A surgical tool 903, for example, a biopsy needle 903 or an ablation device 903, such as by cryosurgery or laser, or a knife 903, may be built onto the mammograph 900, its frame of reference correlated with the frame of reference 80, using position tracking devices or a linkage system, as known.
In
As seen in
Referring further to the drawings,
Specifically,
In
A first motion is a rotational motion of all the blocks 90, moving as a single body, with the shaft 85 and the internal housing 21, around the x-axis, in the direction between +ω and −ω, as illustrated by the arrow 52. The first motion is powered by the motor 88.
A second motion is an oscillatory motion of the individual blocks 90, powered by the secondary motor 86, the secondary shaft 84, and the motion transfer link 74, the motion transfer link 74 moving in a linear, sliding motion, as shown by the arrow 71.
At each orientation of the internal housing 21 with respect to ω, around x, the second, oscillatory motion about r takes place, individually by each of the block 90, the oscillatory motion about r being between −φ and +φ, as illustrated by the arrow 50, and as taught hereinabove, in conjunction with
Thus, the overall motion is as illustrated hereinabove, in conjunction with
Further as seen in
Thus, for the radioactive-emission-measuring probe 1000, for the breast:
It is important to point out that during the operation of the probe 1000, the sheath 985 of the imaging portion 980 (
Referring further to the drawings,
Preferably, as seen in
Additionally, as seen in
An alternative embodiment is illustrated in
It will be appreciated that edge probes 1000, may be added to the embodiment of
In accordance with embodiments of the present invention, frames may be provided for mounting the radioactive-emission-measuring probes 1000 on the plates 902 and 904.
As seen in
Alternatively, as seen in
Additionally, as seen in
Furthermore, as seen in
As seen in
As seen in
In accordance with embodiments of the present invention, nuclear imaging by radioactive-emission-measurements, co-registered with x-ray mammography, may be obtained as follows:
It will be appreciated that steps 2 and 3 may be performed in any order.
Preferably, the images of the x-ray mammography and the nuclear imaging are co-registered and analyzed together.
However, it will be appreciated that only nuclear imaging by radioactive-emission measurements may be performed, without x-ray imaging.
Where ultrasound imaging co-registered with nuclear imaging by radioactive-emission-measurements is desired, a method applies, as follows:
It will be appreciated that the steps 3 and 4 may be performed in any order.
Preferably, the images of the x-ray mammography and the nuclear imaging are co-registered and analyzed together.
Referring further to the drawings,
As seen in
A vacuum ring 936, for example of natural or synthetic rubber, helps maintain the vacuum in the cup 934.
The vacuum cup 934 defines the frame of reference 80 and a plurality of the blocks 90 are arranged along the walls 938 of the suction cup 934, each adapted for at least one, and preferably two rotational motions, for example, as illustrated in conjunction with
A surgical tool may be attached to the probe 930, and correlated to its frame of reference, for example as taught in conjunction with
The motions of the blocks 90 are preferably automatic, controlled by the control unit 890 (
Preferably, the inner walls 938 of the cup 934 are substantially transparent to radioactive emission.
Referring further to the drawings,
As seen in
Additionally, the patient may be positioned on a chair 960, as seen in
The control unit 890 is illustrated in
The control unit 890 may be used for controlling the motions of the blocks 90 (
The probe 950 defines the frame of reference 80, while each assembly 92 has a reference cylindrical coordinate system of x;r, with rotation around x denoted by the arrow 62 and oscillatory motion about r, denoted by the arrow 50.
It will be appreciated that imaging, in accordance with embodiments of the present invention relates to the imaging of the whole breast, or to a portion of the breast, the armpits near the breasts, (and) or the two breasts.
Preferably, the radiopharmaceuticals associated with the radioactive-emission-measuring probe for the breast may be Tc99m bound to Sestamibi, a small protein molecule, made for example, by Bristol Myers Squibb, and marketed as Miraluma, used widely for breast cancer detection.
The present invention applies to detecting and differentiating between various types of breast disorders, for example as illustrated in
i. fibroadenomas 8, which are fibrous, benign growths in breast tissue.
ii. cysts 9, which are fluid-filled sacs and may disappear sometimes by themselves, or a doctor may draw out the fluid with a needle.
iii. a breast abscess 11, which is a collection of pus, resulting from an infection.
iv. fibrocystic breast disease 13, which is a common condition characterized by an increase in the fibrous and glandular tissues in the breasts, resulting in small, nodular cysts, noncancerous lumpiness, and tenderness, wherein treatment of the cysts may be all that is needed.
v. a tumor 15, which may be precancerous or cancerous, and which usually shows up as a white area on a mammogram even before it can be felt. In cases where the tumor 15 is cancerous, it may appear as a white area with radiating arms. A cancerous tumor 15 may have no symptoms or may cause swelling, tenderness, discharge from the nipple 4, indentation of the nipple 4, or a dimpled appearance 17 in the skin over the tumor.
Additionally, the present invention applies to detecting various types of breast cancers, such as:
i. ductal cancer, which affects the cells of the ducts;
ii. lobular cancer, which begins in the lobes or lobules of the breast; and
iii. inflammatory breast cancer, which is an uncommon type of breast cancer and causes the breast to be warm, red, and swollen.
It will be appreciated that the present invention further applies to other types breast disorders, which may be cancerous, precancerous, or benign.
Additionally or alternatively, the present invention applies to secondary breast cancer, for example, originating from the lungs, or other parts of the body.
Furthermore, the radioactive-emission-measuring probe for the breast may be to designed for and used on a single breast or designed for and used simultaneously on the two breasts.
It will be appreciated that although breast cancer in men and children is rare, the present invention may be used for the detection of breast cancer in men and children as well.
It will be appreciated that many other probes and probe systems may be considered and the examples here are provided merely to illustrate the many types of combinations that may be examined, in choosing and scoring a probe design, both in terms of information and in terms of secondary considerations, such as rate of data collection, cost, and complexity of the design.
It will be appreciated that the methods of the present invention apply to pathological features that may be modeled as regions of concentrated radiations, or hot regions, regions of low-level radiation, which is nonetheless above background level, and regions of little radiation, or cold regions, below the background level. However, in general, for identifying a pathological feature of the heart, they relate to cold regions.
It will be appreciated that the methods of the present inventions may be operable by computer systems and stored as computer programs on computer-readable storage media.
It will be appreciated that the body may be an animal body or a human body.
It will be appreciated that the radioactive-emission-measuring systems, probes and methods of the present invention may be used with commonly owned US Applications 20040015075 and 20040054248 and commonly owned PCT publication WO2004/042546, all of whose disclosures are incorporated herein by reference. These describe systems and methods for scanning a radioactive-emission source with a radioactive-emission-measuring probe of a wide-aperture collimator, and at the same time, monitoring the position of the radioactive-emission-measuring probe, at very fine time intervals, to obtain the equivalence of fine-aperture collimation. In consequence, high-efficiency, high-resolution, images of a radioactive-emission source are obtained.
Commonly owned US application 20040054248 and commonly owned PCT publication WO2004/042546 further disclose various extracorporeal and intracorporeal systems, of radioactive-emission-measuring probes, of relatively wide apertures, associated with position-tracking devices.
It will be appreciated that the radioactive-emission-measuring systems, probes and methods of the present invention may be used with commonly owned U.S. Pat. No. 6,173,201 to Front, whose disclosure is incorporated herein by reference, as well as by M. W. Vannier and D. E. Gayou, “Automated registration of multimodality images”, Radiology, vol. 169 pp. 860-861 (1988); J. A. Correia, “Registration of nuclear medicine images, J. Nucl. Med., vol. 31 pp. 1227-1229 (1990); J-C Liehn, A. Loboguerrero, C. Perault and L. Demange, “superposition of computed tomography and single photon emission tomography immunoscinigraphic images in the pelvis: validation in patients with colorectal or ovarian carcinoma recurrence”, Eur. J. Nucl. Med., vol. 19 pp. 186-194 (1992); F. Thomas et al., “Description of a prototype emission transmission computed tomography imaging system”, J. Nucl. Med., vol. 33 pp. 1881-1887 (1992); D. A. Weber and M. Ivanovic, “Correlative image registration”, Sem. Nucl. Med., vol. 24 pp. 311-323 (1994); and Hasegawa et al., U.S. Pat. No. 5,376,795.
These relate to the acquisition of both a functional image of the body, such as a radioactive-emission image, and a structural image, such as an ultrasound, an x-ray, or an MRI image, and their co-registration on a single frame of reference.
In essence, several images may be acquired and co-registered to the same frame of reference, as follows:
Thus, a physician may locate the pathological feature in reference to the blood vessels, vital organs, and the bones, and guide a minimally invasive surgical instrument to the pathological feature, while avoiding the blood vessels, vital organs, and bones. The minimally invasive surgical instrument may be a biopsy needle, a wire, for hot resection, a knife for cold resection, an instrument of focused energy, to produce ablation, for example, by ultrasound, or by laser, an instrument for cryosurgery, an instrument for croyetherapy, or an instrument for bractherapy, wherein seeds of a radioactive metal are planted close to a tumor, for operating as a radioactive source near the tumor.
Commonly owned PCT publication WO2004/042546 further discloses that the surgical instrument may be visible on at least one of the images, for example, on the structural image, to enable the physician to see the instrument, the pathological feature, and the surrounding anatomy on the display 129 (
Commonly owned U.S. Pat. No. 6,173,201, to Front further discloses a method of stereotactic therapy, wherein a frame, which includes at least three markers, visible on a structural image, is rigidly secured to a patient. The structural image of a region inside the patient's body, which includes a pathological feature and the markers, is acquired. A functional image of the pathological feature is then acquired and co-registered with the structural image, to correlate the images to the same frame of reference. A stereotactic guide is rigidly attached to the frame and is used to guide a surgical instrument, such as a biopsy needle or a brachytherapy needle, to the pathological feature, with reference to the co-registered images.
Thus the radioactive-emission-measuring systems, probes and methods of the present invention may be used together with position tracking devices, for enhanced image acquisition, they may be used together with structural imager and structural imaging for correlating functional and structural images, and they may be used for guiding minimally invasive surgical instruments, such as a biopsy needle, a wire, for hot resection, a knife for cold resection, an instrument of focused energy, to produce ablation, for example, by ultrasound, or by laser, an instrument for cryosurgery, an instrument for croyetherapy, or an instrument for bractherapy.
It will be appreciated that a structural image, such as by ultrasound may further be used and in order to provide information about the size and location of the body structure 215 for the purpose of creating the model 250 (
It will be appreciated that a structural image, such as by ultrasound may further be used and in order to provide information about tissue attenuation, for example, as taught in conjunction by commonly owned PCT publication WO2004/042546, whose disclosure is incorporated herein by reference. The information may then be used to correct the radioactive-emission measurements.
It is expected that during the life of this patent many relevant radioactive-emission-measuring systems, probes and methods will be developed and the scope of these terms is intended to include all such new technologies a priori.
As used herein the term “about” refers to ±20%.
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 to scope of the appended claims.
All publications, 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, any 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 Application is a continuation of U.S. patent application Ser. No. 11/607,075 filed on Dec. 1, 2006, which is a continuation-in-part of PCT Patent Application No. PCT/IL2005/000575 filed on Jun. 1, 2005, which claims the benefit of priority of U.S. Provisional Patent Application Nos. 60/648,690 filed on Feb. 2, 2005, 60/648,385 filed on Feb. 1, 2005, 60/640,215 filed on Jan. 3, 2005, 60/636,088 filed on Dec. 16, 2004, 60/635,630 filed on Dec. 14, 2004, 60/632,515 filed on Dec. 3, 2004, 60/632,236 filed on Dec. 2, 2004, 60/630,561 filed on Nov. 26, 2004, 60/625,971 filed on Nov. 9, 2004 and 60/575,369 filed on Jun. 1, 2004. Ser. No. 11/607,075 is also a continuation-in-part of pending U.S. patent application Ser. No. 09/641,973 filed on Aug. 21, 2000. Ser. No. 11/607,075 is also a continuation-in-part of pending U.S. patent application Ser. No. 10/343,792 filed on Feb. 4, 2003. Ser. No. 11/607,075 is also a continuation-in-part of pending U.S. patent application Ser. No. 10/616,307 filed on Jul. 10, 2003. Ser. No. 11/607,075 is also a continuation-in-part of U.S. patent application Ser. No. 10/533,568 filed on Jan. 5, 2006, now U.S. Pat. No. 7,652,259. All of the above Applications are incorporated herein by reference
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