Abstract:
This invention is directed to a novel hybrid nuclear and ultrasonic probe comprising a cylindrical outer casing surrounding a nuclear probe comprising two scintillator plates intersecting perpendicularly, each of the scintillator plates having a plurality of parallel collimators; and an ultrasonic probe situated between said casing at the intersection of said scintillator plates.

Description:
CLAIM OF PRIORITY 
     This application is a continuation-in-part of co-pending U.S. Ser. No. 08/717,134, filed Sep. 20, 1996, which is a continuation of U.S. Ser. No. 08/550,516 which was filed on Oct. 20, 1995, now abandoned which is a continuation of U.S. Ser. No. 08/204,581 filed Mar. 2, 1994 now abandoned. 
    
    
     FIELD OF THE INVENTION 
     This invention relates to the detection of diseases. More specifically, this invention relates to a novel apparatus for the detection of diseases using both ultrasonic and nuclear energy. 
     BACKGROUND OF THE INVENTION 
     Devices for examining potentially diseased areas of the body have been used for many years for diagnostic purposes. Magnetic resonance imaging (MRI) machines, ultrasound devices, CAT scanners and X-ray imagers are but a few of the commonly utilized tools that medical radiologists have at their disposal to characterize and understand many of the maladies that afflict patients. 
     Well-known ultrasound devices use acoustical energy to characterize areas in the body for many different reasons. Particularly useful for displaying fluid flow, acoustical energy detected by ultrasound probes can be used in diverse applications, for example, to examine blood flow in and around diseased tissue, or to investigate the health of a fetus growing in the womb. Since ultrasound devices use acoustical energy to perform their function, they are “active” devices which first emit energy, and then detect reflected energy which has been partially absorbed. 
     Recently, the development of nuclear probes has given physicians yet another modality to explore and diagnose disease. Nuclear probes are unique and sophisticated devices that take advantage of the fact that diseased tissue tends to absorb substances that emit radiation. Thus, radiopharmaceuticals or radiolabeled monoclonal antibodies (MaB) that emits gamma radiation can be used to label diseased tissues which can then be examined with a nuclear probe. 
     Generally, the labeled tissue accumulates a higher concentration of the gamma-emitting substance so that the tissue appears “hot” to the probe, that is, more gamma radiation is emitted from the diseased tissue than from other surrounding areas. Since it is known that diseased tissue will more readily absorb the radiopharmaceutical or radiolabeled MaB, the probe thus locates the diseased tissue by detecting the hot area. 
     A typical nuclear probe that performs along the lines mentioned above is the Radiation Monitoring Devices, Inc. (Watertown, Mass.) Nuclear Surgical Probe System. Primarily for use in surgical applications, the Nuclear Surgical Probe System comprises a solid state Cadmium Telluride (CdTe) detector that detects gamma radiation from about 12 keV to about 1 MeV, a high gain field effect transistor preamplifier, and a counting subsystem with a display which performs diagnostic analysis and which can be interfaced to a personal computer. 
     Nuclear probes are reliable and innovative devices for locating diseased areas. However, these devices cannot further evaluate the diseased tissue in relation to the patient&#39;s anatomy after the tissue has been located. The radiological imaging art has therefore lacked an efficient tool which can both pinpoint the presence of the diseased tissue, characterize the diseased tissue and see its relationship to normal anatomic structures to develop a course of medical and/or surgical treatment. 
     There has therefore been a failure in the art to develop versatile clinical tools for disease detection and diagnosis. This has resulted in an inability to effectively treat potentially life-threatening diseases at early stages. Early disease detection allows for more effective treatment, significantly improving a patient&#39;s prognosis. This ability would not only save lives but contribute to the reduced cost of health care. 
     SUMMARY OF THE INVENTION 
     The present invention is directed to a hybrid probe comprising a substantially cylindrical probe for locating and characterizing disease comprising a scintillator having parallel collimators for examining a potentially diseased area as a function of electromagnetic radiation emitted from the area, an ultrasonic sensor situated on said scintillator for examining the potentially diseased area with ultrasonic energy, wherein the scintillator and ultrasonic sensor are adapted to characterize the potentially diseased area interactively, and processing means interfaced to at least the first means for analyzing data collected by at least one of the first or second means and for analyzing the data to characterize the disease in the potentially diseased area. 
     In a further embodiment, the present invention further comprises a novel hybrid probe comprising a cylindrical outer casing surrounding a nuclear probe, said nuclear probe comprising a scintillator extending axially the length of the casing, said scintillator having a plurality of parallel collimators extending therefrom, and an ultrasonic probe affixed within the casing on said scintillator and extending the length of the scintillator. 
     In a further embodiment to the present invention, the scintillator comprises two scintillator plates intersecting substantially perpendicularly, and the ultrasonic probe is situated at the intersection of the scintillator plates and extends their lengths. In a further embodiment of the present invention, the scintillator is curved. In still a further embodiment of the present invention, the scintillator is flat. 
     The hybrid probe of the present invention defines a new modality with unique characteristics and capabilities that produce increased benefits in the detection and diagnosis of diseases. The hybrid probe is designed to detect and diagnose disease using a dual mode, combining ultrasound and nuclear medicine to produce images with specificity that is unattainable with existing and even proposed imaging methods. 
     The hybrid probe of the present invention defines a new “interactive” method and increased versatility for application to the detection and diagnosis of numerous diseases. It is the only imaging modality that combines the unique characteristics of ultrasound and nuclear medicine in the manner described, delivered in a non-invasive, easily portable device for the advanced detection and diagnostic results. 
     This invention allows ultrasound and nuclear medicine images to be obtained simultaneously in real-time three dimension, enables complete integration of ultrasound and nuclear medicine images simultaneously with 3D perspective including, X, Y, Z coordinates of a tumor or other significant disease and with wide field of view to see relationship to normal structures. The images produced will be a hybrid anatomical (ultrasound) and functional (nuclear medicine) image which renders, in one exam, much greater information than each individual exam could produce. The results are images that combine the best qualities of each modality to provide new diagnostic information that is unobtainable with existing or proposed imaging methods and/or devices. 
     Hybrid probes provided in accordance with the present invention will provide superior diagnostic capabilities than individual ultrasound or nuclear probes which have heretofore been known and used in the art. Greater sensitivity and specificity of disease detection and characterization will be accomplished with such hybrid probes, and therefore early detection of diseases will be accomplished. This will inevitably result in saving lives and reducing the cost of health care. Such results have not heretofore been achieved in the art. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 is a schematic representation of a system for diagnosing disease provided in accordance with the present invention which comprises a nuclear probe and an ultrasound device. 
     FIG. 2 is a section view of a novel hybrid probe in accordance with the present invention. 
     FIG. 3 is a side perspective view of a novel hybrid probe of the present invention. 
     FIG. 4 is a plan view of the hybrid probe of the present invention. 
     FIG. 5 is a representation of the output of the novel probe of the present invention. 
     FIG. 6 is a representation of the output of a typical hybrid probe. 
     FIG. 7 is an alternative embodiment of a hybrid probe in accordance with the present invention. 
     FIG. 8 is still a further alternative embodiment of the hybrid probe of the present invention. 
     FIGS. 9A-9C are section views of still further embodiments of the present invention in which the scintillators and ultrasonic sensor are situated axially at the tip of the probe. 
    
    
     DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS 
     Referring now to the Figures, in FIG. 1 a patient  10  undergoes examination with a combined or hybrid probe shown generally at  20 . The patient could be undergoing examination with probe  20  prior to a surgical or therapeutic technique, or could be examined by probe  20  during surgery or as part of the patient&#39;s therapy. For exemplary purposes, the patient is shown with a potentially diseased area  35  that is involved with a cancer or other disease which is potentially life-threatening. Through use of the hybrid probe  20 , a system is provided for diagnosing and characterizing disease efficiently and at an early stage. 
     In a preferred embodiment, hybrid probe  20  comprises an ultrasound probe shown at  30  and a nuclear probe shown at  40 . Ultrasound probes are known to those with skill in the art. They generally consist of a probe body  50 , and an excitation head  60  which emits acoustical or ultrasonic energy shown generally at  70  which is used to examine the potentially diseased area  35 . The ultrasonic probe  30  is excited by a power supply  80  which impresses a sinusoidally varying electrical signal on probe  30  to cause head  60  to stimulate the output of the acoustical energy  70 . 
     When the acoustical energy interacts with potentially diseased area  35 , the diseased area  35  reflects back a portion of this energy and so the potentially diseased area can be characterized. Ultrasound probes of this nature are described fully in the patent literature, and particularly in U.S. Pat. No. 5,211,169, Freeland, the teachings of which are specifically incorporated herein by reference. 
     The nuclear probe  40  preferably comprises a probe body  90  which contains a NaI or CdTe detector shown generally at  100  and a detector pre-amplifier  110 . The nuclear probe  40  is preferably sensitive to gamma radiation at energies between about 12 keV and about 1 MeV. The probe body  90  is further preferably interfaced to a counter and power supply  120 . The power supply and counting system  120  is preferably powered by a rechargeable nickel cadmium battery. Counter and power supply  120  further comprises a pre-amplifier power supply, a detector biased control, a signal amplifier, a counter-time with nine counting periods and a continuous count setting, upper and lower user settable energy discriminator levels, a single channel analyzer, a six-digit LCD display, and outputs for standard recorders, rate meters or personal computers. 
     The CdTe detector&#39;s bias is preferably adjustable by the counter and power supply  120  in a range of about 0 to 30 volts and at settings of 45 volts and 60 volts. The nine counting periods can be set from between about 1 to about 500 seconds. A continuous count mode is also provided by the counter and power supply  120 . The energy window of the counter is between about 0 to about 200 keV, or about 0 to about 1 MeV. The energy window is preferably adjustable for both upper and lower energy ranges. The pre-amplifier in the power supply  120  operates on negative pulses of about 1.5 mV per keV. The amplifier itself in the counter and power supply  120  operates on positive pulses and has gain settings of 3 or 5 mV per keV. 
     In order to begin the diagnosis and characterization procedure provided in accordance with the invention, patient  10  first usually is injected with a radiolabeled pharmaceutical or radiolabeled MaB. Nuclear probe  40  is particularly sensitive to the radiolabeled pharmaceuticals or MaB that will emit gamma radiation up to 140 keV, that is, the technetium-99m energy level. After the patient is injected with the radiolabeled compound, this material tends to pool or accumulate in a higher concentration in potentially diseased area  35 . Potentially diseased area  35  then emits a “hot spot”, shown generally at  130 , which is the gamma radiation that can be detected at the CdTe solid state detector  100  of probe  40 . This initially locates the diseased area, a task which ultrasound probe  30  is usually unable to accomplish by itself. After nuclear probe  40  locates and makes an initial characterization of potentially diseased area  35  and surrounding structures, ultrasound probe  30  is utilized to fully evaluate the potentially diseased area  35 . Many different kinds of diseases can be evaluated, diagnosed and characterized in this manner. For example, radiolabeled MaB have been used in evaluating ovarian and colon malignancies and prostate. Thus, identification of primary ovarian malignancy can be accomplished by injecting a radiolabeled MaB and then performing transvaginal ultrasound studies using the hybrid probe  20 . This leads to more accurate characterization of ovarian masses with greater sensitivity and specificity for ovarian tumors as compared to present day ultrasound or CAT scanning/MRI devices. Furthermore, staging of ovarian malignancies will be more accurate using a hybrid probe  20  such as that shown in FIG.  1 . 
     Similarly, identification of primary colon neoplasm by using hybrid probe  20  after administration of radiolabeled MaB will show marked improvements over routine colonoscopy or barium enema examinations. It is envisioned that when radiolabeled MaB are developed for breast cancers or other cancers, a hybrid probe  20  in accordance with the present invention could also be used for superior identification and characterization of these diseases. 
     Hybrid probes in accordance with the present invention could also be used in conjunction with laproscopic and colonoscopic instruments to better stage ovarian and colon malignancies. Furthermore in the past, intraoperative ultrasound devices and nuclear probes have been used individually to stage other diseases, for example, tumor metastasis to the liver. With probes provided in accordance with the present invention that comprise both ultrasound and nuclear probes to locate and characterize diseases interactively, the sensitivity and specificity of probes will be improved as compared to individual ultrasound and nuclear probes. Therefore, by interactively using ultrasound probe  30  and nuclear probe  40  in a modality wherein disease is first located and then fully characterized, the physician will be provided with a superior tool for early stage diagnosis and treatment of diseases. 
     The technetium 99m radioisotope has been used for blood clot detection in the lungs, heart and extremities. Recently Acutect™, a functional imaging agent which incorporates technetium 99m radioisotope from Diatide, Inc. has been made commercially available. This is the only effective nuclear agent to target acute venous thrombosis in the lower extremities above and below the knee. Ultrasound itself is unreliable for differentiating chronic v. acute blood clots in the legs, a very important clinical issue. Using the combination of Acutect™ with the hybrid probe more accurate assessment of venous thrombosis in the lower extremities or elsewhere within the body could most certainly be achieved. Such a combination would take advantage of the functional imaging agent and functional nuclear imaging component of the hybrid probe and the high resolution anatomic imaging capability of the ultrasound component of the probe. 
     The hybrid probe will also be fully adaptable to cardiac imaging. However, as is typical with many radioisotope MaB, they experience a poor target-to-background ratio signal strength. This problem will also be obviated with a hybrid probe  20  provided in accordance with the present invention since, for example, in the case of a lower extremity or heart, the technetium-99m agent could be injected such that the hybrid probe  20  could be used to first locate the clot with nuclear probe  40  and then fully characterize the clot using ultrasound. Such a technique will be fully adaptable to cardiac imaging also. In instances of, for example, “stunned myocardium” which cannot be detected with present day imaging modalities, the hybrid probe  20  would markedly increase sensitivity and specificity in evaluating this type of heart abnormality. Cardiac ejection fractions (both right and left ventricles) as well as cardiac wall motion could be studied with the hybrid probe. 
     Hybrid probe  20  could also be used in a very similar manner to a present day transesophageal ultrasound probes. In this fashion, following administration of a I123IPPA radioisotope imaging agent, the heart would be scanned with the hybrid probe  20 . Anatomical structures of the heart could be quickly identified by the ultrasound probe and wall motion abnormalities noted. Any areas of abnormal activity, for example, as a result of ischemia, could then be identified by nuclear probe  40  and correlated with the ultrasound findings picked up by the ultrasound probe  30  portion of hybrid probe  20 . 
     Other areas where hybrid probe  20  will be useful in the future is in the identification and characterization of prostate carcinoma with mononoclonal antibody prostascint pancreatic adenocarcinoma and in parathyroid adenomas. Also, the probe may be used in conjunction with I-125 and palladium radioactive seeds used to treat prostate carcinoma to assist their placement in relation to the carcinoma and prostate gland. Prior diagnostic devices alone have simply been unable to fully characterize these tumors at early stages, which has resulted in increased mortality when these diseases are contracted. Hybrid probes provided in accordance with the present invention would provide early stage diagnosis and would therefore save many lives. 
     It is envisioned that hybrid probe  20  will be interfaced with a central processing unit (CPU) shown generally at  140  in FIG.  1 . CPU  140  will have all the necessary and essential software to integrate the outputs of ultrasound probe  30  and nuclear probe  40  so that accurate and efficient location, characterization and diagnosis of the potentially diseased area  35  can be accomplished. Ultrasound probe  30  may be directly interfaced at  150  to CPU  140 . Similarly, nuclear probe  40  may be directly interfaced at  160  to CPU  140 . Optionally, counter and power supply  120  may also be interfaced at  170  to CPU  140 . More preferably, CPU  140  can be interfaced to a display unit  180 . Display unit  180  could be a cathode ray tube (CRT) device or any other device such as a rate meter, recorder, or other personal computer which is adapted to display data gathered by hybrid probe  20 . 
     Referring to FIGS. 2 through 8, further embodiments of the novel hybrid probe  220  in accordance with the present invention are shown in detail. As shown in FIG. 2, the probe  220  is cylindrical  222  and circular in cross-section. In one embodiment, the probe  220  comprises a nuclear detector  224  comprising substantially perpendicular scintillator plates  226  disposed axially along the length of the probe  220  which meet at an intersection  228  and which includes multiple parallel extending collimators  230 . In addition, at the intersection between the scintillator plates  226  the probe has an ultrasonic sensor  330  which extends the length of the scintillator plates  226 . The ultrasonic sensor  330  can be a phased array, annular array or linear array scanner, depending upon the desired application. The ultrasonic sensor may comprise a 1.5 D scanner, and may further be electronically steered. 
     The choice of scanner will depend upon the application required. Electronic array ultrasound scanners are particularly useful for certain types of imaging because they require no moving parts and can be made smaller. Also, linear or even curvilinear array probes offer a larger field of view, which may make anatomic orientation less difficult for the operator. Combinations of array scanners such as linear array with a radial sector phased array scanner or the mounting of separate transducer assemblies on the same ultrasound probe allows visualization of different anatomic planes without exchange of the probe itself during the examination of a patient. 
     The parallel collimators  230  comprise members having at least one aperture in the radioactive ray detecting direction and made of a radioactive ray attenuating material. Such a material weakens the intensity of radioactive rays and may comprise lead, tungsten, stainless steel lead glass or mercury. 
     The scintillator surfaces  226  preferably include an aluminum foil surface which functions as a moisture barrier. In the embodiment of FIGS. 2-4, the dual exposed surface areas allow for a greater number of radioactive events to be detected and for the possibility of three dimensional imaging. The physical disposition of the respective ultrasonic  330  and nuclear probes  224  provides for simultaneous ultrasonic and nuclear monitoring with a minimum of interference. 
     Referring now to FIGS. 7 and 8, further embodiments of the present invention. As shown in FIG. 7, the scintillator plate  226  is curved and includes parallel collimators  230  as in the embodiment of FIGS. 2-4. As with the embodiment in FIG. 7, in FIG. 8, a single flat scintillator plate  226 , in association with parallel collimators  230  is used in conjunction with the ultrasonic probe  330 . 
     The probe of FIGS. 2-4 and  7 - 8  creates new detection capabilities and diagnostic information gathering by enabling efficient evaluation of diseased tissue in relation to patients anatomy whereby the hybrid probe can both pinpoint the presence of diseased tissue, characterize the diseased tissue and see the relationship to normal anatomic structures. As shown in FIG. 5, X, Y, Z coordinates that coincide with shape, size and relation to vital normal anatomic structures including vascular structures may be shown by the present invention. The X, Y, Z coordinates are obtained by the special design and relationship of the plate-like nuclear detectors and ultrasound probe. Similar coordinates and a 3D perspective cannot be obtained by radioactive ray detecting means arranged in the tip part of an endoscope as described in the Inaba patent. As shown in the FIG. 6, prior art systems by contrast observe the direction of the ultrasonic image device and the detecting direction of the radioactive ray detecting device substantially so as to coincide with each other. Such systems do not provide a single unified view. 
     The present invention thus provides for the creation of a three dimensional perspective of normal anatomic structures and pathology such as tumors or other disease processes. The result is a fused image where the two modalities are co-existing. 
     FIGS. 9A-9C illustrate still further embodiments of the invention. In these embodiments, rather than extending longitudinally through the probe length, the respective ultrasonic  330  and nuclear probes  226  extend axially at the tip of the probe  220  which is enclosed within a barrier  340 . In FIGS. 9A-9C, the hybrid probe configuration extends axially at the tip of the device. FIG. 9A illustrates an embodiment including perpendicular scintillator plates  226  and parallel collimators  230 . FIG. 9B illustrates an embodiment having a flat scintillator plate  226  and parallel collimators  230  and FIG. 9C illustrates an embodiment having a curved scintillator plate. It is to be appreciated that the scintillator plate  226  of this embodiment may be dish shaped  326  as shown in FIG.  9 C. In all three embodiments, ultrasonic detector  330  is situated at the center of the scintillator  226  located at the tip of the device behind barrier  340 . 
     The present invention can be applied to a number of applications in the surgical field intraoperatively, whereas endoscopes cannot be used in this fashion. Endoscopes are introduced into a hollow viscous such as the esophagus or colon and have restricted applications. Multiple applications for the present invention extend the utilization of one singular, portable device including numerous cancers such as prostate, breast, ovary and colon. 
     The design of the probe of the present invention allows for easy integration of acquired images to produce a single, unified image maximizing the abilities of the combined methods. Hybrid probes provided in accordance with the present invention improves the physician&#39;s ability to diagnose and characterize potentially harmful diseases. By first locating a diseased area during surgery or otherwise with a nuclear probe, and then interactively fully characterizing the area with an ultrasound probe, diseases which are potentially life-threatening can be detected early and will be more quickly diagnosed. Such results have not heretofore been achieved in the art. 
     There have thus been described certain preferred embodiments of hybrid ultrasound and nuclear medicine probes provided in accordance with the present invention. While preferred embodiments have been described and disclosed, it will be recognized by those with skill in the art that modifications are within the true spirit and scope of the invention. The appended claims are intended to cover all such modifications.