Abstract:
A surgical guidance system offering different levels of imaging capability while maintaining the same hand-held convenient small size of light-weight intra-operative probes. The surgical guidance system includes a second detector, typically an imager, located behind the area of surgical interest to form a coincidence guidance system with the hand-held probe. This approach is focused on the detection of positron emitting biomarkers with gamma rays accompanying positron emissions from the radiolabeled nuclei.

Description:
The United States of America may have certain rights to this invention under Management and Operating Contract DE-AC05-060R23177 from the United States Department of Energy. 
    
    
     FIELD OF THE INVENTION 
     The present invention relates to surgical guidance systems and more particularly to such a system using a hand-held probe in combination with an accompanying positron coincidence detector. 
     BACKGROUND OF THE INVENTION 
     To assist with surgical removal of cancerous lesions, surgeons use hand-held guiding instruments such as intra-operative probes. Before surgery, patients are injected with radio-labeled biomarker which is predominantly uptaken by the cancer tissue. 
     Usually these devices are simple and work on the “Geiger counter” principle i.e. they only measure intensity of the radioactive signal in the vicinity of the probe sensor/tip and provide audio and/or visual feedback to the operator/surgeon (see for example, Ramsey et al., U.S. Pat. No. 4,889,991, Dec. 26, 1989, Denen et al., U.S. Pat. No. 5,151,598, Sep. 29, 1992, and Yarnall et al., U.S. Pat. No. 6,331,703, Dec. 18, 2001). By scanning the probe in front of the tissue and zooming on the region producing the strongest signal, the information on the lesion location is obtained, directly correlated with the anatomical detail, as visually analyzed by the surgeon. This time-consuming procedure suffers generally from poor probe sensitivity and, therefore, poor cancer margin definition. 
     There have been many attempts to address the issue of providing better, faster and more accurate cancer tissue position information by constructing small imaging probes. These mini-imagers can be for gamma imaging or for positron imaging, or for both. Several companies are producing such probes (for example, Gamma Medica and IntraMedical Imaging and many more designs are described in scientific literature and in patents such as U.S. Pat. No. 6,628,984 by Weinberg, Sep. 30, 2003. 
     However, all these instruments suffer from a major inconvenience from the surgeon&#39;s point of view which is that they locally obstruct the view of the surgical field and do not actually help with the exact location of the tissue to be surgically removed. More accurate and larger image of the scanned region per se but without optical etc co-registration with anatomical detail is deemed not to be that useful by surgeons. 
     In addition, these mini-imagers are not actually easily “hand-held” because their weight is usually in the range of 1-3 pounds. While mechanical support systems were designed to support the imaging probes in place, these devices further exacerbate the above mentioned viewing field obstruction issue. To remedy the obstruction and weight issues some of the proposed imaging probes are made compact with even smaller field of view, however then their utility as imagers is limited. Another approach is to limit the size of the instrument at the surgical end by installing thereon only a scintillator gamma sensor which is optically connected to a distant position sensitive photodetector via a flexible optical fiberoptic lightguide (Daghighian et al., U.S. Pat. No. 5,325,855, Jul. 5, 1994). However, in this case there are the same issues of visual field obstruction and limited field of view. Flexible light guides usually limit the field of view even more. 
     OBJECTS OF THE INVENTION 
     It is therefore an object of the present invention to provide a surgical guidance system that provides the greatest detailed view of the area of concern to the surgeon without the limitation of the visual field prevalent in prior art systems. 
     It is another object of the present invention to provide a surgical guidance system that is small and light enough to allow the surgeon to easily manipulate it without the need for visually impairing support systems. 
     SUMMARY OF THE INVENTION 
     In the system of the present invention, the imaging scan is of a larger surgical field, and thus providing much more accurate guidance in cancer removal. These benefits are obtained by the use of a device offering different levels of imaging capability while maintaining the same hand-held convenient small size of light-weight intra-operative probes. This is achieved by adding a second detector, typically an imager, located below or behind the patient or the area being surgically addressed to form a coincidence guidance system with the hand-held probe. This approach is focused on detection of positron emitting biomarkers with two 511 keV gamma rays accompanying positron emissions from the radiolabel nuclei. 
    
    
     
       DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a schematic perspective view of the surgical guidance system of the present invention. 
         FIG. 2  is a schematic graphic representation of the use of the surgical guidance system of the present invention. 
         FIG. 3  represents a demonstration of the spot guiding principle using the surgical guidance system of the present invention. 
         FIG. 4  is a graphic representation of the image generated by a modular coincidence detector in accordance with the present invention. 
         FIG. 5  is a schematic representation of a three-element beta/gamma sensor made from three scintillation materials in optical contact in accordance with one preferred embodiment of the present invention. 
         FIG. 6  is a schematic representation of a prostate imaging variant of the surgical guidance system of the present invention. 
         FIG. 7  a partially cutaway view of one embodiment of the probe portion of the surgical guidance system of the present invention. 
         FIG. 8  is a graph showing the results of a test performed to compare the accuracy of the device of the present invention with single element hand-held probes. 
     
    
    
     DETAILED DESCRIPTION 
     Referring now to accompanying  FIGS. 1 and 2 , the positron surgical guidance system  10  of the present invention is composed of three major components: 1) a compact hand-held detection probe  12  manipulated by the operator; 2) a coincidence imager  14  operating in conjunction with hand-held probe  12  and placed on the opposite side of the area being surgically addressed from probe  12 , i.e. behind the organ, or body of the patient  16 A and  16  respectively; and a set of fast hardware processors and software algorithms  17  providing immediate on the spot feedback to the operator/surgeon after analyzing multi-parametrical information received from the probe and coincident detector/imager. 
     In the case of several hot spots  18 ,  20  and  22  (see  FIGS. 3 and 4 ) or an extended uptake field  24 , adding a coincidence requirement with a corresponding region in the imaging coincidence detector system  14  and  12  will guide the probe to that particular hot spot or region, such as hot spot  18 , without interference from the neighboring hot spots  20  and  22 . During the operation of a standard prior art intraoperative probe with no accompanying imaging detector, this interference and signal overlap is unavoidable and even if some collimating schemes are considered, the efficiency of such a simple approach cannot match the advantages of the coincident system of the present invention. As depicted in  FIG. 3 , a spot selection condition  26  dependent upon the  20  “aim point” of hand-held probe  12  is defined such that coincidence imaging of primary “lesion” or spot  18  is obtained while secondary spot  20  is not coincidentally imaged by both hand-held probe  12  and coincidence imager  14 . 
     In the surgical guidance system of the present invention  10 , the geometry of a small size probe sensor  12  and a large imaging detector  14  on the opposite side of the organ  16 A or patient body  16 , sensitivity of the system (defined by number of coincidences) decreases quickly with distance from the probe sensor. This effect limits substantially the signal due to radiation background from radiation distributed in tissue behind the cancer tissue. 
     In the example represented in  FIGS. 3 and 4 , a spot guiding principle is demonstrated where a coincidence requirement between probe  12  and the selected region in the imager projection  26  helps in picking up signal from one of the neighboring spots, e.g.  18 , while the second spot  22  is also seen in a more distant part of the coincidence imager. After removing (or biopsing) the first spot  18 , the coincidence condition can be changed to focus on and guide the probe to second spot  22 . 
     As depicted in  FIG. 4 , while not providing detailed images of the radiation distribution in tissue, surgical guidance system  10  can assist with differentiating between neighboring structures for better guidance to the hot spots or regions  18 ,  20  and  22 . Coincident signal pattern can involve single or multiple detector  20  segments/tiles  31 . 
     As described more fully below and depicted schematically in  FIGS. 4 and 5 , hand-held probe  12  can have different structures, with different levels of complexity and functionality. The basic design is composed of a single gamma radiation sensor (external size limits are from −1 mm3 to −10000 mm3 in volume). Typically, to keep balance between sensitivity and size of probe  12 , the sensor will be a scintillator crystal on the order of a 5×5×15 mm 3 . The primary role of the radiation sensor will be detecting 511 keV annihilation gamma rays, independently and in coincidence with the coincidence imager. 
     Coincidence imager  14 , can be of differing sizes, varying from about 1 cm 2  to a 1 m 2  size. In special cases, it can be also a non-imaging type and usually larger than probe detector that operates in coincidence with the probe, and is placed on the opposite side of the organ, extremity or patient torso  16  as shown in  FIGS. 1 and 6 . As an intermediate option, the coincidence detector  14  can produce images of separate sectors with their coincidence signals (with probe  12 ) constantly analyzed to define radiation pattern and provide guidance to the operator/surgeon. 
     Coincidence detector  14  may comprise any of a long list of conventional materials including: solid state material, such as CdZnTe, CdTe, Si, etc.; scintillator materials such as high stopping power crystal scintillators (BGO, LSO, LYSO, GSO, LGSO, etc.) other inorganic scintillators such as NaI(Tl), CsI(Tl), CsI(Na), LaBr3, etc.; scintillating glasses; hybrid heavy converters (lead, tungsten, etc) with a gaseous electron amplification medium; hybrid with heavy converters (lead, tungsten, etc) with a plastic scintillator; hybrid with heavy converter (lead, tungsten, etc) and a liquid scintillator; hybrid with heavy converter (lead, tungsten, etc) and a high pressure gas scintillator; and liquid xenon or mixtures of xenon with krypton and other additives. 
     The active gamma sensitive element of the coincidence detector can be either a continuous material, forexample a plate of NaI(Tl) scintillator, or pixellated for example, an array of BGO pixels. 
     Probe  12  can be provided with increased functionally to detect betas (positrons) and gammas to enhance its positron detection capabilities (as described by Yamamoto et al., Annals of Nuclear Medicine Vol. 19, No. 1, 23-28, 2005). Two or even three types of materials can be used in such a dual-mode probe. The role of a thin entry detection element is to directly detect positrons (beta particles) emitted from radiolabel used in the applied biomarker. The beta detection element can be composed of a single layer or can be a set of two consecutive layers, operating in coincidence. In the latter case the beta sensor is highly selective for beta particles, a fraction of which will traverse the first layer and deposit another energy signal in the second layer. Gamma interactions will not produce simultaneous (coincident) signals from these two layers for the same events. By this signal differentiation, beta signals can be separated from the gamma background signals. 
     An example of a practical and preferred three element beta/gamma sensor is: 0.25 mm thick plastic scintillator (element  32  in  FIG. 5 ) and 0.5 mm CaF(Eu) scintillator (element  30  in  FIG. 5 ) for positrons, and 15 mm thick BGO scintillator (element  34  in  FIG. 5 ) for 511 keV gammas.  FIG. 5  depicts an example of a three-element beta/gamma sensor, probe  28  made of three scintillation materials in optical contact. Beta and gamma radiations  40  and  42  respectively enter sensor  28 , beta radiation  40  is detected by beta sensitive layers  30  and  32 , gamma radiation  42  is detected by gamma sensitive scintillator  34 . Scintillation light  44  from all elements of this phoswich reaches the same photodetector  46  placed behind the gamma detecting sensor. The beta (positron) signals  40  require simultaneous scintillation from both two thin entry layers  30  and  32 . The gamma sensor  34  is thick enough to have sufficient stopping power for 511 keV annihilation gamma rays. The three optically mixed scintillation signals are separated on the basis of their different time decay and amplitude characteristics. 
     Positron (beta) only probes have also been devised (for example those described by Raylman et al., U.S. Pat. No. 6,456,869. Sep. 24, 2002) to avoid signal interference from scattered gamma background, but their sensitivity is limited to only very shallow (&lt;2-5 mm) tissue layers due to limited range of positrons in tissue. Therefore, while providing a clear signal from the exposed cancer tissue (providing that positron labeled biomarker is uptaken by the lesion/cancer) the beta only probe cannot detect emissions from deeper layers. 
     Compact hand-held gamma probes with directional guidance were designed (f.e. Majewski et al., U.S. Pat. No. 6,643,538, Nov. 4, 2003) but their guidance capability is limited to lower energy gamma rays (˜140 keV) and positrons, i.e. they do not provide good directional guidance in detecting higher energy 511 keV gamma rays from the positron decays. 
     In the case of multilayer beta/gamma sensors comprising scintillation materials, the materials are preferably selected to have different pulse shapes so that a single photodetector can be used and the beta and gamma contributions are separated on the basis of this pulse shape. This so-called phoswitch structure can be built of a large variety of materials. Two simple examples are thin plastic scintillators or YAP crystal scintillators as used as beta sensors and optically attached to a gamma sensor such as GSO. 
     At another level of functionality, the probe sensors can be built from an array of sub-sensors, to provide additional more accurate spatial resolution (i.e. more precise surgical guidance) while maintaining or increasing probe sensitivity. 
     In the case of solid state probes, each sub-element is read separately by multi-channel readout electronics placed in probe  12 . In the case of scintillation probes, multi-element photo-detectors are used either incorporated in probe  12 , or placed at the end of multi-fiber light guide in optical contact with probe  12 . 
     The gamma radiation sensor  34  in probe  12  can be made of, for example: a solid state material, such as CdZnTe, CdTe, etc, or a scintillator material such as high stopping power crystal scintillators (BGO, LSO, LYSO, GSO, LGSO, etc). The additional positron sensitive material can be also made of a thin solid state material such as silicon, or a thin bright scintillator such as plastic scintillator, CsI(Tl), CaF(Eu), YAP, YAG, CsF, etc. 
     Scintillation light from the scintillator sensor can be detected by a directly coupled or via a light guide coupled photosensor. Several types of photodetectors can be used: photomultipliers, silicon photodiodes, avalanche photodiodes, silicon photomultipliers, and hybrid photomultipliers (with silicon element) 
     Two major variants or configurations of the system can be utilized: a flexible version when used during biopsy or surgery primarily involving organs such as breast, head, neck, extremities, in this case a smaller and also compact coincidence imager is used attached to, for example, an articulated arm for easy manipulation around the organ(s) in the surgery field; and a more static version with a larger field of view coincidence imager  14 , for example, placed under or directly embedded in the patient bed  13  (see  FIG. 1 ). The more fixed position of imager  14  in this implementation as compared to the flexible version, can offer more accurate and stable position calibration for more precise guidance information about uptake region(s) position and extent. 
     During surgery the feedback information provided to the probe operator/surgeon has to be prompt, provided with minimal delay. Therefore, while the in-depth analysis of the collected and/or available data from the probe and coincident imager  14  is important, fast feedback to the operator/surgeon is of prime value. 
     Different aspects of the formed coincident image in coincidence imager  14  can be used to provide precise information to the probe operator as to the existence and position of the uptake region (lesion etc): average position (center of gravity of the count distribution); size and shape of the projected distribution, providing information about the extent and size of the uptake, for example isolated hot spots vs larger area/volume; information about the depth of the uptake (in the case of simpler point-like uptake regions). 
     In the special implementation of the concept for prostate cancer depicted in  FIG. 6 , a small coincidence imager  14 A can be trans-rectally inserted into the patient and placed behind or under the prostate  15  to provide high sensitivity and high spatial resolution in mapping prostate cancer tissue and specifically assist in defining cancer margins and any residual cancer tissue during and after a surgical procedure. The function of such an arrangement is two-fold: guide the surgeon before and during cancer surgery, and provide feedback if the cancerous tissue is entirely removed while assuring minimal damage to healthy surrounding tissue. Through the proximity of both detectors to the organ, the detection sensitivity is highly maximized. The trans-rectal probe can be either simple non-imaging or an imaging device composed of an array of small sensor elements to provide better spatial resolution and sensitivity. An example of such a sensor array is a pixellated LYSO/LSO/GSO phoswich structure of 2×2×2 mm pixels optically coupled to position sensitive photodetector via a fiberoptic lightguide. 
     EXAMPLES 
     Example 1 
     A probe comprising an about 1 cm cube LSO crystal attached to a 1.4 cm diameter R647 Hamamatsu PMT; and an imaging detector comprising a 20×15 cm LYSO array of 2×2×15 mm LYSO pixels (pitch 2.1 mm) optically attached to a 4×3 array of Hamamatsu flat panel H8500 PSPMTs is used to image a “point” microCi: Na22 source  50  embedded in acrylic  52  representing a lesion in a housing  54  (see  FIG. 7 ). 
     Geometry: 
     In this example, the “lesion” is about 2 cm from the probe sensor center. The lesion-to-imaging detector distance is about 13 cm. 
     Example 2 
     A smaller probe comprising a 3×3×10 mm BGO crystal is attached to a R1635 Hamamatsu PMT. Count rate curves are measured while moving (scanning) the probe close to the source. Both single mode and coincidence mode are used. The results of using these two systems are shown in Table 1. 
     
       
         
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 1 
               
               
                   
               
               
                   
                   
                   
                 Image ROI (2 min 
               
               
                 Position (mm) 
                 Single Rate (Hz) 
                 Coinc. Rate (Hz) 
                 counts) 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 0 
                 1310 
                 665 
                 1633 
               
               
                 2.5 
                 1650 
                 815 
                 1625 
               
               
                 5.0 
                 1990 
                 985 
                 3255 
               
               
                 7.5 
                 2295 
                 1120  
                 4079 
               
               
                 10 
                 2380 
                 1125  
                 2496 
               
               
                 12.5 
                 2220 
                 1065  
                 1859 
               
               
                 15 
                 1840 
                 875 
                 1795 
               
               
                 17.5 
                 1530 
                 620 
                   
               
               
                 Random 
                   
                   
                 1400 
               
               
                   
               
             
          
         
       
     
     The above data are represented graphically in  FIG. 8 . Curve  3  shows signal in coincidence with the full detector. Curve  2  shows the singles (non-coincidence) rate result. Curve  1  depicts the results using coincidence with a selected ROI sector in the imaging detector. 
     The observed sharper position definition is due to a coincidence effect between the probe and the region in the imager. This demonstrates much better guidance capabilities of the system, as compared to a simple gamma/beta probe. 
     As the invention has been described, it will be apparent to those skilled in the art that the same may be varied in many ways without departing from the spirit and scope of the invention. Any and all such modifications are intended to be included within the scope of the appended claims.