Core-needle biopsies are generally the first diagnostic approach for a variety of cancers. We propose to build a novel beta-ray imaging probe incorporated in the biopsy needle to locate a PET-positive lesion and to verify that the removed tissue appropriately represents the area of interest with elevated radioactive concentration. We will exploit a recent breakthrough in photodetector technology - the Solid State Photomultiplier (SSPM) that operates at 30-60 V, making it safe for use inside the body; is small (1x1 mm) with a gain of one million. This will enable us to construct 1-dimensional arrays of detector modules that fit in needles as small as 1.5 mm diameter. Definitive diagnosis of re-occurrence of many cancers depends on biopsy confirmation. Also, the future course of treatment is determined by the histological analysis of these biopsy samples. In the increasingly frequent scenario of pre-clinical, image-detected lesions, detecting radioactivity in the core sample obtained from a PET-positive abnormality would be a great advance in confirming accurate sampling, and therefore, definitive histologic diagnosis. The proposed beta-imaging biopsy system would be especially helpful in establishing successful tissue sampling in patients with lesions thought to represent metastatic melanoma, lymphadenopathy suspicious for metastatic disease or primary lymphoma, suspicious liver lesions, breast lesions scored Bi-Rads 4-5, suspicious pulmonary nodules, and a wide variety of intraperitoneal masses. In surgery of gastric cancers, the extent of resections depends largely on the assessment of whether or not lymph nodes have cancer. The proposed beta-imaging biopsy-probe will be a valuable adjunct to the operative resections, as the surgeon would be able to have a real-time intra-operative determination of lymph node's radioactivity and test it for cancer during surgery. For pancreatic cancer, the discovery of a positive distant lymph node or an unsuspected liver or peritoneal lesion, would allow better staging of patients intra-operatively to avoid an unnecessary extensive pancreatic surgery. For the Phase I of this project , we will first utilize the commercially available SSPM or MPPC by Hamamatsu Corp. (MPPC 1X1 mm MPPC SMD SPL). It is a ceramic mounted chip with a foot-print of 1.9 x 2.4 mm and thickness of 0.85 mm. We will fix 8 of these SSPMs to a semi-cylinder of plastic scintillator using optical epoxy, such that the 1x8 array is mechanically held together by the plastic scintillator. A layer of stain-less steel foil will cover the scintillator. The thickness of this foil is 10 micro-meter. This detector module will yield a one-dimensional image of beta ray distribution in a 18 mm length along the axis of the needle. The same work will be done with an even smaller MPPC with foot-print of 1x1mm that can fit in a 1.5 mm diameter needle. These needles will have openings on their sides to allow beta detection with the array of detectors, and a cutting inner cylinder that will move forward when desired, and cut the sample and trap it inside the biopsy needle. Therefore the detection and the sampling will be done in one setting almost simultaneously. Once a functioning prototype has been built, we will test the intrinsic uniformity, uniformity correction, and resolution of the imaging probes. We will also test the method of reducing electronic noise by coincidence counting of adjacent detectors. The spurious background gamma rays in the detector will be rejected by either energy discrimination, or based on the image contrast. Because the gamma ray background is approximately uniform along the open window of the biopsy probe, and since the beta imaging probe provides a one-dimensional or linear image, the visual comparison of a hot spot with its surroundings helps identify the tumor region. We will experiment with a variety of image analysis to minimize the effect of the background. For example we will subtract the mean value of counts-per-pixel from the entire image, and represent the one-dimensional image as percent above the mean. We will acquire images along the axis at various places and compare them on screen to quickly identify the "hot pots". We will conduct a set of phantom experiments to determine the limit of tumor detection with the beta imaging probe. Two cancer surgeons and one radiologist who are consultants to this project will participate in these studies. We have worked with Dr. Dahlbom of UCLA on various applications of SSPM and published on a prototype 2-D beta camera. This experience will facilitate the present project. Our company has a good track record of commercialization of novel nuclear medicine instrument for surgical detection of cancer. Our gamma and beta probes have been sold to more than 200 hospitals throughout the world in the last five years, and GE is our exclusive distributor in major markets around the world. During the Phase II will further develop the hardware and software of this system and conduct animal testing, as well as human trials on a variety of cancer, both in radiology setting and in surgical and laparoscopic settings. PUBLIC HEALTH RELEVANCE: This Application has a direct impact on the outcome of cancer surgery. If successful, the proposed method and instrument will result in reduction of the rate of reoccurrence of breast and prostate cancer among others. These two diseases alone afflict half a million of Americans every year. The reoccurrence of cancer causes major emotional trauma in American families and is responsible for rising healthcare costs. [unreadable] [unreadable] [unreadable]