Beta Imaging Probe Incorporated Needle for Biopsy of cancer

描述(申请人提供)：芯针活检通常是各种癌症的第一种诊断方法。我们建议在活检针中加入一种新型的β射线成像探头，以定位PET阳性病变，并验证切除的组织是否适当地代表了放射性浓度升高的感兴趣区域。我们将利用光电探测器技术的最新突破-固态光电倍增管(SSPM)，其工作电压为30-60 V，在体内使用是安全的；它很小(1x1 Mm)，增益为100万。这将使我们能够构建适合直径为1.5毫米的针头的探测器模块的一维阵列。许多癌症复发的明确诊断依赖于活检的确认。此外，未来的疗程取决于对这些活检样本的组织学分析。在越来越频繁的临床前图像检测病变的情况下，检测从PET阳性异常获得的核心样本中的放射性将是确认准确样本的一大进步，因此，确定组织学诊断。对于那些被认为代表转移性黑色素瘤、疑似转移性疾病或原发淋巴瘤的淋巴结病、可疑的肝脏病变、双拉得4-5分的乳腺病变、可疑的肺结节以及各种腹膜内肿块的患者，建议的Beta成像活检系统将特别有助于建立成功的组织采样。在胃癌外科手术中，切除的程度在很大程度上取决于对淋巴结是否有癌的评估。拟议的贝塔成像活组织检查探头将是手术切除的一个有价值的辅助工具，因为外科医生将能够在手术中实时测定淋巴结的放射性，并在手术中测试它是否有癌症。对于胰腺癌，如果发现远处淋巴结阳性或意外的肝脏或腹膜病变，将有助于术中更好地对患者进行分期，以避免不必要的广泛胰腺手术。对于本项目的第一阶段，我们将首先使用滨松株式会社的商用SSPM或MPPC(MPPC 1x1 Mm MPPC SMD SPL)。它是一块陶瓷贴装芯片，基板面积为1.9 x 2.4 mm，厚度为0.85 mm。我们将这些SSPM中的8个固定到使用光学环氧体的半圆柱形塑料闪烁体上，这样1x8阵列通过塑料闪烁体机械地保持在一起。一层无污染的钢箔将覆盖在闪烁体上。这片铝箔的厚度是10微米。该探测器模块将产生沿针轴18 mm长度的贝塔射线分布的一维图像。同样的工作将用一个更小的1x1 mm的MPPC来完成，它可以放入1.5 mm直径的针中。这些针的侧面将有开口，以允许利用探测器阵列进行贝塔检测，以及一个切割内圆筒，可以在需要时向前移动，切割样本并将其捕获到活检针内。因此，检测和采样将几乎同时在一个设置中完成。一旦建立了一个正常工作的原型，我们将测试成像探头的内在一致性、一致性校正和分辨率。我们还将测试通过相邻探测器的符合计数来降低电子噪声的方法。探测器中的虚假本底伽马射线将被能量判别法或基于图像对比度的方法滤除。由于伽马射线背景沿活组织检查探头的开放窗口大致相同，并且由于β成像探头提供一维或线性图像，因此热点与其周围环境的视觉比较有助于识别肿瘤区域。我们将尝试各种图像分析，以最大限度地减少背景的影响。例如，我们将从整个图像中减去每像素计数的平均值，并将一维图像表示为高于平均值的百分比。我们将采集轴线上不同位置的图像，并在屏幕上进行比较，以快速识别“火锅”。我们将进行一系列体模实验，以确定使用Beta成像探针检测肿瘤的极限。作为该项目顾问的两名癌症外科医生和一名放射科医生将参与这些研究。我们与加州大学洛杉矶分校的Dahlbom博士就SSPM的各种应用进行了合作，并在2-D测试版相机原型上发表了这一成果。这一经验将促进目前的项目。我们公司在用于外科癌症检测的新型核医学仪器商业化方面有着良好的记录。在过去的五年里，我们的伽马和贝塔探头已销往全球200多家医院，通用电气是我们在全球主要市场的独家分销商。在第二阶段期间，将进一步开发该系统的硬件和软件，并在放射科环境以及外科和腹腔镜环境中进行动物试验以及各种癌症的人体试验。公共卫生相关性：该应用程序对癌症手术的结果有直接影响。如果成功，所提出的方法和仪器将导致乳腺癌和前列腺癌等疾病的复发率降低。仅这两种疾病每年就困扰着50万美国人。癌症的复发在美国家庭中造成了重大的情感创伤，并导致了医疗费用的上升。

DESCRIPTION (provided by applicant): 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.