Beta Camera and Laparoscopic Probe for Surgical Cancer Removal.

描述（由申请人提供）：固态光电倍增器（SSPM）的最新发展为开发用于癌症手术的安全、高灵敏度和紧凑型β相机以及用于腹腔内癌症检测的腹腔镜β探针创造了前所未有的机会。我们将制造这些设备，将其纳入我们已上市的术中控制单元，用Phantom对其进行测试，并在II期临床试验中最终使用安全认证。重要性：手术是唯一确定的癌症治疗方法;然而，其治疗能力受到留下肿瘤显微镜痕迹（称为边缘）的可能性的影响。例如，在乳腺癌中，由于边缘遗漏，保乳手术（乳房肿瘤切除术）后有20%的复发率。能够在手术中测量肿瘤床并对视觉上无法检测到的微量癌细胞进行成像的β相机可以显着降低许多癌症（如黑色素瘤，乳腺癌和前列腺癌）的复发率，并提高生存率。此外，它可以使更多的乳腺癌患者成为乳房保留乳房切除术的候选人，并改善乳腺癌的心理康复。腹腔镜β探针将为外科医生提供新的“视野”，并有助于以微创方式检测和完全切除腹部癌症。背景：F-18原子发射正电子（β射线），反过来产生伽马射线。伽马射线在组织中传播数十厘米，而β射线的范围为~ 2毫米。β放射性同位素是术中成像的理想选择，因为背景辐射不会干扰边缘的识别。到目前为止，beta相机还存在两个严重缺陷之一，这两个缺陷阻碍了它们在癌症手术中的使用。正电子检测所需的薄屏蔽层与高压光电倍增管（PMT）的绝缘不足，或2。用于将高压与患者隔离的长光纤耦合大大降低了灵敏度。 初步数据：我们之前已经开发了一种beta相机，其分辨率和灵敏度可以检测到微小（5 mg）的癌症沉积物。在过去的一年里，我们测试了各种配置的SSPM和放大器;我们的研究表明，SSPM在~ 50伏工作时的灵敏度高于光电倍增管。它们也很小（1x 1 mm）。我们进行了初步测试，其中，我们测量的绝对效率为15%的小塑料闪烁体直接耦合到SSPM，而不是0.2%的光纤耦合到PMT的相同的闪烁体。我们已经建立了一个原型的SSPM的Beta相机在一个小规模，并证明了其可行性。 研究和开发计划：我们将建立一个红色塑料闪烁体和二维阵列的SSPM相机。我们还将构建一个直径为5 mm的双探测器β探头，用于使用SSPM和塑料闪烁器进行腹腔镜检查。然后，我们将研究25至37 oC温度变化的影响，并研究各种方法来补偿温度依赖性。一旦这些问题得到解决，我们将优化相机的灵敏度，并进行表征实验。在设计过程中，我们将执行所有适用的电气和生物安全标准。然后，我们将确定该相机的肿瘤检测与现实的幻影的限制。在第二阶段，我们将与约翰·韦恩癌症研究所的长期合作者一起对黑色素瘤和乳腺癌患者、康奈尔大学的前列腺癌患者以及纪念斯隆·凯特琳医院的腹部腹腔镜癌症检测进行试验。

DESCRIPTION (provided by applicant): The recent development of the Solid State Photo-Multiplier (SSPM) has created an unprecedented opportunity to develop a safe, highly sensitive and compact beta camera for use during cancer surgery, and a Laparoscopic beta probe for intra-abdominal cancer detection. We will build these devices, incorporate them into our marketed intra-operative control unit, test them with phantoms and pursue safety certifications for their eventual use in clinical trials during the Phase II. Significance: Surgery is the only certain cure for cancer; however, its curative ability is compromised by the potential of leaving behind microscopic traces of the tumor, known as margins. In breast cancer, for example, there is a 20% recurrence rate after breast-conserving surgery (lumpectomy) due to missed margins. A beta camera capable of surveying the tumor bed, intraoperatively, and imaging visually undetectable, minute amounts of cancer cells, could significantly reduce recurrence rate of many cancers such as melanoma, breast and prostate, and increase survival. In addition, it may enable more breast cancer patients to become candidates for breast saving lumpectomies and improve the psychological recovery from breast cancer. A Laparoscopic beta probe would give a new "vision" to the surgeon and facilitate detection and complete removal of abdominal cancer in a minimally invasive manner. Background: F-18 atoms emit positrons (beta rays) that in turn generate gamma rays. Gamma rays travel tens of cm in tissue, while beta rays have a range of~2mm. Beta emitting isotopes are ideal for intraoperative imaging since background radiation would not interfere with identification of margins. Until now, beta cameras have suffered from one of two serious flaws that prevent their use in cancer surgery 1. The thin shielding required for positron detection provides insufficient insulation from the high voltage photomultiplier tubes (PMTs), or 2. The long fiber-optic coupling used to separate the high voltage from the patient greatly reduces sensitivity. Preliminary Data: We have previously developed a beta camera with the resolution and sensitivity to detect minute (5 mg) cancer deposits. Over the last year we have tested various configurations of SSPMs and scintillators; our research shows that SSPMs have higher sensitivity than photomultiplier tubes while operating at ~ 50 volts. They are also very small (1x1 mm). We conducted preliminary testing, in which we measured an absolute efficiency of 15% for a small plastic scintillator directly coupled to an SSPM, as opposed to 0.2% for an identical scintillator coupled fiber-optically to a PMT. We have built a prototype of the SSPM based beta camera in an small scale and demonstrated its feasibility. Research and Development Plan: We will build the camera with a sheet of red plastic scintillator and a 2 dimensional array of SSPMs. We will also build a dual detector beta probe in a 5 mm diameter for laparoscopy using SSPMs and plastic scintillators. We will then study the effect of temperature variance from 25 to 37 oC, and investigate various methods to compensate for temperature dependence. Once these issues have been addressed we will optimize the sensitivity of the camera, and perform characterization experiments. During the design process we will implement all applicable electrical and biological safety standards. Then we will determine limits of tumor detection of this camera with realistic phantoms. In Phase II we will conduct trials with our long-time collaborators at the John Wayne Cancer Institute on melanoma and breast cancer patients, at Cornell on prostate cancer, and at Memorial Sloan Kettering in abdominal Laparoscopic cancer detection.