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，高灵敏度和紧凑的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，将它们整合到我们上市的术中控制单元中，用幻影进行测试，并在第二阶段的临床试验中寻求安全认证。意义：手术是治疗癌症唯一确定的方法；然而，它的治疗能力受到可能留下肿瘤的微观痕迹（称为边缘）的影响。以乳腺癌为例，由于切除边缘，保乳手术（乳房肿瘤切除术）后复发率为20%。一种能够在手术中观察肿瘤床，并对肉眼无法检测到的微小癌细胞进行成像的beta相机，可以显著降低许多癌症的复发率，如黑色素瘤、乳腺癌和前列腺癌，并提高生存率。此外，它可能使更多的乳腺癌患者成为保乳肿瘤切除术的候选者，并改善乳腺癌患者的心理恢复。腹腔镜β探针将为外科医生提供一个新的“视野”，有助于以微创的方式发现和完全切除腹部癌症。背景：F-18原子释放出正电子（射线），而正电子又产生伽马射线。伽马射线在组织中传播数十厘米，而β射线的传播范围约为2mm。放射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相机存在两个严重缺陷之一，阻碍了它们在癌症手术中的应用。正电子检测所需的薄屏蔽不能提供与高压光电倍增管（pmt）的充分绝缘。用于将高电压与患者分离的长光纤耦合大大降低了灵敏度。

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.