Beta Camera and Laparoscopic Probe for Surgical Cancer Removal.

用于癌症手术切除的 Beta 相机和腹腔镜探头。

• 批准号: 7483991
• 负责人: FARHAD DAGHIGHIAN
• 金额: $ 10.03万
• 依托单位: INTRA MEDICAL IMAGING, LLC
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-09 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7483991
• 关键词: Background Radiation; Beta Particle; Breast; Cancerous; Cells; Ceramics; Class; Clinical Trials; Computer software; Condition; Conduct Clinical Trials; Coupling; Deposition; Detection; Devices; Discrimination; Electronics; Enrollment; Excision; Fiber Optics; Gamma Rays; Glutamate Carboxypeptidase II; Housing; Image; Image Analysis; Imaging Device; Isotopes; J591 Monoclonal Antibody; Label; Lead; Left; Localized; Malignant - descriptor; Malignant Neoplasms; Mechanics; Monoclonal Antibodies; Noise; Operative Surgical Procedures; Pathology; Patients; Performance; Phase; Pilot Projects; Plastics; Problem Solving; Prostate; Prostatectomy; Protocols documentation; ROC Curve; Radio; Radiolabeled; Range; Rate; Recurrence; Relapse; Research; Research Design; Research Ethics Committees; Resected; Robotics; Safety; Sensitivity and Specificity; Solutions; Standards of Weights and Measures; Surgeon; Surgical Instruments; Surveys; Technology; Testing; Time; Tissue Sample; Tissues; Tracer; Tube; Tumor Markers; United States Food and Drug Administration; Visual; base; breast lumpectomy; cancer cell; cancer surgery; cold temperature; concept; design; detector; experience; fluorodeoxyglucose; in vivo; instrument; malignant breast neoplasm; milligram; millimeter; novel; photomultiplier; prevent; prototype; radiotracer; research and development; research study; sensor; solid state; tumor; tumor growth; uptake; voltage; wound; Background Radiation; Beta Particle; Breast; Cancerous; Cells; Ceramics; Class; Clinical Trials; Computer software; Condition; Conduct Clinical Trials; Coupling; Deposition; Detection; Devices; Discrimination; Electronics; Enrollment; Excision; Fiber Optics; Gamma Rays; Glutamate Carboxypeptidase II; Housing; Image; Image Analysis; Imaging Device; Isotopes; J591 Monoclonal Antibody; Label; Lead; Left; Localized; Malignant - descriptor; Malignant Neoplasms; Mechanics; Monoclonal Antibodies; Noise; Operative Surgical Procedures; Pathology; Patients; Performance; Phase; Pilot Projects; Plastics; Problem Solving; Prostate; Prostatectomy; Protocols documentation; ROC Curve; Radio; Radiolabeled; Range; Rate; Recurrence; Relapse; Research; Research Design; Research Ethics Committees; Resected; Robotics; Safety; Sensitivity and Specificity; Solutions; Standards of Weights and Measures; Surgeon; Surgical Instruments; Surveys; Technology; Testing; Time; Tissue Sample; Tissues; Tracer; Tube; Tumor Markers; United States Food and Drug Administration; Visual; base; breast lumpectomy; cancer cell; cancer surgery; cold temperature; concept; design; detector; experience; fluorodeoxyglucose; in vivo; instrument; malignant breast neoplasm; milligram; millimeter; novel; photomultiplier; prevent; prototype; radiotracer; research and development; research study; sensor; solid state; tumor; tumor growth; uptake; voltage; wound

DESCRIPTION (provided by applicant): The only certain cure of cancer is the complete removal of the malignant tissue by surgery. A complete removal would prevent the re-growth of the tumor and eliminate the need for a second operation. One of the difficulties during the operation is to determine if all of the cancerous tissue has been removed from the tumor margin. Currently surgeons rely on visual inspection of the surgical cavity and random tissue sampling of the margins, or pathology results on the excised tissue that is often ready after the surgery is concluded. Radiolabeled tumor markers have preferentially high uptake in cancerous cells and offer a unique opportunity for detection of occult tumors at the margin. Background: Beta rays have a range of a few millimeters in tissue. Beta ray detectors, in conjunction with beta emitting isotopes are ideal for detection of occult tumors on the margin since background radiation would not interfere with identification of margins. Previously we have developed a beta probe and beta camera detector and demonstrated that they are selectively sensitive to beta rays. An instrument with imaging capability would further aid the surgeon to quickly and accurately localize any positive tumor margins. Beta cameras have been proposed in the past, but have never been used clinically, because of problems designing a camera that is sensitive and at the same time electrically safe to use during surgeries. Novelty: In this submission, we are proposing a novel beta-camera design based on the use of Solid State Photomultipliers (SSPMs). SSPMs is a relatively new class of photo-sensors that have been shown to have a performance close to that of conventional PMTs, but only requiring operating at tens of volts instead of kV needed for PMTs. Thus, the use of SSPM would significantly alleviate the electrical safety aspect of using the beta-camera intra-operatively. Multiple detector modules will also be tested to increase sensitivity to beta and decrease sensitivity for gamma rays. Preliminary Studies: Recently we performed a pilot study that involved 7 patients that underwent lumpectomy. During the procedure, the surgical cavity and excised tissues were surveyed with a beta-probe. We found that the background in the surgical cavity detected by the beta-probe was only a 12 18 cps, while a 5 mg generated 3518 cps, showing that the gamma background is low enough to allow detection of uptake in small volumes of tissues. Another conclusion from this study was that an imaging device is needed to allow a more rapid and accurate survey of the surgical cavity. We have built a prototype of the SSPM-based beta camera in an small scale and demonstrated its feasibility. Research Plan (Phase I): We will build the camera with a sheet of plastic scintillator and a 5x5 array of new ceramic-mounted SSPMs. We will experiment with Peltier coolers to lower the temperature of the SSPM array. We will optimize the sensitivity of the camera, and perform characterization, and limit of detection tests with phantoms. We will test the novel concept of coincidence discrimination to reduce the electronic noise of SSPMs and increase the sensitivity of the camera to low energy beta rays. We will test a dual detector module design to reduce the background gamma sensitivity. We will test a module for the camera with one layer of SSPMs and 2 layers of different scintillators that are differentiated by decay-time constants and phoswitch circuitry. R&D and Clinical Trials Plan (Phase II): The best detector module concept will be selected for building a beta camera for clinical trial. The electronics, mechanical housing, and software for the camera, as well as a Laparoscopic version of the camera will be built and tested during the first part of the Phase II. The prototypes of these cameras will be designed to pass electrical and environmental standards of surgical instruments, and will be sent to CSA in order to obtain UL safety certificates. We will submit a New Device Exemption (NDE) application to FDA for testing the cameras in breast and prostate. During the later part of Phase II we will conduct clinical trials with our long term collaborator Dr. Armando Giuliano on detection of margins in lumpectomy using FDG. Thirty patients will enroll is this study and the existing IRB protocol for beta probe will be amended to include beta camera. Together with Drs. Bander and Tewari at Cornell we will test the laparoscopic beta camera in robotic prostatectomies, in conjunction with a monoclonal antibody, called J591, against PSMA that is labeled with Lu-177 (a beta emitter). The on going IRB approved studies of Lu-177-J591 Mab will be amended to include beta camera exploration laparoscopically. Statistical Analysis: Both studies are designed to determine the efficacy, sensitivity, and specificity of the beta cameras in detection of tumors on the margins of resection. The ROC analysis of the beta camera with visual detection of the surgeons will show if beta cameras added can help increase the rate of margin detection.

描述（由申请人提供）：唯一的癌症治愈方法是通过手术完全去除恶性组织。完全去除将防止肿瘤的重新生长，并消除对第二次手术的需求。手术过程中的困难之一是确定是否从肿瘤边缘清除了所有癌组织。目前，外科医生依赖于对边缘的手术腔和随机组织采样的视觉检查，或者在手术后通常准备就绪的组织中的病理学结果。放射性标记的肿瘤标记在癌细胞中优先摄取高摄取，并为在边缘检测神秘肿瘤提供了独特的机会。背景：β射线在组织中有几毫米的范围。 β射线探测器与β发射同位素结合使用，非常适合在边缘检测隐匿性肿瘤，因为背景辐射不会干扰边缘的识别。以前，我们已经开发了β探针和β摄像头检测器，并证明它们对β射线有选择性敏感。具有成像能力的仪器将进一步帮助外科医生快速，准确地定位任何阳性肿瘤边缘。过去曾提出过Beta相机，但从未在临床上使用，因为在手术过程中设计了敏感且在手术期间使用电气安全的相机。新颖性：在此提交中，我们提出了一种基于使用固态光电倍增器（SSPM）的新型Beta相机设计。 SSPMS是一类相对较新的照片传感器，已证明其性能接近常规PMT，但仅需要以数十伏而不是PMT所需的KV工作。因此，SSPM的使用将显着缓解使用β相机内部术中使用的电气安全性方面。还将测试多个检测器模块以提高对β的灵敏度并降低对伽马射线的敏感性。初步研究：最近我们进行了一项试点研究，涉及7例接受肿块切除术的患者。在过程中，对手术腔和切除的组织进行了β-探针进行了调查。我们发现，β-探针检测到的手术腔中的背景仅为12 18 cps，而5 mg产生了3518 cps，表明伽马背景足够低，足以允许在少量组织中检测到摄取。这项研究的另一个结论是，需要一个成像装置，以便对手术腔进行更快，准确的调查。我们已经构建了基于SSPM的Beta摄像头的原型，并证明了其可行性。研究计划（I阶段）：我们将使用一张塑料闪烁体和5x5新的陶瓷安装的SSPM构建相机。我们将尝试使用Peltier冷却器来降低SSPM阵列的温度。我们将优化相机的灵敏度，并执行表征以及使用幻影的检测测试极限。我们将测试重合歧视的新颖概念，以减少SSPM的电子噪声，并提高相机对低能β射线的敏感性。我们将测试双检测器模块设计，以降低背景伽马灵敏度。我们将测试一个带有一层SSPM和2层不同闪烁器的摄像机的模块，这些模块由衰减时间常数和Phoswitch电路进行区分。研发和临床试验计划（II阶段）：将选择最佳检测器模块概念以构建用于临床试验的Beta摄像头。将在II阶段的第一部分中构建和测试相机的电子，机械外壳和软件以及相机的腹腔镜版本。这些摄像机的原型将设计为通过手术仪器的电气和环境标准，并将发送到CSA，以获得UL安全证书。我们将向FDA提交新的设备豁免（NDE）申请，以测试乳房和前列腺中的相机。在第二阶段的后期，我们将使用我们的长期合作者Armando Giuliano博士进行临床试验，以使用FDG检测肿块切除术的边缘。这项研究将是30名患者，并且将修改现有的IRB探针IRB方案以包括Beta相机。与博士一起。 Bander和Tewari在康奈尔（Cornell），我们将在机器人前列腺切除术中测试腹腔镜β摄像头，并与单克隆抗体（称为J591）一起测试用LU-177标记的PSMA（beta Emitter）。 IRB批准的对LU-177-J591 MAB的研究将进行修改，以包括β摄像头探索。统计分析：两项研究都旨在确定β摄像机在切除边缘检测肿瘤中的功效，灵敏度和特异性。对β摄像头的ROC分析，可视觉检测外科医生，将表明是否添加了Beta摄像机可以帮助提高利润率检测速率。