DEVELOPMENT OF GOGGLE SYSTEM FOR FLUORESCENCE IMAGE-GUIDED SURGERY

描述（由申请人提供）：尽管在过去十年中开发的新癌症治疗方法在微创或非侵入性根除肿瘤方面显示出前景，但手术仍然是大多数实体瘤的主要治疗模式。外科医生以前依赖于术前图像进行肿瘤切除，但最近在手术室提供图像引导的努力显着改善了肿瘤定位。特别是光学成像技术，由于其相对较低的成本、使用非电离辐射、快速数据采集和实时图像引导，在手术室中已经找到了一个利基。然而，显微光学技术具有小的视场，这限制了其用于对小的组织体积进行采样。当前的术中平面成像系统在计算机监视器上显示2D图像，需要外科医生在手术部位和监视器之间交替。这些系统的大尺寸对其在小型手术室中的使用提出了挑战，并且妨碍了便携性。断层摄影方法能够进行3D显示，但是复杂的仪器和密集的图像分析排除了实时反馈，并且可能需要操作者陡峭的学习曲线。另一个相关的首要问题是手术切缘阳性的普遍性，因为缺乏可靠的成像剂用于术中手术切缘评估，导致昂贵的重复访问。因此，迫切需要开发一种具有实时成像能力的准确、负担得起、用户友好、便携式和通用的术中成像系统。该技术平台还应能够提供手术切缘的实时评估。为了实现这些目标，我们将开发一种术中近红外（NIR）荧光/反射3D成像护目镜系统，该系统可以准确地对肿瘤边界、小阳性结节进行成像，并提供实时图像引导。术中手术切缘评估将通过针对护目镜系统优化的肿瘤选择性光学成像剂来辅助。在开发阶段，护目镜系统将使用来自分子探针的信息来优化检测方案。具体来说，我们将开发和优化免提3D头戴式荧光成像和显示系统，以及用于肿瘤边缘体内染色的近红外成像剂。然后，我们将使用护目镜系统对乳腺癌的小动物模型以及犬乳腺癌患者进行分子成像。这些研究产生的药理学和安全性数据将用于向FDA申请研究性新药（IND）和器械豁免（IDE）。

DESCRIPTION (provided by applicant): Although new cancer treatment methods developed in the past decade have shown promise in minimally or noninvasive eradication of tumors, surgery remains the primary treatment paradigm for most solid tumors. Surgeons previously relied on pre-operative images for tumor resection, but recent efforts to provide image guidance in the operating room have significantly improved tumor localization. Optical imaging techniques, in particular, have found a niche in the operating room because of their relatively low cost, use of non-ionizing radiation, fast data acquisition, and real-time image guidance. However, microscopic optical technologies have small field of view, which confines their use to sampling small tissue volumes. Current intraoperative planar imaging systems display 2D images on computer monitors, requiring the surgeon to alternate between the surgical site and the monitor. The large size of these systems challenges their use in small surgical suites and hampers portability. Tomographic approaches are capable of 3D display, but the complex instrumentation and intensive image analysis precludes real-time feedback and may require steep learning curve for operators. Another related overarching problem is the prevalence of positive surgical margins because of the lack of a reliable imaging agent for intraoperative surgical margin assessment, leading to costly repeat visits. Therefore, there is a compelling need to develop an accurate, affordable, user-friendly, portable, and versatile intraoperative imaging system with real-time imaging capability. The technology platform should also be able of providing real-time assessment of surgical margins. To accomplish these goals, we will develop an intra-operative near-infrared (NIR) fluorescence/reflectance 3D imaging goggle system that can accurately image tumor boundaries, small positive nodules, and provide image guidance in real-time. Intraoperative surgical margin assessment will be aided by a tumor-selective optical imaging agent optimized for the goggle system. At the development stage, the goggle system will use information from the molecular probe to optimize the detection scheme. Specifically, we will develop and optimize a hands-free 3D head-mounted fluorescence imaging and display system, and a near infrared imaging agent for in vivo staining of tumor margins. We will then use the goggle system for molecular imaging of small animal models of breast cancer, as well as canine breast cancer patients. Pharmacology and safety data generated from these studies will be used for investigational new drug (IND) and device exemption (IDE) application to the FDA.