DEVELOPMENT OF GOGGLE SYSTEM FOR FLUORESCENCE IMAGE-GUIDED SURGERY

描述（由申请人提供）：尽管过去十年发展的新的癌症治疗方法在微创或无创根除肿瘤方面显示出希望，但手术仍然是大多数实体瘤的主要治疗模式。外科医生以前依靠术前图像进行肿瘤切除，但最近在手术室提供图像指导的努力已显著改善了肿瘤定位。特别是光学成像技术，由于其成本相对较低、使用非电离辐射、快速数据采集和实时图像引导，已经在手术室中找到了一席之地。然而，显微光学技术具有小视野，这限制了它们的使用，以取样小组织体积。目前的术中平面成像系统在计算机显示器上显示二维图像，要求外科医生在手术部位和显示器之间交替进行。这些系统的大尺寸挑战了它们在小型手术套房中的使用，并妨碍了便携性。层析成像方法能够3D显示，但复杂的仪器和密集的图像分析排除了实时反馈，并且可能需要操作员陡峭的学习曲线。另一个相关的首要问题是手术切缘阳性的普遍存在，因为缺乏可靠的成像剂进行术中手术切缘评估，导致昂贵的重复就诊。因此，迫切需要开发一种准确、经济、用户友好、便携和多功能的术中成像系统，并具有实时成像能力。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，该系统可以准确成像肿瘤边界，小阳性结节，并实时提供图像引导。术中手术切缘评估将由针对护目镜系统优化的肿瘤选择性光学显像剂辅助。在开发阶段，护目镜系统将利用来自分子探针的信息来优化检测方案。具体而言，我们将开发和优化免提3D头戴式荧光成像和显示系统，以及用于肿瘤边缘活体染色的近红外显像剂。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。从这些研究中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.