Precision Optical Guidance for Oral Biopsy Based on Next-Generation Hallmarks of Cancer

项目摘要/摘要： 口腔癌每年新增病例超过30万例，死亡率约为50%，是全球主要的健康问题 问题。诊断阶段是最重要的生存预测因素，不幸的是，大多数患者都被诊断出来了。 在后期阶段。口腔癌之前有明显的粘膜病变，被认为是口腔潜在的恶性病变。 精神障碍(OPMD)。口腔病变的侵入性活检是诊断口腔异型增生和癌症的金标准，以及 异型增生的病理诊断是口腔癌发展风险的最好指标。不典型增生常发生在 OPMDs患者；然而，大多数从业者缺乏区分OPMDs与良性病变的专业知识。这很难 即使对于专家来说，确定哪些口腔病变包含异型增生的风险最高，应该进行活组织检查。目标是 这项提议的目的是开发和验证主动活检引导(ABG)光学成像系统，该系统包括 光学标测范围和高分辨率显微镜，帮助临床医生准确确定何时何地 活体检查可疑口腔病变。ABG系统将把几种光学成像方式集成到非侵入性探头 与下一代癌症特征相关的关键分子和形态变化。 在目标1中，我们将开发一种紧凑型光学测绘范围，它使用数字光处理技术来捕获 白光和自动荧光图像，并主动投射到口腔粘膜上，突出高危区域 用于口腔异型增生和基于胶原荧光丧失(侵袭和转移的信号)和改变的癌症 在上皮细胞中，NAD(P)H和FAD荧光(去调节细胞能量学的信号)。映射范围将为 作为图像引导序列的第一步，将高危区域的可见地图投影到口腔组织上。 我们将开发跟踪算法来调整投影地图，以确保无论患者是谁都能准确定位 有动静。在目标2中，我们将开发一种低成本的荧光和反射高分辨率显微镜，能够 口腔上皮细胞核形态成像(持续增殖信号、基因组不稳定性和 突变)和微血管密度和形态(血管生成的信号)。高分辨率探测器将作为一种 确认方式，以提高特异性。在目标3中，我们将把光学测绘范围和高分辨率 将显微镜转换为单个紧凑的主动活检引导系统，并验证其提供实时精确检查的能力 口腔癌监测高危患者研究中口腔活检点选择指南。 结合广域自发荧光成像和核和微血管形态的高分辨率成像将 提供生物导向的方法，帮助临床医生准确地确定何时何地对可疑口腔进行活检 实现了高灵敏度和高特异度。 这项研究的影响将是提供交互式成像技术，使更早地检测口腔 肿瘤和更好的患者预后解决了一个长期的、重大的全球卫生挑战。

Project Summary/Abstract: With over 300,000 new cases per year and a mortality rate of approximately 50%, oral cancer is a major global health issue. The stage at diagnosis is the most important predictor of survival, and unfortunately, most patients are diagnosed at a late stage. Oral cancer is preceded by visible mucosal changes which are designated oral potentially malignant disorders (OPMD). Invasive biopsy of oral lesions is the gold standard to diagnose oral dysplasia and cancer, and pathologic diagnosis of dysplasia is the best indicator of risk for oral cancer development. Dysplasia often arises in patients with OPMDs; however, most practitioners lack expertise to distinguish OPMDs from benign lesions. It is difficult even for experts to determine which oral lesions are at highest risk to contain dysplasia and should be biopsied. The goal of this proposal is to develop and validate an Active Biopsy Guidance (ABG) optical imaging system, consisting of an optical mapping scope and a high resolution microscope, to help clinicians determine precisely when and where to biopsy suspicious oral lesions. The ABG system will integrate several optical imaging modalities to non-invasively probe key molecular and morphologic changes associated with the next-generation hallmarks of cancer. In Aim 1, we will develop a compact optical mapping scope that uses Digital Light Processing technology to capture white light and auto-fluorescence images and actively project onto the oral mucosa a map highlighting areas at high risk for oral dysplasia and cancer based on loss of collagen fluorescence (a signal of invasion and metastasis) and alterations in epithelial NAD(P)H and FAD fluorescence (a signal of de-regulated cellular energetics). The mapping scope will function as the first step in the image guidance sequence, projecting a visible map of high-risk regions on the oral tissue. We will develop tracking algorithms to adjust the projected map to ensure accurate positioning despite patient movement. In Aim 2, we will develop a low-cost fluorescence and reflectance high resolution microscope capable of imaging nuclear morphology in the oral epithelium (a signal of sustained proliferative signaling, genome instability and mutation) and microvascular density and morphology (a signal of angiogenesis). The high resolution probe will serve as a confirmation modality to improve specificity. In Aim 3, we will integrate the optical mapping scope and high resolution microscope into a single, compact Active Biopsy Guidance system and validate its ability to provide real-time precise guidance for selection of oral biopsy sites in a study of high-risk patients undergoing surveillance for oral cancer. Combining widefield autofluorescence imaging and high resolution imaging of nuclear and microvessel morphology will provide a biologically directed approach to help clinicians precisely determine where and when to biopsy suspicious oral lesions, achieving both high sensitivity and high specificity. The impact of this research will be to provide interactive imaging technology that will enable earlier detection of oral neoplasia and better patient outcomes addressing a long-standing, significant global health challenge.