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

基于下一代癌症标志的口腔活检精密光学引导

• 批准号: 10565685
• 负责人: Ann M Gillenwater
• 金额: $ 63.98万
• 依托单位: RICE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-25 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10565685
• 关键词: Address; Affect; Algorithms; Area; Back; Benign; Biopsy; Blood Vessels; Cancer Patient; Cells; Collagen; Development; Diagnosis; Disease; Dysplasia; Early Diagnosis; Early treatment; Ensure; Epithelium; Excision; Fluorescence; Future; Genomic Instability; Goals; High grade dysplasia; Image; Imaging technology; Incidence; Invaded; Lesion; Leukoplakia; Light; Malignant - descriptor; Malignant Neoplasms; Maps; Microscope; Mild Dysplasia; Modality; Molecular; Morbidity - disease rate; Morphology; Mouth Neoplasms; Movement; Mucous Membrane; Multimodal Imaging; Mutation; Neoplasm Metastasis; Neoplasms; Nuclear; Optics; Oral; Oral Diagnosis; Oral mucous membrane structure; Outcome; Pathologic; Patient-Focused Outcomes; Patients; Positioning Attribute; Process; Prognosis; Property; Research; Resolution; Risk; Screening for Oral Cancer; Severities; Signal Transduction; Site; Specificity; Stage at Diagnosis; Surface; Survival Rate; System; Technology; Time; Tissues; Work; angiogenesis; cost; density; digital; fluorescence imaging; global health; high resolution imaging; high risk; image guided; imaging capabilities; imaging modality; imaging probe; imaging system; improved; malignant mouth neoplasm; mortality; mouth squamous cell carcinoma; multimodality; neoplastic; next generation; novel; optical imaging; oral carcinogenesis; oral cavity epithelium; oral dysplasia; oral lesion; oral tissue; prevent; survival prediction

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.

项目概要/摘要： 口腔癌每年新发病例超过30万例，死亡率约为50%，是全球主要的健康问题。 问题.诊断时的分期是最重要的生存预测因素，不幸的是，大多数患者在确诊时 在后期阶段。口腔癌发生之前会出现可见的粘膜变化，这些变化被认为是口腔潜在的恶性病变 疾病（OPMD）。口腔病变的侵入性活检是诊断口腔发育不良和癌症的金标准， 病理诊断的发育异常是最好的指标的风险，口腔癌的发展。发育不良通常发生在 OPMD患者;然而，大多数医生缺乏区分OPMD和良性病变的专业知识。很难 甚至对于专家来说，确定哪些口腔病变具有最高的包含发育不良的风险，并且应该进行活检。目标 该提案的一个目的是开发和验证主动活检引导（ABG）光学成像系统，该系统由以下部分组成： 光学映射范围和高分辨率显微镜，以帮助临床医生准确地确定何时何地 活检可疑的口腔病变。ABG系统将集成几种光学成像模式， 与下一代癌症标志相关的关键分子和形态学变化。 在目标1中，我们将开发一种紧凑的光学映射范围，该范围使用数字光处理技术来捕获 白色光和自体荧光图像，并主动将突出显示高危区域的地图投射到口腔粘膜上 基于胶原荧光的丧失（侵袭和转移的信号）和改变， 在上皮NAD（P）H和FAD荧光（细胞能量失调的信号）。映射范围将 作为图像引导序列中的第一步，在口腔组织上投影高风险区域的可见图。 我们将开发跟踪算法来调整投影图，以确保准确定位， 运动在目标2中，我们将开发低成本的荧光和反射高分辨率显微镜， 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 确认模式，以提高特异性。在目标3中，我们将集成光学映射范围和高分辨率 将显微镜整合到一个紧凑的主动活检引导系统中，并验证其提供实时精确 在接受口腔癌监测的高危患者研究中选择口腔活检部位的指南。 将宽视野自体荧光成像与核和微血管形态的高分辨率成像相结合， 提供一种生物学指导的方法，帮助临床医生精确地确定何时何地对可疑的口腔进行活检。 病变，实现高灵敏度和高特异性。 这项研究的影响将是提供交互式成像技术，使口腔癌的早期检测成为可能。 肿瘤和更好的患者结局，解决长期存在的重大全球健康挑战。