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: 10326402
• 负责人: Ann M Gillenwater
• 金额: $ 63.41万
• 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/10326402
• 关键词: Address; Affect; Algorithms; Area; Back; Benign; Biopsy; Cancer Patient; Cells; Collagen; Development; Diagnosis; Disease; Dysplasia; Early Diagnosis; Early treatment; Ensure; Epithelial; Excision; Fluorescence; Future; Genomic Instability; Goals; Gold; High grade dysplasia; Image; Imaging technology; Incidence; 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; base; cost; density; digital; fluorescence imaging; global health; high resolution imaging; high risk; image guided; imaging modality; imaging probe; imaging system; improved; malignant mouth neoplasm; mortality; mouth squamous cell carcinoma; multimodality; neoplastic; next generation; novel; optical imaging; 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.

项目摘要/摘要： 口腔癌是每年超过300,000例新病例，死亡率约为50％，是全球主要的健康状况 问题。诊断阶段是生存的最重要预测指标，不幸的是，大多数患者被诊断 在后期。口腔癌之前是可见的粘膜变化，这些变化被指定为口服潜在的恶性肿瘤 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黄金标准，以及 发育不良的病理诊断是口腔癌发展风险的最佳指标。发育不良经常出现 OPMD的患者；但是，大多数从业者缺乏将OPMD与良性病变区分开的专业知识。这很困难 即使对于专家来说，确定哪些口腔病变患有发育异常的风险最高，应进行活检。目标 该建议的是开发和验证主动活检指南（ABG）光学成像系统，由 光学映射范围和高分辨率显微镜，以帮助临床医生确切地确定何时何地 活检可疑口腔病变。 ABG系统将将几种光学成像方式整合到非侵入性探针 关键分子和形态学变化与癌症的下一代标志有关。 在AIM 1中，我们将开发一个紧凑的光学映射范围，该范围使用数字光处理技术来捕获 白光和自动荧光图像，并主动投射到口腔粘膜上A地图突出显示高风险的区域 基于胶原蛋白荧光的丧失（一种侵袭和转移的信号）和改变的口腔发育不良和癌症 在上皮NAD（P）H和FAD荧光中（一种流失的细胞能量学信号）。映射范围将 作为图像引导序列的第一步，在口腔组织上投射了高风险区域的可见图。 我们将开发跟踪算法以调整投影图，以确保尽管有耐心 移动。在AIM 2中，我们将开发低成本的荧光和反射率高分辨率显微镜 在口腔上皮中成像核形态（持续增生信号传导，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 确认方式提高特异性。在AIM 3中，我们将集成光学映射范围和高分辨率 显微镜成一个单一的紧凑活检引导系统，并验证其提供实时精确的能力 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。 将广场自动荧光成像和核和微血管形态的高分辨率成像结合在一起 提供一种生物学定向的方法，以帮助临床医生精确确定活检可疑口腔的何时何地 病变，达到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，以便早期检测口服 肿瘤和更好的患者结果应对长期，重大的全球健康挑战。