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.

项目总结/文摘: