Bimodal Intraoral imaging device for detection of oral epithelial neoplasia

用于检测口腔上皮瘤变的双模口内成像装置

• 批准号: 10530654
• 负责人: Xingde Li
• 金额: $ 48.58万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-12-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10530654
• 关键词: Address; Affect; Agreement; Animal Model; Animals; Area; Biochemical; Biopsy; Carcinoma; Cervix Uteri; Clinic; Clinical; Coupled; Detection; Development; Devices; Diagnostic; Early Diagnosis; Early identification; Early treatment; Engineering; Epithelium; Evaluation; Excision; Eye; Feedback; Fluorescence; Generations; Goals; Histology; Histopathology; Human; Human Papillomavirus; Image; Imaging Device; Incidence; Intraepithelial Neoplasia; Knowledge; Label; Lesion; Light; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Measures; Metabolic; Methodology; Methods; Microscopic; Microscopy; Modality; Molecular; Morbidity - disease rate; Morphology; Mucous Membrane; Neoplasms; Operative Surgical Procedures; Optical Biopsy; Optics; Oral; Oral cavity; Oral mucous membrane structure; Oropharyngeal; Oropharyngeal Squamous Cell Carcinoma; Outcome; Outcomes Research; Palpation; Pathology; Patient-Focused Outcomes; Patients; Performance; Pilot Projects; Recurrence; Recurrent disease; Resolution; Robotics; Sampling; Sampling Studies; Screening for Oral Cancer; Sensitivity and Specificity; Site; Specificity; Spectrum Analysis; Surface; Survival Rate; Testing; Tissues; Translating; Treatment outcome; Visual; biomarker identification; cellular imaging; clinical translation; detection sensitivity; high risk; human imaging; human tissue; imaging biomarker; imaging capabilities; improved; in vivo; in vivo imaging; instrument; malignant mouth neoplasm; malignant oropharynx neoplasm; microscopic imaging; molecular imaging; mortality; multi-photon; neoplastic; non-invasive imaging; novel; oral cavity epithelium; performance tests; pre-clinical; preclinical study; premalignant; public health relevance; screening; second harmonic

ABSTRACT The goal of this project is to develop a novel bimodal intraoral imaging device for assessment of the oral and oropharynx mucosa for detection of neoplasia, aiding in early detection. Oral and oropharyngeal cancers account for 640,000 new cases of cancer worldwide each year. The number of cases increases each year, in part due to the spread of human papillomavirus. The 5-year survival rate has remained relatively unchanged over several decades, despite accessibility of the oral cavity and oropharynx for examination. With early detection, the 5-year survival rate increases to 80%, providing hope of improved patient outcomes given development of effective early detection approaches. The current clinical approach of detection by visual examination with palpation to guide biopsy acquisition, is insufficient to reliably detect neoplasia at the earliest, most treatable stages, including oral epithelial dysplasia (OED) and early oral/oropharyngeal squamous cell carcinoma (OSCC). Our preclinical and pilot clinical sample studies indicate that label-free nonlinear optical microscopy (NLOM), consisting of multiphoton autofluorescence microscopy and second harmonic generation, is highly promising as an optical biopsy method. It provides deep mucosal imaging at subcellular resolution and detects parameters associated with neoplasia that parallel histology. In addition to optical histology, NLOM provides additional spectroscopic metrics based on the metabolic and biochemical microenvironment, which may add to optical histology metrics. Our results assessing NLOM for this application show high sensitivity and specificity for detection of neoplasia, and a high degree of agreement with histopathology. Despite these advantages, a limitation of microscopy is the inherently limited image field of view on the order of hundreds of microns. On the other hand, clinical large area screening methods comprised of widefield autofluorescence (WF) imaging provide the fields needed (centimeters) with high sensitivity for detection, but lack specificity and cannot image below the surface or assess microscopic features. In this project, we will combine the benefits of both approaches into a single handheld intraoral imaging device that will provide large area screening for regions of suspicion for neoplasia using WF coupled with detailed, depth-resolved subsurface imaging by NLOM for highly sensitive and specific detection of high risk lesions (OED) and early OSCC. To accomplish this goal we will 1) construct a biomodal WF-NLOM intraoral imaging device and optimize performance and suitability for noninvasive evaluation of neoplasia in human oral/oropharyngeal mucosa; 2) refine and translate methodology and metrics defined in preclinical studies, to the intraoral device for use in human OSCC; and 3) evaluate the bimodal intraoral imaging device performance and conduct a pilot study to evaluate the device in patients in vivo, obtaining valuable feedback regarding potential for detection of neoplasia and adaptability for the clinic.

抽象的 该项目的目标是开发一种新型双模口内成像设备，用于评估口腔和口腔 口咽粘膜用于检测肿瘤，有助于早期发现。口腔癌和口咽癌账户 全球每年新增 640,000 例癌症病例。案件数量逐年增加，部分原因是 人乳头瘤病毒的传播。 5年生存率在数年中保持相对不变 几十年来，尽管口腔和口咽部可以进行检查。通过早期发现，5 年 生存率提高至 80%，鉴于开发有效的治疗方法，为改善患者预后带来了希望 早期检测方法。目前临床上主要通过目视检查和触诊来检测 引导活检采集不足以在最早、最可治疗的阶段可靠地检测肿瘤，包括 口腔上皮发育不良（OED）和早期口腔/口咽鳞状细胞癌（OSCC）。我们的临床前 和试点临床样本研究表明，无标记非线性光学显微镜（NLOM），包括 多光子自发荧光显微镜和二次谐波产生，作为一种非常有前途的光学 活检方法。它提供亚细胞分辨率的深层粘膜成像并检测相关参数 与组织学平行的肿瘤形成。除了光学组织学之外，NLOM 还提供额外的光谱 基于代谢和生化微环境的指标，这可能会增加光学组织学指标。 我们针对该应用评估 NLOM 的结果显示出检测肿瘤的高灵敏度和特异性， 且与组织病理学高度一致。尽管有这些优点，但显微镜的局限性是 图像视场本质上有限，约为数百微米。另一方面，临床大面积 由宽场自发荧光 (WF) 成像组成的筛选方法提供了所需的场 （厘米），检测灵敏度高，但缺乏特异性，无法在表面以下成像或评估 微观特征。在这个项目中，我们将把两种方法的优点结合到一个手持设备中 口内成像设备将使用 WF 对疑似肿瘤区域进行大面积筛查 与 NLOM 详细的深度分辨地下成像相结合，可实现高度灵敏和特异性的检测 高风险病变（OED）和早期 OSCC。为了实现这一目标，我们将 1) 构建生物模态 WF-NLOM 口腔内成像设备并优化肿瘤无创评估的性能和适用性 人类口腔/口咽粘膜； 2) 完善和翻译临床前定义的方法和指标 研究用于人类口腔鳞癌的口内装置； 3) 评估双模口内成像装置 性能并进行试点研究以评估患者体内的设备，获得有价值的反馈 关于肿瘤检测的潜力和临床适应性。