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: 10064018
• 负责人: Xingde Li
• 金额: $ 58.23万
• 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/10064018
• 关键词: Address; Affect; Agreement; Animal Model; Animals; Area; Biochemical; Biopsy; Cancer Etiology; Carcinoma; Cervix Uteri; Clinic; Clinical; Coupled; Detection; Development; Devices; Diagnostic; Early Diagnosis; Early identification; Early treatment; Engineering; Epithelial; 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; 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; base; 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; neoplastic; non-invasive imaging; novel; oral cavity epithelium; performance tests; pre-clinical; preclinical study; 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 该项目的目的是开发一种新型的双峰内部成像装置，以评估口服和 口咽粘膜可检测肿瘤，帮助早期检测。口服和口咽癌症帐户 每年在全球640,000例新的癌症病例。案件数量每年增加，部分原因是 人乳头瘤病毒的传播。 5年的存活率在几个方面保持相对不变 几十年来，尽管口腔和口咽可访问进行检查。通过早期检测，5年 生存率提高到80％，鉴于有效的发展，生存率提供了改善的患者结局 早期检测方法。当前通过视觉检查检测的临床检测方法与触诊 指导活检审计，不足以最早，最可治疗的阶段可靠地检测到肿瘤 口腔上皮发育不良（OED）和早期口腔/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，不含标签的非线性光学显微镜（NLOM），由 多光子自动荧光显微镜和第二次谐波生成，作为光学很有希望 活检方法。它在亚细胞分辨率下提供深层粘膜成像并检测相关的参数 与该平行组织学的肿瘤有关。除了光学组织学外，NLOM还提供了其他光谱学 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。 我们评估本申请的NLOM的结果表明，检测肿瘤的敏感性和特异性， 与组织病理学高度同意。尽管有这些优势，但显微镜的局限性是 固有的有限图像视野在数百微米的顺序上。另一方面，临床大面积 筛选方法由广场自动荧光（WF）成像组成，提供所需的字段 （厘米）具有高灵敏度的检测，但缺乏特异性，无法在表面下方图像或评估 微观特征。在这个项目中，我们将将两种方法的好处结合在一起 口腔成像装置将对使用WF提供大量的肿瘤区域筛查 结合NLOM的详细，深度分辨地下成像，以高度敏感和特定的检测 高风险病变（OED）和早期OSCC。为了实现这一目标，我们将1）构建生物植物WF-NLOM 口腔成像设备，优化性能和适用性，以评估肿瘤中的肿瘤性 人口腔/口咽粘膜； 2）精炼和翻译临床前定义的方法和指标 研究，用于人类OSCC的口腔内装置； 3）评估双峰式内成像装置 性能和进行试点研究，以评估体内患者的设备，获得宝贵的反馈 关于检测肿瘤和适应性的潜力。