Optical Sensing of Dysplasia and Aneuploidy in Upper GI Endoscopy

上消化道内窥镜检查中不典型增生和非整倍体的光学传感

• 批准号: 8392965
• 负责人: SATISH K SINGH
• 金额: --
• 依托单位: VA BOSTON HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8392965
• 关键词: Advocate; Algorithms; Aneuploidy; Area; Barrett Esophagus; Barrett' s Adenocarcinoma; Biopsy; Biopsy Specimen; Blinded; Cancer Detection; Caring; Cells; Cessation of life; Chronic; Clinical; Computer software; Coupled; Custom; DNA; Data; Detection; Development; Devices; Diagnosis; Diagnostic; Diploidy; Disease; Dysplasia; Early treatment; Elastic scattering spectroscopy; Endoscopy; Esophageal; Esophagus; Event; FDA approved; Forcep; Frequencies; Gastroesophageal reflux disease; Goals; Histocompatibility Testing; Histology; Image; Image Cytometry; Imaging Techniques; Incidence; Informed Consent; Intestinal Metaplasia; Investigation; Lesion; Light; Low Prevalence; Malignant Neoplasms; Maps; Measurement; Measures; Methodology; Methods; Mucous Membrane; Nature; Normal tissue morphology; Optical Biopsy; Optics; Outcome; Pathologic; Pathologist; Pathology; Patients; Pattern; Performance; Phase; Ploidies; Population; Positioning Attribute; Predictive Value; Premalignant; Prevention; Probability; Prospective Studies; Randomized; Reading; Reporting; Research; Research Design; Risk; Sample Size; Scanning; Schedule; Sensitivity and Specificity; Slide; Stratification; Study Subject; Symptoms; System; Testing; Time; Tissues; Training; Validation; Veterans; aneuploidy analysis; arm; base; cancer prevention; cancer risk; cohort; computerized; cost; design; imaging modality; improved; in vivo; innovation; next generation; novel; prevent; prospective; public health relevance; screening; standard care; surveillance strategy; theories; tool; upper GI series

DESCRIPTION (provided by applicant): Optical Sensing of Dysplasia and Aneuploidy at Upper GI Endoscopy Objectives: 1. To establish the "real-world" feasibility of using ESS integrated biopsy tools for in vivo sensing of dysplasia and aneuploidy in BE. a. Utilizing integrated ESS-optical forceps, we will develop a diagnostic algorithm and determine its sensitivity, specificity, and negative predictive value for classifying ESS spectra in the detection of dysplasia and aneuploidy. b. We will develop a next-generation biopsy forcep that can seamlessly scan and assess larger mucosal areas in order to hone in on foci of flat, invisible dysplasia and/or aneuploidy within a Barrett's segment. 2. To prospectively validate the diagnostic algorithm (based on the results first objective) in a cohort of Barrett's patients to establish whether ESS-guided biopsy improves per- biopsy dysplasia and/or aneuploidy detection rates over standard random surveillance biopsies. The potential benefit of this research is the validation of this integrated diagnostic biopsy tool for upper GI endoscopy. Use of the device could cost-effectively enhance Barrett's Esophagus screening strategies and patient outcomes. Research design: This will be a two-phase prospective study. Since tissue type cannot be determined with standard endoscopic views and the ESS is a computerized reading, subjects will not need to be randomized and endoscopists need not be blinded. The pathologists will be blinded to the ESS reading and aneuploidy analysis results. Methodology: Candidate subjects for this study will be drawn from an extant pool of patients who are scheduled for an endoscopy of the esophagus to determine whether they have pathologic conditions, or to determine whether their disease has advanced. Upon obtaining a signed Informed Consent, all patients will receive standard treatment i.e., routine esophageal endoscopy with random multiple physical biopsies using a predetermined geometric pattern as indicated for their care. Prior to the standard physical biopsy, an optical biopsy will be taken of the exact same tissue with the same forceps. The FDA approved device fitted with custom optics will take a 2 second reading consisting of flashes of white light and measurement of light reflected and refracted from the tissue. The forceps device is designed to then be able to biopsy the exact tissue measured by ESS. The tissue will then be sent for pathology in standard fashion with an additional independent pathologist review to confirm histology. In the event of a disagreement a third pathologist will review the slides. The outcome will be the correlation of the ESS reading and the tissue pathology. For the detection of aneuploidy, DNA histograms representing the frequency distribution of the DNA index values of the population of cells will be constructed using the ACIS DNA ploidy software with lesions classified as diploid, tetraploid or aneuploid. ESS spectra and the corresponding DNA index will be correlated as above for grades of dysplasia. In phase two of the study, the algorithm trained with the data collected in the previous phase will be tested for real-time detection of dysplasia to increase the per-biopsy yield of dysplastic and/or aneuploidy tissue.

描述（由申请人提供）： 上GI内窥镜检查目标的异常增生和非整倍性的光学感知：1。建立使用ESS积分活检工具的“现实世界”可行性，以在体内感应异常增生和BE中的异倍型。一个。利用综合的静电钳，我们将开发出一种诊断算法，并确定其在检测异常增生和非整倍性中对ESS光谱进行分类的敏感性，特异性和负预测值。 b。我们将开发下一代活检的武器，可以无缝扫描和评估较大的粘膜区域，以磨削Barrett段内平坦，无形的发育异常和/或非整倍性的焦点。 2。为了前瞻性验证Barrett患者队列中的诊断算法（基于结果的第一个目标），以确定ESS引导的活检是否改善了活检发育异常和/或非整倍性检测率，而不是标准的随机监测活检。这项研究的潜在优势是对上GI内窥镜检查的综合诊断活检工具的验证。该设备的使用可能会成本增强Barrett的食管筛查策略和患者结果。研究设计：这将是一项两阶的前瞻性研究。由于组织类型不能用标准的内窥镜视图确定，ESS是计算机化的，因此不需要随机分组，并且内镜医生不必蒙蔽。病理学家将对ESS阅读和非整倍性分析结果视而不见。方法论：这项研究的候选受试者将从现存的一组患者库中提取，这些患者计划进行食管的内窥镜检查，以确定他们是否患有病理状况，或者确定他们的疾病是否疗法。在获得签署的知情同意书后，所有患者将接受标准治疗，即常规的食管内窥镜检查，随机多个物理活检，使用预定的几何模式，如他们的护理所示。在进行标准的身体活检之前，将对具有相同镊子的完全相同的组织进行光学活检。 FDA批准的装有自定义光学器件的设备将需要2秒的读数，包括白光的闪光以及反射和从组织折射的光的测量。镊子装置设计为可以通过ESS测量的精确组织进行活检。然后，将以标准方式将组织以病理学的形式发送，并进行其他独立的病理学家审查，以确认组织学。如果出现分歧，第三个病理学家将审查幻灯片。结果将是ESS阅读与组织病理学的相关性。为了检测非整倍性，将使用ACIS DNA倍而言软件构建代表细胞群体群体DNA指数频率分布的DNA直方分布，其病变分类为二倍体，四倍体或非倍倍倍相。 ESS光谱和相应的DNA指数将与上述发育不良相关。在研究的第二阶段中，将测试接受上一阶段数据的数据的算法，以实时检测发育异常，以增加异常和/或非整倍性组织的每种生物疾病产率。