Optical Sensing of Dysplasia and Aneuploidy in Upper GI Endoscopy

描述（由申请人提供）： 上消化道内窥镜检查中异型增生和非整倍体的光学传感目的：1。建立使用ESS集成活检工具在BE中体内感测发育异常和非整倍性的“真实世界”可行性。a.利用集成的ESS光学钳，我们将开发一种诊断算法，并确定其灵敏度，特异性和阴性预测值分类ESS光谱在异型增生和非整倍体的检测。B.我们将开发下一代活检钳，可以无缝扫描和评估更大的粘膜区域，以便在Barrett节段内的扁平、不可见的异型增生和/或非整倍体病灶上进行定位。2.在Barrett患者队列中前瞻性验证诊断算法（基于第一个目标的结果），以确定ESS引导活检是否比标准随机监测活检提高了每次活检异型增生和/或非整倍体检出率。本研究的潜在受益是验证了这种用于上消化道内窥镜检查的集成诊断活检工具。使用该设备可以经济有效地提高巴雷特食管筛查策略和患者结局。研究设计：这将是一项两阶段的前瞻性研究。由于组织类型无法通过标准内镜视图确定，且ESS是计算机化阅读，因此受试者无需随机化，内镜医师无需设盲。病理学家将对ESS阅读和非整倍性分析结果设盲。方法学：本研究的候选受试者将从计划进行食管内窥镜检查的现有患者库中抽取，以确定他们是否患有病理状况，或确定他们的疾病是否已进展。在获得签署的知情同意书后，所有患者将接受标准治疗，即，常规食管内窥镜检查，随机进行多次物理活检，使用预定的几何图案进行护理。在标准物理活检之前，将使用相同的活检钳对完全相同的组织进行光学活检。FDA批准的配备定制光学器件的器械将进行2秒阅读，包括白色光闪烁和组织反射和折射光的测量。活检钳器械设计用于对ESS测量的精确组织进行活检。然后将组织以标准方式送去进行病理学检查，并由额外的独立病理学家进行审查以确认组织学。如果出现分歧，第三位病理学家将审查切片。结果将是ESS阅读与组织病理学的相关性。对于非整倍性检测，将使用ACIS DNA倍性软件构建代表细胞群体DNA指数值频率分布的DNA直方图，病变分类为二倍体、四倍体或非整倍体。ESS光谱和相应的DNA指数将与上述异型增生等级相关。在研究的第二阶段，将测试用前一阶段收集的数据训练的算法，以实时检测异型增生，以增加异型增生和/或非整倍性组织的每次活检产率。

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.