Optical Sensing of Dysplasia and Aneuploidy in Upper GI Endoscopy

描述(由申请人提供)： 上消化道内窥镜下异型增生和异倍体的光学传感目的：1.建立使用ESS综合活检工具在体内检测BE中异型增生和异倍体的“真实”可行性。A.利用集成的ESS-光学钳，我们将开发一种诊断算法，并确定其在ESS频谱分类中检测异型增生和非整倍体的敏感性、特异性和阴性预测值。B.我们将开发下一代活检钳，它可以无缝扫描和评估较大的粘膜区域，以精确定位Barrett氏节段内扁平、不可见的异型增生和/或非整倍体的病灶。2.前瞻性地在Barrett‘s患者队列中验证诊断算法(基于第一个目标的结果)，以确定ESS引导的活检是否比标准的随机监测活检提高了每次活检的异型增生和/或非整倍体的检出率。这项研究的潜在好处是验证了这种用于上消化道内窥镜检查的综合诊断活组织检查工具。使用该设备可以经济高效地提高Barrett的食道筛查策略和患者结果。研究设计：这将是一项两阶段的前瞻性研究。由于组织类型不能用标准的内窥镜观察来确定，而且ESS是计算机化的读数，受试者将不需要随机，内窥镜医生也不需要失明。病理学家会对ESS读数和非整倍体分析结果视而不见。方法：这项研究的候选对象将从现有的患者池中挑选出来，这些患者计划接受食道内窥镜检查，以确定他们是否有病理状况，或确定他们的疾病是否已经进展。在获得签署的知情同意后，所有患者将接受标准治疗，即常规食道内窥镜检查，随机进行多次物理活组织检查，按照他们的护理指示进行预定的几何图案。在标准的物理活检之前，将用同样的钳子对完全相同的组织进行光学活检。FDA批准的配备定制光学装置的设备将读取2秒的读数，包括白光闪烁以及从组织反射和折射的光的测量。钳子装置的设计是为了能够对ESS测量的准确组织进行活组织检查。然后，组织将以标准方式被送往病理检查，并由额外的独立病理学家进行审查，以确认组织学。如果有不同意见，第三位病理学家将审查幻灯片。结果将是ESS读数与组织病理学的相关性。对于非整倍体的检测，将使用ACIS DNA倍体软件构建代表细胞群体DNA指标值的频率分布的DNA直方图，将病变分为二倍体、四倍体或非整倍体。ESS频谱和相应的DNA指数将与上面所述的不典型增生级别相关。在研究的第二阶段，用前一阶段收集的数据训练的算法将被测试用于异型增生的实时检测，以增加异常增生和/或非整倍体组织的每次活检产量。

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.