Screening for Barrett's Esophagus Progressors with Multimodality Tethered Capsule Image-Guided Biopsy

使用多模态系留胶囊图像引导活检筛查巴雷特食管进展者

• 批准号: 10591985
• 负责人: Guillermo J Tearney
• 金额: $ 64.35万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-30 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10591985
• 关键词: 3-Dimensional; Aneuploidy; Area; Back; Barrett Esophagus; Biological Markers; Biopsy; Cells; Clinical; Clinical Research; Color; Columnar Cell; Conscious Sedation; Cyclin A; Data; Deglutition; Devices; Diagnosis; Disease Surveillance; Dysplasia; Early Intervention; Endoscopic Biopsy; Endoscopy; Epithelial; Esophageal Adenocarcinoma; Esophageal Intraepithelial Neoplasia; Esophageal Tissue; Esophagus; Fiber; Fluorescence; Forcep; Freezing; Future; Gastroesophageal reflux disease; General Population; Genes; Grant; Healthcare Systems; High Prevalence; Histologic; Histology; Image; Image Analysis; Image Guided Biopsy; Imaging technology; Incidence; Intercept; Intervention; Laboratories; Light; Light-Scattering Spectroscopy; Location; Malignant Neoplasms; Malignant neoplasm of esophagus; Metabolic; Metaplasia; Metaplastic Cell; Methods; Methylation; Microscopy; Modification; Molecular; Molecular Abnormality; Molecular Genetics; Mutation; Nurses; Optical Coherence Tomography; Optics; Oxidation-Reduction; Patients; Persons; Population; Proxy; Research; Risk; Sampling; Screening procedure; Sedation procedure; Site; Spectrum Analysis; System; TP53 gene; Techniques; Technology; Testing; Time; Tissue Sample; Tissues; Validation; Work; base; biomarker discovery; capsule; cohort; cost; deep learning; deep learning algorithm; design; follow-up; high risk; image guided; imaging biomarker; improved; in vivo; innovation; microendoscopy; microscopic imaging; mortality; multimodality; novel; overexpression; population based; predictive marker; primary care setting; progression marker; real-time images; screening; spectrograph; standard of care; targeted imaging; tissue biomarkers

Esophageal adenocarcinoma (EAC) is a deadly cancer that is preceded by a metaplastic change called Barrett's esophagus (BE). It has long been thought that endoscopic screening for BE followed by endoscopic surveillance can significantly decrease the mortality of EAC. This unfortunately has not borne out as the cost and inconvenience of conscious sedation prohibits endoscopy from being used as a population-based screening tool. BE screening may become possible in the future, owing to innovative swallowable tethered capsule endomicroscopes or cell sampling devices that can detect BE without requiring sedation. Yet, even if these capsules were to identify the large number of people in the US who have BE (~15M), endoscopic surveillance of this group would be prohibitively expensive. If we could use tissue biomarkers to identify the 5% of those with BE who will develop EAC in their lifetimes, then endoscopic intervention could be given to those who really need it, and those with low-risk BE would not require further follow up. Recognition of this need has motivated the field to identify BE progression biomarkers derived from esophageal tissue samples obtained by autofluorescence/reflectance-targeted endoscopy. This research has identified biomarkers such as aneuploidy and aberrant p53/cyclin A expression as strong predictors of BE progression. Unfortunately, the only way to target and obtain these tissues today is through sedated endoscopy. With the modifications proposed here, a new BE screening technology that we have developed called optical coherence tomography (OCT) tethered capsule endomicroscopy (TCE), could enable targeted biopsy without sedation. OCT-TCE obtains 3D microscopic images of the entire esophagus in unsedated subjects, accurately identifies BE, and has been successfully used by nurses and technicians in primary care settings. Here, we propose to advance OCT-TCE for targeted biopsy by adding autofluorescence and reflectance spectral imaging technology that can help identify tissue enriched in molecular alterations associated with BE progression risk. The new capsule will also have a cryobiopsy mechanism for acquiring targeted tissue samples under real time image guidance. In Aim 1 of this proposal, we will develop this multimodality TCE with biopsy (MM-TCEB) device and show that it works as intended in a study of 20 BE patients. Then, we will conduct a clinical study in 100 unsedated BE patients to demonstrate that MM-TCEB collects tissue and identifies BE progression biomarkers as well as sedated endoscopy. In Aim 3, we will develop image analysis and deep learning algorithms to mine the Aim 2 data, uncovering new relationships between OCT, autofluorescence, and reflectance spectroscopy and tissue-derived BE progression biomarkers. By acquiring targeted biopsies using a swallowable tethered capsule in unsedated subjects, MM-TCEB can become a powerful technique for obtaining esophageal tissue samples for BE progression biomarker discovery, validation, and ultimately population-based screening.

食管腺癌（EAC）是一种致命的癌症，之前是一种称为Barrett's的变质变化 食道（BE）。长期以来一直认为内窥镜检查后进行内窥镜监测 可以显着降低EAC的死亡率。不幸的是，这并没有作为成本和 有意识镇静的不便禁止内窥镜被用作基于人群的筛查工具。 由于可吞咽的束缚胶囊，将来可能会进行筛查 可以检测到的无需镇静的内体显微镜或细胞采样装置。但是，即使这些 胶囊要识别美国的大量人（约15m），内窥镜监视 这组的价格将非常昂贵。如果我们可以使用组织生物标志物来识别5％的患有 成为谁一生中开发EAC的人，然后可以将内窥镜干预给那些真正需要的人 它和那些低风险的人不需要进一步跟进。 认识到这种需求的促使该领域确定了从食管中得出的进展生物标志物 通过自动荧光/反射率靶向内窥镜检查获得的组织样品。这项研究已经确定 生物标志物（例如非整倍性和异常p53/cyclin a表达）作为强大的BE进展预测指标。 不幸的是，靶向和获取这些组织的唯一方法是通过镇静的内窥镜检查。与 这里提出的修改，我们开发的一种新的筛选技术称为光学连贯性 断层扫描（OCT）束缚胶囊内部显微镜检查（TCE）可以无需镇静而进行靶向活检。 Oct-TCE在未经预科生的受试者中获得了整个食道的3D显微镜图像，准确识别 是并且已经在初级保健环境中成功使用了护士和技术人员。在这里，我们建议 通过添加自动荧光和反射光谱成像技术，用于靶向活检的OCT-TCE 这可以帮助识别与进展风险相关的分子改变中富含的组织。新的 胶囊还将具有一个冷冻生物检查机制，用于在实时图像下获取靶向组织样品 指导。在本提案的AIM 1中，我们将使用活检（MM-TCEB）设备和 证明它的工作原则是针对20名患者的研究。然后，我们将在100中进行临床研究 未经预科的患者证明MM-TCEB收集组织并确定是进展生物标志物 以及镇静的内窥镜检查。在AIM 3中，我们将开发图像分析和深度学习算法来开采 AIM 2数据，发现OCT，自动荧光和反射率光谱之间的新关系 和组织衍生的是进展生物标志物。通过使用可吞咽的束缚来获取目标活检 在未编辑的受试者中，MM-TCEB可以成为获得食管组织的强大技术 BE进展生物标志物发现，验证以及最终基于人群的筛查的样本。