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，发生前会发生称为巴雷特氏癌的化生性改变 食道（BE）。长期以来，人们一直认为内镜筛查 BE 后进行内镜监测 可以显着降低EAC的死亡率。不幸的是，这并没有得到证实，因为成本和 清醒镇静的不便阻碍了内窥镜检查作为基于人群的筛查工具。 由于创新的可吞咽系留胶囊，BE 筛查在未来可能成为可能 无需镇静即可检测 BE 的内窥镜或细胞采样装置。然而，即使这些 胶囊旨在识别美国大量患有 BE (~15M) 的人，内窥镜监测 这个群体的费用将非常昂贵。如果我们可以使用组织生物标志物来识别 5% 的患者 BE那些一生中会发生EAC的人，那么可以对那些真正需要的人进行内镜干预 那些具有低风险 BE 的患者不需要进一步随访。 对这一需求的认识促使该领域识别源自食管的 BE 进展生物标志物 通过自发荧光/反射目标内窥镜检查获得的组织样本。这项研究已确定 非整倍体和异常 p53/细胞周期蛋白 A 表达等生物标志物是 BE 进展的强预测因子。 不幸的是，当今瞄准和获取这些组织的唯一方法是通过镇静内窥镜检查。随着 这里提出的修改是我们开发的一种新的 BE 筛选技术，称为光学相干性 断层扫描（OCT）系留胶囊内显微镜（TCE）可以在不使用镇静剂的情况下进行靶向活检。 OCT-TCE 获得未镇静受试者整个食道的 3D 显微图像，准确识别 BE，并已被初级保健机构的护士和技术人员成功使用。在此，我们建议 通过添加自发荧光和反射光谱成像技术，推进用于靶向活检的 OCT-TCE 这可以帮助识别富含与 BE 进展风险相关的分子改变的组织。新的 胶囊还将具有冷冻活检机制，用于在实时图像下获取目标组织样本 指导。在本提案的目标 1 中，我们将开发这种带有活检的多模态 TCE (MM-TCEB) 设备和 一项对 20 名 BE 患者进行的研究显示，它的作用符合预期。然后，我们将进行100年的临床研究 未镇静的 BE 患者证明 MM-TCEB 收集组织并识别 BE 进展生物标志物 以及镇静内窥镜检查。在目标3中，我们将开发图像分析和深度学习算法来挖掘 Aim 2 数据，揭示 OCT、自发荧光和反射光谱之间的新关系 和组织来源的 BE 进展生物标志物。通过使用可吞咽式系绳获取目标活组织检查 在未镇静的受试者中使用胶囊，MM-TCEB 可以成为获取食管组织的强大技术 用于 BE 进展生物标志物发现、验证和最终基于人群的筛查的样本。