Natural History of Barrett's Esophagus Using Capsule Endomicroscopy

使用胶囊内镜检查巴雷特食管的自然史

• 批准号: 9277434
• 负责人: Guillermo J Tearney
• 金额: $ 67.83万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-04 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9277434
• 关键词: Ablation; Acids; Address; Architecture; Area; Barrett Esophagus; Biopsy; Biopsy Specimen; Cell Nucleus; Cellular Morphology; Chronic; Clinical Research; Clinical Trials; Columnar Metaplasia; Complex; Confocal Microscopy; Data; Data Set; Deglutition; Development; Devices; Diagnosis; Dimensions; Disease; Dysplasia; Effectiveness; Endoscopic Biopsy; Endoscopy; Engineering; Epithelial; Esophageal; Esophageal Adenocarcinoma; Esophageal mucous membrane; Esophagus; Evolution; Failure; Goblet Cells; Histologic; Image; Incidence; Inpatients; Knowledge; Laboratories; Left; Location; Longitudinal Studies; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of esophagus; Maps; Medicine; Metaplasia; Metaplastic; Methods; Microscopic; Mucous Membrane; Natural History; Nature; Optical Coherence Tomography; Oral cavity; Organ; Outpatients; Patients; Penetration; Peristalsis; Pharmacology; Positioning Attribute; Practice Guidelines; Procedures; Reflux; Research; Resolution; Sampling; Sampling Errors; Site; Societies; Spatial Distribution; Specimen; Speed; Squamous Epithelium; Structure; Surface; Techniques; Technology; Testing; Thick; Time; Tissues; Uncertainty; Validation; Withdrawal; base; cancer type; capsule; clinically significant; cost; design; disease natural history; imaging modality; improved; in vivo; microendoscopy; microscopic imaging; mortality; pill; prevent; prospective; prototype; public health relevance; radiofrequency; reflectance confocal microscopy; response; safety and feasibility; screening; sensor; standard of care

DESCRIPTION (provided by applicant): Barrett's esophagus (BE) is a condition where normal esophageal squamous mucosa changes to metaplastic columnar mucosa in response to chronic acid reflux. BE can progress to esophageal adenocarcinoma (EAC), a prevalent (~12,000 cases per year) and deadly cancer (~15% 5-year mortality rate). Current BE management strategies of anti-reflux therapy, endoscopic screening, and regular endoscopic biopsy surveillance and ablation therapy, has been largely ineffective for decreasing the mortality of EAC. One important reason for the failure of the standard of care is our lack of understanding of the microscopic natural history/evolution of BE which has led to controversies about its definition, uncertainty regarding its progression and clinical significance, and an inability to evaluate the effectiveness of pharmacologic and ablative therapies. These questions have arisen in part because the only method used to study BE is endoscopic biopsy, which is invasive, costly, and suffers from severe biopsy sampling limitations. Our laboratory has developed a new imaging concept termed tethered capsule endomicroscopy (TCE) that overcomes these limitations of endoscopic biopsy. TCE involves swallowing a tethered capsule that acquires three-dimensional microscopic images of the entire esophageal wall as it traverses the luminal organ via peristalsis or is pulled up towards the mouth using the tether. As opposed to endoscopy, TCE mitigates sampling error by evaluating the microscopic structure of the entire esophagus. The TCE procedure can be conducted in unsedated patients, making it simpler, faster, better tolerated, and less expensive than endoscopy. The first TCE prototype that we have demonstrated uses optical coherence tomography (OCT) to obtain cross-sectional images of the microscopic architecture of the esophagus at a resolution of 10 �m. In this proposal, we will advance TCE technology further by combining OCT with a high-speed reflectance confocal microscopy technique called spectrally encoded confocal microscopy (SECM) so that obtain both architectural and cellular morphologic information can be obtained from the same device. We will additionally incorporate a position sensor that will allow microscopic datasets acquired from the same patients at different time points to be registered to one another. Once this device is developed, we will utilize TCE in a multicenter (5-site) clinical trial to study the natural history of BE in 500 patients. Imaging will be conducted on a yearly basis in all patients for a duration of 3 years (1500 patient-years) and the TCE images will be evaluated to determine how BE changes over time. The results of this study will significantly contribute to the knowledge of BE, allowing us to answer longstanding questions about its microscopic definition, its progression and clinical significance, and the effectiveness of ablativ BE therapies. The knowledge gained from this study will be used to improve BE management strategies based on strong scientific evidence about the natural history of this disease.

描述（由适用提供）：Barrett的食管（BE）是一种正常食管鳞状粘膜变成慢性酸反流的变性柱状粘膜。 BE可以发展为食管腺癌（EAC），普遍存在（每年约12,000例）和致命癌症（约15％5年死亡率）。当前是抗反复治疗，内窥镜筛查以及定期内窥镜活检监测和消融疗法的管理策略，对于降低EAC的死亡率而言，基本上是无效的。护理标准失败的一个重要原因是，我们缺乏对微观自然历史/BE的演变的了解，这导致了有关其定义，其进展和临床意义的不确定性以及无法评估药理学和含量疗法的有效性的争议。这些问题之所以出现，部分原因是研究是内窥镜活检，它具有侵入性，昂贵，并且受到严重的活检采样限制。我们的实验室已经开发了一种新的成像概念，称为束缚胶囊内分子镜（TCE），该概念克服了内窥镜活检的这些局限性。 TCE涉及吞咽束缚胶囊，该胶囊获得了整个食管壁的三维显微镜图像，因为它通过蠕动遍历了腔内器官，或使用系绳将其拉向嘴。与内窥镜相反，TCE通过评估整个食道的微观结构来减轻采样误差。可以在未编辑的患者中进行TCE手术，使其比内窥镜更简单，更快，耐受性且价格便宜。我们展示的第一个TCE原型使用光学相干断层扫描（OCT）以10 r分辨率的分辨率获得食道显微镜结构的横截面图像。在此提案中，我们将通过将OCT与称为光谱编码的共聚焦显微镜（SECM）结合使用OCT来进一步推进TCE技术，从而可以从同一设备中获得架构和细胞形态学信息。我们还将合并一个位置传感器，该传感器将允许在不同时间点从同一患者获取的微观数据集彼此注册。一旦开发了该设备，我们将在多中心（5点）临床试验中使用TCE来研究500名患者的BE的自然病史。成像将在所有患者中每年进行3年（1500名患者年）的时间，并将评估TCE图像，以确定随时间变化的变化。这项研究的结果将极大地有助于BE的知识，使我们能够回答有关其微观定义，其进展和临床意义以及Ablativ的有效性的长期问题。这项研究所获得的知识将用于改善基于有关该疾病自然史的有力科学证据的管理策略。