Natural History of Barrett's Esophagus Using Capsule Endomicroscopy

描述（由申请方提供）：Barrett食管（BE）是一种正常食管鳞状粘膜因慢性酸反流而变为化生柱状粘膜的疾病。BE可进展为食管腺癌（EAC），这是一种流行（每年约12，000例）和致命的癌症（5年死亡率约15%）。目前的BE管理策略，如抗反流治疗、内镜筛查和定期内镜活检监测和消融治疗，在很大程度上对降低EAC的死亡率无效。标准治疗失败的一个重要原因是我们对BE的微观自然史/演变缺乏了解，这导致了对其定义的争议、其进展和临床意义的不确定性以及无法评价药理学和消融治疗的有效性。出现这些问题的部分原因是用于研究BE的唯一方法是内窥镜活检，这是侵入性的，昂贵的，并受到严重的活检取样限制。我们的实验室已经开发出一种新的成像概念，称为栓系胶囊显微内镜（TCE），克服了这些局限性的内镜活检。TCE涉及吞咽拴系胶囊，当其通过食道穿过管腔器官或使用系绳被拉向口腔时，该胶囊获取整个食管壁的三维显微图像。与内窥镜检查相反，TCE通过评估整个食管的显微结构来减少采样误差。TCE手术可以在未使用镇静剂的患者中进行，使其比内窥镜检查更简单，更快，耐受性更好，并且更便宜。我们展示的第一个TCE原型使用光学相干断层扫描（OCT）以10 μ m的分辨率获得食管微观结构的横截面图像。在这个建议中，我们将进一步推进TCE技术相结合的OCT与高速反射共聚焦显微镜技术称为光谱编码共聚焦显微镜（SECM），以便获得建筑和细胞形态信息可以从同一设备。此外，我们还将整合一个位置传感器，允许在不同时间点从同一患者处采集的显微镜数据集相互配准。一旦开发出这种器械，我们将在一项多中心（5个中心）临床试验中使用TCE来研究500名患者的BE自然史。每年对所有患者进行一次成像，持续3年（1500患者-年），并对TCE图像进行评价，以确定BE如何随时间变化。这项研究的结果将大大有助于BE的知识，使我们能够回答长期存在的问题，其微观定义，其进展和临床意义，以及消融BE治疗的有效性。从这项研究中获得的知识将用于改善BE管理策略的基础上，强有力的科学证据，这种疾病的自然史。

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.