A tethered capsule endoscopic-endomicroscopic (TEEM) approach for improving upper GI tract diagnosis

大多数上消化道疾病的诊断目前是通过上消化道内镜检查和活检来完成的 （EGD）。EGD是昂贵的，主要是因为它需要清醒镇静，需要程序是 由医生在专门的内窥镜检查室进行，患者需要从工作中抽出时间， 家人另一个限制是采样错误-内窥镜活检经常是随机的，导致许多 错过的疾病。已经提出了诸如非镇静经鼻内窥镜检查（uTNE）的方法 降低EGD的成本。虽然原则上uTNE技术可以在大多数情况下使用，但医生- 相关的费用，病人接受度差，以及无法获得足够的活检，阻碍了其 领养因此，仍然存在未满足的临床需求，需要一种不镇静、更便宜、更安全的药物。 可以取代诊断EGD的技术。 在这项资助中，我们将开发一种结合视频内窥镜和细胞- 在可吞咽的栓系胶囊中的体内显微镜分辨率。一旦被吞下，系留舱 内窥镜-显微内窥镜（TEEM）装置将采集大面积白色光和显微镜图像， 食道、胃和十二指肠。由于患者将不使用镇静剂，因此可以通过以下方式进行手术： 非医生人员在门诊设置，从而提高患者的耐受性，提高效率， 降低成本，从而更好地筛查和治疗这一重要的死亡率/发病率来源。在 目标1，我们将开发TEEM成像系统和胶囊，该系统和胶囊将采用新的横截面，1微米- 分辨率成像模式称为µOCT，这是一种刚度和关节连接的系绳， 胃的导航、侧视白色光图像采集、前视视频，以及用于 配准µOCT和内窥镜成像数据以进行离线审查。在目标2中，我们将进行组织病理学检查 相关活检研究，以确定µOCT诊断最常见上消化道的准确性 疾病TEEM公差，观察者间/观察者内变异性和重测重现性将在55 患者，以验证该技术符合上消化道筛查的临床要求（目标3）。

The diagnosis of most upper GI tract conditions is currently accomplished by upper endoscopy with biopsy (EGD). EGD is costly primarily because it requires conscious sedation, necessitating that procedures be conducted by physicians in a specialized endoscopy suite, and that patients take time away from work and family. Another limitation is sampling error - endoscopic biopsies are frequently random, resulting in many instances of missed disease. Methods such as unsedated transnasal endoscopy (uTNE) have been proposed to decrease the cost of EGD. While in principle uTNE techniques could be used in most cases, physician- associated expense, poor patient acceptance, and an inability to obtain adequate biopsies have hampered its adoption. As a result, there remains an unmet clinical need for an unsedated, less expensive, and more accessible technique that could supersede diagnostic EGD. In this grant, we will develop a replacement for diagnostic EGD that combines video endoscopy with cellular- resolution in vivo microscopy in a swallowable, tethered capsule. Once swallowed, the tethered capsule endoscopy-endomicroscopy (TEEM) device will acquire wide area white light and microscopic images of the esophagus, stomach, and duodenum. Because patients will be unsedated, the procedure can be performed by non-physician personnel in an outpatient setting, thereby improving patient tolerance, increasing efficiency, and lowering costs, resulting in better screening and treatment of this important source of mortality/morbidity. In Aim 1, we will develop the TEEM imaging system and capsule that will incorporate a new cross-sectional, 1-µm- resolution imaging modality known as µOCT, a controllable-stiffness and articulating tether that will facilitate navigation of the stomach, side-viewing white light image acquisition, forward-viewing video, and algorithms for registering µOCT and endoscopy imaging data for offline review. In Aim 2, we will conduct a histopathologic correlative biopsy study to determine the accuracy of µOCT for diagnosing the most common upper GI tract diseases. TEEM tolerance, inter/intra-observer variability, and test-retest reproducibility will then be tested in 55 patients to verify that this technology meets the clinical requirements for upper GI tract screening (Aim 3).