Celiac Disease Diagnosis using Tethered Capsule Endomicroscopy

使用系留胶囊内镜检查进行乳糜泻诊断

• 批准号: 8760911
• 负责人: Guillermo J Tearney
• 金额: $ 47.26万
• 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: 2014-09-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8760911
• 关键词: Adherence; Affect; Age; Architecture; Area; Autoimmune Diseases; Autoimmune Responses; Back; Biopsy; Cauterization - action; Celiac Disease; Cells; Cereals; Clinical; Clinical Research; Color; Confocal Microscopy; Data Set; Deglutition; Devices; Diabetes Mellitus; Diagnosis; Diagnostic; Diet; Disease; Duodenum; Endoscopic Biopsy; Endoscopy; Engineering; Epithelial; Epithelium; Esophagus; Excision biopsy; Family suidae; Food; Gastrointestinal Diseases; Gastrointestinal tract structure; General Population; Gluten; Goals; Gold; Guidelines; Health; Healthcare Systems; Height; Histologic; Histology; Hyperplasia; Image; Immune response; Incidence; Individual; Inflammation; Inflammatory; Lasers; Life Style; Lymphocyte; Lymphocytic Infiltrate; Malabsorption Syndromes; Malignant Neoplasms; Malnutrition; Medicine; Microscope; Microscopic; Morphologic artifacts; Morphology; Mucous Membrane; Nature; Optical Coherence Tomography; Organ; Painless; Patients; Peristalsis; Population; Procedures; Proteins; Pylorus; Reaction; Reading; Regimen; Relative (related person); Research; Resolution; Safety; Sampling; Sampling Errors; Sedation procedure; Sensitivity and Specificity; Site; Small Intestines; Speed; Stomach; Symptoms; System; Techniques; Technology; Testing; Time; Tissues; Uncertainty; Upper digestive tract structure; Variant; Villous; Villus; Vitamins; Wheat; capsule; cost; cost effective; design; disease diagnosis; gastrointestinal symptom; human subject; imaging modality; improved; in vivo; intraepithelial; mortality; multimodality; new technology; pill; psychosocial; sex; standard of care; tissue processing; tool; validation studies

DESCRIPTION (provided by applicant): Celiac disease (CD) is an autoimmune response to gluten proteins that affects 3M people in the US and 50M worldwide. These proteins incite an inflammatory reaction that eventually destroys the absorptive villi in the duodenum, resulting in gastrointestinal symptoms, malabsorption, malnutrition, and an increased incidence of other autoimmune diseases, diabetes, and cancer. A definitive diagnosis of CD is made by random endoscopic biopsy with microscopic findings of cellular and architectural changes in the duodenal mucosa. CD can be effectively cured by adherence to a gluten free diet (GFD). Since a GFD is a lifelong commitment that is expensive, difficult to comply with, and can have psychosocial implications, the vast majority of patients are not placed on this regimen unless they have biopsy-confirmed disease. Duodenal endoscopic biopsy is a poor gold standard that suffers from many flaws. Because endoscopic biopsy typically requires sedation, the procedures are expensive and can be difficult to tolerate. Random duodenal biopsy also only samples a very small portion of the duodenal wall. Since the disease is often patchy, it is very common for those with the disease to have multiple negative biopsy results. Tissue processing artifacts and lack of standards for acquiring and interpreting the biopsies also contribute to diagnostic uncertainty. To a large part, these problems with endoscopic biopsy have led to massive delays and underdiagnosis of CD in the population. This problem must be solved because untreated CD is associated with a 2-4x increase in mortality, the cost of which exceeds $30B/year in the US. We have developed a new technology called tethered capsule endomicroscopy (TCE) that overcomes the limitations of endoscopic biopsy. TCE involves swallowing an optomechanically-engineered pill that captures three-dimensional microscopic images of the gastrointestinal (GI) tract as it descends via peristalsis. Our first results with this technology demonstrated that the microstructure of the entire esophagus can be imaged in just a few minutes in a simple, rapid, and painless procedure. In this proposal, we will advance TCE technology further so that it is optimized for imaging the entire duodenum and diagnosing CD. The new device, termed multimodality TCE (MM-TCE) will incorporate multiple imaging modalities that are specifically designed for CD diagnosis in vivo: 1) optical coherence tomography (OCT) for imaging the depth-dependent architectural changes such as duodenal blunting, 2) SECM for visualizing the lymphocytic infiltrate in the epithelium, and 3) video imaging so that the device can be quickly navigated through the stomach into the duodenum. Once the MM-TCE system and device has been constructed, clinical validation studies will be conducted to determine the accuracy of this device compared to corresponding histology and the diagnostic yield relative to endoscopic duodenal biopsy. The end product of this research will be a swallowable capsule microscope that avoids sampling error by imaging the entire duodenum, is less expensive, and better tolerated than the current standard of care. Beyond its immediate clinical impact for CD, this capsule technology will also transform how we obtain microscopic tissue diagnoses for other disorders of the upper GI tract.

描述（由申请人提供）：乳糜泻（CD）是对面筋蛋白的自身免疫反应，影响了美国和全球50m的3M人。这些蛋白会引起炎症反应，最终破坏了十二指肠的吸收性绒毛，导致胃肠道症状，吸收不良，营养不良，以及其他自身免疫性疾病，糖尿病和癌症的发病率增加。 CD的明确诊断是通过随机内窥镜活检对十二指肠粘膜中细胞和建筑变化的微观发现进行的。 CD可以通过遵守无麸质饮食（GFD）有效地治愈。由于GFD是一生的承诺，很昂贵，难以遵守并且可能具有社会心理意义，因此，除非患有活检证实的疾病，否则绝大多数患者不在该方案上。十二指肠内窥镜活检是遭受许多缺陷的差黄金标准。由于内窥镜活检通常需要镇静，因此该程序很昂贵，而且很难容忍。随机十二指肠活检也只为十二指肠壁的一小部分采样。由于该疾病通常是斑点的，因此患有多次活检的患者非常普遍。组织处理工件以及缺乏获取和解释活检的标准也有助于诊断不确定性。在很大程度上，这些内窥镜活检的问题导致人群中CD的延迟和诊断不足。必须解决此问题，因为未经处理的CD与死亡率增加了2-4倍，其成本超过了美国/年的30B美元。我们已经开发了一种称为束缚胶囊内镜（TCE）的新技术，该技术克服了内窥镜活检的局限性。 TCE涉及吞咽光学工程的药丸，该药丸捕获了胃肠道（GI）的三维显微镜图像，因为它通过蠕动下降。这项技术的第一个结果表明，在简单，快速且无痛的过程中，可以在几分钟内成像整个食道的微观结构。在此建议中，我们将进一步推进TCE技术，以便对整个十二指肠和诊断CD进行优化。该新设备称为多模式TCE（MM-TCE）将结合多种成像模式，专门为CD诊断而设计，用于体内CD诊断：1）光学相干性层析成像（OCT），用于成像深度依赖性的建筑变化，例如Duododenal blunting，2），2）可视化淋巴细胞的自然插入设备，并逐渐渗透性，并在透明度上进行视频，并3型透明式渗透性，并3）胃进入十二指肠。一旦构建了MM-TCE系统和设备，将进行临床验证研究，以确定该设备的准确性与相应的组织学和相对于内窥镜十二指肠活检的诊断产量相比。这项研究的最终产物将是可吞咽的胶囊显微镜，通过对整个十二指肠进行成像，避免采样误差，比当前的护理标准更便宜，并且耐受性更好。除了其对CD的直接临床影响外，该胶囊技术还将改变我们如何获得上胃肠道其他疾病的微观组织诊断。