Assessing biomarkers of intestinal fibrosis and inflammation in Crohn's Disease via an endoscopic imaging catheter

通过内窥镜成像导管评估克罗恩病肠道纤维化和炎症的生物标志物

• 批准号: 10033948
• 负责人: Peter D.R. Higgins
• 金额: $ 53.08万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10033948
• 关键词: Acute; Affect; Animal Model; Animals; Anti-Inflammatory Agents; Balloon Dilatation; Biological Markers; Biopsy; Catheters; Chronic; Clinical; Clinical Management; Collagen; Colonoscopes; Complement; Crohn' s disease; Diagnostic; Diagnostic Imaging; Diagnostic Procedure; Digestive System Disorders; Disease; Endoscopic Biopsy; Endoscopy; Excision; Extracellular Matrix; Fibrosis; Future; Gastroenterology; Genes; Hemoglobin; Histopathology; Human; Hyperplasia; Hypertrophy; Image; Imaging Techniques; Imaging technology; Inflammation; Inflammatory; Intestinal Diseases; Intestinal Fibrosis; Intestinal Obstruction; Intestines; Length; Magnetic Resonance Imaging; Measurement; Mechanics; Modality; Modeling; Molecular; Monitor; Morphology; Mucous Membrane; Multivariate Analysis; Muscle; Myofibroblast; Operative Surgical Procedures; Optics; Oryctolagus cuniculus; Outcomes Research; Pathologic; Pathology; Patient-Focused Outcomes; Patients; Performance; Phenotype; Pilot Projects; Procedures; Prognostic Marker; Publishing; Research; Resected; Sampling; Sensitivity and Specificity; Signal Transduction; Small Intestines; Stenosis; Techniques; Technology; Testing; Time; Tissue Sample; Tissues; Translations; Ultrasonic Transducer; Ultrasonography; United States; X-Ray Computed Tomography; absorption; accurate diagnosis; base; chronic autoimmune disease; clinical translation; clinically relevant; elastography; experimental study; human subject; human tissue; imaging approach; imaging biomarker; imaging modality; improved; in vivo; in vivo Model; inflammatory disease of the intestine; innovation; instrument; molecular marker; molecular pathology; novel; personalized therapeutic; photoacoustic imaging; pressure; prognostic; success; tool

ABSTRACT Crohn’s disease (CD) produces chronic intestinal bowel damage and stenosis in the majority of patients. Accurate characterization of these strictures is critical, as acute inflammatory strictures can respond to anti- inflammatory therapy, but chronic strictures, which include both fibrosis and muscular hypertrophy, require surgical resection. Intestinal fibrosis is an important predictor of future intestinal obstruction and penetrating complications of CD. The standard diagnostic procedure for CD is endoscopic biopsy, in which small pieces of tissue are removed from the innermost layer of the intestine for histopathology. Due to limited sampling depth, endoscopic biopsy does not assess fibrosis in submucosal and muscular layers. Conventional non-invasive modalities, such as MRI, CT and ultrasound (US), have shown limited sensitivity for intestinal fibrosis. Intestinal strictures are often a mixture of chronic fibrosis and acute inflammation, which are respectively correlated with increased collagen and hemoglobin in tissues, which act as molecular markers of distinct CD pathologies. In addition, extensive previous studies of compressional US elastography have documented that increased stiffness is a mechanical marker of chronic fibrotic strictures. These molecular and mechanical markers complement each other, providing orthogonal diagnostic information. A diagnostic imaging procedure that can simultaneously assess these phenotypes of CD is highly desirable for personalized therapeutic planning and improved patient outcomes. Our preliminary studies in animals in vivo, human tissue samples ex vivo, and in human subjects have validated that the molecular and mechanical markers of CD stricture pathology can be characterized by advanced photoacoustic (PA)-US dual modality imaging approaches, including spectroscopic PA imaging, US elastography, and our recent innovation of strain-PA imaging. An imaging catheter probe compatible with standard ileocolonoscopy procedures, integrating all these imaging technologies, has been developed and validated with tissue samples and in animals in vivo. Encouraged by our exciting preliminary results, we propose to fill this long-standing prognostic gap with accurate characterization of molecular and mechanical phenotypes of CD. In the proposed project, we will first objectively assess the sensitivity and specificity of each molecular and mechanical marker quantified by the proposed imaging technology through experiments on clinically relevant rabbit models. In addition, to pave the road to clinical translation, we will examine the feasibility and identify the limitations of the proposed technique for use during clinical ileocolonoscopy via a pilot study in CD patients. The success of this project will advance these molecular and mechanical biomarkers of distinct pathologies in CD strictures to practical clinical measurement with PA-US dual modality endoscopic imaging, enabling accurate prognostic assessment and treatment monitoring in CD.

摘要