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Early MRI Prediction of Response to Medical Therapy and Mucosal Healing in Small Bowel Crohn's Disease

小肠克罗恩病药物治疗和粘膜愈合反应的早期 MRI 预测

基本信息

批准号：
9767806
负责人：
Jonathan Russell Dillman
金额：
$ 22.2万
依托单位：
CINCINNATI CHILDRENS HOSP MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-21 至 2021-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9767806
关键词：
Acute Address Adult Affect Aftercare Anti-inflammatory Azathioprine Biological Biological Response Modifier Therapy Blood flow Brain Child Childhood Chronic Cicatrix Cine Magnetic Resonance Imaging Clinical Combined Modality Therapy Contrast Media Crohn&apos s disease Data Deposition Development Diagnosis Diagnostic Procedure Diffusion Magnetic Resonance Imaging Disease Disease remission Dose Endoscopy Evaluation Excision Frequencies Functional Magnetic Resonance Imaging Future Gadolinium Gastrointestinal tract structure Goals Health Care Costs Hospitalization Image Imaging Techniques Immunomodulators Incidence Inflammation Inflammatory Inflammatory disease of the intestine Intestinal Motility Intestines Investigation Ionizing radiation Laboratories Lead Magnetic Resonance Imaging Measurement Measures Medical Mesentery Methods Molecular Monitor Morphology Motion Mucous Membrane Newly Diagnosed Operative Surgical Procedures Outcome Patient Care Patients Pattern Perforation Perfusion Peristalsis Pharmaceutical Preparations Phase Physical shape Pilot Projects Radiation Radiation exposure Radiology Specialty Recurrence Reference Standards Reproducibility Research Risk Safety Signal Transduction Surrogate Endpoint TNF gene Techniques Testing Thick Tissues Translating United States Work base cell motility clinical care contrast enhanced effective therapy follow-up healing health related quality of life illness length imaging biomarker improved improved outcome infliximab neonate noninvasive diagnosis novel predicting response programs prospective public health relevance response small bowel Crohn&apos s disease standard of care success treatment response water diffusion young adult

项目摘要

PROJECT SUMMARY Crohn's disease (CD) is a chronic inflammatory condition affecting the gastrointestinal tract of nearly 800,000 children and adults in the United States, and it is characterized by recurrent bouts of acute bowel wall inflammation that frequently lead to intestinal scarring, perforations, and blockages. Currently, effective treatment is limited, with many CD patients undergoing surgical removal of intestine within 10 years of diagnosis. Recent advances in aggressive medical approaches (including biologic therapies, immunomodulators, or combinations thereof) may lead to improved outcomes, including longer remissions with greater mucosal healing and fewer disease-related complications. Radiologic evaluation of CD is typically accomplished by contrast-enhanced CT or MRI. However, both have safety concerns, and our preliminary data suggest it may require months to detect response to biologic therapies. Hence, there is a critical unmet need for safe, objective radiologic measures of intestinal inflammation that can be used for early prediction of durable responses to medical therapy. The long- term objective of this research program is to optimize and test the accuracy of novel nonionizing, noninvasive methods for detecting, measuring, and serially monitoring intestinal inflammation and for predicting ultimate response to medical therapy in small bowel CD. We propose to evaluate the accuracy of several noncontrast, quantitative MRI techniques, including both novel and current standard of care approaches. The central hypothesis of this proposal is that novel functional objective MRI measures can detect and quantify intestinal inflammation as well as provide accurate, early prediction of eventual response to treatment, including endoscopic mucosal healing, particularly when compared to conventional CT and MRI morphologic measurements. Novel MRI techniques to be evaluated in our studies will measure: 1) mesenteric flow (ml/min) and velocity (cm/sec), 2) intestinal peristalsis frequency and pattern, and 3) bowel wall perfusion and molecular water diffusion using an intravoxel incoherent motion (IVIM) approach. Preliminary work by our group has shown that these novel MRI methods can be used to successfully image the bowel of children and adults, including neonates. This application aims to: 1) refine and test novel noncontrast MRI techniques for bowel assessment in healthy control subjects in order to acquire normative data; 2) test novel noncontrast MRI techniques in newly diagnosed small bowel CD patients in order to determine how these markers change in the setting of active intestinal inflammation; and 3) assess the abilities of novel MRI techniques for early prediction of clinical, laboratory, and endoscopic responses to medical therapy in newly diagnosed small bowel CD patients. Data acquired in this pilot study will be used to plan subsequent larger prospective investigations to evaluate if these MRI techniques can guide more personalized patient management strategies, contribute to improved health-related quality of life, lower healthcare costs, and provide new opportunities to test candidate anti-inflammatory medications using noninvasive MRI as a surrogate endpoint.

项目摘要克罗恩病（CD）是一种慢性炎症性疾病，在美国的儿童和成人中，其特征在于急性肠壁的反复发作经常导致肠道瘢痕、穿孔和堵塞的炎症。目前，有效的治疗许多CD患者在确诊后10年内接受了肠切除手术。最近积极的医学方法（包括生物疗法、免疫调节剂或联合疗法）的进展可能导致改善的结果，包括更长的缓解期，粘膜愈合更好，疾病相关并发症。CD的放射学评估通常通过对比增强CT完成或者核磁共振成像然而，两者都有安全问题，我们的初步数据表明，它可能需要几个月的时间来检测对生物疗法的反应。因此，存在对安全、客观的放射学测量的关键未满足的需求，肠道炎症，可用于早期预测药物治疗的持久反应。很长的- 这项研究计划的长期目标是优化和测试新的非电离，非侵入性的准确性，用于检测、测量和连续监测肠道炎症以及预测最终炎症的方法对小肠CD药物治疗的反应。我们建议评估几种非对比定量MRI技术的准确性，包括新的和当前的护理方法标准。这个提议的核心假设是，目的MRI检查可以检测和量化肠道炎症，并提供准确，早期诊断，预测对治疗的最终反应，包括内镜下粘膜愈合，特别是当比较常规CT和MRI形态学测量。在我们的研究中评价的新型MRI技术将测量：1）肠系膜流量（ml/min）和速度（cm/sec），2）肠蠕动频率和模式，和3）使用体素内非相干运动（IVIM）方法的肠壁灌注和分子水扩散。我们小组的初步工作表明，这些新型MRI方法可用于成功成像儿童和成人（包括新生儿）的肠道。该应用程序旨在：1）改进和测试新的非对比度在健康对照受试者中使用MRI技术进行肠道评估，以获得规范数据; 2）新试验在新诊断的小肠CD患者中使用非对比MRI技术，以确定这些在活动性肠道炎症的情况下标志物的变化;和3）评估新的MRI的能力，早期预测临床、实验室和内镜对药物治疗反应的新技术确诊的小肠CD患者。在这项试验性研究中获得的数据将用于规划随后的更大规模的前瞻性研究，以评估这些MRI技术是否可以指导更个性化的患者管理战略，有助于改善与健康相关的生活质量，降低医疗成本，并提供新的使用无创MRI作为替代终点来测试候选抗炎药物的机会。