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

项目总结 克罗恩病(CD)是一种慢性炎症性疾病，影响着近80万人的胃肠道 在美国的儿童和成人，它的特点是急性肠壁反复发作 经常导致肠道结疤、穿孔和堵塞的炎症。目前，有效的治疗 是有限的，许多CD患者在确诊后10年内接受了肠道切除手术。近期 侵略性医学方法(包括生物疗法、免疫调节剂或其组合)的进展 可能导致改善结果，包括缓解时间更长，粘膜愈合更好，而粘膜愈合更少 与疾病相关的并发症。CD的放射学评估通常通过增强CT来完成 或者核磁共振。然而，两者都存在安全问题，我们的初步数据表明，可能需要几个月的时间才能检测到 对生物疗法的反应。因此，存在对安全、客观的放射治疗措施的迫切需求。 肠道炎症可用于早期预测药物治疗的持久反应。长的- 本研究计划的学期目标是优化和测试新型非电离、非侵入性 检测、测量和连续监测肠道炎症并预测最终结果的方法 小肠CD对药物治疗的反应。 我们建议评估几种非对比度、定量磁共振成像技术的准确性，包括两者 新的和当前的护理标准方法。这一提议的中心假设是新的功能 目的MRI检查可以检测和量化肠道炎症，并能准确、早期地提供 预测最终的治疗反应，包括内窥镜下的粘膜愈合，特别是当进行比较时 常规CT和MRI的形态测量。新的磁共振成像技术将在我们的研究中进行评估 将测量：1)肠系膜血流量(毫升/分钟)和速度(厘米/秒)，2)肠蠕动频率和模式， (3)采用体素内非相干运动(IVIM)方法进行肠壁灌注和分子水扩散。 我们课题组的初步工作表明，这些新的MRI方法可以成功地用于成像 儿童和成人的肠道，包括新生儿的肠道。这个应用程序的目的是：1)提炼和测试新的非对比度 用于健康对照受试者肠道评估的MRI技术，以获得标准化数据；2)测试新奇 新诊断的小肠CD患者的MRI平扫技术 活动性肠炎环境中标志物的变化；3)评估新MRI的能力 早期预测新药治疗的临床、实验室和内窥镜反应的技术 诊断为小肠CD患者。在这项初步研究中获得的数据将用于规划后续更大规模的 评估这些MRI技术是否可以指导更个性化的患者管理的前瞻性研究 战略，有助于提高与健康相关的生活质量，降低医疗成本，并提供新的 使用非侵入性MRI作为替代终点测试候选抗炎药物的机会。

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.