Novel MRI Imaging Tools and Software for Assessing Pediatric Crohn's Disease

描述（由申请人提供）：美国估计有140万人患有炎症性肠病（IBD），其中一半被认为患有克罗恩病（CD），这是IBD的两种主要形式之一，沿着溃疡性结肠炎。至少有10%的人<18岁。我们对PAR-07-344“用于评估小儿克罗恩病的新型MRI成像工具和软件”（pCD）下的生物医学和计算科学与技术创新的回应旨在开发和改进一种新型参数成像-加速空间约束非相干运动MRI（aSCIM-MRI）-作为细胞增殖、密度和大小以及组织灌注的高度准确的定量生物标志物-表征疾病活动程度的所有指标（即，炎症）在肠的组织微结构中。如果成功的话，这种非侵入性、无辐射的技术将构成对当前参考标准（即，磁共振肠造影术（MRE）、临床检查、血液检查和组织学）。具体而言，a-SCIM-MRI有望大幅提高我们评估pCD炎症活动的能力;监测对治疗的反应;评估手术干预的需要;制定针对个体疾病特征的治疗计划;并预测复发的可能性。在这些雄心勃勃的目标，我们将承担以下具体目标：1）以确定是否空间约束的信号衰减模型（SCIM-MRI）提高了弥散加权MRI（DW-MRI）的快速和慢速弥散定量的可靠性; 2）使用基于贝叶斯模型的重建加速SCIM-MRI采集时间（aSCIM-MRI）;和3）评估快速和缓慢扩散组分在区分pCD中的活动性炎症与纤维化方面的功效，如通过组织病理学发现所确定的。在美国国立卫生研究院的支持下，这些预期的研究成果将大大改善对最衰弱的肠道疾病的管理，这种疾病的诊断通常是难以捉摸的，并且在诊断时，治疗具有挑战性;部分原因是最佳疗法对儿童来说有些有限。部分原因是目标人群开始就很脆弱，因此更容易受到强生物药物的毒性和与手术相关的并发症（短期和长期）的影响。鉴于高达75%的CD儿童在其生命中的某个时刻必须接受肠切除术，并且鉴于这些手术很少治愈的事实，对提高评估能力的需求从未如此之大。因此，这种高度创新的成像方法aSCIM-MRI不仅有望创建一种新的参考标准，用于评估、监测和治疗pCD;一旦将其引入常规临床成像，还有望产生快速的转化影响。该项目的第二个重要总体目标是开发和广泛传播开源软件，该软件将使目前使用DW-MRI评估的其他疾病的标准化评估成为可能，并将受益于aSCIM-MRI的先进诊断和评估能力。

DESCRIPTION (provided by applicant): An estimated 1.4 million people in the United States suffer from inflammatory bowel disease (IBD), half of whom are believed to have Crohn's disease (CD), one of two primary forms of IBD along with ulcerative colitis. At least 10% are <18. Our response to Innovations in Biomedical and Computational Science and Technology under PAR-07-344, "Novel MRI Imaging Tools and Software for Assessing Pediatric Crohn's Disease" (pCD), is aimed at developing and refining a new type of parametric imaging- accelerated spatially constrained incoherent motion MRI (aSCIM-MRI)-as a highly accurate quantitative biomarker for cell proliferation, density and size, and tissue perfusion-all indices tat characterize the extent of disease activity (i.e., inflammation) in the tissue micro-structure of te bowel. If successful, this non-invasive, radiation-free technique will constitute a dramatic improvement over current reference standards (i.e., magnetic resonance enterography (MRE), clinical exam, blood tests, and histology), separately, and in combination. Specifically, a-SCIM-MRI is expected to substantially improve our ability to assess inflammatory activity in pCD; monitor response-to-therapy; evaluate the need for surgical intervention; develop treatment plans that are tailored to individual disease profiles; and predict the likelihood of recurrence. T these ambitious ends, we will undertake the following Specific Aims: 1) to determine whether a spatially constrained signal decay model (SCIM-MRI) improves the reliability of fast and slow diffusion quantification from diffusion-weighted MRI (DW-MRI); 2) to accelerate SCIM-MRI acquisition time with a Bayesian model-based reconstruction (aSCIM-MRI); and 3) to assess the efficacy of fast and slow diffusion components at distinguishing active inflammation from fibrosis in pCD as determined by histopathological findings. With the support of the NIH, these anticipated research accomplishments will result in vastly improved management of a most debilitating bowel disease, the diagnosis of which is often elusive, and on diagnosis, challenging to treat; in part because optimal therapies are somewhat limited for children; and in part because the target population is developmentally fragile to begin with, and thus more susceptible to toxicity from strong biologic drugs and to the complications (both short- and long-term) associated with surgery. Given the fact that up to 75% of children with CD must undergo a bowel resection as some point in their lives, and given the fact that these surgeries are rarely curative; the demand to improve assessment capabilities has never been greater. This highly innovative imaging approach, aSCIM-MRI, is therefore expected not only to create a new reference standard by which pCD is evaluated, monitored, and treated; it is also expected to have rapid translational impact once it is introduced into routine clinical imaging. A second, important overall goal of this project is to develop and broadly disseminate open source software will enable the standardized evaluation of other diseases that are presently evaluated with DW-MRI and would benefit from the advanced diagnostic and assessment capabilities of aSCIM-MRI.