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

描述(申请人提供)：据估计，美国有140万人患有炎症性肠病(IBD)，其中一半人被认为患有克罗恩病(CD)，这是IBD的两种主要形式之一，并伴有溃疡性结肠炎。我们根据PAR-07-344《用于评估儿科克罗恩病的新型MRI成像工具和软件》(PCD)对生物医学和计算科学与技术的创新的响应，旨在开发和完善一种新型的参数成像-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度的高精度定量生物标志物-所有指标TAT都表征肠道组织微结构中的疾病活动程度(即炎症)。如果成功，这种非侵入性、无辐射的技术将构成对当前参考标准(即磁共振肠成像(MRE)、临床检查、血液测试和组织学)的显著改进，无论是单独还是联合使用。具体地说，a-SCIM-MRI有望显著提高我们评估PCD炎症活动、监测治疗反应、评估手术干预的必要性、制定针对个别疾病特征量身定制的治疗计划以及预测复发可能性的能力。为了实现这些雄心勃勃的目标，我们将致力于以下具体目标：1)确定空间受限信号衰减模型(SCIM-MRI)是否提高了扩散加权MRI(DW-MRI)快速和慢速扩散量化(DW-MRI)的可靠性；2)通过基于贝叶斯模型的重建(aSCIM-MRI)加快SCIM-MRI的采集时间；以及3)评估快速和慢速扩散成分在区分PCD活动性炎症和纤维化方面的有效性。在美国国立卫生研究院的支持下，这些预期的研究成果将极大地改善对一种最虚弱的肠道疾病的管理，这种疾病的诊断往往难以捉摸，而且在诊断时，治疗起来具有挑战性；部分原因是儿童的最佳治疗方法在某种程度上是有限的；部分原因是目标人群从一开始就发育脆弱，因此更容易受到强效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。鉴于多达75%的CD儿童在一生中的某个阶段必须接受肠道切除，而且这些手术很少治愈，因此对提高评估能力的需求从未像现在这样大。因此，这种高度创新的成像方法aSCIM-MRI不仅有望创造一个新的参考标准，用于评估、监测和治疗PCD；一旦将其引入常规临床成像，也有望产生快速的翻译影响。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，该软件将能够对目前使用DW-MRI评估的其他疾病进行标准化评估，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.