Robust quantitative MR imaging markers of response to therapy in Crohn’s Disease

项目总结： 克罗恩病(CD)是一种慢性胃肠道炎症性疾病，患病率为 仅在美国就有超过80万人。经济影响非常大，因为它主要影响年轻人 个人。特殊的缓解期和复发期需要频繁住院。那里 最近在临床实践中从被动的CD治疗策略转变为主动的CD治疗策略，最近发明 作为“治疗对目标”，患者的治疗不仅是为了达到最初的治疗反应，而且还包括 更长的临床缓解时间和改善的粘膜愈合。但是，这种方法需要常规的 使用客观标记物评估疾病活动性，使治疗能够针对个人量身定做 有耐心的。因此，对提高诊断准确性、量化疾病的新工具的需求尚未得到满足 负担，并监测治疗效果。我们的应用程序响应PAR-19-056 克隆氏病治疗反应的定量磁共振成像标记物“旨在开发 以及评估非侵入性、对比度和无辐射的定量成像标记物 疾病活动和监测对治疗的反应。目前可用的非对比磁共振成像 (MRI)序列，例如扩散加权MRI(DW-MRI)和计算的表观扩散系数 (ADC)地图很有吸引力，但在提供健壮和可重现的标记方面存在局限性。不同的成像协议 或者不同的扫描仪产生不同的ADC值。我们的首要目标是开发健壮可靠的 定量DW-MR成像标记物用于CD的非对比度和非侵入性评估。建议数 新的磁共振成像采集和模型拟合技术也将提供慢扩散和快扩散的测量 作为快速扩散的一部分，作为细胞增殖、密度和大小的高精度、定量的生物标志物， 和组织灌注-所有表征组织中疾病活动(即炎症)程度的指标 肠道的微结构。为了实现这一目标，我们将首先开发和实施高级失真 和运动校正(DIMOCO)DW-MRI技术和空间受限概率体素 非相干运动(SPIM)模型，用于计算健壮且可重现的标记。接下来，我们将减少 通过加速的图像采集和全新的高级深度，估计x4加速的成像时间 基于学习的参数估计技术。拟议的成像技术和软件工具将 提供可靠的量化指标，从而能够准确评估裁谈会的活动和对 心理治疗。它们还将减少对侵入性内窥镜检查程序的需求，以及其他 通常用于监测疾病的检查，有效地减轻了疾病负担和总成本 在医疗保健方面。另一个重要目标是开发和广泛传播开放源码软件， 实现目前使用DW-MRI评估的其他疾病的标准化评估，这些疾病将受益于 建议的DIMOCO SPIM-DW-MRI技术的高级诊断和评估能力。

Project Summary: Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract that has a prevalence of over 800,000 in the US alone. The economic impact is disproportionally high because it affects primarily young individuals. The characteristic periods of remission and relapse necessitate frequent hospitalizations. There has been a recent shift in clinical practice from a reactive to a proactive CD treatment strategy, recently coined as “treat-to-target”, where patients are treated to achieve not only an initial response-to-therapy, but also longer clinical remissions and improved mucosal healing. However, this approach requires the regular assessment of disease activity using objective markers enabling treatments to be tailored to the individual patient. Therefore, there is an unmet need for new tools to improve diagnostic accuracy, to quantify disease burden, and to monitor treatment efficacy. Our application in response to PAR-19-056, “Robust quantitative MR imaging markers of response to therapy in Crohn's disease” is aimed at developing and evaluating noninvasive, contrast and radiation-free quantitative imaging markers for assessing disease activity and for monitoring response to therapy. Currently available non-contrast MR imaging (MRI) sequences such as diffusion-weighted MRI (DW-MRI) and the calculated apparent diffusion coefficient (ADC) maps are attractive but limited in providing robust and reproducible markers. Different imaging protocols or different scanners result in different ADC values. Our primary goal is to develop robust and reliable quantitative DW-MR imaging markers for the non-contrast and non-invasive assessment of CD. The proposed novel MRI acquisition and model fitting techniques will provide measurements of slow and fast diffusion as well as fraction of fast diffusion, as highly accurate, quantitative biomarkers for cell proliferation, density and size, and tissue perfusion—all indices that characterize the extent of disease activity (i.e., inflammation) in the tissue micro-structure of the bowel. To achieve this goal, we will first develop and implement an advanced distortion and motion corrected (DiMoCo) DW-MRI technique and a spatially constrained probabilistic intravoxel incoherent motion (SPIM) model to compute robust and reproducible markers. Next, we will reduce the imaging time with estimated x4 acceleration with an accelerated image acquisition and a new, advanced deep learning-based parameter estimation technique. The proposed imaging techniques and software tools will provide robust quantitative markers, thereby enabling the accurate assessment of CD activity and response to therapy. They will also reduce the need for invasive endoscopy procedures as well as the total number of other tests typically ordered for monitoring disease, effectively reducing both the disease burden and the overall cost of healthcare. Another important goal is to develop and broadly disseminate open source software that will enable the standardized evaluation of other diseases presently evaluated with DW-MRI that would benefit from the advanced diagnostic and assessment capabilities of the proposed DiMoCo SPIM-DW-MRI technique.