Project 3: A Novel Simultaneous Multiparametric MRI Approach for the Quantitative Assessment of Non-alcoholic Fatty Liver Disease

项目摘要-项目3（Rettenmeier） 非酒精性脂肪性肝病（NAFLD）已成为世界上主要的健康问题， 由于营养过剩和久坐不动， 生活方式因此，改善饮食习惯对于降低疾病发作和进展的风险至关重要。但是，在这方面， 疾病进展的驱动因素尚未完全了解，可靠的非侵入性工具来监测和 因此，迫切需要对肝脏变化进行表征，以改善风险评估和干预措施。NAFLD是 其特征在于肝脏中的脂肪积累，包括单纯性非酒精性脂肪肝和更多的 进行性非酒精性脂肪性肝炎（NASH）。NASH与纤维化的发展密切相关， 肝硬化和肝细胞癌使用电流区分良性NAFLD和NASH 非侵入性诊断工具仍然具有挑战性，并且通常需要活组织检查来进行明确的诊断。关键 NASH的组织学特征包括脂肪变性、坏死性炎症和纤维化的程度， 与铁超载有关。其中，纤维化阶段已被证明是最可靠的预测因子 肝脏相关的死亡率，并提出了一个突出的目标，为发展新的成像技术。 磁共振弹性成像（MRE）被认为是成像的金标准，其目标是增加 基于硬度测量的纤维化肝组织中的细胞外基质。最近，多参数MRI（mp- MRI）方法已经发展到使用MR弛豫法来评估细胞外液（ECF）的增加 体积作为纤维化的量度。这些方法使用T2* 映射来解释铁沉积， ECF体积评估中的主要混杂因素。磁共振成像和核磁共振成像技术都显示 然而，仍需要改进特异性和准确性。我们的长期目标是 开发了一种新的基于QSM的多参数MRI方法（QSMmp-MRI），该方法解决了 先前的mp-MRI技术，通过将定量磁化率映射（QSM）的方法。QSM 对磁活性铁化合物如铁蛋白和含铁血黄素具有高特异性， 改善NASH患者铁负荷的定量，从而间接提高 在肝组织中的相应ECF体积测量。总的来说，这项新技术将使评估 肝组织参数，如纤维化、炎症、脂肪变性和铁负荷。的目的 建议是实施QSMmp-MRI序列，并在试点研究中进行初步测试， 无创MRE作为参考。在目标1中，我们将开发一组MR序列，以量化T1、T2*、磁共振成像（MRI）和磁共振成像（MRI）。 磁化率和基于运动鲁棒径向采样的质子密度脂肪分数图。不同采集 将测试模式，并在离体模和健康志愿者上评价性能。在目标2中， 将进行一项非侵入性初步研究，以比较新的QSMmp-MRI技术与MRE在48例NASH中的应用 患者作为主要验证步骤。该研究将与Waitland Coast合作进行 综合健康中心和女王医疗中心，并将通过与当地社区接触， Waithehana产品处方（WOPRx）项目（GusNIP，美国农业部）。

Project Summary – Project 3 (Rettenmeier) Nonalcoholic fatty liver disease (NAFLD) has emerged as a major health concern in the world and is fueled by the growing pandemic of obesity and insulin resistance as a consequence of overnutrition and a more sedentary lifestyle. Thus, improving dietary habits is crucial to reduce the risk of disease onset and progression. However, the drivers for disease progression are not fully understood, and reliable noninvasive tools to monitor and characterize hepatic changes are urgently needed to improve risk assessment and interventions. NAFLD is characterized by fat accumulation in the liver and encompasses simple nonalcoholic fatty liver and the more progressive nonalcoholic steatohepatitis (NASH). NASH is strongly associated with the development of fibrosis, cirrhosis and hepatocellular carcinoma. The differentiation between benign NAFLD and NASH using current noninvasive diagnostic tools remains challenging and biopsy is often needed for a definitive diagnosis. The key histological features of NASH include the degree of steatosis, necroinflammation and fibrosis and is often associated with iron overload. Among them, the stage of fibrosis has been shown to be the most reliable predictor of liver-related mortality and presents a prominent target for the development of new imaging techniques. Magnetic resonance elastography (MRE) is considered the imaging gold standard which targets the increase in extracellular matrix in fibrotic liver tissue based on stiffness measurements. Recently, multiparametric MRI (mp- MRI) approaches have evolved that use MR relaxometry to assess the increase of extracellular fluid (ECF) volume as a measure of fibrosis. These methods use T2* mapping to account for iron deposition which presents a major confounding factor in the assessment of ECF volumes. Both, MRE and MRI techniques have shown promising results, however, improvements in specificity and accuracy are still needed. Our long-term goal is to develop a novel QSM based multiparametric MRI approach (QSMmp-MRI) that addresses shortcomings of previous mp-MRI techniques by incorporating quantitative susceptibility mapping (QSM) into the method. QSM has high specificity towards magnetically active iron compounds such as ferritin and hemosiderin and could improve the quantification of iron load in NASH patients and thereby indirectly enhance the accuracy of the corresponding ECF volume measurements in liver tissue. Overall, this new technique will enable the assessment of hepatic tissue parameters such as fibrosis, inflammation, steatosis, and iron load. The objective of this proposal is to implement the QSMmp-MRI sequences and to perform initial testing in a pilot study that uses noninvasive MRE as reference. In Aim 1, we will develop a set of MR sequences to quantify T1, T2*, magnetic susceptibility, and proton density fat fraction maps based on motion-robust radial sampling. Different acquisition modes will be tested, and performance will be evaluated on ex vivo phantoms and healthy volunteers. In Aim 2, a noninvasive pilot study will be conducted to compare the new QSMmp-MRI technique with MRE on 48 NASH patients as a primary validation step. The study will be performed in collaboration with the Waianae Coast Comprehensive Health Center and Queen’s Medical Center and will engage with the local community through the Waianae ‘Ohana Produce Prescription (WOPRx) Project (GusNIP, USDA).