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

项目 3：一种用于非酒精性脂肪肝定量评估的新型同步多参数 MRI 方法

• 批准号: 10594473
• 负责人: Christoph Alexander Rettenmeier
• 金额: $ 32.91万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-20 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10594473
• 关键词: Address; Adverse effects; Affect; Benign; Berry; Biopsy; Blood; Centers of Research Excellence; Characteristics; Chemistry; Cirrhosis; Clinical assessments; Collaborations; Collagen; Communities; Deposition; Development; Diagnosis; Diagnostic; Diet Habits; Disease Outcome; Disease Progression; Doctor of Philosophy; Economic Burden; Extracellular Fluid; Extracellular Matrix; Fatty acid glycerol esters; Ferritin; Fibrosis; Funding; Goals; Hawaii; Health; Health Benefit; Hemosiderin; Hepatic; Hepatic Tissue; Histologic; Human; Image; Imaging Techniques; Imaging technology; Individual; Inflammation; Insulin Resistance; Intervention; Iron; Iron Compounds; Iron Overload; Liver; Liver Fibrosis; Liver diseases; Magnetic Resonance Elastography; Magnetic Resonance Imaging; Magnetism; Malnutrition; Maps; Measurement; Measures; Medical center; Medicine; Mentors; Methods; Modeling; Monitor; Motion; Nature; Obesity; Onset of illness; Overnutrition; Patients; Performance; Personal Satisfaction; Pilot Projects; Population; Predisposition; Primary carcinoma of the liver cells; Protons; Radial; Reference Values; Research; Research Personnel; Resources; Risk Assessment; Risk Factors; Risk Reduction; Sampling; Scanning; Secure; Severities; Severity of illness; Specificity; Techniques; Testing; Tissues; United States; United States Department of Agriculture; Universities; Validation; career; career development; clinical diagnosis; clinical phenotype; density; diagnostic tool; dietary control; disease phenotype; effectiveness evaluation; fibrogenesis; healthy volunteer; improved; interest; life time cost; liver biopsy; liver imaging; liver transplantation; low socioeconomic status; member; minimal risk; mortality; non-alcoholic fatty liver; non-alcoholic fatty liver disease; non-invasive imaging; nonalcoholic steatohepatitis; noninvasive diagnosis; novel; novel strategies; nutrition; pandemic disease; patient population; precision nutrition; research study; screening; sedentary lifestyle; tool

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).

项目摘要 – 项目 3 (Rettenmeier) 非酒精性脂肪性肝病 (NAFLD) 已成为世界上的一个主要健康问题，其推动因素是 由于营养过剩和久坐，肥胖和胰岛素抵抗日益流行 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。 疾病进展的驱动因素尚不完全清楚，可靠的非侵入性工具可以监测和 迫切需要表征肝脏变化以改进 NAFLD 的风险评估和干预措施。 以肝脏脂肪堆积为特征，包括单纯性非酒精性脂肪肝等 进行性非酒精性脂肪性肝炎 (NASH) 与纤维化的发展密切相关， 使用电流来区分良性 NAFLD 和 NASH。 无创诊断工具仍然具有挑战性，而活检往往是确诊的关键。 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，通常与 其中，纤维化阶段已被证明是最可靠的预测因素。 与肝脏相关的死亡率，并为新成像技术的发展提供了一个突出的目标。 磁共振弹性成像（MRE）被认为是成像黄金标准，其目标是增加 基于刚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）方法已发展为使用 MR 松弛测量法来评估细胞外液 (ECF) 的增加 这些方法使用 T2* 映射来解释铁沉积。 MRE 和 MRI 技术都表明，这是评估 ECF 体积的一个主要混杂因素。 尽管取得了有希望的结果，但仍需要提高特异性和准确性。 开发一种基于 QSM 的新型多参数 MRI 方法 (QSMmp-MRI)，该方法解决了 以前的 mp-MRI 技术通过将定量磁化率图 (QSM) 纳入 QSM 方法中。 对铁蛋白和含铁血黄素等磁性活性铁化合物具有高度特异性，可以 改善NASH患者铁负荷的量化，从而间接提高铁负荷的准确性 总体而言，这项新技术将使评估成为可能。 肝组织参数，如纤维化、炎症、脂肪变性和铁负荷。 建议实施 QSMmp-MRI 序列并在试点研究中进行初步测试，该研究使用 在目标 1 中，我们将开发一组 MR 序列来量化 T1、T2*、磁性。 基于运动鲁棒径向采样的磁化率和质子密度脂肪分数图。 在目标 2 中，将测试模式，并评估离体模型和健康志愿者的性能。 将进行一项无创试点研究，以比较新的 QSMmp-MRI 技术与 MRE 对 48 例 NASH 的治疗效果 作为主要验证步骤，该研究将与怀阿奈海岸合作进行。 综合健康中心和女王医疗中心，并将通过以下方式与当地社区互动 Waianae ‘Ohana 农产品处方 (WOPRx) 项目（GusNIP，美国农业部）。