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） 非酒精性脂肪肝病（NAFLD）已成为世界上主要的健康问题，并助长了 由于营养不良和更久坐的肥胖和胰岛素抵抗的大流行 生活方式。这对于降低疾病发作和进展的风险至关重要。然而， 尚未完全了解疾病进展的驱动因素，也是可靠的无创工具来监测和 迫切需要特征肝变化以改善风险评估和干预措施。 nafld是 其特征是肝脏中脂肪积累，并包含简单的非酒精脂肪肝脏的特征 进行性非酒精性脂肪性肝炎（NASH）。纳什与纤维化的发展密切相关， 肝硬化和肝细胞癌。使用电流的良性NAFLD和NASH之间的区分 非侵入性诊断工具仍然受到挑战，并且经常需要进行活检才能进行确定的诊断。钥匙 NASH的组织学特征包括脂肪变性，坏死炎和纤维化的程度，通常是 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 与实时死亡率相关的死亡率，并为开发新成像技术提供了一个重要的目标。 磁共振弹性图（MRE）被认为是成像黄金标准，其靶向增加 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）方法已经进化出来，使用MR松弛评估细胞外液（ECF）的增加 体积作为纤维化的量度。这些方法使用t2*映射来说明铁沉积 评估ECF体积的主要混杂因素。 MRE和MRI技术都显示 但是，仍然需要提高特异性和准确性的结果。我们的长期目标是 开发一种基于QSM的新型多参数MRI方法（QSMMP-MRI），以解决 以前的MP-MRI技术通过将定量敏感性映射（QSM）纳入该方法。 QSM 对磁性活性铁化合物（例如铁蛋白和铁霉素）具有很高的特异性，并且可以 改善NASH患者的铁负荷数量，从而间接提高 肝组织中相应的ECF体积测量。总体而言，这项新技术将使评估能够 肝组织参数（例如纤维化，注射，脂肪变性和铁负荷）。这个目的 建议是实施QSMMP-MRI序列，并在使用的试点研究中执行初始测试 无创MRE作为参考。在AIM 1中，我们将开发一组MR序列来量化T1，T2*，磁性 敏感性和质子密度脂肪分数图基于运动合作径向采样。不同的收购 将测试模式，并将在离体幻影和健康志愿者上评估性能。在AIM 2中， 将进行一项无创试验研究，以将新的QSMMP-MRI技术与48 NASH上的MRE进行比较 患者是主要验证步骤。该研究将与怀亚纳海岸合作进行 全面的健康中心和皇后医疗中心，将通过 Waianae‘Ohana生产处方（WOPRX）项目（Gusnip，USDA）。