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)已成为世界上一个主要的健康问题，由 由于营养过剩和久坐不动导致的肥胖和胰岛素抵抗的日益流行 生活方式。因此，改善饮食习惯对于降低疾病发生和发展的风险至关重要。然而， 疾病进展的驱动因素尚未完全了解，也没有可靠的非侵入性工具来监测和 迫切需要确定肝脏变化的特征，以改进风险评估和干预。NAFLD是 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)NASH与纤维化的发展密切相关， 肝硬变和肝细胞癌。应用电流鉴别良性非酒精性脂肪肝与非酒精性脂肪肝 非侵入性诊断工具仍然具有挑战性，通常需要活检才能做出明确的诊断。钥匙 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 与铁超载有关。其中，纤维化分期已被证明是最可靠的预测指标。 与肝脏相关的死亡率，并成为开发新的成像技术的一个突出目标。 磁共振弹性成像(MRE)被认为是成像的黄金标准，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。近年来，多参数磁共振成像(MP- 核磁共振成像)的方法已经发展，使用磁共振弛豫来评估细胞外液(ECF)的增加。 作为衡量纤维化程度的体积。这些方法使用T2*映射来解释呈现的铁沉积 ECF数量评估中的一个主要混杂因素。MRE和MRI技术都表明 然而，有希望的结果是，在特异性和准确性方面仍然需要改进。我们的长期目标是 提出了一种新的基于QSM的多参数磁共振成像方法(QSMMP-MRI)。 将定量磁化率图(QSM)结合到MP-MRI技术中。QSM 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，并可能 改善NASH患者铁负荷的量化，从而间接提高检测的准确性 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 肝组织参数，如纤维化、炎症、脂肪变性和铁负荷。这样做的目的是 建议实施QSMMP-MRI序列并在一项试点研究中执行初始测试，该研究使用 以无创性磁共振血管成像为参考。在目标1中，我们将开发一组MR序列来量化T1，T2*，磁性 基于运动稳健径向采样的磁化率和质子密度脂肪分数图。不同的收购 模式将被测试，性能将在体外幻影和健康志愿者上进行评估。在目标2中， 将进行一项无创性的先导性研究，将新的QSMMP-MRI技术与MRE技术在48例NASH中进行比较 患者作为主要的验证步骤。这项研究将与怀亚奈海岸合作进行 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接触 Waianae的Ohana生产处方(WOPRx)项目(GusNIP，美国农业部)。