Technical Validation of MRI Biomarkers of Liver Fat

肝脏脂肪 MRI 生物标志物的技术验证

• 批准号: 8304615
• 负责人: Scott B. Reeder
• 金额: $ 10.94万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-15 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8304615
• 关键词: Address; Adoption; Adult; Affect; American; Ancillary Study; Biochemical; Biological Markers; Biopsy; Body Weight decreased; California; Cardiovascular Diseases; Characteristics; Child; Chronic; Cirrhosis; Classification; Clinical; Clinical Research; Cohort Studies; Data; Development; Diagnosis; Disease Progression; Early Diagnosis; Early treatment; Enrollment; Epidemiologic Studies; Error Sources; Fatty Liver; Fatty acid glycerol esters; Goals; Gold; Health; Hepatic; Hepatocyte; Histology; Imaging Techniques; Laboratories; Liver; Liver Failure; Liver diseases; Magnetic Resonance; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measurement; Measures; Methods; Monitor; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Operative Surgical Procedures; Patient Care; Patients; Performance; Prevention; Process; Protons; Reader; Recommendation; Reference Standards; Relaxation; Reproducibility; Research; Research Design; Research Methodology; Resources; Risk; Signal Transduction; Site; Specimen; Techniques; Time; Tissues; Triglycerides; United States; Universities; Validation; Weight; Wisconsin; bariatric surgery; clinical care; clinical practice; common treatment; density; design; human subject; imaging modality; improved; liver biopsy; non-alcoholic fatty liver; programs; prospective; public health relevance; response; tool; validation studies

DESCRIPTION (provided by applicant): The proposal's broad, long-term objective is to improve the health of millions of Americans with or at risk for non-alcoholic fatty liver disease (NAFLD). The immediate goal is to technically validate magnetic resonance imaging (MRI) determined proton density fat fraction (PDFF) as a biomarker of liver fat by demonstrating: Aim 1. Accuracy against an independent, definitive reference standard. We will determine and compare the accuracy of PDFF as measured by two MRI techniques, using tissue triglyceride concentration as the reference standard. We hypothesize that PDFF will accurately predict TG concentration. We will identify the more accurate technique. Aim 2. Precision with high repeatability and reproducibility. We will assess the repeatability within subjects and reproducibility across sites, scanners and readers of PDFF values as measured by two MRI techniques. We hypothesize that PDFF will be repeatable and reproducible. We will identify the more repeatable and reproducible technique. Aim 3. Clinical and research value. We will use PDFF as a biomarker to define the relationship between weight loss and liver fat in obese adults undergoing gastric banding, demonstrating its utility as an objective tool for repeated measures of liver fat content. We hypothesize that PDFF will decrease monotonically in response to weight loss. Factors that modulate this relationship will be identified. Significance: NAFLD is the most common chronic liver disease of adults and children in the United States. It may progress to cirrhosis and contribute to the development of cardiovascular disease and type 2 diabetes. Liver biopsy, the current clinical gold standard to assess liver fat and diagnose NAFLD, is invasive. This limitation has hindered progress in the diagnosis, treatment, and prevention of NAFLD. A valid non-invasive biomarker of liver fat content is needed for clinical care and research. New breath-hold MRI methods refined at the University of California, San Diego and the University of Wisconsin address the sources of errors in conventional MRI for measuring liver fat. These new methods permit rapid estimation of PDFF, the fraction of mobile protons in liver attributable to fat. Preliminary data suggests that PDFF accurately predicts liver TG concentration, the biochemical measure of liver fat content; but rigorous validation is required to establish MRI-determined PDFF as a reliable and useful biomarker. Research design and methods: We plan a two-site prospective cohort study. The two-site design provides unbiased comparison of competing techniques, adequate patient enrollment, and the ability to compare performance characteristics across sites. We will enroll 140 obese adults (70 per site) participating in a surgical weight loss program (laparoscopic adjustable gastric banding). Enrolled subjects will have variable baseline liver fat content; have multiple intra-operative biopsies providing a definitive reference standard with which to compare PDFF measurements; and lose weight and liver fat at variable rates. PDFF will be measured using two MRI techniques at multiple time points before and after surgery. PUBLIC HEALTH RELEVANCE: This proposal will show that magnetic resonance imaging is a safe, rapid, relatively inexpensive, and accurate alternative to liver biopsy for measuring liver fat in the tens of millions of Americans affected by or at risk for fatty liver disease.

描述（由申请人提供）：该提案的广泛，长期目标是改善数百万美国人或有非酒精性脂肪肝病（NAFLD）风险的美国人的健康。直接目标是通过证明：目标1。针对独立的，确定的参考标准的准确性，在技术上验证磁共振成像（MRI）确定为肝脂肪的生物标志物作为肝脂肪的生物标志物。我们将使用组织甘油三酸酯浓度作为参考标准来确定和比较PDFF的准确性。我们假设PDFF将准确预测TG浓度。我们将确定更准确的技术。目标2。精度具有高可重复性和可重复性。我们将评估受试者内部的可重复性以及通过两种MRI技术测量的位点，扫描仪和PDFF值的读者的可重复性。我们假设PDFF将是可重复的且可再现的。我们将确定更可重复和可重复的技术。目标3。临床和研究价值。我们将使用PDFF作为生物标志物来定义肥胖成年人进行胃谱带的体重减轻和肝脏脂肪之间的关系，这表明其用作肝脏脂肪含量重复测量的客观工具。我们假设PDFF会响应体重减轻而单调减少。调节这种关系的因素将被确定。意义：NAFLD是美国最常见的成年人和儿童的慢性肝病。它可能会发展为肝硬化，并有助于心血管疾病和2型糖尿病的发展。肝活检是评估肝脏脂肪和诊断NAFLD的当前临床黄金标准，具有侵入性。这种局限性阻碍了NAFLD诊断，治疗和预防的进展。临床护理和研究需要有效的肝脂肪含量的无创生物标志物。加利福尼亚大学，圣地亚哥大学和威斯康星大学的新呼吸备值MRI方法提出了用于测量肝脏脂肪的常规MRI错误来源。这些新方法允许对PDFF的快速估计，PDFF是可归因于脂肪的肝脏中移动质子的比例。初步数据表明，PDFF准确地预测了肝脂肪含量的生化量度。但是需要严格的验证才能确定MRI确定的PDFF作为可靠且有用的生物标志物。研究设计和方法：我们计划一项两端的前瞻性队列研究。两场设计提供了竞争技术，足够的患者入学以及比较跨站点性能特征的能力的公正比较。我们将招募140名肥胖成年人（每个站点70）参加手术减肥计划（可腹腔镜调节胃体带）。注册受试者将具有可变的基线肝脂肪含量；具有多个术中活检，提供了一个明确的参考标准，可以比较PDFF测量；并以可变速率减肥和肝脏脂肪。 PDFF将在手术前后的多个时间点使用两种MRI技术进行测量。 公共卫生相关性：该提案将表明，磁共振成像是一种安全，快速，相对廉价且准确的肝活检替代方法，用于测量受脂肪肝病或面临危险的数以百万计的美国人的肝脏脂肪。