Novel hyperpolarized 13C molecular imaging techniques for differentiating NAFLD and NASH

用于区分 NAFLD 和 NASH 的新型超极化 13C 分子成像技术

• 批准号: 10469466
• 负责人: Michael Ohliger
• 金额: $ 41.55万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-20 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10469466
• 关键词: Address; Alanine; Biochemical; Biological Assay; Biopsy; Breathing; Calibration; Cardiovascular Diseases; Characteristics; Cirrhosis; Clinical; Clinical Management; Clinical Markers; Complex; Diagnosis; Dihydroxyacetone; Disease; Disease Marker; Disease Progression; Echo-Planar Imaging; Energy Metabolism; Goals; Gold; Grant; Hepatic; High Fat Diet; Human; Human Volunteers; Image; Imaging Techniques; Imaging technology; Inflammation; International; Lipids; Liver; Liver diseases; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of liver; Manganese; Measures; Metabolic; Metabolism; Methods; Modeling; Monitor; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Oxidative Stress; Pathology; Patients; Physiologic pulse; Positioning Attribute; Pre-Clinical Model; Pyruvate; RF coil; Rattus; Research Project Grants; Rodent Model; Sampling Errors; Site; System; Testing; Time; Tissue Sample; Translations; base; cancer transplantation; clinical translation; diabetic; diagnostic tool; high risk; human imaging; image reconstruction; imaging approach; imaging biomarker; imaging modality; imaging probe; improved; liver biopsy; liver imaging; liver metabolism; liver transplantation; metabolic imaging; molecular imaging; non-alcoholic fatty liver; non-alcoholic fatty liver disease; nonalcoholic steatohepatitis; novel; novel diagnostics; novel strategies; public health relevance; radio frequency; respiratory; response; simple steatosis; standard measure; tool; treatment response

PROJECT SUMMARY / ABSTRACT Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent condition characterized by ectopic hepatic lipid accumulation in association with obesity and type 2 diabetes. A progressive derangement of hepatic energy metabolism underlies the progression of simple fatty liver to non-alcoholic steatohepatitis (NASH), a condition that carries high risk for progression to critical liver disease states. Unfortunately, the current method for monitoring NAFLD is liver biopsy, which has major limitations especially its high degree of invasiveness. Hyperpolarized 13C magnetic resonance imaging (MRI) is an emerging molecular imaging modality with a unique capability to access intermediary energy metabolism in a non-invasive manner, which is currently undergoing translation into human studies at several sites internationally in studies of cancer and cardiovascular disease. The goal of this new R01 project is to investigate a new application of this new molecular imaging modality to the assessment of NAFLD. The association between detected changes in hyperpolarized 13C MRI and progression of NAFLD will first be investigated in a preclinical model of the progression of NAFLD to NASH (Aim 1), specifically Zucker diabetic fatty (ZDF) rats fed a high fat diet. Two promising hyperpolarized probes of hepatic energy metabolism, [1- 13C]pyruvate and [2-13C]dihydroxyacetone, will be applied to these studies. These new hyperpolarized markers will be compared against gold standard measures of NAFLD derived from pathology, as well as biochemical assays of hepatic energy state and oxidative stress. Next, novel MRI methods will be developed to enable clinical translation of hyperpolarized 13C imaging of the liver (Aim 2). The proposed approach aims to enable dynamic free-breathing imaging of the entire liver by accelerated echo planar imaging (EPI) acquisition with sixteen-channel parallel imaging. To address the key challenge of array sensitivity calibration, a highly novel approach to parallel imaging will be deployed based on continuous tracking of receiver coil positions using an integrated manganese-55 MRI based fiducial marker system. Finally, initial clinical hyperpolarized [1- 13C]pyruvate MRI will be performed in normal subjects and patients with simple steatosis and NASH, with comparison to liver biopsy (Aim 3). By the end of this new five-year R01 Research Project Grant, we aim to deliver a valuable new clinical tool for non-invasively assessing the progression of NAFLD based on associated metabolic changes measured using hyperpolarized 13C MRI.

项目摘要/摘要

项目成果

Hyperpolarized carbon 13 MRI in liver diseases: Recent advances and future opportunities.

• DOI: 10.1111/liv.15222
• 发表时间: 2022-05
• 期刊: LIVER INTERNATIONAL
• 影响因子: 6.7
• 作者: Ye, Zheng;Song, Bin;Lee, Philip M.;Ohliger, Michael A.;Laustsen, Christoffer
• 通讯作者: Laustsen, Christoffer