The purpose of this proposal is to refine magnetic resonance (MR) imaging and spectroscopy to provide a comprehensive non-invasive assessment of patients with non-alcoholic fatty liver disease (NAFLD).
The specific aims are to implement and develop MR methods to qualitatively and quantitatively assess liver: (1) fat, (2) fibrosis, and (3) inflammation. Dixon variant imaging and spectroscopy will be used to assess fat. Morphological and textural analysis of images obtained with combined contrast enhancement, as well as diffusion weighted and perfusion imaging will be used to assess fibrosis. A combination of these techniques will be used to assess inflammation. Both qualitative and quantitative pathology obtained from liver biopsies will be used as the reference standard. Prospective single-center cross-sectional and longitudinal clinical studies will be performed in children and adults. Specific imaging and spectroscopic features will be correlation by histological, biochemical, and clinical findings. The proposed study is ancillary to the Non-Alcoholic Steahohepatitis Clinical Research Network, one of the obesity-related clinical trials identified by the RFA to which this proposal responds. The proposed study will be fully integrated into the University of California San Diego (UCSD) site of the Research Netowrk. UCSD is one of eight Clinical Centers in the Network. The existing clinical gold standard for diagnosis and monitoring NAFLD is biopsy. This is associated with small but definite risks and samples only a small and possibly unrepresentative region of the liver. Because of the increasing prevalence of obesity, and the risk of progression of NAFLD to steatohepatltis, cirrhosis, and hepatocellular carcinoma, the need for accurate non-invasive diagnosis is increasing. Public health statement. NAFLD is an important cause of liver disease in the United States, is becoming more and more common and affects children and adults. Developing a safe and accurate method to diagnose and follow this disease may lead to earlier diagnosis and more effective treatment.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Study Section
Special Emphasis Panel (ZDK1-GRB-8 (J2))
Program Officer
Doo, Edward
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University of California San Diego
Schools of Medicine
La Jolla
United States
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Yu, N Y; Wolfson, T; Middleton, M S et al. (2017) Bone marrow fat content is correlated with hepatic fat content in paediatric non-alcoholic fatty liver disease. Clin Radiol 72:425.e9-425.e14
Hamilton, Gavin; Schlein, Alexandra N; Middleton, Michael S et al. (2017) In vivo triglyceride composition of abdominal adipose tissue measured by 1 H MRS at 3T. J Magn Reson Imaging 45:1455-1463
Manning, Paul; Murphy, Paul; Wang, Kang et al. (2017) Liver histology and diffusion-weighted MRI in children with nonalcoholic fatty liver disease: A MAGNET study. J Magn Reson Imaging 46:1149-1158
Heba, Elhamy R; Desai, Ajinkya; Zand, Kevin A et al. (2016) Accuracy and the effect of possible subject-based confounders of magnitude-based MRI for estimating hepatic proton density fat fraction in adults, using MR spectroscopy as reference. J Magn Reson Imaging 43:398-406
Smorodinsky, Emmanuil; Ansdell, David S; Foster, Zeke W et al. (2015) Risk of nephrogenic systemic fibrosis is low in patients with chronic liver disease exposed to gadolinium-based contrast agents. J Magn Reson Imaging 41:1259-67
Murphy, Paul; Hooker, Jonathan; Ang, Brandon et al. (2015) Associations between histologic features of nonalcoholic fatty liver disease (NAFLD) and quantitative diffusion-weighted MRI measurements in adults. J Magn Reson Imaging 41:1629-38
Tang, An; Chen, Joshua; Le, Thuy-Anh et al. (2015) Cross-sectional and longitudinal evaluation of liver volume and total liver fat burden in adults with nonalcoholic steatohepatitis. Abdom Imaging 40:26-37
Achmad, Emil; Yokoo, Takeshi; Hamilton, Gavin et al. (2015) Feasibility of and agreement between MR imaging and spectroscopic estimation of hepatic proton density fat fraction in children with known or suspected nonalcoholic fatty liver disease. Abdom Imaging 40:3084-90
Hamilton, Gavin; Middleton, Michael S; Hooker, Jonathan C et al. (2015) In vivo breath-hold (1) H MRS simultaneous estimation of liver proton density fat fraction, and T1 and T2 of water and fat, with a multi-TR, multi-TE sequence. J Magn Reson Imaging 42:1538-43
Tyagi, Avishkar; Yeganeh, Omid; Levin, Yakir et al. (2015) Intra- and inter-examination repeatability of magnetic resonance spectroscopy, magnitude-based MRI, and complex-based MRI for estimation of hepatic proton density fat fraction in overweight and obese children and adults. Abdom Imaging 40:3070-7

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