Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK075128-04
Application #
7609083
Study Section
Special Emphasis Panel (ZDK1-GRB-8 (J2))
Program Officer
Doo, Edward
Project Start
2006-09-01
Project End
2011-03-31
Budget Start
2009-04-01
Budget End
2010-03-31
Support Year
4
Fiscal Year
2009
Total Cost
$469,604
Indirect Cost

  Institution

Name
University of California San Diego
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093

  Publications

Bydder, Mark; Hamilton, Gavin; de Rochefort, Ludovic et al. (2018) Sources of systematic error in proton density fat fraction (PDFF) quantification in the liver evaluated from magnitude images with different numbers of echoes. NMR Biomed 31:
Hooker, Jonathan C; Hamilton, Gavin; Park, Charlie C et al. (2018) Inter-reader agreement of magnetic resonance imaging proton density fat fraction and its longitudinal change in a clinical trial of adults with nonalcoholic steatohepatitis. Abdom Radiol (NY) :
Fazeli Dehkordy, Soudabeh; Fowler, Kathryn J; Wolfson, Tanya et al. (2018) Technical report: gadoxetate-disodium-enhanced 2D R2* mapping: a novel approach for assessing bile ducts in living donors. Abdom Radiol (NY) 43:1656-1660
Mamidipalli, Adrija; Hamilton, Gavin; Manning, Paul et al. (2018) Cross-sectional correlation between hepatic R2* and proton density fat fraction (PDFF) in children with hepatic steatosis. J Magn Reson Imaging 47:418-424
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

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