The broad long-term objective of this study is to improve the management of patients with non-alcoholic fatty liver disease (NAFLD) by developing a non-invasive alternative to liver biopsy for the evaluation and monitoring of hepatic steatosis, necroinflammatory change, and fibrosis leading to cirrohsis using novel MR imaging (MRI) and MR spectroscopic (MRS) markers. NAFLD is increasingly recognized as an important clinical problem in both adults and children, fueled by the burgeoning obesity epidemic. Non-alcoholic steatohepatititis (NASH) is characterized by the presence of necroinflammatory changes in addition to simple steatois and carries an increased risk of progression to cirrhosis. The distinction of NASH from simple steatois is therefore of great interest, particularly given the emergence of potential therapies, but currently requires biopsy for both recognition and monitoring. The central hypothesis of this study is that analysis of non-invasive MRI markers of steatosis, inflammation and fibrosis will provide equivalent and/or additional diagnostic information to liver biopsy in patients with NAFLD.
The specific aims are: 1) determine if apparent diffusion coefficient (ADC) values derived from diffusion MR imaging and MR spectroscopic (MRS) markers (lipids, water, and choline containing compounds) correlate with the grade of necroinflammatory change in NASH; 2) determine if ADC values and MRS markers correlate with the stage of fibrosis in NASH; 3) determine if MRI (relative signal loss of liver on out-of-phase versus in-phase T1-weighted and with and without fat-suppression T2-weighted sequences) and MRS markers correlate with detection of steatosis in NAFLD; 4) determine if MRI visceral fat area measurements correlate with histopathologic parameters of disease severity. A multidisciplinary prospective cohort study involving MR studies will be performed on 50 control subjects (healthy liver donors) and 150 consecutive eligible patients with NAFLD. All subjects will have liver biopsy as part of their clinical evaluation within 1 month of imaging. The patients will undergo an MRI examination including diffusion imaging, and MRS. Histopathologic variables will be correlated with MRI and MRS variables. The relevance of this research to public health is the improved management of NAFLD, which affects over two-thirds of the 60 million obese adults in the United States and is also increasing among children. Determination of MRI and MRS markers of hepatic complications of NAFLD would enable the non-invasive diagnosis, and monitoring of both disease progression and response to emerging therapeutic interventions. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK074718-01A1
Application #
7208691
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Doo, Edward
Project Start
2007-07-01
Project End
2012-06-30
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
1
Fiscal Year
2007
Total Cost
$218,488
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Eatesam, Mamak; Noworolski, Susan M; Tien, Phyllis C et al. (2012) Liver diffusivity in healthy volunteers and patients with chronic liver disease: comparison of breathhold and free-breathing techniques. J Magn Reson Imaging 35:103-9
Qayyum, Aliya; Nystrom, Michelle; Noworolski, Susan M et al. (2012) MRI steatosis grading: development and initial validation of a color mapping system. AJR Am J Roentgenol 198:582-8
Ghotb, Alireza; Noworolski, Susan M; Madden, Erin et al. (2010) Adipose tissue and metabolic factors associated with steatosis in HIV/HCV coinfection: histology versus magnetic resonance spectroscopy. J Acquir Immune Defic Syndr 55:228-31
Noworolski, Susan M; Tien, Phyllis C; Merriman, Raphael et al. (2009) Respiratory motion-corrected proton magnetic resonance spectroscopy of the liver. Magn Reson Imaging 27:570-6
Qayyum, Aliya (2009) MR spectroscopy of the liver: principles and clinical applications. Radiographics 29:1653-64
Qayyum, Aliya (2009) Diffusion-weighted imaging in the abdomen and pelvis: concepts and applications. Radiographics 29:1797-810
Qayyum, Aliya; Chen, Daryl M; Breiman, Richard S et al. (2009) Evaluation of diffuse liver steatosis by ultrasound, computed tomography, and magnetic resonance imaging: which modality is best? Clin Imaging 33:110-5
Bahl, Manisha; Qayyum, Aliya; Westphalen, Antonio C et al. (2008) Liver steatosis: investigation of opposed-phase T1-weighted liver MR signal intensity loss and visceral fat measurement as biomarkers. Radiology 249:160-6