Hepatic lipid composition analysis using 3.0-T MR spectroscopy in a steatotic rat model.

PURPOSE To investigate the feasibility of in vivo assessment of hepatic lipid composition using 3.0-T proton magnetic resonance spectroscopy ((1)H-MRS) in a steatotic rat model and compare it to histopathological and biochemical assessment. MATERIALS AND METHODS Hepatic steatosis was induced by feeding rats with a methionine/choline-deficient (MCD) diet for 1, 2, 3, 5 or 7 weeks (n=5 per group). At the end of the diet period, (1)H-MRS of the liver was performed, and rats were sacrificed for histopathological and biochemical assessment of the liver. Spectra were acquired in a single voxel (1.2 cc) using a point-resolved spectroscopic sequence with TE/TR=35/2000 ms and 64 signal acquisitions. From the MR spectra, peak area ratios were calculated to estimate hepatic lipid composition. RESULTS During MCD diet periods, hepatic steatosis significantly increased on histopathology (P<.001). The (1)H-MRS measurements of total hepatic fat content [1.3/(1.3+4.65) ppm] correlated strongly with histological macrovesicular hepatic steatosis (r=0.93, P<.001) and with the biochemical total hepatic fatty acids (r=0.94, P<.001). Total unsaturated fatty acids [TUFA, 5.4/(1.3+4.65) ppm] estimated with (1)H-MRS strongly correlated with the biochemical unsaturated fatty acids (r=0.90, P<.001). Polyunsaturated fatty acids [PUFA, 2.8/(1.3+4.65) ppm] estimated with (1)H-MRS strongly correlated with biochemical PUFA (r=0.91, P<.001). The proportion of total unsaturated fatty acids relative to the amount of total fatty acids (rTUFA, 5.4/1.3 ppm) measured with (1)H-MRS strongly correlated with the biochemical amount of unsaturated relative to total hepatic fatty acids (r=0.81, P<.001). The proportion of PUFA relative to the amount of total fatty acids (rPUFA, 2.8/1.3 ppm) measured with (1)H-MRS correlated with the biochemical amount of PUFA relative to total fatty acids (r=0.59, P=0.005,) and with the biochemical amount of omega-6 PUFA relative to total fatty acids (r=0.73, P<.001). PUFA at (1)H-MRS correlated with the histopathologically assessed degree of lobular inflammation in the liver (r=0.57, P=.001). CONCLUSION 3.0 T (1)H-MRS is able to measure poly- and unsaturated hepatic fatty acids and this strongly correlates with biochemical assessment. This study provides evidence that 3.0-T (1)H-MRS is a noninvasive technique to assess hepatic lipid composition.

[1]  J. Hoogduin,et al.  Reproducibility of 3.0 Tesla magnetic resonance spectroscopy for measuring hepatic fat content , 2009, Journal of magnetic resonance imaging : JMRI.

[2]  P. Hayes,et al.  Review article: omega‐3 fatty acids – a promising novel therapy for non‐alcoholic fatty liver disease , 2009, Alimentary pharmacology & therapeutics.

[3]  C. Tiribelli,et al.  Proton MR spectroscopy in quantitative in vivo determination of fat content in human liver steatosis , 1995, Journal of magnetic resonance imaging : JMRI.

[4]  A. Simopoulos,et al.  The importance of the ratio of omega-6/omega-3 essential fatty acids. , 2002, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[5]  Seong Ho Park,et al.  Non-invasive assessment of hepatic steatosis: prospective comparison of the accuracy of imaging examinations. , 2010, Journal of hepatology.

[6]  B. Mittal,et al.  An Improved, Single Step Standardized Method of Lipid Extraction from Human Skeletal Muscle Tissue , 2006 .

[7]  D. Graveron-Demilly,et al.  Java-based graphical user interface for the MRUI quantitation package , 2001, Magnetic Resonance Materials in Physics, Biology and Medicine.

[8]  Vanhamme,et al.  Improved method for accurate and efficient quantification of MRS data with use of prior knowledge , 1997, Journal of magnetic resonance.

[9]  P. Hayes,et al.  Review article: omega-3 fatty acids - a promising novel therapy for non-alcoholic fatty liver disease. , 2010, Alimentary pharmacology & therapeutics.

[10]  H. Cortez‐Pinto,et al.  How different is the dietary pattern in non-alcoholic steatohepatitis patients? , 2006, Clinical nutrition.

[11]  P. Giral,et al.  Sampling variability of liver biopsy in nonalcoholic fatty liver disease. , 2005, Gastroenterology.

[12]  C. Thomsen,et al.  Quantification of liver fat using magnetic resonance spectroscopy. , 1994, Magnetic resonance imaging.

[13]  B. Zauscher,et al.  Omega-3 fatty acids improve hepatic steatosis in a murine model: potential implications for the marginal steatotic liver donor. , 2005, Transplantation.

[14]  O. Cummings,et al.  Design and validation of a histological scoring system for nonalcoholic fatty liver disease , 2005, Hepatology.

[15]  Roger Williams.  Global challenges in liver disease , 2006, Hepatology.

[16]  R. Rodrigo,et al.  Increase in long-chain polyunsaturated fatty acid n - 6/n - 3 ratio in relation to hepatic steatosis in patients with non-alcoholic fatty liver disease. , 2004, Clinical science.

[17]  L. Ferrell,et al.  Correlation of paired liver biopsies in morbidly obese patients with suspected nonalcoholic fatty liver disease , 2006, Hepatology.

[18]  K. Lindor,et al.  Nonalcoholic fatty liver disease. , 2007, Annals of epidemiology.

[19]  C. Sirlin,et al.  Effect of PRESS and STEAM sequences on magnetic resonance spectroscopic liver fat quantification , 2009, Journal of magnetic resonance imaging : JMRI.

[20]  S. Piro,et al.  Effects of n-3 polyunsaturated fatty acids in subjects with nonalcoholic fatty liver disease. , 2008, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[21]  J. Stoker,et al.  The diagnostic accuracy of US, CT, MRI and 1H-MRS for the evaluation of hepatic steatosis compared with liver biopsy: a meta-analysis , 2010, European Radiology.

[22]  Michelle M Wiest,et al.  A lipidomic analysis of nonalcoholic fatty liver disease , 2007, Hepatology.

[23]  B. Song,et al.  Prevention of alcoholic fatty liver and mitochondrial dysfunction in the rat by long-chain polyunsaturated fatty acids. , 2008, Journal of hepatology.

[24]  Jonathan C. Cohen,et al.  Prevalence of hepatic steatosis in an urban population in the United States: Impact of ethnicity , 2004, Hepatology.

[25]  J. Stoker,et al.  Noninvasive quantification of hepatic steatosis inrats using 3.0 T 1H‐magnetic resonance spectroscopy , 2010, Journal of magnetic resonance imaging : JMRI.

[26]  F. Schick,et al.  Measurement of intracellular triglyceride stores by H spectroscopy: validation in vivo. , 1999, American journal of physiology. Endocrinology and metabolism.

[27]  G. Bedogni,et al.  The epidemiology of fatty liver , 2004, European journal of gastroenterology & hepatology.

[28]  Michelle M Wiest,et al.  The plasma lipidomic signature of nonalcoholic steatohepatitis , 2009, Hepatology.

[29]  P. Clavien,et al.  Omega 3 - Omega 6: What is right for the liver? , 2007, Journal of hepatology.

[30]  P. Angulo,et al.  Nonalcoholic fatty liver disease. , 2002, Revista de gastroenterologia de Mexico.

[31]  J. Stoker,et al.  Hepatic unsaturated fatty acids in patients with non-alcoholic fatty liver disease assessed by 3.0T MR spectroscopy. , 2010, European journal of radiology.

[32]  A. Zhu,et al.  Metabolic syndrome and hepatocellular carcinoma , 2009, Cancer.

[33]  E. Furth,et al.  In vivo assessment of hepatic triglycerides in murine non-alcoholic fatty liver disease using magnetic resonance spectroscopy. , 2009, Biochimica et biophysica acta.