Quantification of Hepatic Steatosis With Dual-Energy Computed Tomography: Comparison With Tissue Reference Standards and Quantitative Magnetic Resonance Imaging in the ob/ob Mouse

ObjectiveThe aim of this study was to compare dual-energy computed tomography (DECT) and magnetic resonance imaging (MRI) for fat quantification using tissue triglyceride concentration and histology as references in an animal model of hepatic steatosis. Materials and MethodsThis animal study was approved by our institution’s Research Animal Resource Center. After validation of DECT and MRI using a phantom consisting of different triglyceride concentrations, a leptin-deficient obese mouse model (ob/ob) was used for this study. Twenty mice were divided into 3 groups based on expected levels of hepatic steatosis: low (n = 6), medium (n = 7), and high (n = 7) fat. After MRI at 3 T, a DECT scan was immediately performed. The caudate lobe of the liver was harvested and analyzed for triglyceride concentration using a colorimetric assay. The left lateral lobe was also extracted for histology. Magnetic resonance imaging fat-fraction (FF) and DECT measurements (attenuation, fat density, and effective atomic number) were compared with triglycerides and histology. ResultsPhantom results demonstrated excellent correlation between triglyceride content and each of the MRI and DECT measurements (r2 ≥ 0.96, P ⩽ 0.003). In vivo, however, excellent triglyceride correlation was observed only with attenuation (r2 = 0.89, P < 0.001) and MRI-FF (r2 = 0.92, P < 0.001). Strong correlation existed between attenuation and MRI-FF (r2 = 0.86, P < 0.001). Nonlinear correlation with histology was also excellent for attenuation and MRI-FF. ConclusionsDual-energy computed tomography (CT) data generated by the current Gemstone Spectral Imaging analysis tool do not improve the accuracy of fat quantification in the liver beyond what CT attenuation can already provide. Furthermore, MRI may provide an excellent reference standard for liver fat quantification when validating new CT or DECT methods in human subjects.

[1]  Hatem Alkadhi,et al.  Quantification of Liver Fat in the Presence of Iron and Iodine: An Ex-Vivo Dual-Energy CT Study , 2011, Investigative radiology.

[2]  S. Reeder,et al.  Fat quantification with IDEAL gradient echo imaging: Correction of bias from T1 and noise , 2007, Magnetic resonance in medicine.

[3]  S. Reeder,et al.  Multiecho water‐fat separation and simultaneous R  2* estimation with multifrequency fat spectrum modeling , 2008, Magnetic resonance in medicine.

[4]  M. De Maria,et al.  Gold storage in the liver: appearance on CT scans. , 1986, Radiology.

[5]  L Axel,et al.  Difference between liver and spleen CT numbers in the normal adult: its usefulness in predicting the presence of diffuse liver disease. , 1980, Radiology.

[6]  G. Gold,et al.  Iterative decomposition of water and fat with echo asymmetry and least‐squares estimation (IDEAL): Application with fast spin‐echo imaging , 2005, Magnetic resonance in medicine.

[7]  M. Holmqvist,et al.  Long‐term follow‐up of patients with NAFLD and elevated liver enzymes , 2006, Hepatology.

[8]  Namkug Kim,et al.  Hepatic Fat Quantification: A Prospective Comparison of Magnetic Resonance Spectroscopy and Analysis Methods for Chemical-Shift Gradient Echo Magnetic Resonance Imaging With Histologic Assessment as the Reference Standard , 2012, Investigative radiology.

[9]  S. Reeder,et al.  Multiecho reconstruction for simultaneous water‐fat decomposition and T2* estimation , 2007, Journal of magnetic resonance imaging : JMRI.

[10]  Maili Liu,et al.  1H NMR spectroscopic evidence of interaction between ibuprofen and lipoproteins in human blood plasma. , 2004, Analytical biochemistry.

[11]  S. Curley,et al.  Comparison of CT methods for determining the fat content of the liver. , 2007, AJR. American journal of roentgenology.

[12]  Daniel T Boll,et al.  Diffuse liver disease: strategies for hepatic CT and MR imaging. , 2009, Radiographics : a review publication of the Radiological Society of North America, Inc.

[13]  G H Glover,et al.  Three‐point dixon technique for true water/fat decomposition with B0 inhomogeneity correction , 1991, Magnetic resonance in medicine.

[14]  S. Horgan,et al.  Estimation of hepatic proton-density fat fraction by using MR imaging at 3.0 T. , 2011, Radiology.

[15]  D. Sautereau,et al.  Dual-energy CT in the diagnosis and quantification of fatty liver: limited clinical value in comparison to ultrasound scan and single-energy CT, with special reference to iron overload. , 1998, Journal of hepatology.

[16]  Hiroshi Honda,et al.  Noninvasive estimation of hepatic steatosis using plain CT vs. Chemical‐shift MR imaging: Significance for living donors , 2008, Journal of magnetic resonance imaging : JMRI.

[17]  A. Gamst,et al.  Nonalcoholic fatty liver disease: diagnostic and fat-grading accuracy of low-flip-angle multiecho gradient-recalled-echo MR imaging at 1.5 T. , 2009, Radiology.

[18]  David H. Kim,et al.  Hepatic steatosis (fatty liver disease) in asymptomatic adults identified by unenhanced low-dose CT. , 2010, AJR. American journal of roentgenology.

[19]  S. Reeder,et al.  Validation of MRI biomarkers of hepatic steatosis in the presence of iron overload in the ob/ob mouse , 2012, Journal of magnetic resonance imaging : JMRI.

[20]  Scott B Reeder,et al.  Water–fat separation with IDEAL gradient‐echo imaging , 2007, Journal of magnetic resonance imaging : JMRI.

[21]  S. Reeder,et al.  T1 independent, T2* corrected MRI with accurate spectral modeling for quantification of fat: Validation in a fat‐water‐SPIO phantom , 2009, Journal of magnetic resonance imaging : JMRI.

[22]  W. T. Dixon Simple proton spectroscopic imaging. , 1984, Radiology.

[23]  E. Fishman,et al.  Amiodarone pulmonary toxicity: CT findings in symptomatic patients. , 1990, Radiology.

[24]  D. Aguirre,et al.  Fatty liver: imaging patterns and pitfalls. , 2013, Radiographics : a review publication of the Radiological Society of North America, Inc.

[25]  S. Grundy,et al.  Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population. , 2005, American journal of physiology. Endocrinology and metabolism.

[26]  A. Nanji Animal models of nonalcoholic fatty liver disease and steatohepatitis. , 2004, Clinics in liver disease.

[27]  B. Wang,et al.  Quantitative diagnosis of fatty liver with dual-energy CT: An experimental study in rabbits , 2003, Acta radiologica.

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

[29]  R. Nelson,et al.  Dual-energy multidetector CT: how does it work, what can it tell us, and when can we use it in abdominopelvic imaging? , 2010, Radiographics : a review publication of the Radiological Society of North America, Inc.

[30]  L. A. Menahan,et al.  Age-related changes in lipid and carbohydrate metabolism of the genetically obese mouse. , 1983, Metabolism: clinical and experimental.

[31]  Z. Gao,et al.  Quantitative Diagnosis of Fatty Liver With Dual-Energy CT , 2003 .

[32]  G. Bydder,et al.  Accuracy of computed tomography in diagnosis of fatty liver. , 1980, British medical journal.

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

[34]  Scott B Reeder,et al.  Quantification of hepatic steatosis with T1-independent, T2-corrected MR imaging with spectral modeling of fat: blinded comparison with MR spectroscopy. , 2011, Radiology.

[35]  A Karellas,et al.  Value of dual-energy CT in differentiating focal fatty infiltration of the liver from low-density masses. , 1991, AJR. American journal of roentgenology.

[36]  C. Sirlin,et al.  Relaxation effects in the quantification of fat using gradient echo imaging. , 2008, Magnetic resonance imaging.

[37]  S. Reeder,et al.  Quantification of hepatic steatosis with 3-T MR imaging: validation in ob/ob mice. , 2010, Radiology.

[38]  C. Sirlin,et al.  In vivo characterization of the liver fat 1H MR spectrum , 2011, NMR in biomedicine.

[39]  S. Reeder,et al.  Quantitative assessment of liver fat with magnetic resonance imaging and spectroscopy , 2011, Journal of magnetic resonance imaging : JMRI.

[40]  Sang Won Lee,et al.  Macrovesicular hepatic steatosis in living liver donors: use of CT for quantitative and qualitative assessment. , 2006, Radiology.

[41]  K. Washington,et al.  Assessment of Hepatic Steatosis by Expert Pathologists: The End of a Gold Standard , 2009, Annals of surgery.

[42]  J. Doppman,et al.  Computed Tomography of the Liver and Kidneys in Glycogen Storage Disease , 1982, Journal of computer assisted tomography.

[43]  Michael Markl,et al.  Multicoil Dixon chemical species separation with an iterative least‐squares estimation method , 2004, Magnetic resonance in medicine.