Combined approach for non-invasive measurement of liver pathology by MR
Authors: Gary J. Cowin, Julie R. Jonsson, Stuart McPherson, Andrew D. Clouston, Mark Benson, Elizabeth E. Powell, Graham J. Galloway
Journal: Journal of Hepatology (2009)

We welcome the response from Guiu et al. regarding our recently published study [[1]McPherson S. Jonsson J.R. Cowin G.J. O'Rourke P. Clouston A.D. Volp A. et al.Magnetic resonance imaging and spectroscopy accurately estimate the severity of steatosis provided the stage of fibrosis is considered.J Hepatol. 2009; 51: 389-397Abstract Full Text Full Text PDF PubMed Scopus (136) Google Scholar]. We fully agree that for MR methods to become a clinical tool, standardization of the techniques is required. Our results were obtained at 1.5 T, which remains the predominant clinical MRI system. The authors fully recognise that there will be benefits in using 3 T, but the aim of this paper was to present results that are relevant to the broader clinical community. The lack of a true "gold standard" is a potential limiting factor for assessing the potential of new methods. The latter point has been recently discussed in an editorial and several articles in this Journal (vol. 50, 2009) earlier this year. In the absence of a true "gold standard" our analysis is based on clinically accepted measures, scored by a single expert in liver histopathology (co-author A.C.). MRS is not a clinically accepted measure. We intentionally used the combined peak intensity from CH2 + CH3 in the spectra, as we argue that the CH3 signal contributes to the lipid fraction in both imaging methods. The Dixon method uses TE values that result in the water and CH2 protons being π radians out-of-phase, based on the frequency shift between the protons. The small frequency difference between CH2 and CH3 protons, results in the CH3 spins being almost out-of-phase and so also contributes to the net lipid signal. Given the separation of the CH2 and CH3 is only 0.4 ppm, (25.5 Hz at 1.5 T), the fat saturation methods cannot suppress only CH2 protons, but also significantly suppress the CH3 signal. Cirrhosis can be associated with increased liver iron [[2]Stuart K.A. Fletcher L.M. Clouston A.D. Lynch S.V. Purdie D.M. Kerlin P. et al.Increased hepatic iron and cirrhosis: no evidence for an adverse effect on patient outcome following liver transplantation.Hepatology. 2000; 32: 1200-1207Crossref PubMed Scopus (49) Google Scholar]. We suggest caution in assuming that liver fibrosis universally increases T2, particularly as increased iron decreases T2. The conclusions presented are consistent with the difference in scoring lipid content by the two methods. MR methods measure lipid fraction per unit volume, irrespective of the hepatocyte count in the volume. The histology method scores lipid content as hepatocytes with visible fat. The number of hepatocyte nuclei per unit volume decreased with fibrosis, consistent with reduced hepatocytes per unit volume with fibrosis. In conclusion, a combined approach should be the goal for non-invasive measurement of liver pathology by MR. Lipid content or fibrosis are unlikely to be universally measured in isolation, particularly without a measure of iron content. However, with a combination of lipid selective imaging, relaxometry, diffusion, spectroscopy and elastography, the future looks promising.