Multiparametric magnetic resonance for the non-invasive diagnosis of liver disease

Abstract

Background & aims: With the increasing prevalence of liver disease worldwide, there is an urgent clinical need for reliable methods to diagnose and stage liver pathology. Liver biopsy, the current gold standard, is invasive and limited by sampling and observer dependent variability. In this study, we aimed to assess the diagnostic accuracy of a novel magnetic resonance protocol for liver tissue characterisation.

Methods: We conducted a prospective study comparing our magnetic resonance technique against liver biopsy. The individual components of the scanning protocol were T1 mapping, proton spectroscopy and T2* mapping, which quantified liver fibrosis, steatosis and haemosiderosis, respectively. Unselected adult patients referred for liver biopsy as part of their routine care were recruited. Scans performed prior to liver biopsy were analysed by physicians blinded to the histology results. The associations between magnetic resonance and histology variables were assessed. Receiver-operating characteristic analyses were also carried out.

Results: Paired magnetic resonance and biopsy data were obtained in 79 patients. Magnetic resonance measures correlated strongly with histology (r(s)=0.68 p<0.0001 for fibrosis; r(s)=0.89 p<0.001 for steatosis; r(s)=-0.69 p<0.0001 for haemosiderosis). The area under the receiver operating characteristic curve was 0.94, 0.93, and 0.94 for the diagnosis of any degree of fibrosis, steatosis and haemosiderosis respectively.

Conclusion: The novel scanning method described here provides high diagnostic accuracy for the assessment of liver fibrosis, steatosis and haemosiderosis and could potentially replace liver biopsy for many indications. This is the first demonstration of a non-invasive test to differentiate early stages of fibrosis from normal liver.

Keywords: (1)H MRS; ANOVA; AUROC; Analysis of Variance; Area Under the Receiver Operating Characteristic Curve; BMI; Body Mass Index; CPA; CoV; Coefficient of Variance; Collagen Proportionate Area; HLC; Hepatic Lipid Content; Iron corrected T1; Liver fibrosis; Liver haemosiderosis; Liver steatosis; MR; Magnetic Resonance; Magnetic resonance T1 mapping; Magnetic resonance T2(⁎) mapping; NAFLD; Non-Alcoholic Fatty Liver Disease; Proton Magnetic Resonance Spectroscopy; Proton magnetic resonance spectroscopy; ROI; Region of interest; shMOLLI; shortened Modified Look Locker Inversion.

Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Figures

Fig. 1

Study protocol with examples of normal and abnormal MR measurements. The images show MR T1 maps from patients with no liver fibrosis on biopsy (A) and cirrhosis (B) and MR T2⁎ maps from patients with negative Perls’ stain for iron (C) and grade 1 haemosiderosis (D). T1 and T2⁎ measured in milliseconds are translated into colours according to the shown pre-specified colour scales. Water-unsuppressed 1H MR spectra from a patient with steatosis grade 0 (E), and steatosis grade 3 (F) also shown. MRI, magnetic resonance imaging; cT1, iron-corrected T1; HIC, hepatic iron content; HLC, hepatic lipid content; 1H MRS, 1H magnetic resonance spectroscopy. ⁎Liver.

Fig. 2

cT1 values in 77 patients and 7 healthy volunteers (presumed with no fibrosis) plotted against their biopsy proven fibrosis stage. Iron-corrected T1 (cT1) correlates with the degree of fibrosis in all subjects (rs = 0.68, p <0.0001, 95% CI 0.54–0.78). Mean ± SD cT1 for each group was as follows: healthy volunteers 717 ± 48 ms, no fibrosis 750 ± 42 ms (those two are grouped as “normal liver”), mild fibrosis 870 ± 104 ms, moderate 873 ± 63 ms, and severe 1025 ± 102 ms. ANOVA with Bonferroni’s correction showed significant differences (⁎⁎⁎) between all groups apart from mild vs. moderate fibrosis (n.s., not significant; Table 2). Liver biopsy patients are shown as red dots, and healthy volunteers as blue squares.

Fig. 3

Viral hepatitis fibrosis staging with MR T1 mapping and iron-corrected T1 measurements in the regions of interest. Examples of transverse liver MR T1 maps from 4 patients with viral hepatitis (left column). The white circles indicate typical areas of interest corresponding to tissue volume of 25–30 ml, where the T1 and T2⁎ would be measured in order to estimate cT1, which is included for each patient. The corresponding liver biopsy slides stained with Sirius Red for fibrosis (Ishak F0–F6; magnification 4×) for each patient are shown for comparison (right column). The appearance of the MR T1 map and the quantitative measure of fibrosis (cT1), clearly correlate with the degree of fibrosis as assessed by the Ishak score.

Fig. 4

The assessment of hepatic steatosis with1H MRS and hepatic haemosiderosis with T2⁎ mapping. (A) There was a very strong correlation between steatosis grade hepatic lipid content measured by 1H MRS (rs = 0.89, p <0.0001). MRS thresholds of 1.5% and 7.5% steatosis respectively identified a steatosis grade of ⩾1 (sensitivity 80%, specificity 100%) and a steatosis grade of >2 (sensitivity 100%, specificity 97%). (B) There was a strong negative correlation between histological grading of iron deposition and T2⁎ (rs = −0.69, p <0.0001, 95% CI −0.79 to −0.55). A T2⁎ cut off at 12.5 ms identified any degree of haemosiderosis with a sensitivity of 86% and a specificity of 93%.