Christina Levick

Purpose: Direct-acting antiviral therapies (DAAs) for treatment of chronic hepatitis C virus (HCV) have excellent rates of viral eradication, but their effect on regression of liver fibrosis is unclear. The primary aim was to use magnetic resonance imaging (MRI) and spectroscopy (MRS) to evaluate changes in liver fibrosis, liver fat and liver iron content (LIC) in patients with chronic HCV following treatment with DAAs. Methods: In this prospective study, 15 patients with chronic HCV due to start treatment with DAAs and with transient elastography (TE) > 8 kPa were recruited consecutively. Patients underwent MRI and MRS at baseline (before treatment), and at 24 weeks and 48 weeks after the end of treatment (EoT) for the measurement of liver cT₁ (fibroinflammation), liver fat and T₂* (LIC). Results: All patients achieved a sustained virological response. Liver cT₁ showed significant decreases from baseline to 24 weeks post EoT (876 vs 806 ms, p = 0.002, n = 15), baseline to 48 weeks post EoT (876 vs 788 ms, p = 0.0002, n = 13) and 24 weeks post EoT to 48 weeks post EoT (806 vs 788 ms, p = 0.016, n = 13). Between baseline and 48 weeks EoT significant reduction in liver fat (5.17% vs 2.65%, p = 0.027) and an increase in reported LIC (0.913 vs 0.950 mg/g, p = 0.021) was observed. Conclusion: Liver cT₁ decreases in patients with chronic HCV undergoing successful DAA treatment. The relatively fast reduction in cT₁ suggests a reduction in inflammation rather than regression of fibrosis.

Non-invasive assessment of portal hypertension is an area of unmet need. This proof of concept study aimed to evaluate the diagnostic accuracy of a multi-parametric magnetic resonance technique in the assessment of portal hypertension. Comparison to other non-invasive technologies was a secondary aim. T₁ and T₂* maps through the liver and spleen were acquired prior to trans-jugular liver biopsy and hepatic vein pressure gradient (HVPG) measurement. T₁ measurements reflect changes in tissue water content, but this relationship is confounded by the presence of iron, which in turn can be quantified accurately from T₂* maps. Data were analysed using LiverMultiScan (Perspectum Diagnostics, Oxford, UK) which applies an algorithm to remove the confounding effect of iron, yielding the “iron corrected T₁” (cT₁). Sensitivity, specificity, diagnostic values and area under the curve were derived for spleen cT₁, liver cT₁, transient elastography, and serum fibrosis scores. HVPG was the reference standard. Nineteen patients (15 men) with median age 57 years were included. Liver disease aetiologies included non-alcoholic fatty liver disease (n = 9; 47%) and viral hepatitis (n = 4; 21%). There was strong correlation between spleen cT₁ and HVPG (r = 0.69; p = 0.001). Other non-invasive biomarkers did not correlate with HVPG. Spleen cT₁ had excellent diagnostic accuracy for portal hypertension (HVPG >5 mmHg) and clinically significant portal hypertension (HVPG ≥10 mmHg) with an area under the receiver operating characteristic curve of 0.92 for both. Spleen cT₁ is a promising biomarker of portal pressure that outperforms other non-invasive scores and should be explored further.

Modified Look‐Locker inversion recovery (MOLLI) T₁ mapping sequences can be useful in cardiac and liver tissue characterization, but determining underlying water T₁ is confounded by iron, fat and frequency offsets. This article proposes an algorithm that provides an independent water MOLLI T₁ (referred to as on‐resonance water T₁) that would have been measured if a subject had no fat and normal iron, and imaging had been done on resonance. Fifteen NiCl₂‐doped agar phantoms with different peanut oil concentrations and 30 adults with various liver diseases, nineteen (63.3%) with liver steatosis, were scanned at 3 T using the shortened MOLLI (shMOLLI) T₁ mapping, multiple‐echo spoiled gradient‐recalled echo and ¹H MR spectroscopy sequences. An algorithm based on Bloch equations was built in MATLAB, and water shMOLLI T₁ values of both phantoms and human participants were determined. The quality of the algorithm's result was assessed by Pearson's correlation coefficient between shMOLLI T₁ values and spectroscopically determined T₁ values of the water, and by linear regression analysis. Correlation between shMOLLI and spectroscopy‐based T₁ values increased, from r = 0.910 (P < 0.001) to r = 0.998 (P < 0.001) in phantoms and from r = 0.493 (for iron‐only correction; P = 0.005) to r = 0.771 (for iron, fat and off‐resonance correction; P < 0.001) in patients. Linear regression analysis revealed that the determined water shMOLLI T₁ values in patients were independent of fat and iron. It can be concluded that determination of on‐resonance water (sh)MOLLI T₁ independent of fat, iron and macroscopic field inhomogeneities was possible in phantoms and human subjects.

Purpose: Phosphorus (³¹P) metabolites are emerging liver disease biomarkers. Of particular interest are phosphomonoester and phosphodiester (PDE) “peaks” that comprise multiple overlapping resonances in ³¹P spectra. This study investigates the effect of improved spectral resolution at 7 Tesla (T) on quantifying hepatic metabolites in cirrhosis.Methods: Five volunteers were scanned to determine metabolite T₁s. Ten volunteers and 11 patients with liver cirrhosis were scanned at 7T. Liver spectra were acquired in 28 min using a 16‐channel ³¹P array and 3D chemical shift imaging. Concentrations were calculated using γ‐adenosine‐triphosphate (γ‐ATP) = 2.65 mmol/L wet tissue.Results: T₁ means ± standard deviations: phosphatidylcholine 1.05 ± 0.28 s, nicotinamide‐adenine‐dinucleotide (NAD⁺) 2.0 ± 1.0 s, uridine‐diphosphoglucose (UDPG) 3.3 ± 1.4 s. Concentrations in healthy volunteers: α‐ATP 2.74 ± 0.11 mmol/L wet tissue, inorganic phosphate 2.23 ± 0.20 mmol/L wet tissue, glycerophosphocholine 2.34 ± 0.46 mmol/L wet tissue, glycerophosphoethanolamine 1.50 ± 0.28 mmol/L wet tissue, phosphocholine 1.06 ± 0.16 mmol/L wet tissue, phosphoethanolamine 0.77 ± 0.14 mmol/L wet tissue, NAD⁺ 2.37 ± 0.14 mmol/L wet tissue, UDPG 2.00 ± 0.22 mmol/L wet tissue, phosphatidylcholine 1.38 ± 0.31 mmol/L wet tissue. Inorganic phosphate and phosphatidylcholine concentrations were significantly lower in patients; glycerophosphoethanolamine concentrations were significantly higher (P < 0.05).Conclusion: We report human in vivo hepatic T₁s for phosphatidylcholine, NAD⁺, and UDPG for the first time at 7T. Our protocol allows high signal‐to‐noise, repeatable measurement of metabolite concentrations in human liver. The splitting of PDE into its constituent peaks at 7T may allow more insight into changes in metabolism. Magn Reson Med 78:2095–2105, 2017. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.