Regional phase correction of inversion-recovery MR images

Many MR imaging systems are limited in their ability to successfully display inversion-recovery images. The reason is that part of the contrast is encoded as phase differences between pixels, whereas in the more commonly used spin-echo pulse sequence all the information is contained in the pixel magnitude. Inversion-recovery images are often displayed in magnitude form, resulting in loss of potentially useful phase information contained in the data. Before this phase information can be used, phase errors which result from scanner imperfections must be removed. While most of the necessary correction can be accomplished using data obtained by scanning a uniform phantom, this approach has several disadvantages. An alternative method by which phase errors can be readily removed without phantom data is described. This method has been applied to images of the head, knee, and liver with good results. It is concluded that this technique is useful for producing phase corrected inversion-recovery MR images © 1990 Academic Press, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38482/1/1910140107_ftp.pd

Randomised clinical trial: a leucine-metformin-sildenafil combination (NS-0200) vs placebo in patients with non-alcoholic fatty liver disease

BACKGROUND: Sirtuin 1 (Sirt1) is suppressed in non-alcoholic fatty liver disease (NAFLD), while its' stimulation or overexpression results in reduced disease severity in pre-clinical NAFLD models. Leucine allosterically activates Sirt1 and synergise with other Sirt/AMPK/NO pathway activators. We developed a triple combination of leucine, metformin and sildenafil (NS-0200), which was effective in a mouse model of non-alcoholic steatohepatitis (NASH). AIM: To report the results from a Phase 2, randomised clinical trial of of NS-0200 in 91 subjects with NAFLD (liver fat ≥15% by magnetic resonance imaging-proton-density fat fraction (MRI-PDFF)). METHODS: Subjects were randomised to placebo, low-dose (1.1 g leucine/0.5 g metformin/0.5 mg sildenafil) or high-dose NS-0200 (1.1 g leucine/0.5 g metformin/1.0 mg sildenafil) b.d. for 16 weeks; change in hepatic fat was assessed via MRI-PDFF, and lipid metabolism was assessed via changes in the lipidomic signature. Seventy subjects completed the trial and met a priori compliance criteria. Analyses were conducted on the full cohort and on those with alanine aminotransferase (ALT) values above median (50 U/L; n = 35). RESULTS: In the full cohort, active treatments did not separate from placebo. High dose NS-0200 reduced hepatic fat by 15.7% (relative change from baseline) in the high ALT group (P < 0.005) while low dose NS-0200 and placebo did not significantly change hepatic fat. Lipidomic analysis showed dose-responsive treatment effects in both overall and high ALT cohorts, with significant decreases in metabolically active lipids and up-regulation of fatty acid oxidation. CONCLUSION: These data support further evaluation of high-dose NS-0200 for treating NASH, especially in those with elevated ALT (NCT 02546609)

Stereological analysis of liver biopsy histology sections as a reference standard for validating non-invasive liver fat fraction measurements by MRI

© 2016 St. Pierre et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background and Aims: Validation of non-invasive methods of liver fat quantification requires a reference standard. However, using standard histopathology assessment of liver biopsies is problematical because of poor repeatability. We aimed to assess a stereological method of measuring volumetric liver fat fraction (VLFF) in liver biopsies and to use the method to validate a magnetic resonance imaging method for measurement of VLFF. Methods: VLFFs were measured in 59 subjects (1) by three independent analysts using a stereological point counting technique combined with the Delesse principle on liver biopsy histological sections and (2) by three independent analysts using the HepaFat-Scan® technique on magnetic resonance images of the liver. Bland Altman statistics and intraclass correlation (IC) were used to assess the repeatability of each method and the bias between the methods of liver fat fraction measurement. Results: Inter-analyst repeatability coefficients for the stereology and HepaFat-Scan® methods were 8.2 (95% CI 7.7-8.8)% and 2.4 (95% CI 2.2-2.5)% VLFF respectively. IC coefficients were 0.86 (95% CI 0.69-0.93) and 0.990 (95% CI 0.985-0.994) respectively. Small biases (=3.4%) were observable between two pairs of analysts using stereology while no significant biases were observable between any of the three pairs of analysts using Hepa-Fat-Scan®. A bias of 1.4±0.5% VLFF was observed between the HepaFat-Scan® method and the stereological method. Conclusions: Repeatability of the stereological method is superior to the previously reported performance of assessment of hepatic steatosis by histopathologists and is a suitable reference standard for validating non-invasive methods of measurement of VLFF

Diagnostic performance of a rapid magnetic resonance imaging method of measuring hepatic steatosis

Objectives: Hepatic steatosis is associated with an increased risk of developing serious liver disease and other clinical sequelae of the metabolic syndrome. However, visual estimates of steatosis from histological sections of biopsy samples are subjective and reliant on an invasive procedure with associated risks. The aim of this study was to test the ability of a rapid, routinely available, magnetic resonance imaging (MRI) method to diagnose clinically relevant grades of hepatic steatosis in a cohort of patients with diverse liver diseases. Materials and Methods: Fifty-nine patients with a range of liver diseases underwent liver biopsy and MRI. Hepatic steatosis was quantified firstly using an opposed-phase, in-phase gradient echo, single breath-hold MRI methodology and secondly, using liver biopsy with visual estimation by a histopathologist and by computer-assisted morphometric image analysis. The area under the receiver operating characteristic (ROC) curve was used to assess the diagnostic performance of the MRI method against the biopsy observations. Results: The MRI approach had high sensitivity and specificity at all hepatic steatosis thresholds. Areas under ROC curves were 0.962, 0.993, and 0.972 at thresholds of 5%, 33%, and 66% liver fat, respectively. MRI measurements were strongly associated with visual (r2 = 0.83) and computer-assisted morphometric (r2 = 0.84) estimates of hepatic steatosis from histological specimens. Conclusions: This MRI approach, using a conventional, rapid, gradient echo method, has high sensitivity and specificity for diagnosing liver fat at all grades of steatosis in a cohort with a range of liver diseases

Spatial distribution of MRI-determined hepatic proton density fat fraction in adults with nonalcoholic fatty liver disease

PURPOSE: To describe the spatial distribution of liver fat, using magnetic resonance imaging (MRI)-estimated proton density fat fraction (PDFF), in adults with non-alcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS: This IRB-approved, HIPAA-compliant study prospectively enrolled fifty adults (30 women, 20 men) with biopsy-proven NAFLD. Hepatic PDFF was measured by low-flip-angle multiecho spoiled gradient-recalled-echo MRI at 3T. Three non-overlapping regions of interest were placed within each liver segment. Statistical analyses included Pearson’s correlation, multivariable linear regression, and permutation-based paired tests. RESULTS: The study population’s mean whole-liver PDFF was 16.1% (range: 1.6–39.6%). The mean whole-liver PDFF variability was 1.9% (range: 0.7–4.5%). Higher variability was associated with higher PDFF (r=0.34, p=0.0156). The mean PDFF was significantly higher in the right lobe than the left (16.5% vs. 15.3%, p=0.0028). The mean PDFF variability was higher in the left lobe than the right (1.86% vs. 1.28%, p<0.0001). Segment II had the lowest mean segmental PDFF (14.8%); segment VIII had the highest (16.7%). Segments V (0.71%) and VI (0.70%) had the lowest mean segmental PDFF variability; segment II had the highest (1.32%). CONCLUSION: In adult NAFLD there are small but significant differences in fat content and variability between lobes and some of the segments