Abstract Purpose To evaluate the test–retest repeatability of a rapid, free‐breathing two‐dimensional (2D) MR elastography (MRE) technique and to assess the reliability of the liver‐stiffness measurements compared with conventional breath‐hold MREs. Methods Fifteen and 115 participants were enrolled in the technical repeatability and measurement equivalence assessment cohorts, respectively. All participants underwent rapid free‐breathing and conventional breath‐hold 2D MRE (twice in repeatability cohort) on 1.5T scanners. Both methods have four phase offsets over one harmonic motion cycle at 60 Hz; one and 10 cycles were collected and processed in breath‐hold and free‐breathing MREs, respectively. The liver stiffness measurements of free‐breathing (LS F ) and breath‐hold MRE (LS B ) were calculated from manually drawn regions of interest. The repeatability coefficients and Spearman correlation were used to assess technical repeatability and measurement agreement between LS F and LS B . Univariable and multivariable linear regressions were performed to identify potential influencing factors, including age, sex, body mass index, and fat fraction, in the measurement agreement between LS B and LS F . Results The repeatability coefficient of free‐breathing 2D MRE is comparable to breath‐hold MRE (LS F : 20.8%, LS B : 20.4%). LS F showed a strong agreement and significant correlation with LS B (LS F = 1.01 × LS B , ρ = 0.94, p < 0.001). The measurement agreement between LS F and LS B was only significantly affected by sex ( p = 0.047) after adjusting for confounding factors of age, body mass index, and fat fraction. Conclusions The nongated, free‐breathing, multislice 2D MRE technique can provide reliable liver stiffness measurements compared with conventional breath‐hold 2D MRE. It could provide a comfortable alternative method with reliable liver stiffness measurements for patients who have difficulty in suspending respiration.
Automated Analysis of Multiparametric Magnetic Resonance Imaging/Magnetic Resonance Elastography Exams for Prediction of Nonalcoholic Steatohepatitis
BackgroundNonalcoholic fatty liver disease (NAFLD) affects 25% of the global population. The standard of diagnosis, biopsy, is invasive and affected by sampling error and inter‐reader variability. We hypothesized that widely available rapid MRI techniques could be used to predict nonalcoholic steatohepatitis (NASH) noninvasively by measuring liver stiffness, with magnetic resonance elastography (MRE), and liver fat, with chemical shift‐encoded (CSE) MRI. Besides, we validate an automated image analysis technique to maximize the utility of these methods.PurposeTo implement and test an automated system for analyzing CSE‐MRI and MRE data coupled with model‐based prediction of NASH.Study TypeProspective.SubjectsEighty‐three patients with suspected NAFLD.Field Strength/SequenceA 1.5 T using a flow‐compensated motion‐encoded gradient echo MRE sequence and a multiecho CSE‐MRI sequence.AssessmentsThe MRE and CSE‐MRI data were analyzed by two readers (5+ and 1 years of experience) and an automated algorithm. A logistic regression model to predict pathology‐diagnosed NASH was trained based on stiffness and proton density fat fraction, and the area under the receiver operating characteristic curve (AUROC) was calculated using 10‐fold cross validation for models based on both automated and manual measurements. A separate model was trained to predict the NASH severity score (NAS).Statistical TestsPearson's correlation, Bland–Altman, AUROC, C‐statistic.ResultsThe agreement between automated measurements and the more experienced reader (R2 = 0.87 for stiffness and R2 = 0.99 for proton density fat fraction [PDFF]) was slightly better than the agreement between readers (R2 = 0.85 and 0.98). The model for predicting biopsy‐diagnosed NASH had an AUROC of 0.87. The NAS‐prediction model had a C‐statistic of 0.85.Data ConclusionWe demonstrated a workflow that used a limited MRI acquisition protocol and fully automated analysis to predict NASH with high accuracy. These methods show promise to provide a reliable noninvasive alternative to biopsy for NASH‐screening in populations with NAFLD.Level of Evidence2Technical Efficacy Stage2
Assessment of advanced hepatic MR elastography methods for susceptibility artifact suppression in clinical patients
PurposeTo assess the success rate, image quality, and the ability to stage liver fibrosis of a standard 2D gradient‐recalled echo (GRE) and four different spin‐echo (SE) magnetic resonance elastography (MRE) sequences in patients with different liver iron concentrations.Materials and MethodsA total of 332 patients who underwent 3T MRE examinations that included liver fat and iron quantification were enrolled, including 136 patients with all five MRE techniques. Thirty‐four patients had biopsy results for fibrosis staging. The liver stiffness, region of interest area, image quality, and success rate of the five sequences were compared in 115/136 patients. The area under the receiver operating characteristic curves (AUCs) and the accuracies for diagnosing early‐stage fibrosis and advanced fibrosis were compared. The effect of BMI (body mass index), the R2* relaxation time, and fat fraction on the image quality and liver stiffness measurements were analyzed.ResultsThe success rates were significantly higher in the four SE sequences (99.1–100%) compared with GRE MRE (85.3%) (all P < 0.001). There were significant differences of the mean ROI area between every pair of sequences (all P < 0.0001). There were no significant differences in the AUC of the five MRE sequences for discriminating advanced fibrosis (10 P‐values ranging from 0.2410–0.9171). R2* had a significant effect on the success rate and image quality for the noniron 2D echo‐planar imaging (EPI), 3D EPI and 2D GRE (all P < 0.001) sequences. BMI had a significant effect on the iron 2D EPI (P = 0.0230) and iron 2D SE (P = 0.0040) sequences.ConclusionAll five techniques showed good diagnostic performance in staging liver fibrosis. The SE MRE sequences had higher success rates and better image quality than GRE MRE in 3T clinical hepatic imaging.Level of Evidence: 3Technical Efficacy: Stage 5J. Magn. Reson. Imaging 2018;47:976–987.
Magnetic resonance elastography measured shear stiffness as a biomarker of fibrosis in pediatric nonalcoholic fatty liver disease
Magnetic resonance elastography (MRE) is a promising technique for noninvasive assessment of fibrosis, a major determinant of outcome in nonalcoholic fatty liver disease (NAFLD). However, data in children are limited. The purpose of this study was to determine the accuracy of MRE for the detection of fibrosis and advanced fibrosis in children with NAFLD and to assess agreement between manual and novel automated reading methods. We performed a prospective, multicenter study of two‐dimensional (2D) MRE in children with NAFLD. MR elastograms were analyzed manually at two reading centers, and using a new automated technique. Analysis using each approach was done independently. Correlations were determined between MRE analysis methods and fibrosis stage. Thresholds for classifying the presence of fibrosis and of advanced fibrosis were computed and cross‐validated. In 90 children with a mean age of 13.1 ± 2.4 years, median hepatic stiffness was 2.35 kPa. Stiffness values derived by each reading center were strongly correlated with each other (r = 0.83). All three analyses were significantly correlated with fibrosis stage (center 1, ρ = 0.53; center 2, ρ = 0.55; and automated analysis, ρ = 0.52; P < 0.001). Overall cross‐validated accuracy for detecting any fibrosis was 72.2% for all methods (95% confidence interval [CI], 61.8%‐81.1%). Overall cross‐validated accuracy for assessing advanced fibrosis was 88.9% (95% CI, 80.5%‐94.5%) for center 1, 90.0% (95% CI, 81.9%‐95.3%) for center 2, and 86.7% (95% CI, 77.9%‐92.9%) for automated analysis. Conclusion : 2D MRE can estimate hepatic stiffness in children with NAFLD. Further refinement and validation of automated analysis techniques will be an important step in standardizing MRE. How to best integrate MRE into clinical protocols for the assessment of NAFLD in children will require prospective evaluation. (H epatology 2017;66:1474–1485)
AbstractBackground and Aim:Liver stiffness (LS) measured by magnetic resonance elastography (MRE) is emerging as an important biomarker in chronic liver diseases. We examined the diagnostic performance of MRE, factors associated with an increased LS and the prognostic value of LS as measured by MRE among patients with primary sclerosing cholangitis (PSC).Methods:We performed a retrospective review of 266 patients with PSC to examine whether LS was associated with the primary endpoint of hepatic decompensation (ascites, variceal hemorrhage and hepatic encephalopathy). The ability of MRE to differentiate stages of fibrosis was examined in a subset of patients who underwent a liver biopsy (n = 20).Results:An LS of 4.93 kPa was the optimal point to detected F4 fibrosis (sensitivity, 1.00; 95% confidence interval (CI), 0.40–1.00; specificity, 0.94; 95%CI, 0.68–1.00). While a serum alkaline phosphatase <1.5 times the upper limit of normal excluded the presence of advanced LS, it was not associated with the primary endpoint (hazard ratio, 0.26; 95%CI, 0.01–1.33). However, LS was associated with the development of decompensated liver disease (hazard ratio, 1.55; 95%CI, 1.41–1.70). The optimal LS thresholds that stratified patients at a low, medium and high risk for hepatic decompensation were <4.5, 4.5–6.0 and >6.0 kPa (respectively).Conclusion:Magnetic resonance elastography is able to detect cirrhosis with high specificity and an alkaline phosphatase <1.5 times the upper limit of normal makes the presence of advanced LS unlikely. Moreover, LS obtained by MRE is predictive of hepatic decompensation in PSC.
Evaluation of liver stiffness with magnetic resonance elastography in patients with constrictive pericarditis: Preliminary findings
PurposeTo evaluate with magnetic resonance elastography (MRE) whether patients with constrictive pericarditis (CP) have increased hepatic stiffness. CP results in reduced pericardial compliance, ventricular interdependence, and right heart failure. Patients with untreated CP may develop liver fibrosis and ultimately cirrhosis due to chronic venous congestion. Chronic venous congestion ± fibrosis may lead to increased liver stiffness.Materials and MethodsProspectively, patients with suspected CP underwent 2D transthoracic echocardiography, cardiac MRI, and liver MRE. An automated method was used to draw regions of interest (ROIs) on the stiffness maps to calculate the mean liver stiffness in kilopascals (kPa). A t‐test with α = 0.05 was performed between stiffness values of patients with positive and negative CP findings based on previously published echocardiography criteria.ResultsNineteen patients met inclusion criteria with a mean ± standard deviation (SD) age of 51 ± 16 years. Nine patients (47%) had CP. Mean liver stiffness trended higher in patients with CP compared to those without CP (4.04 kPa vs. 2.46; P = 0.045). Liver stiffness correlated with MRI septal bounce (P = 0.04), inferior vena cava size (P = 0.003), echo abnormal septal motion (P = 0.04), and echo mitral inflow variation >25% (P = 0.02). Only MRI septal bounce predicted CP by echocardiography (P < 0.001).ConclusionCP was associated with increased liver stiffness. The increased stiffness is most likely secondary to chronic hepatic venous congestion and/or fibrosis. MRE may be useful for noninvasive liver stiffness assessment in CP. J. Magn. Reson. Imaging 2016;44:81–88.
Automated liver elasticity calculation for MR elastography
PurposeMR elastography (MRE) is a phase‐contrast MRI technique that is used to quantitatively assess liver stiffness for staging hepatic fibrosis. The current approach requires manual selection of a region of interest (ROI) with good wave quality from which to measure stiffness. The purpose of this work was to develop and evaluate a fully automated approach for measuring hepatic stiffness from MRE images to further reduce measurement variability.Materials and MethodsAn automated liver elasticity calculation (ALEC) algorithm was developed to address reader stiffness measurement variability. ALEC has three stages: initial tissue estimation, segmentation, and ROI cleanup. Stiffnesses measured by the algorithm were compared with technicians and an expert radiologist in a set of 121 clinical cases acquired at 1.5 Tesla. Intra‐class correlation (ICC), Bland‐Altman analysis, and a noninferiority test were performed to evaluate whether the algorithm can be used in place of manual analysis by technicians.ResultsThe stiffness measurement difference with the expert was 1.42% ± 11.17% (mean ± standard deviation) for the algorithm and 1.82% ± 13.65% for the technicians. The ICCs were 0.981 and 0.984, respectively. Both the algorithm and technicians were equivalent to the expert within a 5% significance margin (P < 0.01). The algorithm had no failures in the 119 cases that were considered analyzable by the human readers.ConclusionThe results of this study show that the newly developed automated algorithm is able to measure stiffness in clinical liver MRE exams with an accuracy that is equivalent to that of an expert radiologist. ALEC may be useful for analysis of archived data and suitable for performing multi‐center studies. J. Magn. Reson. Imaging 2016;43:1055–1063.
Automated liver stiffness measurements with magnetic resonance elastography