Ehman, Richard L.

Purpose Magnetic resonance elastography (MRE) is a rapidly growing noninvasive imaging technique for measuring tissue mechanical properties in vivo. Previous studies have compared two‐dimensional MRE measurements with material properties from dynamic mechanical analysis (DMA) devices that were limited in frequency range. Advanced DMA technology now allows broad frequency range testing, and three‐dimensional (3D) MRE is increasingly common. The purpose of this study was to compare 3D MRE stiffness measurements with those of DMA over a wide range of frequencies and shear stiffnesses. Methods 3D MRE and DMA were performed on eight different polyvinyl chloride samples over 20–205 Hz with stiffness between 3 and 23 kPa. Driving frequencies were chosen to create 1.1, 2.2, 3.3, 4.4, 5.5, and 6.6 effective wavelengths across the diameter of the cylindrical phantoms. Wave images were analyzed using direct inversion and local frequency estimation algorithm with the curl operator and compared with DMA measurements at each corresponding frequency. Samples with sufficient spatial resolution and with an octahedral shear strain signal‐to‐noise ratio > 3 were compared. Results Consistency between the two techniques was measured with the intraclass correlation coefficient (ICC) and was excellent with an overall ICC of 0.99. Conclusions 3D MRE and DMA showed excellent consistency over a wide range of frequencies and stiffnesses. Magn Reson Med 77:1184–1192, 2017. © 2016 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‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

Objective The aim of this study was to compare 2-dimensional (2D) gradient recalled echo (GRE) and 2D spin echo echoplanar imaging (SE-EPI) magnetic resonance elastography (MRE) sequences of the liver in terms of image quality and quantitative liver stiffness (LS) measurement. Materials and Methods This prospective study involved 50 consecutive subjects (male/female, 33/17; mean age, 58 years) who underwent liver magnetic resonance imaging at 3.0 T including 2 MRE sequences, 2D GRE, and 2D SE-EPI (acquisition time 56 vs 16 seconds, respectively). Image quality scores were assessed by 2 independent observers based on wave propagation and organ coverage on the confidence map (range, 0–15). A third observer measured LS on stiffness maps (in kilopascal). Mean LS values, regions of interest size (based on confidence map), and image quality scores between SE-EPI and GRE-MRE were compared using paired nonparametric Wilcoxon test. Reproducibility of LS values between the 2 sequences was assessed using intraclass coefficient correlation, coefficient of variation, and Bland-Altman limits of agreement. T2* effect on image quality was assessed using partial Spearman correlation. Results There were 4 cases of failure with GRE-MRE and none with SE-EPI-MRE. Image quality scores and region of interest size were significantly higher using SE-EPI-MRE versus GRE-MRE (P < 0.0001 for both measurements and observers). Liver stiffness measurements were not significantly different between the 2 sequences (3.75 ± 1.87 kPa vs 3.55 ± 1.51 kPa, P = 0.062), were significantly correlated (intraclass coefficient correlation, 0.909), and had excellent reproducibility (coefficient of variation, 10.2%; bias, 0.023; Bland-Altman limits of agreement, −1.19; 1.66 kPa). Image quality scores using GRE-MRE were significantly correlated with T2* while there was no correlation for SE-EPI-MRE. Conclusions Our data suggest that SE-EPI-MRE may be a better alternative to GRE-MRE. The diagnostic performance of SE-EPI-MRE for detection of liver fibrosis needs to be assessed in a future study.

PurposeTo investigate the feasibility of utilizing brain stiffness as a potential biomarker for behavioral variant frontotemporal dementia (bvFTD) patients. Magnetic resonance elastography (MRE) is a noninvasive technique for evaluating the mechanical properties of brain tissue in vivo. MRE has demonstrated decreased brain stiffness in patients with Alzheimer's disease.Materials and MethodsWe examined five male subjects with bvFTD and nine cognitively normal age‐matched male controls (NC) with brain 3T MRE. Stiffness was calculated in nine regions of interest (ROIs): whole brain (entire cerebrum excluding cerebellum), frontal lobes, occipital lobes, parietal lobes, temporal lobes, deep gray matter / white matter (GM/WM; insula, deep gray nuclei and white matter tracts), cerebellum, sensorimotor cortex (pre‐ and postcentral gyri), and a composite region labeled FT (frontal and temporal lobes excluding the pre‐ and postcentral gyri).ResultsSignificantly lower stiffness values were observed in the whole brain (P = 0.007), frontal lobe (P = 0.001), and temporal lobes (P = 0.005) of bvFTD patients compared to NC. No significant stiffness differences were observed in any other ROIs of bvFTD patients compared to NC (P > 0.05). These results demonstrate that statistically significant brain softening occurs in the frontal and temporal lobes of bvFTD patients, which corresponds to the expected pathophysiology of bvFTD.ConclusionFuture studies evaluating the feasibility of brain MRE for early disease detection and monitoring disease progression could shed new insights into understanding the mechanisms involved in bvFTD. J. Magn. Reson. Imaging 2016;43:474–478.

Purpose Noninvasive stiffness imaging techniques (elastography) can image myocardial tissue biomechanics in vivo. For cardiac MR elastography (MRE) techniques, the optimal vibration frequency for in vivo experiments is unknown. Furthermore, the accuracy of cardiac MRE has never been evaluated in a geometrically accurate phantom. Therefore, the purpose of this study was to determine the necessary driving frequency to obtain accurate three‐dimensional (3D) cardiac MRE stiffness estimates in a geometrically accurate diastolic cardiac phantom and to determine the optimal vibration frequency that can be introduced in healthy volunteers. Methods The 3D cardiac MRE was performed on eight healthy volunteers using 80 Hz, 100 Hz, 140 Hz, 180 Hz, and 220 Hz vibration frequencies. These frequencies were tested in a geometrically accurate diastolic heart phantom and compared with dynamic mechanical analysis (DMA). Results The 3D Cardiac MRE was shown to be feasible in volunteers at frequencies as high as 180 Hz. MRE and DMA agreed within 5% at frequencies greater than 180 Hz in the cardiac phantom. However, octahedral shear strain signal to noise ratios and myocardial coverage was shown to be highest at a frequency of 140 Hz across all subjects. Conclusion This study motivates future evaluation of high‐frequency 3D MRE in patient populations. Magn Reson Med 77:351–360, 2017. © 2016 Wiley Periodicals, Inc.

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.

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.

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.

PurposeTo assess interplatform reproducibility of liver stiffness (LS) and spleen stiffness (SS) measured with magnetic resonance elastography (MRE) based on a 2D gradient echo (GRE) sequence.Materials and MethodsThis prospective Health Insurance Portability and Accountability Act (HIPAA)‐compliant and Institutional Review Board (IRB)‐approved study involved 12 subjects (five healthy volunteers and seven patients with liver disease). A multislice 2D‐GRE‐based MRE sequence was performed using two systems from different vendors (3.0T GE and 1.5T Siemens) on the same day. Two independent observers measured LS and SS on confidence maps. Bland–Altman analysis (with coefficient of reproducibility, CR), coefficient of variability (CV), and intraclass correlation (ICC) were used to analyze interplatform, intra‐ and interobserver variability. Human data were validated using a gelatin‐based phantom.ResultsThere was excellent reproducibility of phantom stiffness measurement (CV 4.4%). Mean LS values were 3.44–3.48 kPa and 3.62–3.63 kPa, and mean SS values were 7.54–7.91 kPa and 8.40–8.85 kPa at 3.0T and 1.5T for observers 1 and 2, respectively. The mean CVs between platforms were 9.2%–11.5% and 13.1%–14.4% for LS and SS, respectively, for observers 1 and 2. There was excellent interplatform reproducibility (ICC >0.88 and CR <36.2%) for both LS and SS, and excellent intra‐ and interobserver reproducibility (intraobserver: ICC >0.99, CV <2.1%, CR <6.6%; interobserver: ICC >0.97, CV and CR <16%).ConclusionThis study demonstrates that 2D‐GRE MRE provides platform‐ and observer‐independent LS and SS measurements. J. Magn. Reson. Imaging 2016;43:1064–1072.

PurposeTo investigate the feasibility of utilizing brain stiffness as a potential biomarker for behavioral variant frontotemporal dementia (bvFTD) patients. Magnetic resonance elastography (MRE) is a noninvasive technique for evaluating the mechanical properties of brain tissue in vivo. MRE has demonstrated decreased brain stiffness in patients with Alzheimer's disease.Materials and MethodsWe examined five male subjects with bvFTD and nine cognitively normal age‐matched male controls (NC) with brain 3T MRE. Stiffness was calculated in nine regions of interest (ROIs): whole brain (entire cerebrum excluding cerebellum), frontal lobes, occipital lobes, parietal lobes, temporal lobes, deep gray matter / white matter (GM/WM; insula, deep gray nuclei and white matter tracts), cerebellum, sensorimotor cortex (pre‐ and postcentral gyri), and a composite region labeled FT (frontal and temporal lobes excluding the pre‐ and postcentral gyri).ResultsSignificantly lower stiffness values were observed in the whole brain (P = 0.007), frontal lobe (P = 0.001), and temporal lobes (P = 0.005) of bvFTD patients compared to NC. No significant stiffness differences were observed in any other ROIs of bvFTD patients compared to NC (P > 0.05). These results demonstrate that statistically significant brain softening occurs in the frontal and temporal lobes of bvFTD patients, which corresponds to the expected pathophysiology of bvFTD.ConclusionFuture studies evaluating the feasibility of brain MRE for early disease detection and monitoring disease progression could shed new insights into understanding the mechanisms involved in bvFTD. J. Magn. Reson. Imaging 2016;43:474–478.

Ezetimibe inhibits intestinal cholesterol absorption and lowers low‐density lipoprotein cholesterol. Uncontrolled studies have suggested that it reduces liver fat as estimated by ultrasound in nonalcoholic steatohepatitis (NASH). Therefore, we aimed to examine the efficacy of ezetimibe versus placebo in reducing liver fat by the magnetic resonance imaging‐derived proton density‐fat fraction (MRI‐PDFF) and liver histology in patients with biopsy‐proven NASH. In this randomized, double‐blind, placebo‐controlled trial, 50 patients with biopsy‐proven NASH were randomized to either ezetimibe 10 mg orally daily or placebo for 24 weeks. The primary outcome was a change in liver fat as measured by MRI‐PDFF in colocalized regions of interest within each of the nine liver segments. Novel assessment by two‐dimensional and three‐dimensional magnetic resonance elastography was also performed. Ezetimibe was not significantly better than placebo at reducing liver fat as measured by MRI‐PDFF (mean difference between the ezetimibe and placebo arms ‐1.3%, P = 0.4). Compared to baseline, however, end‐of‐treatment MRI‐PDFF was significantly lower in the ezetimibe arm (15%‐11.6%, P < 0.016) but not in the placebo arm (18.5%‐16.4%, P = 0.15). There were no significant differences in histologic response rates, serum alanine aminotransferase and aspartate aminotransferase levels, or longitudinal changes in two‐dimensional and three‐dimensional magnetic resonance elastography‐derived liver stiffness between the ezetimibe and placebo arms. Compared to histologic nonresponders (25/35), histologic responders (10/35) had a significantly greater reduction in MRI‐PDFF (‐4.35 ± 4.9% versus ‐0.30 ± 4.1%, P < 0.019). Conclusions : Ezetimibe did not significantly reduce liver fat in NASH. This trial demonstrates the application of colocalization of MRI‐PDFF‐derived fat maps and magnetic resonance elastography‐derived stiffness maps of the liver before and after treatment to noninvasively assess treatment response in NASH. (H epatology 2015;61:1239–1250)