Glaser, Kevin J.

Background: Accurate identification of patients with metabolic dysfunction–associated steatohepatitis (MASH) at risk of disease progression (at-risk MASH) is critical for guiding resmetirom and semaglutide therapy. Inconsistent definitions of at-risk MASH complicate clinical risk classification and comparisons across studies. This study aimed to standardize the definition of at-risk MASH and propose optimized MRE-based liver stiffness (LS-MRE) cutoffs to improve noninvasive risk stratification and better guide pharmacotherapy. Methods: In this prospective study, 413 patients with suspected or diagnosed MASLD from two medical centers underwent liver biopsy and MRE. Results: A simplified definition of at-risk MASH (MASH with fibrosis stage≥2) identified a broader group of patients requiring clinical attention than a stricter definition requiring NAFLD Activity Score≥4 with ≥1 point in steatosis, inflammation, and ballooning (n=122 vs. 77). LS-MRE alone showed the highest diagnostic accuracy for identifying at-risk MASH using the simplified definition (AUC 0.91 [0.87, 0.95]) and cirrhosis (AUC 0.93 [0.88, 0.99]), compared with FIB-4 and individual laboratory parameters (AST, ALT, and platelet count) ( p <0.01 for all, paired DeLong tests). Optimized LS-MRE cutoffs (2.8–6.4 kPa) captured 25 additional biopsy-proven pharmacotherapy candidates (28% of all eligible patients) compared to AASLD guidelines–recommended cutoffs (3.1–4.4 kPa), improving sensitivity (80% vs. 50%) with acceptable specificity (73% vs. 88%). Conclusions: A simplified definition of at-risk MASH enables broader identification of treatment candidates. LS-MRE demonstrates excellent diagnostic performance and improves noninvasive risk stratification when paired with optimized cutoffs. These findings support the use of MRE to guide resmetirom and semaglutide eligibility and improve access to emerging therapies.

Abstract Background Cardiac magnetic resonance elastography (MRE) allows the non-invasive quantification of myocardial stiffness, but long-interval reproducibility data at 3.0 T single-frequency 140-Hz remain limited. Purpose To evaluate the short- and long-interval reproducibility of 3.0 T cardiac MRE for left ventricular (LV) myocardial stiffness across healthy volunteers and patients with conditions associated with elevated myocardial stiffness. Materials and Methods This prospective single-center study included 69 participants: 60 healthy volunteers and 9 with cardiovascular disease (6 with aortic stenosis and 3 with long-standing hypertension). All participants underwent baseline cardiac MRE (scanner: Signa Premier 3.0 T, GE Healthcare, driver: Resoundant), an immediate short-interval rescan (SIR) within 5 minutes, and a long-interval rescan (LIR) after approximately 1 month. Left ventricular myocardial stiffness and octahedral shear strain signal-to-noise ratio were measured independently by 2 readers. Reproducibility was assessed using Bland-Altman analysis, intraclass correlation coefficients (ICCs), within-subject coefficient of variation, standard error of measurement, and smallest detectable change at the 95% confidence (SDC95) level. Results Baseline LV myocardial stiffness was higher in the disease group than in healthy volunteers, 11.73 ± 1.01 kPa and 7.80 ± 0.70 kPa (mean ± SD; P &lt; .001), respectively. Inter-reader agreement was excellent across all timepoints, with ICCs of 0.970 at baseline (95% CI, 0.953-0.982), 0.966 for SIR (95% CI, 0.945-0.979), and 0.962 for LIR (95% CI, 0.939-0.976). Within-reader scan-rescan reproducibility was also excellent. For Reader 1, stiffness ICC was 0.979 for the SIR (95% CI, 0.966-0.987) and 0.957 for the LIR (95% CI, 0.932-0.973), with SDC95 values of 0.616 kPa (95% CI, 0.528-0.741) and 0.869 kPa (95% CI, 0.744-1.044), respectively. Reader 2 showed excellent reproducibility, with ICCs ≤0.943. Conclusions 3D single-frequency 140-Hz cardiac MRE at 3.0 T provides excellent short- and long-interval reproducibility for LV myocardial stiffness quantification. The SDC95 values may help distinguish true longitudinal stiffness changes from measurement variability.

ABSTRACT Purpose Magnetic resonance elastography (MRE) of the heart has predominantly utilized breath‐held acquisitions with limited anatomic coverage. This work investigates the feasibility of 3D, free‐breathing cardiac MRE. Methods A 3D hybrid radial and EPI acquisition is utilized and combined with retrospective binning of k ‐space via physiologic monitoring, iterative reconstruction, MRE processing and inversions, and post‐processing specialized for cardiac imaging. Results Feasibility of free‐breathing stiffness mapping of the left ventricular myocardium was demonstrated in 11 participants. Myocardial stiffness estimates were obtained throughout the left ventricle for seven temporal states of the cardiac cycle. Stiffness estimates were presented in participant‐specific images, 17‐segment bullseye plots, and stiffness plots throughout the cardiac cycle. Results indicate increased stiffness in systolic states, with localized stiffness heterogeneity observed between participants, illustrating a key benefit of 3D cardiac MRE acquisition. Mean stiffness estimates obtained through 11 subjects were 4.44 ± 0.68 kPa (begin‐systole), 5.74 ± 0.94, 5.42 ± 0.87 (end‐systole), 3.84 ± 0.71 (begin‐diastole), 3.51 ± 0.74, 3.54 ± 0.52, and 3.55 ± 0.59 kPa (end‐diastole). Statistical testing indicated significant differences in stiffness across cardiac states with one‐way, repeated‐measures ANOVA ( p < 0.001) and Friedman's test ( p < 0.001). Experiments in scanning three participants with and without applied motion indicated that stiffness changes were more robustly detected in systole than in diastole, although patterns were subject‐specific. Comparison of free‐breathing stiffness measurements against reference breath‐held measurements yielded similar systolic stiffness estimates. Conclusions This study establishes the feasibility of free‐breathing, 3D cardiac MRE in healthy volunteers. With the current framework, stiffness estimation appears more robust in systole, and the reliability of diastolic estimates is limited and subject‐specific.

AbstractPurposeWhile standard MR elastography (MRE) uses harmonic mechanical waves, there are some applications in which imaging and analysis of transient mechanical motion are of interest. Wavelet MRE has been developed for detecting broadband motion from transient excitation. The goal of this study was to evaluate the accuracy and efficiency of wavelet MRE for transient displacement detection in brain MRE applications.MethodsTransient motion was induced in a gel phantom, while MRE images were acquired using bipolar motion‐encoding gradient (MEG) at multiple frequencies (20–200 Hz). Displacements were estimated using (1) combinations of multiple MEGs forming the wavelet MRE and (2) deconvolution from a single MEG. These estimated displacements were used to calculate the MRE phase for each MEG. Correlation (r2) between the calculated and acquired phases was evaluated.Three healthy volunteers were scanned twice in a clinical scanner using wavelet MRE with an occipital impact. Time‐resolved brain translation, rotation, and maximal principal strain were calculated. Repeatability was assessed both qualitatively and through Pearson correlation.ResultsWavelet MRE outperformed standard MRE in displacement estimation, showing higher correlations between calculated and acquired phase, even with fewer phase offsets. In the volunteer study, consistent temporal motion dynamics and spatial maximal principal strain distributions across repeated scans demonstrated the repeatability of wavelet MRE.ConclusionThis study validated the accuracy and efficiency of wavelet MRE for broadband motion detection and demonstrated its feasibility and repeatability in vivo. This technique shows promise for advancing our understanding of the injury risks and mechanisms associated with sports‐related head trauma.

Spatial heterogeneity of liver viscoelasticity, measured at three-dimensional vector MR elastography, positively correlated with metabolic dysfunction–associated steatotic liver disease progression.

ABSTRACTThe goal of the present study was to investigate the effect of positioning a soft flexible tube‐based actuator parallel or orthogonal to the principle muscle fibre direction, on measurements of the stiffness of upper trapezius (UT) muscle obtained using magnetic resonance elastography (MRE). The effects of using three different vibration frequencies (60 Hz, 80 Hz and 100 Hz) and studying left and right sides of the body were also investigated. The relevant MRE datasets were acquired on a 1.5 T MRI system using a 2D gradient‐echo (GRE) MRE sequence, and corresponding wave images produced using multimodel direct inversion (MMDI) were analysed by two observers using the manual caliper technique. Except for two of the 108 individual datasets, when the agreement was moderate, there was substantial to perfect agreement between wave quality scores obtained by the two observers, with an identical mean value. Similarly, and again with only two exceptions, there was good to excellent agreement between the measurements of UT stiffness obtained by the two observers. UT stiffness values obtained when the acoustic waves were propagating along the principle muscle fibre direction were significantly higher than when the waves were propagating orthogonal to the principle muscle fibre direction at all vibration frequencies (p < 0.005), and only for the former was a significant dispersion effect observed whereby stiffness increased as frequency increased (p < 0.05). No significant asymmetry was observed in measurements of UT stiffness obtained for the left and right sides of the body (p = 0.29). In conclusion, the new soft and flexible tube‐based actuator is comfortable and produced very good wave propagation in UT when positioned in either orientation. However, it is recommended for wave propagation to be induced in the principle fibre direction and there was found to be no advantage in using a vibration frequency above 60 Hz.

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.

BackgroundMR elastography (MRE) at 60 Hz is widely used for staging liver fibrosis. MRE with lower frequencies may provide inflammation biomarkers.PurposeTo establish a practical simultaneous dual‐frequency liver MRE protocol at both 30 Hz and 60 Hz during a single examination and validate the occurrence of second harmonic waves at 30 Hz.Study TypeRetrospective.SubjectsOne hundred six patients (48 females, age: 50.0 ± 13.4 years) were divided as follows: Cohort One (15 patients with chronic liver disease [CLD] and 25 healthy volunteers) with simultaneous dual‐frequency MRE. Cohort Two (66 patients with CLD) with second harmonic MRE.Field Strength/Sequence3‐T, single‐ or dual‐frequency MRE at 30 Hz and 60 Hz.AssessmentLiver stiffness (LS) in both cohorts was evaluated with manually placed volumetric ROIs by two independent analyzers. Image quality was assessed by three independent readers on a 4‐point scale (0–3: none/failed, fair, moderate, excellent) based on the depth of wave propagation with 1/3 incremental penetration. The success rate was derived from the percentage of nonzero quality scores.Statistical TestsMeasurement agreement, bias, and repeatability of LS were assessed using intraclass correlation coefficients (ICCs), Bland–Altman plots, and repeatability coefficient (RC). Mann–Whitney U tests were used to evaluate the differences in image quality between different methods. A P‐value <0.05 was considered statistically significant.ResultsSuccess rate was 97.5% in Cohort One and 91% success rate for the second harmonic MRE in Cohort Two. The second harmonic and conventional MRE showed excellent agreement in LS (all ICCs >0.90). The quality scores for the second harmonic wave images were lower than those from the conventional MRE (Z = −4.523).Data ConclusionCompared with conventional and second harmonic methods, simultaneous dual‐frequency had better image quality, high success rate and the advantage of intrinsic co‐registration, while the second harmonic method can be an alternative if custom waveform is not available.Evidence Level3Technical EfficacyStage 1

Abstract Functional MRI (fMRI) is widely used to spatially localize neural activity in the brain associated with functional stimuli. Functional MR Elastography (fMRE) has recently been introduced as a complementary approach that measures the mechanical response to functional stimulus. The hypothesis of the current study is that the stiffness change in fMRE is proportional to the underlying neural activity. This hypothesis is tested by measuring the median stiffness change in the visual cortex as a function of luminance-matched contrast intensity of a checkerboard visual stimulus in 16 healthy subjects. The fMRE signal in the visual cortex was observed to be proportional to the contrast intensity of the visual stimulus. In regions of activation, fMRE signal increased in the range of 2 ± 1% to 5.8 ± 1% and fMRI signal increased by the expected 0.4 ± 0.2% to 0.9 ± 0.2%, for contrast levels of 5% to 100%, respectively. In conclusion, this study shows that the fMRE signal in the visual cortex can be directly modulated by the contrast intensity of a visual stimulus. The presence of some overlap between fMRI and fMRE regions of activation may suggest two distinct mechanisms governing the fMRI and fMRE signals, which will be investigated in future studies.