Wavelet MRE: Imaging propagating broadband acoustic waves with wavelet-based motion-encoding gradients.

PURPOSE: To demonstrate a novel MR elastography (MRE) technique, termed here wavelet MRE. With this technique, broadband motion sensitivity is achievable. Moreover, the true tissue displacement can be reconstructed with a simple inverse transform. METHODS: A wavelet MRE sequence was developed with motion-encoding gradients based on Haar wavelets. From the phase images' displacement was estimated using an inverse transform. Simulations were performed using a frequency sweep and a transient as ground-truth motions. A PVC phantom was scanned using wavelet MRE and standard MRE with both transient (one and 10 cycles of 90-Hz motion) and steady-state dual-frequency motion (30 and 60 Hz) for comparison. The technique was tested in a human brain, and motion trajectories were estimated for each voxel. RESULTS: In simulation, the displacement information estimated from wavelet MRE closely matched the true motion. In the phantom test, the MRE phase data generated from the displacement information derived from wavelet MRE agreed well with standard MRE data. Testing of wavelet MRE to assess transient motion waveforms in the brain was successful, and the tissue motion observed was consistent with a previous study. CONCLUSION: The uniform and broadband frequency response of wavelet MRE makes it a promising method for imaging transient, multifrequency motion, or motion with unknown frequency content. One potential application is measuring the response of brain tissue undergoing low-amplitude, transient vibrations as a model for the study of traumatic brain injury.

Head-to-head comparison of magnetic resonance elastography-based liver stiffness, fat fraction, and T1 relaxation time in identifying at-risk NASH.

BACKGROUND AND AIMS: The presence of at-risk NASH is associated with an increased risk of cirrhosis and complications. Therefore, noninvasive identification of at-risk NASH with an accurate biomarker is a critical need for pharmacologic therapy. We aim to explore the performance of several magnetic resonance (MR)-based imaging parameters in diagnosing at-risk NASH. APPROACH AND RESULTS: This prospective clinical trial (NCT02565446) includes 104 paired MR examinations and liver biopsies performed in patients with suspected or diagnosed NAFLD. Magnetic resonance elastography-assessed liver stiffness (LS), 6-point Dixon-derived proton density fat fraction (PDFF), and single-point saturation-recovery acquisition-calculated T1 relaxation time were explored. Among all predictors, LS showed the significantly highest accuracy in diagnosing at-risk NASH [AUC LS : 0.89 (0.82, 0.95), AUC PDFF : 0.70 (0.58, 0.81), AUC T1 : 0.72 (0.61, 0.82), z -score test z >1.96 for LS vs any of others]. The optimal cutoff value of LS to identify at-risk NASH patients was 3.3 kPa (sensitivity: 79%, specificity: 82%, negative predictive value: 91%), whereas the optimal cutoff value of T1 was 850 ms (sensitivity: 75%, specificity: 63%, and negative predictive value: 87%). PDFF had the highest performance in diagnosing NASH with any fibrosis stage [AUC PDFF : 0.82 (0.72, 0.91), AUC LS : 0.73 (0.63, 0.84), AUC T1 : 0.72 (0.61, 0.83), |z| <1.96 for all]. CONCLUSION: Magnetic resonance elastography-assessed LS alone outperformed PDFF, and T1 in identifying patients with at-risk NASH for therapeutic trials.

Acquisition Efficiency and Technical Repeatability of Dual-Frequency 3D Vector MR Elastography of the Liver.

BACKGROUND: MR elastography (MRE) at 60 Hz is widely used for staging liver fibrosis. MRE with lower frequencies may provide inflammation biomarkers. PURPOSE: To 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 TYPE: Retrospective. SUBJECTS: One 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/SEQUENCE: 3-T, single- or dual-frequency MRE at 30 Hz and 60 Hz. ASSESSMENT: Liver 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 TESTS: Measurement 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. RESULTS: Success 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 CONCLUSION: Compared 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 LEVEL: 3 TECHNICAL EFFICACY: Stage 1.

Evaluation of a PEGylated Fibroblast Growth Factor 21 Variant Using Novel Preclinical Magnetic Resonance Imaging and Magnetic Resonance Elastography in a Mouse Model of Nonalcoholic Steatohepatitis.

BACKGROUND: Treatments for nonalcoholic steatohepatitis (NASH) are urgently needed. Hepatic fat fraction and shear stiffness quantified by magnetic resonance imaging (MRI-HFF) and magnetic resonance elastography (MRE-SS), respectively, are biomarkers for hepatic steatosis and fibrosis. PURPOSE: This study assessed the longitudinal effects of fibroblast growth factor 21 variant (polyethylene glycol [PEG]-FGF21v) on MRI-HFF and MRE-SS in a NASH mouse model. STUDY TYPE: Preclinical. ANIMAL MODEL: This study included a choline-deficient, amino acid-defined, high-fat diet (CDAHFD) model and 6-week-old, male C57BL/6J mice (N = 78). FIELD STRENGTH/SEQUENCE: This study was performed using: 3T: gradient-echo two-point Dixon and spin-echo (SE) echo-planar imaging elastography (200 Hz) and 7T: SE two-point Dixon and SE elastography (200 Hz). ASSESSMENT: MRI and MRE were performed before control diet (CD) or CDAHFD (BD), before PEG-FGF21v dosing (baseline), and after PEG-FGF21v treatment (WK4/8). Regions of interest for MRI-HFF and MRE-SS were delineated by J.L. and H.T. (>5 years of experience each). Fibrosis and steatosis were measured histologically after picrosirius red and H&E staining. Alkaline phosphatase, alanine transaminase, bile acids, and triglycerides (TGs) were measured. STATISTICAL TESTS: Two-tailed Dunnett's tests were used for statistical analysis; untreated CDAHFD or baseline was used for comparisons. Imaging and histology/biochemistry data were determined using Spearman correlations. Bayesian posterior distributions for MRE-SS at WK8, posterior means, and 95% credible intervals were presented. RESULTS: CDAHFD significantly increased baseline MRI-HFF (3T: 21.97% ± 0.29%; 7T: 40.12% ± 0.35%) and MRE-SS (3T: 1.25 ± 0.02; 7T: 1.78 ± 0.06 kPa) vs. CD (3T: 3.45% ± 0.7%; 7T: 12.06% ± 1.4% and 3T: 1.01 ± 0.02; 7T: 0.89 ± 0.06 kPa). At 7T, PEG-FGF21v significantly decreased MRI-HFF (WK4: 28.97% ± 1.22%; WK8: 20.93% ± 1.15%) and MRE-SS (WK4: 1.57 ± 0.04; WK8: 1.36 ± 0.05 kPa) vs. untreated (WK4: 36.36% ± 0.62%; WK8: 30.58% ± 0.81% and WK4: 2.03 ± 0.06; WK8: 2.01 ± 0.04 kPa); 3T trends were similar. WK8 SS posterior mean percent attenuation ratios (RDI ) were -68% (-90%, -44%; 3T) and -64% (-78%, -52%; 7T). MRI-HFF was significantly correlated with H&E (3T, r = 0.93; 7T, r = 0.94) and TGs (both, r = 0.92). DATA CONCLUSIONS: MRI-HFF and MRE-SS showed PEG-FGF21v effects on hepatic steatosis and fibrosis across 3 and 7T, consistent with histological and biochemical data. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

Fast 3D MR elastography of the whole brain using spiral staircase: Data acquisition, image reconstruction, and joint deblurring.

PURPOSE: To address the need for a method to acquire 3D data for MR elastography (MRE) of the whole brain with substantially improved spatial resolution, high SNR, and reduced acquisition time compared with conventional methods. METHODS: We combined a novel 3D spiral staircase data-acquisition method with a spoiled gradient-echo pulse sequence and MRE motion-encoding gradients (MEGs). The spiral-out acquisition permitted use of longer-duration motion-encoding gradients (ie, over two full oscillatory cycles) to enhance displacement SNR, while still maintaining a reasonably short TE for good phase-SNR. Through-plane parallel imaging with low noise penalties was implemented to accelerate acquisition along the slice direction. Shared anatomical information was exploited in the deblurring procedure to further boost SNR for stiffness inversion. RESULTS: In vivo and phantom experiments demonstrated the feasibility of the proposed method in producing brain MRE results comparable to the spin-echo-based approaches, both qualitatively and quantitatively. High-resolution (2-mm isotropic) brain MRE data were acquired in 5 minutes using our method with good SNR. Joint deblurring with shared anatomical information produced SNR-enhanced images, leading to upward stiffness estimation. CONCLUSION: A novel 3D gradient-echo-based approach has been designed and implemented, and shown to have promising potential for fast and high-resolution in vivo MRE of the whole brain.

TURBINE-MRE: A 3D hybrid radial-Cartesian EPI acquisition for MR elastography.

PURPOSE: To develop a novel magnetic resonance elastography (MRE) acquisition using a hybrid radial EPI readout scheme (TURBINE), and to demonstrate its feasibility to obtain wave images and stiffness maps in a phantom and in vivo brain. METHOD: The proposed 3D TURBINE-MRE is based on a spoiled gradient-echo MRE sequence with the EPI readout radially rotating about the phase-encoding axis to sample a full 3D k-space. A polyvinyl chloride phantom and 6 volunteers were scanned on a compact 3T GE scanner with a 32-channel head coil at 80 Hz and 60 Hz external vibration, respectively. For comparison, a standard 2D, multislice, spin-echo (SE) EPI-MRE acquisition was also performed with the same motion encoding and resolution. The TURBINE-MRE images were off-line reconstructed with iterative SENSE algorithm. The regional ROI analysis was performed on the 6 volunteers, and the median stiffness values were compared between SE-EPI-MRE and TURBINE-MRE. RESULTS: The 3D wave-field images and the generated stiffness maps were comparable between TURBINE-MRE and standard SE-EPI-MRE for the phantom and the volunteers. The Bland-Altman plot showed no significant difference in the median regional stiffness values between the two methods. The stiffness measured with the 2 methods had a strong linear relationship with a Pearson correlation coefficient of 0.943. CONCLUSION: We demonstrated the feasibility of the new TURBINE-MRE sequence for acquiring the desired 3D wave-field data and stiffness maps in a phantom and in-vivo brains. This pilot study encourages further exploration of TURBINE-MRE for functional MRE, free-breathing abdominal MRE, and cardiac MRE applications.

The Role of Three-Dimensional Magnetic Resonance Elastography in the Diagnosis of Nonalcoholic Steatohepatitis in Obese Patients Undergoing Bariatric Surgery.

The lack of reliable, noninvasive methods to diagnose early nonalcoholic steatohepatitis (NASH) is a major unmet need. We aimed to determine the diagnostic accuracy of three-dimensional magnetic resonance elastography (3D-MRE), with shear stiffness measured at 60 Hz, damping ratio at 40 Hz, and magnetic resonance imaging proton density fat fraction (MRI-PDFF) in the detection of NASH in individuals undergoing bariatric surgery. Obese adults at risk for NASH were enrolled between 2015 and 2017 (prospective cohort, n = 88) and 2010 and 2013 (retrospective cohort, n = 87). The imaging protocol consisted of multifrequency 3D-MRE (mf3D-MRE) with shear waves delivered at different frequencies to explore parameters that best correlated with histologic NASH, and MRI-PDFF to estimate steatosis. The prospective cohort was used to establish the optimal mf3D-MRE technical parameters for NASH detection. The two cohorts were then combined to derive predictive models of NASH and disease activity by nonalcoholic fatty liver disease activity score (NAS) using the three imaging parameters that correlated with NASH. A total of 175 patients (median age 45, 81% women, and 81 [46%] with histologic NASH) were used for model derivation. From the complex shear modulus output generated by mf3D-MRE, the damping ratio at 40 Hz and shear stiffness at 60 Hz best correlated with NASH. The fat fraction obtained from MRI-PDFF correlated with steatosis (P < 0.05 for all). These three parameters were fit into a logistic regression model that predicted NASH with cross-validated area under the receiver operating characteristic curve (AUROC) = 0.73, sensitivity = 0.67, specificity = 0.80, positive predictive value = 0.73 and negative predictive value = 0.74, and disease activity by NAS with cross-validated AUROC = 0.82. Conclusion: The mf3D-MRE allows identification of imaging parameters that predict early NASH and disease activity. This imaging biomarker represents a promising alternative to liver biopsy for NASH diagnosis and monitoring. The results provide motivation for further studies in nonbariatric cohorts.

Multiparametric magnetic resonance imaging/magnetic resonance elastography assesses progression and regression of steatosis, inflammation, and fibrosis in alcohol-associated liver disease.

BACKGROUND: Magnetic resonance imaging (MRI) and MRI-based elastography (MRE) are the most promising noninvasive techniques in assessing liver diseases. The purpose of this study was to evaluate an advanced multiparametric imaging method for staging disease and assessing treatment response in realistic preclinical alcohol-associated liver disease (ALD). METHODS: We utilized four different preclinical mouse models in our study: Model 1-mice were fed a fast-food diet and fructose water for 48 weeks to induce nonalcoholic fatty liver disease; Model 2-mice were fed chronic-binge ethanol (EtOH) for 10 days or 8 weeks to induce liver steatosis/inflammation. Two groups of mice were treated with interleukin-22 at different time points to induce disease regression; Model 3-mice were administered CCl4 for 2 to 4 weeks to establish liver fibrosis followed by 2 or 4 weeks of recovery; and Model 4-mice were administered EtOH plus CCl4 for 12 weeks. Mouse liver imaging biomarkers including proton density fat fraction (PDFF), liver stiffness (LS), loss modulus (LM), and damping ratio (DR) were assessed. Liver and serum samples were obtained for histologic and biochemical analyses. Ordinal logistic regression and generalized linear regression analyses were used to model the severity of steatosis, inflammation, and fibrosis, and to assess the regression of these conditions. RESULTS: Multiparametric models with combinations of biomarkers (LS, LM, DR, and PDFF) used noninvasively to predict the histologic severity and regression of steatosis, inflammation, and fibrosis were highly accurate (area under the curve > 0.84 for all). A three-parameter model that incorporates LS, DR, and ALT predicted histologic fibrosis progression (r = 0.84, p < 0.0001) and regression (r = 0.79, p < 0.0001) as measured by collagen content in livers. CONCLUSION: This preclinical study provides evidence that multiparametric MRI/MRE can be used noninvasively to assess disease severity and monitor treatment response in ALD.

Comparison of the diagnostic performance of 2D and 3D MR elastography in staging liver fibrosis.

OBJECTIVES: To compare the diagnostic performance and image quality of state-of-the-art 2D MR elastography (MRE) and 3D MRE in the basic application of liver fibrosis staging. METHODS: This retrospective study assessed data from 293 patients who underwent 2D and 3D MRE examinations. MRE image quality was assessed with a qualitative 2-point grading system by evaluating artifacts. Two experienced analysts independently measured mean liver stiffness values. The interobserver agreement of liver stiffness measurement was assessed by the intraclass correlation coefficient (ICC). The area under the receiver operating characteristic curve (AUC) was used to assess the diagnostic performance of 2D and 3D MRE and blood-based markers for fibrosis staging using the pathology-proven liver fibrosis stage as the gold standard. RESULTS: The image quality provided by 3D MRE was graded as significantly higher than that obtained with the 2D MRE method (p < 0.01). Interobserver agreement in liver stiffness measurements was higher for 3D MRE (ICC: 3D 0.979 vs 2D 0.955). The AUC values for discriminating ≥ F1, ≥ F2, ≥ F3, and F4 fibrosis for 3D MRE (0.89, 0.92, 0.95, and 0.93) were similar to those for 2D MRE (0.89, 0.91, 0.94, and 0.92). Both the 2D and 3D MRE methods provided superior accuracy to the blood-based biomarkers, including APRI, FIB-4, and Forns index, especially for ≥ F2, ≥ F3, and F4 fibrosis stages (all p < 0.01). CONCLUSIONS: While 3D MRE offers certain advantages and opportunities for new applications of MRE, current widely deployed 2D MRE technology has comparable performance in the basic application of detecting and staging liver fibrosis. KEY POINTS: • 2D MRE and 3D MRE have comparable diagnostic performance in detecting and staging liver fibrosis. • 3D MRE has superior image quality and interobserver agreement compared to 2D MRE.

Quantitative assessment of portal hypertension with bi-parametric dual-frequency hepatic MR elastography in mouse models.

OBJECTIVES: To determine the potential of bi-parametric dual-frequency hepatic MR elastography (MRE) for predicting portal pressure (PP) in mouse models of portal hypertension (PHTN) with the presence of varying hepatic fibrosis. METHODS: We studied 73 wild-type male mice, including 22 mice with hepatic congestion, 20 mice with cholestatic liver injury, and 31 age-matched sham mice. Hepatic shear stiffness (SS) and volumetric strain (VS) were calculated by 3D MRE acquired at 80 and 200 Hz. We measured PP immediately after MRE. Liver fibrosis was verified by hydroxyproline assay. We predicted PP by fitting generalized linear models with single- and dual-frequency SS and VS, respectively. The relationship between predicted and actual PP was evaluated by Spearman's correlation. We compared the prediction accuracy of portal hypertension for all models with DeLong tests at a significance level of 0.05. RESULTS: Animals with congestive or cholestatic liver disease developed significant PHTN and hepatic fibrosis to varying degrees. In both models, SS increased, while VS decreased significantly compared with shams. All bi-parametric models had high diagnostic accuracy for PHTN. The dual-frequency models (AUCs: 0.90 [81-95%], 0.91 [81-95%]) had substantially or significantly higher accuracy than single-frequency ones (AUCs: 0.83 [71-91%], and 0.78 [66-87%]). The predicted PP of dual-frequency models also showed stronger correlations with actual PP than single-frequency predictions. CONCLUSIONS: The bi-parametric dual-frequency model improved the diagnostic accuracy of liver MRE in diagnosing PHTN in preclinical models. This technical advance has the potential to monitor PHTN progression and treatment efficacy in the presence of varying fibrosis. KEY POINTS: • Bi-parametric hepatic MR elastography can predict portal pressure. • The prediction models of shear stiffness and volumetric strain with dual-frequency measurements demonstrate high diagnostic accuracy (AUCs > 0.9) in two different portal hypertension mouse models with varying fibrosis.

Magnetic resonance elastography biomarkers for detection of histologic alterations in nonalcoholic fatty liver disease in the absence of fibrosis.

OBJECTIVES: To investigate associations between histology and hepatic mechanical properties measured using multiparametric magnetic resonance elastography (MRE) in adults with known or suspected nonalcoholic fatty liver disease (NAFLD) without histologic fibrosis. METHODS: This was a retrospective analysis of 88 adults who underwent 3T MR exams including hepatic MRE and MR imaging to estimate proton density fat fraction (MRI-PDFF) within 180 days of liver biopsy. Associations between MRE mechanical properties (mean shear stiffness (|G*|) by 2D and 3D MRE, and storage modulus (G'), loss modulus (G″), wave attenuation (α), and damping ratio (ζ) by 3D MRE) and histologic, demographic and anthropometric data were assessed. RESULTS: In univariate analyses, patients with lobular inflammation grade ≥ 2 had higher 2D |G*| and 3D G″ than those with grade ≤ 1 (p = 0.04). |G*| (both 2D and 3D), G', and G″ increased with age (rho = 0.25 to 0.31; p ≤ 0.03). In multivariable regression analyses, the association between inflammation grade ≥ 2 remained significant for 2D |G*| (p = 0.01) but not for 3D G″ (p = 0.06); age, sex, or BMI did not affect the MRE-inflammation relationship (p > 0.20). CONCLUSIONS: 2D |G*| and 3D G″ were weakly associated with moderate or severe lobular inflammation in patients with known or suspected NAFLD without fibrosis. With further validation and refinement, these properties might become useful biomarkers of inflammation. Age adjustment may help MRE interpretation, at least in patients with early-stage disease. KEY POINTS: • Moderate to severe lobular inflammation was associated with hepatic elevated shear stiffness and elevated loss modulus (p =0.04) in patients with known or suspected NAFLD without liver fibrosis; this suggests that with further technical refinement these MRE-assessed mechanical properties may permit detection of inflammation before the onset of fibrosis in NAFLD. • Increasing age is associated with higher hepatic shear stiffness, and storage and loss moduli (rho = 0.25 to 0.31; p ≤ 0.03); this suggests that age adjustment may help interpret MRE results, at least in patients with early-stage NAFLD.

Imaging brain function with simultaneous BOLD and viscoelasticity contrast: fMRI/fMRE.

Magnetic resonance elastography (MRE) is emerging as a new tool for studying viscoelastic changes in the brain resulting from functional processes. Here, we demonstrate a novel time series method to generate robust functional magnetic resonance elastography (fMRE) activation maps in response to a visual task with a flashing checkerboard stimulus. Using a single-shot spin-echo (SS-SE) pulse sequence, the underlying raw images inherently contain blood-oxygen-level dependent (BOLD) contrast, allowing simultaneous generation of functional magnetic resonance imaging (fMRI) activation maps from the magnitude and functional magnetic resonance elastography (fMRE) maps from the phase. This allows an accurate comparison of the spatially localized stiffness (fMRE) and BOLD (fMRI) changes within a single scan, eliminating confounds inherent in separately acquired scans. Results indicate that tissue stiffness within the visual cortex increases 6-11% with visual stimuli, whereas the BOLD signal change was 1-2%. Furthermore, the fMRE and fMRI activation maps have strong spatial overlap within the visual cortex, providing convincing evidence that fMRE is possible in the brain. However, the fMRE temporal SNR (tSNRfMRE) maps are heterogeneous across the brain. Using a dictionary matching approach to characterize the time series, the viscoelastic changes are consistent with a viscoelastic response function (VRF) time constant of 12.1 â€‹s ± 3.0 â€‹s for a first-order exponential decay, or a shape parameter of 8.1 â€‹s ± 1.4 â€‹s for a gamma-variate.

Influence of Age on Global and Regional Brain Stiffness in Young and Middle-Aged Adults.

BACKGROUND: An understanding of potential age-related changes in brain stiffness and its regional variation is important for further clinical application of MR elastography. PURPOSE: To investigate the effect of age on global and regional brain stiffness in young and middle-aged adults. STUDY TYPE: Prospective. SUBJECTS: Fifty subjects with normal brains and aged in their 20s, 30s, 40s, 50s, or 60s (five men, five women per decade). FIELD STRENGTH/SEQUENCE: 3.0T MRI and elastography with a vibration frequency of 60 Hz. ASSESSMENT: Stiffness was measured in nine brain regions (cerebrum, temporal lobes, sensorimotor areas, frontotemporal composite region, deep gray matter and white matter (deep GM/WM), parietal lobes, occipital lobes, frontal lobes, and cerebellum) using an atlas-based region-of-interest approach. The influence of age on regional brain stiffness was evaluated. STATISTICAL TESTS: Multiple linear regression analysis, followed by Dunnett's multiple comparisons test, using subjects in their 20s as controls. RESULTS: Following adjustment for sex, multiple linear regression revealed a significant negative correlation between age and stiffness of the cerebrum (P < 0.0001), temporal lobes (P < 0.0001), sensorimotor areas (P < 0.0001), frontotemporal composite region (P < 0.0001), deep GM/WM (P = 0.0028), parietal lobes (P < 0.0001), occipital lobes (P = 0.0055), and frontal lobes (P < 0.0001). Dunnett's multiple comparison test showed that the stiffness of the sensorimotor areas, frontotemporal composite region, and frontal lobes was significantly decreased in subjects in their 40s (P < 0.0367), 50s (P < 0.0001), and 60s (P < 0.0001), while that of the cerebrum, temporal lobes, and parietal lobes was significantly decreased only in subjects in their 50s (P < 0.0012) and 60s (P < 0.0031) when compared with the controls. DATA CONCLUSION: There is an age-related decrease in brain stiffness that varies across the different regions. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:727-733.

Normal range for MR elastography measured liver stiffness in children without liver disease.

BACKGROUND: Magnetic resonance elastography (MRE) can determine the presence and stage of liver fibrosis. Data on normative MRE values, while reported in adults, are limited in children. PURPOSE: To determine the distribution of MRE-measured liver stiffness in children without liver disease. STUDY TYPE: Prospective, observational. POPULATION: Eighty-one healthy children (mean 12.6 ± 2.6 years, range 8-17 years). FIELD STRENGTH/SEQUENCE: 3.0T Signa HDxt, General Electric MR Scanner; 2D GRE MRE sequence. ASSESSMENT: History, examination, laboratory evaluation, and (MR) exams (proton density fat fraction, PDFF, and MRE) were performed. MR elastograms were analyzed manually at two reading centers and compared with each other for agreement and with published values in healthy adults and thresholds for fibrosis in adult and pediatric patients. STATISTICAL TESTS: Descriptive statistics, Bland-Altman analysis, t-test to compare hepatic stiffness values with reference standards. RESULTS: Stiffness values obtained at both reading centers were similar, without significant bias (P = 0.362) and with excellent correlation (intraclass correlation coefficient [ICC] = 0.782). Mean hepatic stiffness value for the study population was 2.45 ± 0.35 kPa (95th percentile 3.19 kPa), which was significantly higher than reported values for healthy adult subjects (2.10 ± 0.23 kPa, P < 0.001). In all, 74-85% of subjects had stiffness measurements suggestive of no fibrosis. DATA CONCLUSION: Mean liver stiffness measured with MRE in this cohort was significantly higher than that reported in healthy adults. Despite rigorous screening, some healthy children had stiffness measurements suggestive of liver fibrosis using current published thresholds. Although MRE has the potential to provide noninvasive assessment in patients with suspected hepatic disease, further refinement of this technology will help advance its use as a diagnostic tool for evidence of fibrosis in pediatric populations. LEVEL OF EVIDENCE: 1 Technical Efficacy: 5 J. Magn. Reson. Imaging 2020;51:919-927.

3D MR Elastography of Hepatocellular Carcinomas as a Potential Biomarker for Predicting Tumor Recurrence.

BACKGROUND: Preoperative prediction of tumor recurrence is important in the management of patients with hepatocellular carcinoma (HCC). PURPOSE: To investigate whether tumor stiffness derived by magnetic resonance elastography (MRE) could predict early recurrence of HCC after hepatic resection. STUDY TYPE: Retrospective. POPULATION: In all, 99 patients with pathologically confirmed HCCs after surgical resection. FIELD STRENGTH/SEQUENCE: 3.0T; preoperative MRE with 60-Hz mechanical vibrations using an active acoustic driver. ASSESSMENT: Regions of interest (ROIs) were manually drawn in the tumors to measure mean tumor stiffness. Surgical specimens were reviewed for histological grade, capsule, vascular invasion, and surgical margins. The early recurrence of HCC was defined as that occurring within 2 years after resection. STATISTICAL TESTS: Cox proportional hazard models were used to evaluate risk factors associated with the time to early recurrence. RESULTS: HCCs with recurrence had higher tumor stiffness, higher rate of advanced T stage, vascular invasion, lower rate of capsule formation, larger tumor size, higher aspartate aminotransferase (AST), and hepatitis B virus (HBV)-DNA level and aspartate aminotransferase / alanine aminotransferase ratio (P = 0.031, 0.007, 0.01, <0.001, 0.015, 0.034, 0.01, and 0.014, respectively) than HCCs without recurrence. Vascular invasion (hazard ratio [HR] = 2.922; 95% confidence interval [CI]: [1.079, 7.914], P = 0.035) and mean tumor stiffness (HR = 1.163; 95% CI: [1.055, 1.282], P = 0.002) were risk factors associated with early recurrence. Each 1-kPa increase in tumor stiffness was associated with a 16.3% increase in the risk for tumor recurrence. DATA CONCLUSION: The mean stiffness of HCCs may be a useful, noninvasive, quantitative biomarker for the prediction of early HCC recurrence after hepatic resection. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2019;49:719-730.

Prediction of nonalcoholic fatty liver disease (NAFLD) activity score (NAS) with multiparametric hepatic magnetic resonance imaging and elastography.

OBJECTIVES: To investigate the use of MR elastography (MRE)-derived mechanical properties (shear stiffness (|G*|) and loss modulus (G″)) and MRI-derived fat fraction (FF) to predict the nonalcoholic fatty liver disease (NAFLD) activity score (NAS) in a NAFLD mouse model. METHODS: Eighty-nine male mice were studied, including 64 training and 25 independent testing animals. An MRI/MRE exam and histologic evaluation were performed. Pairwise, nonparametric comparisons and multivariate analyses were used to evaluate the relationships between the three imaging parameters (FF, |G*|, and G″) and histologic features. A virtual NAS score (vNAS) was generated by combining three imaging parameters with an ordinal logistic model (OLM) and a generalized linear model (GLM). The prediction accuracy was evaluated by ROC analyses. RESULTS: The combination of FF, |G*|, and G″ predicted NAS > 1 with excellent accuracy in both training and testing sets (AUROC > 0.84). OLM and GLM predictive models misclassified 3/54 and 6/54 mice in the training, and 1/25 and 1/25 in the testing cohort respectively, in distinguishing between "not-NASH" and "definite-NASH." "Borderline-NASH" prediction was poorer in the training set, and no borderline-NASH mice were available in the testing set. CONCLUSION: This preliminary study shows that multiparametric MRI/MRE can be used to accurately predict the NAS score in a NAFLD animal model, representing a promising alternative to liver biopsy for assessing NASH severity and treatment response. KEY POINTS: • MRE-derived liver stiffness and loss modulus and MRI-assessed fat fraction can be used to predict NAFLD activity score (NAS) in our preclinical mouse model (AUROC > 0.84 for all NAS levels greater than 1). • The overall agreement between the histological-determined NASH diagnosis and the imaging-predicted NASH diagnosis is 80-92%. • The multiparametric hepatic MRI/MRE has great potential for noninvasively assessing liver disease severity and treatment efficacy.

Pancreatic Stiffness Quantified with MR Elastography: Relationship to Postoperative Pancreatic Fistula after Pancreaticoenteric Anastomosis.

Purpose To describe the relationship between conventional magnetic resonance (MR) imaging parameters and MR elastography of the pancreas in association with pancreatic histologic features and occurrence of postoperative pancreatic fistula (POPF). Materials and Methods Patients who underwent preoperative MR imaging (MR elastography and diffusion-, T1-, and T2-weighted imaging) followed by pancreatectomy with pancreaticoenteric anastomosis were included. The relationships between preoperative MR imaging parameters, demographic data, and intraoperative factors with POPF risk were analyzed with logistic regression analyses. The correlation of MR imaging parameters with histologic characteristics was evaluated with multivariate regression analysis. Results A total of 112 patients (64 men, 48 women; median age, 58 years) were evaluated. Forty-two patients (37.5%) developed POPF and 20 (17.9%) developed high-grade POPF (grades B and C). Lower pancreatic stiffness (≤1.43 kPa; odds ratio [OR], 9.196; 95% confidence interval [CI]: 1.92, 43.98), nondilated main pancreatic duct (MPD) diameter (<3 mm; OR, 7.298; 95% CI: 1.51, 35.34), and larger stump area (≥211 mm2; OR, 9.210; 95% CI: 1.53, 55.26) were risk factors for POPF. Lower pancreatic stiffness (≤1.27 kPa; OR, 8.389; 95% CI: 1.88, 37.41) was the only independent predictor of high-grade POPF. Log-transformed pancreatic stiffness was independently associated with fibrosis (ß = 0.060; 95% CI: 0.052, 0.068), acinar atrophy (ß = 0.015; 95% CI: 0.003, 0.028), and lipomatosis (ß = -0.016; 95% CI: -0.026, -0.006). Conclusion Preoperative MR assessment of pancreatic stiffness, MPD diameter, and stump area are important predictors of POPF.

Artificial neural networks for stiffness estimation in magnetic resonance elastography.

PURPOSE: To investigate the feasibility of using artificial neural networks to estimate stiffness from MR elastography (MRE) data. METHODS: Artificial neural networks were fit using model-based training patterns to estimate stiffness from images of displacement using a patch size of ∼1 cm in each dimension. These neural network inversions (NNIs) were then evaluated in a set of simulation experiments designed to investigate the effects of wave interference and noise on NNI accuracy. NNI was also tested in vivo, comparing NNI results against currently used methods. RESULTS: In 4 simulation experiments, NNI performed as well or better than direct inversion (DI) for predicting the known stiffness of the data. Summary NNI results were also shown to be significantly correlated with DI results in the liver (R2 = 0.974) and in the brain (R2 = 0.915), and also correlated with established biological effects including fibrosis stage in the liver and age in the brain. Finally, repeatability error was lower in the brain using NNI compared to DI, and voxel-wise modeling using NNI stiffness maps detected larger effects than using DI maps with similar levels of smoothing. CONCLUSION: Artificial neural networks represent a new approach to inversion of MRE data. Summary results from NNI and DI are highly correlated and both are capable of detecting biologically relevant signals. Preliminary evidence suggests that NNI stiffness estimates may be more resistant to noise than an algebraic DI approach. Taken together, these results merit future investigation into NNIs to improve the estimation of stiffness in small regions. Magn Reson Med 80:351-360, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Cardiac MR elastography using reduced-FOV, single-shot, spin-echo EPI.

PURPOSE: To implement a reduced field of view (rFOV) technique for cardiac MR elastography (MRE) and to demonstrate the improvement in image quality of both magnitude images and post-processed MRE stiffness maps compared to the conventional full field of view (full-FOV) acquisition. METHODS: With Institutional Review Board approval, 17 healthy volunteers underwent both full-FOV and rFOV cardiac MRE scans using 140-Hz vibrations. Two cardiac radiologists blindly compared the magnitude images and stiffness maps and graded the images based on several image quality attributes using a 5-point ordinal scale. Fisher's combined probability test was performed to assess the overall evaluation. The octahedral shear strain-based signal-to-noise ratio (OSS-SNR) and median stiffness over the left ventricular myocardium were also compared. RESULTS: One volunteer was excluded because of an inconsistent imaging resolution during the exam. In the remaining 16 volunteers (9 males, 7 females), the rFOV scans outperformed the full-FOV scans in terms of subjective image quality and ghosting artifacts in the magnitude images and stiffness maps, as well as the overall preference. The quantitative measurements showed that rFOV had significantly higher OSS-SNR (median: 1.4 [95% confidence interval (CI): 1.2-1.5] vs. 2.1 [95% CI: 1.8-2.4]), P < 0.05) compared to full-FOV. Although no significant change was found in the median myocardial stiffness between the 2 scans, we observed a decrease in the stiffness variation within the myocardium from 2.1 kPa (95% CI: [1.9, 2.3]) to 1.9 kPa (95% CI: [1.7, 2.0]) for full-FOV and rFOV, respectively (P < 0.05) in a subgroup of 7 subjects with ghosting present in the myocardium. CONCLUSION: This pilot volunteer study demonstrated that rFOV cardiac MRE has the capability to reduce ghosting and to improve image quality in both MRE magnitude images and stiffness maps. Magn Reson Med 80:231-238, 2018. © 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 NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Regional assessment of in vivo myocardial stiffness using 3D magnetic resonance elastography in a porcine model of myocardial infarction.

PURPOSE: The stiffness of a myocardial infarct affects the left ventricular pump function and remodeling. Magnetic resonance elastography (MRE) is a noninvasive imaging technique for measuring soft-tissue stiffness in vivo. The purpose of this study was to investigate the feasibility of assessing in vivo regional myocardial stiffness with high-frequency 3D cardiac MRE in a porcine model of myocardial infarction, and compare the results with ex vivo uniaxial tensile testing. METHODS: Myocardial infarct was induced in a porcine model by embolizing the left circumflex artery. Fourteen days postinfarction, MRE imaging was performed in diastole using an echocardiogram-gated spin-echo echo-planar-imaging sequence with 140-Hz vibrations and 3D MRE processing. The MRE stiffness and tensile modulus from uniaxial testing were compared between the remote and infarcted myocardium. RESULTS: Myocardial infarcts showed increased in vivo MRE stiffness compared with remote myocardium (4.6 ± 0.7 kPa versus 3.0 ± 0.6 kPa, P = 0.02) within the same pig. Ex vivo uniaxial mechanical testing confirmed the in vivo MRE results, showing that myocardial infarcts were stiffer than remote myocardium (650 ± 80 kPa versus 110 ± 20 kPa, P = 0.01). CONCLUSIONS: These results demonstrate the feasibility of assessing in vivo regional myocardial stiffness with high-frequency 3D cardiac MRE. Magn Reson Med 79:361-369, 2018. © 2017 International Society for Magnetic Resonance in Medicine.