Ehman, Richard L.

BackgroundMagnetic 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.PurposeTo determine the distribution of MRE‐measured liver stiffness in children without liver disease.Study TypeProspective, observational.PopulationEighty‐one healthy children (mean 12.6 ± 2.6 years, range 8–17 years).Field Strength/Sequence3.0T Signa HDxt, General Electric MR Scanner; 2D GRE MRE sequence.AssessmentHistory, 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 TestsDescriptive statistics, Bland–Altman analysis, t‐test to compare hepatic stiffness values with reference standards.ResultsStiffness 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 ConclusionMean 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: 1Technical Efficacy: 5J. Magn. Reson. Imaging 2020;51:919–927.

BackgroundAn understanding of potential age‐related changes in brain stiffness and its regional variation is important for further clinical application of MR elastography.PurposeTo investigate the effect of age on global and regional brain stiffness in young and middle‐aged adults.Study TypeProspective.SubjectsFifty subjects with normal brains and aged in their 20s, 30s, 40s, 50s, or 60s (five men, five women per decade).Field Strength/Sequence3.0T MRI and elastography with a vibration frequency of 60 Hz.AssessmentStiffness 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 TestsMultiple linear regression analysis, followed by Dunnett's multiple comparisons test, using subjects in their 20s as controls.ResultsFollowing 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 ConclusionThere is an age‐related decrease in brain stiffness that varies across the different regions.Level of Evidence: 1Technical Efficacy Stage: 2J. Magn. Reson. Imaging 2020;51:727–733.

In this paper, we present our preliminary findings regarding magnetic resonance elastography (MRE) on the livers of 10 patients with systemic amyloidosis. Mean liver stiffness measurements (LSM) and spleen stiffness measurements (SSM) were obtained. Magnetic resonance imaging (MRI) images were analyzed for the distribution pattern of amyloid deposition. Pearson correlation analysis was performed in order to study the correlation between LSM, SSM, liver span, liver volume, spleen span, spleen volume, serum alkaline phosphatase (ALP), N-terminal pro b-type natriuretic peptide (NT pro BNP), and the kappa and lambda free light chains. An increase in mean LSM was seen in all patients. Pearson correlation analysis showed a statistically significant correlation between LSM and liver volume (r = 0.78, p = 0.007) and kappa chain level (r = 0.65, p = 0.04). Interestingly, LSM did not correlate significantly with SSM (r = 0.45, p = 0.18), liver span (r = 0.57, p = 0.08), or serum ALP (r = 0.60, p = 0.07). However, LSM correlated significantly with serum ALP when corrected for liver volume (partial correlation, r = 0.71, p = 0.03) and NT pro BNP levels (partial correlation, r = 0.68, p = 0.04). MRI review revealed that amyloid deposition in the liver can be diffuse, lobar, or focal. MRE is useful for the evaluation of hepatic amyloidosis and shows increased stiffness in hepatic amyloidosis. MRE has the potential to be a non-invasive quantitative imaging marker for hepatic amyloidosis.

Abstract Soft tissue sarcomas are a rare and heterogeneous group of malignancies that present significant diagnostic and therapeutic challenges. Patient stratification based on tumor aggressiveness and early therapeutic response based on quantitative imaging may improve prediction of treatment response and the evaluation of new treatment strategies in clinical trials. The purpose of this pilot study was to determine the technical feasibility of magnetic resonance elastography (MRE) and dynamic contrast-enhanced (DCE) MRI for the evaluation of sarcoma stiffness and perfusion in 9 patients with histologically confirmed sarcoma. Additionally, we assessed the feasibility of utilizing MRE and DCE-MRI for the early evaluation of response to radiation therapy in 4 patients to determine the utility of further evaluation in a larger cohort study. Tumor size, stiffness, and perfusion parameters all decreased from baseline at the time of the pre-surgery or follow-up MRI, and results were compared to pathology or conventional imaging. MRE and DCE-MRI may be useful for the quantitative evaluation of tumor stiffness and perfusion, and therapy response assessment in soft tissue sarcomas.

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.

BackgroundPreoperative prediction of tumor recurrence is important in the management of patients with hepatocellular carcinoma (HCC).PurposeTo investigate whether tumor stiffness derived by magnetic resonance elastography (MRE) could predict early recurrence of HCC after hepatic resection.Study TypeRetrospective.PopulationIn all, 99 patients with pathologically confirmed HCCs after surgical resection.Field Strength/Sequence3.0T; preoperative MRE with 60‐Hz mechanical vibrations using an active acoustic driver.AssessmentRegions 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 TestsCox proportional hazard models were used to evaluate risk factors associated with the time to early recurrence.ResultsHCCs 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 ConclusionThe mean stiffness of HCCs may be a useful, noninvasive, quantitative biomarker for the prediction of early HCC recurrence after hepatic resection.Level of Evidence: 4Technical Efficacy: Stage 5J. Magn. Reson. Imaging 2019;49:719–730.

There is increasing scrutiny from healthcare organizations towards the utility and associated costs of imaging. MRI has traditionally been used as a high‐end modality, and although shown extremely important for many types of clinical scenarios, it has been suggested as too expensive by some. This editorial will try and explain how value should be addressed and gives some insights and practical examples of how value of MRI can be increased. It requires a global effort to increase accessibility, value for money, and impact on patient management. We hope this editorial sheds some light and gives some indications of where the field may wish to address some of its research to proactively demonstrate the value of MRI.Level of Evidence: 5Technical Efficacy: Stage 5J. Magn. Reson. Imaging 2019;49:e14–e25.

Magnetic resonance elastography (MRE) is increasingly being applied to thin or small structures in which wave propagation is dominated by waveguide effects, which can substantially bias stiffness results with common processing approaches. The purpose of this work was to investigate the importance of such biases and artifacts on MRE inversion results in: (i) various idealized 2D and 3D geometries with one or more dimensions that are small relative to the shear wavelength; and (ii) a realistic cardiac geometry. Finite element models were created using simple 2D geometries as well as a simplified and a realistic 3D cardiac geometry, and simulated displacements acquired by MRE from harmonic excitations from 60 to 220 Hz across a range of frequencies. The displacement wave fields were inverted with direct inversion of the Helmholtz equation with and without the application of bandpass filtering and/or the curl operator to the displacement field. In all geometries considered, and at all frequencies considered, strong biases and artifacts were present in inversion results when the curl operator was not applied. Bandpass filtering without the curl was not sufficient to yield accurate recovery. In the 3D geometries, strong biases and artifacts were present in 2D inversions even when the curl was applied, while only 3D inversions with application of the curl yielded accurate recovery of the complex shear modulus. These results establish that taking the curl of the wave field and performing a full 3D inversion are both necessary steps for accurate estimation of the shear modulus both in simple thin‐walled or small structures and in a realistic cardiac geometry when using simple inversions that neglect the hydrostatic pressure term. In practice, sufficient wave amplitude, signal‐to‐noise ratio, and resolution will be required to achieve accurate results.

PurposeTo introduce newly developed MR elastography (MRE)‐based dual‐saturation imaging and dual‐sensitivity motion encoding schemes to directly measure in vivo skull–brain motion, and to study the skull–brain coupling in volunteers with these approaches.MethodsSix volunteers were scanned with a high‐performance compact 3T‐MRI scanner. The skull–brain MRE images were obtained with a dual‐saturation imaging where the skull and brain motion were acquired with fat‐ and water‐suppression scans, respectively. A dual‐sensitivity motion encoding scheme was applied to estimate the heavily wrapped phase in skull by the simultaneous acquisition of both low‐ and high‐sensitivity phase during a single MRE exam. The low‐sensitivity phase was used to guide unwrapping of the high‐sensitivity phase. The amplitude and temporal phase delay of the rigid‐body motion between the skull and brain was measured, and the skull–brain interface was visualized by slip interface imaging (SII).ResultsBoth skull and brain motion can be successfully acquired and unwrapped. The skull–brain motion analysis demonstrated the motion transmission from the skull to the brain is attenuated in amplitude and delayed. However, this attenuation (%) and delay (rad) were considerably greater with rotation (59 ± 7%, 0.68 ± 0.14 rad) than with translation (92 ± 5%, 0.04 ± 0.02 rad). With SII the skull–brain slip interface was not completely evident, and the slip pattern was spatially heterogeneous.ConclusionThis study provides a framework for acquiring in vivo voxel‐based skull and brain displacement using MRE that can be used to characterize the skull–brain coupling system for understanding of mechanical brain protection mechanisms, which has potential to facilitate risk management for future injury.