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Purpose: The aim of this study was to estimate inter-rater reliability and validate magnetic resonance elastography (MRE) as a tool to measure liver elasticity.Materials and Methods: The study protocol was approved by the institutional review board at our institution. In all, 10 normal volunteers and 110 patients, who provided written informed consent, were enrolled. The pathological fibrosis score was applied as a standard reference of liver fibrosis in 21 patients. MRE was performed with a 1.5-T magnetic resonance imaging scanner with a cylindrical passive longitudinal shear wave driver placed over the right chest wall to deliver vibrations. A gradient-echo MRE sequence was used to acquire axial wave images, which were automatically converted to elastograms representing elasticity (in kilopascals, or kPa). The region of interest was placed in the right lobe of the liver on elastograms by two raters independently. To evaluate interrater reliability, the intraclass correlation coefficient was calculated. The elasticity measurements correlated with the pathological fibrosis score (F1-F4) in 21 patients.Results: The intraclass correlation coefficient was almost perfect (0.993) between the elasticities measured by the two raters. The mean elasticity value for patients with F4 was 5.7 kPa; F3, 4.4 kPa; F2, 3.1 kPa; F1, 2.2 kPa; and F0, 2.1 kPa.Conclusion: MRE is a reliable tool to measure liver elasticity. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the feasibility of spatially resolving the shear modulus of lung parenchyma using conventional (1)H magnetic resonance elastography (MRE) imaging techniques in a small animal model.Materials and Methods: A 10-cm diameter transmit-receive radiofrequency coil was modified to include a specimen stage, an MRE pneumatic drum driver, and needle system. MRE was performed on 10 female Sprague-Dawley rats using a (1)H spin-echo based MRE imaging sequence with a field of view of 7 cm and slice thickness of 5 mm. Air-filled lungs were imaged at transpulmonary inflation pressures of 5, 10, and 15 cm H(2)O while fluid-filled lungs were imaged after infusion of 4 mL of normal saline.Results: The average shear modulus of air-filled lungs was 0.840 +/- 0.0524 kPa, 1.07 +/- 0.114 kPa and 1.30 +/- 0.118 kPa at 5, 10, and 15 cm H(2)O, respectively. Analysis of variance indicated that these population means were statistically significantly different from one another (F-value = 26.279, P = 0.00004). The shear modulus of the fluid-filled lungs was 1.65 +/- 0.360 kPa.Conclusion: It is feasible to perform lung MRE in small animals using conventional MR imaging technologies. [ABSTRACT FROM AUTHOR]

Objectives: To investigate associations between tissue diffusion, stiffness, and different tumor microenvironment features in resected hepatocellular carcinoma (HCC)., Methods: Seventy-two patients were prospectively included for preoperative magnetic resonance (MR) diffusion-weighted imaging and MR elastography examination. The mean apparent diffusion coefficient (ADC) and stiffness value were measured on the central three slices of the tumor and peri-tumor area. Cell density, tumor-stroma ratio (TSR), lymphocyte-rich HCC (LR-HCC), and CD8 + T cell infiltration were estimated in resected tumors. The interobserver agreement of MRI measurements and subjective pathological evaluation was assessed. Variables influencing ADC and stiffness were screened with univariate analyses, and then identified with multivariable linear regression. The potential relationship between explored imaging biomarkers and histopathological features was assessed with linear regression after adjustment for other influencing factors., Results: Seventy-two patients (male/female: 59/13, mean age: 56 ± 10.2 years) were included for analysis. Inter-reader agreement was good or excellent regarding MRI measurements and histopathological evaluation. No correlation between tumor ADC and tumor stiffness was found. Multivariable linear regression confirmed that cell density was the only factor associated with tumor ADC (Estimate = -0.03, p = 0.006), and tumor-stroma ratio was the only factor associated with tumor stiffness (Estimate = -0.18, p = 0.03). After adjustment for fibrosis stage (Estimate = 0.43, p < 0.001) and age (Estimate = 0.04, p < 0.001) in the multivariate linear regression, intra-tumoral CD8 + T cell infiltration remained a significant factor associated with peri-tumor stiffness (Estimate = 0.63, p = 0.02)., Conclusions: Tumor ADC surpasses tumor stiffness as a biomarker of cellularity. Tumor stiffness is associated with tumor-stroma ratio and peri-tumor stiffness might be an imaging biomarker of intra-tumoral immune microenvironment., Clinical Relevance Statement: Tissue stiffness could potentially serve as an imaging biomarker of the intra-tumoral immune microenvironment of hepatocellular carcinoma and aid in patient selection for immunotherapy., Key Points: Apparent diffusion coefficient reflects cellularity of hepatocellular carcinoma. Tumor stiffness reflects tumor-stroma ratio of hepatocellular carcinoma and is associated with tumor-infiltrating lymphocytes. Tumor and peri-tumor stiffness might serve as imaging biomarkers of intra-tumoral immune microenvironment., (© 2024. The Author(s).)

Parotid glands are one of the most common sites for salivary gland tumors. Conventional imaging techniques have limited usefulness in the quantitative assessment of the parotid glands, making it difficult to differentiate between healthy tissue and tumors, as well as between benign and malignant tumors. Magnetic resonance elastography (MRE) is a non-invasive technique that may potentially overcome these limitations. Nevertheless, due to the size of the parotid gland, increased elastographic resolution is required. This may be achieved by applying shear waves at higher frequencies. However, it also results in stronger attenuation, making the illumination of the parotid challenging. Here, we describe a novel passive driver tailored to the anatomy of the human face, which minimizes the distance shear waves need to travel from the source to the area of interest and thus decreases shear wave attenuation, making high-frequency shear wave MRE feasible., (© 2024. The Author(s).)

Background: Magnetic resonance elastography (MRE) is a rapidly developing medical imaging technique that allows for quantitative assessment of the biomechanical properties of the tissue. MRE is now regarded as the most accurate noninvasive test for detecting and staging liver fibrosis. A two-dimensional (2D MRE) acquisition version is currently deployed at >2000 locations worldwide. 2D MRE allows for the evaluation of the magnitude of the complex shear modulus, also referred to as stiffness. The development of 3D vector MRE has enabled researchers to assess the biomechanical properties of small organs where wave propagation cannot be adequately analyzed with the 2D MRE imaging approach used in the liver. In 3D vector MRE, the shear waves are imaged and processed throughout a 3D volume and processed with an algorithm that accounts for wave propagation in any direction. Additionally, the motion is also imaged in x, y, and z directions at each voxel, allowing for more advanced processing to be applied., Purpose: This review describes the technical principles of 3D vector MRE, surveys its clinical applications in small organs, and discusses potential clinical significance of 3D vector MRE., Conclusion: 3D vector MRE is a promising tool for characterizing the biomechanical properties of small organs such as the uterus, pancreas, thyroid, prostate, and salivary glands. However, its potential has not yet been fully explored., Competing Interests: Declaration of competing interest The Mayo Clinic, R.L.E., and J.C. have intellectual property rights and a financial interest in magnetic resonance elastography technology. The remaining authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Abnormal adherence at functional myofascial interfaces is hypothesized as an important phenomenon in myofascial pain syndrome. This study aimed to investigate the feasibility of MR elastography (MRE)-based slip interface imaging (SII) to visualize and assess myofascial mobility in healthy volunteers., Methods: SII was used to assess local shear strain at functional myofascial interfaces in the flexor digitorum profundus (FDP) and thighs. In the FDP, MRE was performed at 90 Hz vibration to each index, middle, ring, and little finger. Two thigh MRE scans were performed at 40 Hz with knees flexed and extended. The normalized octahedral shear strain (NOSS) maps were calculated to visualize myofascial slip interfaces. The entropy of the probability distribution of the gradient NOSS was computed for the two knee positions at the intermuscular interface between vastus lateralis and vastus intermedius, around rectus femoris, and between vastus intermedius and vastus medialis., Results: NOSS map depicted distinct functional slip interfaces in the FDP for each finger. Compared to knee flexion, clearer slip interfaces and larger gradient NOSS entropy at the vastus lateralis-vastus intermedius interface were observed during knee extension, where the quadriceps are not passively stretched. This suggests the optimal position for using SII to visualize myofascial slip interface in skeletal muscles is when muscles are not subjected to any additional force., Conclusion: The study demonstrated that MRE-based SII can visualize and assess myofascial interface mobility in extremities. The results provide a foundation for investigating the hypothesis that myofascial pain syndrome is characterized by changes in the mobility of myofascial interfaces., (© 2024 International Society for Magnetic Resonance in Medicine.)

Purpose: To evaluate magnetic resonance elastography (MRE)-based liver stiffness measurement as a biomarker to predict the onset of cirrhosis in early-stage alcohol-related liver disease (ALD) patients, and the transition from compensated to decompensated cirrhosis in ALD., Methods: Patients with ALD and at least one MRE examination between 2007 and 2020 were included in this study. Patient demographics, liver chemistries, MELD score (within 30 days of the first MRE), and alcohol abstinence history were collected from the electronic medical records. Liver stiffness and fat fraction were measured. Disease progression was assessed in the records by noting cirrhosis onset in early-stage ALD patients and decompensation in those initially presenting with compensated cirrhosis. Nomograms and cut-off values of liver stiffness, derived from Cox proportional hazards models were created to predict the likelihood of advancing to cirrhosis or decompensation., Results: A total of 182 patients (132 men, median age 57 years) were included in this study. Among 110 patients with early-stage ALD, 23 (20.9%) developed cirrhosis after a median follow-up of 6.2 years. Among 72 patients with compensated cirrhosis, 33 (45.8%) developed decompensation after a median follow-up of 4.2 years. MRE-based liver stiffness, whether considered independently or adjusted for age, alcohol abstinence, fat fraction, and sex, was a significant and independent predictor for both future cirrhosis (Hazard ratio [HR] = 2.0-2.2, p = 0.002-0.003) and hepatic decompensation (HR = 1.2-1.3, p = 0.0001-0.006). Simplified Cox models, thresholds, and corresponding nomograms were devised for practical use, excluding non-significant or biased variables., Conclusions: MRE-based liver stiffness assessment is a useful predictor for the development of cirrhosis or decompensation in patients with ALD., (© 2024. The Author(s).)

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., (© 2024 International Society for Magnetic Resonance in Medicine.)

Meningiomas, the most prevalent primary benign intracranial tumors, often exhibit complicated levels of adhesion to adjacent normal tissues, significantly influencing resection and causing postoperative complications. Surgery remains the primary therapeutic approach, and when combined with adjuvant radiotherapy, it effectively controls residual tumors and reduces tumor recurrence when complete removal may cause a neurologic deficit. Previous studies have indicated that slip interface imaging (SII) techniques based on MR elastography (MRE) have promise as a method for sensitively determining the presence of tumor-brain adhesion. In this study, we developed and tested an improved algorithm for assessing tumor-brain adhesion, based on recognition of patterns in MRE-derived normalized octahedral shear strain (NOSS) images. The primary goal was to quantify the tumor interfaces at higher risk for adhesion, offering a precise and objective method to assess meningioma adhesions in 52 meningioma patients. We also investigated the predictive value of MRE-assessed tumor adhesion in meningioma recurrence. Our findings highlight the effectiveness of the improved SII technique in distinguishing the adhesion degrees, particularly complete adhesion. Statistical analysis revealed significant differences in adhesion percentages between complete and partial adherent tumors (p = 0.005), and complete and non-adherent tumors (p<0.001). The improved technique demonstrated superior discriminatory ability in identifying tumor adhesion patterns compared to the previously described algorithm, with an AUC of 0.86 vs. 0.72 for distinguishing complete adhesion from others (p = 0.037), and an AUC of 0.72 vs. 0.67 for non-adherent and others. Aggressive tumors exhibiting atypical features showed significantly higher adhesion percentages in recurrence group compared to non-recurrence group (p = 0.042). This study validates the efficacy of the improved SII technique in quantifying meningioma adhesions and demonstrates its potential to affect clinical decision-making. The reliability of the technique, coupled with potential to help predict meningioma recurrence, particularly in aggressive tumor subsets, highlights its promise in guiding treatment strategies., Competing Interests: M.C.M., A.M., J.H., R.L.E., and Mayo Clinic have intellectual property rights and a financial interest in MRE technology. For the remaining authors, no competing financial interests exist. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Zheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose To investigate the feasibility of using quantitative MR elastography (MRE) to characterize the influence of aging and sex on left ventricular (LV) shear stiffness. Materials and Methods In this prospective study, LV myocardial shear stiffness was measured in 109 healthy volunteers (age range: 18-84 years; mean age, 40 years ± 18 [SD]; 57 women, 52 men) enrolled between November 2018 and September 2019, using a 5-minute MRE acquisition added to a clinical MRI protocol. Linear regression models were used to estimate the association of cardiac MRI and MRE characteristics with age and sex; models were also fit to assess potential age-sex interaction. Results Myocardial shear stiffness significantly increased with age in female (age slope = 0.03 kPa/year ± 0.01, P = .009) but not male (age slope = 0.008 kPa/year ± 0.009, P = .38) volunteers. LV ejection fraction (LVEF) increased significantly with age in female volunteers (0.23% ± 0.08 per year, P = .005). LV end-systolic volume (LVESV) decreased with age in female volunteers (-0.20 mL/m 2 ± 0.07, P = .003). MRI parameters, including T1, strain, and LV mass, did not demonstrate this interaction ( P > .05). Myocardial shear stiffness was not significantly correlated with LVEF, LV stroke volume, body mass index, or any MRI strain metrics ( P > .05) but showed significant correlations with LV end-diastolic volume/body surface area (BSA) (slope = -3 kPa/mL/m 2 ± 1, P = .004, r 2 = 0.08) and LVESV/BSA (-1.6 kPa/mL/m 2 ± 0.5, P = .003, r 2 = 0.08). Conclusion This study demonstrates that female, but not male, individuals experience disproportionate LV stiffening with natural aging, and these changes can be noninvasively measured with MRE. Keywords: Cardiac, Elastography, Biological Effects, Experimental Investigations, Sexual Dimorphisms, MR Elastography, Myocardial Shear Stiffness, Quantitative Stiffness Imaging, Aging Heart, Myocardial Biomechanics, Cardiac MRE Supplemental material is available for this article . Published under a CC BY 4.0 license.

Background and Purpose: Spontaneous intracranial hypotension is a condition resulting from a leak of CSF from the spinal canal arising independent of a medical procedure. Spontaneous intracranial hypotension can present with normal brain MR imaging findings and nonspecific symptoms, leading to the underdiagnosis in some patients and unnecessary invasive myelography in others who are found not to have the condition. Given the likelihood that spontaneous intracranial hypotension alters intracranial biomechanics, the goal of this study was to evaluate MR elastography as a potential noninvasive test to diagnose the condition., Materials and Methods: We performed MR elastography in 15 patients with confirmed spontaneous intracranial hypotension from September 2022 to April 2023. Age, sex, symptom duration, and brain MR imaging Bern score were collected. MR elastography data were used to compute stiffness and damping ratio maps, and voxelwise modeling was performed to detect clusters of significant differences in mechanical properties between patients with spontaneous intracranial hypotension and healthy control participants. To evaluate diagnostic accuracy, we summarized each examination by 2 spatial pattern scores (one each for stiffness and damping ratio) and evaluated group-wise discrimination by receiver operating characteristic curve analysis., Results: Patients with spontaneous intracranial hypotension exhibited significant differences in both stiffness and damping ratio (false discovery rate-corrected, Q < 0.05). Pattern analysis discriminated patients with spontaneous intracranial hypotension from healthy controls with an area under the curve of 0.97 overall, and the area under the curve was 0.97 in those without MR imaging findings of spontaneous intracranial hypotension., Conclusions: Results from this pilot study demonstrate MR elastography as a potential imaging biomarker and a noninvasive method for diagnosing spontaneous intracranial hypotension, including patients with normal brain MR imaging findings., (© 2024 by American Journal of Neuroradiology.)

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., (© 2023 International Society for Magnetic Resonance in Medicine.)

Background MR elastography (MRE) has been shown to have excellent performance for noninvasive liver fibrosis staging. However, there is limited knowledge regarding the precision and test-retest repeatability of stiffness measurement with MRE in the multicenter setting. Purpose To determine the precision and test-retest repeatability of stiffness measurement with MRE across multiple centers using the same phantoms. Materials and Methods In this study, three cylindrical phantoms made of polyvinyl chloride gel mimicking different degrees of liver stiffness in humans (phantoms 1-3: soft, medium, and hard stiffness, respectively) were evaluated. Between January 2021 and January 2022, phantoms were circulated between five different centers and scanned with 10 MRE-equipped clinical 1.5-T and 3-T systems from three major vendors, using two-dimensional (2D) gradient-recalled echo (GRE) imaging and/or 2D spin-echo (SE) echo-planar imaging (EPI). Similar MRE acquisition parameters, hardware, and reconstruction algorithms were used at each center. Mean stiffness was measured by a single observer for each phantom and acquisition on a single section. Stiffness measurement precision and same-session test-retest repeatability were assessed using the coefficient of variation (CV) and the repeatability coefficient (RC), respectively. Results The mean precision represented by the CV was 5.8% (95% CI: 3.8, 7.7) for all phantoms and both sequences combined. For all phantoms, 2D GRE achieved a CV of 4.5% (95% CI: 3.3, 5.7) whereas 2D SE EPI achieved a CV of 7.8% (95% CI: 3.1, 12.6). The mean RC of stiffness measurement was 5.8% (95% CI: 3.7, 7.8) for all phantoms and both sequences combined, 4.9% (95% CI: 2.7, 7.0) for 2D GRE, and 7.0% (95% CI: 2.9, 11.2) for 2D SE EPI (all phantoms). Conclusion MRE had excellent in vitro precision and same-session test-retest repeatability in the multicenter setting when similar imaging protocols, hardware, and reconstruction algorithms were used. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Tang in this issue.

This study sought to identify whether an anatomical indicator of injury severity as measured by multiparametric magnetic resonance imaging (MRI) including magnetic resonance elastography (MRE), is predictive of a clinical measure of injury severity after moderate-severe traumatic brain injury (TBI). Nine individuals who were admitted to acute inpatient rehabilitation after moderate-to-severe TBI completed a comprehensive MRI protocol prior to discharge from rehabilitation, which included conventional MRI with diffusion tensor imaging (DTI). Of those, five of nine also underwent brain MRE to measure the brain parenchyma stiffness. Clinical severity of injury was measured by the length of post-traumatic amnesia (PTA). MRI-assessed non-hemorrhage contusion score and hemorrhage score, DTI-measured white matter fractional anisotropy, and MRE-measured lesion stiffness were all assessed. A higher hemorrhagic score was significantly associated with a longer length of PTA ( p  = 0.026). Participants with a longer PTA tended to have a higher non-hemorrhage contusion score and softer contusion lesions than the contralateral control side, although the small sample size did not allow for assessment of a significant association. To our knowledge, this is the first report applying MRI/MRE imaging protocol to quantitate altered brain anatomy after moderate-severe TBI and its association with PTA, a known clinical predictor of post-acute outcome. Future larger studies could lead to the development of prediction models that integrate clinical data with anatomical (MRI), structural (DTI), and mechanical (MRE) changes caused by TBI, to inform prognosis and care planning., Competing Interests: Richard L. Ehman, Matthew C. Murphy, and the Mayo Clinic have intellectual property rights and a financial interest in MRE technology. The other authors have nothing to disclose., (© Dmitry Esterov et al., 2024; Published by Mary Ann Liebert, Inc.)

Background and Purpose: Normal pressure hydrocephalus is a treatable cause of dementia associated with distinct mechanical property signatures in the brain as measured by MR elastography. In this study, we tested the hypothesis that specific anatomic features of normal pressure hydrocephalus are associated with unique mechanical property alterations. Then, we tested the hypothesis that summary measures of these mechanical signatures can be used to predict clinical outcomes., Materials and Methods: MR elastography and structural imaging were performed in 128 patients with suspected normal pressure hydrocephalus and 44 control participants. Patients were categorized into 4 subgroups based on their anatomic features. Surgery outcome was acquired for 68 patients. Voxelwise modeling was performed to detect regions with significantly different mechanical properties between each group. Mechanical signatures were summarized using pattern analysis and were used as features to train classification models and predict shunt outcomes for 2 sets of feature spaces: a limited 2D feature space that included the most common features found in normal pressure hydrocephalus and an expanded 20-dimensional (20D) feature space that included features from all 4 morphologic subgroups., Results: Both the 2D and 20D classifiers performed significantly better than chance for predicting clinical outcomes with estimated areas under the receiver operating characteristic curve of 0.66 and 0.77, respectively ( P < .05, permutation test). The 20D classifier significantly improved the diagnostic OR and positive predictive value compared with the 2D classifier ( P < .05, permutation test)., Conclusions: MR elastography provides further insight into mechanical alterations in the normal pressure hydrocephalus brain and is a promising, noninvasive method for predicting surgical outcomes in patients with normal pressure hydrocephalus., (© 2024 by American Journal of Neuroradiology.)

Vascular brain injury results in loss of structural and functional connectivity and leads to cognitive impairment. Its various manifestations, including microinfarcts, microhaemorrhages and white matter hyperintensities, result in microstructural tissue integrity loss and secondary neurodegeneration. Among these, tissue microstructural alteration is a relatively early event compared with atrophy along the aging and neurodegeneration continuum. Understanding its association with cognition may provide the opportunity to further elucidate the relationship between vascular health and clinical outcomes. Magnetic resonance elastography offers a non-invasive approach to evaluate tissue mechanical properties, providing a window into the microstructural integrity of the brain. This retrospective study evaluated brain stiffness as a potential biomarker for vascular brain injury and its role in mediating the impact of vascular dysfunction on cognitive impairment. Seventy-five participants from the Mayo Clinic Study of Aging underwent brain imaging using a 3T MR imager with a spin-echo echo-planar imaging sequence for magnetic resonance elastography and T 1 - and T 2 -weighted pulse sequences. This study evaluated the effects of vascular biomarkers (white matter hyperintensities and cardiometabolic condition score) on brain stiffness using voxelwise analysis. Partial correlation analysis explored associations between brain stiffness, white matter hyperintensities, cardiometabolic condition and global cognition. Mediation analysis determined the role of stiffness in mediating the relationship between vascular biomarkers and cognitive performance. Statistical significance was set at P-values < 0.05. Diagnostic accuracy of magnetic resonance elastography stiffness for white matter hyperintensities and cardiometabolic condition was evaluated using receiver operator characteristic curves. Voxelwise linear regression analysis indicated white matter hyperintensities negatively correlate with brain stiffness, specifically in periventricular regions with high white matter hyperintensity levels. A negative association between cardiovascular risk factors and stiffness was also observed across the brain. No significant patterns of stiffness changes were associated with amyloid load. Global stiffness (µ) negatively correlated with both white matter hyperintensities and cardiometabolic condition when all other covariables including amyloid load were controlled. The positive correlation between white matter hyperintensities and cardiometabolic condition weakened and became statistically insignificant when controlling for other covariables. Brain stiffness and global cognition were positively correlated, maintaining statistical significance after adjusting for all covariables. These findings suggest mechanical alterations are associated with cognitive dysfunction and vascular brain injury. Brain stiffness significantly mediated the indirect effects of white matter hyperintensities and cardiometabolic condition on global cognition. Local cerebrovascular diseases (assessed by white matter hyperintensities) and systemic vascular risk factors (assessed by cardiometabolic condition) impact brain stiffness with spatially and statistically distinct effects. Global brain stiffness is a significant mediator between vascular disease measures and cognitive function, highlighting the value of magnetic resonance elastography-based mechanical assessments in understanding this relationship., Competing Interests: This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and is being conducted in compliance with Mayo Clinic Conflict of Interest policies. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Mayo Clinic, J.H., R.L.E., A.M. and M.C.M. have a financial interest in MRE technology., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Magnetic resonance elastography (MRE) is an accurate noninvasive diagnostic tool for assessing the stiffness of parenchymal organs, including the spleen. However, this measurement may be biased due to postprandial changes in splenic stiffness. The aim of the current study was to evaluate postprandial changes in spleen stiffness assessed by MRE in a large sample of healthy volunteers. This was a prospective institutional research ethics board-approved study. Healthy volunteers with no history of liver disease were recruited for an MRE test and blood draw from December 2018 to July 2019. Each participant underwent spleen MRE after at least 4 h of fasting and again 30 min after a 1000 kcal meal. Also, 14 randomly selected volunteers underwent additional MRE examinations at 1.5 and 2.5 h after food intake. The MRE data were acquired at 60 Hz using a 1.5-T MRI scanner. The spleen stiffness was assessed using a weighted mean of stiffness values from regions of interest manually drawn on three to five spleen slices. Spearman's rank correlation, Wilcoxon signed-rank, Friedman, and Mann-Whitney tests were used for statistical analysis. A total of 100 volunteers met the inclusion criteria and were eventually enrolled in this study (age 23 ± 2 years; 65 women). The mean spleen stiffness for the whole group increased by 7.9% (p < 0.001) from the mean ± SD value of 5.09 ± 0.63 (95% CI: 4.96-5.21) kPa in the fasting state to 5.47 ± 0.66 (95% CI 5.34-5.60) kPa 30 min after the meal and then gradually decreased. However, even 2 h 30 min after the meal, the spleen stiffness was higher than in the fasting state. This difference was statistically significant at p less than 0.001. It was concluded that meal intake results in a statistically significant elevation of spleen stiffness that persists for 2.5 h. This finding supports the recommendation for routine fasting for more than 2.5 h prior to assessing MRE-based spleen stiffness., (© 2023 John Wiley & Sons Ltd.)

MR elastography (MRE), first described in 1995 and FDA-cleared in 2009, has emerged as an important tool for noninvasively detecting and staging liver fibrosis in patients with known or suspected chronic liver disease. This review focuses on a series of practical questions about the clinical use of MRE. Most head-to-head comparison studies with other laboratory and imaging-based tests have concluded that MRE has the highest diagnostic performance among tests for staging liver fibrosis. Limitations in the accuracy of biopsy as a standard of truth in staging liver fibrosis are increasingly being recognized. MRE-based measurements show promise as quantitative surrogates of disease severity and predictors of important clinical outcomes. The appropriate role of MRE in the management of patients with chronic liver disease is being actively incorporated into recognized clinical guidelines. Growing evidence shows that MRI measurement of elevated liver fat is the most important single biomarker for detecting nonalcoholic steatohepatitis (NASH) and that MRE-based liver stiffness is the most important single biomarker for detecting at-risk NASH (i.e., NASH with stage ≥ F2 fibrosis). Advances in MRE technology are offering higher precision and new biomarkers, which have potential to allow independent assessment of inflammation and other histologic processes in addition to fibrosis.

Non-alcoholic fatty liver disease (NAFLD) is the liver manifestation of the metabolic syndrome with global prevalence reaching epidemic levels. Despite the high disease burden in the population only a small proportion of those with NAFLD will develop progressive liver disease, for which there is currently no approved pharmacotherapy. Identifying those who are at risk of progressive NAFLD currently requires a liver biopsy which is problematic. Firstly, liver biopsy is invasive and therefore not appropriate for use in a condition like NAFLD that affects a large proportion of the population. Secondly, biopsy is limited by sampling and observer dependent variability which can lead to misclassification of disease severity. Non-invasive biomarkers are therefore needed to replace liver biopsy in the assessment of NAFLD. Our study addresses this unmet need. The LITMUS Imaging Study is a prospectively recruited multi-centre cohort study evaluating magnetic resonance imaging and elastography, and ultrasound elastography against liver histology as the reference standard. Imaging biomarkers and biopsy are acquired within a 100-day window. The study employs standardised processes for imaging data collection and analysis as well as a real time central monitoring and quality control process for all the data submitted for analysis. It is anticipated that the high-quality data generated from this study will underpin changes in clinical practice for the benefit of people with NAFLD. Study Registration: clinicaltrials.gov: NCT05479721., Competing Interests: Declaration of Competing Interest FEM, SA, KW, JC, MA, EMG, SF, MRG, JC, IFL, RA, RSG, JMP, JB, VR, MW, SP, MA, RF, LM, ET, ME, PL, ATH, GP, HYJ, KP and PMB declare no conflicts of interest. MP is a shareholder in Perspectum Ltd. EMT is a shareholder in Perspectum Ltd. SA is currently employed by Boehringer Ingelheim (but was not during his participation in the project). GPA has served as a consultant and an advisory board member for Pfizer Inc., Inventiva Pharma, GlaxoSmithKline and KaNDy Therapeutics; he has been a consultant to BerGenBio ASA, Median Technologies, FRACTYL, Amryt Pharmaceuticals and AstraZeneca; and has given presentations on behalf of Roche Diagnostics and Medscape all through the University of Nottingham contract. CA declares the following potential conflicts of interest: Hologic: Support of study and expert; Guerbet: Member of board, PI of study; Siemens: Expert. EB has served as a consultant or advisory board member for Boehringer Ingelheim, Gilead Sciences, Intercept, Merck, Novo Nordisk, Pfizer, ProSciento; and a speaker for Gilead Sciences, Intercept, Merck, Novo Nordisk, Pfizer. She has also received a research grant from Gilead Sciences for fatty liver research. AG served as a speaker and consultant for AbbVie, Alexion, AstraZeneca, Bayer, BMS, CSL Behring, Eisai, Falk, Gilead, Heel, Intercept, Ipsen, Merz, MSD, Novartis, Pfizer, Roche, Sanofi-Aventis, Sequana; received research funding from Intercept, Falk, Novartis. JMS reports consultancy for BMS, Boehringer Ingelheim, Echosens, Genfit, Gilead Sciences, Intercept Pharmaceuticals, Madrigal, Novartis, Pfizer, Roche, Sanofi; received research funding from Gilead Sciences and was on the speaker's bureau for Falk Foundation MSD Sharp & Dohme GmbH. MJS and PH are employed by Antaros Medical AB, Mölndal, Sweden. ES is employed by Perspectum Ltd., Oxford, UK. RB is a shareholder and employed (CEO) by Perspectum Ltd., Oxford, UK. KP and MK are employed by Resoundant Inc., Rochester, MN, USA. RLE and the Mayo Clinic have intellectual property rights and a financial interest in magnetic resonance elastography technology. AT is employed by ADVANZPHARMA, Capital House, 1st Floor, 85 King William Street, London, EC4N 7BL, United Kingdom. HC is employed by Boehringer Ingelheim Pharma GmbH & Co. MM is employed by Novartis AG, Basel, Switzerland. CY is employed by Pfizer Inc., Lake Mary, FL, USA. TT was employed by Pfizer at the time of her involvement with the project. QMA is coordinator of the EU IMI-2 LITMUS consortium, which is funded by the EU Horizon 2020 programme and EFPIA. This multistakeholder consortium includes industry partners. QMA has received research grant funding from AstraZeneca, Boehringer Ingelheim, and Intercept Pharmaceuticals, Inc.; has served as a consultant on behalf of Newcastle University for Alimentiv, Akero, AstraZeneca, Axcella, 89bio, Boehringer Ingelheim, Bristol Myers Squibb, Galmed, Genfit, Genentech, Gilead, GSK, Hanmi, HistoIndex, Intercept Pharmaceuticals, Inc., Inventiva, Ionis, IQVIA, Janssen, Madrigal, Medpace, Merck, NGM Bio, Novartis, Novo Nordisk, PathAI, Pfizer, Poxel, Resolution Therapeutics, Roche, Ridgeline Therapeutics, RTI, Shionogi, and Terns; has served as a speaker for Fishawack, Integritas Communications, Kenes, Novo Nordisk, Madrigal, Medscape, and Springer Healthcare; and receives royalties from Elsevier Ltd. SN is a shareholder in Perspectum Ltd. SAH has research grants from Akero, Altimmune, Axcella-Cirius, CiVi Biopharma, Cymabay, Galectin, Genfit, Gilead Sciences, Hepion Pharmaceuticals, Hightide Therapeutics, Intercept, Madrigal, Metacrine, NGM Bio, Northsea Therapeutics, Novartis, Novo Nordisk, Poxel, Sagimet, Viking. He has received consulting fees from Akero, Altimmune, Alentis, Arrowhead, Axcella, Echosens, Enyo, Foresite Labs, Galectin, Genfit, Gilead Sciences, Hepion, HIghtide, HistoIndex, Intercept, Kowa, Madrigal, Metacrine, NeuroBo, NGM, Northsea, Novartis, Novo Nordisk, Poxel, Perspectum, Sagimet, Terns, and Viking., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Increasing concerns have been raised about the long-term negative effects of subconcussive repeated head impact (RHI). To elucidate RHI injury mechanisms, many efforts have studied how head impacts affect the skull-brain biomechanics and have found that mechanical interactions at the skull-brain interface dampen and isolate brain motions by decoupling the brain from the skull. Despite intense interest, in vivo quantification of the functional state of the skull-brain interface remains difficult. This study developed a magnetic resonance elastography (MRE) based technique to non-invasively assess skull-brain mechanical interactions (i.e., motion transmission and isolation function) under dynamic loading. The full MRE displacement data were separated into rigid body motion and wave motion. The rigid body motion was used to calculate the brain-to-skull rotational motion transmission ratio ( R tr ) to quantify skull-brain motion transmissibility, and the wave motion was used to calculate the cortical normalized octahedral shear strain ( NOSS ) (calculated based on a partial derivative computing neural network) to evaluate the isolation capability of the skull-brain interface. Forty-seven healthy volunteers were recruited to investigate the effects of age/sex on R tr and cortical NOSS , and 17 of 47 volunteers received multiple scans to test the repeatability of the proposed techniques under different strain conditions. The results showed that both R tr and NOSS were robust to MRE driver variations and had good repeatability, with intraclass correlation coefficient (ICC) values between 0.68 and 0.97 (fair to excellent). No age or sex dependence were observed with R tr , whereas a significant positive correlation between age and NOSS was found in the cerebrum, frontal, temporal, and parietal lobes (all p  < 0.05), but not in the occipital lobe ( p  = 0.99). The greatest change in NOSS with age was found in the frontal lobe, one of the most frequent locations of traumatic brain injury (TBI). Except for the temporal lobe ( p  = 0.0087), there was no significant difference in NOSS between men and women. This work provides motivation for utilizing MRE as a non-invasive tool for quantifying the biomechanics of the skull-brain interface. It evaluated the age and sex dependence and may lead to a better understanding of the protective role and mechanisms of the skull-brain interface in RHI and TBI, as well as improve the accuracy of computational models in simulating the skull-brain interface.

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., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background & Aims: We conducted an individual patient data meta-analysis to establish stiffness cut-off values for magnetic resonance elastography (MRE) in staging liver fibrosis and to assess potential confounding factors., Methods: A systematic review of the literature identified studies reporting MRE data in patients with NAFLD. Data were obtained from the corresponding authors. The pooled diagnostic cut-off value for the various fibrosis stages was determined in a two-stage meta-analysis. Multilevel modelling methods were used to analyse potential confounding factors influencing the diagnostic accuracy of MRE in staging liver fibrosis., Results: Eight independent cohorts comprising 798 patients were included in the meta-analysis. The area under the receiver operating characteristic curve (AUROC) for MRE in detecting significant fibrosis was 0.92 (sensitivity, 79%; specificity, 89%). For advanced fibrosis, the AUROC was 0.92 (sensitivity, 87%; specificity, 88%). For cirrhosis, the AUROC was 0.94 (sensitivity, 88%, specificity, 89%). Cut-offs were defined to explore concordance between MRE and histopathology: ≥F2, 3.14 kPa (pretest probability, 39.4%); ≥F3, 3.53 kPa (pretest probability, 24.1%); and F4, 4.45 kPa (pretest probability, 8.7%). In generalized linear mixed model analysis, histological steatohepatitis with higher inflammatory activity (odds ratio 2.448, 95% CI 1.180-5.079, p <0.05) and high gamma-glutamyl transferase (GGT) concentration (>120U/L) (odds ratio 3.388, 95% CI 1.577-7.278, p <0.01] were significantly associated with elevated liver stiffness, and thus affecting accuracy in staging early fibrosis (F0-F1). Steatosis, as measured by magnetic resonance imaging proton density fat fraction, and body mass index(BMI) were not confounders., Conclusions: MRE has excellent diagnostic performance for significant, advanced fibrosis and cirrhosis in patients with NAFLD. Elevated inflammatory activity and GGT level may lead to overestimation of early liver fibrosis, but anthropometric measures such as BMI or the degree of steatosis do not., Impact and Implications: This individual patient data meta-analysis of eight international cohorts, including 798 patients, demonstrated that MRE achieves excellent diagnostic accuracy for significant, advanced fibrosis and cirrhosis in patients with NAFLD. Cut-off values (significant fibrosis, 3.14 kPa; advanced fibrosis, 3.53 kPa; and cirrhosis, 4.45 kPa) were established. Elevated inflammatory activity and gamma-glutamyltransferase level may affect the diagnostic accuracy of MRE, leading to overestimation of liver fibrosis in early stages. We observed no impact of diabetes, obesity, or any other metabolic disorder on the diagnostic accuracy of MRE., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: Magnetic resonance elastography (MRE) has been established as the most accurate noninvasive technique for diagnosing liver fibrosis. Recent publications have suggested that the measurement of splenic stiffness is useful in setting where portal hypertension may be present. The goal of the current study was to compile normative data for MRE-assessed stiffness measurements of the spleen in young adults., Materials and Methods: A total of 100 healthy young Caucasian volunteers (65 females and 35 males) in the age range of 20 to 32 years were enrolled in this study. The participants reported no history of chronic spleen and liver disease, normal alcohol consumption, and a normal diet. The MRE data were acquired by using a 1.5 T whole-body scanner and a 2D GRE pulse sequence with 60 Hz excitation. Spleen stiffness was calculated as a weighted mean of stiffness values in the regions of interest manually drawn by the radiologist on three to five spleen slices., Results: Mean spleen stiffness was 5.09 ± 0.65 kPa for the whole group. Male volunteers had slightly higher splenic stiffness compared to females: 5.28 ± 0.78 vs. 4.98 ± 0.51 kPa, however, this difference was not statistically significant ( p = 0.12). Spleen stiffness did not correlate with spleen fat content and liver stiffness but a statistically significant correlation with spleen volume was found., Conclusions: The findings of this study provide normative values for 2D MRE-based measurement of spleen stiffness in young adults, a basis for assessing the value of this biomarker in young patients with portal system pathologies., Competing Interests: The Mayo Clinic, R.L.E. and M.Y. have intellectual property rights and a financial interest in magnetic resonance technology. The remaining authors declare no conflict of interest.

Purpose: To evaluate the performance and repeatability assessing liver, spleen, and kidney stiffness with magnetic resonance elastography (MRE), using arrays of pneumatic passive drivers., Methods: An array of four flexible, pneumatically activated passive drivers for abdominal MRE were developed and tested in this study. Multiple MRE acquisitions were performed prospectively in a series of eleven volunteers, with activation of all combinations of the four drivers, individually and simultaneously. MRE exams were repeated three times to study within-day and between-day test-retest repeatability. Semi-quantitative evaluation of wave propagation and penetration, and quantitative assessment of tissue stiffness was conducted for liver, spleen, and kidneys., Results: When driver location and amplitude were sufficient to achieve necessary shear wave illumination in any given region of interest, the results showed excellent test-retest repeatability in abdominal organ stiffness with both single and multiple driver configurations. The results confirmed that multiple driver arrays provided suitable shear wave illumination over a larger region of the abdomen, allowing more reliable stiffness measurements in multiple organs. MRE assessment of the spleen was found to be prone to effects of excessive shear wave amplitude, however., Conclusion: A multiple driver array provides shear wave illumination over a larger region of the abdomen than obtained with a single driver, for MRE assessment of multiple abdominal organs, providing excellent test-retest repeatability in stiffness measurements. However, careful tuning of the location and amplitude of each driver is essential to achieve consistent results., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background & Aims: FALCON 1 was a phase IIb study of pegbelfermin in patients with non-alcoholic steatohepatitis (NASH) and stage 3 fibrosis. This FALCON 1 post hoc analysis aimed to further assess the effect of pegbelfermin on NASH-related biomarkers, correlations between histological assessments and non-invasive biomarkers, and concordance between the week 24 histologically assessed primary endpoint response and biomarkers., Methods: Blood-based composite fibrosis scores, blood-based biomarkers, and imaging biomarkers were evaluated for patients with available data from FALCON 1 at baseline through week 24. SomaSignal tests assessed protein signatures of NASH steatosis, inflammation, ballooning, and fibrosis in blood. Linear mixed-effect models were fit for each biomarker. Correlations and concordance were assessed between blood-based biomarkers, imaging, and histological metrics., Results: At week 24, pegbelfermin significantly improved blood-based composite fibrosis scores (ELF, FIB-4, APRI), fibrogenesis biomarkers (PRO-C3 and PC3X), adiponectin, CK-18, hepatic fat fraction measured by MRI-proton density fat fraction, and all four SomaSignal NASH component tests. Correlation analyses between histological and non-invasive measures identified four main categories: steatosis/metabolism, tissue injury, fibrosis, and biopsy-based metrics. Concordant and discordant effects of pegbelfermin on the primary endpoint vs . biomarker responses were observed; the most clear and concordant effects were on measures of liver steatosis and metabolism. A significant association between hepatic fat measured histologically and by imaging was observed in pegbelfermin arms., Conclusions: Pegbelfermin improved NASH-related biomarkers most consistently through improvement of liver steatosis, though biomarkers of tissue injury/inflammation and fibrosis were also improved. Concordance analysis shows that non-invasive assessments of NASH support and exceed the improvements detected by liver biopsy, suggesting that greater consideration should be given to the totality of available data when evaluating the efficacy of NASH therapeutics., Clinical Trial Number: Post hoc analysis of NCT03486899., Impact and Implications: FALCON 1 was a study of pegbelfermin vs . placebo in patients with non-alcoholic steatohepatitis (NASH) without cirrhosis; in this study, patients who responded to pegbelfermin treatment were identified through examination of liver fibrosis in tissue samples collected through biopsy. In the current analysis, non-invasive blood- and imaging-based measures of fibrosis, liver fat, and liver injury were used to determine pegbelfermin treatment response to see how they compared with the biopsy-based results. We found that many of the non-invasive tests, particularly those that measured liver fat, identified patients who responded to pegbelfermin treatment, consistent with the liver biopsy findings. These results suggest that there may be additional value in using data from non-invasive tests, along with liver biopsy, to evaluate how well patients with NASH respond to treatment., Competing Interests: EA Brown and G Cizza were employees of Bristol Myers Squibb at the time of the study; S Du, J Schwarz, and ED Charles are employees of Bristol Myers Squibb and may own company stock. A Minnich is a consultant for Bristol Myers Squibb. AJ Sanyal has been a consultant for 89Bio, Albireo, Alnylam, Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Covance, Eli Lilly, Fractyl Health, Genentech, Genfit, Gilead Sciences, HemoShear, HistoIndex, Intercept Pharmaceuticals, Inventiva Pharma, Janssen Pharmaceuticals, Madrigal Pharmaceuticals, Mallinckrodt, Merck, NGM Biopharmaceuticals, Novartis, Novo Nordisk, PathAI, Pfizer, Poxel, Prosciento, Regeneron, Roche, Salix Pharmaceuticals, Sequana Medical, Siemens, and Terns Pharmaceuticals; received grants from Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Fractyl Health, Gilead Sciences, Inventiva Pharma, Madrigal, Mallinckrodt, Merck, Novartis, and Novo Nordisk; has an ongoing research collaboration with but has received no direct funds from Echosens-Sandhill and Siemens; owns stock in Durect, Exhalenz, Genfit, HemoShear, Indalo Therapeutics, Northsea Therapeutics, Rivus Pharmaceuticals, and Tiziana Life Sciences; and has received royalties from Elsevier and UpToDate. R Loomba has been a consultant for and received grants from Galmed Pharmaceuticals, Madrigal Pharmaceuticals, and NGM Biopharmaceuticals; has been a consultant for Arrowhead Pharmaceuticals, Bird Rock Bio, Celgene, Enanta Pharmaceuticals, Gir Pharmaceuticals, GRI Bio, Metacrine, and Receptos; has received grants from Allergan, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi-Sankyo, Galectin Therapeutics, GE, Genfit, Gilead Sciences, Intercept Pharmaceuticals, Janssen Pharmaceuticals, Merck, Pfizer, Prometheus, Siemens, and Sirius; and is employed by Liponexus. M Karsdal and DJ Leeming own stock in Nordic Bioscience and are among the original inventors and patent holders for assays for PRO-C3. The Mayo Clinic and RL Ehman have intellectual property rights and a financial interest related to MR elastography technology. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2023 The Author(s).)

Obesity-related chronic inflammation contributes to nonalcoholic fatty liver disease (NAFLD) progression in obese patients (body mass index [BMI] >30 kg/m 2 ). 1 The early detection of inflammation with noninvasive imaging technology may help identify individuals with a high risk of developing NAFLD., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Aging and dementia involve the disruption of brain molecular pathways leading to the alterations in tissue composition and gross morphology of the brain. Phenotypic and biomarker overlap between various etiologies of dementia supports a need for new modes of information to more accurately distinguish these disorders. Brain mechanical properties, which can be measured noninvasively by MR elastography, represent one understudied feature that are sensitive to neurodegenerative processes. In this study, we used two stiffness estimation schemes to test the hypothesis that different etiologies of dementia are associated with unique patterns of mechanical alterations across the cerebral cortex., Methods: MR elastography data were acquired for six clinical groups including amyloid-negative cognitively unimpaired (CU), amyloid-positive cognitively unimpaired (A + CU), amyloid-positive participants with mild cognitive impairment (A + MCI), amyloid-positive participants with Alzheimer's clinical syndrome (A + ACS), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD). Stiffness maps were computed using two neural network inversions with the objective to at least partially separate the parenchyma-specific and morphological effects of neurodegeneration on mechanical property estimates. A tissue-confined inversion algorithm was designed to obtain the best estimate of stiffness in the brain parenchyma itself, while a regionally-aware inversion algorithm was used to measure the tissue stiffness along with the surroundings. Mean stiffness of 15 bilateral gray matter cortical regions were considered for statistical analysis. First, we tested the hypothesis that cortical stiffness changes in the aging brain. Next, we tested the overall study hypothesis by first comparing stiffness in each clinical group to the CU group, and then comparing the clinical groups against one another. Finally, we assessed the spatial and statistical overlap between atrophy and stiffness changes for both inversions., Results: Cortical brain regions become softer with age for both inversions with larger effects observed using regionally-aware stiffness. Stiffness decreases in the range 0.010-0.027 kPa per year were observed. Pairwise comparisons of each clinical group with cognitively unimpaired participants demonstrated 5 statistically significant differences in stiffness for tissue-confined measurements and 19 statistically different stiffness changes for the regionally-aware stiffness measurements. Pairwise comparisons between clinical groups further demonstrated unique patterns of stiffness differences. Analysis of the atrophy-versus-stiffness relationship showed that regionally-aware stiffness measurements exhibit higher sensitivity to neurodegeneration with findings that are not fully explained by partial volume effects or atrophy., Conclusions: Both tissue-confined and regionally-aware stiffness estimates exhibited unique and complementary stiffness differences in various etiologies of dementia. Our results suggest that mechanical alterations measured by MRE reflect both tissue-specific differences as well as environmental effects. Multi-inversion schemes in MRE may provide new insights into the relationships between neuropathology and brain biomechanics., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Mayo Clinic, K.P., J.H., R.L.E., A.M., M.C.M., have financial interest in MRE technology. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and is being conducted in compliance with Mayo Clinic Conflict of Interest policies., (Published by Elsevier Inc.)

Background and Aims: The impact of disease progression in NAFLD on liver outcomes remains poorly understood. We aimed to investigate NAFLD progression using longitudinal liver stiffness measurements (LSM) by serial magnetic resonance elastography (MRE) and the association with liver outcomes., Approach and Results: All adult patients with NAFLD who underwent at least two serial MREs for clinical evaluation at Mayo Clinic, Rochester, between 2007 and 2019 were identified from the institutional database. Progression and regression were defined based on LSM change of 19% above or below 19% of initial LSM, respectively, based on Quantitative Imaging Biomarker Alliance consensus. The association between change in LSM and liver-related outcomes occurring after the last MRE was examined using time-to-event analysis. A total of 128 participants underwent serial MREs (53% female, median age 59 years). The median time between paired MREs was 3.4 (range 1-10.7) years. NAFLD progression (LSM = +0.61 kPa/year) was identified in 17 patients (13.3%). NAFLD regression (-0.40 kPa/year) occurred in 35 patients (27.3%). Stable LSM was noted in 76 participants (59.4%). In NAFLD without cirrhosis at baseline ( n = 75), cirrhosis development occurred in 14% of LSM progressors and 2.9% of non-progressors ( p = 0.059) over a median 2.7 years of follow-up from the last MRE. Among those with compensated cirrhosis at baseline MRE ( n = 29), decompensation or death occurred in 100% of LSM progressors and 19% of non-progressors ( p  < 0.001) over a median 2.5 years of follow-up after the last MRE., Conclusions: Noninvasive monitoring of LSM by conventional MRE is a promising method of longitudinal NAFLD monitoring and risk estimation of liver-related outcomes in NAFLD., (Copyright © 2022 American Association for the Study of Liver Diseases.)

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 (R DI ) 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., (© 2022 Bristol Myers Squibb and Mayo Clinic. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

In 1995, a vivid image of diffracting waves in red and blue was published on the cover of the journal SCIENCE. An article in that issue described a new imaging technology called magnetic resonance elastography (MRE) (Muthupillai in Science 269:1854-1857, 1995). In 2004, quantitative images of liver stiffness in vivo, obtained with MRE, were demonstrated for the first time at the annual meeting of the International Society for Magnetic Resonance in Medicine. Only five years later, the technology had become widely available as an FDA-cleared diagnostic tool for patient care. MRE has emerged as a reliable non-invasive diagnostic method for detecting and staging liver fibrosis. Deployed on more than 2000 MRI systems worldwide, MRE has received a Category I CPT code from the American Medical Association, based on clinical availability and efficacy. For many patients, MRE now provides a safe, more comfortable, and much less expensive alternative to liver biopsy for diagnosing liver fibrosis. Although progress in radiology is notable for a history of very rapid translation of technology innovations to patient care, the path is rarely linear. This article reflects on the story of MRE, the advances and the setbacks, and the lessons that were learned in the process., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Inversion algorithms used to convert acquired MR elastography wave data into material property estimates often assume that the underlying materials are locally homogeneous. Here we evaluate the impact of that assumption on stiffness estimates in gray-matter regions of interest in brain MR elastography., Methods: We describe an updated neural network inversion framework using finite-difference model-derived data to train convolutional neural network inversion algorithms. Neural network inversions trained on homogeneous simulations (homogeneous learned inversions [HLIs]) or inhomogeneous simulations (inhomogeneous learned inversions [ILIs]) are generated with a variety of kernel sizes. These inversions are evaluated in a brain MR elastography simulation experiment and in vivo in a test-retest repeatability experiment including 10 healthy volunteers., Results: In simulation and in vivo, HLI and ILI with small kernels produce similar results. As kernel size increases, the assumption of homogeneity has a larger effect, and HLI and ILI stiffness estimates show larger differences. At each inversion's optimal kernel size in simulation (7 × 7 × 7 for HLI, 11 × 11 × 11 for ILI), ILI is more sensitive to true changes in stiffness in gray-matter regions of interest in simulation. In vivo, there is no difference in the region-level repeatability of stiffness estimates between the inversions, although ILI appears to better maintain the stiffness map structure as kernel size increases, while decreasing the spatial variance in stiffness estimates., Conclusions: This study suggests that inhomogeneous inversions provide small but significant benefits even when large stiffness gradients are absent., (© 2022 International Society for Magnetic Resonance in Medicine.)

Background and Aims: Despite that hepatic fibrosis often affects the liver globally, spatial distribution can be heterogeneous. This study aimed to investigate the effect of liver stiffness (LS) heterogeneity on concordance between MR elastography (MRE)-based fibrosis staging and biopsy staging in patients with NAFLD., Approach and Results: We retrospectively evaluated data from 155 NAFLD patients who underwent liver biopsy and 3 Tesla MRE and undertook a retrospective validation study of 169 NAFLD patients at three hepatology centers. Heterogeneity of stiffness was assessed by measuring the range between minimum and maximum MRE-based LS measurement (LSM). Variability of LSM was defined as the stiffness range divided by the maximum stiffness value. The cohort was divided into two groups (homogenous or heterogeneous), according to whether variability was below or above the average for the training cohort. Based on histopathology and receiver operating characteristic (ROC) analysis, optimum LSM thresholds were determined for MRE-based fibrosis staging of stage 4 (4.43, kPa; AUROC, 0.89) and stage ≥3 (3.93, kPa; AUROC, 0.89). In total, 53 had LSM above the threshold for stage 4. Within this group, 30 had a biopsy stage of <4. In 86.7% of these discordant cases, variability of LSM was classified as heterogeneous. In MRE-based LSM stage ≥3, 88.9% of discordant cases were classified as heterogeneous. Results of the validation cohort were similar to those of the training cohort., Conclusions: Discordance between biopsy- and MRE-based fibrosis staging is associated with heterogeneity in LSM, as depicted with MRE., (© 2022 The Authors. Hepatology published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Purpose: To investigate the diagnostic performance of preoperative MR elastography (MRE) in predicting early recurrence (ER) and late recurrence (LR) of HCC after hepatectomy., Method: In total, 180 patients (median age, 52 years; interquartile range, 41-50 years; 161 men) who underwent conventional MRI and MRE before hepatectomy between December 2014 and April 2020 were retrospectively recruited. A preoperative clinic-radiologic model and a combined postoperative clinic-pathologic and radiologic model were built using quantitatively MRE-derived stiffnesses, and image features to predict tumor ER and LR after hepatectomy. The Cox proportional hazards model and ROC analyses were used to identify the value of parameters to predict ER and LR., Results: Seventy-three (40.5%) and 16 (8.9%) developed ER and LR after hepatectomy, respectively. For prediction of ER, the preoperative model integrated higher tumor stiffness (TS) (hazard ratio [HR],1.142; p < 0.001) with AFP ≥ 400 ng/mL (HR,1.761; p = 0.022), multifocal tumors (HR,3.229; p < 0.001) and lower ADC (HR,0.998; p = 0.017) variables; and the postoperative model incorporated higher TS, microvascular invasion, multifocal tumors, Child-Pugh class and ADC predictors. The two models provided comparable predictive performance (pre- 0.812 vs. post- 0.834, p = 0.283). Moreover, TS alone had a high sensitivity (90.4%) for predicting ER. Liver stiffness (LS) (HR, 1.757; p < 0.001) was the only independent predictor for LR in multivariate analysis in both the pre- and postoperative models with high specificity (90.0%), and its AUC with an optimal cut-off of 3.62 kPa was 0.860., Conclusions: Quantitative MRE-based stiffness is a useful biomarker for preoperative prediction of ER and LR of HCC., (Copyright © 2022. Published by Elsevier B.V.)

Objectives: To evaluate the potential of MR elastography (MRE)-based shear strain mapping to noninvasively predict the presence of microvascular invasion (MVI) in hepatocellular carcinoma (HCC)., Methods: Fifty-nine histopathology-proven HCC patients with conventional 60-Hz MRE examinations (+/-MVI, n = 34/25) were enrolled retrospectively between December 2016 and October 2019, with one subgroup comprising 29/59 patients (+/-MVI, n = 16/13) who also underwent 40- and 30-Hz MRE examinations. Octahedral shear strain (OSS) maps were calculated, and the percentage of peritumoral interface length with low shear strain (i.e., a low-shear-strain length, pLSL, %) was recorded. For OSS-pLSL, differences between the MVI (+) and MVI (-) groups and diagnostic performance at different MRE frequencies were analyzed using the Mann-Whitney test and area under the receiver operating characteristic curve (AUC), respectively., Results: The peritumor OSS-pLSL was significantly higher in the MVI (+) group than in the MVI (-) group at the three frequencies (all p < 0.01). The AUC of peritumor OSS-pLSL for predicting MVI was good/excellent in all frequency groups (60-Hz: 0.73 (n = 59)/0.80 (n = 29); 40-Hz: 0.84; 30-Hz: 0.90). On further analysis of the 29 cases with all frequencies, the AUCs were not significantly different. As the frequency decreased from 60-Hz, the specificity of OSS increased at 40-Hz (53.8-61.5%) and further increased at 30-Hz (53.8-76.9%), and the sensitivity remained high at lower frequencies (100.0-93.8%) (all p > 0.05)., Conclusions: MRE-based shear strain mapping is a promising technique for noninvasively predicting the presence of MVI in patients with HCC, and the most recommended frequency for OSS is 30-Hz., Key Points: • MR elastography (MRE)-based shear strain mapping has the potential to predict the presence of microvascular invasion (MVI) in hepatocellular carcinoma preoperatively. • The low interface shear strain identified at tumor-liver boundaries was highly correlated with the presence of MVI., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Objectives: To assess reproducibility and fibrosis classification accuracy of magnetic resonance elastography (MRE)-determined liver stiffness measured manually at two different centers, and by automated analysis software in adults with nonalcoholic fatty liver disease (NAFLD), using histopathology as a reference standard., Methods: This retrospective, cross-sectional study included 91 adults with NAFLD who underwent liver MRE and biopsy. MRE-determined liver stiffness was measured independently for this analysis by an image analyst at each of two centers using standardized manual analysis methodology, and separately by an automated analysis. Reproducibility was assessed pairwise by intraclass correlation coefficient (ICC) and Bland-Altman analysis. Diagnostic accuracy was assessed by receiver operating characteristic (ROC) analyses., Results: ICC of liver stiffness measurements was 0.95 (95% CI: 0.93, 0.97) between center 1 and center 2 analysts, 0.96 (95% CI: 0.94, 0.97) between the center 1 analyst and automated analysis, and 0.94 (95% CI: 0.91, 0.96) between the center 2 analyst and automated analysis. Mean bias and 95% limits of agreement were 0.06 ± 0.38 kPa between center 1 and center 2 analysts, 0.05 ± 0.32 kPa between the center 1 analyst and automated analysis, and 0.11 ± 0.41 kPa between the center 2 analyst and automated analysis. The area under the ROC curves for the center 1 analyst, center 2 analyst, and automated analysis were 0.834, 0.833, and 0.847 for distinguishing fibrosis stage 0 vs. ≥ 1, and 0.939, 0.947, and 0.940 for distinguishing fibrosis stage ≤ 2 vs. ≥ 3., Conclusion: MRE-determined liver stiffness can be measured with high reproducibility and fibrosis classification accuracy at different centers and by an automated analysis., Key Points: • Reproducibility of MRE liver stiffness measurements in adults with nonalcoholic fatty liver disease is high between two experienced centers and between manual and automated analysis methods. • Analysts at two centers had similar high diagnostic accuracy for distinguishing dichotomized fibrosis stages. • Automated analysis provides similar diagnostic accuracy as manual analysis for advanced fibrosis., (© 2021. The Author(s).)