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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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. 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. [Display omitted] • 3D Vector MRE has high clinical potential for the assessment of small organs. • 3D Vector MRE of the uterus, pancreas, thyroid, prostate, and parotid is feasible. • 3D Vector MRE provides information on the biomechanical properties of small organs. • 3D Vector MRE helps to differentiate between healthy and pathological tissue. • More research is needed to optimize the performance of 3D Vector MRE in small organs. [ABSTRACT FROM AUTHOR]

Magnetic resonance elastography (MRE) is recognized as the most precise imaging technology for assessing liver fibrosis in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to investigate the clinical factors and pathological characteristics that may impact LSM in MASLD patients. This cross-sectional study recruited 124 patients who concurrently performed MRE, MRI-PDFF, and biopsy-proven MASLD. Linear regression models, Spearman's correlation, and subgroup analysis were employed to identify the variables affecting LSM. The AUROC (95 % CI) of MRE for diagnosing fibrosis stage ≥ 1, 2, 3, and 4 was 0.80 (0.70–0.90), 0.76 (0.66–0.85), 0.92 (0.86–0.99), and 0.99 (0.99–1.00), with corresponding cutoffs of 2.56, 2.88, 3.35, and 4.76 kPa, respectively. Multivariate analyses revealed that AST was the only independent clinical variable significantly correlated with LSM. Furthermore, LSM exhibited a notable association with the grade of lobular inflammation and hepatocellular ballooning. Subgroup analysis showed that when AST ≥ 2 ULN or inflammation grade ≥ 2, LSM of patients with early fibrosis stages showed a slight but significant increase. MRE demonstrates significant diagnostic accuracy in predicting liver fibrosis stages for MASLD patients, especially for advanced liver fibrosis and cirrhosis. However, elevated AST and the severity of liver inflammation may impact its accuracy in staging early liver fibrosis. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to establish the shear wave measurement (SWM) cut‐off value for each fibrosis stage using magnetic resonance (MR) elastography values as a reference standard. Methods: We prospectively analyzed 594 patients with chronic liver disease who underwent SWM and MR elastography. Correlation coefficients (were analyzed, and the diagnostic value was evaluated by the area under the receiver operating characteristic curve. Liver stiffness was categorized by MR elastography as F0 (<2.61 kPa), F1 (≥2.61 kPa, <2.97 kPa, any fibrosis), F2 (≥2.97 kPa, <3.62 kPa, significant fibrosis), F3 (≥3.62 kPa, <4.62 kPa, advanced fibrosis), or F4 (≥4.62 kPa, cirrhosis). Results: The median SWM values increased significantly with increasing fibrosis stage (p < 0.001). The correlation coefficient between SWM and MR elastography values was 0.793 (95% confidence interval 0.761–0.821). The correlation coefficients between SWM and MR elastography values significantly decreased with increasing body mass index and skin–capsular distance; skin–capsular distance values were associated with significant differences in sensitivity, specificity, accuracy, or positive predictive value, whereas body mass index values were not. The best cut‐off values for any fibrosis, significant fibrosis, advanced fibrosis, and cirrhosis were 6.18, 7.09, 8.05, and 10.89 kPa, respectively. Conclusions: This multicenter study in a large number of patients established SWM cut‐off values for different degrees of fibrosis in chronic liver diseases using MR elastography as a reference standard. It is expected that these cut‐off values will be applied to liver diseases in the future. [ABSTRACT FROM AUTHOR]

Purpose: Liver stiffness measurement (LSM) by transient elastography has been shown to underperform in high-risk varices (HRVs) prediction in obese non-alcoholic fatty liver disease (NAFLD) compensated cirrhosis (CC). LSM by magnetic resonance elastography (MRE) and acoustic force radiation impulse (ARFI) has been shown to be useful in prediction of oesophageal varices (EVs), but has limited evidence in obese NAFLD-CC. Methods: Obese patients with NAFLD-CC who underwent MRE and ARFI for LSM and endoscopy for screening of varices were enrolled. Performance of MRE and ARFI for predicting EVs or HRVs was evaluated using area under receiver operating characteristics (AUROC) curves and regression analyses were performed for predictor variables. Results: One hundred eight patients [mean age 54.7 ± 9.6 years, median BMI, 28.5 (26.4–30.0) kg/m2. 72.2% diabetics, 45.4% hypertensive] were enrolled. Fifty-two (48.1%) had no varices, while 29 (26.8%) and 27 (25%) had low-risk varices (LRVs) and HRVs, respectively. MRE-LSM was higher in patients with LRVs (p = 0.01) or HRVs (p = 0.001) against those without varices. ARFI-LSM did not differ significantly between those without and with LRVs or HRVs (p > 0.05 for all). There was a low correlation between ARFI-LSM and MRE-LSM in the overall cohort (r = 0.19). Only platelet count (PC) [0.98 (0.97–0.99)] and MRE-LSM [1.8 (1.26–2.79)] were predictors of HRVs. At a cut-off of 4.75, MRE showed a sensitivity of 96.3%. Model combining MRE-LSM with PC had a diagnostic AUROC of 0.77 and 0.76 for EVs and HRVs. Conclusion: In obese NAFLD-CC, MRE-LSM is significantly higher in patients with varices. MRE combined with PC predicts EVs and HRVs with better accuracy than ARFI. [ABSTRACT FROM AUTHOR]

Abstract 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.

Abstract Background Colorectal cancer is the third most common tumour entity in the world and up to 50% of the patients develop liver metastases (CRLM) within five years. To improve and personalize therapeutic strategies, new diagnostic tools are urgently needed. For instance, biomechanical tumour properties measured by magnetic resonance elastography (MRE) could be implemented as such a diagnostic tool. We postulate that ex vivo MRE combined with histological and radiological evaluation of CRLM could provide biomechanics-based diagnostic markers for cell viability in tumours. Methods 34 CRLM specimens from patients who had undergone hepatic resection were studied using ex vivo MRE in a frequency range from 500 Hz to 5300 Hz with increments of 400 Hz. Single frequency evaluation of shear wave speed and wave penetration rate as proxies for stiffness and viscosity was performed, along with rheological model fitting based on the spring-pot model and powerlaw exponent α, ranging between 0 (complete solid behaviour) and 1 (complete fluid behaviour). For histological analysis, samples were stained with H&E and categorized according to the degree of regression. Quantitative histologic analysis was performed to analyse nucleus size, aspect ratio, and density. Radiological response was assessed according to RECIST-criteria. Results Five samples showed major response to chemotherapy, six samples partial response and 23 samples no response. For higher frequencies (> 2100 Hz), shear wave speed correlated significantly with the degree of regression (p ≤ 0.05) indicating stiffer properties with less viable tumour cells. Correspondingly, rheological analysis of α revealed more elastic-solid tissue properties at low cell viability and major response (α = 0.43 IQR 0.36, 0.47) than at higher cell viability and no response (α = 0.51 IQR 0.48, 0.55; p = 0.03). Quantitative histological analysis showed a decreased nuclear area and density as well as a higher nuclear aspect ratio in patients with major response to treatment compared to patients with no response (all p

Abstract Variations in the biomechanical stiffness of brain tumors can not only influence the difficulty of surgical resection but also impact postoperative outcomes. In a prospective, single-blinded study, we utilize pre-operative magnetic resonance elastography (MRE) to predict the stiffness of intracranial tumors intraoperatively and assess the impact of increased tumor stiffness on clinical outcomes following microsurgical resection of vestibular schwannomas (VS) and meningiomas. MRE measurements significantly correlated with intraoperative tumor stiffness and baseline hearing status of VS patients. Additionally, MRE stiffness was elevated in patients that underwent sub-total tumor resection compared to gross total resection and those with worse postoperative facial nerve function. Furthermore, we identify tumor microenvironment biomarkers of increased stiffness, including αSMA + myogenic fibroblasts, CD163 + macrophages, and HABP (hyaluronic acid binding protein). In a human VS cell line, a dose-dependent upregulation of HAS1-3, enzymes responsible for hyaluronan synthesis, was observed following stimulation with TNFα, a proinflammatory cytokine present in VS. Taken together, MRE is an accurate, non-invasive predictor of tumor stiffness in VS and meningiomas. VS with increased stiffness portends worse preoperative hearing and poorer postoperative outcomes. Moreover, inflammation-mediated hyaluronan deposition may lead to increased stiffness.

Mechanically, the brain is characterized by both solid and fluid properties. The resulting unique material behavior fosters proliferation, differentiation, and repair of cellular and vascular networks, and optimally protects them from damaging shear forces. Magnetic resonance elastography (MRE) is a noninvasive imaging technique that maps the mechanical properties of the brain in vivo. MRE studies have shown that abnormal processes such as neuronal degeneration, demyelination, inflammation, and vascular leakage lead to tissue softening. In contrast, neuronal proliferation, cellular network formation, and higher vascular pressure result in brain stiffening. In addition, brain viscosity has been reported to change with normal blood perfusion variability and brain maturation as well as disease conditions such as tumor invasion. In this article, the contributions of the neuronal, glial, extracellular, and vascular networks are discussed to the coarse‐grained parameters determined by MRE. This reductionist multi‐network model of brain mechanics helps to explain many MRE observations in terms of microanatomical changes and suggests that cerebral viscoelasticity is a suitable imaging marker for brain disease. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer is the third most common tumour entity in the world and up to 50% of the patients develop liver metastases (CRLM) within five years. To improve and personalize therapeutic strategies, new diagnostic tools are urgently needed. For instance, biomechanical tumour properties measured by magnetic resonance elastography (MRE) could be implemented as such a diagnostic tool. We postulate that ex vivo MRE combined with histological and radiological evaluation of CRLM could provide biomechanics-based diagnostic markers for cell viability in tumours. Methods: 34 CRLM specimens from patients who had undergone hepatic resection were studied using ex vivo MRE in a frequency range from 500 Hz to 5300 Hz with increments of 400 Hz. Single frequency evaluation of shear wave speed and wave penetration rate as proxies for stiffness and viscosity was performed, along with rheological model fitting based on the spring-pot model and powerlaw exponent α, ranging between 0 (complete solid behaviour) and 1 (complete fluid behaviour). For histological analysis, samples were stained with H&E and categorized according to the degree of regression. Quantitative histologic analysis was performed to analyse nucleus size, aspect ratio, and density. Radiological response was assessed according to RECIST-criteria. Results: Five samples showed major response to chemotherapy, six samples partial response and 23 samples no response. For higher frequencies (> 2100 Hz), shear wave speed correlated significantly with the degree of regression (p ≤ 0.05) indicating stiffer properties with less viable tumour cells. Correspondingly, rheological analysis of α revealed more elastic-solid tissue properties at low cell viability and major response (α = 0.43 IQR 0.36, 0.47) than at higher cell viability and no response (α = 0.51 IQR 0.48, 0.55; p = 0.03). Quantitative histological analysis showed a decreased nuclear area and density as well as a higher nuclear aspect ratio in patients with major response to treatment compared to patients with no response (all p < 0.05). Discussion: Our results suggest that MRE could be useful in the characterization of biomechanical property changes associated with cell viability in CRLM. In the future, MRE could be applied in clinical diagnosis to support individually tailored therapy plans for patients with CRLM. [ABSTRACT FROM AUTHOR]

Magnetic resonance elastography (MRE) and diffusion-weighted imaging (DWI) are complementary imaging techniques that detect disease based on viscoelasticity and water mobility, respectively. However, the relationship between viscoelasticity and water diffusion is still poorly understood, hindering the clinical translation of combined DWI-MRE markers. We used DWI-MRE to study 129 biomaterial samples including native and cross-linked collagen, glycosaminoglycans (GAGs) with different sulfation levels, and decellularized specimens of pancreas and liver, all with different proportions of solid tissue, or solid fractions. We developed a theoretical framework of the relationship between mechanical loss and tissue-water mobility based on two parameters, solid and fluid viscosity. These parameters revealed distinct DWI-MRE property clusters characterizing weak, moderate, and strong water-network interactions. Sparse networks interacting weakly with water, such as collagen or diluted decellularized tissue, resulted in marginal changes in water diffusion over increasing solid viscosity. In contrast, dense networks with larger solid fractions exhibited both free and hindered water diffusion depending on the polarity of the solid components. For example, polar and highly sulfated GAGs as well as native soft tissues hindered water diffusion despite relatively low solid viscosity. Our results suggest that two fundamental properties of tissue networks, solid fraction and network polarity, critically influence solid and fluid viscosity in biological tissues. Since clinical DWI and MRE are sensitive to these viscosity parameters, the framework we present here can be used to detect tissue remodeling and architectural changes in the setting of diagnostic imaging. The viscoelastic properties of biological tissues provide a wealth of information on the vital state of cells and host matrix. Combined measurement of viscoelasticity and water diffusion by medical imaging is sensitive to tissue microarchitecture. However, the relationship between viscoelasticity and water diffusion is still poorly understood, hindering full exploitation of these properties as a combined clinical biomarker. Therefore, we analyzed the parameter space accessible by diffusion-weighted imaging (DWI) and magnetic resonance elastography (MRE) and developed a theoretical framework for the relationship between water mobility and mechanical parameters in biomaterials. Our theory of solid material properties related to particle motion can be translated to clinical radiology using clinically established MRE and DWI. [Display omitted] [ABSTRACT FROM AUTHOR]

Agarose gels are often used as a tissue mimic. The goal of this work was to determine the appropriate agarose concentrations that result in mechanical properties that match three different porcine organs. Strain tests were carried out with an amplitude varying from 0.01% to 10% at a frequency of 1 Hz on a range of agarose concentrations and porcine organs. Frequency sweep tests were performed from 0.1 Hz to a maximum of 9.5 Hz at a shear strain amplitude of 0.1% for agarose and porcine organs. In agarose samples, the effect of pre-compression of the samples up to 10% axial strain was considered during frequency sweep tests. The experimental measurements from agarose samples were fit to a fractional order viscoelastic (springpot) model. The model was then used to predict stress relaxation in response to a step strain of 0.1%. The prediction was compared to experimental relaxation data, and the results agreed within 12%. The agarose concentrations (by mass) that gave the best fit were 0.25% for the liver, 0.3% for the kidney, and 0.4% for the heart. At a frequency of 0.1 Hz and a shear strain of 0.1%, the agarose concentrations that best matched the shear storage modulus of the porcine organs were 0.4% agarose for the heart, 0.3% agarose for the kidney, and 0.25% agarose for the liver. [ABSTRACT FROM AUTHOR]

Objectives: The aims of the present study were to investigate a combination of magnetic resonance elastography (MRE) and vibration-controlled transient elastography (VCTE) or MRE and fibrosis score 4 (FIB-4) in the detection of significant fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: Between November 5, 2021, and March 4, 2022, a total of 119 consecutive patients with MASLD were included. Liver stiffness was measured using liver biopsy, MRE, VCTE, and FIB-4. Data were collected from outpatient visit charts. Significant fibrosis was defined as ≥ stage 2 fibrosis. Results: All 119 MASLD patients were Caucasian, and their median age was 55 years. MRE, VCTE, and FIB-4 demonstrated significant accuracy in the detection of significant fibrosis with an area under the ROC curve (AUC) of 0.848 ± 0.036 (p < 0.001), 0.632 ± 0.052 (p = 0.012), and 0.664 ± 0.051 (p = 0.001), respectively. However, the diagnostic performance of MRE was superior compared to that of VCTE (AUC difference: 0.216 ± 0.053, p < 0.001) and FIB-4 (AUC difference: 0.184 ± 0.058, p = 0.001). With logistic regression analysis, it was determined that when compared to MRE alone, a combination of MRE and TE (p = 0.880) or MRE and FIB-4 (p = 0.455) were not superior for detecting significant fibrosis. Conclusions: MRE alone is an accurate and non-invasive method for the identification of MASLD patients with significant fibrosis. Clinical relevance statement: Magnetic resonance elastography alone accurately detects significant fibrosis in patients with metabolic dysfunction-associated steatotic liver disease. Key Points: • In routine clinical practice, several non-invasive biochemical-based biomarkers and imaging methods are widely used to assess liver fibrosis in patients with metabolic dysfunction-associated steatotic liver disease. • Magnetic resonance elastography (MRE) is more accurate than vibration-controlled transient elastography (VCTE) or fibrosis score 4 (FIB-4) for assessing liver fibrosis and identifying significant fibrosis in patients with metabolic dysfunction-associated steatotic liver disease. • The combination of MRE and VCTE or MRE and FIB-4 was not superior to MRE alone. [ABSTRACT FROM AUTHOR]

The utilization of a reverberant shear-wave field in shear-wave elastography has emerged as a promising technique for achieving robust shear-wave speed (SWS) estimation. However, many types of estimators cannot accurately measure SWS within such a complicated 3D wave field. This study introduces an advanced autocorrelation estimator based on angular integration known as the angular integral autocorrelation (AIA) approach to address this issue. The AIA approach incorporates all the autocorrelation data from various angles during measurements, resulting in enhanced robustness to both noise and imperfect distributions in SWS estimation. The effectiveness of the AIA estimator for SWS estimation is first validated using a k-Wave simulation of a stiff branching tube in a uniform background. Furthermore, the AIA estimator is applied to ultrasound elastography experiments, magnetic resonance imaging (MRI) experiments, and optical coherence tomography (OCT) studies across a range of different excitation frequencies on tissues and phantoms, including in vivo scans. The results verify the capacity of the AIA approach to enhance the accuracy of SWS estimation and the signal-to-noise ratio (SNR), even within an imperfect reverberant shear-wave field. Compared to simple autocorrelation approaches, the AIA approach can also successfully visualize and define lesions while significantly improving the estimated SWS and SNR in homogeneous background materials and providing improved elastic contrast between structures within the scans. These findings demonstrate the robustness and effectiveness of the AIA approach across a wide range of applications, including ultrasound elastography, magnetic resonance elastography (MRE), and optical coherence elastography (OCE), for accurately identifying the elastic properties of biological tissues in diverse excitation scenarios. [ABSTRACT FROM AUTHOR]

Background: In vivo quantification of the structure–function relationship of the intervertebral disc (IVD) via quantitative MRI has the potential to aid objective stratification of disease and evaluation of restorative therapies. Magnetic resonance elastography (MRE) is an imaging technique that assesses tissue shear properties and combined with quantitative MRI metrics reflective of composition can inform structure–function of the IVD. The objectives of this study were to (1) compare MRE‐ and rheometry‐derived shear modulus in agarose gels and nucleus pulposus (NP) tissue and (2) correlate MRE and rheological measures of NP tissue with composition and quantitative MRI. Method: MRE and MRI assessment (i.e., T1ρ and T2 mapping) of agarose samples (2%, 3%, and 4% (w/v); n = 3–4/%) and of bovine caudal IVDs after equilibrium dialysis in 5% or 25% PEG (n = 13/PEG%) was conducted. Subsequently, agarose and NP tissue underwent torsional mechanical testing consisting of a frequency sweep from 1 to 100 Hz at a rotational strain of 0.05%. NP tissue was additionally evaluated under creep and stress relaxation conditions. Linear mixed‐effects models and univariate regression analyses evaluated the effects of testing method, %agarose or %PEG, and frequency, as well as correlations between parameters. Results: MRE‐ and rheometry‐derived shear moduli were greater at 100 Hz than at 80 Hz in all agarose and NP tissue samples. Additionally, all samples with lower water content had higher complex shear moduli. There was a significant correlation between MRE‐ and rheometry‐derived modulus values for homogenous agarose samples. T1ρ and T2 relaxation times for agarose and tissue were negatively correlated with complex shear modulus derived from both techniques. For NP tissue, shear modulus was positively correlated with GAG/wet‐weight and negatively correlated with %water content. Conclusion: This work demonstrates that MRE can assess hydration‐induced changes in IVD shear properties and further highlights the structure–function relationship between composition and shear mechanical behaviors of NP tissue. [ABSTRACT FROM AUTHOR]

Pregnancy places a metabolic burden on the body including the liver, which is responsible for ensuring adequate nutrition for the maternal and fetal systems. To gain a better understanding of liver adaptation, this study investigates metabolic shifts occurring in livers of pregnant rats. Metabolic capacities of the livers of pregnant and non-pregnant female Wistar rats were assessed using comprehensive metabolic models. Kinetic metabolic models were generated for each animal based on protein abundance data from proteomics analysis allowing for a subject-specific assessment of hepatic metabolic functions. Data are available via ProteomeXchange with identifier PXD050758. Additionally, tissue stiffness, viscosity, and water diffusion obtained from magnetic resonance imaging and elastography were correlated with metabolic capabilities to study the relationship between metabolic function and biophysical properties. Proteome profiling revealed differences in protein expression in the livers of pregnant and non-pregnant animals. Functional analysis showed significant variations in metabolic capacities. Livers of pregnant rats had reduced capacities in carbohydrate and fatty acid metabolism, along with altered urea synthesis. Additionally, there were associations between metabolic functions and biophysical properties highlighting potential links between changes in liver structure and metabolic capacities during pregnancy. In summary, our work reveals extensive hepatic metabolic changes in pregnant rats. The liver adapts its metabolic capacities to ensure whole-body metabolic homeostasis but may struggle to counteract nutritional challenges, such as hypoglycemia. The study, employing a personalized approach combining proteomics, kinetic modeling, and advanced imaging, sheds light on the intricate interplay between hepatic adaptations and medical imaging markers, providing a foundation for further investigations into the implications for maternal and fetal health.

Background & aimsFALCON 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.MethodsBlood-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.ResultsAt 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.ConclusionsPegbelfermin 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 numberPost hoc analysis of NCT03486899.Impact and implicationsFALCON 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.

Background & aimsLean patients with non-alcoholic fatty liver disease (NAFLD) represent 10-20% of the affected population and may have heterogeneous drivers of disease. We have recently proposed the evaluation of patients with lean NAFLD without visceral adiposity for rare monogenic drivers of disease. Here, we aimed to validate this framework in a well-characterised cohort of patients with biopsy-proven NAFLD by performing whole exome sequencing.MethodsThis prospective study included 124 patients with biopsy-proven NAFLD and paired liver biopsies who underwent standardised research visits including advanced magnetic resonance imaging (MRI) assessment of liver fat and stiffness.ResultsSix patients with lean NAFLD were identified and underwent whole exome sequencing. Two lean patients (33%) were identified to have monogenic disorders. The lean patients with monogenic disorders had similar age, and anthropometric and MRI characteristics to lean patients without a monogenic disorder. Patient 1 harbours a rare homozygous pathogenic mutation in ALDOB (aldolase B) and was diagnosed with hereditary fructose intolerance. Patient 2 harbours a rare heterozygous mutation in apolipoprotein B (APOB). The pathogenicity of this APOB variant (p.Val1856CysfsTer2) was further validated in the UK Biobank and associated with lower circulating APOB levels (beta = -0.51 g/L, 95% CI -0.65 to -0.36 g/L, p = 1.4 × 10-11) and higher liver fat on MRI (beta = +10.4%, 95% CI 4.3-16.5%, p = 8.8 × 10-4). Hence, patient 2 was diagnosed with heterozygous familial hypobetalipoproteinaemia.ConclusionsIn this cohort of well-characterised patients with lean NAFLD without visceral adiposity, 33% (2/6) had rare monogenic drivers of disease, highlighting the importance of genomic analysis in this NAFLD subtype.Impact and implicationsAlthough most people with non-alcoholic fatty liver disease (NAFLD) are overweight or obese, a subset are lean and may have unique genetic mutations that cause their fatty liver disease. We show that 33% of study participants with NAFLD who were lean harboured unique mutations that cause their fatty liver, and that these mutations had effects beyond the liver. This study demonstrates the value of genetic assessment of NAFLD in lean individuals to identify distinct subtypes of disease.

The utilization of a reverberant shear-wave field in shear-wave elastography has emerged as a promising technique for achieving robust shear-wave speed (SWS) estimation. However, many types of estimators cannot accurately measure SWS within such a complicated 3D wave field. This study introduces an advanced autocorrelation estimator based on angular integration known as the angular integral autocorrelation (AIA) approach to address this issue. The AIA approach incorporates all the autocorrelation data from various angles during measurements, resulting in enhanced robustness to both noise and imperfect distributions in SWS estimation. The effectiveness of the AIA estimator for SWS estimation is first validated using a k-Wave simulation of a stiff branching tube in a uniform background. Furthermore, the AIA estimator is applied to ultrasound elastography experiments, magnetic resonance imaging (MRI) experiments, and optical coherence tomography (OCT) studies across a range of different excitation frequencies on tissues and phantoms, including in vivo scans. The results verify the capacity of the AIA approach to enhance the accuracy of SWS estimation and the signal-to-noise ratio (SNR), even within an imperfect reverberant shear-wave field. Compared to simple autocorrelation approaches, the AIA approach can also successfully visualize and define lesions while significantly improving the estimated SWS and SNR in homogeneous background materials and providing improved elastic contrast between structures within the scans. These findings demonstrate the robustness and effectiveness of the AIA approach across a wide range of applications, including ultrasound elastography, magnetic resonance elastography (MRE), and optical coherence elastography (OCE), for accurately identifying the elastic properties of biological tissues in diverse excitation scenarios.

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.

Background & aimsA two-step strategy combining a serum marker and magnetic resonance elastography (MRE) for detecting advanced fibrosis (stage 3-4) among patients with nonalcoholic fatty liver disease (NAFLD) has been proposed, but its diagnostic accuracy has not been evaluated. In this multicenter study, we aimed to investigate the diagnostic accuracy of a two-step strategy including Fibrosis-4 (FIB-4) followed by MRE.MethodsIn this multicenter study, 806 patients with biopsy-proven NAFLD who underwent contemporaneous MRE were enrolled and randomly assigned to training and validation cohorts. As a first step, patients with FIB-4

Background: Current liver magnetic resonance elastography (MRE) scans often require adjustments to driver amplitude to produce acceptable images. This could lead to time wastage and the potential loss of an opportunity to capture a high-quality image. Purpose: To construct a linear regression model of individualized driver amplitude to improve liver MRE image quality. Material and Methods: Data from 95 liver MRE scans of 61 participants, including abdominal missing volume ratio (AMVR), breath-holding status, the distance from the passive driver on the skin surface to the liver edge (Dd−l), body mass index (BMI), and lateral deflection of the passive driver with respect to the human sagittal plane (Angle α), were continuously collected. The Spearman correlation analysis and lasso regression were conducted to screen the independent variables. Multiple linear regression equations were developed to determine the optimal amplitude prediction model. Results: The optimal formula for linear regression models: driver amplitude (%) = −16.80 + 78.59 × AMVR − 11.12 × breath-holding (end of expiration = 1, end of inspiration = 0) + 3.16 × Dd−l + 1.94 × BMI + 0.34 × angle α, with the model passing the F test (F = 22.455, P <0.001) and R2 value of 0.558. Conclusion: The individualized amplitude prediction model based on AMVR, breath-holding status, Dd−l, BMI, and angle α is a valuable tool in liver MRE examination. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Pancreatic ductal adenocarcinoma (PDAC) stromal viscoelasticity can be measured using MR elastography (MRE). Bowel preparation regimens could affect MRE quality and knowledge on repeatability is crucial for clinical implementation. Purpose: To assess effects of four bowel preparation regimens on MRE quality and to evaluate repeatability and differentiate patients from healthy controls. Study Type: Prospective. Population: 15 controls (41 ± 16 years; 47% female), 16 PDAC patients (one excluded, 66 ± 12 years; 40% female) with 15 age‐/sex‐matched controls (65 ± 11 years; 40% female). Final sample size was 25 controls and 15 PDAC. Field Strength/Sequence: 3‐T, spin‐echo echo‐planar‐imaging, turbo spin‐echo, and fast field echo gradient‐echo. Assessment: Four different regimens were used: fasting; scopolaminebutyl; drinking 0.5 L water; combination of 0.5 L water and scopolaminebutyl. MRE signal‐to‐noise ratio (SNR) was compared between all regimens. MRE repeatability (test–retest) and differences in shear wave speed (SWS) and phase angle (ϕ) were assessed in PDAC and controls. Regions‐of‐interest were defined for tumor, nontumorous (n = 8) tissue in PDAC, and whole pancreas in controls. Two radiologists delineated tumors twice for evaluation of intraobserver and interobserver variability. Statistical Tests: Repeated measures analysis of variance, coefficients of variation (CoVs), Bland–Altman analysis, (un)paired t‐test, Mann–Whitney U‐test, and Wilcoxon signed‐rank test. P‐value<0.05 was considered statistically significant. Results: Preparation regimens did not significantly influence MRE‐SNR. Therefore, the least burdensome preparation (fasting only) was continued. CoVs for tumor SWS were: intrasession (12.8%) and intersession (21.7%), and intraobserver (7.9%) and interobserver (10.3%) comparisons. For controls, CoVs were intrasession (4.6%) and intersession (6.4%). Average SWS for tumor, nontumor, and healthy tissue were: 1.74 ± 0.58, 1.38 ± 0.27, and 1.18 ± 0.16 m/sec (ϕ: 1.02 ± 0.17, 0.91 ± 0.07, and 0.85 ± 0.08 rad), respectively. Significant differences were found between all groups, except for ϕ between healthy–nontumor (P = 0.094). Data Conclusion: The proposed bowel preparation regimens may not influence MRE quality. MRE may be able to differentiate between healthy tissue–tumor and tumor–nontumor. Level of Evidence: 2 Technical Efficacy Stage: 2 [ABSTRACT FROM AUTHOR]

Introduction and objectives: Diffusion-weighted imaging (DWI) has shown potential in characterizing hepatic fibrosis. However, there are no widely accepted apparent diffusion coefficient (ADC) values for the b value combination. This study aims to determine the optimal high and low b values of DWI to assess hepatic fibrosis in patients with chronic liver disease. Materials and methods: The prospective study included 81 patients with chronic liver disease and 21 healthy volunteers who underwent DWI, Magnetic resonance elastography (MRE), and liver biopsy. The ADC was calculated by twenty combinations of nine b values (0, 50, 100, 150, 200, 800, 1000, 1200, and 1500 s/mm2). Results: All ADC values of the healthy volunteers were significantly higher than those of the hepatic fibrosis group (all P < 0.01). With the progression of hepatic fibrosis, ADC values significantly decreased in b value combinations (100 and 1000 s/mm2, 150 and 1200 s/mm2, 200 and 800 s/mm2, and 200 and 1000 s/mm2). ADC values derived from b values of both 200 and 800 s/mm2 and 200 and 1000 s/mm2 were found to be more discriminative for differentiating the stages of hepatic fibrosis. An excellent correlation was between the ADC200–1000 value and MRE shear stiffness (r = − 0.750, P < 0.001). Conclusion: DWI offers an alternative to MRE as a useful imaging marker for detecting and staging hepatic fibrosis. Clinically, ADC values for b values ranging from 200–800 s/mm2 to 200–1000 s/mm2 are recommended for the assessment of hepatic fibrosis. [ABSTRACT FROM AUTHOR]

Background: Fetal alcohol spectrum disorders (FASD), a group of prevalent conditions resulting from prenatal alcohol exposure, affect the maturation of cerebral white matter as first identified with neuroimaging. However, traditional methods are unable to track subtle microstructural alterations to white matter. This preliminary study uses a highly sensitive and clinically translatable magnetic resonance elastography (MRE) protocol to assess brain tissue microstructure through its mechanical properties following an exercise intervention in a rat model of FASD. Methods: Female rat pups were either alcohol‐exposed (AE) via intragastric intubation of alcohol in milk substitute (5.25 g/kg/day) or sham‐intubated (SI) on postnatal days (PD) four through nine to model alcohol exposure during the brain growth spurt. On PD 30, half of AE and SI rats were randomly assigned to either a wheel‐running or standard cage for 12 days. Magnetic resonance elastography was used to measure whole brain and callosal mechanical properties at the end of the intervention (around PD 42) and at 1 month post‐intervention, and findings were validated with histological quantification of oligoglia. Results: Alcohol exposure reduced forebrain stiffness (p = 0.02) in standard‐housed rats. The adolescent exercise intervention mitigated this effect, confirming that increased aerobic activity supports proper neurodevelopmental trajectories. Forebrain damping ratio was lowest in standard‐housed AE rats (p < 0.01), but this effect was not mitigated by intervention exposure. At 1 month post‐intervention, all rats exhibited comparable forebrain stiffness and damping ratio (p > 0.05). Callosal stiffness and damping ratio increased with age. With cessation of exercise, there was a negative rebound effect on the quantity of callosal oligodendrocytes, irrespective of treatment group, which diverged from our MRE results. Conclusions: This is the first application of MRE to measure the brain's mechanical properties in a rodent model of FASD. MRE successfully captured alcohol‐related changes in forebrain stiffness and damping ratio. Additionally, MRE identified an exercise‐related increase to forebrain stiffness in AE rats. [ABSTRACT FROM AUTHOR]

Abstract Mechanically, the brain is characterized by both solid and fluid properties. The resulting unique material behavior fosters proliferation, differentiation, and repair of cellular and vascular networks, and optimally protects them from damaging shear forces. Magnetic resonance elastography (MRE) is a noninvasive imaging technique that maps the mechanical properties of the brain in vivo. MRE studies have shown that abnormal processes such as neuronal degeneration, demyelination, inflammation, and vascular leakage lead to tissue softening. In contrast, neuronal proliferation, cellular network formation, and higher vascular pressure result in brain stiffening. In addition, brain viscosity has been reported to change with normal blood perfusion variability and brain maturation as well as disease conditions such as tumor invasion. In this article, the contributions of the neuronal, glial, extracellular, and vascular networks are discussed to the coarse‐grained parameters determined by MRE. This reductionist multi‐network model of brain mechanics helps to explain many MRE observations in terms of microanatomical changes and suggests that cerebral viscoelasticity is a suitable imaging marker for brain disease.

Abstract Background In vivo quantification of the structure–function relationship of the intervertebral disc (IVD) via quantitative MRI has the potential to aid objective stratification of disease and evaluation of restorative therapies. Magnetic resonance elastography (MRE) is an imaging technique that assesses tissue shear properties and combined with quantitative MRI metrics reflective of composition can inform structure–function of the IVD. The objectives of this study were to (1) compare MRE‐ and rheometry‐derived shear modulus in agarose gels and nucleus pulposus (NP) tissue and (2) correlate MRE and rheological measures of NP tissue with composition and quantitative MRI. Method MRE and MRI assessment (i.e., T1ρ and T2 mapping) of agarose samples (2%, 3%, and 4% (w/v); n = 3–4/%) and of bovine caudal IVDs after equilibrium dialysis in 5% or 25% PEG (n = 13/PEG%) was conducted. Subsequently, agarose and NP tissue underwent torsional mechanical testing consisting of a frequency sweep from 1 to 100 Hz at a rotational strain of 0.05%. NP tissue was additionally evaluated under creep and stress relaxation conditions. Linear mixed‐effects models and univariate regression analyses evaluated the effects of testing method, %agarose or %PEG, and frequency, as well as correlations between parameters. Results MRE‐ and rheometry‐derived shear moduli were greater at 100 Hz than at 80 Hz in all agarose and NP tissue samples. Additionally, all samples with lower water content had higher complex shear moduli. There was a significant correlation between MRE‐ and rheometry‐derived modulus values for homogenous agarose samples. T1ρ and T2 relaxation times for agarose and tissue were negatively correlated with complex shear modulus derived from both techniques. For NP tissue, shear modulus was positively correlated with GAG/wet‐weight and negatively correlated with %water content. Conclusion This work demonstrates that MRE can assess hydration‐induced changes in IVD shear properties and further highlights the structure–function relationship between composition and shear mechanical behaviors of NP tissue.

Knowledge of the mechanical properties of brain tissue in vivo is essential to understanding the mechanisms underlying traumatic brain injury (TBI) and to creating accurate computational models of TBI and neurosurgical simulation. Brain white matter, which is composed of aligned, myelinated, axonal fibers, is structurally anisotropic. White matter in vivo also exhibits mechanical anisotropy, as measured by magnetic resonance elastography (MRE), but measurements of anisotropy obtained by mechanical testing of white matter ex vivo have been inconsistent. The minipig has a gyrencephalic brain with similar white matter and gray matter proportions to humans and therefore provides a relevant model for human brain mechanics. In this study, we compare estimates of anisotropic mechanical properties of the minipig brain obtained by identical, non-invasive methods in the live (in vivo) and dead animals (in situ). To do so, we combine wave displacement fields from MRE and fiber directions derived from diffusion tensor imaging (DTI) with a finite element-based, transversely-isotropic nonlinear inversion (TI-NLI) algorithm. Maps of anisotropic mechanical properties in the minipig brain were generated for each animal alive and at specific times post-mortem. These maps show that white matter is stiffer, more dissipative, and more anisotropic than gray matter when the minipig is alive, but that these differences largely disappear post-mortem, with the exception of tensile anisotropy. Overall, brain tissue becomes stiffer, less dissipative, and less mechanically anisotropic post-mortem. These findings emphasize the importance of testing brain tissue properties in vivo. Statement of Significance: In this study, MRE and DTI in the minipig were combined to estimate, for the first time, anisotropic mechanical properties in the living brain and in the same brain after death. Significant differences were observed in the anisotropic behavior of brain tissue post-mortem. These results demonstrate the importance of measuring brain tissue properties in vivo as well as ex vivo, and provide new quantitative data for the development of computational models of brain biomechanics.

BackgroundMagnetic resonance (MR) elastography of the liver measures hepatic stiffness, which correlates with the histopathological staging of liver fibrosis. Conventional Cartesian gradient-echo (GRE) MR elastography requires breath-holding, which is challenging for children. Non-Cartesian radial free-breathing MR elastography is a potential solution to this problem.ObjectiveTo investigate radial free-breathing MR elastography for measuring hepatic stiffness in children.Materials and methodsIn this prospective pilot study, 14 healthy children and 9 children with liver disease were scanned at 3 T using 2-D Cartesian GRE breath-hold MR elastography (22 s/slice) and 2-D radial GRE free-breathing MR elastography (163 s/slice). Each sequence was acquired twice. Agreement in the stiffness measurements was evaluated using Lin's concordance correlation coefficient (CCC) and within-subject mean difference. The repeatability was assessed using the within-subject coefficient of variation and intraclass correlation coefficient (ICC).ResultsFourteen healthy children and seven children with liver disease completed the study. Median (±interquartile range) normalized measurable liver areas were 62.6% (±26.4%) and 44.1% (±39.6%) for scan 1, and 60.3% (±21.8%) and 43.9% (±44.2%) for scan 2, for Cartesian and radial techniques, respectively. Hepatic stiffness from the Cartesian and radial techniques had close agreement with CCC of 0.89 and 0.94, and mean difference of 0.03 kPa and -0.01 kPa, for scans 1 and 2. Cartesian and radial techniques achieved similar repeatability with within-subject coefficient of variation=1.9% and 3.4%, and ICC=0.93 and 0.92, respectively.ConclusionIn this pilot study, radial free-breathing MR elastography was repeatable and in agreement with Cartesian breath-hold MR elastography in children.

Magnetic resonance elastography (MRE) is an imaging technique that combines low-frequency mechanical vibrations with magnetic resonance imaging to create visual maps and quantify liver parenchyma stiffness. As in recent years, diffuse liver diseases have become highly prevalent worldwide and could lead to a chronic condition with different stages of fibrosis. There is a strong necessity for a non-invasive, highly accurate, and standardised quantitative assessment to evaluate and manage patients with different stages of fibrosis from diagnosis to follow-up, as the actual reference standard for the diagnosis and staging of liver fibrosis is biopsy, an invasive method with possible peri-procedural complications and sampling errors. MRE could quantitatively evaluate liver stiffness, as it is a rapid and repeatable method with high specificity and sensitivity. MRE is based on the propagation of mechanical shear waves through the liver tissue that are directly proportional to the organ's stiffness, expressed in kilopascals (kPa). To obtain a valid assessment of the real hepatic stiffness values, it is mandatory to obtain a high-quality examination. To understand the pearls and pitfalls of MRE, in this review, we describe our experience after one year of performing MRE from indications and patient preparation to acquisition, quality control, and image analysis. [ABSTRACT FROM AUTHOR]

Background: Liver involvement is an important cause of morbidity and mortality in patients with cystic fibrosis (CF). While liver biopsy is the gold standard for demonstrating involvement, its invasiveness prompts a search for noninvasive alternatives. Objective: To evaluate liver involvement in pediatric patients with CF (versus healthy controls) using magnetic resonance (MR) elastography/spectroscopy and to correlate the imaging findings with clinical/laboratory characteristics. Materials and methods: This was a single-center, prospective cross-sectional study conducted between April 2020 and March 2022 in patients with CF versus healthy controls. Patients with CF were divided into two subgroups: those with CF-related liver disease and those without. MR images were acquired on a 1.5-tesla machine. Kilopascal (kPa) values were derived from processing MR elastography images. MR spectroscopy was used to measure liver fat fraction, as an indication of hepatosteatosis. Groups were compared using either the Student's t test or the Mann‒Whitney U test. The chi-square test or Fisher's exact test were used to compare qualitative variables. Results: Fifty-one patients with CF (12 ± 3.3 years, 32 boys) and 24 healthy volunteers (11.1 ± 2.4 years, 15 boys) were included in the study. Median liver stiffness (P=0.003) and fat fraction (P=0.03) were higher in the CF patients than in the controls. Median liver stiffness values were higher in CF patients with CF-related liver disease than in those without CF-related liver disease (P=0.002). Liver stiffness values of CF patients with high alanine aminotransferase (ALT), high gamma-glutamyl transferase, and thrombocytopenia were found to be higher than those without (P=0.004, P<0.001, P<0.001, respectively). Only the high ALT group showed a high fat fraction (P=0.002). Conclusions: Patients with CF had higher liver stiffness than the control group, and patients with CF-related liver disease had higher liver stiffness than both the CF patients without CF-related liver disease and the control group. Patients with CF had a higher fat fraction than the control group. Noninvasive assessment of liver involvement using MR elastography/spectroscopy can support the diagnosis of CF-related liver disease and the follow-up of patients with CF. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Pancreatic ductal adenocarcinoma (PDAC) stromal disposition is thought to influence chemotherapy efficacy and increase tissue stiffness, which could be quantified noninvasively via MR elastography (MRE). Current methods cause position‐based errors in pancreas location over time, hampering accuracy. It would be beneficial to have a single breath‐hold acquisition. Purpose: To develop and test a single breath‐hold three‐dimensional MRE technique utilizing prospective undersampling and a compressed sensing reconstruction (CS‐MRE). Study Type: Prospective. Population: A total of 30 healthy volunteers (HV) (31 ± 9 years; 33% male) and five patients with PDAC (69 ± 5 years; 80% male). Field Strength/Sequence: 3‐T, GRE Ristretto MRE. Assessment: First, optimization of multi breath‐hold MRE was done in 10 HV using four combinations of vibration frequency, number of measured wave‐phase offsets, and TE and looking at MRE quality measures in the pancreas head. Second, viscoelastic parameters delineated in the pancreas head or tumor of CS‐MRE were compared against (I) 2D and (II) 3D four breath‐hold acquisitions in HV (N = 20) and PDAC patients. Intrasession repeatability was assessed for CS‐MRE in a subgroup of healthy volunteers (N = 15). Statistical Tests: Tests include repeated measures analysis of variance (ANOVA), Bland–Altman analysis, and coefficients of variation (CoVs). A P‐value <.05 was considered statistically significant. Results: Optimization of the four breath‐hold acquisitions resulted in 40 Hz vibration frequency, five wave‐phases, and echo time (TE) = 6.9 msec as the preferred method (4BH‐MRE). CS‐MRE quantitative results did not differ from 4BH‐MRE. Shear wave speed (SWS) and phase angle differed significantly between HV and PDAC patients using 4BH‐MRE or CS‐MRE. The limits of agreement for SWS were [−0.09, 0.10] m/second and the within‐subject CoV was 4.8% for CS‐MRE. Data Conclusion: CS‐MRE might allow a single breath‐hold MRE acquisition with comparable SWS and phase angle as 4BH‐MRE, and it may still enable to differentiate between HV and PDAC. Level of Evidence: 2 Technical Efficacy Stage: 2 [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic neuroinflammatory disease that involves both white and gray matter. Although gray matter damage is a major contributor to disability in MS patients, conventional clinical magnetic resonance imaging (MRI) fails to accurately detect gray matter pathology and establish a clear correlation with clinical symptoms. Using magnetic resonance elastography (MRE), we previously reported global brain softening in MS and experimental autoimmune encephalomyelitis (EAE). However, it needs to be established if changes of the spatiotemporal patterns of brain tissue mechanics constitute a marker of neuroinflammation. Here, we use advanced multifrequency MRE with tomoelastography postprocessing to investigate longitudinal and regional inflammation-induced tissue changes in EAE and in a small group of MS patients. Surprisingly, we found reversible softening in synchrony with the EAE disease course predominantly in the cortex of the mouse brain. This cortical softening was associated neither with a shift of tissue water compartments as quantified by T2-mapping and diffusion-weighted MRI, nor with leukocyte infiltration as seen by histopathology. Instead, cortical softening correlated with transient structural remodeling of perineuronal nets (PNNs), which involved abnormal chondroitin sulfate expression and microgliosis. These mechanisms also appear to be critical in humans with MS, where tomoelastography for the first time demonstrated marked cortical softening. Taken together, our study shows that neuroinflammation (i) critically affects the integrity of PNNs in cortical brain tissue, in a reversible process that correlates with disease disability in EAE, (ii) reduces the mechanical integrity of brain tissue rather than leading to water accumulation, and (iii) shows similar spatial patterns in humans and mice. These results raise the prospect of leveraging MRE and quantitative MRI for MS staging and monitoring treatment in affected patients. [ABSTRACT FROM AUTHOR]

Background: The prognosis of metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly associated with liver fibrosis. We aimed to investigate whether liver stiffness measurement (LSM) and changes in LSM (ΔLSM) on magnetic resonance elastography (MRE) can predict clinical events in patients with MASLD. Methods: We included 405 patients with MASLD who underwent at least two MREs. The patients were divided into five groups corresponding to fibrosis stages (0–4) based on initial LSM and classified as progressors (ΔLSM ≥ 19%) or non-progressors (ΔLSM < 19%) based on the difference between the first and last LSM. Results: The mean follow-up period was 72.6 months, and the mean interval between MREs was 23.5 months. There were 52 (12.8%) progressors and 353 (87.2%) non-progressors. The initial LSM was significantly associated with the cumulative probabilities of decompensated cirrhosis, hepatocellular carcinoma (HCC), liver-related events, extrahepatic malignancies, and overall mortality but not with cardiovascular disease. Progressors had significantly higher hazard ratios (HRs) for decompensated cirrhosis, HCC, and liver-related events but not for extrahepatic malignancies, cardiovascular disease, or overall mortality. Among patients without cirrhosis, the HR for developing cirrhosis among progressors was 60.15. Progressors had a significantly higher risk of liver-related events, even in the low initial LSM (fibrosis stage 0–2) subgroups. Conclusions: Both initial LSM and ΔLSM can predict liver-related events in patients with MASLD, even for low initial LSM. This integrated assessment can allow more detailed risk stratification compared with single LSM assessments and identify high-risk patients with MASLD among those previously considered as low risk. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection can lead to hepatic fibrosis. The advent of direct-acting antivirals (DAAs) has substantially improved sustained virological response (SVR) rates. In this context, kidney transplant recipients (KTRs) are of particular interest due to their higher HCV infection rates and uncertain renal excretion and bioavailability of DAAs. We investigated liver stiffness after DAA treatment in 15 HCV-infected KTRs using ultrasound shear wave elastography (SWE) in comparison with magnetic resonance elastography (MRE). KTRs were treated with DAAs (daclatasvir and sofosbuvir) for three months and underwent SWE at baseline, end of therapy (EOT), and 3 (EOT+3) and 12 months (EOT+12) after EOT. Fourteen patients achieved SVR12. Shear wave speed (SWS)—as a surrogate parameter for tissue stiffness—was substantially lower at all three post-therapeutic timepoints compared with baseline (EOT: −0.42 m/s, p < 0.01; CI = −0.75–−0.09, EOT+3: −0.43 m/s, p < 0.01; CI = −0.75–−0.11, and EOT+12: −0.52 m/s, p < 0.001; CI = −0.84–−0.19), suggesting liver regeneration after viral eradication and end of inflammation. Baseline SWS correlated positively with histopathological fibrosis scores (r = 0.48; CI = −0.11–0.85). Longitudinal results correlated moderately with APRI (r = 0.41; CI = 0.12–0.64) but not with FIB-4 scores (r = 0.12; CI = −0.19–0.41). Although higher on average, SWE-derived measurements correlated strongly with MRE (r = 0.64). In conclusion, SWE is suitable for non-invasive therapy monitoring in KTRs with HCV infection. [ABSTRACT FROM AUTHOR]

Conventional magnetic resonance imaging (MRI) can detect tumors consistency, but it can't predict tumor stiffness or adherence of the tumor to nearby structures. Magnetic resonance elastography (MRE) is a known non-invasive MRI based imaging technique used to assess the viscoelasticity of the tissues particularly liver fibrosis. This study discussed the importance of preoperative MRE in skull base tumors and the future implications of this new imaging modality. We did review of the English literature (by searching PubMed) regarding the use of MRE in preoperative assessment of skull base tumours stiffness and adherence to surrounding tissues. Recent research demonstrated that MRE can detect the stiffness and adherence of skull base tumors to surrounding structures by recording the spread of mechanical waves in the different tissues. In addition to non-radiation exposure, this technique is fast and can be incorporated into the conventional (MRI) study. MRE can palpate skull base tumours by imaging, allowing the stiffness of the tumour to be assessed. Preoperative assessment of brain tumours consistency, stiffness, and adherence to surrounding tissues is critical to avoid injury of important nearby structures and better preoperative patient counselling regarding surgical approach (endoscopic or open), operative time, and suspected surgical complications. However, the accuracy of MRE is less in small and highly vascular tumors. Also, MRE can't accurately detect tumour-brain adherence, but the new modality (slip-interface imaging) can. Hence, adding MRE to the conventional MRI study may help in preoperative diagnosis and treatment of skull base tumours. [ABSTRACT FROM AUTHOR]

Patients with metabolic dysfunction-associated steatohepatitis (MASH) and significant fibrosis (fibrosis stage≥2), known as Fibro-MASH, are at increased risk of liver-related outcomes and lower rates of spontaneous disease regression. The aim was to investigate three-dimensional MR elastography (3D-MRE) combining proton-density fat fraction (PDFF) as a means of identifying Fibro-MASH. Forty-eight New Zealand rabbits were fed a high-fat/cholesterol or standard diet to obtain different disease activity and fibrosis stages. Shear stiffness (SS) and Damping Ratio (DR) were derived from 3D-MRE, whereas PDFF was from a volumetric 3D imaging sequence. Steatosis grade, metabolic dysfunction-associated steatotic liver disease activity score (MAS), and fibrosis stage were diagnosed histologically. Serum markers of fibrosis and inflammation were also measured. Correlation and comparison analysis, Receiver operating characteristic curves (ROC), Delong test, logistic regression analysis, and Net reclassification improvement (NRI) were performed. PDFF correlated with steatosis grade (rho = 0.853). SS increased with developed liver fibrosis (rho = 0.837). DR correlated with MAS grade (rho = 0.678). The areas under the ROC (AUROCs) of SS for fibrosis grading were 0.961 and 0.953 for ≥F2, and ≥ F3, respectively. All the biochemical parameters were considered but excluded from the logistic regression analysis to identify Fibro-MASH. FF, SS, and DR were finally included in the further analysis. The three-parameter model combining PDFF, SS, and DR showed significant improvement in NRI over the model combining SS and PDFF (AUROC 0.973 vs. 0.906, P = 0.081; NRI 0.28, P < 0.05). 3D-MRE combining PDFF may characterize the state of fat content, disease activity and fibrosis, thus precisely identify Fibro-MASH. [ABSTRACT FROM AUTHOR]

Background: The aim of this meta-analysis was to assess the performance of magnetic resonance elastography (MRE) in detecting gastroesophageal varices (GEV) in patients with chronic liver disease (CLD). Methods: A literature search in English and Chinese databases such as PubMed, EMBASE, Cochrane Library, Web of Science, and China National Knowledge Infrastructure was conducted. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) of the summary receiver-operating characteristic (SROC) curve with a 95% CI were calculated. A quality analysis of the included study was conducted using the QUADAS-2 tool, and a meta-analysis was performed using Stata16. The clinical practical value of MRE in detecting GEV was evaluated using the Fagan plot. Heterogeneity across studies was explored through meta-regression and subgroup analyses. Results: A total of nine relevant articles that compared liver stiffness (LS) or spleen stiffness (SS) using MRE with esophagogastroduodenoscopy (EGD) to detect the existence of GEV were identified. The pooled summary sensitivity, specificity, PLR, NLR, and DOR of LS or SS for the detection of GEV were 81% (95% CI: 74%, 87%), 72% (95% CI: 62%, 80%), 2.89 (95% CI: 2.12, 3.94), 0.26 (95% CI: 0.19, 0.36), and 10.91 (95% CI: 6.53, 18.24), respectively. The year of publication, study design, and MR equipment are the sources of heterogeneity. There was no significant difference in the publication bias (p > 0.05). Conclusions: Based on these findings, MRE demonstrates good diagnostic accuracy for detecting GEV in patients with CLD. [ABSTRACT FROM AUTHOR]

ObjectivesTo compare the diagnostic accuracy of US shear wave elastography (SWE) and magnetic resonance elastography (MRE) for classifying fibrosis stage in patients with nonalcoholic fatty liver disease (NAFLD).MethodsPatients from a prospective single-center cohort with clinical liver biopsy for known or suspected NAFLD underwent contemporaneous SWE and MRE. AUCs for classifying biopsy-determined liver fibrosis stages ≥ 1, ≥ 2, ≥ 3, and = 4, and their respective performance parameters at cutoffs providing ≥ 90% sensitivity or specificity were compared between SWE and MRE.ResultsIn total, 100 patients (mean age, 51.8 ± 12.9 years; 46% males; mean BMI 31.6 ± 4.7 kg/m2) with fibrosis stage distribution (stage 0/1/2/3/4) of 43, 36, 5, 10, and 6%, respectively, were included. AUCs (and 95% CIs) for SWE and MRE were 0.65 (0.54-0.76) and 0.81 (0.72-0.89), 0.81 (0.71-0.91) and 0.94 (0.89-1.00), 0.85 (0.74-0.96) and 0.95 (0.89-1.00), and 0.91 (0.79-1.00) and 0.92 (0.83-1.00), for detecting fibrosis stage ≥ 1, ≥ 2, ≥ 3, and = 4, respectively. The differences were significant for detecting fibrosis stage ≥ 1 and ≥ 2 (p

Abstract Background Intrahepatic cholangiocarcinoma (iCCA) is an aggressive primary liver cancer with dismal outcome, high Ki-67 expression is associated with active progression and poor prognosis of iCCA, the application of MRE in the prediction of iCCA Ki-67 expression has not yet been investigated until now. We aimed to evaluate the value of magnetic resonance elastography (MRE) in assessing Ki-67 expression for iCCA. Results In the whole cohort, 97 patients (57 high Ki-67 and 40 low Ki-67; 58 males, 39 females; mean age, 58.89 years, ranges 36–70 years) were included. At the multivariate analysis, tumor stiffness (odds ratio (OR) = 1.669 [95% CI: 1.307–2.131], p

Abstract Background Creeping fat is a pathological feature of small bowel Crohn’s disease (CD), with literature suggesting that bowel resection with extended mesenteric resection is related to less postoperative recurrences. Conventional imaging is unable to accurately quantify the disease involvement (i.e., fibrosis) of creeping fat. Quantification of disease involvement could be useful in decision-making for additional extended mesenteric resection. We investigated the feasibility of magnetic resonance elastography (MRE) of the mesentery and if MRE is capable to detect fibrotic disease involvement of mesentery in active CD. Methods Multifrequency MRE yielded spatial stiffness (shear wave speed, SWS, |G*|) and fluidity maps (φ). Viscoelastic properties of seven CD patients’ mesentery were compared to age- and sex-matched healthy volunteers (HV) (Mann–Whitney U-test). Within CD patients, the affected and “presumably” unaffected mesentery were compared (Wilcoxon-signed rank test). Repeatability was tested in 15 HVs (Bland–Altman analysis, coefficient of variation [CoV]). Spearman rank correlations were used to investigate the relation between microscopically scored amount of mesenteric fibrosis and viscoelastic parameters. Results SWS, |G*|, and φ of affected mesentery in CD were higher compared to HV (p = 0.017, p = 0.001, p = 0.017). Strong correlations were found between percentage of area of mesenteric fibrosis and SWS and |G*| (p

Agarose gels are often used as a tissue mimic. The goal of this work was to determine the appropriate agarose concentrations that result in mechanical properties that match three different porcine organs. Strain tests were carried out with an amplitude varying from 0.01% to 10% at a frequency of 1 Hz on a range of agarose concentrations and porcine organs. Frequency sweep tests were performed from 0.1 Hz to a maximum of 9.5 Hz at a shear strain amplitude of 0.1% for agarose and porcine organs. In agarose samples, the effect of pre-compression of the samples up to 10% axial strain was considered during frequency sweep tests. The experimental measurements from agarose samples were fit to a fractional order viscoelastic (springpot) model. The model was then used to predict stress relaxation in response to a step strain of 0.1%. The prediction was compared to experimental relaxation data, and the results agreed within 12%. The agarose concentrations (by mass) that gave the best fit were 0.25% for the liver, 0.3% for the kidney, and 0.4% for the heart. At a frequency of 0.1 Hz and a shear strain of 0.1%, the agarose concentrations that best matched the shear storage modulus of the porcine organs were 0.4% agarose for the heart, 0.3% agarose for the kidney, and 0.25% agarose for the liver.

Introduction: Brain viscoelasticity as assessed by magnetic resonance elastography (MRE) has been discussed as a promising surrogate of microstructural alterations due to neurodegenerative processes. Existing studies indicate that multiple sclerosis (MS) is associated with a global reduction in brain stiffness. However, no study to date systematically investigated the MS-related characteristics of brain viscoelasticity separately in normal-appearing white matter (NAWM), deep gray matter (DGM) and T2-hyperintense white matter (WM) lesions. Methods: 70 MS patients and 42 healthy volunteers underwent whole-cerebral MRE using a stimulated echo sequence (DENSE) with a low-frequency mechanical excitation at 20 Hertz. The magnitude |G∗| (Pa) and phase angle φ (rad) of the complex shear modulus G∗ were reconstructed by multifrequency dual elasto-visco (MDEV) inversion and related to structural imaging and clinical parameters. Results: We observed φ in the thalamus to be higher by 4.3 % in patients relative to healthy controls (1.11 ± 0.07 vs. 1.06 ± 0.07, p