New scores were developed to identify at-risk metabolic dysfunction-associated steatohepatitis (MASH) using multiparametric MRI (mpMRI).

A prospective study was conducted on 176 patients with suspected or diagnosed metabolic dysfunction-associated steatotic liver disease (MASLD) paired with an MR scan, vibration-controlled transient elastography (VCTE), and liver biopsy. Liver stiffness measurement (LSM) using magnetic resonance elastography (MRE), proton density fat fraction (PDFF), and mpMRI-based corrected T1 (cT1) were combined to develop a one-step strategy, named MPcT (MRE + PDFF + cT1, combined score), and a two-step strategy-MRE-based LSM followed by PDFF with cT1 (M-PcT, paired score) for diagnosing at-risk MASH. Each model was categorized using rule-in and rule-out criteria (three categorized analyses). To avoid overfitting, the diagnostic accuracies were evaluated based on 5-fold cross-validation.

PDFF + cT1 (PcT) had the highest diagnostic performance for severe activity (hepatic inflammation plus ballooning grade ≥ 3) and for NAS ≥ 4 (active MASH). Areas under receiver operating characteristic curves (AUROCs) of M-PcT (0.832) for detecting at-risk MASH were significantly higher than those of Fibroscan-AST (FAST) (0.744, p = 0.017), MRI-AST (MAST) (0.710, p = 0.002), and MPcT (0.695, p < 0.001) in three categorized analysis. Following the rule-in criteria, positive predictive values of M-PcT (84.5%) were higher than those of FAST (73.5%), MAST (70.0%), and MPcT (66.7%). Following the rule-out criteria, negative predictive values of M-PcT (88.7%) were higher than those of FAST (84.0%), MAST (73.9%), and MPcT (84.9%).

The two-step strategy, M-PcT (paired score), showed the reliability of rule-in/-out for at-risk MASH, with better predictive performance compared with FAST and MAST (combined score).

This study is registered with ClinicalTrials.gov (number, UMIN000012757).

Question There is no mpMRI-based method for detecting as-risk MASH (NAFLD activity score ≥ 4 with fibrosis stage ≥ 2) like FAST and MAST scores. Findings MRE-based LSMs followed by PDFF with cT1 (M-PcT) were more useful in detecting at-risk MASH than the combined score (FAST and MAST). Clinical relevance By combining MRE and PDFF with cT1, it becomes possible to evaluate the pathology of MASH without the need for a liver biopsy, assisting in prognosis prediction and decision-making for treatment options.

Weight loss (WL) is important for improving steatotic liver. However, there have been no sufficient reports comparing WL with liver fibrosis and steatotic changes using magnetic resonance imaging (MRI).

The study included 111 patients with metabolic dysfunction associated steatotic liver disease who did not take any new drugs during the study period. They were evaluated using MRI and FibroScan®, and then were given a mild low-carbohydrate diet. One year later, they were evaluated again, and changes in alanine transaminase (ALT), MRI proton density fat fraction (MRI-PDFF), and magnetic resonance elastography were examined.

The patients achieved an average WL of 4.2 kg. MRI-PDFF was significantly improved by 0.68-fold for 5%-7% WL, 0.61-fold for 7-10 %WL, and 0.35-fold for 10% or more WL (vs. gain: p < 0.01). In patients with a WL of 5% or more, magnetic resonance elastography was decreased. MRI-PDFF reduction of 30% was observed in 56% of patients with 5%-7% WL, 75 % with 7%-10% WL, and 94% with 10% or more WL (p < 0.01). ALT normalization or 30% reduction was well associated with WL, with 73% for 5%-7% WL, 64% for 7%-10% WL, and 93% for 10% or more WL (p < 0.01). The optimal cutoff for MRI-PDFF improvement and ALT improvement was 5.3% WL in both tests according to receiver operating characteristic analysis (p < 0.01).

Many patients achieved improvement in MRI-PDFF and ALT with WL. WL of 5.3% can improve MRI-PDFF and ALT, contributing to a better prognosis for metabolic dysfunction associated steatotic liver disease patients.

The ductular reaction (DR) is a dynamic adaptive cellular response within the liver, triggered by various hepatic insults and characterized by an expansion of dysmorphic biliary epithelial cells and liver progenitors. This complex response presents a dual role, playing a pivotal function in liver regeneration but, paradoxically, contributing to the progression of liver diseases, depending upon specific contextual factors and signaling pathways involved. This comprehensive review aims to offer a holistic perspective on the DR, focusing into its intricate cellular and molecular mechanisms, highlighting its pathological significance, and exploring its potential therapeutic implications. An up-to-date understanding of the DR in the context of different liver injuries is provided, analyzing its contributions to liver regeneration, inflammation, fibrosis, and ultimately carcinogenesis. Moreover, the review highlights the role of multiple microenvironmental factors, including the influence of extracellular matrix, tissue mechanics and the interplay with the intricate hepatic cell ecosystem in shaping the DR's regulation. Finally, in vitro and in vivo experimental models of the DR will be discussed, providing insights into how researchers can study and manipulate this critical cellular response. By comprehensively addressing the multifaceted nature of the DR, this review contributes to a more profound understanding of its pathophysiological role in liver diseases, thus offering potential therapeutic avenues for hepatic disorders and improving patient outcomes.

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

Magnetic resonance elastography (MRE) can quantify tissue biomechanics noninvasively, including pathological hepatic states like metabolic dysfunction-associated steatohepatitis.

To compare the performance of 2D/3D-MRE using the gravitational (GT) transducer concept with the current commercial acoustic (AC) solution utilizing a 2D-MRE approach. Additionally, quality index markers (QIs) were proposed to identify image pixels with sufficient quality for reliably estimating tissue biomechanics.

Prospective.

One hundred seventy participants with suspected or confirmed liver disease (median age, 57 years [interquartile range (IQR), 46-65]; 66 females), and 11 healthy volunteers (median age, 31 years [IQR, 27-34]; 5 females).

Participants were scanned twice at 1.5 T and 60 Hz vibration frequency: first, using AC-MRE (2D-MRE, spin-echo EPI sequence, 11 seconds breath-hold), and second, using GT-MRE (2D- and 3D-MRE, gradient-echo sequence, 14 seconds breath-hold).

Image analysis was performed by four independent radiologists and one biomedical engineer. Additionally, superimposed analytic plane shear waves of known wavelength and attenuation at fixed shear modulus were used to propose pertinent QIs.

Spearman's correlation coefficient (r) was applied to assess the correlation between modalities. Interreader reproducibility was evaluated using Bland-Altman bias and reproducibility coefficients. P-values <0.05 were considered statistically significant.

Liver stiffness quantified via GT-2D/3D correlated well with AC-2D (r ≥ 0.89 [95% CI: 0.85-0.92]) and histopathological grading (r ≥ 0.84 [95% CI: 0.72-0.91]), demonstrating excellent agreement in Bland-Altman plots and between readers (κ ≥ 0.86 [95% CI: 0.81-0.91]). However, GT-2D showed a bias in overestimating stiffness compared to GT-3D. Proposed QIs enabled the identification of pixels deviating beyond 10% from true stiffness based on a combination of total wave amplitude, temporal sinusoidal nonlinearity, and wave signal-to-noise ratio for GT-3D.

GT-MRE represents an alternative to AC-MRE for noninvasive liver tissue characterization. Both GT-2D and 3D approaches correlated strongly with the established commercial approach, offering advanced capabilities in abdominal imaging compared to AC-MRE.

1 TECHNICAL EFFICACY: Stage 2.

The need for early non-invasive diagnostic tools for chronic liver fibrosis is growing, particularly in individuals with obesity, non-alcoholic fatty liver disease (NAFLD), and the metabolic syndrome (MetS) since prevalence of these conditions is increasing. This case-control study compared non-invasive liver fibrosis markers in obesity with NAFLD and MetS (NAFLD-MetS, n = 33), in obese (n = 28) and lean (n = 27) control groups. We used MRI (T1 relaxation times (T1) and liver stiffness), circulating biomarkers (CK18, PIIINP, and TIMP1), and algorithms (FIB-4 index, Forns score, FNI, and MACK3 score) to assess their potential in predicting liver fibrosis risk. We found that T1 (892 ± 81 ms vs. 818 ± 64 ms, p < 0.001), FNI (15 ± 12% vs. 9 ± 7%, p = 0.018), CK18 (166 ± 110 U/L vs. 113 ± 41 U/L, p = 0.019), and MACK3 (0.18 ± 0.15 vs. 0.05 ± 0.04, p < 0.001) were higher in the NAFLD-MetS group compared with the obese control group. Moreover, correlations were found between CK18 and FNI (r = 0.69, p < 0.001), CK18 and T1 (r = 0.41, p < 0.001), FNI and T1 (r = 0.33, p = 0.006), MACK3 and FNI (r = 0.79, p < 0.001), and MACK3 and T1 (r = 0.50, p < 0.001). We show that liver fibrosis markers are increased in obese individuals with NAFLD and MetS without clinical signs of liver fibrosis. More studies are needed to validate the use of these non-invasive biomarkers for early identification of liver fibrosis risk.

Prior work has shown that MRI-derived proton density fat fraction (PDFF) can diagnose metabolic dysfunction-associated steatotic liver disease (MASLD) noninvasively, but there is a paucity of data on the performance of PDFF to classify more advanced forms of the MASLD spectrum. The purpose of this study was to assess the diagnostic performance of PDFF for the diagnoses of MASLD, metabolic dysfunction-associated steatohepatitis (MASH), and fibrotic MASH in adults with obesity undergoing bariatric surgery, using contemporaneous intraoperative liver biopsy as a reference.

PDFF was evaluated alone and with other potential classifiers (imaging, serum and anthropometric), using Bayesian Information Criterion-based stepwise logistic regression models. Areas under the receiver operating characteristic (ROC) curves (AUC) were computed for all models and single classifiers. Cross-validated sensitivity and specificity were calculated at Youden-based PDFF classification thresholds. Data analysis from 140 patients demonstrated that PDFF was the most accurate single classifier, with high AUC for MASLD (0.95), MASH (0.85), and fibrotic MASH (0.82) (all p <0.001). Multivariable models, including PDFF, outperformed those without PDFF. The Youden-based threshold for PDFF was 4.4% for MASLD (sensitivity: 87%, specificity: 86%), 6.9% for MASH (sensitivity: 77%, specificity: 66%), and 13.5% for fibrotic MASH (sensitivity: 67%, specificity: 85%).

PDFF was the most accurate single classifier for diagnosing MASLD, MASH, and fibrotic MASH. The most accurate multivariable classification models for MASLD, MASH, and fibrotic MASH included PDFF, demonstrating the central importance of PDFF for noninvasive assessment of the MASLD spectrum.

In a rapidly changing technology landscape, "Clinical Decision Support" (CDS) has become an important tool to improve patient management. CDS systems offer medical professionals new insights to improve diagnostic accuracy, therapy planning, and personalized treatment. In addition, CDS systems provide cost-effective options to augment conventional screening for secondary prevention. This review aims to (i) describe the purpose and mechanisms of CDS systems, (ii) discuss different entities of algorithms, (iii) highlight quality features, and (iv) discuss challenges and limitations of CDS in clinical practice. Furthermore, we (v) describe contemporary algorithms in oncology, acute care, cardiology, and nephrology. In particular, we consolidate research on algorithms across diseases that imply a significant disease and economic burden, such as lung cancer, colorectal cancer, hepatocellular cancer, coronary artery disease, traumatic brain injury, sepsis, and chronic kidney disease.

Conventional liver magnetic resonance elastography (MRE) requires breath-holding (BH) to avoid motion artifacts, which is challenging for children. While radial free-breathing (FB)-MRE is an alternative for quantifying liver stiffness (LS), previous methods had limitations of long scan times, acquiring two slices in 5 minutes, and not resolving motion during reconstruction.

To reduce FB-MRE scan time to 4 minutes for four slices and to investigate the impact of self-gated (SG) motion compensation on FB-MRE LS quantification in terms of agreement, intrasession repeatability, and technical quality compared to conventional BH-MRE.

Prospective.

Twenty-six children without fibrosis (median age: 12.9 years, 15 females).

3 T; Cartesian gradient-echo (GRE) BH-MRE, research application radial GRE FB-MRE.

Participants were scanned twice to measure repeatability, without moving the table or changing the participants' position. LS was measured in areas of the liver with numerical confidence ≥90%. Technical quality was examined using measurable liver area (%).

Agreement of LS between BH-MRE and FB-MRE was evaluated using Bland-Altman analysis for SG acceptance rates of 40%, 60%, 80%, and 100%. LS repeatability was assessed using within-subject coefficient of variation (wCV). The differences in LS and measurable liver area were examined using Kruskal-Wallis and Wilcoxon signed-rank tests. P < 0.05 was considered significant.

FB-MRE with 60% SG achieved the closest agreement with BH-MRE (mean difference 0.00 kPa). The LS ranged from 1.70 to 1.83 kPa with no significant differences between BH-MRE and FB-MRE with varying SG rates (P = 0.52). All tested methods produced repeatable LS with wCV from 4.4% to 6.5%. The median measurable liver area was smaller for FB-MRE (32%-45%) than that for BH-MRE (91%-93%) (P < 0.05).

FB-MRE with 60% SG can quantify LS with close agreement and comparable repeatability with respect to BH-MRE in children.

2 TECHNICAL EFFICACY: Stage 1.

Transient elastography (TE), shear wave elastography, and/or magnetic resonance elastography (MRE), each providing liver stiffness measurement (LSM), are the most studied imaging-based noninvasive liver disease assessment (NILDA) techniques. To support the American Association for the Study of Liver Diseases guidelines on NILDA, we summarized the evidence on the accuracy of these LSM methods to stage liver fibrosis (F).

A comprehensive search for studies assessing LSM by TE, shear wave elastography, or MRE for the identification of significant fibrosis (F2-4), advanced fibrosis (F3-4), or cirrhosis (F4), using histopathology as the standard of reference by liver disease etiology in adults or children from inception to April 2022 was performed. We excluded studies with <50 patients with a single disease entity and mixed liver disease etiologies (with the exception of HCV/HIV coinfection). Out of 9447 studies, 240 with 61,193 patients were included in this systematic review. In adults, sensitivities for the identification of F2-4 ranged from 51% to 95%, for F3-4 from 70% to 100%, and for F4 from 60% to 100% across all techniques/diseases, whereas specificities ranged from 36% to 100%, 74% to 100%, and 67% to 99%, respectively. The largest body of evidence available was for TE; MRE appeared to be the most accurate method. Imaging-based NILDA outperformed blood-based NILDA in most comparisons, particularly for the identification of F3-4/F4. In the pediatric population, imaging-based NILDA is likely as accurate as in adults.

LSM from TE, shear wave elastography, and MRE shows acceptable to outstanding accuracy for the detection of liver fibrosis across various liver disease etiologies. Accuracy increased from F2-4 to F3-4 and was the highest for F4. Further research is needed to better standardize the use of imaging-based NILDA, particularly in pediatric liver diseases.

Three-dimensional shear wave absolute vibro-elastography (S-WAVE) is a steady-state, volumetric elastography imaging technique similar to magnetic resonance elastography (MRE), with the additional advantage of multifrequency imaging and a significantly shorter examination time. We present a novel ultrasound matrix array implementation of S-WAVE for high-volume refresh rate acquisition. This new imaging setup is equipped with real-time shear wave monitoring for an improved data collection workflow and image quality. The image processing and elasticity reconstruction pipeline is tailored for high body mass index (BMI) subjects. We characterized this system with tissue phantoms and a human study cohort composed of 7 healthy volunteers and 25 patients with nonalcoholic fatty liver disease. The validation results show that S-WAVE can maintain a high agreement with the liver tissue stiffness measurements obtained with both the 2-D and 3-D MRE techniques, with an average cross correlation >93% and an average , which outperforms the conventional transient elasticity technique. Our findings show that the matrix array-based 3-D S-WAVE is a suitable volumetric elastography imaging solution for delivering a similar assessment of liver fibrosis as MRE in a more accessible, flexible, and cost-effective way.

Chronic liver disease (CLD) is a substantial cause of morbidity and mortality worldwide. Liver stiffness, as measured by MR elastography (MRE), is well-accepted as a surrogate marker of liver fibrosis.

To develop and validate deep learning (DL) models for predicting MRE-derived liver stiffness using routine clinical non-contrast abdominal T1-weighted (T1w) and T2-weighted (T2w) data from multiple institutions/system manufacturers in pediatric and adult patients.

We identified pediatric and adult patients with known or suspected CLD from four institutions, who underwent clinical MRI with MRE from 2011 to 2022. We used T1w and T2w data to train DL models for liver stiffness classification. Patients were categorized into two groups for binary classification using liver stiffness thresholds (≥ 2.5 kPa, ≥ 3.0 kPa, ≥ 3.5 kPa, ≥ 4 kPa, or ≥ 5 kPa), reflecting various degrees of liver stiffening.

We identified 4695 MRI examinations from 4295 patients (mean ± SD age, 47.6 ± 18.7 years; 428 (10.0%) pediatric; 2159 males [50.2%]). With a primary liver stiffness threshold of 3.0 kPa, our model correctly classified patients into no/minimal (< 3.0 kPa) vs moderate/severe (≥ 3.0 kPa) liver stiffness with AUROCs of 0.83 (95% CI: 0.82, 0.84) in our internal multi-site cross-validation (CV) experiment, 0.82 (95% CI: 0.80, 0.84) in our temporal hold-out validation experiment, and 0.79 (95% CI: 0.75, 0.81) in our external leave-one-site-out CV experiment. The developed model is publicly available ( https://github.com/almahdir1/Multi-channel-DeepLiverNet2.0.git ).

Our DL models exhibited reasonable diagnostic performance for categorical classification of liver stiffness on a large diverse dataset using T1w and T2w MRI data.

Question Can DL models accurately predict liver stiffness using routine clinical biparametric MRI in pediatric and adult patients with CLD? Findings DeepLiverNet2.0 used biparametric MRI data to classify liver stiffness, achieving AUROCs of 0.83, 0.82, and 0.79 for multi-site CV, hold-out validation, and external CV. Clinical relevance Our DeepLiverNet2.0 AI model can categorically classify the severity of liver stiffening using anatomic biparametric MR images in children and young adults. Model refinements and incorporation of clinical features may decrease the need for MRE.

Background: The accurate staging of liver fibrosis is crucial for managing chronic liver disease (CLD). Although magnetic resonance elastography (MRE) is the reference standard for noninvasive fibrosis assessment, its cost, specialized hardware, and operational demands restrict accessibility. In contrast, two-dimensional shear-wave elastography (2D-SWE) is more affordable, accessible, and widely integrated into routine ultrasound systems. Objective: Our aim was to determine the optimal 2D-SWE cut-offs for detecting significant fibrosis (≥F2) and evaluate its diagnostic performance across fibrosis stages. Methods: In this prospective study, 71 patients with suspected CLD underwent same-day MRE and 2D-SWE. MRE-defined cut-offs categorized fibrosis stages (≥3.5 kPa for significant fibrosis). Sensitivity, specificity, area under the receiver operating characteristic curve (AUROC), and likelihood ratios were calculated for various 2D-SWE thresholds. Results: At a 2D-SWE cut-off of 7.0 kPa, sensitivity for detecting ≥F2 fibrosis was 100% with a specificity of 85.7% and a positive likelihood ratio (LR+) of 7.0. Increasing the threshold to 8.0 kPa improved specificity to 91.8% while maintaining a sensitivity of 86.4% and achieving an AUROC of 0.89. For cirrhosis, a cut-off of 11.0 kPa achieved 100% sensitivity and 96.9% specificity. A 5.0 kPa cut-off reliably excluded abnormal stiffness with 89.1% sensitivity. Conclusions: Two-dimensional SWE is a reliable method for staging liver fibrosis. Thresholds of 7.0 kPa for screening significant fibrosis, 8.0 kPa for confirmation, and 11.0 kPa for diagnosing cirrhosis demonstrate high diagnostic accuracy. A 5.0 kPa cut-off effectively excludes abnormal liver stiffness.

MR elastography is a non-invasive imaging technique that provides quantitative maps of tissue biomechanical properties, i.e., elasticity and viscosity. Currently, hepatic MR elastography is deployed in the clinic to assess liver fibrosis in MAFLD patients. In addition, research has demonstrated MR elastography's ability to non-invasively assess chronic liver disease and to characterize breast cancer lesions and brain tumors. MR elastography requires efficient mechanical wave generation and penetration, motion-sensitized MRI sequences, and MR elastography inversion algorithms to retrieve the biomechanical properties of the tissue. MR elastography promises to enable non-invasive and versatile assessment of tissue, leading to better diagnosis and staging of several clinical conditions.

To analyze the role of qualitative and quantitative 3 T MR imaging assessment as a non-invasive method for the evaluation of disease severity in patients with primary sclerosing cholangitis (PSC).

A series of 26 patients, with histological diagnosis of PSC undergoing 3 T MRI and hepatological evaluation, was retrospectively enrolled. All MR examinations included diffusion-weighted imaging (DWI), T2-weighted (T2w) and T1-weighted (T1w) sequences, before and after administration of Gd-EOB-DTPA with the acquisition of both dynamic and hepato-biliary phase (HBP). Qualitative analysis was performed by assessment of liver parenchyma and biliary tract changes, also including biliary excretion of gadoxetic acid on HBP. Quantitative evaluation was conducted on liver parenchyma by measurement of apparent diffusion coefficient (ADC) and relative enhancement (RE) on 3-minute delayed phase and on HBP. Results of blood tests (ALT, ALP, GGT, total and direct bilirubin, albumin, and platelets) and transient elastography-derived liver stiffness measurements (TE-LSM) were collected and correlated with qualitative and quantitative MRI findings.

Among qualitative and quantitative findings, fibrosis visual assessment and RE had the best performance in estimating disease severity, showing a statistically significant correlation with both biomarkers of cholestasis and TE-LSM. Statistical analysis also revealed a significant correlation of gadoxetic acid biliary excretion with ALT and direct bilirubin, as well as of ADC with total bilirubin.

Qualitative and quantitative 3 T MR evaluation is a promising non-invasive method for the assessment of disease severity in patients with PSC.

Autoimmune hepatitis is a rare chronic liver disease, associated with a high level of morbidity and high mortality; approximately 40% of patients with severe untreated disease die within 6 months of diagnosis. It should be treated to achieve complete biochemical and histologic resolution of the disease using corticosteroids and immunosuppression to prevent further progression to cirrhosis. The use of invasive liver biopsy is recommended for the staging and assessment of inflammation and fibrosis for treatment decision-making in the face of an unsatisfactory response or clinical remission, including being a determinant for withdrawal of immunosuppression. On the other hand, liver biopsy is invasive, costly, and not free of complications. It also has potential sampling error and poor interobserver agreement. The limitations of liver biopsy highlight the importance of developing new imaging biomarkers that allow accurate and non-invasive assessment of autoimmune hepatitis in terms of liver inflammation and fibrosis, developing the virtual biopsy concept. Therefore, we review the state-of-the-art of Magnetic Resonance Imaging sequences for the noninvasive evaluation of autoimmune hepatitis, including historical advances and future directions.

Different MR elastography (MRE) systems may produce different stiffness measurements, making direct comparison difficult in multi-center investigations.

To assess the repeatability and reproducibility of liver stiffness measured by three typical MRE systems.

Prospective.

Thirty volunteers without liver disease history (20 males, aged 21-28)/5 gel phantoms.

3.0 T United Imaging Healthcare (UIH), 1.5 T Siemens Healthcare, 3.0 T General Electric Healthcare (GE)/Echo planar imaging-based MRE sequence.

Wave images of volunteers and phantoms were acquired by three MRE systems. Tissue stiffness was evaluated by two observers, while phantom stiffness was assessed automatically by code. The reproducibility across three MRE systems was quantified based on the mean stiffness of each volunteer and phantom.

Intraclass correlation coefficients (ICC), coefficients of variation (CV), and Bland-Altman analyses were used to assess the interobserver reproducibility, the interscan repeatability, and the intersystem reproducibility. Paired t-tests were performed to assess the interobserver and interscan variation. Friedman tests with Dunn's multiple comparison correction were performed to assess the intersystem variation. P values less than 0.05 indicated significant difference.

The reproducibility of stiffness measured by the two observers demonstrated consistency with ICC > 0.92, CV < 4.32%, Mean bias < 2.23%, and P > 0.06. The repeatability of measurements obtained using the electromagnetic system for the liver revealed ICC > 0.96, CV < 3.86%, Mean bias < 0.19%, P > 0.90. When considering the range of reproducibility across the three systems for liver evaluations, results ranged with ICCs from 0.70 to 0.87, CVs from 6.46% to 10.99%, and Mean biases between 1.89% and 6.30%. Phantom studies showed similar results. The values of measured stiffness differed across all three systems significantly.

Liver stiffness values measured from different MRE systems can be different, but the measurements across the three MRE systems produced consistent results with excellent reproducibility.

1 TECHNICAL EFFICACY: Stage 2.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is now the most prevalent chronic liver disease in children in industrialized countries mainly due to the rise in obesity and overweight. Besides risk of progressive liver damage, MASLD also carries an increased risk of extra-hepatic morbidity, most importantly type 2 diabetes mellitus and cardiovascular disease. Important challenges remain in the prevention, detection, and treatment of this prevalent disorder. This review outlines the epidemiology and risk factors of MASLD and provides an approach to screening, diagnosis, and treatment based on current best available evidence and expert opinion. What is known: • NAFLD/MASLD is a common disorder in children strongly related to obesity/overweight and insulin resistance. • This silent disorder is underdiagnosed due to lack of awareness and lack of simple diagnostic criteria. What is new: • New diagnostic criteria have transformed NAFLD/MASLD from a diagnosis of exclusion to a positive diagnosis with simple criteria. • Effective treatments are emerging for adults and will likely become available for children. • Identifying children with NAFLD/MASLD has become even more important due to this new treatment perspective.

Magnetic resonance elastography (MRE) is an emerging clinical imaging modality for characterizing the viscoelastic properties of soft biological tissues. MRE shows great promise in the noninvasive diagnosis of various diseases, especially those associated with soft tissue changes involving the extracellular matrix, cell density, or fluid turnover including altered blood perfusion - all hallmarks of inflammation from early events to cancer development. This review covers the fundamental principles of measuring tissue viscoelasticity by MRE, which are based on the stimulation and encoding of shear waves and their conversion into parameter maps of mechanical properties by inverse problem solutions of the wave equation. Technical challenges posed by real-world biological tissue properties such as viscosity, heterogeneity, anisotropy, and nonlinear elastic behavior of tissues are discussed. Applications of MRE measurement in both humans and animal models are presented, with emphasis on the detection, characterization, and staging of diseases related to the cascade of biomechanical property changes from early to chronic inflammation in the liver and brain. Overall, MRE provides valuable insights into the biophysics of soft tissues for imaging-based detection and staging of inflammation-associated tissue changes.

We aimed to explore the extent to which individuals previously diagnosed with nonalcoholic fatty liver disease (NAFLD) meet the criteria fulfilled with the new nomenclature, metabolic dysfunction-associated steatotic liver disease (MASLD), within an Asian primary clinic cohort. Additionally, we assessed the reliability of the diagnostic performance of FIB-4 and NAFLD fibrosis score (NFS) for MASLD within the primary clinic cohort.

This retrospective cross-sectional study included participants who underwent magnetic resonance elastography and abdominal ultrasonography during their health checkups at nationwide health promotion centers (n = 6740).

The prevalence rates of NAFLD and MASLD diagnosed based on ultrasonography results were 36.7% and 38.0%, respectively. Notably, 96.8% of patients in the NAFLD cohort fulfilled the new criteria for MASLD. A small proportion of patients with NAFLD (n = 80, 3.2%) did not meet the MASLD criteria. Additionally, 168 patients (6.6%) were newly added to the MASLD group. The areas under the receiver operating characteristic curves for diagnosing advanced hepatic fibrosis for FIB-4 (0.824 in NAFLD vs. 0.818 in MASLD, p = 0.891) and NFS (0.803 in NAFLD vs. 0.781 in MASLD, p = 0.618) were comparable between the MASLD and NAFLD groups. Furthermore, the sensitivity, specificity, positive predictive value, and negative predictive value of FIB-4 and NFS for advanced fibrosis in MASLD were also comparable to those in NAFLD.

Most patients (96.8%) previously diagnosed with NAFLD fulfilled the new criteria for MASLD in an Asian primary clinic cohort. Diagnostic performance of FIB-4 in the MASLD cohort demonstrated satisfactory results.

The aim of the current study is to demonstrate the feasibility of radiofrequency (RF) pulses generated via an optimal control (OC) algorithm to perform magnetic resonance elastography (MRE) and quantify the mechanical properties of materials with very short transverse relaxation times (T2 < 5 ms) for the first time. OC theory applied to MRE provides RF pulses that bring isochromats from the equilibrium state to a fixed target state, which corresponds to the phase pattern of a conventional MRE acquisition. Such RF pulses applied with a constant gradient allow to simultaneously perform slice selection and motion encoding in the slice direction. Unlike conventional MRE, no additional motion-encoding gradients (MEGs) are needed, enabling shorter echo times. OC pulses were implemented both in turbo spin echo (OC rapid acquisition with refocused echoes [RARE]) and ultrashort echo time (OC UTE) sequences to compare their motion-encoding efficiency with the conventional MEG encoding (classical MEG MRE). MRE experiments were carried out on agar phantoms with very short T2 values and on an ex vivo bovine tendon. Magnitude images, wave field images, phase-to-noise ratio (PNR), and shear storage modulus maps were compared between OC RARE, OC UTE, and classical MEG MRE in samples with different T2 values. Shear storage modulus values of the agar phantoms were in agreement with values found in the literature, and that of the bovine tendon was corroborated with rheometry measurements. Only the OC sequences could encode motion in very short T2 samples, and only OC UTE sequences yielded magnitude images enabling proper visualization of short T2 samples and tissues. The OC UTE sequence produced the best PNRs, demonstrating its ability to perform anatomical and mechanical characterization. Its success warrants in vivo confirmation in further studies.

Since 1980, the cumulative effort of scientists and health-care stakeholders has advanced the prerequisites to address metabolic dysfunction-associated steatotic liver disease (MASLD), a prevalent chronic non-communicable liver disease. This effort has led to, among others, the approval of the first drug specific for metabolic dysfunction-associated steatohepatitis (MASH; formerly known as nonalcoholic steatohepatitis). Despite substantial progress, MASLD is still a leading cause of advanced chronic liver disease, including primary liver cancer. This Perspective contextualizes the nomenclature change from nonalcoholic fatty liver disease to MASLD and proposes important considerations to accelerate further progress in the field, optimize patient-centric multidisciplinary care pathways, advance pharmacological, behavioural and diagnostic research, and address health disparities. Key regulatory and other steps necessary to optimize the approval and access to upcoming additional pharmacological therapeutic agents for MASH are also outlined. We conclude by calling for increased education and awareness, enhanced health system preparedness, and concerted action by policy-makers to further the public health and policy agenda to achieve at least parity with other non-communicable diseases and to aid in growing the community of practice to reduce the human and economic burden and end the public health threat of MASLD and MASH by 2030.

This study aimed to facilitate research progress in MR elastography (MRE) by providing a versatile and convenient application for MRE reconstruction, namely the MRE research tool (MRE-rTool). It can be used for a series of MRE image analyses, including phase unwrapping, arbitrary bandpass and directional filtering, noise assessment of the wave propagation image (motion SNR), and reconstruction of the elastogram in both 2D and 3D MRE acquisitions. To reinforce the versatility of MRE-rTool, the conventional method of motion SNR was modified into a new method that reflects the effects of image filtering.

MRE tests of the phantom and liver were performed using different estimation algorithms for stiffness value (algebraic inversion of the differential equation [AIDE], local frequency estimation [LFE] in MRE-rTool, and multimodel direct inversion [MMDI] in clinical reconstruction) and acquiring dimensions (2D and 3D acquisitions). This study also tested the accuracy of masking low SNR regions using modified and conventional motion SNR under various mechanical vibration powers.

The stiffness values estimated using AIDE/LFE in MRE-rTool were comparable to that of MMDI (phantom, 3.71 ± 0.74, 3.60 ± 0.32, and 3.60 ± 0.54 kPa in AIDE, LFE, and MMDI; liver, 2.26 ± 0.31, 2.74 ± 0.16, and 2.21 ± 0.26 kPa in AIDE, LFE, and MMDI). The stiffness value in 3D acquisition was independent of the direction of the motion-encoding gradient and was more accurate than that of 2D acquisition. The masking of low SNR regions using the modified motion SNR worked better than that in the conventional motion SNR for each vibration power, especially when using a directional filter.

The performance of MRE-rTool on test data reached the level required in clinical MRE studies. MRE-rTool has the potential to facilitate MRE research, contribute to the future development of MRE, and has been freely released online.

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.

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.

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).

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.

Studies of cell and tissue mechanics have shown that significant changes in cell and tissue mechanics during lesions and cancers are observed, which provides new mechanical markers for disease diagnosis based on machine learning. However, due to the lack of effective mechanic markers, only elastic modulus and iconographic features are currently used as markers, which greatly limits the application of cell and tissue mechanics in disease diagnosis. Here, we develop a liver pathological state classifier through a support vector machine method, based on high dimensional viscoelastic mechanical data. Accurate diagnosis and grading of hepatic fibrosis facilitates early detection and treatment and may provide an assessment tool for drug development. To this end, we used the viscoelastic parameters obtained from the analysis of creep responses of liver tissues by a self-similar hierarchical model and built a liver state classifier based on machine learning. Using this classifier, we implemented a fast classification of healthy, diseased, and mesenchymal stem cells (MSCs)-treated fibrotic live tissues, and our results showed that the classification accuracy of healthy and diseased livers can reach 0.99, and the classification accuracy of the three liver tissues mixed also reached 0.82. Finally, we provide screening methods for markers in the context of massive data as well as high-dimensional viscoelastic variables based on feature ablation for drug development and accurate grading of liver fibrosis. We propose a novel classifier that uses the dynamical mechanical variables as input markers, which can identify healthy, diseased, and post-treatment liver tissues.

The mechanisms of hepatic fat loss in late-stage metabolic dysfunction-associated fatty liver disease (MASLD) are enigmatic and the prognostic significance of low hepatic fat content (LHF) in chronic liver disease (CLD) is unknown. Proton density fat fraction (PDFF), measured by magnetic resonance imaging (MRI), is considered the most accurate noninvasive method for quantifying hepatic fat content. This study aimed to address these issues by evaluating PDFF.

This is a single-center, retrospective study involving 762 patients with CLD, measuring liver stiffness (LS) using MR elastography and PDFF using MRI. LHF was defined as a PDFF ≤ 2.7 % and hepatic reserve function was assessed using the albumin-bilirubin (ALBI) score. Multivariate analysis explored associations between variables.

LHF was 27 % in the entire cohort, and PDFF was significantly decreased with LS ≥ 5.5 kPa (p < 0.05). On the multivariate analysis, low body mass index and ALBI score were independently associated with LHF (p < 0.05). In advanced CLD (n = 288), ALBI score and PDFF showed a significant negative correlation regardless of etiology (MASLD/non-MASLD: r= -0.613/-0.233), and the prevalence of LHF increased with progression of ALBI grade (p < 0.01 each). In addition, lower PDFF was associated with increased liver-related and all-cause mortality (p < 0.01), and Cox proportional hazards models extracted LHF as an independent prognostic factor, along with ALBI score and hepatocellular carcinoma (p < 0.05 each).

In ACLD, hepatic reserve dysfunction contributed to hepatic fat loss independent of nutritional status, suggesting that LHF may be a poor prognostic factor in all etiologies.

Despite the vital importance of monitoring the progression of nonalcoholic fatty liver disease (NAFLD) and its progressive form, nonalcoholic steatohepatitis (NASH), an efficient imaging modality that is readily available at hospitals is currently lacking. Here, a new magnetic-resonance-imaging (MRI)-based imaging modality is presented that allows for efficient and longitudinal monitoring of NAFLD and NASH progression. The imaging modality uses manganese-ion (Mn2+)-chelated bilirubin nanoparticles (Mn@BRNPs) as a reactive-oxygen-species (ROS)-responsive MRI imaging probe. Longitudinal T1-weighted MR imaging of NASH model mice is performed after injecting Mn@BRNPs intravenously. The MR signal enhancement in the liver relative to muscle gradually increases up to 8 weeks of NASH progression, but decreases significantly as NASH progresses to the cirrhosis-like stage at weeks 10 and 12. A new dual input pseudo-three-compartment model is developed to provide information on NASH stage with a single MRI scan. It is also demonstrated that the ROS-responsive Mn@BRNPs can be used to monitor the efficacy of potential anti-NASH drugs with conventional MRI. The findings suggest that the ROS-responsive Mn@BRNPs have the potential to serve as an efficient MRI contrast for monitoring NASH progression and its transition to the cirrhosis-like stage.

The aim of this study was to develop a vibration pad suitable for renal MR elastography (MRE). Chronic kidney disease (CKD) is a progressive condition affecting >800 million people worldwide. Renal fibrosis is a common pathological feature of CKD that causes fibrotic regions to be much stiffer than those in normal renal tissues. Therefore, MRE can be used to diagnose CKD because it can image organ stiffness. In MRE, the shear modulus is obtained from the wavelength of the shear waves. Therefore, it is highly important to propagate shear waves with sufficient vibration strength in the tissue. By using a three-dimensional (3D) printer, we created a "Flexible Pad" suitable for renal MRE. The Flexible Pad was placed under the back of the participant in the supine position and deformed in response to the participant's weight, adhering closely to the body surface. Six healthy volunteers participated in this study. Our Flexible Pad allowed for coherent shear waves (clear waves with little scattering and interference) to be efficiently transmitted to the kidney deep-lying tissues in the abdomen. The shear moduli of the kidney (n = 6) were 8.95 ± 0.84 kPa in the right kidney and 9.70 ± 0.99 kPa in the left kidney. Our results indicate that using our Flexible Pad for renal MRE can provide a more reliable measurement of renal shear modulus.

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.

Chronic liver disease is highly prevalent and often leads to fibrosis or cirrhosis and complications such as liver failure and hepatocellular carcinoma. The diagnosis and staging of liver fibrosis is crucial to determine management and mitigate complications. Liver biopsy for histologic assessment has limitations such as sampling bias and high interreader variability that reduce precision, which is particularly challenging in longitudinal monitoring. MR elastography (MRE) is considered the most accurate noninvasive technique for diagnosing and staging liver fibrosis. In MRE, low-frequency vibrations are applied to the abdomen, and the propagation of shear waves through the liver is analyzed to measure liver stiffness, a biomarker for the detection and staging of liver fibrosis. As MRE has become more widely used in clinical care and research, different contexts of use have emerged. This review focuses on the latest developments in the use of MRE for the assessment of liver fibrosis; provides guidance for image acquisition and interpretation; summarizes diagnostic performance, along with thresholds for diagnosis and staging of liver fibrosis; discusses current and emerging clinical applications; and describes the latest technical developments.

Magnetic resonance elastography (MRE) is used to measure liver stiffness with gradient-recalled echo (GRE)-based and spin-echo echo planar imaging (SE-EPI)-based sequences. We compared the liver stiffness (LS) values of the two sequences on a 1.5-T MR imaging scanner.

This is a retrospective study. An MRE imaging section was obtained from a horizontal section of the liver. Region of interest was drawn on the elastogram, and the mean LS and pixel values were measured and compared. The correlations between proton density fat fraction, R2* values, and biochemical data from electronic medical records were confirmed, and multivariate analysis was performed.

The mean LS values were 3.01 ± 1.78 kPa for GRE and 3.13 ± 1.57 kPa for SE-EPI, showing excellent agreement and a strong correlation between the two sequences (correlation coefficient r = 0.96). The mean pixel values were 369.5 ± 142.7 pixels for GRE and 490.1 ± 197.9 pixels for SE-EPI, showing a significant difference by the Wilcoxon rank sum test (p < 0.01). There were no LS unmeasurable cases in SE-EPI, but seven (2.5%) were unmeasurable in GRE, and multivariate analysis showed a significant difference with p < 0.001 in R2* values (mean, 92.7 Hz) for the GRE method.

The GRE and SE-EPI methods were comparable for LS measurements in 1.5-T liver MRE, indicating that SE-EPI MRE is more useful because GRE MRE may not measure cases with high R2* values and the region of interest tends to be smaller.

We aimed to evaluate the feasibility of MR elastography (MRE) using a transpelvic approach. Thirty-one patients who underwent prostate MRE and had a pathological diagnosis were included in this study. MRE was obtained using a passive driver placed at the umbilicus and iliac crests. The shear stiffness, clinical data, and conventional imaging findings of prostate cancer and benign prostatic hyperplasia (BPH) were compared. Inter-reader agreements were evaluated using the intraclass coefficient class (ICC). Prostate MRE was successfully performed for all patients (100% technical success rate). Nineteen cancer and 10 BPH lesions were visualized on MRE. The mean shear stiffness of cancer was significantly higher than that of BPH (5.99 ± 1.46 kPa vs. 4.67 ± 1.54 kPa, p = 0.045). One cancer was detected on MRE but not on conventional sequences. Six tiny cancer lesions were not visualized on MRE. The mean size of cancers that were not detected on MRE was smaller than that of cancers that were visible on MRE (0.8 ± 0.3 cm vs. 2.3 ± 1.8 cm, p = 0.001). The inter-reader agreement for interpreting MRE was excellent (ICC = 0.95). Prostate MRE with transpelvic vibration is feasible without intracavitary actuators. Transpelvic prostate MRE is reliable for detecting focal lesions, including clinically significant prostate cancer and BPH.