Liver MR Elastography Research Articles

Self-Gated Radial Free-Breathing Liver MR Elastography: Assessment of Technical Performance in Children at 3 T.

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.

Association Between MR Elastography Liver Stiffness and Histologic Liver Fibrosis in Children and Young Adults With Autoimmune Liver Disease.

BACKGROUND. Liver fibrosis is an important clinical endpoint of the progression of autoimmune liver disease (AILD); its monitoring would benefit from noninvasive imaging tools. OBJECTIVE. The purpose of this study was to assess the relationship between MR elastography (MRE) liver stiffness measurements and histologic liver fibrosis, as well as to evaluate the performance of MRE and biochemical-based clinical markers for stratifying histologic liver fibrosis severity, in children and young adults with AILD. METHODS. This retrospective study used an existing institutional registry of children and young adults diagnosed with AILD (primary sclerosing cholangitis [PSC], autoimmune sclerosing cholangitis [ASC], or autoimmune hepatitis [AIH]). The registry was searched to identify patients who underwent both a research abdominal 1.5-T MRI examination that included liver MRE (performed for registry enrollment) and a clinically indicated liver biopsy within 6 months of that examination. MRE used a 2D gradient-recalled echo sequence. One analyst measured mean liver shear stiffness (in kilopascals) for each examination. Laboratory markers of liver fibrosis (aspartate aminotransferase-to-platelet ratio index [APRI] and fibrosis-4 [FIB-4] score) were recorded. For investigational purposes, one pathologist, blinded to clinical and MRI data, determined histologic Metavir liver fibrosis stage. The Spearman rank order correlation coefficient was calculated between MRE liver stiffness and Metavir liver fibrosis stage. ROC analysis was used to evaluate diagnostic performance for identifying advanced fibrosis (i.e., differentiating Metavir F0-F1 from F2-F4 fibrosis), and sensitivity and specificity were calculated using the Youden index. RESULTS. The study included 46 patients (median age, 16.6 years [IQR, 13.7-17.8 years]; 20 female patients, 26 male patients); 12 had PSC, 10 had ASC, and 24 had AIH. Median MRE liver stiffness was 2.9 kPa (IQR, 2.2-4.0 kPa). MRE liver stiffness and Metavir fibrosis stage showed strong positive correlation (ρ = 0.68). For identifying advanced liver fibrosis, MRE liver stiffness had an AUC of 0.81, with sensitivity of 65.4% and specificity of 90.0%; APRI had an AUC of 0.72, with sensitivity of 64.0% and specificity of 80.0%; and FIB-4 score had an AUC of 0.71, with sensitivity of 60.0% and specificity of 85.0%. CONCLUSION. MRE liver stiffness measurements were associated with histologic liver fibrosis severity. CLINICAL IMPACT. The findings support a role for MRE in noninvasive monitoring of liver stiffness, a surrogate for fibrosis, in children and young adults with AILD. TRIAL REGISTRATION. ClinicalTrials.gov NCT03175471.

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

MR elastography (MRE) at 60 Hz is widely used for staging liver fibrosis. MRE with lower frequencies may provide inflammation biomarkers. To establish a practical simultaneous dual-frequency liver MRE protocol at both 30 Hz and 60 Hz during a single examination and validate the occurrence of second harmonic waves at 30 Hz. Retrospective. One hundred six patients (48 females, age: 50.0 ± 13.4 years) were divided as follows: Cohort One (15 patients with chronic liver disease [CLD] and 25 healthy volunteers) with simultaneous dual-frequency MRE. Cohort Two (66 patients with CLD) with second harmonic MRE. 3-T, single- or dual-frequency MRE at 30 Hz and 60 Hz. Liver stiffness (LS) in both cohorts was evaluated with manually placed volumetric ROIs by two independent analyzers. Image quality was assessed by three independent readers on a 4-point scale (0-3: none/failed, fair, moderate, excellent) based on the depth of wave propagation with 1/3 incremental penetration. The success rate was derived from the percentage of nonzero quality scores. Measurement agreement, bias, and repeatability of LS were assessed using intraclass correlation coefficients (ICCs), Bland-Altman plots, and repeatability coefficient (RC). Mann-Whitney U tests were used to evaluate the differences in image quality between different methods. A P-value <0.05 was considered statistically significant. Success rate was 97.5% in Cohort One and 91% success rate for the second harmonic MRE in Cohort Two. The second harmonic and conventional MRE showed excellent agreement in LS (all ICCs >0.90). The quality scores for the second harmonic wave images were lower than those from the conventional MRE (Z = -4.523). Compared with conventional and second harmonic methods, simultaneous dual-frequency had better image quality, high success rate and the advantage of intrinsic co-registration, while the second harmonic method can be an alternative if custom waveform is not available. 3 TECHNICAL EFFICACY: Stage 1.

Multiparametric magnetic resonance imaging of the liver and spleen in Gaucher disease.

To assess liver and spleen characteristics of a population with Gaucher disease (GD) using multiparametric MRI and MR elastography (MRE) for evaluation of diffuse liver and spleen disease, which includes liver fat fraction, liver and spleen volume and iron deposition, and liver and spleen stiffness correlated with DS3 Severity Scoring System for Gaucher disease (GD-DS3). We prospectively evaluated 41 patients with type 1 Gaucher disease using a 3.0T MRI and MRE between January 2019 and February 2020. Clinical, laboratory, and imaging data was collected. Mann-Whitney, Kruskal-Wallis, and Spearman's correlation were applied to evaluate liver and spleen MRI and MRE, clinical and laboratory variables, and GD-DS3. ERT and SRT treatment groups were compared. Hepatomegaly was seen in 15% and splenomegaly in 42% of the population. Moderate and strong and correlations were found between liver and spleen iron overload (rho = 0.537; p = 0.002); between liver and spleen volume (rho = 0.692, p < 0.001) and between liver and spleen stiffness (rho = 0.453, p = 0.006). Moderate correlations were found between liver stiffness and GD-DS3 (rho = 0.559; p < 0.001) and between splenic volume and GD-DS3 (rho = 0.524; p = 0.001). The prevalence of hepatosplenomegaly, liver fibrosis, and liver iron overload in treated patients with GD is low, which may be related to the beneficial effect of treatment. Liver MRE and splenic volume correlate with severity score and may be biomarkers of disease severity.

Individualized driver amplitude in liver MR elastography: a linear regression study.

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. To construct a linear regression model of individualized driver amplitude to improve liver MRE image quality. 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. 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. 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.

Automated CNN-Based Analysis Versus Manual Analysis for MR Elastography in Nonalcoholic Fatty Liver Disease: Intermethod Agreement and Fibrosis Stage Discriminative Performance.

BACKGROUND. Histologic fibrosis stage is the most important prognostic factor in chronic liver disease. MR elastography (MRE) is the most accurate noninvasive method for detecting and staging liver fibrosis. Although accurate, manual ROI-based MRE analysis is complex, time-consuming, requires specialized readers, and is prone to methodologic variability and suboptimal interreader agreement. OBJECTIVE. The purpose of this study was to develop an automated convolutional neural network (CNN)-based method for liver MRE analysis, evaluate its agreement with manual ROI-based analysis, and assess its performance for classifying dichotomized fibrosis stages using histology as the reference standard. METHODS. In this retrospective cross-sectional study, 675 participants who underwent MRE using different MRI systems and field strengths at 28 imaging sites from five multicenter international clinical trials of nonalcoholic steatohepatitis were included for algorithm development and internal testing of agreement between automated CNN-based and manual ROI-based analyses. Eighty-one patients (52 women, 29 men; mean age, 54 years) who underwent MRE using a single 3-T system and liver biopsy for clinical purposes at a single institution were included for external testing of agreement between the two analysis methods and assessment of fibrosis stage discriminative performance. Agreement was evaluated using intraclass correlation coefficients (ICCs). Bootstrapping was used to compute 95% CIs. Discriminative performance of each method for dichotomized histologic fibrosis stage was evaluated by AUC and compared using bootstrapping. RESULTS. Mean CNN- and manual ROI-based stiffness measurements ranged from 3.21 to 3.34 kPa in trial participants and from 3.21 to 3.30 kPa in clinical patients. ICC for CNN- and manual ROI-based measurements was 0.98 (95% CI, 0.97-0.98) in trial participants and 0.99 (95% CI, 0.98-0.99) in clinical patients. AUCs for classification of dichotomized fibrosis stage ranged from 0.89 to 0.93 for CNN-based analysis and 0.87 to 0.93 for manual ROI-based analysis (p = .23-.75). CONCLUSION. Stiffness measurements using the automated CNN-based method agreed strongly with manual ROI-based analysis across MRI systems and field strengths, with excellent discriminative performance for histology-determined dichotomized fibrosis stages in external testing. CLINICAL IMPACT. Given the high incidence of chronic liver disease worldwide, it is important that noninvasive tools to assess fibrosis are applied reliably across different settings. CNN-based analysis is feasible and may reduce reliance on expert image analysts.

Comparison of Quantitative Liver US and MRI in Patients with Liver Disease.

Background Quantitative US techniques can be used to identify changes of liver disease, but data regarding their diagnostic performance and relationship to MRI measures are sparse. Purpose To define associations between quantitative US and MRI measures of the liver in children, adolescents, and young adults with liver disease and to define the predictive ability of quantitative US measures to detect abnormal liver stiffening and steatosis defined with MRI. Materials and Methods In this prospective study, consecutive patients aged 8-21 years and known to have or suspected of having liver disease and body mass index less than 35 kg/m2 underwent 1.5-T MRI and quantitative liver US during the same visit at a pediatric academic medical center between April 2018 and December 2020. Acquired US parameters included shear-wave speed (SWS) and attenuation coefficient, among others. US parameters were compared with liver MR elastography and liver MRI proton density fat fraction (PDFF). Pearson correlation, multiple logistic regression, and receiver operating characteristic curve analyses were performed to assess associations and determine the performance of US relative to that of MRI. Results A total of 44 study participants (mean age, 16 years ± 4 [SD]; age range, 8-21 years; 23 male participants) were evaluated. There was a positive correlation between US SWS and MR elastography stiffness (r = 0.73, P < .001). US attenuation was positively correlated with MRI PDFF (r = 0.45, P = .001). For the prediction of abnormal (>2.8 kPa) liver shear stiffness, SWS (1.56 m/sec [7.3 kPa] cutoff) had an area under the receiver operating characteristic curve (AUC) of 0.95 with 91% sensitivity (95% CI: 71, 99) (20 of 22 participants) and 95% specificity (95% CI: 76, 99) (20 of 21 participants). For the prediction of abnormal (>5%) liver PDFF, US attenuation (0.55 dB/cm/MHz cutoff) had an AUC of 0.75 with a sensitivity of 73% (95% CI: 39, 94) (eight of 11 participants) and a specificity of 73% (95% CI: 55, 86) (24 of 33 participants). Conclusion In children, adolescents, and young adults with known or suspected liver disease, there was moderate to high correlation between US shear-wave speed (SWS) and MR elastography-derived stiffness. US SWS predicted an abnormal liver shear stiffness with high performance. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Khanna and Alazraki in this issue.

Effect of different driver power amplitudes on liver stiffness measurement in pediatric liver MR elastography.

To assess how different driver power amplitudes affect the measurement of liver stiffness in pediatric liver magnetic resonance elastography (MRE). From January 2018 to May 2018, pediatric patients (≤ 18years) who underwent liver MRE with 20% and 56% driver power amplitudes were included in this retrospective study. Region-of-interests (ROIs) were drawn on four stiffness maps to include the largest area of the liver parenchyma. Intraclass correlation coefficients (ICCs) were used to assess agreements for the area, mean, maximum, minimum and standard deviation of liver stiffness between the driver power amplitudes. 128 MRE stiffness maps from 16 patients (M:F = 10:6, median 12.5years old) were included. On MRE, median ROI areas of liver were 83.1 cm2 (range, 46.9-144.1 cm2) and 63.0 cm2 (range, 5.4-123.4 cm2) for the driver power amplitudes of 20% and 56%, respectively. Median liver stiffness values were 2.3kPa (range, 1.7-8.0kPa) and 2.8kPa (range, 1.7-8.5kPa). Maximum and minimum liver stiffness values were 5.3kPa and 1.0kPa for 20% and 7.8kPa and 1.1kPa for 56%. Standard deviation was 0.6kPa for 20% and 1.0kPa for 56%. ICC values between the two power amplitudes were 0.33-0.51 for the ROI area and the maximum, minimum and standard deviation values of liver stiffness. The ICC value for liver stiffness was 0.857 (95% confidence interval, 0.760-0.915). Liver stiffness with two driver power amplitudes on MRE showed good reliability in pediatric patients. Driver power amplitudes need to be optimized according to the pediatric liver size.

Assessment of agreement between manual and automated processing of liver MR elastography for shear stiffness estimation in children and young adults with autoimmune liver disease.

To compare automated versus standard of care manual processing of 2D gradient recalled echo (GRE) liver MR Elastography (MRE) in children and young adults. 2D GRE liver MRE data from research liver MRI examinations performed as part of an autoimmune liver disease registry between March 2017 and March 2020 were analyzed retrospectively. All liver MRE data were acquired at 1.5T with 60Hz mechanical vibration frequency. For manual processing, two independent readers (R1, R2) traced regions of interest on scanner generated shear stiffness maps. Automated processing was performed using MREplus+ (Resoundant Inc.) using 90% (A90) and 95% (A95) confidence masks. Agreement was evaluated using intra-class correlation coefficients (ICC) and Bland-Altman analyses. Classification performance was evaluated using receiver operating characteristic curve (ROC) analyses. In 65 patients with mean age of 15.5 ± 3.8years (range 8-23years; 35 males) median liver shear stiffness was 2.99kPa (mean 3.55 ± 1.69kPa). Inter-reader agreement for manual processing was very strong (ICC = 0.99, mean bias = 0.01kPa [95% limits of agreement (LoA): -0.41 to 0.44kPa]). Correlation between manual and A95 automated processing was very strong (R1: ICC = 0.988, mean bias = 0.13kPa [95% LoA: -0.40 to 0.68kPa]; R2: ICC = 0.987, mean bias = 0.13kPa [95% LoA: -0.44 to 0.69kPa]). Automated measurements were perfectly replicable (ICC = 1.0; mean bias = 0kPa). Liver shear stiffness values obtained using automated processing showed excellent agreement with manual processing. Automated processing of liver MRE was perfectly replicable.

Imaging Biomarkers of Hepatic Fibrosis: Reliability and Accuracy of Hepatic Periportal Space Widening and Other Morphologic Features on MRI.

OBJECTIVE. The purpose of this article was to assess the reliability and accuracy of hepatic periportal space widening and other qualitative imaging features for the prediction of hepatic fibrosis. MATERIALS AND METHODS. This single-center retrospective study identified consecutive patients who had undergone liver MR elastography. Two abdominal radiologists independently reviewed anatomic images, assessing multiple qualitative features of chronic liver disease (CLD) including periportal space widening. Each reader also measured the periportal space at the main portal vein (MPV) and right portal vein (RPV). Interrater reliability analysis was then performed. Sensitivity and specificity were determined for the detection of any hepatic fibrosis (stage I or higher) and of advanced fibrosis (stage III or higher) using stiffness on MR elastography as the reference standard. RESULTS. Of 229 subjects, 157 (69%) had fibrosis and 78 (34%) had advanced fibrosis. Agreement for periportal space widening was moderate (κ = 0.47), and agreement for remaining features was moderate to substantial (κ = 0.42-0.80). Agreement for the periportal space at the MPV was moderate (ICC, 0.55), and agreement for the periportal space at the RPV was near perfect (ICC, 0.83). Periportal space widening had the highest sensitivity (83.0%) for any fibrosis, with limited specificity (61.3%). Surface nodularity had the highest specificity (94.4%) for any fibrosis, with limited sensitivity (51.6%). Periportal space widening plus one or more additional imaging feature of CLD or the presence of surface nodularity alone had sensitivity of 72.6% and specificity of 76.1%. A periportal space at the MPV greater than 9.5 mm had substantial agreement with qualitative periportal space widening (κ = 0.74). CONCLUSION. Periportal space widening has a high sensitivity for hepatic fibrosis, with moderate specificity when combined with additional anatomic features of CLD.

Development of a Suitable Actuator for Magnetic Resonance Elastography of the Psoas Major Muscle

This study aimed to develop a refined actuator suitable for psoas major muscle (PM) MR elastography (MRE) and evaluate its measurement precision. MRE was performed on nine healthy volunteers. Discomfort under PM-MRE examinations was evaluated by discomfort scores using a four-point subjective scale. The performance of refined actuator was evaluated in detail; repeatability was evaluated using repeatability coefficients (%RC) according to the Quantitative Imaging Biomarker Alliance (QIBA) and reproducibility with different operators was evaluated using interclass correlation coefficients (ICC). The discomfort score was 1.4 ± 0.53 and it indicated refined actuator was sufficiently comfortable (no pain). In the repeatability study (n = 9), the %RC was approximately 19%, which was comparable to the limit required for clinical liver MREs by the QIBA (19%). In the reproducibility study, the ICCs were > 0.90 (n = 3), indicating that the refined actuator had almost perfect reproducibility. The refined actuator was suitable for PM-MREs and had acceptable repeatability and reproducibility. Refined actuator was expected to meet the standard set by the QIBA (for liver MRE).

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

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

Normal Liver Stiffness Measured with MR Elastography in Children.

Background Stiffness thresholds for liver MR elastography in children vary between studies and may differ from thresholds in adults. Normative liver stiffness data are needed to optimize diagnostic thresholds for children. Purpose To determine normal liver stiffness, and associated normal ranges for children, as measured with MR elastography across vendors and field strengths. Materials and Methods This was a prospective multicenter cohort study (ClinicalTrials.gov identifier: NCT03235414). Volunteers aged 7-17.9 years without a known history of liver disease were recruited at four sites for a research MRI and blood draw between February 2018 and October 2019. MRI was performed on three vendor platforms and at two field strengths (1.5 T and 3.0 T). All MRI scans were centrally analyzed; stiffness, proton density fat fraction (PDFF), and R2* values were expressed as means of means. Mean and 95% confidence intervals (CIs) for liver stiffness were calculated. Pearson correlation coefficient (r), two-sample t test, or analysis of variance was used to assess univariable associations. Results Seventy-one volunteers had complete data and no documented exclusion criterion (median age, 12 years; interquartile range [IQR], 10-15 years; 39 female participants). Median body mass index percentile was 54% (IQR, 32.5%-69.5%). Mean liver stiffness was 2.1 kPa (95% CI: 2.0, 2.2 kPa) with mean ± 1.96 kPa standard deviation of 1.5-2.8 kPa. Median liver PDFF was 2.0% (IQR, 1.7%-2.6%). There was no association between liver stiffness and any patient variable or MRI scanner factor. Conclusion Mean liver stiffness measured with MR elastography in children without liver disease was 2.1 kPa (similar to that in adults). The 95th percentile of normal liver stiffness was 2.8 kPa. Liver stiffness was independent of sex, age, or body mass index and did not vary with MRI scanner vendor or field strength. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Yin in this issue.

MR elastography of liver: current status and future perspectives.

Non-invasive evaluation of liver fibrosis has evolved over the last couple of decades. Currently, elastography techniques are the most widely used non-invasive methods for clinical evaluation of chronic liver disease (CLD). MR elastography (MRE) of the liver has been used in the clinical practice for nearly a decade and continues to be widely accepted for detection and staging of liver fibrosis. With MRE, one can directly visualize propagating shear waves through the liver and an inversion algorithm in the scanner automatically converts the shear wave properties into an elastogram (stiffness map) on which liver stiffness can be calculated. The commonly used MRE method, two-dimensional gradient recalled echo (2D-GRE) sequence has produced excellent results in the evaluation of liver fibrosis in CLD from various etiologies and newer clinical indications continue to emerge. Advances in MRE technique, including 3D MRE, automated liver elasticity calculation, improvements in shear wave delivery and patient experience, are promising to provide a faster and more reliable MRE of liver. Innovations, including evaluation of mechanical parameters, such as loss modulus, displacement, and volumetric strain, are promising for comprehensive evaluation of CLD as well as understanding pathophysiology, and in differentiating various etiologies of CLD. In this review, the current status of the MRE of liver in CLD are outlined and followed by a brief description of advanced techniques and innovations in MRE of liver.

MR elastography, T1 and T2 relaxometry of liver: role in noninvasive assessment of liver function and portal hypertension.

To evaluate the correlation between liver stiffness as measured on MR elastography and T1 and T2 relaxation times from T1 and T2 mapping with clinical parameters of liver disease, including the MELD score, MELD-Na and ALBI grade, and endoscopically visible esophageal varices. 223 patients with known or suspected liver disease underwent MRI of the liver with T1 mapping (Look-Locker sequence) and 2D SE-EPI MR elastography (MRE) sequences. 139 of these patients also underwent T2 mapping with radial T2 FS sequence. Two readers measured liver stiffness, T1 relaxation times and T2 relaxation times, and assessed qualitative features such as presence or absence of cirrhosis, ascites, spleen length, and varices on conventional MRI images. A third reader collected the clinical data (MELD score, MELD-Na Score, ALBI grade, and results of endoscopy in 78 patients). Significant moderate correlation was found between MELD score and all three imaging techniques for both readers (MRE, r = 0.35 and 0.28; T1 relaxometry, r = 0.30 and 0.29; T2 relaxometry, r = 0.45, and 0.37 for reader 1 and reader 2 respectively). Correlation with MELD-Na score was even higher (MRE, r = 0.49 and 0.40; T1, r = 0.45 and 0.41; T2, r = 0.47 and 0.35 for reader 1 and reader 2 respectively). Correlations between MRE and ALBI grade was significant and moderate for both readers: r = 0.39 and 0.37, higher than T1 relaxometry (r = 0.22 and 0.20) and T2 relaxometry (r = 0.17, and r = 0.24). Significant moderate correlations were found for both readers between MRE and the presence of varices on endoscopy (r = 0.28 and 0.30). MRE and T1 relaxometry were significant predictors of varices at endoscopy for both readers (MRE AUC 0.923 and 0.873; T1 relaxometry AUC = 0.711 and 0.675 for reader 1 and reader 2 respectively). Cirrhotic morphology (AUC = 0.654), spleen length (AUC = 0.610) and presence of varices in the upper abdomen on MRI (AUC of 0.693 and 0.595) were all significant predictors of endoscopic varices. Multivariable logistic regression model identified that spleen length and liver MRE were significant independent predictors of endoscopic varices for both readers. MR elastography, T1 and T2 relaxometry demonstrated moderate positive correlation with the MELD score and MELD-Na Score. Correlation between MRE and ALBI grade was superior to T1 and T2 relaxometry methods. MRE performed better than T1 and T2 relaxometry to predict the presence of varices at endoscopy. On multivariate analyses, spleen length and MRE were the only two significant independent predictors of endoscopic varices.

Diagnostic accuracy of texture analysis and machine learning for quantification of liver fibrosis in MRI: correlation with MR elastography and histopathology.

To compare the diagnostic accuracy of texture analysis (TA)-derived parameters combined with machine learning (ML) of non-contrast-enhanced T1w and T2w fat-saturated (fs) images with MR elastography (MRE) for liver fibrosis quantification. In this IRB-approved prospective study, liver MRIs of participants with suspected chronic liver disease who underwent liver biopsy between August 2015 and May 2018 were analyzed. Two readers blinded to clinical and histopathological findings performed TA. The participants were categorized into no or low-stage (0-2) and high-stage (3-4) fibrosis groups. Confusion matrices were calculated using a support vector machine combined with principal component analysis. The diagnostic accuracy of ML-based TA of liver fibrosis and MRE was assessed by area under the receiver operating characteristic curves (AUC). Histopathology served as reference standard. A total of 62 consecutive participants (40 men; mean age ± standard deviation, 48 ± 13years) were included. The accuracy of TA and ML on T1w was 85.7% (95% confidence interval [CI] 63.7-97.0) and 61.9% (95% CI 38.4-81.9) on T2w fs for classification of liver fibrosis into low-stage and high-stage fibrosis. The AUC for TA on T1w was similar to MRE (0.82 [95% CI 0.59-0.95] vs. 0.92 [95% CI 0.71-0.99], p = 0.41), while the AUC for T2w fs was significantly lower compared to MRE (0.57 [95% CI 0.34-0.78] vs. 0.92 [95% CI 0.71-0.99], p = 0.008). Our results suggest that liver fibrosis can be quantified with TA-derived parameters of T1w when combined with a ML algorithm with similar accuracy compared to MRE. • Liver fibrosis can be categorized into low-stage fibrosis (0-2) and high-stage fibrosis (3-4) using texture analysis-derived parameters of T1-weighted images with a machine learning approach. • For the differentiation of low-stage fibrosis and high-stage fibrosis, the diagnostic accuracy of texture analysis on T1-weighted images combined with a machine learning algorithm is similar compared to MR elastography.

Usefulness of iodine-blood material density images in estimating degree of liver fibrosis by calculating extracellular volume fraction obtained from routine dual-energy liver CT protocol equilibrium phase data: preliminary experience.

To assess whether extracellular volume fraction (ECV) calculated from iodine(-blood) density images (I-B) of dual-energy liver CT (DECT) equilibrium phase data (EqD) is useful in estimating the degree of liver fibrosis. Consecutive 52 patients with chronic liver disease who underwent fast kV switching DECT and liver MR elastography (MRE) were retrospectively enrolled. Iodine(-water) density images (I-W) and I-B generated from EqD and ECV were calculated. As blood pools, abdominal aorta (Ao) and suprahepatic inferior vena cava (IVC) were chosen, and, therefore, 4 types of ECV (ECVI-W Ao, ECVI-W IVC, ECVI-B Ao, ECVI-B IVC) were obtained. ECV was also calculated using conventional method (ECVconv Ao). The correlation coefficients (R2 or rho) of these five ECVs versus liver stiffness (MRE) or pathologically proven fibrosis grades were compared. As for correlation with liver stiffness, R2 for ECVconv.Ao, ECVI-W Ao, ECVI-B Ao, ECVI-W IVC, and ECVI-B IVC, were 0.26, 0.34, 0.44, 0.39, and 0.52, respectively (all p < 0.0001). Histopathological correlation was available in 28 patients, and rho values were 0.61, 0.60, 0.71, 0.68, and 0.76, respectively (all p < 0.001). ECVI-B IVC calculated from EqD of DECT is useful in estimating the degree of liver fibrosis.

Liver MR Elastography Technique and Image Interpretation: Pearls and Pitfalls.

Liver MR elastography is an imaging technique used to measure liver stiffness in the evaluation for possible fibrosis or cirrhosis. Liver stiffness measurement (LSM) is useful for predicting the stage of liver fibrosis. However, obtaining and reporting accurate and reliable LSMs with MR elastography require an understanding of the three core components of liver MR elastography: optimization of imaging technique, prompt quality control of images, and proper interpretation and reporting of elastogram findings. When performing MR elastography, six important technical parameters that should be optimized are patient fasting before the examination, proper passive driver placement, proper MR elastography section positioning over the largest area of the liver, use of MR elastography-related sequences at end expiration, choosing the best timing of the MR elastography sequence, and optimization of several essential pulse sequence parameters. As soon as the MR elastography examination is performed, the elastograms should be reviewed to ensure that they are of diagnostic quality so that corrective steps can be taken, if needed, and MR elastography can be repeated before the diagnostic portion of the examination concludes. Finally, the interpreting radiologist needs to understand and be able to perform the proper technique for LSMs, including determining which areas of the liver to include or avoid in the measurements; knowing which conditions, other than fibrosis or cirrhosis, can increase liver stiffness; and understanding how to report elastography results. This article reviews the proper technique for performing liver MR elastography and subsequent quality control assessment, as well as the principles for interpreting and reporting studies. This review may be helpful for implementing and operating a clinical liver MR elastography service.Online supplemental material is available for this article.©RSNA, 2019.

Immunotherapy response evaluation with MR elastography (MRE) in advanced HCC.

230 Background: To determine changes in MRE HCC stiffness as predictor of immunotherapy response in patients with advanced HCC. Methods: This was a prospective, Institutional Review Board approved study of 15 patients with biopsy proven advanced HCC (not amenable to curative therapy), who were to be treated with Pembrolizumab. Eligible patients were &gt; 18 years old with radiographic disease progression/intolerance to sorafenib. All patients had liver MRI with MR Elastography (MRE) and liver biopsy at baseline and at 9 weeks of therapy. HCC stiffness (kilopascals, kPa) was measured on liver MRE elastograms (stiffness maps). Change in HCC stiffness on MRE was compared with overall survival, time to disease progression, and total number of lymphocytes on targeted liver biopsy. Data cutoff date was September 1st 2018. Analysis was performed using descriptive statistics including Spearman correlation ( R), Cox regression, Wilcoxon rank sum test and Fisher’s exact test. Results: Of the initial 15 patients, 4 withdrew from therapy, 1 patient did not undergo MRE scan, and 1 patient had MRE failure. The final 9 patients included 6 men. Median age was 70 years (range, 54-78). Etiology of liver disease was HCV (n = 4) and NASH (n = 5). HCC was moderately differentiated in 8 of 9 patients and well-differentiated in 1 patient. Median overall survival and time to progression were 52 weeks (range, 16-112) and 18 weeks (range, 9-48), respectively. Average non-tumorous liver stiffness was 3.2 kPa (range, 2.1-4.3). No significant change in non-tumor liver stiffness was seen at 9 weeks (p = 0.12). Median baseline tumor stiffness was 4.5 kPa (range, 2.4-7.5). Increase in HCC stiffness at 9 weeks was seen in 5 patients, decrease in 3 patients and no change in 1. Change in HCC stiffness at 9 weeks correlated significantly with overall survival ( R = 0.83), and time to progression ( R = 0.96), (p &lt; 0.05). Nine patients had liver biopsy at baseline and 7 had biopsy at 9 weeks. HCC T lymphocytes on biopsy (n/mm2) significantly correlated with HCC stiffness ( R = 0.79), (p &lt; 0.01). Conclusions: Our pilot data suggests early change in tumor stiffness may help predict better immunotherapy response in patients with advanced HCC.

Diagnostic performance of quantitative magnetic resonance imaging biomarkers for predicting portal hypertension in children and young adults with autoimmune liver disease.

Primary sclerosing cholangitis, autoimmune hepatitis and autoimmune sclerosing cholangitis are forms of chronic, progressive autoimmune liver disease (AILD) that can affect the pediatric population. To determine whether quantitative MRI- and laboratory-based biomarkers are associated with conventional imaging findings of portal hypertension (radiologic portal hypertension) in children and young adults with AILD. Forty-four patients with AILD enrolled in an institutional registry underwent a research abdominal MRI examination at 1.5 tesla(T). Five quantitative MRI techniques were performed: liver MR elastography, spleen MR elastography, liver iron-corrected T1 mapping, liver T2 mapping, and liver diffusion-weighted imaging (DWI, quantified as apparent diffusion coefficients). Two anatomical sequences were used to document splenomegaly, varices and ascites. We calculated aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4) scores - laboratory-based biomarkers of liver fibrosis. We used receiver operating characteristic (ROC) curve analyses to establish the diagnostic performance of quantitative MRI and laboratory biomarkers for indicating the presence of radiologic portal hypertension. Twenty-three (52%) patients were male; mean age was 15.2±4.0years. Thirteen (30%) patients had radiologic portal hypertension. Liver and spleen stiffness demonstrated the greatest diagnostic performance for indicating the presence of portal hypertension (area-under-the-ROC-curve [AUROC]=0.98 and 0.96, respectively). The APRI and FIB-4 scores also demonstrated good diagnostic performance (AUROC=0.87 and 0.88, respectively). MRI-derived measures of liver and spleen stiffness as well as laboratory-based APRI and FIB-4 scores are highly associated with imaging findings of portal hypertension in children and young adults with AILD and thus might be useful for predicting portal hypertension impending onset and directing personalized patient management.