Comparative diagnostic performance of ultrasound shear wave elastography and magnetic resonance elastography for classifying fibrosis stage in adults with biopsy-proven nonalcoholic fatty liver disease.

OBJECTIVES: To compare the diagnostic accuracy of US shear wave elastography (SWE) and magnetic resonance elastography (MRE) for classifying fibrosis stage in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: Patients from a prospective single-center cohort with clinical liver biopsy for known or suspected NAFLD underwent contemporaneous SWE and MRE. AUCs for classifying biopsy-determined liver fibrosis stages ≥ 1, ≥ 2, ≥ 3, and = 4, and their respective performance parameters at cutoffs providing ≥ 90% sensitivity or specificity were compared between SWE and MRE. RESULTS: In total, 100 patients (mean age, 51.8 ± 12.9 years; 46% males; mean BMI 31.6 ± 4.7 kg/m2) with fibrosis stage distribution (stage 0/1/2/3/4) of 43, 36, 5, 10, and 6%, respectively, were included. AUCs (and 95% CIs) for SWE and MRE were 0.65 (0.54-0.76) and 0.81 (0.72-0.89), 0.81 (0.71-0.91) and 0.94 (0.89-1.00), 0.85 (0.74-0.96) and 0.95 (0.89-1.00), and 0.91 (0.79-1.00) and 0.92 (0.83-1.00), for detecting fibrosis stage ≥ 1, ≥ 2, ≥ 3, and = 4, respectively. The differences were significant for detecting fibrosis stage ≥ 1 and ≥ 2 (p < 0.01) but not otherwise. At ≥ 90% sensitivity cutoff, MRE yielded higher specificity than SWE at diagnosing fibrosis stage ≥ 1, ≥ 2, and ≥ 3. At ≥ 90% specificity cutoff, MRE yielded higher sensitivity than SWE at diagnosing fibrosis stage ≥ 1 and ≥ 2. CONCLUSIONS: In adults with NAFLD, MRE was more accurate than SWE in diagnosing stage ≥ 1 and ≥ 2 fibrosis, but not stage ≥ 3 or 4 fibrosis. KEY POINTS: • For detecting any fibrosis or mild fibrosis, MR elastography was significantly more accurate than shear wave elastography. • For detecting advanced fibrosis and cirrhosis, MRE and SWE did not differ significantly in accuracy. • For excluding advanced fibrosis and potentially ruling out the need for biopsy, SWE and MRE did not differ significantly in negative predictive value. • Neither SWE nor MRE had sufficiently high positive predictive value to rule in advanced fibrosis.

Liver Fat Assessment in Multiview Sonography Using Transfer Learning With Convolutional Neural Networks.

OBJECTIVES: To develop and evaluate deep learning models devised for liver fat assessment based on ultrasound (US) images acquired from four different liver views: transverse plane (hepatic veins at the confluence with the inferior vena cava, right portal vein, right posterior portal vein) and sagittal plane (liver/kidney). METHODS: US images (four separate views) were acquired from 135 participants with known or suspected nonalcoholic fatty liver disease. Proton density fat fraction (PDFF) values derived from chemical shift-encoded magnetic resonance imaging served as ground truth. Transfer learning with a deep convolutional neural network (CNN) was applied to develop models for diagnosis of fatty liver (PDFF ≥ 5%), diagnosis of advanced steatosis (PDFF ≥ 10%), and PDFF quantification for each liver view separately. In addition, an ensemble model based on all four liver view models was investigated. Diagnostic performance was assessed using the area under the receiver operating characteristics curve (AUC), and quantification was assessed using the Spearman correlation coefficient (SCC). RESULTS: The most accurate single view was the right posterior portal vein, with an SCC of 0.78 for quantifying PDFF and AUC values of 0.90 (PDFF ≥ 5%) and 0.79 (PDFF ≥ 10%). The ensemble of models achieved an SCC of 0.81 and AUCs of 0.91 (PDFF ≥ 5%) and 0.86 (PDFF ≥ 10%). CONCLUSION: Deep learning-based analysis of US images from different liver views can help assess liver fat.

Magnetic resonance elastography biomarkers for detection of histologic alterations in nonalcoholic fatty liver disease in the absence of fibrosis.

OBJECTIVES: To investigate associations between histology and hepatic mechanical properties measured using multiparametric magnetic resonance elastography (MRE) in adults with known or suspected nonalcoholic fatty liver disease (NAFLD) without histologic fibrosis. METHODS: This was a retrospective analysis of 88 adults who underwent 3T MR exams including hepatic MRE and MR imaging to estimate proton density fat fraction (MRI-PDFF) within 180 days of liver biopsy. Associations between MRE mechanical properties (mean shear stiffness (|G*|) by 2D and 3D MRE, and storage modulus (G'), loss modulus (G″), wave attenuation (α), and damping ratio (ζ) by 3D MRE) and histologic, demographic and anthropometric data were assessed. RESULTS: In univariate analyses, patients with lobular inflammation grade ≥ 2 had higher 2D |G*| and 3D G″ than those with grade ≤ 1 (p = 0.04). |G*| (both 2D and 3D), G', and G″ increased with age (rho = 0.25 to 0.31; p ≤ 0.03). In multivariable regression analyses, the association between inflammation grade ≥ 2 remained significant for 2D |G*| (p = 0.01) but not for 3D G″ (p = 0.06); age, sex, or BMI did not affect the MRE-inflammation relationship (p > 0.20). CONCLUSIONS: 2D |G*| and 3D G″ were weakly associated with moderate or severe lobular inflammation in patients with known or suspected NAFLD without fibrosis. With further validation and refinement, these properties might become useful biomarkers of inflammation. Age adjustment may help MRE interpretation, at least in patients with early-stage disease. KEY POINTS: • Moderate to severe lobular inflammation was associated with hepatic elevated shear stiffness and elevated loss modulus (p =0.04) in patients with known or suspected NAFLD without liver fibrosis; this suggests that with further technical refinement these MRE-assessed mechanical properties may permit detection of inflammation before the onset of fibrosis in NAFLD. • Increasing age is associated with higher hepatic shear stiffness, and storage and loss moduli (rho = 0.25 to 0.31; p ≤ 0.03); this suggests that age adjustment may help interpret MRE results, at least in patients with early-stage NAFLD.

Assessment of Hepatic Steatosis in Nonalcoholic Fatty Liver Disease by Using Quantitative US.

Background Advanced confounder-corrected chemical shift-encoded MRI-derived proton density fat fraction (PDFF) is a leading parameter for fat fraction quantification in nonalcoholic fatty liver disease (NAFLD). Because of the limited availability of this MRI technique, there is a need to develop and validate alternative parameters to assess liver fat. Purpose To assess relationship of quantitative US parameters to MRI PDFF and to develop multivariable quantitative US models to detect hepatic steatosis and quantify hepatic fat. Materials and Methods Adults with known NAFLD or who were suspected of having NAFLD were prospectively recruited between August 2015 and February 2019. Participants underwent quantitative US and chemical shift-encoded MRI liver examinations. Liver biopsies were performed if clinically indicated. The correlation between seven quantitative US parameters and MRI PDFF was evaluated. By using leave-one-out cross validation, two quantitative US multivariable models were evaluated: a classifier to differentiate participants with NAFLD versus participants without NAFLD and a fat fraction estimator. Classifier performance was summarized by area under the receiver operating characteristic curve and area under the precision-recall curve. Fat fraction estimator performance was evaluated by correlation, linearity, and bias. Results Included were 102 participants (mean age, 52 years ± 13 [standard deviation]; 53 women), 78 with NAFLD (MRI PDFF ≥ 5%). A two-variable classifier yielded a cross-validated area under the receiver operating characteristic curve of 0.89 (95% confidence interval: 0.82, 0.96) and an area under the precision-recall curve of 0.96 (95% confidence interval: 0.93, 0.99). The cross-validated fat fraction predicted by a two-variable fat fraction estimator was correlated with MRI PDFF (Spearman ρ = 0.82 [P < .001]; Pearson r = 0.76 [P < .001]). The mean bias was 0.02% (P = .97), and 95% limits of agreement were ±12.0%. The predicted fat fraction was linear with MRI PDFF (R 2 = 0.63; slope, 0.69; intercept, 4.3%) for MRI PDFF of 34% or less. Conclusion A multivariable quantitative US approach yielded excellent correlation with MRI proton density fat fraction for hepatic steatosis assessment in nonalcoholic fatty liver disease. © RSNA, 2020 Online supplemental material is available for this article.

Liver fibrosis imaging: A clinical review of ultrasound and magnetic resonance elastography.

Liver fibrosis is a histological hallmark of most chronic liver diseases, which can progress to cirrhosis and liver failure, and predisposes to hepatocellular carcinoma. Accurate diagnosis of liver fibrosis is necessary for prognosis, risk stratification, and treatment decision-making. Liver biopsy, the reference standard for assessing liver fibrosis, is invasive, costly, and impractical for surveillance and treatment response monitoring. Elastography offers a noninvasive, objective, and quantitative alternative to liver biopsy. This article discusses the need for noninvasive assessment of liver fibrosis and reviews the comparative advantages and limitations of ultrasound and magnetic resonance elastography techniques with respect to their basic concepts, acquisition, processing, and diagnostic performance. Variations in clinical contexts of use and common pitfalls associated with each technique are considered. In addition, current challenges and future directions to improve the diagnostic accuracy and clinical utility of elastography techniques are discussed. Level of Evidence: 5 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:25-42.

Diagnostic accuracy of hepatic proton density fat fraction measured by magnetic resonance imaging for the evaluation of liver steatosis with histology as reference standard: a meta-analysis.

OBJECTIVES: The aim of this meta-analysis was to evaluate the diagnostic accuracy of hepatic magnetic resonance imaging-proton density fat fraction (MRI-PDFF) for the assessment of liver steatosis (LS) with histology as reference standard. METHODS: A systematic literature search was performed to identify pertinent studies. Quality analyses were conducted by Quality Assessment of Diagnostic Accuracy Studies-2. Diagnostic data were extracted and inconsistency index was calculated for LS≥G1, LS≥G2, and LS=G3, respectively. The area under summary receiver operating characteristic curve (AUC) served as the indicator of diagnostic accuracy. The pooled sensitivity and specificity were calculated if threshold effect was absent. RESULTS: Thirteen studies containing 1100 subjects were included. There was significant threshold effect for LS≥G1. The AUCs for LS≥G1, LS≥G2, and LS=G3 were 0.98 (95% confidence interval (CI) 0.76, 1.00), 0.91 (95% CI 0.89, 0.94), and 0.92 (95% CI 0.89, 0.94), respectively. The pooled sensitivities for LS≥G2 and LS=G3 were 0.83 (95% CI 0.75, 0.88) and 0.79 (95% CI 0.63, 0.90), respectively; the pooled specificities for LS≥G2 and LS=G3 were 0.89 (95% CI 0.84, 0.92) and 0.89 (95% CI 0.84, 0.92), respectively. CONCLUSIONS: MRI-PDFF has high diagnostic accuracy at detecting and grading LS with histology as reference standard, suggesting that MRI-PDFF is able to provide an accurate quantification of LS in clinical trials and patient care. KEY POINT: • MRI-PDFF is able to provide an accurate quantification of LS in clinical trials and patient care.

Inter-platform reproducibility of ultrasonic attenuation and backscatter coefficients in assessing NAFLD.

OBJECTIVES: To assess inter-platform reproducibility of ultrasonic attenuation coefficient (AC) and backscatter coefficient (BSC) estimates in adults with known/suspected nonalcoholic fatty liver disease (NAFLD). METHODS: This HIPAA-compliant prospective study was approved by an institutional review board; informed consent was obtained. Participants with known/suspected NAFLD were recruited and underwent same-day liver examinations with clinical ultrasound scanner platforms from two manufacturers. Each participant was scanned by the same trained sonographer who performed multiple data acquisitions in the right liver lobe using a lateral intercostal approach. Each data acquisition recorded a B-mode image and the underlying radio frequency (RF) data. AC and BSC were calculated using the reference phantom method. Inter-platform reproducibility was evaluated for AC and log-transformed BSC (logBSC = 10log10BSC) by intraclass correlation coefficient (ICC), Pearson's correlation, Bland-Altman analysis with computation of limits of agreement (LOAs), and within-subject coefficient of variation (wCV; applicable to AC). RESULTS: Sixty-four participants were enrolled. Mean AC values measured using the two platforms were 0.90 ± 0.13 and 0.94 ± 0.15 dB/cm/MHz while mean logBSC values were - 30.6 ± 5.0 and - 27.9 ± 5.6 dB, respectively. Inter-platform ICC was 0.77 for AC and 0.70 for log-transformed BSC in terms of absolute agreement. Pearson's correlation coefficient was 0.81 for AC and 0.80 for logBSC. Ninety-five percent LOAs were - 0.21 to 0.13 dB/cm/MHz for AC, and - 9.48 to 3.98 dB for logBSC. The wCV was 7% for AC. CONCLUSIONS: Hepatic AC and BSC are reproducible across two different ultrasound platforms in adults with known or suspected NAFLD. KEY POINTS: • Ultrasonic attenuation coefficient and backscatter coefficient are reproducible between two different ultrasound platforms in adults with NAFLD. • This inter-platform reproducibility may qualify quantitative ultrasound biomarkers for generalized clinical application in patients with suspected/known NAFLD.

Liver fat imaging-a clinical overview of ultrasound, CT, and MR imaging.

Hepatic steatosis is a frequently encountered imaging finding that may indicate chronic liver disease, the most common of which is non-alcoholic fatty liver disease. Non-alcoholic fatty liver disease is implicated in the development of systemic diseases and its progressive phenotype, non-alcoholic steatohepatitis, leads to increased liver-specific morbidity and mortality. With the rising obesity epidemic and advent of novel therapeutics aimed at altering metabolism, there is a growing need to quantify and monitor liver steatosis. Imaging methods for assessing steatosis range from simple and qualitative to complex and highly accurate metrics. Ultrasound may be appropriate in some clinical instances as a screening modality to identify the presence of abnormal liver morphology. However, it lacks sufficient specificity and sensitivity to constitute a diagnostic modality for instigating and monitoring therapy. Newer ultrasound techniques such as quantitative ultrasound show promise in turning qualitative assessment of steatosis on conventional ultrasound into quantitative measurements. Conventional unenhanced CT is capable of detecting and quantifying moderate to severe steatosis but is inaccurate at diagnosing mild steatosis and involves the use of radiation. Newer CT techniques, like dual energy CT, show potential in expanding the role of CT in quantifying steatosis. MRI proton-density fat fraction is currently the most accurate and precise imaging biomarker to quantify liver steatosis. As such, proton-density fat fraction is the most appropriate noninvasive end point for steatosis reduction in clinical trials and therapy response assessment.