MR elastography in nonalcoholic fatty liver disease: inter-center and inter-analysis-method measurement reproducibility and accuracy at 3T.

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

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.

Normal range for MR elastography measured liver stiffness in children without liver disease.

BACKGROUND: Magnetic resonance elastography (MRE) can determine the presence and stage of liver fibrosis. Data on normative MRE values, while reported in adults, are limited in children. PURPOSE: To determine the distribution of MRE-measured liver stiffness in children without liver disease. STUDY TYPE: Prospective, observational. POPULATION: Eighty-one healthy children (mean 12.6 ± 2.6 years, range 8-17 years). FIELD STRENGTH/SEQUENCE: 3.0T Signa HDxt, General Electric MR Scanner; 2D GRE MRE sequence. ASSESSMENT: History, examination, laboratory evaluation, and (MR) exams (proton density fat fraction, PDFF, and MRE) were performed. MR elastograms were analyzed manually at two reading centers and compared with each other for agreement and with published values in healthy adults and thresholds for fibrosis in adult and pediatric patients. STATISTICAL TESTS: Descriptive statistics, Bland-Altman analysis, t-test to compare hepatic stiffness values with reference standards. RESULTS: Stiffness values obtained at both reading centers were similar, without significant bias (P = 0.362) and with excellent correlation (intraclass correlation coefficient [ICC] = 0.782). Mean hepatic stiffness value for the study population was 2.45 ± 0.35 kPa (95th percentile 3.19 kPa), which was significantly higher than reported values for healthy adult subjects (2.10 ± 0.23 kPa, P < 0.001). In all, 74-85% of subjects had stiffness measurements suggestive of no fibrosis. DATA CONCLUSION: Mean liver stiffness measured with MRE in this cohort was significantly higher than that reported in healthy adults. Despite rigorous screening, some healthy children had stiffness measurements suggestive of liver fibrosis using current published thresholds. Although MRE has the potential to provide noninvasive assessment in patients with suspected hepatic disease, further refinement of this technology will help advance its use as a diagnostic tool for evidence of fibrosis in pediatric populations. LEVEL OF EVIDENCE: 1 Technical Efficacy: 5 J. Magn. Reson. Imaging 2020;51:919-927.

Assessment of a high-SNR chemical-shift-encoded MRI with complex reconstruction for proton density fat fraction (PDFF) estimation overall and in the low-fat range.

BACKGROUND: Improving the signal-to-noise ratio (SNR) of chemical-shift-encoded MRI acquisition with complex reconstruction (MRI-C) may improve the accuracy and precision of noninvasive proton density fat fraction (PDFF) quantification in patients with hepatic steatosis. PURPOSE: To assess the accuracy of high SNR (Hi-SNR) MRI-C versus standard MRI-C acquisition to estimate hepatic PDFF in adult and pediatric nonalcoholic fatty liver disease (NAFLD) using an MR spectroscopy (MRS) sequence as the reference standard. STUDY TYPE: Prospective. POPULATION/SUBJECTS: In all, 231 adult and pediatric patients with known or suspected NAFLD. FIELD STRENGTH/SEQUENCE: PDFF estimated at 3T by three MR techniques: standard MRI-C; a Hi-SNR MRI-C variant with increased slice thickness, decreased matrix size, and no parallel imaging; and MRS (reference standard). ASSESSMENT: MRI-PDFF was measured by image analysts using a region of interest coregistered with the MRS-PDFF voxel. STATISTICAL TESTS: Linear regression analyses were used to assess accuracy and precision of MRI-estimated PDFF for MRS-PDFF as a function of MRI-PDFF using the standard and Hi-SNR MRI-C for all patients and for patients with MRS-PDFF <10%. RESULTS: In all, 271 exams from 231 patients were included (mean MRS-PDFF: 12.6% [SD: 10.4]; range: 0.9-41.9). High agreement between MRI-PDFF and MRS-PDFF was demonstrated across the overall range of PDFF, with a regression slope of 1.035 for the standard MRI-C and 1.008 for Hi-SNR MRI-C. Hi-SNR MRI-C, compared to standard MRI-C, provided small but statistically significant improvements in the slope (respectively, 1.008 vs. 1.035, P = 0.004) and mean bias (0.412 vs. 0.673, P < 0.0001) overall. In the low-fat patients only, Hi-SNR MRI-C provided improvements in the slope (1.058 vs. 1.190, P = 0.002), mean bias (0.168 vs. 0.368, P = 0.007), intercept (-0.153 vs. -0.796, P < 0.0001), and borderline improvement in the R2 (0.888 vs. 0.813, P = 0.01). DATA CONCLUSION: Compared to standard MRI-C, Hi-SNR MRI-C provides slightly higher MRI-PDFF estimation accuracy across the overall range of PDFF and improves both accuracy and precision in the low PDFF range. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:229-238.

Longitudinal evolution of CT and MRI LI-RADS v2014 category 1, 2, 3, and 4 observations.

OBJECTIVES: This study assesses the risk of progression of Liver Imaging Reporting and Data System (LI-RADS) categories, and the effects of inter-exam changes in modality or radiologist on LI-RADS categorization. METHODS: Clinical LI-RADS v2014 CT and MRI exams at our institution between January 2014 and September 2017 were retrospectively identified. Untreated LR-1, LR-2, LR-3, and LR-4 observations with at least one follow-up exam were included. Three hundred and seventy-two observations in 214 patients (149 male, 65 female, mean age 61 ± 10 years) were included during the study period (715 exams total). Cumulative incidence curves for progression to malignant LI-RADS categories (LR-5 or LR-M) and to LR-4 or higher were generated for each index category and compared using log-rank tests with a resampling extension. Relationships between inter-exam changes in LI-RADS category and modality or radiologist, adjusted for inter-exam time intervals, were modeled using mixed effect logistic regressions. RESULTS: Median inter-exam follow-up interval and total follow-up duration were 123 and 227 days, respectively. Index LR-1, LR-2, LR-3, and LR-4 differed significantly in their cumulative incidences of progression to malignant categories (p < 0.0001), which were 0%, 2%, 7%, and 32% at 6 months, respectively. Index LR-1, LR-2, and LR-3 differed significantly in cumulative incidences of progression to LR-4 or higher (p = 0.003). MRI-MRI exam pairs had more stable LI-RADS categorization compared to CT-CT (OR = 0.460, p = 0.0018). CONCLUSIONS: LI-RADS observations demonstrate increasing risk of progression to malignancy with increasing category ranging from 0% for LR-1 to 32% for LR-4 at 6 months. Inter-exam modality changes are associated with LI-RADS category changes. KEY POINTS: • While the majority of LR-2 observations remain stable over long-term follow-up, LR-3 and especially LR-4 observations have a higher risk for category progression. • Category transitions between sequential exams using different modalities (CT vs. MRI) may reflect modality differences rather than biological change. MRI, especially with the same type of contrast agent, may provide the most reproducible categorization, although this needs additional validation. • In a clinical practice setting, in which radiologists refer to prior imaging and reports, there was no significant association between changes in radiologist and changes in LI-RADS categorization.

Hepatic steatosis and reduction in steatosis following bariatric weight loss surgery differs between segments and lobes.

OBJECTIVES: The purpose of this study was to (1) evaluate proton density fat fraction (PDFF) distribution across liver segments at baseline and (2) compare longitudinal segmental PDFF changes across time points in adult patients undergoing a very low-calorie diet (VLCD) and subsequent bariatric weight loss surgery (WLS). METHODS: We performed a secondary analysis of data from 118 morbidly obese adult patients enrolled in a VLCD-WLS program. PDFF was estimated using magnitude-based confounder-corrected chemical-shift-encoded (CSE) MRI in each hepatic segment and lobe at baseline (visit 1), after completion of VLCD (visit 2), and at 1, 3, and 6 months (visits 3-5) following WLS. Linear regressions were used to estimate the rate of PDFF change across visits. Lobar and segmental rates of change were compared pairwise. RESULTS: Baseline PDFF was significantly higher in the right lobe compared to the left lobe (p < 0.0001). Lobar and segmental PDFF declined by 3.9-4.5% per month between visits 1 and 2 (preoperative period) and by 4.3-4.8% per month between visits 1 and 3 (perioperative period), but no significant pairwise differences were found in slope between segments and lobes. For visits 3-5 (postoperative period), lobar and segmental PDFF reduction was much less overall (0.4-0.8% PDFF per month) and several pairwise differences were significant; in each case, a right-lobe segment had greater decline than a left-lobe segment. CONCLUSIONS: Baseline and longitudinal changes in fractional fat content in the 5-month postoperative period following WLS vary across segments, with right-lobe segments having higher PDFF at baseline and more rapid reduction in liver fat content. KEY POINTS: • Baseline and longitudinal changes in liver fat following bariatric weight loss surgery vary across liver segments. • Methods that do not provide whole liver fat assessment, such as liver biopsy, may be unreliable in monitoring longitudinal changes in liver fat following weight loss interventions.

MRI proton density fat fraction is robust across the biologically plausible range of triglyceride spectra in adults with nonalcoholic steatohepatitis.

BACKGROUND: Proton density fat fraction (PDFF) estimation requires spectral modeling of the hepatic triglyceride (TG) signal. Deviations in the TG spectrum may occur, leading to bias in PDFF quantification. PURPOSE: To investigate the effects of varying six-peak TG spectral models on PDFF estimation bias. STUDY TYPE: Retrospective secondary analysis of prospectively acquired clinical research data. POPULATION: Forty-four adults with biopsy-confirmed nonalcoholic steatohepatitis. FIELD STRENGTH/SEQUENCE: Confounder-corrected chemical-shift-encoded 3T MRI (using a 2D multiecho gradient-recalled echo technique with magnitude reconstruction) and MR spectroscopy. ASSESSMENT: In each patient, 61 pairs of colocalized MRI-PDFF and MRS-PDFF values were estimated: one pair used the standard six-peak spectral model, the other 60 were six-peak variants calculated by adjusting spectral model parameters over their biologically plausible ranges. MRI-PDFF values calculated using each variant model and the standard model were compared, and the agreement between MRI-PDFF and MRS-PDFF was assessed. STATISTICAL TESTS: MRS-PDFF and MRI-PDFF were summarized descriptively. Bland-Altman (BA) analyses were performed between PDFF values calculated using each variant model and the standard model. Linear regressions were performed between BA biases and mean PDFF values for each variant model, and between MRI-PDFF and MRS-PDFF. RESULTS: Using the standard model, mean MRS-PDFF of the study population was 17.9 ± 8.0% (range: 4.1-34.3%). The difference between the highest and lowest mean variant MRI-PDFF values was 1.5%. Relative to the standard model, the model with the greatest absolute BA bias overestimated PDFF by 1.2%. Bias increased with increasing PDFF (P < 0.0001 for 59 of the 60 variant models). MRI-PDFF and MRS-PDFF agreed closely for all variant models (R2 = 0.980, P < 0.0001). DATA CONCLUSION: Over a wide range of hepatic fat content, PDFF estimation is robust across the biologically plausible range of TG spectra. Although absolute estimation bias increased with higher PDFF, its magnitude was small and unlikely to be clinically meaningful. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:995-1002.

Optimization of region-of-interest sampling strategies for hepatic MRI proton density fat fraction quantification.

BACKGROUND: Clinical trials utilizing proton density fat fraction (PDFF) as an imaging biomarker for hepatic steatosis have used a laborious region-of-interest (ROI) sampling strategy of placing an ROI in each hepatic segment. PURPOSE: To identify a strategy with the fewest ROIs that consistently achieves close agreement with the nine-ROI strategy. STUDY TYPE: Retrospective secondary analysis of prospectively acquired clinical research data. POPULATION: A total of 391 adults (173 men, 218 women) with known or suspected NAFLD. FIELD STRENGTH/SEQUENCE: Confounder-corrected chemical-shift-encoded 3T MRI using a 2D multiecho gradient-recalled echo technique. ASSESSMENT: An ROI was placed in each hepatic segment. Mean nine-ROI PDFF and segmental PDFF standard deviation were computed. Segmental and lobar PDFF were compared. PDFF was estimated using every combinatorial subset of ROIs and compared to the nine-ROI average. STATISTICAL TESTING: Mean nine-ROI PDFF and segmental PDFF standard deviation were summarized descriptively. Segmental PDFF was compared using a one-way analysis of variance, and lobar PDFF was compared using a paired t-test and a Bland-Altman analysis. The PDFF estimated by every subset of ROIs was informally compared to the nine-ROI average using median intraclass correlation coefficients (ICCs) and Bland-Altman analyses. RESULTS: The study population's mean whole-liver PDFF was 10.1 ± 8.9% (range: 1.1-44.1%). Although there was no significant difference in average segmental (P = 0.452) or lobar (P = 0.154) PDFF, left and right lobe PDFF differed by at least 1.5 percentage points in 25.1% (98/391) of patients. Any strategy with ≥4 ROIs had ICC >0.995. 115 of 126 four-ROI strategies (91%) had limits of agreement (LOA) <1.5%, including four-ROI strategies with two ROIs from each lobe, which all had LOA <1.5%. 14/36 (39%) of two-ROI strategies and 74/84 (88%) of three-ROI strategies had ICC >0.995, and 2/36 (6%) of two-ROI strategies and 46/84 (55%) of three-ROI strategies had LOA <1.5%. DATA CONCLUSION: Four-ROI sampling strategies with two ROIs in the left and right lobes achieve close agreement with nine-ROI PDFF. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:988-994.

LI-RADS Version 2018 Ancillary Features at MRI.

The Liver Imaging Reporting and Data System (LI-RADS) standardizes performance of liver imaging in patients at risk for hepatocellular carcinoma (HCC) as well as interpretation and reporting of the results. Developed by experts in liver imaging and supported by the American College of Radiology, LI-RADS assigns to observations categories that reflect the relative probability of benignity, HCC, or other malignancy. While category assignment is based mainly on major imaging features, ancillary features may be applied to improve detection and characterization, increase confidence, or adjust LI-RADS categories. Ancillary features are classified as favoring malignancy in general, HCC in particular, or benignity. Those favoring malignancy in general or HCC in particular may be used to upgrade by a maximum of one category up to LR-4; those favoring benignity may be used to downgrade by a maximum of one category. If there are conflicting ancillary features (ie, one or more favoring malignancy and one or more favoring benignity), the category should not be adjusted. Ancillary features may be seen at diagnostic CT, MRI performed with extracellular agents, or MRI performed with hepatobiliary agents, with the exception of one ancillary feature assessed at US. This article focuses on LI-RADS version 2018 ancillary features seen at MRI. Specific topics include rules for ancillary feature application; definitions, rationale, and illustrations with clinical MRI examples; summary of evidence and diagnostic performance; pitfalls; and future directions. ©RSNA, 2018.

How bariatric surgery affects liver volume and fat density in NAFLD patients.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is an epidemic in the obese population. Bariatric surgery is known to reverse multiple metabolic complications of obesity such as diabetes, dyslipidemia, and NAFLD, but the timing of liver changes has not been well described. MATERIALS AND METHODS: This was an IRB-approved, two-institutional prospective study. Bariatric patients received MRIs at baseline and after a pre-operative liquid diet. Liver biopsies were performed during surgery and if NAFLD positive, the patients received MRIs at 1, 3, and 6 months. Liver volumes and proton-density fat fraction (PDFF) were calculated from offline MRI images. Primary outcomes were changes in weight, body mass index (BMI), percent excess weight loss (EWL%), liver volume, and PDFF. Resolution of steatosis, as defined as PDFF < 6.4% based on previously published cutoffs, was assessed. Secondarily, outcomes were compared between patients who underwent laparoscopic sleeve gastrectomy (LSG) versus laparoscopic Roux-en-Y gastric bypass (LRYGB). RESULTS: From October 2010 to June 2015, 124 patients were recruited. 49 patients (39.5%) completed all five scans. EWL% at 6 months was 55.6 ± 19.0%. BMI decreased from 45.3 ± 5.9 to 34.4 ± 5.1 kg/m2 and mean liver volume decreased from 2464.6 ± 619.4 to 1874.3 ± 387.8 cm3 with a volume change of 21.4 ± 11.4%. PDFF decreased from 16.6 ± 7.8 to 4.4 ± 3.4%. At 6 months, 83.7% patients had resolution of steatosis. Liver volume plateaued at 1 month, but PDFF and BMI continued to decrease. There were no statistically significant differences in liver volume or PDFF reduction from baseline to 6 months between the LSG versus LRYGB subgroups. CONCLUSION: Patients with NAFLD undergoing bariatric surgery can expect significant decreases in liver volume and hepatic steatosis at 6 months, with 83.7% of patients achieving resolution of steatosis. Liver volume reduction plateaus 1-month post-bariatric surgery, but PDFF continues to decrease. LSG and LRYGB did not differ in efficacy for inducing regression of hepatosteatosis.

Accuracy of PDFF estimation by magnitude-based and complex-based MRI in children with MR spectroscopy as a reference.

PURPOSE: To assess and compare the accuracy of magnitude-based magnetic resonance imaging (MRI-M) and complex-based MRI (MRI-C) for estimating hepatic proton density fat fraction (PDFF) in children, using MR spectroscopy (MRS) as the reference standard. A secondary aim was to assess the agreement between MRI-M and MRI-C. MATERIALS AND METHODS: This was a HIPAA-compliant, retrospective analysis of data collected in children enrolled in prospective, Institutional Review Board (IRB)-approved studies between 2012 and 2014. Informed consent was obtained from 200 children (ages 8-19 years) who subsequently underwent 3T MR exams that included MRI-M, MRI-C, and T1 -independent, T2 -corrected, single-voxel stimulated echo acquisition mode (STEAM) MRS. Both MRI methods acquired six echoes at low flip angles. T2*-corrected PDFF parametric maps were generated. PDFF values were recorded from regions of interest (ROIs) drawn on the maps in each of the nine Couinaud segments and three ROIs colocalized to the MRS voxel location. Regression analyses assessing agreement with MRS were performed to evaluate the accuracy of each MRI method, and Bland-Altman and intraclass correlation coefficient (ICC) analyses were performed to assess agreement between the MRI methods. RESULTS: MRI-M and MRI-C PDFF were accurate relative to the colocalized MRS reference standard, with regression intercepts of 0.63% and -0.07%, slopes of 0.998 and 0.975, and proportion-of-explained-variance values (R2 ) of 0.982 and 0.979, respectively. For individual Couinaud segments and for the whole liver averages, Bland-Altman biases between MRI-M and MRI-C were small (ranging from 0.04 to 1.11%) and ICCs were high (≥0.978). CONCLUSION: Both MRI-M and MRI-C accurately estimated hepatic PDFF in children, and high intermethod agreement was observed. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1641-1647.

2017 Version of LI-RADS for CT and MR Imaging: An Update.

The Liver Imaging Reporting and Data System (LI-RADS) is a reporting system created for the standardized interpretation of liver imaging findings in patients who are at risk for hepatocellular carcinoma (HCC). This system was developed with the cooperative and ongoing efforts of an American College of Radiology-supported committee of diagnostic radiologists with expertise in liver imaging and valuable input from hepatobiliary surgeons, hepatologists, hepatopathologists, and interventional radiologists. In this article, the 2017 version of LI-RADS for computed tomography and magnetic resonance imaging is reviewed. Specific topics include the appropriate population for application of LI-RADS; technical recommendations for image optimization, including definitions of dynamic enhancement phases; diagnostic and treatment response categories; definitions of major and ancillary imaging features; criteria for distinguishing definite HCC from a malignancy that might be non-HCC; management options following LI-RADS categorization; and reporting. ©RSNA, 2017.

Magnetic resonance imaging and liver histology as biomarkers of hepatic steatosis in children with nonalcoholic fatty liver disease.

UNLABELLED: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children. In order to advance the field of NAFLD, noninvasive imaging methods for measuring liver fat are needed. Advanced magnetic resonance imaging (MRI) has shown great promise for the quantitative assessment of hepatic steatosis but has not been validated in children. Therefore, this study was designed to evaluate the correlation and diagnostic accuracy of MRI-estimated liver proton density fat fraction (PDFF), a biomarker for hepatic steatosis, compared to histologic steatosis grade in children. The study included 174 children with a mean age of 14.0 years. Liver PDFF estimated by MRI was significantly (P < 0.01) correlated (0.725) with steatosis grade. The correlation of MRI-estimated liver PDFF and steatosis grade was influenced by both sex and fibrosis stage. The correlation was significantly (P < 0.01) stronger in girls (0.86) than in boys (0.70). The correlation was significantly (P < 0.01) weaker in children with stage 2-4 fibrosis (0.61) than children with no fibrosis (0.76) or stage 1 fibrosis (0.78). The diagnostic accuracy of commonly used threshold values to distinguish between no steatosis and mild steatosis ranged from 0.69 to 0.82. The overall accuracy of predicting the histologic steatosis grade from MRI-estimated liver PDFF was 56%. No single threshold had sufficient sensitivity and specificity to be considered diagnostic for an individual child. CONCLUSIONS: Advanced magnitude-based MRI can be used to estimate liver PDFF in children, and those PDFF values correlate well with steatosis grade by liver histology. Thus, magnitude-based MRI has the potential for clinical utility in the evaluation of NAFLD, but at this time no single threshold value has sufficient accuracy to be considered diagnostic for an individual child.

In vivo breath-hold (1) H MRS simultaneous estimation of liver proton density fat fraction, and T1 and T2 of water and fat, with a multi-TR, multi-TE sequence.

PURPOSE: To examine the intra-examination repeatability of proton density fat fraction (PDFF) and T1 and T2 of liver water and fat as estimated by a novel multi-repetition time (TR)-echo time (TE) (1) H magnetic resonance spectroscopy (MRS)-stimulated echo acquisition mode (STEAM) sequence that acquires 32 spectra for a range of TRs and TEs in single breath-hold. MATERIALS AND METHODS: Sixty-seven subjects undergoing liver MRI examinations at 3T had three multi-TR-TE sequences acquired consecutively in a single session. This sequence was designed to allow accurate estimation of T1 and T2 of both water and fat, as well as PDFF, in a single breath-hold. A standard long-TR, multi-TE sequence was also acquired to allow comparison of estimated PDFF. Regression and interclass correlation (ICC) analyses were performed. RESULTS: There was strong agreement between PDFF estimated by the multi-TR-TE and long-TR, multi-TE sequences (slope 0.997; intercept -0.03; R = 0.997). The multi-TR-TE sequence had high repeatability for estimating PDFF (ICC = 0.999), water T2 (ICC = 0.920), water T1 (ICC = 0.845), and fat T2 (ICC = 0.760), and moderate repeatability for estimating fat T1 (ICC = 0.556). CONCLUSION: A novel multi-TR-TE sequence can estimate PDFF and water and fat T1 and T2 in a single breath-hold. Refinement may be needed to improve repeatability for fat T1 estimation.

Accuracy of multiecho magnitude-based MRI (M-MRI) for estimation of hepatic proton density fat fraction (PDFF) in children.

PURPOSE: To assess accuracy of magnitude-based magnetic resonance imaging (M-MRI) in children to estimate hepatic proton density fat fraction (PDFF) using two to six echoes, with magnetic resonance spectroscopy (MRS) -measured PDFF as a reference standard. METHODS: This was an IRB-approved, HIPAA-compliant, single-center, cross-sectional, retrospective analysis of data collected prospectively between 2008 and 2013 in children with known or suspected nonalcoholic fatty liver disease (NAFLD). Two hundred eighty-six children (8-20 [mean 14.2 ± 2.5] years; 182 boys) underwent same-day MRS and M-MRI. Unenhanced two-dimensional axial spoiled gradient-recalled-echo images at six echo times were obtained at 3T after a single low-flip-angle (10°) excitation with ≥ 120-ms recovery time. Hepatic PDFF was estimated using the first two, three, four, five, and all six echoes. For each number of echoes, accuracy of M-MRI to estimate PDFF was assessed by linear regression with MRS-PDFF as reference standard. Accuracy metrics were regression intercept, slope, average bias, and R(2) . RESULTS: MRS-PDFF ranged from 0.2-40.4% (mean 13.1 ± 9.8%). Using three to six echoes, regression intercept, slope, and average bias were 0.46-0.96%, 0.99-1.01, and 0.57-0.89%, respectively. Using two echoes, these values were 2.98%, 0.97, and 2.72%, respectively. R(2) ranged 0.98-0.99 for all methods. CONCLUSION: Using three to six echoes, M-MRI has high accuracy for hepatic PDFF estimation in children.

Intra- and inter-examination repeatability of magnetic resonance spectroscopy, magnitude-based MRI, and complex-based MRI for estimation of hepatic proton density fat fraction in overweight and obese children and adults.

PURPOSE: Determine intra- and inter-examination repeatability of magnitude-based magnetic resonance imaging (MRI-M), complex-based magnetic resonance imaging (MRI-C), and magnetic resonance spectroscopy (MRS) at 3T for estimating hepatic proton density fat fraction (PDFF), and using MRS as a reference, confirm MRI-M and MRI-C accuracy. METHODS: Twenty-nine overweight and obese pediatric (n = 20) and adult (n = 9) subjects (23 male, 6 female) underwent three same-day 3T MR examinations. In each examination MRI-M, MRI-C, and single-voxel MRS were acquired three times. For each MRI acquisition, hepatic PDFF was estimated at the MRS voxel location. Intra- and inter-examination repeatability were assessed by computing standard deviations (SDs) and intra-class correlation coefficients (ICCs). Aggregate SD was computed for each method as the square root of the average of first repeat variances. MRI-M and MRI-C PDFF estimation accuracy was assessed using linear regression with MRS as a reference. RESULTS: For MRI-M, MRI-C, and MRS acquisitions, respectively, mean intra-examination SDs were 0.25%, 0.42%, and 0.49%; mean intra-examination ICCs were 0.999, 0.997, and 0.995; mean inter-examination SDs were 0.42%, 0.45%, and 0.46%; and inter-examination ICCs were 0.995, 0.992, and 0.990. Aggregate SD for each method was <0.9%. Using MRS as a reference, regression slope, intercept, average bias, and R (2), respectively, for MRI-M were 0.99%, 1.73%, 1.61%, and 0.986, and for MRI-C were 0.96%, 0.43%, 0.40%, and 0.991. CONCLUSION: MRI-M, MRI-C, and MRS showed high intra- and inter-examination hepatic PDFF estimation repeatability in overweight and obese subjects. Longitudinal hepatic PDFF change >1.8% (twice the maximum aggregate SD) may represent real change rather than measurement imprecision. Further research is needed to assess whether examinations performed on different days or with different MR technologists affect repeatability of MRS voxel placement and MRS-based PDFF measurements.

Feasibility of and agreement between MR imaging and spectroscopic estimation of hepatic proton density fat fraction in children with known or suspected nonalcoholic fatty liver disease.

PURPOSE: To assess feasibility of and agreement between magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) for estimating hepatic proton density fat fraction (PDFF) in children with known or suspected nonalcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS: Children were included in this study from two previous research studies in each of which three MRI and three MRS acquisitions were obtained. Sequence acceptability, and MRI- and MRS-estimated PDFF were evaluated. Agreement of MRI- with MRS-estimated hepatic PDFF was assessed by linear regression and Bland-Altman analysis. Age, sex, BMI-Z score, acquisition time, and artifact score effects on MRI- and MRS-estimated PDFF agreement were assessed by multiple linear regression. RESULTS: Eighty-six children (61 boys and 25 girls) were included in this study. Slope and intercept from regressing MRS-PDFF on MRI-PDFF were 0.969 and 1.591%, respectively, and the Bland-Altman bias and 95% limits of agreement were 1.17% ± 2.61%. MRI motion artifact score was higher in boys than girls (by 0.21, p = 0.021). Higher BMI-Z score was associated with lower agreement between MRS and MRI (p = 0.045). CONCLUSION: Hepatic PDFF estimation by both MRI and MRS is feasible, and MRI- and MRS-estimated PDFF agree closely in children with known or suspected NAFLD.

Inter-reader agreement of magnetic resonance imaging proton density fat fraction and its longitudinal change in a clinical trial of adults with nonalcoholic steatohepatitis.

PURPOSE: To determine the inter-reader agreement of magnetic resonance imaging proton density fat fraction (PDFF) and its longitudinal change in a clinical trial of adults with nonalcoholic steatohepatitis (NASH). STUDY TYPE: We performed a secondary analysis of a placebo-controlled randomized clinical trial of a bile acid sequestrant in 45 adults with NASH. A six-echo spoiled gradient-recalled-echo magnitude-based fat quantification technique was performed at 3 T. Three independent readers measured MRI-PDFF by placing one primary and two additional regions of interest (ROIs) in each segment at both time points. Cross-sectional agreement between the three readers was evaluated using intra-class correlation coefficients (ICCs) and coefficients of variation (CV). Additionally, we used Bland-Altman analyses to examine pairwise agreement between the three readers at baseline, end of treatment (EOT), and for longitudinal change. RESULTS: Using all ROIs by all readers, mean PDFF at baseline, at EOT, and mean change in PDFF was 16.1%, 16.0%, and 0.07%, respectively. The 27-ROI PDFF measurements had 0.998 ICC and 1.8% CV at baseline, 0.998 ICC and 1.8% CV at EOT, and 0.997 ICC for longitudinal change. The 9-ROI PDFF measurements had corresponding values of 0.997 and 2.6%, 0.996 and 2.4%, and 0.994. Using 27 ROIs, the magnitude of the bias between readers for whole-liver PDFF measurement ranged from 0.03% to 0.06% points at baseline, 0.01% to 0.07% points at EOT, and 0.01% to 0.02% points for longitudinal change. CONCLUSION: Inter-reader agreement for measuring whole-liver PDFF and its longitudinal change is high. 9-ROI measurements have only slightly lower agreement than 27-ROI measurements.

Measurement of spleen fat on MRI-proton density fat fraction arises from reconstruction of noise.

PURPOSE: This study compares splenic proton density fat fraction (PDFF) measured using confounder-corrected chemical shift-encoded (CSE)-MRI to magnetic resonance spectroscopy (MRS) in human patients at 3T. METHODS: This was a prospectively designed ancillary study to various previously described single-center studies performed in adults and children with known or suspected nonalcoholic fatty liver disease. Patients underwent magnitude-based MRI (MRI-M), complex-based MRI (MRI-C), high signal-to-noise variants (Hi-SNR MRI-M and Hi-SNR MRI-C), and MRS at 3T for spleen PDFF estimation. PDFF from CSE-MRI methods were compared to MRS-PDFF using Wilcoxon signed-rank tests. Demographics were summarized descriptively. Spearman's rank correlations were computed pairwise between CSE-MRI methods. Individual patient measurements were plotted for qualitative assessment. A significance level of 0.05 was used. RESULTS: Forty-seven patients (20 female, 27 male) including 12 adults (median 55 years old) and 35 children (median 12 years old). Median PDFF estimated by MRS, MRI-M, Hi-SNR MRI-M, MRI-C, and Hi-SNR MRI-C was 1.0, 2.3, 1.9, 2.2, and 2.0%. The four CSE-MRI methods estimated statistically significant higher spleen PDFF values compared to MRS (p < 0.0001 for all). Pairwise associations in spleen PDFF values measured by different CSE-MRI methods were weak, with the highest Spearman's rank correlations being 0.295 between MRI-M and Hi-SNR MRI-M; none were significant after correction for multiple comparisons. No qualitative relationship was observed between PDFF measurements among the various methods. CONCLUSION: Overestimation of PDFF by CSE-MRI compared to MRS and poor agreement between related CSE-MRI methods suggest that non-zero PDFF values in human spleen are artifactual.

Technical report: gadoxetate-disodium-enhanced 2D R2* mapping: a novel approach for assessing bile ducts in living donors.

PURPOSE: Gadoxetate-disodium (Gd-EOB-DTPA)-enhanced 3D T1- weighted (T1w) MR cholangiography (MRC) is an efficient method to evaluate biliary anatomy due to T1 shortening of excreted contrast in the bile. A method that exploits both T1 shortening and T2* effects may produce even greater bile duct conspicuity. The aim of our study is to determine feasibility and compare the diagnostic performance of two-dimensional (2D) T1w multi-echo (ME) spoiled gradient-recalled-echo (SPGR) derived R2* maps against T1w MRC for bile duct visualization in living liver donor candidates. MATERIALS AND METHODS: Ten potential living liver donor candidates underwent pretransplant 3T MRI and were included in our study. Following injection of Gd-EOBDTPA and a 20-min delay, 3D T1w MRC and 2D T1w ME SPGR images were acquired. 2D R2* maps were generated inline by the scanner assuming exponential decay. The 3D T1w MRC and 2D R2* maps were retrospectively and independently reviewed in two separate sessions by three radiologists. Visualization of eight bile duct segments was scored using a 4-point ordinal scale. The scores were compared using mixed effects regression model. RESULTS: Imaging was tolerated by all donors and R2* maps were successfully generated in all cases. Visualization scores of 2D R2* maps were significantly higher than 3D T1w MRC for right anterior (p = 0.003) and posterior (p = 0.0001), segment 2 (p < 0.0001), segment 3 (p = 0.0001), and segment 4 (p < 0.0001) ducts. CONCLUSIONS: Gd-EOB-DTPA-enhanced 2D R2* mapping is a feasible method for evaluating the bile ducts in living donors and may be a valuable addition to the living liver donor MR protocol for delineating intrahepatic biliary anatomy.