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.

Repeatability and accuracy of various region-of-interest sampling strategies for hepatic MRI proton density fat fraction quantification.

PURPOSE: To evaluate repeatability of ROI-sampling strategies for quantifying hepatic proton density fat fraction (PDFF) and to assess error relative to the 9-ROI PDFF. METHODS: This was a secondary analysis in subjects with known or suspected nonalcoholic fatty liver disease who underwent MRI for magnitude-based hepatic PDFF quantification. Each subject underwent three exams, each including three acquisitions (nine acquisitions total). An ROI was placed in each hepatic segment on the first acquisition of the first exam and propagated to other acquisitions. PDFF was calculated for each of 511 sampling strategies using every combination of 1, 2, …, all 9 ROIs. Intra- and inter-exam intra-class correlation coefficients (ICCs) and repeatability coefficients (RCs) were estimated for each sampling strategy. Mean absolute error (MAE) was estimated relative to the 9-ROI PDFF. Strategies that sampled both lobes evenly ("balanced") were compared with those that did not ("unbalanced") using two-sample t tests. RESULTS: The 29 enrolled subjects (23 male, mean age 24 years) had mean 9-ROI PDFF 11.8% (1.1-36.3%). With more ROIs, ICCs increased, RCs decreased, and MAE decreased. Of the 60 balanced strategies with 4 ROIs, all (100%) achieved inter- and intra-exam ICCs > 0.998, 55 (92%) achieved intra-exam RC < 1%, 50 (83%) achieved inter-exam RC < 1%, and all (100%) achieved MAE < 1%. Balanced sampling strategies had higher ICCs and lower RCs, and lower MAEs than unbalanced strategies in aggregate (p < 0.001 for comparisons between balanced vs. unbalanced strategies). CONCLUSION: Repeatability improves and error diminishes with more ROIs. Balanced 4-ROI strategies provide high repeatability and low error.

Examining LI-RADS recommendations: should observation size only be measured on non-arterial phases?

OBJECTIVE: To investigate if size measurements of liver observations is more variable in the arterial phase as suggested by LI-RADS and assess potential higher instability in categorization in this particular phase. Secondarily, to assess inter- and intra-reader agreement for size across phases. MATERIALS AND METHODS: Patients with liver cirrhosis who underwent multi-arterial phase MRI between 2017 and 2018 were retrospectively selected. Three radiologists measured liver observations in each phase, independently, in a random order. Mean size between early and late arterial phases (AP), 2, 3 and 10 min delay and the number of observations crossing the LI-RADS size thresholds (10 and 20 mm) per phase were compared using McNemar's test. Reader agreement was evaluated using intraclass correlation coefficient (ICC) and bootstrap-based comparisons. Bonferroni's correction was applied to pairwise comparisons. RESULTS: 94 observations (LR-3, LR-4, LR-5, and LR-M) were included. Mean sizes (mm) were late AP: 19.9 (95% CI 17.2, 24.2), 2 min delay: 19.8 (95% CI 17.1, 24.0), 3 min delay: 19.8 (95% CI 17.2, 24.0), 10 min delay: 20.2 (95% CI 17.5, 24.5) (p = 0.10-0.88). There was no difference between phases in number of observations that could have changed category due to variability in size (p = 0.546-1.000). Inter- and intra-reader agreement was excellent (ICC = 0.952-0.981). CONCLUSION: Measurements of focal liver observations were consistent across all post-contrast imaging phases and we found no higher instability in LI-RADS category in any particular phase. Inter- and intra-reader agreement for size was excellent for each phase. Based on these findings, size measurement could be allowed on any post-contrast phase, including the arterial phase, if deemed appropriate by the radiologist.

A Comparison of E-Cigarette Use Patterns and Smoking Cessation Behavior among Vapers by Primary Place of Purchase.

BACKGROUND: E-cigarettes are purchased through multiple channels, including general retail, online, and specialty smoke and vape shops. We examine how e-cigarette users' primary purchase place relates to e-cigarette use and smoking cessation behaviors. METHODS: Probability-based samples of the U.S. population who were current e-cigarette users were surveyed in 2014 (N = 879) and 2016 (N = 743), with responses combined for most analyses. E-cigarette use and smoking cessation behaviors were compared across users' primary purchase place. RESULTS: Higher percentages of vape shop (59.1%) and internet (42.9%) customers were current daily users of e-cigarettes compared to retail (19.7%) and smoke shop (23.2%) customers (p-values < 0.001). Higher percentages of vape shop (40.2%) and internet (35.1%) customers were also former smokers, compared to 17.7% of retail and 19.3% of smoke shop customers (p's < 0.001). Among those smoking 12 months prior to survey, smoking cessation rates were higher for vape shop (22.2%) and internet customers (22.5%) than for retail customers (10.7%, p = 0.010 and p = 0.022, respectively), even though retail customers were more likely to use FDA-approved smoking cessation aids. The percentage of customers purchasing from vape shops increased from 20.4% in 2014 to 37.6% in 2016, surpassing general retail (27.7%) as the most likely channel in 2016. CONCLUSIONS: E-cigarette customers differed in significant ways by channels of purchase, most notably in their smoking cessation behaviors. Previous population studies have relied mostly on retail channel data, which accounted for less than 30% of all products sold by 2016. Future studies of e-cigarette use should consider a broader set of channels.

Treating hyperglycemia in early pregnancy: a randomized controlled trial.

BACKGROUND: Treating women with gestational diabetes mellitus in the third trimester improves perinatal outcomes. It is unknown whether treating women with mild glucose intolerance earlier in pregnancy would be beneficial in the reduction of maternal and neonatal morbidities. OBJECTIVE: In women with hyperglycemia (hemoglobin A1c ≥5.7% and/or fasting glucose ≥92 mg/dL) in early pregnancy, we sought to determine whether immediate treatment improved maternal and neonatal outcomes. STUDY DESIGN: This unblinded randomized controlled trial enrolled women with hyperglycemia at ≤15+0 weeks gestation between 2013 and 2015. Participants were assigned randomly to early pregnancy or third-trimester treatment of hyperglycemia that included nutrition counseling, glucose monitoring, and medications as needed. Participants underwent a blinded 2-hour glucose tolerance test at 24-28 weeks gestation. Exclusion criteria were pregestational diabetes mellitus and multiple gestations. The primary outcome was the proportion of infants with neonatal umbilical cord C-peptide >1.77 nmoL (90th percentile). Secondary outcomes were neonatal fat mass, infant World Health Organization weight-for-length percentile at birth, maternal gestational weight gain, and diagnosis of gestational diabetes mellitus on glucose tolerance test. Mann-Whitney-Wilcoxon test and Fisher's exact test were used, as appropriate. RESULTS: A total of 202 women were assigned randomly; 45 women dropped out before delivery, which left cases 157 for analysis (82 with early pregnancy and 75 with third-trimester treatment). The trial was terminated early because of low enrollment. Baseline characteristics were similar between groups. There was no difference in C-peptide >90th percentile between groups (1 [1.5%] vs 4 [6.7%]; P=.19) in the early pregnancy and third-trimester groups, respectively). There was also no difference in fat mass (0.37±0.16 vs 0.36±0.17 kg; P=.91), weight-for-length percentile at birth (25% vs 25%; P=.46), or macrosomia (1.5 vs 5.0%; P=.84). Maternal gestational weight gain was 22.6±12.9 lb and 23.9±11.2 lb in the early pregnancy and third-trimester groups, respectively (P=.88). Gestational diabetes mellitus was diagnosed in 19.0% of the cohort and did not differ between groups (14.2% vs 25.8%; P=.17). CONCLUSION: In this population of women with hyperglycemia, treatment in early pregnancy did not appear to improve maternal or neonatal outcomes significantly. Given comparable results in both groups, caution should be used in the initiation of an intensive diabetes mellitus treatment protocol for women with the diagnosis of hyperglycemia in early gestation.

Hepatic R2* is more strongly associated with proton density fat fraction than histologic liver iron scores in patients with nonalcoholic fatty liver disease.

BACKGROUND: The liver R2* value is widely used as a measure of liver iron but may be confounded by the presence of hepatic steatosis and other covariates. PURPOSE: To identify the most influential covariates for liver R2* values in patients with nonalcoholic fatty liver disease (NAFLD). STUDY TYPE: Retrospective analysis of prospectively acquired data. POPULATION: Baseline data from 204 subjects enrolled in NAFLD/NASH (nonalcoholic steatohepatitis) treatment trials. FIELD STRENGTH: 1.5T and 3T; chemical-shift encoded multiecho gradient echo. ASSESSMENT: Correlation between liver proton density fat fraction and R2*; assessment for demographic, metabolic, laboratory, MRI-derived, and histological covariates of liver R2*. STATISTICAL TESTS: Pearson's and Spearman's correlations; univariate analysis; gradient boosting machines (GBM) multivariable machine-learning method. RESULTS: Hepatic proton density fat fraction (PDFF) was the most strongly correlated covariate for R2* at both 1.5T (r = 0.652, P < 0.0001) and at 3T (r = 0.586, P < 0.0001). In the GBM analysis, hepatic PDFF was the most influential covariate for hepatic R2*, with relative influences (RIs) of 61.3% at 1.5T and 47.5% at 3T; less influential covariates had RIs of up to 11.5% at 1.5T and 16.7% at 3T. Nonhepatocellular iron was weakly associated with R2* at 3T only (RI 6.7%), and hepatocellular iron was not associated with R2* at either field strength. DATA CONCLUSION: Hepatic PDFF is the most influential covariate for R2* at both 1.5T and 3T; nonhepatocellular iron deposition is weakly associated with liver R2* at 3T only. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1456-1466.

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.

Monitoring Fatty Liver Disease with MRI Following Bariatric Surgery: A Prospective, Dual-Center Study.

Purpose To longitudinally monitor liver fat before and after bariatric surgery by using quantitative chemical shift-encoded (CSE) MRI and to compare with changes in body mass index (BMI), weight, and waist circumference (WC). Materials and Methods For this prospective study, which was approved by the internal review board, a total of 126 participants with obesity who were undergoing evaluation for bariatric surgery with preoperative very low calorie diet (VLCD) were recruited from June 27, 2010, through May 5, 2015. Written informed consent was obtained from all participants. Participants underwent CSE MRI measuring liver proton density fat fraction (PDFF) before VLCD (2-3 weeks before surgery), after VLCD (1-3 days before surgery), and 1, 3, and 6-10 months following surgery. Linear regression was used to estimate rates of change of PDFF (ΔPDFF) and body anthropometrics. Initial PDFF (PDFF0), initial anthropometrics, and anthropometric rates of change were evaluated as predictors of ΔPDFF. Mixed-effects regression was used to estimate time to normalization of PDFF. Results Fifty participants (mean age, 51.0 years; age range, 27-70 years), including 43 women (mean age, 50.8 years; age range, 27-70 years) and seven men (mean age, 51.7 years; age range, 36-62 years), with mean PDFF0 ± standard deviation of 18.1% ± 8.6 and mean BMI0 of 44.9 kg/m2 ± 6.5 completed the study. By 6-10 months following surgery, mean PDFF decreased to 4.9% ± 3.4 and mean BMI decreased to 34.5 kg/m2 ± 5.4. Mean estimated time to PDFF normalization was 22.5 weeks ± 11.5. PDFF0 was the only strong predictor for both ΔPDFF and time to PDFF normalization. No body anthropometric correlated with either outcome. Conclusion Average liver proton density fat fraction (PDFF) decreased to normal (< 5%) by 6-10 months following surgery, with mean time to normalization of approximately 5 months. Initial PDFF was a strong predictor of both rate of change of PDFF and time to normalization. Body anthropometrics did not predict either outcome. Online supplemental material is available for this article. © RSNA, 2018.

Evaluation of the Tobacco-Use Prevention Education (TUPE) program in California.

BACKGROUND AND AIMS: The California Tobacco-Use Prevention Education (TUPE) program promotes the use of evidence-based tobacco-specific prevention and cessation programs for adolescents within the school setting. Through a competitive grant process, schools are funded to provide programs for grades 6-12. This research evaluates the association between TUPE funding and tobacco prevention activities and tobacco use prevalence. METHODS: This study utilized two data sources: (1) 2016 California Educator Tobacco Survey (CETS), and (2) 2015-2016 California Student Tobacco Survey (CSTS). The CETS collected data from educators about school prevention efforts, priority of tobacco prevention, and confidence in addressing tobacco issues with students. A total of 3,564 educators from 590 schools participated in CETS. The CSTS collected data from 8th, 10th, and 12th graders in California on their exposure to, attitudes about, and utilization of tobacco products. A total of 47,981 students from 117 schools participated in CSTS. RESULTS: This study found that TUPE-funded schools were more likely to provide tobacco-specific health education programs, to place a priority on tobacco-prevention efforts, and to prepare educators to address tobacco use than non-TUPE schools. Educators at both types of schools felt better prepared to talk with students about traditional tobacco products than about emerging products such as e-cigarettes. Overall, students at TUPE-funded schools were more likely to report receiving anti-tobacco messages from school-based programs than those at non-TUPE schools. The former were also less likely to use tobacco products, even when the analysis controlled for demographics and school-level characteristics (OR = 0.82 [95% CI = 0.70-0.96]). CONCLUSIONS: TUPE funding was associated with an increase in schools' tobacco-specific prevention activities and these enhanced activities were associated with lower tobacco use among students. This study also found that education and prevention efforts regarding emerging tobacco products need to be strengthened across all schools.

Incentives and Patches for Medicaid Smokers: An RCT.

INTRODUCTION: Most successful trials of financial incentives for smoking cessation have offered large rewards contingent on outcomes. This study examines whether more modest incentives to encourage engagement, non-contingent on outcomes, also increase cessation; whether sending medications directly to participants boosts quitting; and whether these strategies are effective in Medicaid. STUDY DESIGN: Three-group RCT of usual care (UC); nicotine patch (NP); and NP and financial incentive (NP+FI). SETTING/PARTICIPANTS: Medicaid beneficiaries calling the California Smokers' Helpline, 2012-2013 (N=3,816). Data were analyzed in 2017. INTERVENTION: All participants enrolled in evidence-based, multisession telephone counseling. All received proof of enrollment with which they could obtain free quitting aids at their pharmacy. NP and NP+FI also received nicotine patches sent to their homes. NP+FI received up to $60 for completing counseling calls. MAIN OUTCOME MEASURES: Quit attempt rate, 7-day and 30-day abstinence at 2 and 7 months, and 6-month prolonged abstinence (primary outcome). RESULTS: In both complete-case and intention-to-treat analyses, outcomes trended upward from UC to NP to NP+FI. Differences between NP and UC were generally nonsignificant. By contrast, the NP+FI group significantly outperformed the other groups on all measures. In intention-to-treat analysis, compared with UC, NP+FI was more likely to make a quit attempt (68.4% vs 54.3%, p<0.001); be abstinent for 7 days at 2 months (36.1% vs 25.5%, p<0.001) and 7 months (21.2% vs 16.1%, p=0.002); be abstinent for 30 days at 2 months (30.0% vs 18.9%, p<0.001) and 7 months (21.5% vs 16.7%, p=0.004); and achieve 6-month prolonged abstinence (13.2% vs 9.0%, p=0.001). CONCLUSIONS: Financial incentives increased treatment engagement and short- and long-term smoking cessation, despite being modest and non-contingent on outcomes. The study found that incentives can be effective in a Medicaid population, and can feasibly be integrated into existing quitline services. TRIAL REGISTRATION: The trial is registered at www.clinicaltrials.gov NCT01502306. SUPPLEMENT INFORMATION: This article is part of a supplement entitled Advancing Smoking Cessation in California's Medicaid Population, which is sponsored by the California Department of Public Health.

Fibrinogen and the prediction of residual obstruction manifested after pulmonary embolism treatment.

Residual pulmonary vascular obstruction (RPVO) and chronic thromboembolic pulmonary hypertension (CTEPH) are both long-term complications of acute pulmonary embolism, but it is unknown whether RPVO can be predicted by variants of fibrinogen associated with CTEPH.We used the Akaike information criterion to select the best predictive models for RPVO in two prospectively followed cohorts of acute pulmonary embolism patients, using as candidate variables the extent of the initial obstruction, clinical characteristics and fibrinogen-related data. We measured the selected models' goodness of fit by analysis of deviance and compared models using the Chi-squared test.RPVO occurred in 29 (28.4%) out of 102 subjects in the first cohort and 46 (25.3%) out of 182 subjects in the second. The best-fit predictive model derived in the first cohort (p=0.0002) and validated in the second cohort (p=0.0005) implicated fibrinogen Bß-chain monosialylation in the development of RPVO. When the derivation procedure excluded clinical characteristics, fibrinogen Bß-chain monosialylation remained a predictor of RPVO in the best-fit predictive model (p=0.00003). Excluding fibrinogen characteristics worsened the predictive model (p=0.03).Fibrinogen Bß-chain monosialylation, a common structural attribute of fibrin, helped predict RPVO after acute pulmonary embolism. Fibrin structure may contribute to the risk of developing RPVO.

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.

Interreader Reliability of LI-RADS Version 2014 Algorithm and Imaging Features for Diagnosis of Hepatocellular Carcinoma: A Large International Multireader Study.

Purpose To determine in a large multicenter multireader setting the interreader reliability of Liver Imaging Reporting and Data System (LI-RADS) version 2014 categories, the major imaging features seen with computed tomography (CT) and magnetic resonance (MR) imaging, and the potential effect of reader demographics on agreement with a preselected nonconsecutive image set. Materials and Methods Institutional review board approval was obtained, and patient consent was waived for this retrospective study. Ten image sets, comprising 38-40 unique studies (equal number of CT and MR imaging studies, uniformly distributed LI-RADS categories), were randomly allocated to readers. Images were acquired in unenhanced and standard contrast material-enhanced phases, with observation diameter and growth data provided. Readers completed a demographic survey, assigned LI-RADS version 2014 categories, and assessed major features. Intraclass correlation coefficient (ICC) assessed with mixed-model regression analyses was the metric for interreader reliability of assigning categories and major features. Results A total of 113 readers evaluated 380 image sets. ICC of final LI-RADS category assignment was 0.67 (95% confidence interval [CI]: 0.61, 0.71) for CT and 0.73 (95% CI: 0.68, 0.77) for MR imaging. ICC was 0.87 (95% CI: 0.84, 0.90) for arterial phase hyperenhancement, 0.85 (95% CI: 0.81, 0.88) for washout appearance, and 0.84 (95% CI: 0.80, 0.87) for capsule appearance. ICC was not significantly affected by liver expertise, LI-RADS familiarity, or years of postresidency practice (ICC range, 0.69-0.70; ICC difference, 0.003-0.01 [95% CI: -0.003 to -0.01, 0.004-0.02]. ICC was borderline higher for private practice readers than for academic readers (ICC difference, 0.009; 95% CI: 0.000, 0.021). Conclusion ICC is good for final LI-RADS categorization and high for major feature characterization, with minimal reader demographic effect. Of note, our results using selected image sets from nonconsecutive examinations are not necessarily comparable with those of prior studies that used consecutive examination series. © RSNA, 2017.

Magnetic resonance elastography measured shear stiffness as a biomarker of fibrosis in pediatric nonalcoholic fatty liver disease.

Magnetic resonance elastography (MRE) is a promising technique for noninvasive assessment of fibrosis, a major determinant of outcome in nonalcoholic fatty liver disease (NAFLD). However, data in children are limited. The purpose of this study was to determine the accuracy of MRE for the detection of fibrosis and advanced fibrosis in children with NAFLD and to assess agreement between manual and novel automated reading methods. We performed a prospective, multicenter study of two-dimensional (2D) MRE in children with NAFLD. MR elastograms were analyzed manually at two reading centers, and using a new automated technique. Analysis using each approach was done independently. Correlations were determined between MRE analysis methods and fibrosis stage. Thresholds for classifying the presence of fibrosis and of advanced fibrosis were computed and cross-validated. In 90 children with a mean age of 13.1 ± 2.4 years, median hepatic stiffness was 2.35 kPa. Stiffness values derived by each reading center were strongly correlated with each other (r = 0.83). All three analyses were significantly correlated with fibrosis stage (center 1, ρ = 0.53; center 2, ρ = 0.55; and automated analysis, ρ = 0.52; P < 0.001). Overall cross-validated accuracy for detecting any fibrosis was 72.2% for all methods (95% confidence interval [CI], 61.8%-81.1%). Overall cross-validated accuracy for assessing advanced fibrosis was 88.9% (95% CI, 80.5%-94.5%) for center 1, 90.0% (95% CI, 81.9%-95.3%) for center 2, and 86.7% (95% CI, 77.9%-92.9%) for automated analysis. CONCLUSION: 2D MRE can estimate hepatic stiffness in children with NAFLD. Further refinement and validation of automated analysis techniques will be an important step in standardizing MRE. How to best integrate MRE into clinical protocols for the assessment of NAFLD in children will require prospective evaluation. (Hepatology 2017;66:1474-1485).

Smoking prevalence in Medicaid has been declining at a negligible rate.

BACKGROUND: In recent decades the overall smoking prevalence in the US has fallen steadily. This study examines whether the same trend is seen in the Medicaid population. METHODS AND FINDINGS: National Health Interview Survey (NHIS) data from 17 consecutive annual surveys from 1997 to 2013 (combined N = 514,043) were used to compare smoking trends for 4 insurance groups: Medicaid, the Uninsured, Private Insurance, and Other Coverage. Rates of chronic disease and psychological distress were also compared. RESULTS: Adjusted smoking prevalence showed no detectable decline in the Medicaid population (from 33.8% in 1997 to 31.8% in 2013, trend test P = 0.13), while prevalence in the other insurance groups showed significant declines (38.6%-34.7% for the Uninsured, 21.3%-15.8% for Private Insurance, and 22.6%-16.8% for Other Coverage; all P's<0.005). Among individuals who have ever smoked, Medicaid recipients were less likely to have quit (38.8%) than those in Private Insurance (62.3%) or Other Coverage (69.8%; both P's<0.001). Smokers in Medicaid were more likely than those in Private Insurance and the Uninsured to have chronic disease (55.0% vs 37.3% and 32.4%, respectively; both P's<0.01). Smokers in Medicaid were also more likely to experience severe psychological distress (16.2% for Medicaid vs 3.2% for Private Insurance and 7.6% for the Uninsured; both P's<0.001). CONCLUSIONS: The high and relatively unchanging smoking prevalence in the Medicaid population, low quit ratio, and high rates of chronic disease and severe psychological distress highlight the need to focus on this population. A targeted and sustained campaign to help Medicaid recipients quit smoking is urgently needed.

A Pilot Comparative Study of Quantitative Ultrasound, Conventional Ultrasound, and MRI for Predicting Histology-Determined Steatosis Grade in Adult Nonalcoholic Fatty Liver Disease.

OBJECTIVE: The purpose of this study is to explore the diagnostic performance of two investigational quantitative ultrasound (QUS) parameters, attenuation coefficient and backscatter coefficient, in comparison with conventional ultrasound (CUS) and MRI-estimated proton density fat fraction (PDFF) for predicting histology-confirmed steatosis grade in adults with nonalcoholic fatty liver disease (NAFLD). SUBJECTS AND METHODS: In this prospectively designed pilot study, 61 adults with histology-confirmed NAFLD were enrolled from September 2012 to February 2014. Subjects underwent QUS, CUS, and MRI examinations within 100 days of clinical-care liver biopsy. QUS parameters (attenuation coefficient and backscatter coefficient) were estimated using a reference phantom technique by two analysts independently. Three-point ordinal CUS scores intended to predict steatosis grade (1, 2, or 3) were generated independently by two radiologists on the basis of QUS features. PDFF was estimated using an advanced chemical shift-based MRI technique. Using histologic examination as the reference standard, ROC analysis was performed. Optimal attenuation coefficient, backscatter coefficient, and PDFF cutoff thresholds were identified, and the accuracy of attenuation coefficient, backscatter coefficient, PDFF, and CUS to predict steatosis grade was determined. Interobserver agreement for attenuation coefficient, backscatter coefficient, and CUS was analyzed. RESULTS: CUS had 51.7% grading accuracy. The raw and cross-validated steatosis grading accuracies were 61.7% and 55.0%, respectively, for attenuation coefficient, 68.3% and 68.3% for backscatter coefficient, and 76.7% and 71.3% for MRI-estimated PDFF. Interobserver agreements were 53.3% for CUS (κ = 0.61), 90.0% for attenuation coefficient (κ = 0.87), and 71.7% for backscatter coefficient (κ = 0.82) (p < 0.0001 for all). CONCLUSION: Preliminary observations suggest that QUS parameters may be more accurate and provide higher interobserver agreement than CUS for predicting hepatic steatosis grade in patients with NAFLD.

In vivo triglyceride composition of abdominal adipose tissue measured by 1 H MRS at 3T.

PURPOSE: To investigate the regional variability of adipose tissue triglyceride composition in vivo using 1 H MRS, examining potential confounders and corrections for artifacts, to allow for adipose tissue spectrum estimation. MATERIALS AND METHODS: 1 H magnetic resonance (MR) stimulated echo acquisition mode (STEAM) spectra were acquired in vivo at 3T from 340 adult patients (mean age 48.9 years, range 21-79 years; 172 males, 168 females; mean body mass index [BMI] 34.0, range 22-49 kg/m2 ) with known or suspected nonalcoholic fatty liver disease (NAFLD) in deep (dSCAT), surface (sSCAT) subcutaneous adipose tissue, and visceral adipose tissue (VAT). Triglyceride composition was characterized by the number of double bonds (ndb) and number of methylene-interrupted double bonds (nmidb). A subset of patients (dSCAT n = 80, sSCAT n = 55, VAT n = 194) had the acquisition repeated three times to examine the repeatability of ndb and nmidb estimation. RESULTS: Mean ndb and nmidb showed significant (P < 0.0001) differences between depots except for dSCAT and sSCAT nmidb (dSCAT ndb 2.797, nmidb 0.745; sSCAT ndb 2.826, nmidb 0.737; VAT ndb 2.723, nmidb 0.687). All ndb and nmidb estimates were highly repeatable (VAT ndb ICC = 0.888, nmidb ICC = 0.853; sSCAT: ndb ICC = 0.974, nmidb ICC = 0.964; dSCAT: ndb ICC = 0.959, nmidb ICC = 0.948). CONCLUSION: Adipose tissue composition can be estimated repeatably using 1 H MRS and different fat depots have different triglyceride compositions. LEVEL OF EVIDENCE: 2 J. MAGN. RESON. IMAGING 2017;45:1455-1463.

Helping Hospitalized Smokers: A Factorial RCT of Nicotine Patches and Counseling.

INTRODUCTION: Most smokers abstain from smoking during hospitalization but relapse upon discharge. This study tests the effectiveness of two proven treatments (i.e., nicotine patches and telephone counseling) in helping these patients stay quit after discharge from the hospital, and assesses a model of hospital-quitline partnership. STUDY DESIGN: This study had a 2×2 factorial design in which participants were stratified by recruitment site and smoking rate and randomly assigned to usual care, nicotine patches only, counseling only, or patches plus counseling. They were evaluated at 2 and 6 months post-randomization. SETTING/PARTICIPANTS: A total of 1,270 hospitalized adult smokers were recruited from August 2011 to November 2013 from five hospitals within three healthcare systems. INTERVENTION: Participants in the patch condition were provided 8 weeks of nicotine patches at discharge (or were mailed them post-discharge). Quitline staff started proactively calling participants in the counseling condition 3 days post-discharge to provide standard quitline counseling. MAIN OUTCOME MEASURES: The primary outcome measure was self-reported 30-day abstinence at 6 months using an intention-to-treat analysis. Data were analyzed from September 2015 to May 2016. RESULTS: The 30-day abstinence rate at 6 months was 22.8% for the nicotine patch condition and 18.3% for the no-patch condition (p=0.051). Nearly all participants (99%) in the patch condition were provided nicotine patches, although 36% were sent post-discharge. The abstinence rates were 20.0% and 21.1% for counseling and no counseling conditions, respectively (p=0.651). Fewer than half of the participants in the counseling condition (47%) received counseling (mean follow-up sessions, 3.6). CONCLUSIONS: Provision of nicotine patches proved feasible, although their effectiveness in helping discharged patients stay quit was not significant. Telephone counseling was not effective, in large part because of low rates of engagement. Future interventions will need to be more immediate to be effective. TRIAL REGISTRATION: This study is registered at www.clinicaltrials.gov NCT01289275.

Imaging Outcomes of Liver Imaging Reporting and Data System Version 2014 Category 2, 3, and 4 Observations Detected at CT and MR Imaging.

Purpose To determine the proportion of untreated Liver Imaging Reporting and Data System (LI-RADS) version 2014 category 2, 3, and 4 observations that progress, remain stable, or decrease in category and to compare the cumulative incidence of progression in category. Materials and Methods In this retrospective, longitudinal, single-center, HIPAA-compliant, institutional review board-approved study, 157 patients (86 men and 71 women; mean age ± standard deviation, 59.0 years ± 9.7) underwent two or more multiphasic computed tomographic (CT) or magnetic resonance (MR) imaging examinations for hepatocellular carcinoma surveillance, with the first examination in 2011 or 2012. One radiologist reviewed baseline and follow-up CT and MR images (mean follow-up, 614 days). LI-RADS categories issued in the clinical reports by using version 1.0 or version 2013 were converted to version 2014 retrospectively; category modifications were verified with another radiologist. For index category LR-2, LR-3, and LR-4 observations, the proportions that progressed, remained stable, or decreased in category were calculated. Cumulative incidence curves for progression were compared according to baseline LI-RADS category (by using log-rank tests). Results All 63 index LR-2 observations remained stable or decreased in category. Among 166 index LR-3 observations, seven (4%) progressed to LR-5, and eight (5%) progressed to LR-4. Among 52 index LR-4 observations, 20 (38%) progressed to a malignant category. The cumulative incidence of progression to a malignant category was higher for index LR-4 observations than for index LR-3 or LR-2 observations (each P < .001) but was not different between LR-3 and LR-2 observations (P = .155). The cumulative incidence of progression to at least category LR-4 was trend-level higher for index LR-3 observations than for LR-2 observations (P = .0502). Conclusion Observations classified according to LI-RADS version 2014 categories are associated with different imaging outcomes. (©) RSNA, 2016 Online supplemental material is available for this article.

The thermodynamic scale of inorganic crystalline metastability.

The space of metastable materials offers promising new design opportunities for next-generation technological materials, such as complex oxides, semiconductors, pharmaceuticals, steels, and beyond. Although metastable phases are ubiquitous in both nature and technology, only a heuristic understanding of their underlying thermodynamics exists. We report a large-scale data-mining study of the Materials Project, a high-throughput database of density functional theory-calculated energetics of Inorganic Crystal Structure Database structures, to explicitly quantify the thermodynamic scale of metastability for 29,902 observed inorganic crystalline phases. We reveal the influence of chemistry and composition on the accessible thermodynamic range of crystalline metastability for polymorphic and phase-separating compounds, yielding new physical insights that can guide the design of novel metastable materials. We further assert that not all low-energy metastable compounds can necessarily be synthesized, and propose a principle of 'remnant metastability'-that observable metastable crystalline phases are generally remnants of thermodynamic conditions where they were once the lowest free-energy phase.