Endovascular thrombectomy for acute ischaemic stroke with established large infarct: multicentre, open-label, randomised trial.

BACKGROUND: Recent evidence suggests a beneficial effect of endovascular thrombectomy in acute ischaemic stroke with large infarct; however, previous trials have relied on multimodal brain imaging, whereas non-contrast CT is mostly used in clinical practice. METHODS: In a prospective multicentre, open-label, randomised trial, patients with acute ischaemic stroke due to large vessel occlusion in the anterior circulation and a large established infarct indicated by an Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) of 3-5 were randomly assigned using a central, web-based system (using a 1:1 ratio) to receive either endovascular thrombectomy with medical treatment or medical treatment (ie, standard of care) alone up to 12 h from stroke onset. The study was conducted in 40 hospitals in Europe and one site in Canada. The primary outcome was functional outcome across the entire range of the modified Rankin Scale at 90 days, assessed by investigators masked to treatment assignment. The primary analysis was done in the intention-to-treat population. Safety endpoints included mortality and rates of symptomatic intracranial haemorrhage and were analysed in the safety population, which included all patients based on the treatment they received. This trial is registered with ClinicalTrials.gov, NCT03094715. FINDINGS: From July 17, 2018, to Feb 21, 2023, 253 patients were randomly assigned, with 125 patients assigned to endovascular thrombectomy and 128 to medical treatment alone. The trial was stopped early for efficacy after the first pre-planned interim analysis. At 90 days, endovascular thrombectomy was associated with a shift in the distribution of scores on the modified Rankin Scale towards better outcome (adjusted common OR 2·58 [95% CI 1·60-4·15]; p=0·0001) and with lower mortality (hazard ratio 0·67 [95% CI 0·46-0·98]; p=0·038). Symptomatic intracranial haemorrhage occurred in seven (6%) patients with thrombectomy and in six (5%) with medical treatment alone. INTERPRETATION: Endovascular thrombectomy was associated with improved functional outcome and lower mortality in patients with acute ischaemic stroke from large vessel occlusion with established large infarct in a setting using non-contrast CT as the predominant imaging modality for patient selection. FUNDING: EU Horizon 2020.

A multimodal approach to studying the relationship between peripheral glutathione, brain glutamate, and cognition in health and in schizophrenia.

Involvement of oxidative stress in the pathophysiology of schizophrenia (SZ) is suggested by studies of peripheral tissue. Nonetheless, it is unclear how such biological changes are linked to relevant, pathological neurochemistry, and brain function. We designed a multi-faceted study by combining biochemistry, neuroimaging, and neuropsychology to test how peripheral changes in a key marker for oxidative stress, glutathione (GSH), may associate with central neurochemicals or neuropsychological performance in health and in SZ. GSH in dorsal anterior cingulate cortex (dACC) was acquired as a secondary 3T 1H-MRS outcome using a MEGA-PRESS sequence. Fifty healthy controls and 46 patients with SZ were studied cross-sectionally, and analyses were adjusted for effects of confounding variables. We observed lower peripheral total GSH in SZ compared to controls in extracellular (plasma) and intracellular (lymphoblast) pools. Total GSH levels in plasma positively correlated with composite neuropsychological performance across the total population and within patients. Total plasma GSH levels were also positively correlated with the levels of Glx in the dACC across the total population, as well as within each individual group (controls, patients). Furthermore, the levels of dACC Glx and dACC GSH positively correlated with composite neuropsychological performance in the patient group. Exploring the relationship between systemic oxidative stress (in particular GSH), central glutamate, and cognition in SZ will benefit further from assessment of patients with more varied neuropsychological performance.

Impact of bridging thrombolysis on clinical outcome in stroke patients undergoing endovascular thrombectomy: a retrospective analysis of a regional stroke registry.

PURPOSE: It is unclear whether stroke patients undergoing endovascular thrombectomy (EVT) should receive bridging intravenous thrombolysis (IVT), if eligible. This study aims at analyzing the impact of bridging IVT on short-term clinical outcome. METHODS: In a prospective regional stroke registry, all stroke patients with premorbid modified Rankin Scale (mRS) score of 0-2 who were admitted within 4.5 h after onset and treated with EVT were analyzed retrospectively. Patients receiving "IVT prior to EVT" (IVEVT) were compared to those undergoing "EVT only" regarding the ratio of good outcome, discharge mRS, mRS shift, hospital mortality, and occurrence of symptomatic intracranial hemorrhage. RESULTS: In total, 2022 patients were included, 816 patients (40.4%) achieved good clinical outcome; 1293 patients (63.9%) received bridging IVT. There was no significant difference between both groups regarding the ratio of good outcome (IVEVT 41.4% vs. EVT 38.5%, P = 0.231), discharge mRS (median, IVEVT 3 vs. EVT 3, P = 0.178), mRS shift (median, IVEVT 3 vs. EVT 3, P = 0.960), and hospital mortality (IVEVT 19.3% vs. EVT 19.5%, P = 0.984). Bridging IVT was not a predictor of outcome (adjusted OR 1.00, 95% CI 0.79-1.26, P = 0.979). However, it was an independent predictor of symptomatic intracranial hemorrhage (adjusted OR 1.79, 95% CI 1.21-2.72, P = 0.005). CONCLUSIONS: The results of the present study suggest that bridging IVT does not seem to improve short-term clinical outcome of patients undergoing EVT. Nonetheless, there might be a subgroup of patients that benefits from IVT. This needs to be addressed in randomized controlled trials.

Effects of visceral adipose tissue reduction on CVD risk factors independent of weight loss: The Look AHEAD study.

OBJECTIVES: To determine if the reduction of visceral adipose tissue (VAT) volume by lifestyle intervention improved risk factors for cardiovascular disease (CVD) independent of weight loss amount. DESIGN: Ancillary study of randomized-controlled trial. SETTING: Data analysis using multivariable regression models. PARTICIPANTS: Participants of the Look AHEAD (Action for HEAlth in Diabetes) Fatty Liver Ancillary Study. MAIN OUTCOME MEASURES: Correlations between changes in VAT and in CVD risk factors, while adjusting for weight loss and treatment (intensive lifestyle intervention [ILI] vs. diabetes support and education [DSE]). RESULTS: Of 100 participants analyzed, 52% were women, and 36% were black, with a mean age of 61.1 years. In the DSE group, mean weight and VAT changed by 0.1 % (p=0.90) and 4.3% (p=0.39), respectively. In the ILI group, mean weight and VAT decreased by 8.0% (p<0.001) and 7.7% (p=0.01), respectively. Across both groups, mean weight decreased by 3.6% (p<0.001), and mean VAT decreased by 1.2% (p=0.22); the decrease in VAT was correlated with the increase in HDL-cholesterol (HDL-C; R=-0.37; p=0.03). There were no correlations between changes in VAT and blood pressure, triglycerides, LDL-C, glucose, or HbA1c. After adjusting for age, race, gender, baseline metabolic values, fitness, and treatment group, changes in HDL-C were not associated with changes in VAT, while weight changes were independently associated with decrease in glucose, HbA1c, and increase in HDL-C. CONCLUSIONS: VAT reduction was not correlated with improvements of CVD risk factors in a sample of overweight and obese adults with type 2 diabetes after adjusting for weight loss.

Evaluation of Hepatocellular Carcinoma Tumor Response After Transcatheter Arterial Chemoembolization Using Gadobenate Dimeglumine-Enhanced Liver Magnetic Resonance.

OBJECTIVE: Use of gadobenate dimeglumine-enhanced liver magnetic resonance (MR) for evaluation of hepatocellular carcinoma tumor response after transcatheter arterial chemoembolization (TACE). METHODS: Forty-five patients with hepatocellular carcinoma were imaged with multiphase gadobenate dimeglumine-enhanced MR examination at baseline and 1-month follow-up after TACE. Nodule size, enhancement, and apparent diffusion coefficient were measured for both examinations by 2 reviewers. Changes in tumor nodule size, enhancement, and apparent diffusion coefficient were evaluated using the Student t test. RESULTS: Nineteen of 45 patients completed the study, and a total of 34 hepatocellular carcinoma nodules were analyzed. On the posttreatment follow up, there was no significant change in nodule size. Target lesions demonstrated significant decrease in tumor enhancement after TACE (P < 0.001). Intense contrast accumulation along the periphery of the presumed necrotic tumor on the delayed hepatobiliary phase helped to differentiate viable from non-viable tumor. CONCLUSION: Gadobenate dimeglumine-enhanced liver MR may help differentiate between viable and necrotic tumor after TACE.

Volumetric assessment of tumour response using functional MR imaging in patients with hepatocellular carcinoma treated with a combination of doxorubicin-eluting beads and sorafenib.

OBJECTIVE: To prospectively assess treatment response using volumetric functional magnetic resonance imaging (MRI) metrics in patients with hepatocellular carcinoma (HCC) treated with the combination of doxorubicin-eluting bead-transarterial chemoembolization (DEB TACE) and sorafenib. METHODS: A single center study enrolled 41 patients treated with systemic sorafenib, 400 mg twice a day, combined with DEB TACE. All patients had a pre-treatment and 3-4 week post-treatment MRI. Anatomic response criteria (RECIST, mRECIST and EASL) and volumetric functional response (ADC, enhancement) were assessed. Statistical analyses included paired Student's t-test, Kaplan-Meier curves, Cohen's Kappa, and multivariate cox proportional hazard model. RESULTS: Median tumour size by RECIST remained unchanged post-treatment (8.3 ± 4.1 cm vs. 8.1 ± 4.3 cm, p = 0.44). There was no significant survival difference for early response by RECIST (p = 0.93). EASL and mRECIST could not be analyzed in 12 patients. Volumetric ADC increased significantly (1.32 × 10(-3) mm(2)/sec to 1.60 × 10(-3) mm(2)/sec, p < 0.001), and volumetric enhancement decreased significantly in HAP (38.2% to 17.6%, p < 0.001) and PVP (76.6% to 41.2%, p < 0.005). Patients who demonstrated ≥ 65% decrease PVP enhancement had significantly improved overall survival compared to non-responders (p < 0.005). CONCLUSION: Volumetric PVP enhancement was demonstrated to be significantly correlated with survival in the combination of DEB TACE and sorafenib for patients with HCC, enabling precise stratification of responders and non-responders. KEY POINTS: • PVP enhancement is significantly correlated with survival in responders (p < 0.005). • There was no significant survival difference for early response using RECIST (p = 0.93). • mRECIST or EASL could not assess tumour response in 29% of patients.

Association between serum uric acid and nonalcoholic fatty liver disease in the US population.

BACKGROUND/PURPOSE: Studies conducted in Eastern Asia suggest that serum uric acid (SUA) level is highly related to nonalcoholic fatty liver disease (NAFLD). However, limited information is available in the USA. Our objective was to determine the association between NAFLD and SUA levels in the USA and to determine if this is independent of age, sex, and components of metabolic syndrome (MetS). METHODS: We analyzed 5370 men and women aged 20-74 years from the Third National Health and Nutrition Examination Survey (NHANES III) (1988-1994) in the USA. We calculated the prevalence and odds ratio (OR) of NAFLD and elevated liver enzymes by SUA and sex-specific quintiles of SUA, adjusting for multiple factors. RESULTS: The prevalence of NAFLD was higher in participants with higher SUA levels (10.9%, 9.6%, 15.9%, 21.8% and 33.1%, respectively, from the second to the fifth sex-specific quintile of uric acid). After adjustment, individuals with hyperuricemia were more likely to have NAFLD (OR: 1.4, 95% CI: 1.1-1.9). Similarly, the adjusted odds of NAFLD were increasingly higher from the second to the fifth quintile of SUA (ORs: 0.8, 1.2, 1.5 and 1.7, respectively; p < 0.01) as compared to the lowest quintile. Finally, individuals with hyperuricemia were more likely to have elevated liver enzymes (aspartate aminotransferase or alanine aminotransferase) (adjusted OR: 1.8, 95% CI: 1.1-2.7). CONCLUSION: NAFLD and SUA levels were strongly and independently associated in this nationally representative sample of men and women after adjustment for multiple factors.

Response stratification and survival analysis of hepatocellular carcinoma patients treated with intra-arterial therapy using MR imaging-based arterial enhancement fraction.

PURPOSE: To investigate the feasibility that arterial enhancement fraction (AEF) is associated with response of hepatocellular carcinoma (HCC) following intra-arterial therapy (IAT) and to compare AEF response with currently used tumor response metrics. MATERIALS AND METHODS: The AEF, Response Evaluation Criteria in Solid Tumors (RECIST), modified RECIST (mRECIST), and European Association for the Study of the Liver (EASL) of the largest treated index lesion and AEF of the tumor-free hepatic parenchyma was measured on representative axial images in 131 patients (108 male; mean age, 61.9 years). Clinical measures and patient survival were assessed. Statistical analysis included Wilcoxon signed-rank test and the COX proportional hazards model. RESULTS: After IAT, the mean AEF of the tumor decreased by 22% (66.7-44.8%, P < 0.0001), while the mean AEF of the tumor-free parenchyma remained unchanged (27.2-26.5%, P = 0.50). Median survival of all 131 patients with liver cancer was 17 months. Patients were stratified into AEF-responders if they had an AEF-decrease ≥35% (AEF-responders: n = 67; AEF-nonresponders: n = 64). AEF-responders survived longer than nonresponders (34.8 months versus 10.8 months, hazard ratio = 0.39; P < 0.0001). Responders according to RECIST, mRECIST, or EASL did not survive significantly longer compared with nonresponders. CONCLUSION: Evaluating the AEF values based on tri-phasic MRI is associated with tumor response in patients with unresectable HCC treated with IAT.

Spatial distribution of MRI-Determined hepatic proton density fat fraction in adults with nonalcoholic fatty liver disease.

PURPOSE: To describe the spatial distribution of liver fat,using MRI-estimated proton density fat fraction (PDFF), in adults with nonalcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS: This Investigational Review Board-approved, Health Insurance Portability and Accountability Act-compliant study prospectively enrolled 50 adults (30 women, 20 men) with biopsy-proven NAFLD. Hepatic PDFF was measured by low-flip-angle multiecho spoiled gradient-recalled-echo MRI at 3 Tesla. Three nonoverlapping regions of interest were placed within each liver segment. Statistical analyses included Pearson's correlation, multivariable linear regression, and permutation-based paired tests. RESULTS: The study population's mean whole-liver PDFF was 16.1% (range: 1.6­39.6%). The mean whole-liver PDFF variability was 1.9% (range: 0.7­4.5%). Higher variability was associated with higher PDFF (r=0.34;P=0.0156). The mean PDFF was significantly higher in the right lobe than the left (16.5% versus 15.3%, P=0.0028). The mean PDFF variability was higher in the left lobe than the right (1.86% versus 1.28%; P<0.0001). Segment II had the lowest mean segmental PDFF (14.8%);segment VIII had the highest (16.7%). Segments V(0.71%) and VI (0.70%) had the lowest mean segmental PDFF variability; segment II had the highest (1.32%). CONCLUSION: IN adult NAFLD there are small but significant differences in fat content.

Assessing liver fibrosis: comparison of arterial enhancement fraction and diffusion-weighted imaging.

PURPOSE: Noninvasive markers have been developed to reduce the need for liver biopsy. The aim of this study was to compare the strength of association of the arterial enhancement fraction (AEF), apparent diffusion coefficient (ADC), and serum biomarkers for staging hepatic fibrosis. MATERIALS AND METHODS: Eighty-five patients with chronic liver disease underwent triple-phase contrast-enhanced MRI, used to calculate AEF, and diffusion-weighted MRI (b = 0,750 s/mm(2) ), used to calculate ADC. Hepatic fibrosis was staged according METAVIR criteria. The overall association of the four biomarkers (AEF, ADC, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, and aspartate aminotransferase to platelet ratio index [APRI]) was compared using nonparametric tests and receiver operating characteristic (ROC) curve, using histopathologic analysis as the reference standard. RESULTS: AEF and ADC values differed significantly between histopathologic fibrosis stages. AEF values correlated with fibrosis stage, ADC values correlated negatively with fibrosis stage. Compared with ADC, AEF showed a trend toward an improved capability of discriminating fibrosis stages. A weighted composite score of AEF and ADC had significantly better diagnostic accuracy than ADC alone (P ≤ 0.023). Imaging parameters had a significantly better diagnostic accuracy than AST/ALT ratio or APRI. CONCLUSION: AEF may be able to detect the presence of mild, moderate, and advanced liver fibrosis, and its value is increased with concomitant use of ADC.

Cost-effectiveness of endovascular thrombectomy for acute ischemic stroke with established large infarct in Germany: a decision tree and Markov model.

BACKGROUND: Recent studies, including the TENSION trial, support the use of endovascular thrombectomy (EVT) in acute ischemic stroke with large infarct (Alberta Stroke Program Early Computed Tomography Score (ASPECTS) 3-5). OBJECTIVE: To evaluate the cost-effectiveness of EVT compared with best medical care (BMC) alone in this population from a German healthcare payer perspective. METHODS: A short-term decision tree and a long-term Markov model (lifetime horizon) were used to compare healthcare costs and quality-adjusted life years (QALYs) between EVT and BMC. The effectiveness of EVT was reflected by the 90-day modified Rankin Scale (mRS) outcome from the TENSION trial. QALYs were based on published mRS-specific health utilities (EQ-5D-3L indices). Long-term healthcare costs were calculated based on insurance data. Costs (reported in 2022 euros) and QALYs were discounted by 3% annually. Cost-effectiveness was assessed using incremental cost-effectiveness ratios (ICERs). Deterministic and probabilistic sensitivity analyses were performed to account for parameter uncertainties. RESULTS: Compared with BMC, EVT yielded higher lifetime incremental costs (€24 257) and effects (1.41 QALYs), resulting in an ICER of €17 158/QALY. The results were robust to parameter variation in sensitivity analyses (eg, 95% probability of cost-effectiveness was achieved at a willingness to pay of >€22 000/QALY). Subgroup analyses indicated that EVT was cost-effective for all ASPECTS subgroups. CONCLUSIONS: EVT for acute ischemic stroke with established large infarct is likely to be cost-effective compared with BMC, assuming that an additional investment of €17 158/QALY is deemed acceptable by the healthcare payer.

Prevalence of nonalcoholic fatty liver disease in the United States: the Third National Health and Nutrition Examination Survey, 1988-1994.

Previous estimates of the prevalence of nonalcoholic fatty liver disease (NAFLD) in the US population relied on measures of liver enzymes, potentially underestimating the burden of this disease. We used ultrasonography data from 12,454 adults who participated in the Third National Health and Nutrition Examination Survey, conducted in the United States from 1988 to 1994. We defined NAFLD as the presence of hepatic steatosis on ultrasonography in the absence of elevated alcohol consumption. In the US population, the rates of prevalence of hepatic steatosis and NAFLD were 21.4% and 19.0%, respectively, corresponding to estimates of 32.5 (95% confidence interval: 29.9, 35.0) million adults with hepatic steatosis and 28.8 (95% confidence interval: 26.6, 31.2) million adults with NAFLD nationwide. After adjustment for age, income, education, body mass index (weight (kg)/height (m)²), and diabetes status, NAFLD was more common in Mexican Americans (24.1%) compared with non-Hispanic whites (17.8%) and non-Hispanic blacks (13.5%) (P = 0.001) and in men (20.2%) compared with women (15.8%) (P < 0.001). Hepatic steatosis and NAFLD were also independently associated with diabetes, with insulin resistance among people without diabetes, with dyslipidemia, and with obesity. Our results extend previous national estimates of the prevalence of NAFLD in the US population and highlight the burden of this disease. Men, Mexican Americans, and people with diabetes and obesity are the most affected groups.

Association between variants in or near PNPLA3, GCKR, and PPP1R3B with ultrasound-defined steatosis based on data from the third National Health and Nutrition Examination Survey.

BACKGROUND & AIMS: A genome-wide association study associated 5 genetic variants with hepatic steatosis (identified by computerized tomography) in individuals of European ancestry. We investigated whether these variants were associated with measures of hepatic steatosis (HS) in non-Hispanic white (NHW), non-Hispanic black, and Mexican American (MA) participants in the US population-based National Health and Nutrition Examination Survey III, phase 2. METHODS: We analyzed data from 4804 adults (1825 NHW, 1442 non-Hispanic black, and 1537 MA; 51.7% women; mean age at examination, 42.5 y); the weighted prevalence of HS was 37.3%. We investigated whether ultrasound-measured HS, with and without increased levels of alanine aminotransferase (ALT), or level of ALT alone, was associated with rs738409 (patatin-like phospholipase domain-containing protein 3 [PNPLA3]), rs2228603 (neurocan [NCAN]), rs12137855 (lysophospholipase-like 1), rs780094 (glucokinase regulatory protein [GCKR]), and rs4240624 (protein phosphatase 1, regulatory subunit 3b [PPP1R3B]) using regression modeling in an additive genetic model, controlling for age, age-squared, sex, and alcohol consumption. RESULTS: The G allele of rs738409 (PNPLA3) and the T allele of rs780094 (GCKR) were associated with HS with a high level of ALT (odds ratio [OR], 1.36; P = .01; and OR, 1.30; P = .03, respectively). The A allele of rs4240624 (PPP1R3B) and the T allele of rs2228603 (NCAN) were associated with HS (OR, 1.28; P = .03; and OR, 1.40; P = .04, respectively). Variants of PNPLA3 and NCAN were associated with ALT level among all 3 ancestries. Some single-nucleotide polymorphisms were associated with particular races or ethnicities: variants in PNPLA3, NCAN, GCKR, and PPP1R3B were associated with NHW and variants in PNPLA3 were associated with MA. No variants were associated with NHB. CONCLUSIONS: We used data from the National Health and Nutrition Examination Survey III to validate the association between rs738409 (PNPLA3), rs780094 (GCKR), and rs4240624 (PPP1R3B) with HS, with or without increased levels of ALT, among 3 different ancestries. Some, but not all, associations between variants in NCAN, lysophospholipase-like 1, GCKR, and PPP1R3B with HS (with and without increased ALT level) were significant within subpopulations.

Neuroendocrine liver metastasis treated by using intraarterial therapy: volumetric functional imaging biomarkers of early tumor response and survival.

PURPOSE: To determine if volumetric changes of diffusion-weighted and contrast material-enhanced magnetic resonance (MR) imaging can help assess early tumor response to intraarterial therapy (IAT) in neuroendocrine liver metastasis (NELM). MATERIALS AND METHODS: This retrospective single-center comprehensive imaging analysis was performed in compliance with HIPAA and was institutional review board approved. Informed patient consent was waived. Seventy-one patients (39 men; mean age, 62.3 years) with NELM treated with IAT were analyzed retrospectively. MR studies were performed before and 3-4 weeks after therapy. The index lesion was segmented to provide volumetric functional analysis of apparent diffusion coefficient (ADC) and contrast-enhanced MR imaging in the hepatic arterial phase (HAP) and portal venous phase (PVP). Tumor response was defined as increase in volumetric ADC of 15% or greater and decrease in volumetric enhancement of 25% or greater during the HAP or of 50% or greater during the PVP. Patient overall survival was the primary end point after therapy initiation. Univariate analysis included Kaplan-Meier survival curves. The Cox proportional hazards regression model was used to detect interactions between volumetric ADC and contrast-enhanced MR imaging and to calculate the hazard ratio. RESULTS: There was significant increase in mean volumetric ADC (27%, P < .0001) and significant decrease in mean volumetric enhancement during the HAP (-25.3%, P < .0001) and the PVP (-22.4%, P < .0001) in all patients. Patients who had 15% or greater volumetric ADC increase (n = 49) after therapy had better prognosis than those who had less than 15% increase in volumetric ADC (n = 22) (log-rank test, P < .002). Patients who had 25% or greater decrease in volumetric arterial enhancement (n = 40) or 50% or greater decrease in venous enhancement (n = 18) had better prognosis than those who had less than 25% decrease in volumetric arterial enhancement (n = 31) or less than 50% decrease in venous enhancement (n = 53) (log-rank test, P < .02). CONCLUSION: Volumetric functional MR imaging criteria may act as biomarkers of early response, indicating that these criteria may be important to incorporate in future NELM clinical trials.

Unresectable hepatocellular carcinoma: MR imaging after intraarterial therapy. Part I. Identification and validation of volumetric functional response criteria.

PURPOSE: To identify and validate the optimal thresholds for volumetric functional MR imaging response criteria to predict overall survival after intraarterial treatment (IAT) in patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Institutional review board approval and waiver of informed consent were obtained. A total of 143 patients who had undergone MR imaging before and 3-4 weeks after the first cycle of IAT were included. MR imaging analysis of one representative HCC index lesion was performed with proprietary software after initial treatment. Subjects were randomly divided into training (n = 114 [79.7%]) and validation (n = 29 [20.3%]) data sets. Uni- and multivariate Cox models were used to determine the best cutoffs, as well as survival differences, between response groups in the validation data set. RESULTS: Optimal cutoffs in the training data set were 23% increase in apparent diffusion coefficient (ADC) and 65% decrease in volumetric enhancement in the portal venous phase (VE). Subsequently, 25% increase in ADC and 65% decrease in VE were used to stratify patients in the validation data set. Comparison of ADC responders (n = 12 [58.6%]) with nonresponders (n = 17 [34.5%]) showed significant differences in survival (25th percentile survival, 11.2 vs 4.9 months, respectively; P = .008), as did VE responders (n = 9 [31.0%]) compared with nonresponders (n = 20 [69.0%]; 25th percentile survival, 11.5 vs 5.1 months, respectively; P = .01). Stratification of patients with a combination of the criteria resulted in significant differences in survival between patients with lesions that fulfilled both criteria (n = 6 [20.7%]; too few cases to determine 25th percentile), one criterion (n = 9 [31.0%]; 25th percentile survival, 6.0 months), and neither criterion (n = 14 [48.3%]; 25th percentile survival, 5.1 months; P = .01). The association between the two criteria and overall survival remained significant in a multivariate analysis that included age, sex, Barcelona Clinic for Liver Cancer stage, and number of follow-up treatments. CONCLUSION: After IAT for unresectable HCC, patients can be stratified into significantly different survival categories based on responder versus nonresponder status according to MR imaging ADC and VE cutoffs.

Unresectable hepatocellular carcinoma: MR imaging after intraarterial therapy. Part II. Response stratification using volumetric functional criteria after intraarterial therapy.

PURPOSE: To assess whether volumetric functional magnetic resonance (MR) results 3-4 weeks after initial intraarterial therapy can aid accurate distinction between responders and nonresponders, to determine whether overall survival (OS) is improved, and to compare volumetric functional MR response with anatomic response criteria (Response Evaluation Criteria in Solid Tumors [RECIST], modified RECIST [mRECIST], European Association for the Study of the Liver [EASL]), as well as α1-fetoprotein [AFP] level. MATERIALS AND METHODS: In this single-institution HIPAA-compliant retrospective, institutional review board-approved study, informed consent was waived; 143 patients with hepatocellular carcinoma underwent intraarterial therapy between October 2005 and February 2011. Volumetric functional MR response (25% or more increase in apparent diffusion coefficient, 65% or more decrease in enhancement) was stratified as follows: Dual-parameter responders fulfilled both criteria, single-parameter responders fulfilled one criterion, and those with stable disease (SD) fulfilled neither. RECIST, mRECIST, EASL, and AFP response criteria were determined. Kaplan-Meier technique, log-rank tests, and the Cox proportional hazards model were used to test whether OS was different per response. RESULTS: OS differed significantly between single-parameter responders and dual-parameter responders (P = .01) and between single-parameter responders and those with SD (P = .001). Dual-parameter responders' response improved OS compared with single-parameter responders; risk of death decreased (hazard ratio [HR] = 0.28, P = .01). In those with SD compared with single-parameter responders, risk of death increased (HR = 2.09, P = .001). RECIST, mRECIST, and EASL stratification was short of significant; most lesions were classified as SD. Baseline AFP level increased in 55 patients; AFP responders versus AFP nonresponders had decreased risk of death (HR = 0.36, P = .002). Agreement between anatomic response criteria and volumetric functional MR findings (κ = 0.06-0.12) and between AFP response and imaging criteria (κ = -0.04 to 0.14) was low. CONCLUSION: Volumetric functional MR response 3-4 weeks after initial intraarterial therapy showed improved OS. Volumetric functional MR was superior to current imaging (RECIST, mRECIST, and EASL) and biochemical (AFP level) response criteria.

Higher dietary fructose is associated with impaired hepatic adenosine triphosphate homeostasis in obese individuals with type 2 diabetes.

UNLABELLED: Fructose consumption predicts increased hepatic fibrosis in those with nonalcoholic fatty liver disease (NAFLD). Because of its ability to lower hepatic adenosine triphosphate (ATP) levels, habitual fructose consumption could result in more hepatic ATP depletion and impaired ATP recovery. The degree of ATP depletion after an intravenous (IV) fructose challenge test in low- versus high-fructose consumers was assessed. We evaluated diabetic adults enrolled in the Action for Health in Diabetes Fatty Liver Ancillary Study (n = 244) for whom dietary fructose consumption estimated by a 130-item food frequency questionnaire and hepatic ATP measured by phosphorus magnetic resonance spectroscopy and uric acid (UA) levels were performed (n = 105). In a subset of participants (n = 25), an IV fructose challenge was utilized to assess change in hepatic ATP content. The relationships between dietary fructose, UA, and hepatic ATP depletion at baseline and after IV fructose challenge were evaluated in low- (<15 g/day) versus high-fructose (≥ 15 g/day) consumers. High dietary fructose consumers had slightly lower baseline hepatic ATP levels and a greater absolute change in hepatic α-ATP/ inorganic phosphate (Pi) ratio (0.08 versus 0.03; P = 0.05) and γ-ATP /Pi ratio after an IV fructose challenge (0.03 versus 0.06; P = 0.06). Patients with high UA (≥ 5.5 mg/dL) showed a lower minimum liver ATP/Pi ratio postfructose challenge (4.5 versus 7.0; P = 0.04). CONCLUSIONS: High-fructose consumption depletes hepatic ATP and impairs recovery from ATP depletion after an IV fructose challenge. Subjects with high UA show a greater nadir in hepatic ATP in response to fructose. Both high dietary fructose intake and elevated UA level may predict more severe hepatic ATP depletion in response to fructose and hence may be risk factors for the development and progression of NAFLD.

MRI arterial enhancement fraction in hepatic fibrosis and cirrhosis.

OBJECTIVE: Fibrosis leads to altered liver hemodynamics. The arterial enhancement fraction, which is defined as the ratio of hepatic arterial perfusion to the total hepatic perfusion, can provide noninvasive assessment of hepatic perfusion. The aim of this study was to show that the arterial enhancement fraction values correlate with histopathologic stage of liver fibrosis, thus providing a reliable noninvasive radiologic alternative to liver biopsy for the detection and staging of hepatic fibrosis. MATERIALS AND METHODS: We evaluated hepatic fibrosis stage (denoted by Metavir score [F]) and arterial enhancement fraction of patients who underwent standard triphasic liver MRI and liver biopsy within 1 year from January 2005 to December 2010. Prototype software was used to calculate the arterial enhancement fraction. Statistical analysis included nonparametric tests and area under the receiver operating characteristic curve (AUC). RESULTS: One hundred fourteen patients (69 men and 45 women; median age, 52.5 years) were divided into groups according to the Metavir score. The mean arterial enhancement fraction was 24.2% ± 11.6% for F0, 35.2% ± 18.7% for F1, 30.2% ± 12.5% for F2, 37.5% ± 16.4% for F3, and 59.8% ± 16.6% for F4. The mean arterial enhancement fraction values differed significantly between Metavir scores (p < 0.001) and showed a positive correlation with Metavir score (r = 0.693; p < 0.001). The optimal mean arterial enhancement fraction cutoffs were 32.96% or more (AUC = 0.8343) for detection of mild fibrosis, 33.33% or more (AUC = 0.8524) for detection of moderate fibrosis, 38.43% or more (AUC = 0.8819) for detection of severe fibrosis, and 45.76% or more (AUC = 0.9161) for detection of cirrhosis. CONCLUSION: Arterial enhancement fraction using triple-phase MRI can provide a reliable noninvasive method to assess hepatic fibrosis.

Multiparametric magnetic resonance imaging characterization of prostate lesions in the active surveillance population: incremental value of magnetic resonance imaging for prediction of disease reclassification.

OBJECTIVE: This study aimed to characterize prostate lesions by multiparametric magnetic resonance imaging (MRI) in active surveillance (AS) and examine the incremental predictive value of MRI in comparison with clinical parameters for disease reclassification. METHODS: Blinded imaging review of 3-T endorectal mMRI from 50 consecutive men was performed. Multiparametric MRI biomarkers and morphological parameters and the predictive value of a suspicious MR lesion of 10 mm or greater for clinical or histopathologic disease reclassification were assessed. RESULTS: Nine patients were reclassified as AS noneligible during follow-up. Morphological parameters, magnetic resonance spectroscopic imaging, and dynamic contrast-enhanced MRI were associated with disease reclassification. Multiparametric MRI best predicted disease reclassification in patients who did not meet clinical AS enrollment criteria and had a suspicious lesion 10 mm or greater, followed by patients with a suspicious lesion of 10 mm or greater. Not meeting enrollment criteria alone was not a significant predictor of disease reclassification. CONCLUSIONS: Multiparametric MRI demonstrates incremental predictive value when used in combination with clinical AS enrollment criteria and supports the assessment of eligibility for AS.

Agreement and reproducibility of apparent diffusion coefficient measurements of dual-b-value and multi-b-value diffusion-weighted magnetic resonance imaging at 1.5 Tesla in phantom and in soft tissues of the abdomen.

OBJECTIVE: To compare the coefficient of variation (CV) and long-term reproducibility of apparent diffusion coefficient (ADC) in a simple fluid-filled phantom and abdominal organs simultaneously. MATERIALS AND METHODS: Retrospective institutional review board-approved and Health Insurance Portability and Accountability Act-compliant study sequentially selected 100 patients who underwent clinically indicated abdominal magnetic resonance imaging. A subset of 58 patients had repeat scans within 2 to 5 months after the initial magnetic resonance imaging. Two diffusion-weighted imaging techniques (b-values 0-750 mm/s) were performed to compare the ADC values. Mean ADC values were calculated for 10 locations and the reference phantom. The CV and Bland-Altman plots were calculated for the phantom and soft tissues at each session and location. RESULTS: There were no significant differences in the mean ADC values between repeated acquisitions. However, ADC values were statistically higher using dual-b-value than multi-b-value diffusion-weighted imaging. The CV for the phantom was 8.6 versus 10.8 for dual-b-value and multi-b-value, respectively. The CVs for the soft tissues had a wider range compared with that of the phantom (liver, 12.6 vs 9.0; spleen, 11.7 vs 11.2; gallbladder, 11.0 vs 13.6; head of pancreas, 14.6 vs 14.7; body of pancreas, 13.4 vs 13.0; tail of pancreas, 14.8 vs 16.3; right kidney, 9.1 vs 9.6; left kidney, 9.3 vs 9.3; right paraspinal muscle, 7.9 vs 7.5; left paraspinal muscle, 7.3 vs 7.3, respectively). CONCLUSIONS: A change in ADC less than 11% falls into the range of measurement variability. Paraspinal muscle could potentially be used as an internal reference parameter.