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.

ASPECTS Interobserver Agreement of 100 Investigators from the TENSION Study.

PURPOSE: Evaluating the extent of cerebral ischemic infarction is essential for treatment decisions and assessment of possible complications in patients with acute ischemic stroke. Patients are often triaged according to image-based early signs of infarction, defined by Alberta Stroke Program Early CT Score (ASPECTS). Our aim was to evaluate interrater reliability in a large group of readers. METHODS: We retrospectively analyzed 100 investigators who independently evaluated 20 non-contrast computed tomography (NCCT) scans as part of their qualification program for the TENSION study. Test cases were chosen by four neuroradiologists who had previously scored NCCT scans with ASPECTS between 0 and 8 and high interrater agreement. Percent and interrater agreements were calculated for total ASPECTS, as well as for each ASPECTS region. RESULTS: Percent agreements for ASPECTS ratings was 28%, with interrater agreement of 0.13 (95% confidence interval, CI 0.09-0.16), at zero tolerance allowance and 66%, with interrater agreement of 0.32 (95% CI: 0.21-0.44), at tolerance allowance set by TENSION inclusion criteria. ASPECTS region with highest level of agreement was the insular cortex (percent agreement = 96%, interrater agreement = 0.96 (95% CI: 0.94-0.97)) and with lowest level of agreement the M3 region (percent agreement = 68%, interrater agreement = 0.39 [95% CI: 0.17-0.61]). CONCLUSION: Interrater agreement reliability for total ASPECTS and study enrollment was relatively low but seems sufficient for practical application. Individual region analysis suggests that some are particularly difficult to evaluate, with varying levels of reliability. Potential impairment of the supraganglionic region must be examined carefully, particularly with respect to the decision whether or not to perform mechanical thrombectomy.

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.

Direct Admission vs. Secondary Transfer to a Comprehensive Stroke Center for Thrombectomy : Retrospective Analysis of a Regional Stroke Registry with 2797 Patients.

BACKGROUND AND PURPOSE: This study aimed at comparing short-term clinical outcome after thrombectomy in patients directly admitted (DA) to a comprehensive stroke center with patients secondarily transferred (ST) from a primary stroke center. METHODS: In a prospective regional stroke registry, all stroke patients with a premorbid modified Rankin scale (mRS) score 0-2 who were admitted within 24 h after stroke onset and treated with thrombectomy between 2014 and 2017 were retrospectively analyzed. Patients with DA and ST were compared regarding the proportion of good outcome (discharge mRS 0-2), median discharge mRS, mRS shift (difference between premorbid mRS and mRS on discharge) and occurrence of symptomatic intracranial hemorrhage. RESULTS: Out of 2797 patients, 1051 (37.6%) achieved good clinical outcome. In the DA group (n = 1657), proportion of good outcome was higher (DA 42.2% vs. ST 30.9%, P < 0.001) and median discharge mRS (DA 3 vs. ST 4, P < 0.001) and median mRS shift (DA 3 vs. ST 4, P < 0.001) were lower. The rate of symptomatic intracranial hemorrhage was similar in both groups (DA 9.3% vs. ST 7.5%, P = 0.101). Multivariate analysis revealed that direct admission was an independent predictor of good clinical outcome (adjusted odds ratio, OR 1.32, confidence interval, CI 1.09-1.60, P = 0.004). CONCLUSION: These results confirm prior studies stating that DA to a comprehensive stroke center leads to better outcome compared to ST in stroke patients undergoing thrombectomy.

A randomized controlled trial to test efficacy and safety of thrombectomy in stroke with extended lesion and extended time window.

RATIONALE: The benefit of thrombectomy in patients with intracranial large vessel occlusion of the anterior circulation has been shown in selected patients in previous randomized controlled trials, but patients with extended ischemic lesions were excluded in the majority of these trials. TENSION aims to demonstrate efficacy and safety of thrombectomy in patients with extended lesions in an extended time window (up to 12 h from onset or from last seen well). DESIGN: TENSION is an investigator-initiated, randomized controlled, open label, blinded endpoint, European, two-arm, postmarket study to compare the safety and effectiveness of thrombectomy as compared to best medical care alone in stroke patients with extended stroke lesions defined by an Alberta Stroke Program Early Computed Tomography Scan score of 3-5 and in an extended time window. In an adaptive design study, up to 665 patients will be randomized. OUTCOMES: Primary efficacy endpoint will be clinical outcome defined by the modified Rankin Scale at 90-day poststroke. The main safety endpoint will be death and dependency (modified Rankin Scale 4-6) at 90 days. Additional effect measures include adverse events, health-related quality of life, poststroke depression, and costs utility assessment. DISCUSSION: TENSION may make effective treatment available for patients with severe stroke in an extended time window, thereby improving functional outcome and quality of life of thousands of stroke patients and reducing the individual, societal, and economic burden of death and disability resulting from severe stroke. TENSION is registered at ClinicalTrials.gov (ClinicalTrials.gov Identifier NCT03094715).

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.

Comparison of single voxel brain MRS AT 3T and 7T using 32-channel head coils.

PURPOSE: The purpose of this study was to compare magnetic resonance spectroscopy (MRS) of three different regions of the human brain between 3 and 7 Tesla, using the same subjects and closely matched methodology at both field strengths. METHODS: A semi-LASER (sLASER) pulse sequence with TE 32ms was used to acquire metabolite spectrum along with the water reference at 3T and 7T using similar experimental parameters and hardware at both field strengths (n=4 per region and field). Spectra were analyzed in LCModel using a simulated basis set. RESULTS: Signal-to-noise ratio (SNR) at 7T was higher compared to 3T, and linewidths (in ppm) at both field strengths were comparable in ppm scale. Of the 13 metabolites reported in the paper, most metabolites were measured with higher precision at 7T in all three regions. CONCLUSION: The study confirms gains in SNR and measurement precision at 7T in all three representative brain regions using the sLASER pulse sequence coupled with a 32-channel phased-array head coil.

Thrombectomy in patients ineligible for iv tPA (THRILL).

RATIONALE: A relevant proportion of patients with acute ischemic stroke are ineligible for intravenous thrombolysis with recombinant tissue plasminogen activator. Mechanical thrombectomy offers a treatment alternative for these patients; however, only few data are available on its safety and efficacy. AIMS AND/OR HYPOTHESIS: The aim of this study was to compare safety and efficacy of stent retrievers as device class with best medical care alone in acute stroke patients with large intracranial vessel occlusion in the anterior circulation who are not eligible for intravenous thrombolysis with recombinant tissue plasminogen activator up to eight-hours of symptom onset. DESIGN: 'Thrombectomy in patients ineligible for iv tPA' is a prospective, open-label, blinded end-point, binational (Germany and Austria), two-arm, randomized, controlled, post-market study. STUDY OUTCOME(S): Primary end-point is the modified Rankin Score shift analysis 90 days (±14) after stroke. Secondary end-points are excellent neurological outcomes (modified Rankin Score ≤ 1), good neurological outcomes (modified Rankin Score ≤ 2 or National Institutes of Health Stroke Scale improvement ≥ 10), difference between predicted infarct volume and actual core infarct volume (computed tomography or magnetic resonance imaging) at 30 (±6) h post-ictus, successful recanalization (thrombolysis in cerebral infarction score 2b or 3), functional health status 90 (±14) days after stroke (European Quality of Life-5 Dimensions) as well as common safety end-points (adverse event, serious adverse event, symptomatic intracranial haemorrhage at 30 (±6) h, death, or dependency). DISCUSSION: Whether mechanical thrombectomy in patients with acute ischemic stroke who are not eligible for intravenous thrombolysis with recombinant tissue plasminogen activator improves clinical outcomes is unclear. 'Thrombectomy in patients ineligible for iv tPA' may change clinical practice by providing evidence of an effective and safe treatment for such 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.

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.

Functional magnetic resonance imaging response of targeted tumor burden and its impact on survival in patients with hepatocellular carcinoma.

OBJECTIVE: The aim of this study was to evaluate response of the targeted tumor burden by functional magnetic resonance imaging (MRI) including volumetric diffusion-weighted imaging and volumetric contrast-enhanced MRI (CE-MRI) and its impact on survival in patients with hepatocellular carcinoma treated with intra-arterial therapy (IAT). MATERIALS AND METHODS: This institutional review board-approved, Health Insurance Portability and Accountability Act-compliant retrospective study included 157 hepatocellular carcinoma lesions in 97 patients (78 men and 19 women; mean age, 64 years) treated with IAT. All patients had pretreatment and 3- to 4-week follow-up MRI with diffusion-weighted imaging and CE-MRI. All lesions 2 cm or larger that were targeted during the first session of IAT were segmented using research software (MR-Oncotreat) to determine targeted tumor burden relative to liver volume (%). Targeted tumor burden was stratified into low (≤10%) or high (>10%). Response using volumetric functional apparent diffusion coefficient (ADC; increase by ≥25%) and CE-MRI (decrease by ≥50% and ≥65% in arterial and venous enhancement [VE], respectively) was assessed in all targeted tumors (range, 1-11) using paired t tests. Kaplan-Meier survival analysis was performed and log-rank test was used to compare pairs of survival curves. Multivariate Cox regression analysis was performed to determine the simultaneous effect of treatment response and tumor burden on survival after adjusting for age, sex, and Child Pugh status. RESULTS: There was a significant increase in volumetric ADC (median, 15%; P < 0.001) and a decrease in volumetric arterial enhancement (AE) and VE (median AE, -43% and portal venous phase (PVP), -29%, respectively; P < 0.001) 3 to 4 weeks after treatment in the targeted tumor burden. Multivariable Cox regression demonstrated that both ADC response and low tumor burden were independently associated with greater survival (hazard ratios, 0.53 and 0.55; P values, 0.025 and 0.016, respectively) after adjustment for age, sex, and Child Pugh status. Multivariable Cox regression models demonstrated no statistically significant relationship between AE response and survival after adjusting for tumor burden. However, multivariable Cox regression demonstrated that VE response was associated with greater survival only in those with low tumor burden (hazard ratio, 0.10; P = 0.001), indicating a strong interaction between VE response and tumor burden. CONCLUSION: Quantifying targeted tumor burden is important in predicting patient survival when using functional MRI metrics in assessing treatment response.

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.

Interobserver agreement of semi-automated and manual measurements of functional MRI metrics of treatment response in hepatocellular carcinoma.

PURPOSE: To assess the interobserver agreement in 50 patients with hepatocellular carcinoma (HCC) before and 1 month after intra-arterial therapy (IAT) using two semi-automated methods and a manual approach for the following functional, volumetric and morphologic parameters: (1) apparent diffusion coefficient (ADC), (2) arterial phase enhancement (AE), (3) portal venous phase enhancement (VE), (4) tumor volume, and assessment according to (5) the Response Evaluation Criteria in Solid Tumors (RECIST), and (6) the European Association for the Study of the Liver (EASL). MATERIALS AND METHODS: This HIPAA-compliant retrospective study had institutional review board approval. The requirement for patient informed consent was waived. Tumor ADC, AE, VE, volume, RECIST, and EASL in 50 index lesions was measured by three observers. Interobserver reproducibility was evaluated using intraclass correlation coefficients (ICC). P<0.05 was considered to indicate a significant difference. RESULTS: Semi-automated volumetric measurements of functional parameters (ADC, AE, and VE) before and after IAT as well as change in tumor ADC, AE, or VE had better interobserver agreement (ICC=0.830-0.974) compared with manual ROI-based axial measurements (ICC=0.157-0.799). Semi-automated measurements of tumor volume and size in the axial plane before and after IAT had better interobserver agreement (ICC=0.854-0.996) compared with manual size measurements (ICC=0.543-0.596), and interobserver agreement for change in tumor RECIST size was also higher using semi-automated measurements (ICC=0.655) compared with manual measurements (ICC=0.169). EASL measurements of tumor enhancement in the axial plane before and after IAT ((ICC=0.758-0.809), and changes in EASL after IAT (ICC=0.653) had good interobserver agreement. CONCLUSION: Semi-automated measurements of functional changes assessed by ADC and VE based on whole-lesion segmentation demonstrated better reproducibility than ROI-based axial measurements, or RECIST or EASL measurements.

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.

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.

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.