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Introduction Overall, intra-arterial treatment (IAT) proved to be beneficial in patients with acute ischaemic stroke due to a proximal occlusion in the anterior circulation. However, heterogeneity in treatment benefit may be relevant for personalised clinical decision-making. Our aim is to improve selection of patients for IAT by predicting individual treatment benefit or harm. Methods and analysis We will use data collected in the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) trial to analyse the effect of baseline characteristics on outcome and treatment effect. A multivariable proportional odds model with interaction terms will be developed to predict the outcome for each individual patient, both with and without IAT. Model performance will be expressed as discrimination and calibration, after bootstrap resampling and shrinkage of regression coefficients, to correct for optimism. External validation will be conducted on data of patients in the Interventional Management of Stroke III trial (IMS III). Primary outcome will be the modified Rankin Scale (mRS) at 90 days after stroke. Ethics and dissemination The proposed study will provide an internationally applicable clinical decision aid for IAT. Findings will be disseminated widely through peer-reviewed publications, conference presentations and in an online web application tool. Formal ethical approval was not required as primary data were already collected. Trial registration numbers ISRCTN10888758; Post-results and NCT00359424; Post-resultsc.

Background: Successful revascularization after endovascular therapy for acute ischemic stroke is measured by TICI score, yet variability exists in scale definitions and use. We examined the degree of reperfusion and association with outcomes in the HERMES collaboration of recent endovascular trials. Methods: An independent reader of the HERMES Imaging Core, blind to all other data, evaluated the angiography of subjects treated with endovascular therapy in HERMES. A battery of various TICI scores (mTICI, oTICI, oTICI2C) was used to define reperfusion of the initial target occlusion on noninvasive imaging (ITO) and conventional angiography (CATO). Statistical analyses examined all TICI reperfusion metrics and correlation with clinical outcomes. Results: Angiography of 593 subjects was analyzed, including ITO (124 ICA, 413 M1, 47 M2) and CATO (161 ICA, 329 M1, 62 M2). Across the entire scale range (0-3), the mTICI (AUC 0.61), oTICI (AUC 0.61) and oTICI2C (AUC 0.62) revealed similar ROC characteristics (p=0.450) in discriminating that more reperfusion is associated with better clinical outcomes. Using oTICI2C (3=100%, 2C=90-99%, o2B=67-89%, m2B=50-66%) of CATO, there were 44 TICI 3 (8%), 125 TICI 2C (22%), 178 TICI o2B (32%), 80 TICI m2B (14%), 85 TICI 2A (15%), 15 TICI 1 (3%) and 35 TICI 0 (6%). mRS shift analyses from baseline to 90 days revealed increasing TICI grades were linked with better outcomes (Figure), with significant distinctions of m2B vs. 2C (p=0.023) and all 2B combined vs. 3 (p=0.045). Conclusions: The benefit of endovascular therapy in HERMES was strongly associated with increasing degrees of TICI reperfusion. The oTICI2C metric reveals important distinctions in clinical outcomes that should be used in future studies.

Background and purpose: General anesthesia (GA) during endovascular thrombectomy has been associated with worse patient outcomes in observational studies. We examined the association between GA and thrombectomy outcomes in pooled data from five randomized trials. Methods: Patient-level data were pooled from trials comparing endovascular thrombectomy (predominantly using stent retrievers) with standard care in anterior circulation ischemic stroke patients (HERMES Collaboration): MR CLEAN, ESCAPE, REVASCAT, SWIFT PRIME, and EXTEND IA. The primary outcome was ordinal analysis of modified Rankin scale (mRS) at 90 days in the GA and non-GA subgroups, adjusted for baseline prognostic variables. To account for between-trial variance we used mixed-effects modeling with a random effect for trial incorporated in all models. Results: Of 1287 patients, 634 were allocated to endovascular thrombectomy and general anesthesia was used in 153/609 (25%) of endovascular-treated patients with anesthesia information available. Although dysphasic patients are sometimes felt to be less co-operative and require GA, the rate of GA was 25% in both right and left hemisphere patients. At baseline, GA and non-GA patients had similar age, NIHSS and time to randomization. Endovascular thrombectomy was associated with increased odds of improved functional outcome at 3 months, regardless of whether GA (cOR 1.73 95%CI 1.10-2.72, p=0.02) or non-GA (cOR 2.61 95%CI 2.01-3.40, p Conclusions: Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment is still worthwhile in those who require anesthesia for medical reasons.

Background and purpose: Patients estimated to have a large irreversibly injured ischemic core are sometimes excluded from reperfusion therapies. We examined the association between estimated core volume and thrombectomy outcomes. Methods: Patient-level CT perfusion (CTP) and clinical data were pooled from trials comparing endovascular thrombectomy with standard care in anterior circulation ischemic stroke: MR CLEAN, EXTEND IA, ESCAPE, SWIFT PRIME, REVASCAT and PISTE. Ischemic core volume was estimated using relative cerebral blood flow Results: Of 1352 patients, pre-treatment CTP was assessable in 539 after exclusion of 27 patients (12 severe motion, 2 no lesion within coverage, 2 contrast bolus failure, 11 data corruption during transfer from site). There were 264 allocated to endovascular thrombectomy and 275 to control. Baseline characteristics were similar between endovascular and control patients with CTP, median core 9.6 mL (IQR 2.4-26 mL) and with the overall trial demographics. Larger estimated core volume was associated with lower probability of independent outcome (mRS 0-2) in endovascular (OR 0.87 95%CI 0.80-0.95) and control patients (OR 0.85 95%CI 0.77-0.93, core*treatment interaction p=0.62) and increased disability: utility scores derived from mRS reduced by 2% (95%CI 1-4%) per 10mL increase in core volume for both endovascular and control patients (core*treatment interaction p=0.79). However, patients with >70mL core (median 100 mL, IQR 82-144mL) still benefitted from thrombectomy: ordinal mRS cOR 7.0 (2.6 -18.9) and the number needed to treat (NNT) remained stable across the spectrum of core volumes (point estimate NNT Conclusions: Increasing estimated core volume was independently associated with worse outcome but endovascular thrombectomy remained effective versus standard care even in patients with large core who otherwise met eligibility for these trials.

Background & Purpose: Intra-arterial therapy (IAT) is being implemented worldwide as the main treatment option for acute ischemic stroke (AIS). We wondered whether effectiveness and safety results that have been reported in randomized clinical trials can be reproduced in everyday clinical practice. We will report results of the Dutch National post MR CLEAN IAT registry including work flow parameters, primary and secondary outcomes, as well as serious adverse events. Methods: The MR CLEAN Registry is a prospective registry of all patients undergoing IAT for AIS in the Netherlands, started after completion of the MR CLEAN trial in March 2014. Registration was required for reimbursement. A core set was defined, with inclusion criteria similar to those of the MR CLEAN trial, including a proven anterior circulation occlusion and treatment possible withing 6 hours from onset. The primary study outcome is the score on the modified Rankin Scale (mRS) at 90 days. The secondary clinical outcome is NIHSS after 24 to 48 hours. Secondary radiological outcomes include the mTICI score on DSA and final infarct volume and major bleeding on follow up NCCT. We used a propensity weighted and an unadjusted ordinal logistic regression model to compare outcomes in the MR CLEAN Registry core and total dataset with the treatment arm of MR CLEAN. Results: Between March 2014 and August 2016 the inclusion rate of the MR CLEAN Registry has been increasing steadily to an average of 79 (SD 22) per month for a cumulative inclusion of 1548 patients in July 2016 (Figure 1). Conclusions: The MR CLEAN registry data is now being analyzed. Results will be reported at the conference.

Background: Patients treated with thrombectomy for acute ischemic stroke (AIS) under general anesthesia (GA) appear to have less favorable outcomes than patients treated under local anesthesia. Anesthetics used for the induction of GA are known to be associated with decreases in blood pressure. The aim of this study was to determine whether a fall in blood pressure during treatment under GA affects functional outcome. Methods: This subgroup analysis included Patients from the MR CLEAN trial treated with endovascular therapy under GA. The investigated variables were the difference between baseline mean arterial pressure (MAP) and mean MAP during intervention as well as the difference between baseline MAP and the lowest MAP during intervention. Their association with a shift in the outcome on the score on the modified Rankin Scale (mRS) at 90 days from onset was determined using ordinal logistic regression with adjustment for prognostic baseline variables. Results: Sixty of the 85 patients treated with GA in MRCLEAN had sufficient anesthetic information available and were included in this analysis. The difference between baseline MAP and mean MAP during intervention was associated with decreased likelihood of favorable outcome on the mRS (adjusted common odds ratio (acOR) 0.95 per point mmHg, 95%CI 0.92-0.99 ) . For a mean MAP during intervention 10 mmHg lower than baseline MAP this would constitute an odds of favorable outcome ( 1/(0.95^10)= ) 1.67 times lower than patients without this decrease. The association with outcome of the difference between baseline MAP and the lowest MAP during intervention was not significant (acOR 0.97 per point mmHg, 95%CI 0.94-1.00, p=0.09). Conclusion: A decreased MAP during thrombectomy under GA as compared to baseline MAP is associated with a lower likelihood of favorable outcome. This finding underlines the importance of blood pressure management during mechanical thrombectomy under GA.

Background: Collateral circulation is a key factor in the pathophysiology of ischemic stroke. We conducted detailed analyses of angiography acquired immediately prior to endovascular therapy in the HERMES collaboration of recent landmark thrombectomy trials to determine predictors of collateral status and assess impact on clinical outcomes. Methods: The HERMES Imaging Core, blind to all other clinical and imaging data, independently interpreted conventional angiography acquired immediately prior to endovascular therapy. Collaterals were graded with the ASITN scale, based on available data for the site of arterial occlusion defined on initial injections. The statistical core analyzed the association of collateral grade with demographics, baseline NIHSS, site of arterial occlusion and clinical outcomes of day 90 mRS. Results: Angiography of collaterals was available in 376/605 (62%), including ASITN grades 0 in 7 (2%), 1 in 40 (10%), 2 in 182 (48%), 3 in 129 (34%) and 4 in 18 (5%). Elevated blood glucose (p=0.011) and diabetes (p=0.048) were associated with worse collateral grades, but age and NIHSS were unrelated. Better collateral grade was strongly associated with the degree of subsequent TICI reperfusion (p Multivariable regression revealed that better collateral status was a potent determinant (OR 1.37 per grade, p=0.028) of outcomes, equivalent to 4.5 points of NIHSS and 14 years of age in terms of impact on mRS outcomes. Conclusions: Collaterals at angiography were a potent determinant of clinical outcomes in recent landmark thrombectomy trials.

BACKGROUND AND PURPOSE: The Woven EndoBridge device was recently introduced for the intrasaccular treatment of wide-neck aneurysms without the need for adjunctive devices. We present our results of the primary treatment of ruptured aneurysms with the Woven EndoBridge regardless of location or neck size. MATERIALS AND METHODS: Between February 2015 and April 2017, 100 ruptured aneurysms were selectively treated with the Woven EndoBridge. No supporting stents or balloons were used. There were 71 women treated (mean patient age, 59 years; median age, 60 years; range, 23–82 years). RESULTS: The mean aneurysm size was 5.6 mm (range, 3–13 mm), and 42 aneurysms were ≤4 mm. Sixty-six aneurysms (66%) had a wide neck, defined as ≥4 mm or a dome-neck ratio ≤1.5. There was 1 procedural rupture without sequelae. In 9 patients (9%), thromboembolic complications occurred. One poor grade patient died; neurologic deficits remained in 3. Overall treatment-related morbidity-mortality was 4% (4 of 100; 95% CI, 1.2%–10.2%). Two of 100 aneurysms were initially incompletely occluded and were additionally treated early after initial intervention. Of 80 eligible patients, 74 (93%) had 3-month angiographic follow-up. Fifty-four aneurysms (73%) were completely occluded, 17 (23%) had a small neck remnant, and 3 (4%) were incompletely occluded. One patient was additionally treated with a second Woven EndoBridge, and in 2 patients, additional treatment is scheduled. The overall reopening/retreatment rate was 6.8% (5 of 74; 95% CI, 2.6%–15.2%). There were no rebleeds during follow-up. CONCLUSIONS: Treatment of small ruptured aneurysms with the Woven EndoBridge was safe and effective. The Woven EndoBridge proved to be a valuable alternative to coils without the need for stents or balloons.

This study aimed to evaluate cerebral blood flow (CBF) in pediatric human immunodeficiency virus (HIV)-infection, and its role in HIV-related cerebral injury and cognitive impairment. This cross-sectional observational study compared 28 perinatally HIV-infected children (8–18 years) to 34 healthy controls matched for age, sex, ethnicity, and socio-economic status. All participants underwent 3-Tesla magnetic resonance imaging, using arterial spin labeling to assess CBF in gray matter (GM), white matter (WM), basal ganglia, and thalamus. We used linear regression analysis to evaluate group differences and associations with HIV disease and treatment characteristics, macrostructural (volume loss, WM lesions) or microstructural injury (increased WM diffusivity, neurometabolite alterations), or poorer cognitive performance. HIV-infected children had higher CBF in WM (+10.2%; P = 0.042), caudate nucleus (+4.8%; P = 0.002), putamen (+3.6%; P = 0.017), nucleus accumbens (+3.9%; P = 0.031), and thalamus (+5.5%; P = 0.032). Thalamus CBF was highest in children with a Centers for Disease Control and Prevention stage B (Coef. = 6.45; P = 0.005) or C (Coef. = 8.52; P = 0.001) diagnosis. Lower GM CBF was associated with higher WM lesion volume in HIV-infected children (Coef. = −0.053; P = 0.001). No further associations with HIV-related cognitive impairment or cerebral injury were found. CBF was higher in WM, basal ganglia, and thalamus in combination antiretroviral therapy (cART)-treated perinatally HIV-infected children, but this was not associated with cerebral injury or cognitive impairment. HIV-infected children with lower GM CBF had a higher volume of WM lesions, which could reflect vascular disease as potential contributing factor to white matter injury. Lifelong exposure to HIV and cART in this population warrants longitudinal assessment of CBF and how it relates to (neuro)inflammation, vascular dysfunction, and cerebral injury in pediatric HIV.

Item does not contain fulltext OBJECTIVE: To assess if HIV-infected patients on long-term successful combination antiretroviral therapy show cerebral blood flow (CBF) alterations in comparison with HIV-uninfected, otherwise similar controls. To explore whether such alterations are associated with HIV-associated cognitive impairment and to explore potential determinants of CBF alterations in HIV. DESIGN: Cross-sectional comparison of CBF in an observational cohort study. METHODS: Clinical, cognitive and MRI data of 100 middle-aged aviremic HIV-infected men on combination antiretroviral therapy and 69 HIV-uninfected controls were collected and compared. From pseudocontinuous arterial spin labeling MRI data, CBF-maps were calculated. The associations of mean gray matter CBF with clinical and cognitive parameters were explored in regression models, followed by a spatial delineation in a voxel-based analysis. RESULTS: CBF was decreased in HIV-infected patients compared with HIV-uninfected controls (P = 0.02), adjusted for age, ecstasy use and waist circumference. Spatially distinct and independent effects of total gray matter volume and HIV-serostatus on CBF were found. Within the HIV-infected group, decreased CBF was associated with increased triglyceride levels (P = 0.005) and prior clinical AIDS (P = 0.03). No association between CBF and cognitive impairment was found. CONCLUSION: Decreased CBF was observed among HIV-infected patients, which was associated with both vascular risk factors as well as with measures of past immune deficiency. These results provide support for increased vascular disease in HIV-infected patients as represented by hemodynamic alteration, but without overt cognitive consequences within the current cohort of patients on long-term successful treatment.

Objective: To examine brain activation patterns during verbal fluency performance in patients with progressive muscular atrophy (PMA) and amyotrophic lateral sclerosis (ALS).Methods: fMRI was used to examine the blood oxygen level-dependent response during letter and category fluency performance in 18 patients with PMA, 21 patients with ALS, and 17 healthy control subjects, matched for age and education. fMRI results are reported at p < 0.05, family-wise error (FWE)-corrected for multiple comparisons. We analyzed effects of performance, age-related white matter changes (ARWMC), and regional brain volumes; all participants underwent neuropsychological investigation.Results: Disease duration of patients with PMA (mean 26.0 months, SD 13.6) and ALS (22.2 months, SD 11.4) was comparable. Patients with PMA and ALS had mild to moderate disease severity and showed impaired letter fluency compared with controls. Between-group analysis showed a main effect of group in the left inferior frontal gyrus (IFG, Brodmann area 45) during letter fluency, which was unaffected by performance, ARWMC, and IFG volume: patients with PMA showed lower activation than controls but higher than that of patients with ALS (ALS < PMA < healthy controls; pFWE = 0.035; z score 4.11; cluster size = 11). A more caudal region in the IFG showed lower activation in patients with PMA than controls during letter fluency performance (post hoc test; pFWE = 0.026). No activation differences were observed during the category fluency task.Conclusion: Prefrontal activation abnormalities are related to an important clinical measure of executive dysfunction in patients with motor neuron disease with and without upper motor neuron signs.

BACKGROUND AND PURPOSE: Quantification of blood after SAH on initial NCCT is an important radiologic measure to predict patient outcome and guide treatment decisions. In current scales, hemorrhage volume and density are not accounted for. The purpose of this study was to develop and validate a fully automatic method for SAH volume and density quantification. MATERIALS AND METHODS: The automatic method is based on a relative density increase due to the presence of blood from different brain structures in NCCT. The method incorporates density variation due to partial volume effect, beam-hardening, and patient-specific characteristics. For validation, automatic volume and density measurements were compared with manual delineation on NCCT images of 30 patients by 2 radiologists. The agreement with the manual reference was compared with interobserver agreement by using the intraclass correlation coefficient and Bland-Altman analysis for volume and density. RESULTS: The automatic measurement successfully segmented the hemorrhage of all 30 patients and showed high correlation with the manual reference standard for hemorrhage volume (intraclass correlation coefficient = 0.98 [95% CI, 0.96–0.99]) and hemorrhage density (intraclass correlation coefficient = 0.80 [95% CI, 0.62–0.90]) compared with intraclass correlation coefficient = 0.97 (95% CI, 0.77–0.99) and 0.98 (95% CI, 0.89–0.99) for manual interobserver agreement. Mean SAH volume and density were, respectively, 39.3 ± 31.5 mL and 62.2 ± 5.9 Hounsfield units for automatic measurement versus 39.7 ± 32.8 mL and 61.4 ± 7.3 Hounsfield units for manual measurement. The accuracy of the automatic method was excellent, with limits of agreement of −12.9–12.1 mL and −7.6–9.2 Hounsfield units. CONCLUSIONS: The automatic volume and density quantification is very accurate compared with manual assessment. As such, it has the potential to provide important determinants in clinical practice and research.

To systematically review the literature on dating subdural hematomas (SDHs) on CT and MRI scans. We performed a systematic review in MEDLINE, EMBASE and Cochrane to search for articles that described the appearance of SDHs on CT or MRI in relation to time between trauma and scanning. Two researchers independently screened the articles, assessed methodological quality and performed data extraction. Medians with interquartile ranges were calculated. Differences were tested with a Mann-Whitney U or Kruskal-Wallis H test. We included 22 studies describing 973 SDHs on CT and 4 studies describing 83 SDHs on MRI. Data from 17 studies (413 SDHs) could be pooled. There were significant differences between time intervals for the different densities on CT (p

The Hennekam lymphangiectasia-lymphedema syndrome is a genetically heterogeneous disorder. It can be caused by mutations in CCBE1 which are found in approximately 25 % of cases. We used homozygosity mapping and whole-exome sequencing in the original HS family with multiple affected individuals in whom no CCBE1 mutation had been detected, and identified a homozygous mutation in the FAT4 gene. Subsequent targeted mutation analysis of FAT4 in a cohort of 24 CCBE1 mutation-negative Hennekam syndrome patients identified homozygous or compound heterozygous mutations in four additional families. Mutations in FAT4 have been previously associated with Van Maldergem syndrome. Detailed clinical comparison between van Maldergem syndrome and Hennekam syndrome patients shows that there is a substantial overlap in phenotype, especially in facial appearance. We conclude that Hennekam syndrome can be caused by mutations in FAT4 and be allelic to Van Maldergem syndrome.

Objective Intracerebral hemorrhages (ICHs) are common in patients with cerebral venous thrombosis (CVT). We examined whether small juxtacortical hemorrhages (JCHs) are characteristic for CVT and studied their radiological and pathological properties. Methods We identified all patients with CVT and an ICH at baseline admitted between 2000 and 2011 (prospectively from July 2006). JCH was defined as a hemorrhage (diameter

BACKGROUND AND PURPOSE: Comparisons of geometric data of ruptured and unruptured aneurysms may yield risk factors for rupture. Data on changes of geometric measures associated with rupture are, however, sparse, because patients with ruptured aneurysms rarely have undergone previous imaging of the intracranial vasculature. We had the opportunity to assess 3D geometric differences of aneurysms before and after rupture. The purpose of this study was to evaluate possible differences between prerupture and postrupture imaging of a ruptured intracranial aneurysm. MATERIALS AND METHODS: Using high-quality 3D image data, we generated 3D geometric models before and after rupture and compared these for changes in aneurysm volume and displacement. A neuroradiologist qualitatively assessed aneurysm shape change, the presence of perianeurysmal hematoma, and subsequent mass effect exerted on aneurysm and parent vessels. RESULTS: Aneurysm volume was larger in the postrupture imaging in 7 of 9 aneurysms, with a median increase of 38% and an average increase of 137%. Three aneurysms had new lobulations on postrupture imaging; 2 other aneurysms were displaced up to 5 mm and had changed in geometry due to perianeurysmal hematoma. CONCLUSIONS: Geometric comparisons of aneurysms before and after rupture show a large volume increase, origination of lobulations, and displacement due to perianeurysmal hematoma. Geometric and hemodynamic comparison of series of unruptured and ruptured aneurysms in the search for rupture-risk-related factors should be interpreted with caution.

Hypoxic ischemic encephalopathy after perinatal asphyxia is a major cause of mortality and morbidity in infants. Here, we evaluated pathologic changes in the hippocampi of a cohort of 16 deceased full-term asphyxiated infants who died from January 2000 to January 2009. Histochemical and immunocytochemical results for glial and neuronal cells were compared between cases with or without seizures and to adult and sudden infant death syndrome cases (n = 3 each). All asphyxiated infants displayed neuronal cell damage and reactive glial changes. Strong aquaporin-4 immunoreactivity was seen on astroglial cells within hippocampi in 50% of cases. In patients with seizures, the expression of metabotropic glutamate receptors was increased in glial cells. Cases with seizures displayed increased microglial activation and greater expression of the inflammatory markers interleukin 1β and complement 1q compared with those in cases without seizures. All cases with seizures displayed alterations in the blood-brain barrier, as assessed by immunohistochemistry for albumin. These findings confirm the complex cascade of cellular and molecular changes occurring in the human neonatal hippocampus after perinatal asphyxia. These changes may contribute to seizure development leading to secondary brain damage. These data may aid in the development of therapeutic targets for neonatal seizures.

Small retrospective studies have shown the benefit of endovascular treatment with intrasinus thrombolysis (IST) or mechanical thrombectomy (MT) with/without IST (MT+/−IST) in cases of multifocal cerebral venous thrombosis (CVT). Our study compares the mortality, functional outcome and periprocedural complications among patients treated with MT +/– IST versus IST alone. We reviewed clinical and angiographic findings of 63 patients with CVT who received endovascular treatment at three tertiary care centers. Primary outcome variables were discharge mortality and neurological dysfunction, and intermediate (three months) and long-term (>six months) morbidity. The modified Rankin scale (mRS) was used to assess morbidity. mRS ≤1 was considered a good recovery. Neurological dysfunction was rated as neuroscore: 0, normal; 1, mild (ambulatory, communicative); 2, moderate (non-ambulatory, communicative); and 3, severe (non-ambulatory, non-communicative/comatose). In patients who received IST alone, presenting neurological deficits were comparatively minor (p Compared to IST, MT was performed in severe cases with extensive sinus involvement. When adjusted for admission neurological dysfunction, both groups had similar mortality and discharge neurological dysfunction and similar intermediate and long-term morbidity.

Pharmacological magnetic resonance imaging (phMRI) maps the neurovascular response to a pharmacological challenge and is increasingly used to assess neurotransmitter systems. Here we investigated the hemodynamic response to a dopaminergic (DAergic) challenge with dextroamphetamine (dAMPH) in humans using arterial spin labeling (ASL) based phMRI. Twelve healthy male subjects aged 21.0years (±1.5) were included. We used a pseudo-continuous ASL sequence (40min) to quantify cerebral blood flow (CBF) and started dAMPH infusion (0.3mg/kg) after 10min. On another day, we measured baseline dopamine D2/3 receptor availability with [(123)I]IBZM single photon emission computed tomography (SPECT). Baseline measures on mood and impulsivity and subjective behavioral responses to dAMPH were obtained. CBF response was corrected for cardiovascular effects using an occipital cortex mask for internal reference. Corrected CBF (sCBF) was analyzed using ROI-based and voxel-based analysis, in addition to independent component analysis (ICA). CBF data was correlated to D2/3 receptor availability and behavioral measures. Subjects reported experiencing euphoria following dAMPH administration. In the striatum sCBF significantly increased, as demonstrated by all three analysis methods. Voxel-based analysis and ICA also showed increased sCBF in the thalamus, anterior cingulate and cerebellum. Decreased sCBF was observed in several cortical areas, the posterior cingulated and paracingulate cortex. Apart from one ICA component, no correlations were found with sCBF changes and D2/3 receptor availability and behavioral measures. Our observations are in line with literature and provide further evidence that ASL-based phMRI with dAMPH is a promising technique to assess DAergic function in human subjects.

BACKGROUND AND PURPOSE: CFD has been proved valuable for simulating blood flow in intracranial aneurysms, which may add to better rupture risk assessment. However, CFD has drawbacks such as the sensitivity to assumptions needed for the model, which may hinder its clinical implementation. 3D PC-MR imaging is a technique that enables measurements of blood flow. The purpose of this study was to compare flow patterns on the basis of 3D PC-MR imaging with CFD estimates. MATERIALS AND METHODS: 3D PC-MR imaging was performed in 8 intracranial aneurysms. Two sets of patient-specific inflow boundaries for CFD were obtained from a separate 2D PC-MR imaging sequence (2D CFD) and from the 3D PC-MR imaging (3D CFD) data. 3D PC-MR imaging and CFD were compared by calculation of the differences between velocity vector magnitudes and angles. Differences in flow patterns expressed as the presence and strengths of vortices were determined by calculation of singular flow energy. RESULTS: In systole, flow features such as vortex patterns were similar. In diastole, 3D PC-MR imaging measurements appeared inconsistent due to low velocity-to-noise ratios. The relative difference in velocity magnitude was 67.6 ± 51.4% and 27.1 ± 24.9% in systole and 33.7 ± 21.5% and 17.7 ± 10.2% in diastole for 2D CFD and 3D CFD, respectively. For singular energy, this was reduced to 15.5 ± 13.9% at systole and 19.4 ± 17.6% at diastole (2D CFD). CONCLUSIONS: In systole, good agreement between 3D PC-MR imaging and CFD on flow-pattern visualization and singular-energy calculation was found. In diastole, flow patterns of 3D PC-MR imaging differed from those obtained from CFD due to low velocity-to-noise ratios.

Purpose To evaluate wall shear stress (WSS) estimations in an in vitro and in vivo intracranial aneurysm, WSS was estimated from phase contrast magnetic resonance imaging (PC-MRI) and compared with computational fluid dynamics (CFD). Materials and Methods First, WSS was estimated using a high-resolution in vitro PC-MRI measurement under steady and pulsatile flow conditions and compared with CFD simulations. Second, WSS was estimated in steady PC-MRI data acquired at different spatial resolutions. Third, WSS estimations in pulsatile in vivo data were compared with CFD. The direction and magnitude of WSS vectors were computed and compared. Results Quantitative agreement between PC-MRI and CFD-based WSS estimations was moderate for the phantom (Spearman ρ = 0.69). The WSS magnitude derived from PC-MRI data was lower than CFD for both the in vitro and in vivo case. However, there was qualitative agreement between PC-MRI and CFD, i.e. WSS vector direction was similar for both modalities. Circular WSS patterns were found both in vitro and in vivo for PC-MRI and CFD. Increasing PC-MRI resolution increased mean WSS magnitude and uncovered complex WSS patterns. Conclusion WSS patterns can be estimated based on PC-MRI data in in vitro and in vivo aneurysm geometries. Similar WSS directions as CFD can be discerned. J. Magn. Reson. Imaging 2013;38:876–884. © 2013 Wiley Periodicals, Inc.

BACKGROUND AND PURPOSE: Cerebral infarct volume as observed in follow-up CT is an important radiologic outcome measure of the effectiveness of treatment of patients with acute ischemic stroke. However, manual measurement of CIV is time-consuming and operator-dependent. The purpose of this study was to develop and evaluate a robust automated measurement of the CIV. MATERIALS AND METHODS: The CIV in early follow-up CT images of 34 consecutive patients with acute ischemic stroke was segmented with an automated intensity-based region-growing algorithm, which includes partial volume effect correction near the skull, midline determination, and ventricle and hemorrhage exclusion. Two observers manually delineated the CIV. Interobserver variability of the manual assessments and the accuracy of the automated method were evaluated by using the Pearson correlation, Bland-Altman analysis, and Dice coefficients. The accuracy was defined as the correlation with the manual assessment as a reference standard. RESULTS: The Pearson correlation for the automated method compared with the reference standard was similar to the manual correlation (R = 0.98). The accuracy of the automated method was excellent with a mean difference of 0.5 mL with limits of agreement of −38.0–39.1 mL, which were more consistent than the interobserver variability of the 2 observers (−40.9–44.1 mL). However, the Dice coefficients were higher for the manual delineation. CONCLUSIONS: The automated method showed a strong correlation and accuracy with the manual reference measurement. This approach has the potential to become the standard in assessing the infarct volume as a secondary outcome measure for evaluating the effectiveness of treatment.

Novel postprocessing techniques have enabled accurate quantification of intracranial carotid atherosclerotic disease on CT Angiography (CTA). Our purpose was to estimate the prevalence of intracranial carotid artery disease, i.e., stenosis and calcium, on CTA in patients with recent neurological symptoms. The degree of stenosis and calcium volume of 162 extracranial and intracranial internal carotid arteries (ICAs) was quantitatively measured on CTA images of 88 consecutive patients with recent neurological symptoms and extracranial ICA stenosis as screened by ultrasound. The prevalence of intracranial ICA stenosis and presence of calcium was estimated and correlated with extracranial ICA stenosis. Intracranial ICA stenosis was observed in 83 % (95 %CI: 77–89 %) and 39 % (95 %CI: 31–47 %) for a stenosis of ≥30 % and ≥50 %, respectively. Only on the symptomatic side, a statistical significant correlation between intracranial and extracranial stenoses was observed (Pearson's r 0.32, P = 0.006). In the 37 arteries with an extracranial ICA stenosis of ≥70 %, 89 % (95 %CI: 79–99 %) and 46 % (95 %CI: 30–62 %) of the intracranial ICA showed a stenosis of ≥30 % and ≥50 %, respectively. In our population of patients with recent neurological symptoms and extracranial stenosis as screened by ultrasound, CTA imaging resulted in a substantially higher prevalence of intracranial ICA disease than previously reported. This remarkably high prevalence of intracranial ICA disease on CTA may have important future implications for acute and preventive treatment strategies.

Aims Large intracoronary thrombus in patients with acute coronary syndromes remains a challenge in percutaneous coronary intervention, despite technical advances of manual aspiration catheters and mechanical thrombectomy devices. The Trevo® Pro 4 is a novel self-expanding mechanical thrombus retrieval device, designed for removal of occlusive thrombi in the setting of acute ischaemic stroke. We describe the first use of this novel mechanical thrombus retrieval device in the setting of coronary intervention. Methods and results In close collaboration with the interventional radiology department, two patients presenting with an acute coronary syndrome, complicated by refractory large intracoronary thrombus, were treated using the Trevo Pro 4. Both patients were treated successfully, resulting in complete removal of refractory thrombus without the occurrence of adverse events. Conclusions The Trevo Pro 4 can be successfully used in the setting of coronary intervention. It is simple to use, does not require complex preparations, and the handling is straightforward. A larger study to assess the safety and efficacy of this device in the setting of coronary interventions is warranted.

The availability of various first-line treatment modalities for acromegaly and evolving surgical techniques emphasize the need for accurately defined predictors of surgical outcome. We retrospectively analysed the outcome of 30 patients with acromegaly after initial endoscopic transsphenoidal surgery in two university hospitals from 2001 until 2009, and reviewed comparable literature investigating predictive tumor characteristics. Medical records were monitored for patient characteristics. Each pituitary magnetic resonance imaging (MRI) scan was revised independently by two neuroradiologists using a standardised analysis form to record distinctive predefined tumor characteristics. All characteristics were independently analysed as predictors for persistent disease, and a multivariable predictive model was created. Literature from 2000 onwards was searched for studies describing tumor characteristics predictive for surgical outcome. The cohort consisted of 27 macroadenomas with 90 % demonstrating signs of parasellar extension. The surgical cure rate overall was 30 %. Independently, next to male sex and increasing tumor size, infrasellar and parasellar extension based on MRI staging tended to increase the risk of persistent disease. In a multivariable analysis, sex and parasellar extension of the tumor were demonstrated to be the variables allowing for the best fitted predictive model for persistent disease. Earlier studies on preoperative tumor characteristics showed comparable results, although these were based on several different tumor classification systems. This retrospective study demonstrates that accurately defined tumor characteristics based on imaging, especially for cavernous sinus invasion, can be helpful in predicting surgical outcome. Comparative studies on different treatment modalities are essential for clinical practice within the scope of re-evaluation of the role of surgery in GH-secreting adenomas. © 2012 The Author(s).

Objective Computed Tomography Perfusion (CTP) is a promising tool to support treatment decision for acute ischemic stroke patients. However, head movement during acquisition may limit its applicability. Information of the extent of head motion is currently lacking. Our purpose is to qualitatively and quantitatively assess the extent of head movement during acquisition. Methods From 103 consecutive patients admitted with suspicion of acute ischemic stroke, head movement in 220 CTP datasets was qualitatively categorized by experts as none, minimal, moderate, or severe. The movement was quantified using 3D registration of CTP volume data with non-contrast CT of the same patient; yielding 6 movement parameters for each time frame. The movement categorization was correlated with National Institutes of Health Stroke Scale (NIHSS) score and baseline characteristic using multinomial logistic regression and student's t -test respectively. Results Moderate and severe head movement occurred in almost 25% (25/103) of all patients with acute ischemic stroke. The registration technique quantified head movement with mean rotation angle up to 3.6° and 14°, and mean translation up to 9.1 mm and 22.6 mm for datasets classified as moderate and severe respectively. The rotation was predominantly in the axial plane (yaw) and the main translation was in the scan direction. There was no statistically significant association between movement classification and NIHSS score and baseline characteristics. Conclusions Moderate or severe head movement during CTP acquisition of acute stroke patients is quite common. The presented registration technique can be used to automatically quantify the movement during acquisition, which can assist identification of CTP datasets with excessive head movement.

Patients with mild cognitive impairment (MCI) do not always convert to dementia. In such cases, abnormal neuropsychological test results may not validly reflect cognitive symptoms due to brain disease, and the usual brain-behavior relationships may be absent. This study examined symptom validity in a memory clinic sample and its effect on the associations between hippocampal volume and memory performance. Eleven of 170 consecutive patients (6.5%; 13% of patients younger than 65 years) referred to memory clinics showed noncredible performance on symptom validity tests (SVTs, viz. Word Memory Test and Test of Memory Malingering). They were compared to a demographically matched group (n = 57) selected from the remaining patients. Hippocampal volume, measured by an automated volumetric method (Freesurfer), was correlated with scores on six verbal memory tests. The median correlation was r = .49 in the matched group. However, the relation was absent (median r = -.11) in patients who failed SVTs. Memory clinic samples may include patients who show noncredible performance, which invalidates their MCI diagnosis. This underscores the importance of applying SVTs in evaluating patients with cognitive complaints that may signify a predementia stage, especially when these patients are relatively young.

The approach for treatment of large and fusiform intracranial aneurysms has evolved from stent-assisted coiling to treatment with flow-diverting stents. The treatment results for these stents are promising; however, early postprocedural aneurysm rupture has been described. The exact cause of rupture is unknown but might be related to intra-aneurysmal flow and pressure changes. We measured intra-aneurysmal pressure before, during, and after placement of a flow-diverting stent by using a dual-sensor guidewire. The pressure inside the aneurysm momentarily decreased during placement but was restored to baseline values within minutes. The flow-diverting stent does not seem to protect the aneurysm from the stress induced by pressure or pressure changes within the lumen.

Purpose: To assess whether magnetic resonance (MR) angiography can be used as a noninvasive alternative to intraarterial digital subtraction angiography (DSA) to indicate additional treatment in the follow-up of patients with coil-treated intracranial aneurysms. Materials and Methods: This was an ethics committee-approved multicenter study. Consecutive patients who were scheduled for follow-up intraarterial DSA after coil placement were invited for additional MR angiography after providing written informed consent. Interventional neuroradiologists gave treatment advice (additional treatment, extended follow-up imaging, or discharge from follow-up) for each imaging modality. Agreement between treatment advices based on intraarterial DSA and MR angiographic findings and interobserver agreement were assessed with weighted kappa statistics. Results: Agreement between intraarterial DSA- and MR angiography-based treatment recommendations was substantial (kappa = 0.73; 95% confidence interval [CI]: 0.66, 0.80). In 34 of the 310 patients (11%), the advice was additional treatment based on findings of both modalities. In six patients (2%), the advice based on intraarterial DSA findings was additional treatment, while that based on MR angiographic findings was extended follow-up imaging; therefore, none of these patients were discharged from follow-up on the basis of MR angiographic findings. In six other patients (2%), the advice based on MR angiographic findings was additional treatment, while that based on intraarterial DSA findings was extended follow-up imaging (four patients), discharge from follow-up (one patient), and noninterpretable DSA (one patient). Extended follow-up imaging was suggested for 37 patients (12%) after intraarterial DSA and for 49 patients (16%) after MR angiography (difference: 4%; 95% CI: -0.6%, 8.4%). Interobserver agreement was substantial for intraarterial DSA (kappa = 0.73; 95% CI: 0.64, 0.82) and moderate for MR angiography (kappa = 0.53; 95% CI: 0.36, 0.70). Conclusion: The overall proportion of patients advised to undergo additional treatment is similar based on intraarterial DSA and MR angiographic findings, with only few individual discrepancies. MR angiography can therefore be used for therapeutic decision making in the follow-up of patients with coil-treated aneurysms. (C) RSNA, 2012

BACKGROUND AND PURPOSE: The total amount of extravasated blood after aneurysmal subarachnoid hemorrhage, assessed with semiquantitative methods such as the modified Fisher and Hijdra scales, is known to be a predictor of delayed cerebral ischemia. However, prediction rates of delayed cerebral ischemia are moderate, which may be caused by the rough and observer-dependent blood volume estimation used in the prediction models. We therefore assessed the association between automatically quantified total blood volume on NCCT and delayed cerebral ischemia. MATERIALS AND METHODS: We retrospectively studied clinical and radiologic data of consecutive patients with aneurysmal SAH admitted to 2 academic hospitals between January 2009 and December 2011. Adjusted ORs with associated 95% confidence intervals were calculated for the association between automatically quantified total blood volume on NCCT and delayed cerebral ischemia (clinical, radiologic, and both). The calculations were also performed for the presence of an intraparenchymal hematoma and/or an intraventricular hematoma and clinical delayed cerebral ischemia. RESULTS: We included 333 patients. The adjusted OR of total blood volume for delayed cerebral ischemia (clinical, radiologic, and both) was 1.02 (95% CI, 1.01–1.03) per milliliter of blood. The adjusted OR for the presence of an intraparenchymal hematoma for clinical delayed cerebral ischemia was 0.47 (95% CI, 0.24–0.95) and of the presence of an intraventricular hematoma, 2.66 (95% CI, 1.37–5.17). CONCLUSIONS: A higher total blood volume measured with our automated quantification method is significantly associated with delayed cerebral ischemia. The results of this study encourage the use of rater-independent quantification methods in future multicenter studies on delayed cerebral ischemia prevention and prediction.

Early nutritional deprivation might cause irreversible damage to the brain. Prenatal exposure to undernutrition has been shown to be associated with increased central nervous system anomalies at birth and decreased cognitive function in adulthood. Little is known about the potential effect on the brain in older age. We investigated brain size and structure at age 68 years after prenatal famine exposure. T1-weighted structural magnetic resonance images of the brain were made in 118 Dutch famine birth cohort members. Of these 118 (44% male, age range 65-69 years), 41 had been exposed to famine in early gestation and 77 had been prenatally unexposed. Structural volumes were automatically assessed using FreeSurfer. Diffusion tensor imaging was performed and anisotropy and diffusivity were computed. Fluid attenuated inversion recovery was performed to assess white matter hyperintensities. Exposure to famine in early gestation was associated with smaller intracranial volume in males, but not females. Volumes of total brain, grey and white matter were also smaller in early exposed males, but these differences disappeared after adjusting for intracranial volume. Prenatally exposed males but not females, had a smaller intracranial and total brain volume compared to unexposed subjects. Our findings show that prenatal undernutrition permanently affected brain size.media-1vid110.1093/brain/aww132_video_abstractaww132_video_abstract.

The increasing size of medical imaging data, in particular time series such as CT perfusion (CTP), requires new and fast approaches to deliver timely results for acute care. Cloud architectures based on graphics processing units (GPUs) can provide the processing capacity required for delivering fast results. However, the size of CTP datasets makes transfers to cloud infrastructures time-consuming and therefore not suitable in acute situations. To reduce this transfer time, this work proposes a fast and lossless compression algorithm for CTP data. The algorithm exploits redundancies in the temporal dimension and keeps random read-only access to the image elements directly from the compressed data on the GPU. To the best of our knowledge, this is the first work to present a GPU-ready method for medical image compression with random access to the image elements from the compressed data.

Despite treatment with combination antiretroviral therapy (cART), cognitive impairment is still observed in perinatally HIV-infected children. We aimed to evaluate potential underlying cerebral injury by comparing neurometabolite levels between perinatally HIV-infected children and healthy controls. This cross-sectional study evaluated neurometabolites, as measured by Magnetic Resonance Spectroscopy (MRS), in perinatally HIV-infected children stable on cART (n = 26) and healthy controls (n = 36). Participants were included from a cohort of perinatally HIV-infected children and healthy controls, matched group-wise for age, gender, ethnicity, and socio-economic status. N-acetylaspartate (NAA), glutamate (Glu), myo-inositol (mI), and choline (Cho) levels were studied as ratios over creatine (Cre). Group differences and associations with HIV-related parameters, cognitive functioning, and neuronal damage markers (neurofilament and total Tau proteins) were determined using age-adjusted linear regression analyses. HIV-infected children had increased Cho:Cre in white matter (HIV-infected = 0.29 ± 0.03; controls = 0.27 ± 0.03; P value = 0.045). Lower nadir CD4+ T-cell Z-scores were associated with reduced neuronal integrity markers NAA:Cre and Glu:Cre. A Centers for Disease Control and Prevention (CDC) stage C diagnosis was associated with higher glial markers Cho:Cre and mI:Cre. Poorer cognitive performance was mainly associated with higher Cho:Cre in HIV-infected children, and with lower NAA:Cre and Glu:Cre in healthy controls. There were no associations between neurometabolites and neuronal damage markers in blood or CSF. Compared to controls, perinatally HIV-infected children had increased Cho:Cre in white matter, suggestive of ongoing glial proliferation. Levels of several neurometabolites were associated with cognitive performance, suggesting that MRS may be a useful method to assess cerebral changes potentially linked to cognitive outcomes.

Background: The aim of the current study was to assess the influence of anesthetic management on the effect of treatment in the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN). Methods: MR CLEAN was a multicenter, randomized, open-label trial of intra-arterial therapy (IAT) vs no IAT. The intended anesthetic management at the start of the procedure was used for this post hoc analysis. The primary effect parameter was the adjusted common odds ratio (acOR) for a shift in direction of a better outcome on the modified Rankin Scale (mRS) at 90 days, estimated with multivariable ordinal logistic regression analysis, which included a term for general anesthesia (GA). Results: GA was associated with significant ( p = 0.011) effect modification, resulting in estimated decrease of 51% (95% confidence interval [CI] 31%–86%) in treatment effect compared to non-GA. We found a shift in the distribution on the mRS in favor of non-GA compared to control group (acOR 2.18 [95% CI 1.49–3.20]). The shift in distribution between GA and control group was in a similar direction (acOR 1.12 [95% CI 0.71–1.78]) with loss of statistical significance. Conclusions: In this post hoc analysis, we found that the type of anesthetic management influences outcome following IAT. Only treatment without general anesthesia was associated with a significant treatment benefit in MR CLEAN. Classification of evidence: This study provides Class II evidence that for patients with acute ischemic stroke undergoing IAT, mRS scores at 90 days improve only in patients treated without GA.

Background and Purpose Time is brain: benefits of intravenous thrombolysis (IVT) in ischemic stroke last for 4.5 hours but rapidly decrease as time progresses following symptom onset. The goal of the Acute Brain Care (ABC) intervention study was to reduce the door-to-needle time (DNT) to ≤30 minutes by optimizing in-hospital stroke treatment. Methods We performed a single-centre before (pre-intervention period: 2000–2005) versus after (post-intervention period: 2006–2012) comparison in a cohort of consecutive patients treated with IVT. The intervention consisted of the implementation of a multidisciplinary stroke protocol combining simple strategies to reduce the DNT. Primary endpoint was the DNT, presented as proportion ≤30 minutes and median time. Secondary clinical endpoints were symptomatic intracranial hemorrhage (SICH), and favourable outcome defined as a modified Rankin scale (mRs) score of 0–2 at 3 months. Endpoints were additionally adjusted for baseline imbalances between the groups. Results In the pre-intervention period, none (0.0%) of the 100 patients (mean age 63.8 years, median National Institutes of Health Stroke Scale [NIHSS] score 14) treated with IVT had a DNT ≤30 minutes compared to 234 (62.7%) of the 373 patients (mean age 66.7 years, median NIHSS score 10) in the post-intervention period (p

Background Acute stroke care represents a challenge for decision makers. Recent randomized trials showed the benefits of endovascular therapy. Our goal was to provide a visual aid tool to guide clinicians in the decision process of endovascular intervention in patients with acute ischemic stroke. Methods We created visual plots (Cates’ plots; www.nntonline.net ) representing benefits of standard of care vs. endovascular thrombectomy from the pooled analysis of five RCTs using stent retrievers. These plots represent the following clinically relevant outcomes (1) functionally independent state (modified Rankin scale (mRS) 0 to 2 at 90 days) (2) excellent recovery (mRS 0–1) at 90 days, (3) NIHSS 0–2 (4) early neurological recovery, and (5) revascularization at 24 h. Subgroups visually represented include time to treatment and baseline stroke severity strata. Results Overall, 1287 patients (634 assigned to endovascular thrombectomy, 653 assigned to control were included to create the visual plots. Cates’ visual plots revealed that for every 100 patients with acute ischemic stroke and large vessel occlusion, 27 would achieve independence at 90 days (mRS 0–2) in the control group compared to 49 (95% CI 43–56) in the intervention group. Similarly, 21 patients would achieve early neurological recovery at 24 h compared to 54 (95% CI 45–63) out of 100 for the intervention group. Conclusion Cates’ plots may assist clinicians and patients to visualize and compare potential outcomes after an acute ischemic stroke. Our results suggest that for every 100 treated individuals with an acute ischemic stroke and a large vessel occlusion, endovascular thrombectomy would provide 22 additional patients reaching independency at three months and 33 more patients achieving ENR compared to controls.

Item does not contain fulltext BACKGROUND: Whether infarct size modifies intra-arterial treatment effect is not certain, particularly in patients with large infarcts. We examined the effect of the baseline Alberta Stroke Program Early CT Score (ASPECTS) on the safety and efficacy of intra-arterial treatment in a subgroup analysis of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN). METHODS: MR CLEAN was a randomised, controlled, open-label, phase 3 trial of intra-arterial treatment in patients (aged >/=18 years from the Netherlands) with proximal arterial occlusion of the anterior circulation, given intra-arterial treatment within 6 h of stroke onset. The primary outcome was 90 day modified Rankin Scale (mRS) score. We estimated the intra-arterial treatment effect for all patients in MR CLEAN who had ASPECTS graded by using multivariable ordinal logistic regression analysis (a proportional odds model) to calculate the adjusted common odds ratio for a shift towards a better functional outcome according to the mRS for intra-arterial treatment and usual care than for usual care alone. We entered an interaction term into the model to test for interaction with prespecified ASPECTS subgroups: 0-4 (large infarct) versus 5-7 (moderate infarct) versus 8-10 (small infarct). MR CLEAN is registered with the Netherlands Trial Registry, number NTR1804, and the ISRCTN Registry, number ISRCTN10888758. FINDINGS: 496 patients-232 (47%) in the intra-arterial treatment and usual care group and 264 (53%) in the usual care alone group-were included in the analysis. We noted no significant difference in intra-arterial treatment effect between the ASPECTS subgroups according to 90 day ordinal mRS (adjusted common odds ratio interaction term relative to ASPECTS 8-10: ASPECTS 0-4: 0.79 [95% CI 0.20-3.19], p=0.740; and ASPECTS 5-7: 1.02 [0.44-2.35], p=0.966). Intra-arterial treatment did not cause a significant increase in the proportion of patients with at least one serious adverse event in any of the ASPECTS subgroups (ASPECTS 0-4: eight [73%] of 11 patients in treatment and usual care group vs 11 [58%] of 19 in usual care alone group, p=0.42; ASPECTS 5-7: 32 [59%] of 54 vs 19 [49%] of 39, p=0.31; ASPECTS 8-10: 70 [42%] of 167 vs 82 [40%] of 206; p=0.68). For death within 7 days or within 30 days and hemicraniectomy, the differences between the intra-arterial treatment and usual care versus usual care alone groups were not significant by ASPECTS subgroups. A significantly higher proportion of patients had recurrent ischaemic stroke in the intra-arterial treatment plus usual care group than in the usual care alone group in the ASPECTS 8-10 subgroup (eight [5%] vs one [

BACKGROUND AND PURPOSE: The use of stents in the setting of SAH is controversial because of concerns about the efficacy and risk of dual antiplatelet therapy. We compare complications of stent-assisted coil embolization in patients with acutely ruptured aneurysms with complications in patients with unruptured aneurysms. MATERIALS AND METHODS: Between February 2007 and March 2015, 45 acutely ruptured aneurysms and 47 unruptured aneurysms were treated with stent-assisted coiling. Patients with ruptured aneurysms were not pretreated with antiplatelet medication but received intravenous aspirin during the procedure. Thromboembolic events and early rebleeds were recorded. RESULTS: In ruptured aneurysms, 9 of 45 patients had thromboembolic complications. Four patients remained asymptomatic, 4 developed infarctions, and 1 patient died. The permanent complication rate in ruptured aneurysms was 11% (95% CI, 4%–24%). Five of 45 patients (11%; 95% CI, 4%–24%) had an early rebleed from the treated aneurysm after 3–45 days, and in 4, this rebleed was fatal. In 46 patients with 47 unruptured aneurysms, thromboembolic complications occurred in 2. One patient remained asymptomatic; the other had a thalamus infarction. The complication rate in unruptured aneurysms was 2.2% (1 of 46; 95% CI, 0.01%–12%). No first-time hemorrhages occurred in 46 patients with 47 aneurysms during 6 months of follow-up. CONCLUSIONS: The complication rate of stent-assisted coiling with early adverse events in ruptured aneurysms was 10 times higher than that in unruptured aneurysms. Early rebleed accounted for most mortality. In ruptured aneurysms, stent-assisted coil embolization is associated with increased morbidity and mortality and should only be considered when less risky options have been excluded.

The objective of this study was to investigate the performance of k-t BLAST (Broad-use Linear Acquisition Speed-up Technique) accelerated time-resolved 3D PC-MRI compared to SENSE (SENSitivity Encoding) acceleration in an in vitro and in vivo intracranial aneurysm. Non-accelerated, SENSE and k-t BLAST accelerated time-resolved 3D PC-MRI measurements were performed in vivo and in vitro. We analysed the consequences of various temporal resolutions in vitro. Both in vitro and in vivo measurements showed that the main effect of k-t BLAST was underestimation of velocity during systole. In the phantom, temporal blurring decreased with increasing temporal resolution. Quantification of the differences between the non-accelerated and accelerated measurements confirmed that in systole SENSE performed better than k-t BLAST in terms of mean velocity magnitude. In both in vitro and in vivo measurements, k-t BLAST had higher SNR compared to SENSE. Qualitative comparison between measurements showed good similarity. Comparison with SENSE revealed temporal blurring effects in k-t BLAST accelerated measurements.

3,4-Methylenedioxymethamphetamine (MDMA or ecstasy) is a popular recreational drug that has been shown to induce loss of brain serotonin (5-HT) neurons. The purpose of this study was to determine the usefulness of pharmacological magnetic resonance imaging (phMRI) in assessing 5-HT dysfunction by examining the hemodynamic response evoked by infusion with the selective 5-HT reuptake inhibitor citalopram. We studied the effects of MDMA on brain hemodynamics using arterial spin labeling (ASL) based phMRI following a citalopram challenge (7.5 mg/kg, i.v.), combined with [I-123]beta-CIT SPECT imaging in ten male MDMA users and seven healthy non-users. Single photon emission computed tomography (SPECT) imaging was used to assess the availability of 5-HT transporters (SERT). Imaging results were compared with the results of behavioral measures and mood changes following drug administration, in both groups (using the Beck Depression Inventory, Barratt Impulsiveness Scale and a visual analog scale). Reductions in SERT binding were observed in the occipital cortex of MDMA users. In line with this, citalopram induced decreases in cerebral blood flow (CBF) in the occipital cortex of MDMA users. ASL based phMRI also detected a CBF decrease in the thalamus of MDMA users. In concordance with imaging findings, behavioral measures differed significantly between MDMA users and controls. MDMA users had higher impulsivity scores and felt more uncomfortable after citalopram infusion, compared with control subjects. Our findings indicate that phMRI is very well suited for in-vivo assessment of 5-HT dysfunction. (C) 2011 Elsevier B.V. and ECNP. All rights reserved

BACKGROUND AND PURPOSE: Local hemodynamic information may help to stratify rupture risk of cerebral aneurysms. Patient-specific modeling of cerebral hemodynamics requires accurate data on BFV in perianeurysmal arteries as boundary conditions for CFD. The aim was to compare the BFV measured with PC-MR imaging with that obtained by using intra-arterial Doppler sonography and to determine interpatient variation in intracranial BFV. MATERIALS AND METHODS: In 10 patients with unruptured intracranial aneurysms, BFV was measured in the cavernous ICA with PC-MR imaging in conscious patients before treatment, and measured by using an intra-arterial Doppler sonography wire when the patient was anesthetized with either propofol (6 patients) or sevoflurane (4 patients). RESULTS: Both techniques identified a pulsatile blood flow pattern in cerebral arteries. PSV differed >50 cm/s between patients. A mean velocity of 41.3 cm/s (95% CI, 39.3–43.3) was measured with PC-MR imaging. With intra-arterial Doppler sonography, a mean velocity of 29.3 cm/s (95% CI, 25.8–32.8) was measured with the patient under propofol-based intravenous anesthesia. In patients under sevoflurane-based inhaled anesthesia, a mean velocity of 44.9 cm/s (95% CI, 40.6–49.3) was measured. CONCLUSIONS: We showed large differences in BFV between patients, emphasizing the importance of using patient-specific hemodynamic boundary conditions in CFD. PC-MR imaging measurements of BFV in conscious patients were comparable with those obtained with the intra-arterial Doppler sonography when the patient was anesthetized with a sevoflurane-based inhaled anesthetic.

Flow-territory mapping by MR imaging ASL noninvasively provides a unique insight into the distribution of cerebral perfusion. The introduction of planning-free vessel-encoded pCASL made flow-territory mapping feasible for clinical use, though lack of individual planning could impede reproducibility of this technique. We assessed the reproducibility of planning-free vessel-encoded pCASL in patients and controls. Results indicated that planning-free vessel-encoded pCASL is a reproducible method that could assist in clinical decision-making.

BACKGROUND AND PURPOSE: Semiautomated methods for ICA stenosis measurements have the potential to reduce interobserver variability and to speed up its analysis. In this study, we estimate the precision and accuracy of a semiautomated measurement for carotid artery stenosis degree and identify and explain differences compared with the manual method. MATERIALS AND METHODS: In this retrospective study involving 90 patients, 2 observers determined the stenosis degree twice, with both the semiautomated and the manual method. Intra- and interobserver correlations were calculated for both methods. The accuracy was estimated by comparing average semiautomated with manual measurements. The semiautomated stenosis calculations were performed using either the minimal or maximal intersection at the reference site. Individual cases with large differences in measurement were retrospectively inspected by 3 observers. RESULTS: Intra- ( R = 0.93, 0.96) and interobserver ( R = 0.98) correlations for the semiautomated method were excellent and exceeded the manual performance correlations ( R = 0.87, 0.86). The semiautomated measurements correlated well with the manual measurements ( R = 0.87), with high specificity of 96% and lower sensitivity of 63%. Large differences were caused by misinterpretations of the semiautomated method associated with calcified plaques, resulting in overestimations of the minimal diameter, underestimation of stenosis degree, and incorrect centerlines. The effect of using the minimal diameter at the reference position resulted in a small, but significant, underestimation of the stenosis degree by the semiautomated method. CONCLUSIONS: The semiautomated method showed an excellent reproducibility and good correlation with manual measurements with a high specificity and lower sensitivity for detecting a significant stenosis. Erroneous semiautomatic stenosis measurements were associated with the presence of calcium.

Introduction Intracranial carotid artery atherosclerotic disease is an independent predictor for recurrent stroke. However, its quantitative assessment is not routinely performed in clinical practice. In this diagnostic study, we present and evaluate a novel semi-automatic application to quantitatively measure intracranial internal carotid artery (ICA) degree of stenosis and calcium volume in CT angiography (CTA) images. Methods In this retrospective study involving CTA images of 88 consecutive patients, intracranial ICA stenosis was quantitatively measured by two independent observers. Stenoses were categorized with cutoff values of 30% and 50%. The calcification in the intracranial ICA was qualitatively categorized as absent, mild, moderate, or severe and quantitatively measured using the semi-automatic application. Linear weighted kappa values were calculated to assess the interobserver agreement of the stenosis and calcium categorization. The average and the standard deviation of the quantitative calcium volume were calculated for the calcium categories. Results For the stenosis measurements, the CTA images of 162 arteries yielded an interobserver correlation of 0.78 (P

Objective: Cognitive impairment is highly prevalent in HIV-1-infected (HIV) patients, despite adequate suppression of viral replication by combination antiretroviral therapy (cART). Cerebral white matter structure alterations are often associated with cognitive impairment and have commonly been reported in the natural course of HIV infection. However, the existence of these alterations in adequately treated HIVpatients remains unknown, as well as its possible association with cognitive impairment. Design: We used diffusion tensor imaging (DTI) to investigate whether white matter structure alterations exist in HIV patients with sustained suppressed viral replication on cART, and if such alterations are related to HIV-associated cognitive deficits. Methods: We compared 100 aviraemic HIV men on cART with 70 HIV-uninfected, otherwise comparable men. Clinical and neuropsychological assessments were performed. From DTI data, white matter fractional anisotropy and mean diffusion were calculated. Subsequently, tract-based spatial statistics (TBSS) was performed, with and without masking out white matter lesions. Results: HIV patients showed diffuse white matter structure alterations as compared with HIV-uninfected controls, observed as widespread decreased fractional anisotropy and an increasedmean diffusion. Thesewhitematter structure alterations were associated with the number of years spent with a CD4 cell count below 500 cells/ml, but not with HIV-associated cognitive deficits. Conclusion: Cerebral white matter structure alterations are found in middle-aged HIV men with sustained suppression of viraemia on cART, and may result from periods with immune deficiency when viral toxicity and host-inflammatory responses were at their peak. These white matter structure alterations were not associated with the observed subtle HIV-associated cognitive deficits.

Intra- and multicenter reproducibility of currently used arterial spin labeling (ASL) methods were assessed at three imaging centers in the Netherlands, equipped with Philips 3TMR scanners. Six healthy participants were scanned twice at each site. The imaging protocol consisted of continuous ASL (CASL), pseudo-continuous ASL (p-CASL) with and without background suppression, pulsed ASL (PASL) with single and multiple inversion times (TIs), and selective ASL for segmentation. Reproducibility was expressed in terms of the coefficient of repeatability and the repeatability index. Voxelwise analysis of variance was performed, yielding brain maps that reflected regional variability. Intra- and multicenter reproducibility were comparable for all methods, except for single TI PASL, with better intracenter reproducibility (F-test of equality of two variances, P < 0.05). Pseudo-continuous ASL and multi TI PASL varied least between sites. Variability maps of all methods showed most variability near brain-feeding arteries within sessions and in gray matter between sessions. On the basis of the results of this study, one could consider the use of reference values in clinical routine, with whole-brain p-CASL perfusion varying < 20% over repeated measurements within the same individuals considered to be normal. Knowledge on regional variability allows for the use of perfusion-weighted images in the assessment of local cerebral pathology.