In vitro and in silico assessment of flow modulation after deploying the Contour Neurovascular System in intracranial aneurysm models.

BACKGROUND: The novel Contour Neurovascular System (Contour) has been reported to be efficient and safe for the treatment of intracranial, wide-necked bifurcation aneurysms. Flow in the aneurysm and posterior cerebral arteries (PCAs) after Contour deployment has not been analyzed in detail yet. However, this information is crucial for predicting aneurysm treatment outcomes. METHODS: Time-resolved three-dimensional velocity maps in 14 combinations of patient-based basilar tip aneurysm models with and without Contour devices (sizes between 5 and 14 mm) were analyzed using four-dimensionsal (4D) flow MRI and numerical/image-based flow simulations. A complex virtual processing pipeline was developed to mimic the experimental shape and position of the Contour together with the simulations. RESULTS: On average, the Contour significantly reduced intra-aneurysmal flow velocity by 67% (mean w/ = 0.03m/s; mean w/o = 0.12m/s; p-value=0.002), and the time-averaged wall shear stress by more than 87% (mean w/ = 0.17Pa; mean w/o = 1.35Pa; p-value=0.002), as observed by numerical simulations. Furthermore, a significant reduction in flow (P<0.01) was confirmed by the neck inflow rate, kinetic energy, and inflow concentration index after Contour deployment. Notably, device size has a stronger effect on reducing flow than device positioning. However, positioning affected flow in the PCAs, while being robust in effectively reducing flow. CONCLUSIONS: This study showed the high efficacy of the Contour device in reducing flow within aneurysms regardless of the exact position. However, we observed an effect on the flow in PCAs, which needs to be investigated further.

Editor's Choice - Risk of Stroke before Revascularisation in Patients with Symptomatic Carotid Stenosis: A Pooled Analysis of Randomised Controlled Trials.

OBJECTIVE: Current guidelines recommending rapid revascularisation of symptomatic carotid stenosis are largely based on data from clinical trials performed at a time when best medical therapy was potentially less effective than today. The risk of stroke and its predictors among patients with symptomatic carotid stenosis awaiting revascularisation in recent randomised controlled trials (RCTs) and in medical arms of earlier RCTs was assessed. METHODS: The pooled data of individual patients with symptomatic carotid stenosis randomised to stenting (CAS) or endarterectomy (CEA) in four recent RCTs, and of patients randomised to medical therapy in three earlier RCTs comparing CEA vs. medical therapy, were compared. The primary outcome event was any stroke occurring between randomisation and treatment by CAS or CEA, or within 120 days after randomisation. RESULTS: A total of 4 754 patients from recent trials and 1 227 from earlier trials were included. In recent trials, patients were randomised a median of 18 (IQR 7, 50) days after the qualifying event (QE). Twenty-three suffered a stroke while waiting for revascularisation (cumulative 120 day risk 1.97%, 95% confidence interval [CI] 0.75 - 3.17). Shorter time from QE until randomisation increased stroke risk after randomisation (χ2 = 6.58, p = .011). Sixty-one patients had a stroke within 120 days of randomisation in the medical arms of earlier trials (cumulative risk 5%, 95% CI 3.8 - 6.2). Stroke risk was lower in recent than earlier trials when adjusted for time between QE and randomisation, age, severity of QE, and degree of carotid stenosis (HR 0.47, 95% CI 0.25 - 0.88, p = .019). CONCLUSION: Patients with symptomatic carotid stenosis enrolled in recent large RCTs had a lower risk of stroke after randomisation than historical controls. The added benefit of carotid revascularisation to modern medical care needs to be revisited in future studies. Until then, adhering to current recommendations for early revascularisation of patients with symptomatic carotid stenosis considered to require invasive treatment is advisable.

Automated versus manual imaging assessment of early ischemic changes in acute stroke: comparison of two software packages and expert consensus.

AIM: The purpose of our study was to compare the agreement of both the total Alberta Stroke Program Early CT Score (ASPECTS) and region-based scores from two automated ASPECTS software packages and an expert consensus (EC) reading with final ASPECTS in a selected cohort of patients who had prompt reperfusion from endovascular thrombectomy (EVT). METHODS: ASPECTS were retrospectively and blindly assessed by two software packages and EC on baseline non-contrast-enhanced computed tomography (NCCT) images. All patients had multimodal CT imaging including NCCT, CT angiography, and CT perfusion which demonstrated an acute anterior circulation ischemic stroke with a large vessel occlusion. Final ASPECTS on follow-up scans in patients who had EVT and achieved complete reperfusion within 100 min from NCCT served as ground truth and were compared to total and region-based scores. RESULTS: Fifty-two patients met our study criteria. Moderate agreement was obtained between both software packages and EC for total ASPECTS and there was no significant difference in overall performance. However, the software packages differed with respect to regional contribution. In this cohort, the majority of infarcted regions were deep structures. Package A was more sensitive in cortical areas than the other methods, but at a cost of specificity. EC and software package B had greater sensitivity, but lower specificity for deep brain structures. CONCLUSION: In this cohort, using the final ASPECTS as ground truth, no clinically significant difference was observed for total ASPECT score between human or automated packages, but there were differences in the characteristics of the regions scored. KEY POINTS: • Some national stroke guidelines have incorporated ASPECTS in their recommendations for selecting patients for endovascular therapy. • Computer-aided diagnosis is a promising tool to aid the evaluation of early ischemic changes identified on CT. • Software packages for automated ASPECTS assessment differed significantly with respect to regional contribution without any significant difference in the overall ASPECT score.

Optimization of 3D phase contrast venography for the assessment of the cranio-cervical venous system at 1.5 T.

PURPOSE: The aim of this work was to optimize a three-dimensional (3D) phase-contrast venography (PCV) product MR pulse sequence in order to obtain clinically reliable images with less artifacts for an improved depiction of the cranio-cervical venous vessels. METHODS: Starting from the product sequence, the 3D PCV protocol was optimized in eight steps with respect to the velocity encoding (Venc) direction and value, slice thickness, reduction of susceptibility artifacts and arterial contamination, gradient mode and radio-frequency (RF)-spoiling, B0-Shimming, asymmetric echo technique and RF-pulse type, and flip angle. The product and optimized protocol was used to perform 3D PCV in 12 healthy male volunteers with a median age of 50 years using a state-of-the-art 1.5-T MR system. For evaluation, the cranio-cervical venous system was divided into 15 segments. These segments were evaluated by three radiologists with experience in neuroradiology. An ordinal scoring system was used to access the overall diagnostic quality, arterial contamination, and the quality of visualization. RESULTS: Image quality in the optimized 3D PCV was graded as "excellent" by all readers in 65.3% of the cases (p < 0.0001). The visualization of venous segments was strongly improved: it was considered diagnostic in 81.8% of all cases using the optimized sequence and in 47.6% for the product 3D PCV (p < 0.0001), respectively. The optimized protocol improved the imaging of all venous segments (p < 0.0001). CONCLUSION: The optimized 3D PCV pulse sequence showed superior results compared to the product 3D PCV for the visualization and evaluation of the venous system in all healthy volunteers.

Diffusion-weighted imaging or computerized tomography perfusion assessment with clinical mismatch in the triage of wake up and late presenting strokes undergoing neurointervention with Trevo (DAWN) trial methods.

Rationale Efficacy of mechanical thrombectomy for acute stroke due to large vessel occlusion initiated beyond 6 h of time last seen well has not been demonstrated in randomized trials. Aim To establish whether subjects considered to have substantial areas of salvageable brain based on age-adjusted clinical core mismatch who can undergo endovascular treatment within 6-24 h from time last seen well (TLSW) have better outcomes at three months compared to subjects treated with standard medical therapy alone. Age-adjusted clinical core mismatch is defined by age (≤80 or >80 years), baseline National Institutes of Health Stroke Scale (NIHSS) (10-20 or ≥21), and core size (0-20 cm3 in subjects older than 80 and, in subjects younger than 80, 0-30 cm3 with NIHSS 10-20 and 31-50 cm3 with NIHSS ≥21). Design Prospective, randomized, multicenter, Bayesian adaptive-enrichment, open label trial with blinded endpoint assessment. For the purpose of enrolment, ischemic core size will be evaluated by CT perfusion or magnetic resonance imaging-diffusion-weighted imaging measured by automated software (RAPID). Procedures Subjects with acute ischemic stroke due to computed tomography angiography- or magnetic resonance angiogram-proven arterial occlusion of the intracranial internal carotid and/or proximal middle cerebral artery (M1) with age-adjusted clinical core mismatch in whom treatment can be initiated between 6 and 24 h from TSLW are randomized in a 1:1 ratio to receive mechanical embolectomy with the Trevo device or medical management alone. Sequential interim analyses allowing adaptation of enrolment criteria or stopping new enrolment for futility or predicted success will occur in every 50 randomized patients starting at 150 to a maximum of 500 patients. Study outcomes The primary endpoint is the modified Rankin Scale score at 90 days. The primary safety outcome is stroke-related mortality at 90 days. Analysis The primary endpoint, expressed as a utility-weighted modified Rankin Scale score is analyzed using a Bayesian posterior probability with adjustment for ischemic core size. For regulatory reasons, a nested co-primary endpoint analysis was added consisting of the proportion of subjects with modified Rankin Scale 0-2 between the active and control groups also analyzed using a Bayesian model.

Cost-Effectiveness of Solitaire Stent Retriever Thrombectomy for Acute Ischemic Stroke: Results From the SWIFT-PRIME Trial (Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke).

BACKGROUND AND PURPOSE: Clinical trials have demonstrated improved 90-day outcomes for patients with acute ischemic stroke treated with stent retriever thrombectomy plus tissue-type plasminogen activator (SST+tPA) compared with tPA. Previous studies suggested that this strategy may be cost-effective, but models were derived from pooled data and older assumptions. METHODS: In this prospective economic substudy conducted alongside the SWIFT-PRIME trial (Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke), in-trial costs were measured for patients using detailed medical resource utilization and hospital billing data. Utility weights were assessed at 30 and 90 days using the EuroQol-5 dimension questionnaire. Post-trial costs and life-expectancy were estimated for each surviving patient using a model based on trial data and inputs derived from a contemporary cohort of ischemic stroke survivors. RESULTS: Index hospitalization costs were $17 183 per patient higher for SST+tPA than for tPA ($45 761 versus $28 578; P<0.001), driven by initial procedure costs. Between discharge and 90 days, costs were $4904 per patient lower for SST+tPA than for tPA ($11 270 versus $16 174; P=0.014); total 90-day costs remained higher with SST+tPA ($57 031 versus $44 752; P<0.001). Higher utility values for SST+tPA led to higher in-trial quality-adjusted life years (0.131 versus 0.105; P=0.005). In lifetime projections, SST+tPA was associated with substantial gains in quality-adjusted life years (6.79 versus 5.05), cost savings of $23 203 per patient and was economically dominant when compared with tPA in 90% of bootstrap replicates. CONCLUSIONS: Among patients with acute ischemic stroke enrolled in the SWIFT-PRIME trial, SST increased initial treatment costs, but was projected to improve quality-adjusted life-expectancy and reduce healthcare costs over a lifetime horizon compared with tPA. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01657461.

Myocardial Fibrosis in Hypertrophic Cardiomyopathy: Volumetric Assessment of Late Enhancement Provided by Cardiac Computed Tomography.

INTRODUCTION: With subgroups of patients with hypertrophic cardiomyopathy (HCM) confers a 4% to 5% risk for adverse prognosis. Besides left-ventricular muscle mass (LV-MM) myocardial fibrosis (MF) assessable by late gadolinium enhancement in cardiovascular magnetic resonance (LGE-CMR) has been related to that. Myocardial fibrosis can also be demonstrated by late enhancement (LE) in late-enhanced multislice computed tomography (leMDCT). This analysis investigates leMDCT whether to enable quantification of LE load in terms of LE mass by percent LV-MM in HCM. METHODS: In a prospective validation study, we included 30 consecutive patients with HCM who underwent leMDCT (64 slice) and LGE-CMR (1.5 T). The leMDCT scan was performed 7 minutes after injection of iodine contrast (Iopromid). Endocardial and epicardial planimetry served for the assessment of LV-MM. Visually detectable LE was quantified using the manual quantification method resulting in LE by percent LV-MM (%LE). The LGE-CMR data served for validation. RESULTS: Mean (SD) age was 64.1 (13.9) years. Myocardial fibrosis prevalence was 63.3% (19/30 patients indentified by both leMDCT and LGE-CMR). In leMDCT, tissue density in LE areas compared with normal myocardium was higher (138.2 [23.9] HU vs 98.4 [16.5] HU, P < 0.001) but lower than in the LV cavity (138.2 [23.9] HU vs 169.2 [35.9] HU, P < 0.001). Late enhancement mass in leMDCT seemed to be 7.9 (8.5) g LE versus 8.6 [11] g LGE in CMR (P = 0.497, r = 0.95) resulting in a leMDCT/LGE-CMR relation of 1.2. Referring LE mass to LV-MM gave an LE proportion measured by leMDCT of 4 (3.9) %LE versus 3.9 (4.1) %LGE in LGE-CMR (r = 0.88, P = 0.75). Intraobserver/interobserver reliability of LE mass assessment showed an intraclass correlation coefficient of 0.99 and 0.97. CONCLUSIONS: In patients with HCM, leMDCT provides volumetric assessment of LE mass-absolutely and by percent LV-MM.

Assessment of pedophilia using hemodynamic brain response to sexual stimuli.

CONTEXT: Accurately assessing sexual preference is important in the treatment of child sex offenders. Phallometry is the standard method to identify sexual preference; however, this measure has been criticized for its intrusiveness and limited reliability. OBJECTIVE: To evaluate whether spatial response pattern to sexual stimuli as revealed by a change in the blood oxygen level-dependent signal facilitates the identification of pedophiles. DESIGN: During functional magnetic resonance imaging, pedophilic and nonpedophilic participants were briefly exposed to same- and opposite-sex images of nude children and adults. We calculated differences in blood oxygen level-dependent signals to child and adult sexual stimuli for each participant. The corresponding contrast images were entered into a group analysis to calculate whole-brain difference maps between groups. We calculated an expression value that corresponded to the group result for each participant. These expression values were submitted to 2 different classification algorithms: Fisher linear discriminant analysis and κ -nearest neighbor analysis. This classification procedure was cross-validated using the leave-one-out method. SETTING: Section of Sexual Medicine, Medical School, Christian Albrechts University of Kiel, Kiel, Germany. PARTICIPANTS: We recruited 24 participants with pedophilia who were sexually attracted to either prepubescent girls (n = 11) or prepubescent boys (n = 13) and 32 healthy male controls who were sexually attracted to either adult women (n = 18) or adult men (n = 14). MAIN OUTCOME MEASURES: Sensitivity and specificity scores of the 2 classification algorithms. RESULTS: The highest classification accuracy was achieved by Fisher linear discriminant analysis, which showed a mean accuracy of 95% (100% specificity, 88% sensitivity). CONCLUSIONS: Functional brain response patterns to sexual stimuli contain sufficient information to identify pedophiles with high accuracy. The automatic classification of these patterns is a promising objective tool to clinically diagnose pedophilia.

Assessment of thrombus in acute middle cerebral artery occlusion using thin-slice nonenhanced Computed Tomography reconstructions.

BACKGROUND AND PURPOSE: We sought to evaluate how accurately length and volume of thrombotic clots occluding cerebral arteries of patients with acute ischemic stroke can be assessed from nonenhanced CT (NECT) scans reconstructed with different slice widths. METHODS: NECT image data of 58 patients with acute ischemic stroke with vascular occlusion proven by CT angiography were reconstructed with slice widths of 1.25 mm, 2.5 mm, 3.75 mm, and 5 mm. Thrombus lengths and volumes were quantified based on these NECT images by detecting and segmenting intra-arterial hyperdensities. The results were compared with reference values of thrombus length and volume obtained from CT angiography images using Bland-Altman analysis and predefined levels or tolerance to find NECT slice thicknesses that allow for sufficiently accurate thrombus quantification. RESULTS: Thrombus length can be measured with high accuracy using the hyperdense middle cerebral artery sign detected in NECT images with slice thicknesses of 1.25 mm and 2.5 mm. We found mean deviations from the reference values and limits of agreement of -0.1 mm+/-0.6 mm with slice widths of 1.25 mm and 0.1 mm+/-0.7 mm for slice widths of 2.5 mm. Thrombus length measurements in NECT images with higher slice width and all evaluated thrombus volume measurements exhibited severe dependence on the level and did not match the accuracy criteria. CONCLUSIONS: The length of the hyperdense middle cerebral artery sign as detected on thin-slice NECT reconstructions in patients with acute ischemic stroke can be used to quantify thrombotic burden accurately. Thus, it might qualify as a new diagnostic parameter in acute stroke management that indicates and quantifies the extent of vascular obliteration.

Assessment of sexual orientation using the hemodynamic brain response to visual sexual stimuli.

INTRODUCTION: The assessment of sexual orientation is of importance to the diagnosis and treatment of sex offenders and paraphilic disorders. Phallometry is considered gold standard in objectifying sexual orientation, yet this measurement has been criticized because of its intrusiveness and limited reliability. AIM: To evaluate whether the spatial response pattern to sexual stimuli as revealed by a change in blood oxygen level-dependent (BOLD) signal can be used for individual classification of sexual orientation. METHODS: We used a preexisting functional MRI (fMRI) data set that had been acquired in a nonclinical sample of 12 heterosexual men and 14 homosexual men. During fMRI, participants were briefly exposed to pictures of same-sex and opposite-sex genitals. Data analysis involved four steps: (i) differences in the BOLD response to female and male sexual stimuli were calculated for each subject; (ii) these contrast images were entered into a group analysis to calculate whole-brain difference maps between homosexual and heterosexual participants; (iii) a single expression value was computed for each subject expressing its correspondence to the group result; and (iv) based on these expression values, Fisher's linear discriminant analysis and the kappa-nearest neighbor classification method were used to predict the sexual orientation of each subject. MEAN OUTCOME MEASURE: Sensitivity and specificity of the two classification methods in predicting individual sexual orientation. RESULTS: Both classification methods performed well in predicting individual sexual orientation with a mean accuracy of >85% (Fisher's linear discriminant analysis: 92% sensitivity, 85% specificity; kappa-nearest neighbor classification: 88% sensitivity, 92% specificity). CONCLUSION: Despite the small sample size, the functional response patterns of the brain to sexual stimuli contained sufficient information to predict individual sexual orientation with high accuracy. These results suggest that fMRI-based classification methods hold promise for the diagnosis of paraphilic disorders (e.g., pedophilia).

Intraoperative dynamic susceptibility contrast weighted magnetic resonance imaging (iDSC-MRI) - Technical considerations and feasibility.

DSC-MRI was applied intraoperatively during brain tumor removal. Immediately after presumed complete tumor resection an MRI including a dynamic susceptibility contrast T2-weighted EPI sequence was performed in 6 patients while the skull was still open using a flexible two-channel coil system at an intraoperative 1.5-Tesla MR scanner. After an initial baseline period of this iDSC-MRI sequence a bolus of contrast agent was administered intravenously. Maps of relative regional blood flow (rCBF), blood volume (rCBV) and the mean transit time (MTT) were calculated. These maps were compared to preoperatively acquired DSC-MRI data. The extent of the resection was compared with the postoperative MRI performed 24 h after the operation. In five patients complete tumor removal was already achieved at the time of iDSC-MRI and no areas of elevated perfusion values adjacent to the resection cavity were found. Complete removal was again documented on the postoperatively performed MRI. In one case there was residual tumor that showed both contrast enhancement and identical perfusion ratios as in the preoperatively acquired data. Removal of the remaining tumor was performed. iDSC-MRI is technically feasible as there are no significant susceptibility artifacts. DSC-MRI has been used to distinguish different tumor entities preoperatively and recurrent disease from radiation necrosis. Despite brain shift and thus invalidated preoperative image data or contrast leakage caused by intraoperative manipulation, iDCS-MRI furthermore reliably detects residual tumor intraoperatively at a timepoint where further resection is still possible and thus enables the neurosurgeon to complete the resection during the same procedure.

Hemodynamic assessment of carotid stenosis by functional magnetic resonance imaging.

BACKGROUND: Functional magnetic resonance imaging (fMRI) is a method usually used to identify cortical representations of cerebral functions. Some studies and case reports suggest that stenoses of the brain-supplying arteries influence the BOLD (blood-oxygenation-level-dependent) signal. The objective of this study was to find out whether the BOLD signal differs in the ipsilateral hemisphere of patients with hemodynamically relevant and those with irrelevant stenosis of the internal carotid artery (ICA) and if a successful treatment might have an influence on the BOLD signal. METHODS: We included 10 patients with hemodynamically relevant stenosis in group 1; another 10 patients with hemodynamically irrelevant stenosis of the ICA were included in group 2. Patients underwent recanalization by either stenting or operation of the ICA. fMRI with a hand-tapping task was performed before and after treatment. Data were analyzed with 'Statistical Parametric Mapping' 2 for both hemispheres. An asymmetry index (AI, range 0-2) was calculated for the hand motor areas. RESULTS: All data are given as means +/- SD. The mean preinterventional AI in group 1 was 1.08 +/- 0.87 and 0.30 +/- 0.54 in group 2 (p = 0.029). The mean postinterventional AI was 0.32 +/- 0.29 in group 1 and 0.25 +/- 0.21 in group 2 (p = 0.599). CONCLUSION: fMRI is not only capable of delivering spatial information, but also of distinguishing a hemodynamically relevant from an irrelevant stenosis of the ICA.