Charles B. L. M. Majoie

Functional magnetic resonance imaging for neurosurgical planning in neurooncology

Functional magnetic resonance imaging (fMRI) is a non-invasive technique that is widely available and can be used to determine the spatial relationships between tumor tissue and eloquent brain areas. Within certain limits, this functional information can be applied in the field of neurosurgery as a pre-operative mapping tool to minimize damage to eloquent brain areas. In this article, we review the literature on the use of fMRI for neurosurgical planning. The issues addressed are: (1) stimulation paradigms, (2) the influence of tumors on the blood oxygenation level-dependent (BOLD) signal, (3) post-processing the fMRI time course, (4) integration of fMRI results into neuronavigation systems, (5) the accuracy of fMRI and (6) fMRI compared to intra-operative mapping (IOM).

Bevacizumab and dose-intense temozolomide in recurrent high-grade glioma

BACKGROUND Angiogenesis inhibition is a rational treatment strategy for high-grade glioma (HGG). Combined antiangiogenic therapy and chemotherapy could be beneficial, taking advantage of different mechanisms of antitumour activity of both therapies. We carried out a phase I-II clinical trial with the combination of bevacizumab and continuous dose-intense temozolomide (TMZ) for patients with a recurrent HGG after first- or second-line treatment. PATIENTS AND METHODS Twenty-three HGG patients were treated with bevacizumab (10 mg/kg i.v. every 3 weeks) and TMZ (daily 50 mg/m(2)), until clinical or radiological progression. Conventional and dynamic magnetic resonance imaging (MRI) were carried out on days -4, 3 and 21 and until clinical or radiological progression. RESULTS Overall response rate (20%), 6-month progression-free survival (PFS6) (17.4%), median progression-free survival (13.9 weeks) and median overall survival (OS) (17.1 weeks) were considerably lower compared with most other studies with bevacizumab-containing regimens. The dynamic MRI parameters contrast transfer coefficient and relative cerebral blood volume decreased rapidly during the early phases of treatment, reflecting changes in vascularisation and vessel permeability but not in tumour activity. In addition, >50% of patients showed oedema reduction and a reduced shift on T1 images. CONCLUSION Treatment with bevacizumab and TMZ is feasible and well tolerated but did not improve PFS6 and median OS.

A decrease in blood pressure is associated with unfavorable outcome in patients undergoing thrombectomy under general anesthesia

Background Up to two-thirds of patients are either dependent or dead 3 months after thrombectomy for acute ischemic stroke (AIS). Loss of cerebral autoregulation may render patients with AIS vulnerable to decreases in mean arterial pressure (MAP). Objective To determine whether a fall in MAP during intervention under general anesthesia (GA) affects functional outcome. Methods This subgroup analysis included patients from the MR CLEAN trial treated with thrombectomy under GA. The investigated variables were the difference between MAP at baseline and average MAP during GA (ΔMAP) as well as the difference between baseline MAP and the lowest MAP during GA (ΔLMAP). Their association with a shift towards better outcome on the modified Rankin Scale (mRS) after 90 days was determined using ordinal logistic regression with adjustment for prognostic baseline variables. Results Sixty of the 85 patients treated under GA in MR CLEAN had sufficient anesthetic information available for the analysis. A greater ΔMAP was associated with worse outcome (adjusted common OR (acOR) 0.95 per point mm Hg, 95% CI 0.92 to 0.99). An average MAP during GA 10 mm Hg lower than baseline MAP constituted a 1.67 times lower odds of a shift towards good outcome on the mRS. For ΔLMAP this association was not significant (acOR 0.97 per mm Hg, 95% CI 0.94 to 1.00, p=0.09). Conclusions A decrease in MAP during intervention under GA compared with baseline is associated with worse outcome. Trial registration number NTR1804; ISRCTN10888758; post-results.

Endovascular treatment in patients with acute ischemic stroke and apparent occlusion of the extracranial internal carotid artery on CTA

Background Intra-arterial treatment is gaining importance in acute ischemic stroke, but its role in patients with apparent occlusion of the extracranial internal carotid artery (ICA) on computed tomographic angiography (CTA) is inconclusive. Objective To review retrospectively the results of intra-arterial treatment in patients with stroke and apparent extracranial ICA occlusion. Methods In more than 3000 patients with stroke admitted to our institution during 2008–2013, and the subgroup with suboptimal results after intravenous thrombolysis (IVT), CTA showed the absence of contrast in the extracranial ICA in 16 patients. Angiography showed true occlusion of the extracranial ICA in 10 and pseudo-occlusion in 6 patients. Treatment was considered technically successful when Thrombolysis in Cerebral Infarction scale (TICI) scores improved to 2 or 3 and clinically successful when the National Institutes of Health Stroke Scale (NIHSS) improved by at least 10 points or a NIHSS score of 0 or 1 was found at discharge. Results Recanalization was achieved in 5 of 6 patients with pseudo-occlusions and in 6 of 10 patients with true occlusion of the extracranial ICA. Favorable clinical outcomes were seen in 3 of 6 patients with pseudo-occlusions and in 4 of 10 patients with true occlusions. Four patients died, and in these patients infarction of >15% of the affected hemisphere had been seen on admission CT. Conclusions In cases of acute stroke and apparent occlusion of the extracranial ICA, intra-arterial treatment should be considered, especially when IVT fails and <15% of the hemisphere is infarcted on CT. Endovascular treatment may be beneficial especially in pseudo-occlusions but also in true occlusions of the extracranial ICA.

Semi-automatic quantitative measurements of intracranial internal carotid artery stenosis and calcification using CT angiography

IntroductionIntracranial 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.MethodsIn 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.ResultsFor the stenosis measurements, the CTA images of 162 arteries yielded an interobserver correlation of 0.78 (P < 0.001). Kappa values of the categorized stenosis measurements were moderate: 0.45 and 0.58 for cutoff values of 30% and 50%, respectively. The kappa value for the calcium categorization was 0.62, with a good agreement between the qualitative and quantitative calcium assessment.ConclusionsQuantitative degree of stenosis measurement of the intracranial ICA on CTA is feasible with a good interobserver agreement ICA. Qualitative calcium categorization agrees well with quantitative measurements.

Association of Automatically Quantified Total Blood Volume after Aneurysmal Subarachnoid Hemorrhage with Delayed Cerebral Ischemia

The authors retrospectively studied clinical and radiologic data of 333 consecutive patients with aneurysmal SAH between January 2009 and December 2011. Adjusted odds ratios werecalculated for the association between automatically quantified total blood volume on NCCT and delayed cerebral ischemia (clinical, radiologic, and both). The adjusted OR of total blood volume for delayed cerebral ischemia was 1.02 per milliliter of blood. They conclude that a higher total blood volume measured with the automated quantification method is significantly associated with delayed cerebral ischemia. 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.

Topographic distribution of cerebral infarct probability in patients with acute ischemic stroke : mapping of intra-arterial treatment effect

Background Since proof emerged that IA treatment (IAT) is beneficial for patients with acute ischemic stroke, it has become the standard method of care. Despite these positive results, recovery to functional independence is established in only about one-third of treated patients. The effect of IAT is commonly assessed by functional outcome, whereas its effect on brain tissue salvage is considered a secondary outcome measure (at most). Because patient and treatment selection needs to be improved, understanding the treatment effect on brain tissue salvage is of utmost importance. Objective To introduce infarct probability maps to estimate the location and extent of tissue damage based on patient baseline characteristics and treatment type. Methods Cerebral infarct probability maps were created by combining automatically segmented infarct distributions using follow-up CT images of 281 patients from the MR CLEAN trial. Comparison of infarct probability maps allows visualization and quantification of probable treatment effects. Treatment impact was calculated for 10 Alberta Stroke Program Early CT Score (ASPECTS) and 27 anatomical regions. Results The insular cortex had the highest infarct probability in both control and IAT populations (47.2% and 42.6%, respectively). Comparison showed significant lower infarct probability in 4 ASPECTS and 17 anatomical regions in favor of IAT. Most salvaged tissue was found within the ASPECTS M2 region, which was 8.5% less likely to infarct. Conclusions Probability maps intuitively visualize the topographic distribution of infarct probability due to treatment, which makes it a promising tool for estimating the effect of treatment.

Association of follow-up infarct volume with functional outcome in acute ischemic stroke: a pooled analysis of seven randomized trials

Background Follow-up infarct volume (FIV) has been recommended as an early indicator of treatment efficacy in patients with acute ischemic stroke. Questions remain about the optimal imaging approach for FIV measurement. Objective To examine the association of FIV with 90-day modified Rankin Scale (mRS) score and investigate its dependency on acquisition time and modality. Methods Data of seven trials were pooled. FIV was assessed on follow-up (12 hours to 2 weeks) CT or MRI. Infarct location was defined as laterality and involvement of the Alberta Stroke Program Early CT Score regions. Relative quality and strength of multivariable regression models of the association between FIV and functional outcome were assessed. Dependency of imaging modality and acquisition time (≤48 hours vs >48 hours) was evaluated. Results Of 1665 included patients, 83% were imaged with CT. Median FIV was 41 mL (IQR 14–120). A large FIV was associated with worse functional outcome (OR=0.88(95% CI 0.87 to 0.89) per 10 mL) in adjusted analysis. A model including FIV, location, and hemorrhage type best predicted mRS score. FIV of ≥133 mL was highly specific for unfavorable outcome. FIV was equally strongly associated with mRS score for assessment on CT and MRI, even though large differences in volume were present (48 mL (IQR 15–131) vs 22 mL (IQR 8–71), respectively). Associations of both early and late FIV assessments with outcome were similar in strength (ρ=0.60(95% CI 0.56 to 0.64) and ρ=0.55(95% CI 0.50 to 0.60), respectively). Conclusions In patients with an acute ischemic stroke due to a proximal intracranial occlusion of the anterior circulation, FIV is a strong independent predictor of functional outcome and can be assessed before 48 hours, oneither CT or MRI.

Quantitative Collateral Grading on CT Angiography in Patients with Acute Ischemic Stroke

Reliable assessment of collateral blood supply is important in acute ischemic stroke. We propose a quantitative method for evaluation of collateral status on CT angiography (CTA). We collected CTA images of 70 patients from MR CLEAN with an occlusion in the M1 branch. Our proposed quantitative collateral score (qCS) consisted of atlas-based territory-at-risk identification and vessel segmentation using a Hessian-based filter. Ground truth was obtained by manual collateral scoring (mCS). Accuracy was evaluated by analysis of Spearman ρ and one-way ANOVA. Correlation of mCS and qCS with tissue death and functional outcome was assessed. Receiver operating characteristics curves of mCS and qCS were analyzed to distinguish favorable from unfavorable outcome. qCS strongly correlated with mCS and showed reliable correlations with tissue death and functional outcome. qCS showed higher discriminative power between favorable and unfavorable compared to mCS, indicating potential clinical value.

Towards personalised intra-arterial treatment of patients with acute ischaemic stroke: a study protocol for development and validation of a clinical decision aid

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.