Summary Background Intravenous thrombolysis with alteplase alone cannot reperfuse most large-artery strokes. We aimed to determine whether mechanical thrombectomy in addition to intravenous ...thrombolysis improves clinical outcome in patients with acute ischaemic stroke. Methods THRACE is a randomised controlled trial done in 26 centres in France. Patients aged 18–80 years with acute ischaemic stroke and proximal cerebral artery occlusion were randomly assigned to receive either intravenous thrombolysis alone (IVT group) or intravenous thrombolysis plus mechanical thrombectomy (IVTMT group). Intravenous thrombolysis (alteplase 0·9 mg/kg maximum 90 mg, with an initial bolus of 10% of the total dose followed by infusion of the remaining dose over 60 min) had to be started within 4 h and thrombectomy within 5 h of symptom onset. Occlusions had to be confirmed by CT or magnetic resonance angiography. Randomisation was done centrally with a computer-generated sequential minimisation method and was stratified by centre. The primary outcome was the proportion of patients achieving functional independence at 3 months, defined by a score of 0–2 on the modified Rankin scale, assessed in the modified intention-to-treat population (ie, patients lost to follow-up and those with missing data were excluded). Safety outcomes were analysed in the per-protocol population (ie, all patients who did not follow the protocol of their randomisation group precisely were excluded from the analysis). THRACE is registered with ClinicalTrials.gov , NCT01062698. Findings Between June 1, 2010, and Feb 22, 2015, 414 patients were randomly assigned to the IVT group (n=208) or the IVTMT group (n=204). Four patients (two in each group) lost to follow-up and six (four in the IVT group and two in the IVTMT group) with missing data were excluded. 85 (42%) of 202 patients in the IVT group and 106 (53%) of 200 patients in the IVTMT group achieved functional independence at 3 months (odds ratio 1·55, 95% CI 1·05–2·30; p=0·028). The two groups had no significant differences in mortality at 3 months (24 12% deaths of 202 patients vs 27 13% of 206; p=0·70) or symptomatic intracranial haemorrhage at 24 h (four 2% of 185 vs three 2% of 192; p=0·71). Common adverse events related to thrombectomy were vasospasm (33 23% patients) and embolisation in a new territory (nine 6%). Interpretation Mechanical thrombectomy combined with standard intravenous thrombolysis improves functional independence in patients with acute cerebral ischaemia, with no evidence of increased mortality. Bridging therapy should be considered for patients with large-vessel occlusions of the anterior circulation. Funding French Ministry for Health.
Radiomics relies on the extraction of a wide variety of quantitative image-based features to provide decision support. Magnetic resonance imaging (MRI) contributes to the personalization of patient ...care but suffers from being highly dependent on acquisition and reconstruction parameters. Today, there are no guidelines regarding the optimal pre-processing of MR images in the context of radiomics, which is crucial for the generalization of published image-based signatures. This study aims to assess the impact of three different intensity normalization methods (Nyul, WhiteStripe, Z-Score) typically used in MRI together with two methods for intensity discretization (fixed bin size and fixed bin number). The impact of these methods was evaluated on first- and second-order radiomics features extracted from brain MRI, establishing a unified methodology for future radiomics studies. Two independent MRI datasets were used. The first one (DATASET1) included 20 institutional patients with WHO grade II and III gliomas who underwent post-contrast 3D axial T1-weighted (T1w-gd) and axial T2-weighted fluid attenuation inversion recovery (T2w-flair) sequences on two different MR devices (1.5 T and 3.0 T) with a 1-month delay. Jensen-Shannon divergence was used to compare pairs of intensity histograms before and after normalization. The stability of first-order and second-order features across the two acquisitions was analysed using the concordance correlation coefficient and the intra-class correlation coefficient. The second dataset (DATASET2) was extracted from the public TCIA database and included 108 patients with WHO grade II and III gliomas and 135 patients with WHO grade IV glioblastomas. The impact of normalization and discretization methods was evaluated based on a tumour grade classification task (balanced accuracy measurement) using five well-established machine learning algorithms. Intensity normalization highly improved the robustness of first-order features and the performances of subsequent classification models. For the T1w-gd sequence, the mean balanced accuracy for tumour grade classification was increased from 0.67 (95% CI 0.61-0.73) to 0.82 (95% CI 0.79-0.84, P = .006), 0.79 (95% CI 0.76-0.82, P = .021) and 0.82 (95% CI 0.80-0.85, P = .005), respectively, using the Nyul, WhiteStripe and Z-Score normalization methods compared to no normalization. The relative discretization makes unnecessary the use of intensity normalization for the second-order radiomics features. Even if the bin number for the discretization had a small impact on classification performances, a good compromise was obtained using the 32 bins considering both T1w-gd and T2w-flair sequences. No significant improvements in classification performances were observed using feature selection. A standardized pre-processing pipeline is proposed for the use of radiomics in MRI of brain tumours. For models based on first- and second-order features, we recommend normalizing images with the Z-Score method and adopting an absolute discretization approach. For second-order feature-based signatures, relative discretization can be used without prior normalization. In both cases, 32 bins for discretization are recommended. This study may pave the way for the multicentric development and validation of MR-based radiomics biomarkers.
BACKGROUND AND PURPOSE—Arterial wall enhancement on vessel wall MRI was described in intracranial inflammatory arterial disease. We hypothesized that circumferential aneurysmal wall enhancement ...(CAWE) could be an indirect marker of aneurysmal wall inflammation and, therefore, would be more frequent in unstable (ruptured, symptomatic, or undergoing morphological modification) than in stable (incidental and nonevolving) intracranial aneurysms.
METHODS—We prospectively performed vessel wall MRI in patients with stable or unstable intracranial aneurysms. Two readers independently had to determine whether a CAWE was present.
RESULTS—We included 87 patients harboring 108 aneurysms. Interreader and intrareader agreement for CAWE was excellent (κ=0.85; 95% confidence interval, 0.75–0.95 and κ=0.90; 95% confidence interval, 0.83–0.98, respectively). A CAWE was significantly more frequently seen in unstable than in stable aneurysms (27/31, 87% versus 22/77, 28.5%, respectively; P<0.0001). Multivariate logistic regression, including CAWE, size, location, multiplicity of aneurysms, and daily aspirin intake, revealed that CAWE was the only independent factor associated with unstable status (odds ratio, 9.20; 95% confidence interval, 2.92–29.0; P=0.0002).
CONCLUSIONS—CAWE was more frequently observed in unstable intracranial aneurysms and may be used as a surrogate of inflammatory activity in the aneurysmal wall.
BACKGROUND AND PURPOSE—Absence of arterial wall enhancement (AWE) of unruptured intracranial aneurysms (UIA) has shown promise at predicting which aneurysms will not rupture. We here tested the ...hypothesis that increased enhancement during follow-up (increased intensity, extension, or thickness or appearance of de novo enhancement), assessed using vessel wall magnetic resonance imaging, was associated with higher rates of subsequent growth.
METHODS—Patients with UIA were included between 2012 and 2018. Two readers independently rated AWE modification on 3T vessel wall magnetic resonance imaging, and morphological changes on time-of-flight magnetic resonance angiography during follow-up.
RESULTS—A total of 129 patients harboring 145 UIA (mean size 4.1 mm) met study criteria, of which 12 (8.3%) displayed morphological growth at 2 years. Of them, 8 demonstrated increased AWE during follow-up before or concurrently to morphological growth, and 4 had preexisting AWE that remained stable before growth. In the remaining 133 (nongrowing) UIAs, no AWE modifications were found. In multivariable analysis, increased AWE, not size, was associated with UIA growth (relative risk, 26.1 95% CI, 7.4–91.7, P<0.001). Sensitivity, specificity, positive predictive value, and negative predictive value for UIA growth of increased AWE during follow-up were, respectively, of 67%, 100%, 96%, and 100%.
CONCLUSIONS—Increased AWE during follow-up of conservatively managed UIAs predicts aneurysm growth over a 2-year period. This may impact UIA management towards closer monitoring or preventive treatment. Replication in a different setting is warranted.
•Recognition of local cortical folding patterns is hard due to their high variability.•Here, three new methods are proposed for their automatic classification.•They are tested on the Anterior ...Cingulate Cortex patterns and the Power Button Sign.•The CNN-based model is faster to use and has similar performance to the other models.•The two other models seem more effective in managing unbalanced problems.
The study of local cortical folding patterns showed links with psychiatric illnesses as well as cognitive functions. Despite the tools now available to visualize cortical folds in 3D, manually classifying local sulcal patterns is a time-consuming and tedious task. In fact, 3D visualization of folds helps experts to identify different sulcal patterns but fold variability is so high that the distinction between these patterns sometimes requires the definition of complex criteria, making manual classification difficult and not reliable. However, the assessment of the impact of these patterns on the functional organization of the cortex could benefit from the study of large databases, especially when studying rare patterns. In this paper, several algorithms for the automatic classification of fold patterns are proposed to allow morphological studies to be extended and confirmed on such large databases. Three methods are proposed, the first based on a Support Vector Machine (SVM) classifier, the second on the Scoring by Non-local Image Patch Estimator (SNIPE) approach and the third based on a 3D Convolution Neural Network (CNN). These methods are generic enough to be applicable to a wide range of folding patterns. They are tested on two types of patterns for which there is currently no method to automatically identify them: the Anterior Cingulate Cortex (ACC) patterns and the Power Button Sign (PBS). The two ACC patterns are almost equally present whereas PBS is a particularly rare pattern in the general population. The three models proposed achieve balanced accuracies of approximately 80% for ACC patterns classification and 60% for PBS classification. The CNN-based model is more interesting for the classification of ACC patterns thanks to its rapid execution. However, SVM and SNIPE-based models are more effective in managing unbalanced problems such as PBS recognition.
Objective
We aimed to characterize the association between pretreatment lesional volume measured on diffusion‐weighted images and functional outcome, and estimate the impact on thrombectomy efficacy ...for ischemic stroke with anterior proximal intracranial arterial occlusion.
Methods
Anterior circulation ischemic stroke patients who had pretreatment diffusion‐weighted imaging in the THRACE study were included. Lesional volume was semiautomatically segmented. Logistic regression was applied to model clinical outcome as a function of lesional volume. Outcomes included functional independence (modified Rankin Scale mRS 0–2), degree of disability (ordinal mRS 0–6), and mortality at 3 months.
Results
Of 298 included patients, with median lesional volume 17.2ml (interquartile range IQR, 9.2–51.8) and median mRS 2 (IQR, 1–4), 51.0% achieved functional independence. Increased lesional volume was an independent predictor for a lower probability of functional independence (odds ratio OR, 0.90 95% confidence interval {CI}, 0.81–0.99 per 10ml; p < 0.001), a less favorable degree of disability (common OR, 0.86 95% CI, 0.81–0.90 per 10ml; p < 0.001), and a higher mortality rate (OR, 1.21 95% CI, 1.08–1.37 per 10ml; p < 0.001). For additional thrombectomy, the number of patients needed to treat to achieve functional independence in 1 patient increased with lesional volume (10 for a volume of 80ml; 15 for 135ml). No significant treatment‐by‐dichotomized volume interaction for functional independence and mortality was observed.
Interpretation
Pretreatment lesional volume is an independent predictor for functional outcome in acute ischemic stroke with proximal intracranial occlusion. The clinical benefit of adding mechanical thrombectomy to thrombolysis decreased with the increase of lesional volume. Ann Neurol 2018;83:178–185
To assess the efficacy of endovascular treatment (EVT) of intracranial aneurysms for recurrence, bleeding, and de novo aneurysm formation at long-term follow-up (> 10 years after treatment) with ...magnetic resonance (MR) angiography and to identify risk factors for recurrence through a prospective study and a systematic review of the literature.
Clinical examinations and 3-T MR angiography were performed prospectively 10 years after EVT of intracranial aneurysms in a single institution. Ethics committee approval and informed consent were obtained. PubMed, EMBASE, and Cochrane databases were searched to identify studies in which authors reported bleeding and/or aneurysm recurrence rates in patients who received follow-up more than 10 years after EVT. Univariate and multivariate subgroup analyses were performed to identify risk factors (midterm MR angiographic results, aneurysm characteristics, retreatment within 5 years).
In the prospective study, sac recanalization occurred between midterm and long-term MR angiography in 16 of 129 (12.4%) aneurysms. Grade 2 classification on the Raymond scale at midterm MR angiography (relative risk RR, 4.16; 99% confidence interval CI: 2.12, 8.14) and retreatment within 5 years (RR, 4.67; 99% CI: 1.55, 14.03) were risk factors for late recurrence. In the systematic review (15 cohorts, 2773 patients, 2902 aneurysms), bleeding, aneurysm recurrence, and de novo lesion formation rates were, respectively, 0.7% (99% CI: 0.2%, 2.7%; I(2), 0%; one of 694 patients), 11.4% (99% CI: 7.0%, 18.0%; I(2), 21.6%), and 4.1% (99% CI: 1.7, 9.4%; I(2), 54.1%). Raymond grade 2 initial result (RR, 7.08; 99% CI: 1.24, 40.37; I(2), 82.6%) and aneurysm size greater than 10 mm (RR, 4.37; 99% CI: 1.83, 10.44; I(2), 0%) were risk factors for late recurrence.
EVT of intracranial aneurysm is effective for prevention of long-term bleeding, but recurrences occur in a clinically relevant percentage of patients, a finding that may justify follow-up of selected patients for 10 years or more, such as patients with aneurysms larger than 10 mm or classified as Raymond grade 2 at midterm MR angiography.
Functional-based resection under awake conditions had been associated with a nonnegligible rate of intraoperative and postoperative epileptic seizures. The authors assessed the incidence of ...intraoperative and early postoperative epileptic seizures after functional-based resection under awake conditions.
The authors prospectively assessed intraoperative and postoperative seizures (within 1 month) together with clinical, imaging, surgical, histopathological, and follow-up data for 202 consecutive diffuse glioma adult patients who underwent a functional-based resection under awake conditions.
Intraoperative seizures occurred in 3.5% of patients during cortical stimulation; all resolved without any procedure being discontinued. No predictor of intraoperative seizures was identified. Early postoperative seizures occurred in 7.9% of patients at a mean of 5.1 ± 2.9 days. They increased the duration of hospital stay (p = 0.018), did not impact the 6-month (median 95 vs 100, p = 0.740) or the 2-year (median 100 vs 100, p = 0.243) postoperative Karnofsky Performance Status score and did not impact the 6-month (100% vs 91.4%, p = 0.252) or the 2-year (91.7 vs 89.4%, p = 0.857) postoperative seizure control. The time to treatment of at least 3 months (adjusted OR aOR 4.76 95% CI 1.38-16.36, p = 0.013), frontal lobe involvement (aOR 4.88 95% CI 1.25-19.03, p = 0.023), current intensity for intraoperative mapping of at least 3 mA (aOR 4.11 95% CI 1.17-14.49, p = 0.028), and supratotal resection (aOR 6.24 95% CI 1.43-27.29, p = 0.015) were independently associated with early postoperative seizures.
Functional-based resection under awake conditions can be safely performed with a very low rate of intraoperative and early postoperative seizures and good 6-month and 2-year postoperative seizure outcomes. Intraoperatively, the use of the lowest current threshold producing reproducible responses is mandatory to reduce seizure occurrence intraoperatively and in the early postoperative period.
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