Effect of Needle-To-Puncture Time on Reperfusion Outcome in Acute Ischemic Stroke.

INTRODUCTION: The aim of the study was to investigate the impact of time interval between start of intravenous thrombolysis (IVT) to start of endovascular thrombectomy (EVT) on stroke outcomes. METHODS: Data from the Quality Improvement and Clinical Research (QuICR) provincial stroke registry from Alberta, Canada, were used to identify stroke patients who received IVT and EVT from January 2015 to December 2019. We assessed the impact of the time interval between IVT bolus to EVT puncture (needle-to-puncture times [NPT]) on outcomes. Radiological outcomes included successful initial recanalization (revised Arterial Occlusive Lesion 2b-3), successful initial and final reperfusion (modified thrombolysis in cerebral infarction 2b-3). Clinical outcomes were 90-day modified Rankin Scale (mRS) and mortality. RESULTS: Of the 680 patients, 233 patients (median age: 73, 41% females) received IVT + EVT. Median NPT was 38 min (IQR, 24-60). Arrival during working hours was independently associated with shorter NPT (p < 0.001). Successful initial recanalization and initial and final reperfusion were observed in 12%, 10%, and 83% of patients, respectively. NPT was not associated with initial successful recanalization (OR 0.97 for every 10-min increase of NPT, 95% CI: 0.91-1.04), initial successful reperfusion (OR 1.01, 95% CI: 0.96-1.07), or final successful reperfusion (OR: 1.03, 95% CI: 0.97-1.08). Every 10-min delay in NPT was associated with lower odds of functional independence at 90 days (mRS ≤2; OR: 0.93; 95% CI, 0.88-0.97). Patients with shorter NPT (≤38 min) had lower 90-day mRS scores (median 1 vs. 3; OR: 0.54 [0.31-0.91]) and had lower mortality (6.1% vs. 21.2%; OR, 0.23 [0.10-0.57]) than the longer NPT group. CONCLUSION: Shorter NPT did not impact reperfusion outcomes but was associated with better clinical outcome.

Prevalence of high-risk aortic arch atherosclerosis features on computed tomography angiography in embolic stroke of undetermined source.

INTRODUCTION: Embolic stroke of undetermined source (ESUS) comprises a heterogenous group. There is a need to further identify etiologies within this group to guide management strategies. We examined the prevalence of aortic arch atherosclerosis (AAA) on CT angiography (CTA) in patients with embolic stroke of undetermined source (ESUS) to characterize high-risk plaque features. METHODS: All patients from two prospective multicenter acute ischemic stroke studies (INTERRSeCT and PRove-IT) were included if the CTA adequately imaged the proximal aortic arch and the stroke etiology was recorded. Three readers blinded to stroke etiology analyzed the following AAA plaque features on baseline CTA at the time of stroke: 1) thickness in millimetres (mm); 2) morphology (none, smooth, ulcerated, or protruding); 3) location within the aortic arch (proximal, transverse, or distal); and 4) calcification (none, single small, multiple small, single large, or diffuse extensive). RESULTS: We included 1063 patients, of which 293 (27.6%) had ESUS (mean age 67.5 years; 46.4% men; median NIHSS 12; 80.6% large vessel occlusion). Mean AAA thickness was significantly larger in ESUS patients (3.8 mm) compared to non-ESUS patients (3.0 mm; p<0.0001) and to a subgroup of patients with large artery atherosclerosis (2.9 mm; p=0.003). ESUS patients had a significantly higher proportion of ulcerated or protruding plaques (17.4% vs 10.3%; risk ratio 1.7, 95% C.I. 1.2-2.4, p=0.002). The location of AAA in the ESUS group was the ascending aorta in 37.9%, transverse arch in 42.3%, and descending aorta in 84.6%. Although AAA was mostly located in the distal aortic arch, ulcerated or protruding plaques were least common in the distal arch (p=0.002). There was no difference between ESUS and non-ESUS patients in plaque location (p=0.23) or calcification grade (p=0.092). CONCLUSION: ESUS patients in our study had thicker AAA and a higher prevalence of ulcerated or protruding plaques located more proximally within the aortic arch. High-risk plaque features may suggest a causal role of AAA in the ESUS population with visible intracranial occlusions.

Exploring sex differences for acute ischemic stroke clinical, imaging and thrombus characteristics in the INTERRSeCT study.

Women, especially following menopause, are known to have worse outcomes following acute ischemic stroke. One primary postulated biological mechanism for worse outcomes in older women is a reduction in the vasculoprotective effects of estrogen. Using the INTERRseCT cohort, a multicentre international observational cohort studying recanalization in acute ischemic stroke, we explored the effects of sex, and modifying effects of age, on neuroradiological predictors of recanalization including robustness of leptomeningeal collaterals, thrombus burden and thrombus permeability. Ordinal regression analyses were used to examine the relationship between sex and each of the neuroradiological markers. Further, we explored both multiplicative and additive interactions between age and sex. All patients (n = 575) from INTERRseCT were included. Mean age was 70.2 years (SD: 13.1) and 48.5% were women. In the unadjusted model, female sex was associated with better collaterals (OR 1.37, 95% CIs: 1.01-1.85), however this relationship was not significant after adjusting for age and relevant comorbidities. There were no significant interactions between age and sex. In a large prospective international cohort, we found no association between sex and radiological predictors of recanalization including leptomeningeal collaterals, thrombus permeability and thrombus burden.

Impact of vessel tortuosity and radiological thrombus characteristics on the choice of first-line thrombectomy strategy: Results from the ESCAPE-NA1 trial.

INTRODUCTION: Despite improvements in device technology, only one-third of stroke patients undergoing endovascular thrombectomy (EVT) achieve first-pass effect (FPE). We investigated the effect of arterial tortuosity and thrombus characteristics on the relationship between first-line EVT strategy and angiographic outcomes. PATIENTS AND METHODS: Patients with thin-slice baseline CT-angiography from the ESCAPE-NA1 trial (Efficacy and safety of nerinetide for the treatment of acute ischemic stroke) were included. Tortuosity was estimated using the tortuosity index extracted from catheter pathway, and radiological thrombus characteristics were length, non-contrast density, perviousness and hyperdense artery sign. We assessed the association of first-line EVT strategy (stent-retriever [SR] versus contact aspiration [CA] versus combined SR+CA) with FPE (eTICI score 2c/3 after one pass), final eTICI 2b/3, number of passes and procedure duration using multivariable regression. Interaction of tortuosity and thrombus characteristics with first-line technique were assessed using interaction terms. RESULTS: Among 520 included patients, SR as a first-line modality was used in 165 (31.7%) patients, CA in 132 (25.4%), and combined SR+CA in 223 (42.9%). FPE was observed in 166 patients (31.9%). First-line strategy was not associated with FPE. Tortuosity had a significant effect on FPE only in the CA group (aOR = 0.90 [95% CI 0.83-0.98]) compared with stent-retrievers and combined first-line approach (p interaction = 0.03). There was an interaction between thrombus length and first-line strategy for number of passes (p interaction = 0.04). Longer thrombi were associated with higher number of passes only in the CA group (acOR 1.03 [95% CI 1.00-1.06]). CONCLUSION: Our study suggests that vessel tortuosity and longer thrombi may negatively affect the performance of first-line contact aspiration catheters in acute stroke patients undergoing EVT.

Determinants of Leptomeningeal Collateral Status Variability in Ischemic Stroke Patients.

BACKGROUND: Collateral status is an indicator of a favorable outcome in stroke. Leptomeningeal collaterals provide alternative routes for brain perfusion following an arterial occlusion or flow-limiting stenosis. Using a large cohort of ischemic stroke patients, we examined the relative contribution of various demographic, laboratory, and clinical variables in explaining variability in collateral status. METHODS: Patients with acute ischemic stroke in the anterior circulation were enrolled in a multi-center hospital-based observational study. Intracranial occlusions and collateral status were identified and graded using multiphase computed tomography angiography. Based on the percentage of affected territory filled by collateral supply, collaterals were graded as either poor (0-49%), good (50-99%), or optimal (100%). Between-group differences in demographic, laboratory, and clinical factors were explored using ordinal regression models. Further, we explored the contribution of measured variables in explaining variance in collateral status. RESULTS: 386 patients with collateral status classified as poor (n = 64), good (n = 125), and optimal (n = 197) were included. Median time from symptom onset to CT was 120 (IQR: 78-246) minutes. In final multivariable model, male sex (OR 1.9, 95% CIs [1.2, 2.9], p = 0.005) and leukocytosis (OR 1.1, 95% CIs [1.1, 1.2], p = 0.001) were associated with poor collaterals. Measured variables only explained 44.8-53.0% of the observed between-patient variance in collaterals. CONCLUSION: Male sex and leukocytosis are associated with poorer collaterals. Nearly half of the variance in collateral flow remains unexplained and could be in part due to genetic differences.

Time-resolved assessment of cortical venous drainage on multiphase CT angiography in patients with acute ischemic stroke.

PURPOSE: Cortical vein opacification is not routinely assessed in patients presenting with acute ischemic stroke (AIS), and the value of temporal assessment of venous outflow is not known. We evaluated the utility of assessing cortical venous drainage over time using multiphase CT angiography (mCTA). METHODS: Cortical venous drainage was assessed in patients from the Precise and Rapid Assessment of Collaterals Using Multi-Phase CTA in the Triage of Patients With Acute Ischemic Stroke for IA Therapy prospective multicenter cohort study of patients with symptoms of AIS with ICA and/or middle cerebral artery occlusion on baseline mCTA. Opacification of vein of Labbe, sphenoparietal sinus, superficial middle cerebral vein, and vein of Trolard of the affected hemisphere was graded as no (0), partial (1), or full (2) opacification in each mCTA phase. The venous opacification scores for each phase were added to generate a total venous score (TVS) (range 0-24). Primary outcome was 90-day modified Rankin score. Repeated measures analysis was used to assess the effect of phase timing on venous score on outcome. RESULTS: Of 432 patients, 284 (65.7%) had proximal arterial occlusions. Median venous opacification score per phase (range 0-8) was 3 (IQR 1-6) in the first phase and increased in the second and third phases [median (IQR): 6 (5-8) and 8 (6-8), respectively] of the mCTA. In a multivariable analysis adjusting for age, baseline National Institutes of Health Stroke Scale, and Alberta stroke program early CT score, a significant association between TVS and 90-day mRS was noted ([adjusted cOR for TVS 6-11: 0.16 (95% CI 0.05-0.51); TVS 12-17: 0.18 (95% CI 0.06-0.57); TVS 18-24: 0.20 (0.06-0.63)]. Repeated measures analysis of venous scores from all three phases showed a significant effect of time/phase on TVS (p < 0.001). CONCLUSION: This study concludes that venous opacification over time on multiphase CTA is associated with 90-day clinical outcome. There was however no added benefit of venous scoring vis-a-vis arterial collateral assessment in predicting outcome.

Impact of Multiphase Computed Tomography Angiography for Endovascular Treatment Decision-Making on Outcomes in Patients with Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Various imaging paradigms are used for endovascular treatment (EVT) decision-making and outcome estimation in acute ischemic stroke (AIS). We aim to compare how these imaging paradigms perform for EVT patient selection and outcome estimation. METHODS: Prospective multi-center cohort study of patients with AIS symptoms with multi-phase computed tomography angiography (mCTA) and computed tomography perfusion (CTP) baseline imaging. mCTA-based EVT-eligibility was defined as presence of large vessel occlusion (LVO) and moderate-to-good collaterals on mCTA. CTP-based eligibility was defined as presence of LVO, ischemic core (defined on relative cerebral blood flow, absolute cerebral blood flow, and cerebral blood volume maps) <70 mL, mismatch-ratio >1.8, absolute mismatch >15 mL. EVT-eligibility and adjusted rates of good outcome (modified Rankin Scale 0-2) based on these imaging paradigms were compared. RESULTS: Of 289/464 patients with LVO, 263 (91%) were EVT-eligible by mCTA-criteria versus 63 (22%), 19 (7%) and 103 (36%) by rCBF, aCBF, and CBV-CTP-criteria. CTP and mCTA-criteria were discordant in 40% to 53%. Estimated outcomes were best in patients who met both mCTA and CTP eligibility-criteria and were treated with EVT (62% to 87% good outcome). Patients eligible for EVT by mCTA-criteria and not by CTP-criteria receiving EVT achieved good outcome rates of 53% to 57%. Few patients met CTP-criteria and not mCTA-criteria for EVT. CONCLUSIONS: Simpler imaging selection criteria that rely on little else than detection of the occluded blood vessel may be more sensitive and less specific, thus resulting in more patients being offered EVT and arguably benefiting from it.

Workflow and Outcomes of Endovascular Thrombectomy for In-Hospital Stroke a Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Acute strokes due to large vessel occlusion in hospitalized patients is not uncommon. We performed a systematic review and meta-analysis to investigate the timing and outcome of endovascular thrombectomy (EVT) for in-hospital stroke. METHODS: We conducted a meta-analysis of clinical studies published in English until September 2020 in the MEDLINE and Cochrane databases. Studies reporting original data on the characteristics and outcomes of in-hospital stroke patients treated with EVT were included. We extracted data on the time-metrics from last known well (LKW) until reperfusion was achieved. We also collected data on procedural and functional outcomes. RESULTS: Out of 5093 retrieved studies, 8 were included (2,622 patients). The median age was 71.4 years and median NIHSS score on admission was 16. Patients were mostly admitted to the cardiology service (27.3%). The pooled time from LKW to recognition by staff was 72.9 min (95% CI: 40.7 to 105 min). 25.6% received IV tPA. The mean time from stroke recognition to arterial puncture was 134.5 min (95% CI: 94.9 to 174.1). Successful reperfusion occurred in 82.8.% with a pooled mean time from detection to reperfusion of 193.1 min (95% CI: 139.5 to 246.7). The 90-day independent functional outcome was reported in 42% of patients (95% CI 29 to 55%). CONCLUSION: EVT can be performed safely and successfully for in-hospital strokes. Noticeable delays from LKW to detection and then to puncture are noted. This calls for better stroke pathways to identify and treat these patients. BACKGROUND: Stroke in hospitalized patients, referred to as in-hospital stroke (IHS), accounts for 2.2-17% of all strokes.1 The majority of these are ischemic while intracranial hemorrhage represents 2-11% of all IHS.1 These patients are expected to have a rapid diagnosis and treatment given the ongoing medical supervision, and therefore favorable outcomes.1-3 However, existing studies report poor outcomes in patients with IHS with a mortality risk that exceeds that of community-onset stroke (COS): 24.7% vs 9.6%.4 Surviving IHS patients are also less likely to be discharged home compared to COS (27.7% vs 49.9%) and to be functionally independent at 3 months (31.0% vs 50.4%).1-4.

Thrombus Migration and Fragmentation After Intravenous Alteplase Treatment: The INTERRSeCT Study.

BACKGROUND AND PURPOSE: There is interest in what happens over time to the thrombus after intravenous alteplase. We study the effect of alteplase on thrombus structure and its impact on clinical outcome in patients with acute stroke. METHODS: Intravenous alteplase treated stroke patients with intracranial internal carotid artery or middle cerebral artery occlusion identified on baseline computed tomography angiography and with follow-up vascular imaging (computed tomography angiography or first run of angiography before endovascular therapy) were enrolled from INTERRSeCT study (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography). Thrombus movement after intravenous alteplase was classified into complete recanalization, thrombus migration, thrombus fragmentation, and no change. Thrombus migration was diagnosed when occlusion site moved distally and graded according to degrees of thrombus movement (grade 0-3). Thrombus fragmentation was diagnosed when a new distal occlusion in addition to the primary occlusion was identified on follow-up imaging. The association between thrombus movement and clinical outcome was also evaluated. RESULTS: Among 427 patients in this study, thrombus movement was seen in 54% with a median time of 123 minutes from alteplase administration to follow-up imaging, and sub-classified as marked (thrombus migration grade 2-3 + complete recanalization; 27%) and mild to moderate thrombus movement (thrombus fragmentation + thrombus migration grade 0-1; 27%). In patients with proximal M1/internal carotid artery occlusion, marked thrombus movement was associated with a higher rate of good outcome (90-day modified Rankin Scale, 0-2) compared with mild to moderate movement (52% versus 27%; adjusted odds ratio, 5.64 [95% CI, 1.72-20.10]). No difference was seen in outcomes between mild to moderate thrombus movement and no change. In M1 distal/M2 occlusion, marked thrombus movement was associated with improved 90-day good outcome compared with no change (70% versus 56%; adjusted odds ratio, 2.54 [95% CI, 1.21-5.51]). CONCLUSIONS: Early thrombus movement is common after intravenous alteplase. Marked thrombus migration leads to good clinical outcomes. Thrombus dynamics over time should be further evaluated in clinical trials of acute reperfusion therapy.

Utility of Time-Variant Multiphase CTA Color Maps in Outcome Prediction for Acute Ischemic Stroke Due to Anterior Circulation Large Vessel Occlusion.

BACKGROUND: Multiphase CTA (mCTA) is an established tool for endovascular treatment decision-making and outcome prediction in acute ischemic stroke, but its interpretation requires some degree of experience. We aimed to determine whether mCTA-based prediction of clinical outcome and final infarct volume can be improved by assessing collateral status on time-variant mCTA color maps rather than using a conventional mCTA display format. METHODS: Patients from the PRove-IT cohort study with anterior circulation large vessel occlusion were included in this study. Collateral status was assessed with a three-point scale using the conventional display format. Collateral extent and filling dynamics were then graded on a three-point scale using time-variant mCTA color-maps (FastStroke, GE Healthcare, Milwaukee, WI, USA). Multivariable logistic regression was performed to determine the association of conventional collateral score, color-coded collateral extent and color-coded collateral filling dynamics with good clinical outcome and final infarct volume (volume below vs. above median infarct volume in the study sample). RESULTS: A total of 285 patients were included in the analysis and 53% (152/285) of the patients achieved a good outcome. Median infarct volume on follow-up was 12.6 ml. Color-coded collateral extent was significantly associated with good outcome (adjusted odds ratio [adjOR] 0.53, 95% confidence interval [CI]:0.36-0.77) while color-coded collateral filling dynamics (adjOR 1.30 [95%CI:0.88-1.95]) and conventional collateral scoring (adjOR 0.72 [95%C:0.48-1.08]) were not. Both color-coded collateral extent (adjOR 2.67 [95%CI:1.80-4.00]) and conventional collateral scoring (adjOR 1.84 [95%CI:1.21-2.79]) were significantly associated with follow-up infarct volume, while color-coded collateral filling dynamics were not (adjOR 1.21 [95%CI:0.83-1.78]). CONCLUSION: In this study, collateral extent assessment on time-variant mCTA maps improved prediction of good outcome and has similar value in predicting follow-up infarct volume compared to conventional mCTA collateral grading.

Thrombectomy vs medical management in low NIHSS acute anterior circulation stroke.

OBJECTIVE: To undertake an effectiveness and safety analysis of EVT in patients with LVO and NIH Stroke Scale (NIHSS) score ≤6 using datasets of multicenter and multinational nature. METHODS: We pooled patients with anterior circulation occlusion from 3 prospective international cohorts. Patients were eligible if presentation occurred within 12 hours from last known well and baseline NIHSS ≤6. Primary outcome was modified Rankin Scale (mRS) score 0-1 at 90 days. Secondary outcomes included neurologic deterioration at 24 hours (change in NIHSS of ≥2 points), mRS 0-2 at 90 days, and 90-day all-cause mortality. We used propensity score matching to adjust for nonrandomized treatment allocation. RESULTS: Among 236 patients who fit inclusion criteria, 139 received EVT and 97 received medical management. Compared to medical management, the EVT group was younger (65 vs 72 years; p < 0.001), had more proximal occlusions (p < 0.001), and less frequently received concurrent IV thrombolysis (57.7% vs 71.2%; p = 0.04). After propensity score matching, clinical outcomes between the 2 groups were not significantly different. EVT patients had an 8.6% (95% confidence interval [CI] -8.8% to 26.1%) higher rate of excellent 90-day outcome, despite a 22.3% (95% CI, 3.0%-41.6%) higher risk of neurologic deterioration at 24 hours. CONCLUSIONS: EVT for LVO in patients with low NIHSS score was associated with increased risk of neurologic deterioration at 24 hours. However, both EVT and medical management resulted in similar proportions of excellent clinical outcomes at 90 days. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with acute anterior circulation ischemic strokes and LVO with NIHSS < 6, EVT and medical management result in similar outcomes at 90 days.

Validation of an automated ASPECTS method on non-contrast computed tomography scans of acute ischemic stroke patients.

BACKGROUND: The Alberta Stroke Program Early CT Score (ASPECTS) is a systematic method of assessing the extent of early ischemic change on non-contrast computed tomography in patients with acute ischemic stroke. Our objective was to validate an automated ASPECTS scoring method we recently developed on a large data set. MATERIALS AND METHODS: We retrospectively collected 602 acute ischemic stroke patients' non-contrast computed tomography scans. Expert ASPECTS readings on non-contrast computed tomography were compared to automated ASPECTS. Statistical analyses on the total ASPECTS, region level ASPECTS, and dichotomized ASPECTS (≤4 vs. >4) score were conducted. RESULTS: In total, 602 scans were evaluated and 6020 (602 × 10) ASPECTS regions were scored. Median time from stroke onset to computed tomography was 114 min (interquartile range: 73-183 min). Total ASPECTS for the 602 patients generated by the automated method agreed well with expert readings (intraclass correlation coefficient): 0.65 (95% confidence interval (CI): 0.60-0.69). Region level analysis showed that the automated method yielded accuracy of 81.25%, sensitivity of 61.13% (95% CI: 58.4%-63.8%), specificity of 86.56% (95% CI: 85.6%-87.5%), and area under curve of 0.74 (95% CI: 0.73-0.75). For dichotomized ASPECTS (≤4 vs. >4), the automated method demonstrated sensitivity 97.21% (95% CI: 95.4%-98.4%), specificity 57.81% (95% CI: 44.8%-70.1%), accuracy 93.02%, and area under the curve of 0.78 (95% CI: 0.74-0.81). For each individual region (M1-6, lentiform, insula, and caudate), the automated method demonstrated acceptable performance. CONCLUSION: The automated system we developed approached the stroke expert in performance when scoring ASPECTS on non-contrast computed tomography scans of acute ischemic stroke patients.

Comparison of different methods of thrombus permeability measurement and impact on recanalization in the INTERRSeCT multinational multicenter prospective cohort study.

PURPOSE: To compare the association of different measures of intracranial thrombus permeability on non-contrast computerized tomography (NCCT) and computed tomography angiography (CTA) with recanalization with or without intravenous alteplase. METHODS: Patients with anterior circulation occlusion from the INTERRSeCT study were included. Thrombus permeability was measured on non-contrast CT and CTA using the following methods: [1] automated method, mean attenuation increase on co-registered thin (< 2.5 mm) CTA/NCCT; [2] semi-automated method, maximum attenuation increase on non-registered CTA/NCCT (ΔHUmax); [3] manual method, maximum attenuation on CTA (HUmax); and [4] visual method, residual flow grade. Primary outcome was recanalization with intravenous alteplase on the revised AOL scale (2b/3). Regression models were compared using C-statistic, Akaike (AIC), and Bayesian information criterion (BIC). RESULTS: Four hundred eighty patients were included in this analysis. Statistical models using methods 2, 3, and 4 were similar in their ability to discriminate recanalizers from non-recanalizers (C-statistic 0.667, 0.683, and 0.634, respectively); method 3 had the least information loss (AIC = 483.8; BIC = 492.2). A HUmax ≥ 89 measured with method 3 provided optimal sensitivity and specificity in discriminating recanalizers from non-recanalizers [recanalization 55.4% (95%CI 46.2-64.6) when HUmax > 89 vs. 16.8% (95%CI 13.0-20.6) when HUmax ≤ 89]. In sensitivity analyses restricted to patients with co-registered CTA/NCCT (n = 88), methods 1-4 predicted recanalization similarly (C-statistic 0.641, 0.688, 0.640, 0.648, respectively) with Method 2 having the least information loss (AIC 104.8, BIC 109.8). CONCLUSION: Simple methods that measure thrombus permeability are as reliable as complex image processing methods in discriminating recanalizers from non-recanalizers.

Automated brain extraction from head CT and CTA images using convex optimization with shape propagation.

BACKGROUND AND OBJECTIVE: Non-Contrast Computer Tomography (NCCT) and CT angiography (CTA) are the most used and widely acceptable imaging modalities in clinical practice for the diagnosis and treatment of acute ischemic stroke (AIS) patients. Brain extraction of CT/CTA images plays an essential role in stroke imaging research. There is no robust automated brain extraction method in the literature that is well established for both NCCT and CTA images. Thus, a validated and automated brain extraction tool for CT imaging would be of great value for both research and clinical practice. METHODS: The proposed brain extraction method is based on the contour evolution technique, which extracts brain tissues from acquired NCCT and CTA images in a slice-by-slice fashion. Specifically, the proposed approach makes use of a novel propagation framework, which is initialized by a localized slice with the largest brain section in axial views, followed by a geodesic level-set evolution for automatically extracting the brain section in each slice. In particular, the segmented contour propagated from the previous slice is reused to penalize the defined object function for contour evolution to enforce the shape continuity between any two adjacent contours. We show that the defined contour evolution function can be solved iteratively by globally optimal convex optimization. RESULTS: The proposed brain extraction approach is quantitatively evaluated using 40 NCCT and CTA images acquired from 20 AIS patients and drawn from 4 different vendors, compared to manual segmentations using Dice and Jaccard coefficient metrics. The quantitative results show that the proposed segmentation algorithm is consistently accurate for both NCCT and CTA images using Dice metric. The proposed method is further validated on 1736 NCCT and CTA images of 1331 AIS patients acquired from three multi-national multi-centric clinical trials. A visual check performed on these data demonstrates a low failure rate of 0.4% for 1331 NCCT images and a zero-failure rate for 405 CTA images. CONCLUSIONS: Both quantitative and qualitative evaluation suggest that the proposed brain extraction approach for NCCT and CTA images can be used for different clinical imaging settings, thus serving to improve current image analysis in the field of neuroimaging.

Correction to: Accuracy and Reliability of Multiphase CTA Perfusion for Identifying Ischemic Core.

Correction to: Clin Neuroradiol 2018 https://doi.org/10.1007/s00062-018-0717-x Unfortunately, the author list of the original version of this article contains a mistake. The middle name of the author "Rani Gupta Sah" was erroneously tagged as part of the surname in the article's metadata.This mistake.

Accuracy and Reliability of Multiphase CTA Perfusion for Identifying Ischemic Core.

PURPOSE: Acute stroke treatment requires simple, quick and accurate detection of early ischemic changes to facilitate treatment decisions guided by published selection criteria. The aim of this study was to determine the accuracy and reliability of multiphase computed tomography angiography (mCTA) perfusion hypoattenuation for detecting early severe ischemia. METHODS: Non-contrast CT (NCCT), mCTA for regional leptomeningeal score (mCTA-rLMC), and mCTA perfusion lesion visibility (mCTA-arterial and mCTA-venous) were assessed blinded to clinical information in patients treated with endovascular therapy (EVT). The extent of early ischemia defined by regions of hypoattenuation was evaluated by the Alberta Stroke Program Early CT Score (ASPECTS). The ASPECTS scores were dichotomized based on the American Heart Association (AHA) guidelines for EVT selection, ASPECTS ≥6 vs. <6. The diagnostic accuracy was calculated by comparison to 24-h magnetic resonance imaging (MRI) or CT ASPECTS. Inter-observer reliability of NCCT and mCTA ASPECTS was evaluated. Machine learning models were used to predict the clinical follow-up outcome, e.g. National Institutes of Health Stroke scale (NIHSS) and modified Rankin scale (mRS) from baseline imaging data and patient information. RESULTS: A total of 89 acute stroke patients (68 ± 15 years of age) were analyzed (33 TICI-0, 56 TICI-2b or 3). Median baseline NIHSS was 17. The mCTA-venous had a large effect on accurately identifying early ischemia when dichotomized for ASPECTS ≥6 vs <6 (likelihood ratio [LR+] > 10 vs. [LR-] < 0.29) compared to the moderate effect of NCCT ([LR+] = 6.7; [LR-] = 0.56) and mCTA-rLMC [(LR+ = 8.0; (LR-) = 0.83)]. The inter-observer reliability in mCTA-venous was almost perfect for all ASPECTS regions except the internal capsule. The machine learning support factor regression model identified mCTA-venous as the most important imaging covariate for predicting 24-h NIHSS and 90-day mRS. CONCLUSION: The assessment of mCTA-venous permits a more accurate detection of early ischemia than NCCT and mCTA-rLMC score and is predictive of clinical outcome. We would recommend the inclusion of mCTA perfusion lesion in future endovascular trials aiming at extending current AHA guidelines for EVT in stroke patients with low ASPECTS.

Association of Clinical, Imaging, and Thrombus Characteristics With Recanalization of Visible Intracranial Occlusion in Patients With Acute Ischemic Stroke.

Importance: Recanalization of intracranial thrombus is associated with improved clinical outcome in patients with acute ischemic stroke. The association of intravenous alteplase treatment and thrombus characteristics with recanalization over time is important for stroke triage and future trial design. Objective: To examine recanalization over time across a range of intracranial thrombus occlusion sites and clinical and imaging characteristics in patients with ischemic stroke treated with intravenous alteplase or not treated with alteplase. Design, Setting, and Participants: Multicenter prospective cohort study of 575 patients from 12 centers (in Canada, Spain, South Korea, the Czech Republic, and Turkey) with acute ischemic stroke and intracranial arterial occlusion demonstrated on computed tomographic angiography (CTA). Exposures: Demographics, clinical characteristics, time from alteplase to recanalization, and intracranial thrombus characteristics (location and permeability) defined on CTA. Main Outcomes and Measures: Recanalization on repeat CTA or on first angiographic acquisition of affected intracranial circulation obtained within 6 hours of baseline CTA, defined using the revised arterial occlusion scale (rAOL) (scores from 0 [primary occlusive lesion remains the same] to 3 [complete revascularization of primary occlusion]). Results: Among 575 patients (median age, 72 years [IQR, 63-80]; 51.5% men; median time from patient last known well to baseline CTA of 114 minutes [IQR, 74-180]), 275 patients (47.8%) received intravenous alteplase only, 195 (33.9%) received intravenous alteplase plus endovascular thrombectomy, 48 (8.3%) received endovascular thrombectomy alone, and 57 (9.9%) received conservative treatment. Median time from baseline CTA to recanalization assessment was 158 minutes (IQR, 79-268); median time from intravenous alteplase start to recanalization assessment was 132.5 minutes (IQR, 62-238). Successful recanalization occurred at an unadjusted rate of 27.3% (157/575) overall, including in 30.4% (143/470) of patients who received intravenous alteplase and 13.3% (14/105) who did not (difference, 17.1% [95% CI, 10.2%-25.8%]). Among patients receiving alteplase, the following factors were associated with recanalization: time from treatment start to recanalization assessment (OR, 1.28 for every 30-minute increase in time [95% CI, 1.18-1.38]), more distal thrombus location, eg, distal M1 middle cerebral artery (39/84 [46.4%]) vs internal carotid artery (10/92 [10.9%]) (OR, 5.61 [95% CI, 2.38-13.26]), and higher residual flow (thrombus permeability) grade, eg, hairline streak (30/45 [66.7%]) vs none (91/377 [24.1%]) (OR, 7.03 [95% CI, 3.32-14.87]). Conclusions and Relevance: In patients with acute ischemic stroke, more distal thrombus location, greater thrombus permeability, and longer time to recanalization assessment were associated with recanalization of arterial occlusion after administration of intravenous alteplase; among patients who did not receive alteplase, rates of arterial recanalization were low. These findings may help inform treatment and triage decisions in patients with acute ischemic stroke.

Defining CT Perfusion Thresholds for Infarction in the Golden Hour and With Ultra-Early Reperfusion.

In this brief report, computed tomography perfusion (CTP) thresholds predicting follow-up infarction in patients presenting 20 to 23 seconds and cerebral blood flow <5 to 7 ml/min-1/(100 g)-1 or relative cerebral blood flow <0.14 to 0.20 optimally predicted the final infarct. These thresholds are stricter than published thresholds.

Minds treating brains: understanding the interpretation of non-contrast CT ASPECTS in acute ischemic stroke.

INTRODUCTION: The Alberta Stroke Program Early CT Score on non-contrast CT is a key component of prognostication and treatment selection in acute stroke care. Previous findings show that the reliability of this scale must be improved to maximize its clinical utility. Areas covered: This review discusses technical, patient-level, and reader-level sources of variability in ASPECTS reading; relevant concepts in the psychology of medical image perception; and potential interventions likely to improve inter- and intra-rater reliability. Expert commentary: Approaching variability in medical decision making from a psychological perspective will afford cognitively informed insights into the development of interventions and training techniques aimed at improving this issue.

Use of Noncontrast Computed Tomography and Computed Tomographic Perfusion in Predicting Intracerebral Hemorrhage After Intravenous Alteplase Therapy.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage is a feared complication of intravenous alteplase therapy in patients with acute ischemic stroke. We explore the use of multimodal computed tomography in predicting this complication. METHODS: All patients were administered intravenous alteplase with/without intra-arterial therapy. An age- and sex-matched case-control design with classic and conditional logistic regression techniques was chosen for analyses. Outcome was parenchymal hemorrhage on 24- to 48-hour imaging. Exposure variables were imaging (noncontrast computed tomography hypoattenuation degree, relative volume of very low cerebral blood volume, relative volume of cerebral blood flow ≤7 mL/min·per 100 g, relative volume of Tmax ≥16 s with all volumes standardized to z axis coverage, mean permeability surface area product values within Tmax ≥8 s volume, and mean permeability surface area product values within ipsilesional hemisphere) and clinical variables (NIHSS [National Institutes of Health Stroke Scale], onset to imaging time, baseline systolic blood pressure, blood glucose, serum creatinine, treatment type, and reperfusion status). RESULTS: One-hundred eighteen subjects (22 patients with parenchymal hemorrhage versus 96 without, median baseline NIHSS score of 15) were included in the final analysis. In multivariable regression, noncontrast computed tomography hypoattenuation grade (P<0.006) and computerized tomography perfusion white matter relative volume of very low cerebral blood volume (P=0.04) were the only significant variables associated with parenchymal hemorrhage on follow-up imaging (area under the curve, 0.73; 95% confidence interval, 0.63-0.83). Interrater reliability for noncontrast computed tomography hypoattenuation grade was moderate (κ=0.6). CONCLUSIONS: Baseline hypoattenuation on noncontrast computed tomography and very low cerebral blood volume on computerized tomography perfusion are associated with development of parenchymal hemorrhage in patients with acute ischemic stroke receiving intravenous alteplase.