Comparison of Clinical and Radiological Outcomes Between Different (Balloon) Guide Catheter With and Without Inflated Balloon in Acute Ischemic Stroke Patients: A MaSQ-Registry Study.

PURPOSE: Balloon guide catheters (BGCs) are used in endovascular treatment (EVT) for ischemic stroke. Previous literature did not distinguish between BGC use with and without inflated balloon. This study aims to compare outcomes between non-BCG and BGC use with and without inflated balloon during EVT. METHODS: Patients who underwent EVT for anterior circulation ischemic stroke between September 2020 and February 2023 were analyzed. Patients were divided into three groups: non-BGC, BGC with inflated balloon, or BGC without inflated balloon. The primary outcome was the ordinal modified Rankin Scale (mRS) at 90-day follow-up. Secondary outcomes included expanded Thrombolysis In Cerebral Ischemia score (eTICI) and periprocedural complications. Regression analyses with BGC with inflated balloon as comparator were performed with adjustments. Subgroup analyses were conducted based on first-line thrombectomy technique. RESULTS: Out of 511 patients, 428 patients were included. Compared to BCG with inflated balloon, the mRS at 90 days did not differ in the group without inflated balloon (adjusted common [ac]OR: 1.07, 95%CI 0.67-1.73) or non-BGC (acOR: 1.42, 95%CI 0.83-2.42). Compared to patients treated with a BGC with inflated balloon, those treated with BGC without inflated balloon had lower eTICI scores (acOR: 0.59, 95%CI 0.37-0.94), and patients treated with non-BGC had lower chances of periprocedural complications (aOR: 0.41, 95%CI 0.20-0.86). CONCLUSIONS: This study shows no clinical differences in ischemic stroke patients treated with BGC with inflated balloon compared to non-BGC and BGC without inflated balloon, despite lower periprocedural complication rates in the non-BGC group and lower eTICI scores in the BGC without inflated balloon group. LEVEL OF EVIDENCE: Level 3, non-controlled retrospective cohort study.

Procedural blood pressure and contrast extravasation on dual energy computed tomography after endovascular stroke treatment.

BACKGROUND: Blood brain barrier disruption (BBBD) can be visualized by contrast extravasation (CE) after endovascular treatment (EVT) in patients with acute ischemic stroke. Elevated blood pressure is a risk factor for BBBD. However, the association between procedural blood pressure and CE post-EVT is unknown. METHODS: In this single-center retrospective study, we analyzed 501 eligible patients who received a dual energy CT (DECT) immediately post-EVT for acute ischemic stroke. Procedural blood pressure values (SBPmean, SBPmax, SBPmax-min, and MAPmean) were collected. CE was quantified by measuring the maximum parenchymal iodine concentration on DECT iodine overlay map reconstructions. As a measure for the extent of BBBD, we created CE-ASPECTS by deducting one point per hyperdense ASPECTS region on iodine overlay maps. The association between blood pressure and CE was assessed using multivariable linear regression. RESULTS: The procedural SBPmean, SBPmax, and MAPmean were 150 ± 26 mmHg, 173 ± 29 mmHg, and 101 ± 17 mmHg, respectively. The median maximum iodine concentration on post-EVT DECT was 1.2 mg/ml (IQR 0.7-2.0), and median CE-ASPECTS was 8 (IQR 5-11). The maximum iodine concentration was not associated with blood pressure. SBPmean, SBPmax, and MAPmean were significantly associated with CE-ASPECTS (per 10 mmHg, ß = -0.2, 95 % CI -0.31 to -0.09, ß = -0.15, 95 % CI -0.25 to -0.06, ß = -0.33, 95 % CI -0.49 to -0.17, respectively). CONCLUSION: In acute ischemic stroke patients undergoing EVT, particularly in patients achieving successful recanalization, SBPmean, SBPmax, and MAPmean are associated with the extent of BBBD on immediate post-EVT DECT, but not with maximum iodine concentration.

The correlation between CT perfusion deficits and immediate post-endovascular treatment contrast extravasation on dual energy CT in acute ischemic stroke patients.

PURPOSE: After endovascular therapy (EVT) for ischemic stroke, post-EVT CT imaging often shows areas of contrast extravasation (CE) caused by blood brain barrier disruption (BBBD). Before EVT, CT-perfusion (CTP) can be used to estimate salvageable tissue (penumbra) and irrevocably damaged infarction (core). In this study, we aimed to correlate CTP deficits to CE, as a surrogate marker for BBBD, after EVT for ischemic stroke. METHODS: In this single center study, EVT patients between 2010 and 2020 in whom both CTP at baseline and DECT post-EVT was performed were included. The presence of core and penumbra on CTP was assessed per ASPECTS region, resulting in a CTP-ASPECTScore and a CTP-ASPECTScore+penumbra. Likewise, CE on DECT was scored per ASPECTS region, resulting in a CE-ASPECTS. Correlation was assessed using Kendall's tau correlation and positive predictive values (PPV) were calculated per ASPECTS region. Bland-Altman plots were created to visualize the agreement between the two scores. RESULTS: 194 patients met our inclusion criteria. The median core and penumbra were 8 cc (IQR 1-25) and 103 cc (IQR 68-141), respectively. The median CTP-ASPECTScore, CTP-ASPECTScore+penumbra, and CE-ASPECTS were 7 (IQR 4-9), 3 (IQR 1-4), and 6 (IQR 4-9), respectively. The correlation between CTP-ASPECTScore and CE-ASPECTS was τ = 0.21, P <.001, and τ = 0.13, P =.02 between CTP-ASPECTScore+penumbra and CE-ASPECTS. Bland-Altman plots showed a mean difference (CTP-ASPECTS minus CE-ASPECTS) of 0.27 (95 %CI -6.7-7.2) for CTP-ASPECTScore and -3.2 (95 %CI -9.7-3.2) for CTP-ASPECTScore+penumbra. The PPVs of the CTP-ASPECTScore and CTP-ASPECTScore+penumbra were highest for the basal ganglia. CONCLUSION: There is a weak although significant correlation between pre-EVT CTP-ASPECTS and post-EVT CE-ASPECTS. The weak correlation may be attributed to various imaging limitations as well as patient related factors.

Procedural Blood Pressure and Intracranial Hemorrhage on Dual-Energy Computed Tomography After Endovascular Stroke Treatment.

PURPOSE: Optimal systolic blood pressure (SBP) management during endovascular treatment (EVT) for acute ischemic stroke remains a topic of debate. Though BP is associated with worse functional outcome, the relationship between BP and post-procedural intracranial hemorrhage (ICH) is less well-known. We aimed to investigate the association between BP during EVT and post-procedural ICH on dual-energy CT (DECT). METHODS: We included all patients who underwent EVT for an anterior circulation large vessel occlusion between 2010 and 2019, and received DECT < 3 h post-EVT. All BP measurements during the EVT procedure were used to calculate mean arterial pressure (MAPmean), mean SBP (SBPmean), and SBPmax-min (highest minus lowest). ICH was assessed using virtual post-procedural unenhanced DECT reconstructions and classified as intraparenchymal or extraparenchymal. Symptomatic ICH was scored according to the Heidelberg criteria. The association between different BP parameters and ICH was assessed using multivariable logistic regression. RESULTS: We included 478 patients. Seventy-six patients (16%) demonstrated ICH on DECT, of which 26 (34%) were intraparenchymal. Symptomatic intraparenchymal and extraparenchymal ICH occurred in 10 (38%) and 4 (8%) patients. SBPmax, SBPmean, and MAPmean were associated with intraparenchymal ICH with an adjusted odds ratio of 1.19 (95%CI, 1.02-1.39), 1.22 (95%CI, 1.03-1.46), and 1.40 (95%CI, 1.09-1.81) per 10 mmHg, while BP was not significantly associated with extraparenchymal ICH. BP did not differ between asymptomatic and symptomatic ICH. CONCLUSION: Procedural BP is associated with intraparenchymal ICH on post-EVT DECT but not with extraparenchymal ICH. Future studies should evaluate whether individual procedural BP management reduces post-EVT ICH and improves clinical outcome.

Association of hyperglycemia and computed tomographic perfusion deficits in patients who underwent endovascular treatment for acute ischemic stroke caused by a proximal intracranial occlusion: A subgroup analysis of a randomized phase 3 trial (MR CLEAN).

INTRODUCTION: Hyperglycemia is highly prevalent in patients with acute ischemic stroke and is associated with increased risk of symptomatic intracranial hemorrhage, larger infarct size and unfavorable outcome. Furthermore, glucose may modify the effect of endovascular treatment (EVT) in patients with ischemic stroke. Hyperglycemia might lead to accelerated conversion of penumbra into infarct core. However, it remains uncertain whether hyperglycemia on admission is associated with the size of penumbra or infarct core in acute ischemic stroke. In this study, we aimed to assess the association between hyperglycemia and Computed Tomographic Perfusion (CTP) derived parameters in patients who underwent EVT for acute ischemic stroke. METHODS: We used data from the MR CLEAN study (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands). Hyperglycemia was defined as admission serum glucose of >7.8 mmol/L. Dichotomized and quantiles of glucose levels were related to size of core, penumbra and core penumbra ratio. Hypoperfused area is mean transient time 45% higher than that of the contralateral hemisphere. Core is the area with cerebral blood volume of <2 mL/100 g and penumbra is the area with cerebral blood volume > 2 mL/100 g. Core-penumbra ratio is the ischemic core divided by the total volume of hypoperfused tissue (core plus penumbra) multiplied by 100. Adjustments were made for age, sex, NIHSS on admission, onset-imaging time and diabetes mellitus. RESULTS: Hundred seventy-three patients were included. Median glucose level on admission was 6.5 mmol/L (IQR 5.8-7.5 mmol/L) and thirty-five patients (20%) were hyperglycemic. Median core volume was 33.3 mL (IQR 13.6-62.4 mL), median penumbra volume was 80.2 mL (IQR 36.3-123.5 mL) and median core-penumbra ratio was 28.5% (IQR 18.6-45.8%). Patients with hyperglycemia on admission had larger core volumes and core penumbra ratio than normoglycemic patients with a regression coefficient of 15.1 (95% confidence interval (CI), 1.8 to 28.3) and 11.5 (95% confidence interval (CI), 3.4 to 19.7) respectively. CONCLUSION: Hyperglycemia on admission was associated with larger ischemic core volume and larger core-penumbra ratio in patients with acute ischemic stroke who underwent endovascular treatment.

Unsupervised Deep Learning for Stroke Lesion Segmentation on Follow-up CT Based on Generative Adversarial Networks.

BACKGROUND AND PURPOSE: Supervised deep learning is the state-of-the-art method for stroke lesion segmentation on NCCT. Supervised methods require manual lesion annotations for model development, while unsupervised deep learning methods such as generative adversarial networks do not. The aim of this study was to develop and evaluate a generative adversarial network to segment infarct and hemorrhagic stroke lesions on follow-up NCCT scans. MATERIALS AND METHODS: Training data consisted of 820 patients with baseline and follow-up NCCT from 3 Dutch acute ischemic stroke trials. A generative adversarial network was optimized to transform a follow-up scan with a lesion to a generated baseline scan without a lesion by generating a difference map that was subtracted from the follow-up scan. The generated difference map was used to automatically extract lesion segmentations. Segmentation of primary hemorrhagic lesions, hemorrhagic transformation of ischemic stroke, and 24-hour and 1-week follow-up infarct lesions were evaluated relative to expert annotations with the Dice similarity coefficient, Bland-Altman analysis, and intraclass correlation coefficient. RESULTS: The median Dice similarity coefficient was 0.31 (interquartile range, 0.08-0.59) and 0.59 (interquartile range, 0.29-0.74) for the 24-hour and 1-week infarct lesions, respectively. A much lower Dice similarity coefficient was measured for hemorrhagic transformation (median, 0.02; interquartile range, 0-0.14) and primary hemorrhage lesions (median, 0.08; interquartile range, 0.01-0.35). Predicted lesion volume and the intraclass correlation coefficient were good for the 24-hour (bias, 3 mL; limits of agreement, -64-59 mL; intraclass correlation coefficient, 0.83; 95% CI, 0.78-0.88) and excellent for the 1-week (bias, -4 m; limits of agreement,-66-58 mL; intraclass correlation coefficient, 0.90; 95% CI, 0.83-0.93) follow-up infarct lesions. CONCLUSIONS: An unsupervised generative adversarial network can be used to obtain automated infarct lesion segmentations with a moderate Dice similarity coefficient and good volumetric correspondence.

Evolutionary algorithms and decision trees for predicting poor outcome after endovascular treatment for acute ischemic stroke.

Despite the large overall beneficial effects of endovascular treatment in patients with acute ischemic stroke, severe disability or death still occurs in almost one-third of patients. These patients, who might not benefit from treatment, have been previously identified with traditional logistic regression models, which may oversimplify relations between characteristics and outcome, or machine learning techniques, which may be difficult to interpret. We developed and evaluated a novel evolutionary algorithm for fuzzy decision trees to accurately identify patients with poor outcome after endovascular treatment, which was defined as having a modified Rankin Scale score (mRS) higher or equal to 5. The created decision trees have the benefit of being comprehensible, easily interpretable models, making its predictions easy to explain to patients and practitioners. Insights in the reason for the predicted outcome can encourage acceptance and adaptation in practice and help manage expectations after treatment. We compared our proposed method to CART, the benchmark decision tree algorithm, on classification accuracy and interpretability. The fuzzy decision tree significantly outperformed CART: using 5-fold cross-validation with on average 1090 patients in the training set and 273 patients in the test set, the fuzzy decision tree misclassified on average 77 (standard deviation of 7) patients compared to 83 (±7) using CART. The mean number of nodes (decision and leaf nodes) in the fuzzy decision tree was 11 (±2) compared to 26 (±1) for CART decision trees. With an average accuracy of 72% and much fewer nodes than CART, the developed evolutionary algorithm for fuzzy decision trees might be used to gain insights into the predictive value of patient characteristics and can contribute to the development of more accurate medical outcome prediction methods with improved clarity for practitioners and patients.

p64 flow diverter: Results in 108 patients from a single center.

BACKGROUND AND PURPOSE: Flow diverters are increasingly used to treat intracranial aneurysms. We report the safety and efficacy of the p64 flow diverter, a resheathable and detachable device for intracranial aneurysms. MATERIALS AND METHODS: We retrospectively reviewed 108 patients with 109 aneurysms treated with the p64 between March 2014 and July 2019. There were 87 women and 21 men, mean age 57 years. Of 109 aneurysms, 74 were discovered incidentally, 12 were symptomatic, 18 were previously treated, and five were ruptured dissection aneurysms. A total of 10 aneurysms were located in the posterior circulation. The mean aneurysm or remnant size was 8.1 mm. RESULTS: Hemorrhage by perforation with the distal guidewire occurred in two patients with permanent neurological deficits in one. In one patient, acute in-stent occlusion caused infarction with a permanent deficit. Permanent morbidity was 1.9% (2 of 108, 95%CI 0.1-6.9%); there was no mortality. During follow-up, three in-stent occlusions occurred, all asymptomatic. There were no delayed hemorrhagic complications. At six months, 77 of 96 aneurysms (80.2%) were completely occluded, and at last follow-up, this increased to 93 of 96 aneurysms (96.9%). In-stent stenosis at any degree occurred in 11 patients, progressing to asymptomatic complete occlusion in one. In the other patients, stenosis resolved or improved at further follow-up. CONCLUSION: The p64 offers an effective and safe treatment option. Aneurysm occlusion rate was 97% at last follow-up, mostly achieved with a single device. There were no delayed hemorrhagic complications. Delayed in-stent stenosis infrequently progresses to occlusion but remains a matter of concern.

The p48 flow diverter: First clinical results in 25 aneurysms in three centers.

BACKGROUND: The novel low-profile p48 flow diverter has been designed to treat aneurysms on small vessels of 1.75-3mm. We report our first clinical experiences. METHODS: Between March 2018-January 2020, 22 patients with 25 aneurysms were treated with the p48 in 3 centers. One patient had 3 aneurysms covered by one p48 and one patient had 2 aneurysms. There were 5 men, 17 women, with a mean age of 55 years (median 59, range 29-73 years). RESULTS: In 25 aneurysms, 24 p48 flow diverters were placed. In 1 patient additional coils were placed in the aneurysm. Procedural vessel rupture by the micro guidewire occurred in 2 patients and vessel rupture during p48 balloon dilatation occurred in 1 patient. Overall, the permanent morbidity rate was 13.6% (3 of 22, 95%CI 3.9-34.2%) and mortality was 4.5% (1 of 22, 95%CI <0.01-23.5%). Most complications were procedure-related and not device-specific. Of 22 patients with 25 aneurysms treated with p48, 18 patients with 20 aneurysms had angiographic follow-up after 5-18 months. Of 19 aneurysms, 10 were occluded and 7 showed a remnant. Two aneurysms were open after 6 months. Three aneurysms were still not occluded after 12, 14, and 18 months and these 3 were retreated. Retreatment rate was 16% (3 of 19) and the adequate occlusion rate was 90% (17 of 19). CONCLUSIONS: Treatment of aneurysms in small-caliber vessels with the p48 is feasible and effective but is not without complications. More data is needed to establish indications, safety, and efficacy more accurately.

Enhancing Education to Avoid Complications in Endovascular Treatment of Unruptured Intracranial Aneurysms: A Neurointerventionalist's Perspective.

It is of utmost importance to avoid errors and subsequent complications when performing neurointerventional procedures, particularly when treating low-risk conditions such as unruptured intracranial aneurysms. We used endovascular treatment of unruptured intracranial aneurysms as an example and took a survey-based approach in which we reached out to 233 neurointerventionalists. They were asked what they think are the most important points staff should teach their trainees to avoid errors and subsequent complications in endovascular treatment of unruptured intracranial aneurysms. One hundred twenty-one respondents (51.9%) provided answers in the form of free text responses, which were thematically clustered in an affinity diagram and summarized in this Practice Perspectives. The article is primarily intended for neurointerventional radiology fellows and junior staff and will hopefully provide them the opportunity to learn from the mistakes of their more experienced colleagues.

Effect of atrial fibrillation on endovascular thrombectomy for acute ischemic stroke. A meta-analysis of individual patient data from six randomised trials: Results from the HERMES collaboration.

BACKGROUND: Atrial fibrillation is an important risk factor for ischemic stroke, and is associated with an increased risk of poor outcome after ischemic stroke. Endovascular thrombectomy is safe and effective in acute ischemic stroke patients with large vessel occlusion of the anterior circulation. This meta-analysis aims to investigate whether there is an interaction between atrial fibrillation and treatment effect of endovascular thrombectomy, and secondarily whether atrial fibrillation is associated with worse outcome in patients with ischemic stroke due to large vessel occlusion. METHODS: Individual patient data were from six of the recent randomised clinical trials (MR CLEAN, EXTEND-IA, REVASCAT, SWIFT PRIME, ESCAPE, PISTE) in which endovascular thrombectomy plus standard care was compared to standard care alone. Primary outcome measure was the shift on the modified Rankin scale (mRS) at 90 days. Secondary outcomes were functional independence (mRS 0-2) at 90 days, National Institutes of Health Stroke Scale score at 24 h, symptomatic intracranial hemorrhage and mortality at 90 days. The primary effect parameter was the adjusted common odds ratio, estimated with ordinal logistic regression (shift analysis); treatment effect modification of atrial fibrillation was assessed with a multiplicative interaction term. RESULTS: Among 1351 patients, 447 patients had atrial fibrillation, 224 of whom were treated with endovascular thrombectomy. We found no interaction of atrial fibrillation with treatment effect of endovascular thrombectomy for both primary (p-value for interaction: 0.58) and secondary outcomes. Regardless of treatment allocation, we found no difference in primary outcome (mRS at 90 days: aOR 1.11 (95% CI 0.89-1.38) and secondary outcomes between patients with and without atrial fibrillation. CONCLUSION: We found no interaction of atrial fibrillation on treatment effect of endovascular thrombectomy, and no difference in outcome between large vessel occlusion stroke patients with and without atrial fibrillation.

Risk factors for developing heel ulcers for bedridden patients: A finite element study.

BACKGROUND: The heel is one of the most common sites of pressure ulcers and the anatomical location with the highest prevalence of deep tissue injury. Several finite element modeling studies investigate heel ulcers for bedridden patients. In the current study we have added the implementation of the calf structure to the current heel models. We tested the effect of foot posture, mattress stiffness, and a lateral calcaneus displacement to the contact pressure and internal maximum shear strain occurring at the heel. METHODS: A new 3D finite element model is created which includes the heel and calf structure. Sensitivity analyses are performed for the foot orientation relative to the mattress, the Young's modulus of the mattress, and a lateral displacement of the calcaneus relative to the other soft tissues in the heel. FINDINGS: The models predict that a stiffer mattress results in higher contact pressures and internal maximum shear strains at the heel as well as the calf. An abducted foot posture reduces the internal strains in the heel and a lateral calcaneus displacement increases the internal maximum shear strains. A parameter study with different mattress-skin friction coefficients showed that a coefficient below 0.4 decreases the maximum internal shear strains in all of the used loading conditions. INTERPRETATION: In clinical practice, it is advised to avoid internal shearing of the calcaneus of patients, and it could be taken into consideration by medical experts and nurses that a more abducted foot position may reduce the strains in the heel.

Data-efficient deep learning of radiological image data for outcome prediction after endovascular treatment of patients with acute ischemic stroke.

Treatment selection is becoming increasingly more important in acute ischemic stroke patient care. Clinical variables and radiological image biomarkers (old age, pre-stroke mRS, NIHSS, occlusion location, ASPECTS, among others) have an important role in treatment selection and prognosis. Radiological biomarkers require expert annotation and are subject to inter-observer variability. Recently, Deep Learning has been introduced to reproduce these radiological image biomarkers. Instead of reproducing these biomarkers, in this work, we investigated Deep Learning techniques for building models to directly predict good reperfusion after endovascular treatment (EVT) and good functional outcome using CT angiography images. These models do not require image annotation and are fast to compute. We compare the Deep Learning models to Machine Learning models using traditional radiological image biomarkers. We explored Residual Neural Network (ResNet) architectures, adapted them with Structured Receptive Fields (RFNN) and auto-encoders (AE) for network weight initialization. We further included model visualization techniques to provide insight into the network's decision-making process. We applied the methods on the MR CLEAN Registry dataset with 1301 patients. The Deep Learning models outperformed the models using traditional radiological image biomarkers in three out of four cross-validation folds for functional outcome (average AUC of 0.71) and for all folds for reperfusion (average AUC of 0.65). Model visualization showed that the arteries were relevant features for functional outcome prediction. The best results were obtained for the ResNet models with RFNN. Auto-encoder initialization often improved the results. We concluded that, in our dataset, automated image analysis with Deep Learning methods outperforms radiological image biomarkers for stroke outcome prediction and has the potential to improve treatment selection.

Flow Patterns in Carotid Webs: A Patient-Based Computational Fluid Dynamics Study.

BACKGROUND AND PURPOSE: Carotid webs are increasingly recognized as an important cause of (recurrent) ischemic stroke in patients without other cardiovascular risk factors. Hemodynamic flow patterns induced by these lesions might be associated with thrombus formation. The aim of our study was to evaluate flow patterns of carotid webs using computational fluid dynamics. MATERIALS AND METHODS: Patients with a carotid web in the Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN) were selected for hemodynamic evaluation with computational fluid dynamics models based on lumen segmentations obtained from CT angiography scans. Hemodynamic parameters, including the area of recirculation zone, time-averaged wall shear stress, transverse wall shear stress, and the oscillatory shear index, were assessed and compared with the contralateral carotid bifurcation. RESULTS: In our study, 9 patients were evaluated. Distal to the carotid webs, recirculation zones were significantly larger compared with the contralateral bifurcation (63 versus 43 mm2, P = .02). In the recirculation zones of the carotid webs and the contralateral carotid bifurcation, time-averaged wall shear stress values were comparable (both: median, 0.27 Pa; P = .30), while transverse wall shear stress and oscillatory shear index values were significantly higher in the recirculation zone of carotid webs (median, 0.25 versus 0.21 Pa; P = .02 and 0.39 versus 0.30 Pa; P = .04). At the minimal lumen area, simulations showed a significantly higher time-averaged wall shear stress in the web compared with the contralateral bifurcation (median, 0.58 versus 0.45 Pa; P = .01). CONCLUSIONS: Carotid webs are associated with increased recirculation zones and regional increased wall shear stress metrics that are associated with disturbed flow. These findings suggest that a carotid web might stimulate thrombus formation, which increases the risk of acute ischemic stroke.

Follow-up infarct volume as a mediator of endovascular treatment effect on functional outcome in ischaemic stroke.

OBJECTIVE: The putative mechanism for the favourable effect of endovascular treatment (EVT) on functional outcome after acute ischaemic stroke is preventing follow-up infarct volume (FIV) progression. We aimed to assess to what extent difference in FIV explains the effect of EVT on functional outcome in a randomised trial of EVT versus no EVT (MR CLEAN). METHODS: FIV was assessed on non-contrast CT scan 5-7 days after stroke. Functional outcome was the score on the modified Rankin Scale at 3 months. We tested the causal pathway from intervention, via FIV to functional outcome with a mediation model, using linear and ordinal regression, adjusted for relevant baseline covariates, including stroke severity. Explained effect was assessed by taking the ratio of the log odds ratios of treatment with and without adjustment for FIV. RESULTS: Of the 500 patients included in MR CLEAN, 60 died and four patients underwent hemicraniectomy before FIV was assessed, leaving 436 patients for analysis. Patients in the intervention group had better functional outcomes (adjusted common odds ratio (acOR) 2.30 (95% CI 1.62-3.26) than controls and smaller FIV (median 53 vs. 81 ml) (difference 28 ml; 95% CI 13-41). Smaller FIV was associated with better outcome (acOR per 10 ml 0.60, 95% CI 0.52-0.68). After adjustment for FIV the effect of intervention on functional outcome decreased but remained substantial (acOR 2.05, 95% CI 1.44-2.91). This implies that preventing FIV progression explains 14% (95% CI 0-34) of the beneficial effect of EVT on outcome. CONCLUSION: The effect of EVT on FIV explains only part of the treatment effect on functional outcome. KEY POINTS: • Endovascular treatment in acute ischaemic stroke patients prevents progression of follow-up infarct volume on non-contrast CT at 5-7 days. • Follow-up infarct volume was related to functional outcome, but only explained a modest part of the effect of intervention on functional outcome. • A large proportion of treatment effect on functional outcome remains unexplained, suggesting FIV alone cannot be used as an early surrogate imaging marker of functional outcome.

Impact of Ischemic Lesion Location on the mRS Score in Patients with Ischemic Stroke: A Voxel-Based Approach.

BACKGROUND AND PURPOSE: Previous studies indicated that ischemic lesion volume might be a useful surrogate marker for functional outcome in ischemic stroke but should be considered in the context of lesion location. In contrast to previous studies using the ROI approach, which has several drawbacks, the present study aimed to measure the impact of ischemic lesion location on functional outcome using a more precise voxelwise approach. MATERIALS AND METHODS: Datasets of patients with acute ischemic strokes from the Multicenter Randomized Clinical Trial of Endovascular Therapy for Acute Ischemic Stroke in the Netherlands (MR CLEAN) were used. Primary outcome was functional outcome as assessed by the modified Rankin Scale 3 months after stroke. Ischemic lesion volume was determined on CT scans 3-9 days after stroke. Voxel-based lesion-symptom mapping techniques, including covariates that are known to be associated with functional outcome, were used to determine the impact of ischemic lesion location for outcome. RESULTS: Of the 500 patients in the MR CLEAN trial, 216 were included for analysis. The mean age was 63 years. Lesion-symptom mapping with inclusion of covariates revealed that especially left-hemispheric lesions in the deep periventricular white matter and adjacent internal capsule showed a great influence on functional outcome. CONCLUSIONS: Our study confirms that infarct location has an important impact on functional outcome of patients with stroke and should be considered in prediction models. After we adjusted for covariates, the left-hemispheric corticosubcortical fiber tracts seemed to be of higher functional importance compared with cortical lesions.

Accuracy of CT Angiography for Differentiating Pseudo-Occlusion from True Occlusion or High-Grade Stenosis of the Extracranial ICA in Acute Ischemic Stroke: A Retrospective MR CLEAN Substudy.

BACKGROUND AND PURPOSE: The absence of opacification on CTA in the extracranial ICA in acute ischemic stroke may be caused by atherosclerotic occlusion, dissection, or pseudo-occlusion. The latter is explained by sluggish or stagnant flow in a patent artery caused by a distal intracranial occlusion. This study aimed to explore the accuracy of CTA for differentiating pseudo-occlusion from true occlusion of the extracranial ICA. MATERIALS AND METHODS: All patients from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) with an apparent ICA occlusion on CTA and available DSA images were included. Two independent observers classified CTA images as atherosclerotic cause (occlusion/high-grade stenosis), dissection, or suspected pseudo-occlusion. Pseudo-occlusion was suspected if CTA showed a gradual contrast decline located above the level of the carotid bulb, especially in the presence of an occluded intracranial ICA bifurcation (T-occlusion). DSA images, classified into the same 3 categories, were used as the criterion standard. RESULTS: In 108 of 476 patients (23%), CTA showed an apparent extracranial carotid occlusion. DSA was available in 46 of these, showing an atherosclerotic cause in 13 (28%), dissection in 16 (35%), and pseudo-occlusion in 17 (37%). The sensitivity for detecting pseudo-occlusion on CTA was 82% (95% CI, 57-96) for both observers; specificity was 76% (95% CI, 56-90) and 86% (95% CI, 68-96) for observers 1 and 2, respectively. The κ value for interobserver agreement was .77, indicating substantial agreement. T-occlusions were more frequent in pseudo- than true occlusions (82% versus 21%, P < .001). CONCLUSIONS: On CTA, extracranial ICA pseudo-occlusions can be differentiated from true carotid occlusions.

Value of Quantitative Collateral Scoring on CT Angiography in Patients with Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Many studies have emphasized the relevance of collateral flow in patients presenting with acute ischemic stroke. Our aim was to evaluate the relationship of the quantitative collateral score on baseline CTA with the outcome of patients with acute ischemic stroke and test whether the timing of the CTA acquisition influences this relationship. MATERIALS AND METHODS: From the Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN) data base, all baseline thin-slice CTA images of patients with acute ischemic stroke with intracranial large-vessel occlusion were retrospectively collected. The quantitative collateral score was calculated as the ratio of the vascular appearance of both hemispheres and was compared with the visual collateral score. Primary outcomes were 90-day mRS score and follow-up infarct volume. The relation with outcome and the association with treatment effect were estimated. The influence of the CTA acquisition phase on the relation of collateral scores with outcome was determined. RESULTS: A total of 442 patients were included. The quantitative collateral score strongly correlated with the visual collateral score (ρ = 0.75) and was an independent predictor of mRS (adjusted odds ratio = 0.81; 95% CI, .77-.86) and follow-up infarct volume (exponent ß = 0.88; P < .001) per 10% increase. The quantitative collateral score showed areas under the curve of 0.71 and 0.69 for predicting functional independence (mRS 0-2) and follow-up infarct volume of >90 mL, respectively. We found significant interaction of the quantitative collateral score with the endovascular therapy effect in unadjusted analysis on the full ordinal mRS scale (P = .048) and on functional independence (P = .049). Modification of the quantitative collateral score by acquisition phase on outcome was significant (mRS: P = .004; follow-up infarct volume: P < .001) in adjusted analysis. CONCLUSIONS: Automated quantitative collateral scoring in patients with acute ischemic stroke is a reliable and user-independent measure of the collateral capacity on baseline CTA and has the potential to augment the triage of patients with acute stroke for endovascular therapy.

Value of Thrombus CT Characteristics in Patients with Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Thrombus CT characteristics might be useful for patient selection for intra-arterial treatment. Our objective was to study the association of thrombus CT characteristics with outcome and treatment effect in patients with acute ischemic stroke. MATERIALS AND METHODS: We included 199 patients for whom thin-section NCCT and CTA within 30 minutes from each other were available in the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute ischemic stroke in the Netherlands (MR CLEAN) study. We assessed the following thrombus characteristics: location, distance from ICA terminus to thrombus, length, volume, absolute and relative density on NCCT, and perviousness. Associations of thrombus characteristics with outcome were estimated with univariable and multivariable ordinal logistic regression as an OR for a shift toward better outcome on the mRS. Interaction terms were used to investigate treatment-effect modification by thrombus characteristics. RESULTS: In univariate analysis, only the distance from the ICA terminus to the thrombus, length of >8 mm, and perviousness were associated with functional outcome. Relative thrombus density on CTA was independently associated with functional outcome with an adjusted common OR of 1.21 per 10% (95% CI, 1.02-1.43; P = .029). There was no treatment-effect modification by any of the thrombus CT characteristics. CONCLUSIONS: In our study on patients with large-vessel occlusion of the anterior circulation, CT thrombus characteristics appear useful for predicting functional outcome. However, in our study cohort, the effect of intra-arterial treatment was independent of the thrombus CT characteristics. Therefore, no arguments were provided to select patients for intra-arterial treatment using thrombus CT characteristics.

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.