Early Ischemic Changes Research Articles

The treatment effect across ASPECTS in acute ischemic stroke: Analysis from the AcT trial.

Early ischemic changes on baseline imaging are commonly evaluated for acute stroke decision-making and prognostication. We assess the association of early ischemic changes on clinical outcomes and whether it differs between intravenous tenecteplase and Alteplase. Data are from the phase 3, Alteplase compared to Tenecteplase (AcT) trial. Subjects with anterior circulation stroke were included. Early ischemic changes were assessed using the Alberta Stroke Program Early CT score (ASPECTS). Efficacy outcomes included modified Rankin scale (mRS) 0-1, mRS 0-2, and ordinal mRS at 90 days. Safety outcomes included 24-h symptomatic intracerebral hemorrhage (sICH), any hemorrhage on follow-up scan, and 90-day mortality rate. Mixed-effects logistic regression was used to assess the association of ASPECTS (continuous and categorical (0-4 vs 5-7 vs 8-10)) with outcomes and if these associations were modified by thrombolytic type after adjusting for age, sex, and baseline stroke severity. Of the 1577 patients in the trial, 901 patients (56.3%; median age 75 years (IQR 65-84), 50.8% females, median National Institute of Health Stroke Scale (NIHSS) 14 (IQR 17-19)) with anterior circulation stroke were included. mRS 0-1 at 90 days was achieved in 1/14 (0.3%), 43/160 (14.7%), and 252/726 (85.1%) in the ASPECTS 0-4, 5-7, and 8-10 groups respectively. Every one-point decrease in ASPECTS was associated with 2.7% and 1.9% decrease in chances of mRS 0-1 and mRS 0-2 at 90 days, respectively, and 1.9% chances of increase in mortality at 90 days. Subgroup analysis in endovascular thrombectomy (EVT)-treated population showed similar results. Thrombolytic type did not modify this association between ASPECTS and 90-day mRS 0-1 (P-interaction 0.75). There was no significant interaction by thrombolytic type with any other outcomes. Similar to prior studies, we found that every one-point decrease in ASPECTS was associated with poorer clinical and safety outcomes. This effect did not differ between alteplase and tenecteplase. Data shall made available on reasonable request from the PI (BMM).

Deep Learning-Based ASPECTS Algorithm Enhances Reader Performance and Reduces Interpretation Time.

ASPECTS is a long-standing and well documented selection criteria for acute ischemic stroke treatment, however, the interpretation of ASPECTS is a challenging and time-consuming task for physicians with significant interobserver variabilities. We conducted a multi-reader, multi-case study in which readers assessed ASPECTS without and with the support of a deep learning (DL)-based algorithm in order to analyze the impact of the software on clinicians' performance and interpretation time. A total of 200 NCCT scans from 5 clinical sites (27 scanner models, 4 different vendors) were retrospectively collected. Reference standard was established through the consensus of three expert neuroradiologists who had access to baseline CTA and CTP data. Subsequently, eight additional clinicians (four typical ASPECTS reader and four senior neuroradiologists) analyzed the NCCT scans without and with the assistance of CINA-ASPECTS (Avicenna.AI, La Ciotat, France), a DLbased FDA-cleared and CE-marked algorithm designed to automatically compute ASPECTS. Differences were evaluated in both performance and interpretation time between the assisted and unassisted assessments. With software aid, readers demonstrated increased region-based accuracy from 72.4% to 76.5% (p<0.05), and increased ROC AUC from 0.749 to 0.788 (p<0.05). Notably, all readers exhibited an improved ROC AUC when utilizing the software. Moreover, use of the algorithm improved the score-based inter-observer reliability and correlation coefficient of ASPECTS evaluation by 0.222 and 0.087 (p<0.0001), respectively. Additionally, the readers' mean time spent analyzing a case was significantly reduced by 6% (p<0.05) when aided by the algorithm. With the assistance of the algorithm, readers' analyses were not only more accurate but also faster. Additionally, the overall ASPECTS evaluation exhibited greater consistency, less variabilities and higher precision compared to the reference standard. This novel tool has the potential to enhance patient selection for appropriate treatment by enabling physicians to deliver accurate and timely diagnosis of acute ischemic stroke. ASPECTS = Alberta Stroke Program Early Computed Tomography Score; DL = Deep Learning; EIC = Early Ischemic Changes; ICC = Intraclass Correlation Coefficient; IS = Ischemic Stroke; ROC AUC = Receiver Operating Characteristics Area Under the Curve.

Effectiveness of computed tomography perfusion imaging in stroke management.

Current guidelines do not support the use of computed tomography perfusion (CTP) in stroke, except when identifying the penumbra during an extended treatment window. Therefore, this study aimed to define the yield of CTP in diagnosing a stroke diagnosis beyond the imaging of the penumbra in the hyperacute phase (0-6 h) and an extended time window (6-24 h). All consecutive patients with acute onset of symptoms within a 24-h window underwent CTP imaging. The diagnostic value of CTP was calculated against the clinical and radiological diagnoses of stroke. A positive CTP result was determined by the presence of either a core or penumbra on the RAPID summary. Clinical diagnoses corresponded to discharge diagnoses of stroke. A radiological diagnosis was established if early ischemic changes [Alberta Stroke Program Early CT Score (ASPECTS) <10] were observed on the baseline CT scan, acute infarction was confirmed on follow-up imaging, or symptomatic occlusion was evident on baseline CTA. Between November 2018 and November 2019, 585 consecutive patients with an acute neurological deficit underwent multimodal CT imaging. A total of 500 patients (85%) were included, where 274 (55%) were within the hyperacute phase, 153 (31%) had a radiological diagnosis of stroke, and 122 (24%) had a clinical diagnosis of stroke. CTP yielded positive results only in patients with a confirmed stroke (positive predictive value and specificity of 100%). When CTP results were negative, 43% of the cases turned out to stroke mimics. Patients with stroke mimics were younger (66 ± 17 vs. 73 ± 13) and had lower scores on the National Institutes of Health Stroke Scale [median 0; interquartile range (IQR) 0-2 vs. median 4; IQR 2-6] compared to patients with CTP-negative strokes. In our study, CTP consistently indicated brain ischemia; therefore, in stroke management, CTP is most beneficial when it yields a positive result. A positive CTP result should prompt adequate stroke management actions without any delay. Conversely, a negative CTP result necessitates the consideration of both stroke and non-stroke diagnoses.

Worldwide Survey on Approach to Thrombolysis in Acute Ischemic Stroke With Large Vessel Occlusion.

With recent trials suggesting that endovascular thrombectomy (EVT) alone may be noninferior to combined intravenous thrombolysis (IVT) with alteplase and EVT and that tenecteplase is non-inferior to alteplase in treating acute ischemic stroke, we sought to understand current practices around the world for treating acute ischemic stroke with large vessel occlusion (LVO) depending on the center of practice (IVT-capable vs IVT and EVT-capable stroke center). The electronic survey launched by the Practice Current section of Neurology: Clinical Practice included 6 clinical and 8 demographic questions. A single-case scenario was presented of a 65-year-old man presenting with right hemiplegia with aphasia with a duration of 1 hour. Imaging showed left M1-MCA occlusion with no early ischemic changes. The respondents were asked about their treatment approach in 2 settings: the patient presented to (1) the IVT-only capable center and (2) the IVT and EVT-capable center. They were also asked about the thrombolytic agent of choice in current and ideal circumstances for these settings. A total of 203 physicians (42.9% vascular neurologists) from 44 countries completed the survey. Most participants (55.2%) spent ≥50% of their time delivering stroke care. The survey results showed that in current practice, more than 90% of respondents would offer IVT + EVT to patients with LVO stroke presenting to either an EVT-capable (91.1%) or IVT-only-capable center (93.6%). Although nearly 80% currently use alteplase for thrombolysis, around 60% would ideally like to switch to tenecteplase independent of the practice setting. These results were similar between stroke and non-stroke neurologists. Most physicians prefer IVT before EVT in patients with acute ischemic stroke attributable to large vessel occlusion independent of the practice setting.

European stroke organisation and European society for minimally invasive neurological therapy guideline on acute management of basilar artery occlusion.

The aim of the present European Stroke Organisation (ESO) guideline is to provide evidence-based recommendations on the acute management of patients with basilar artery occlusion (BAO). These guidelines were prepared following the Standard Operational Procedure of the ESO and according to the GRADE methodology. Although BAO accounts for only 1%-2% of all strokes, it has very poor natural outcome. We identified 10 relevant clinical situations and formulated the corresponding Population Intervention Comparator Outcomes (PICO) questions, based on which a systematic literature search and review was performed. The working group consisted of 10 voting members (five representing ESO and five ESMINT) and three non-voting junior members. The certainty of evidence was generally very low. In many PICOs, available data were scarce or lacking, hence, we provided expert consensus statements. First, we compared intravenous thrombolysis (IVT) to no IVT, but specific BAO-related data do not exist. Yet, historically, IVT was standard of care for BAO patients who were also included (albeit in small numbers) in IVT trials. Non-randomised studies of IVT-only cohorts showed high proportion of favourable outcomes. Expert Consensus suggests using IVT up to 24 h unless otherwise contraindicated. We further suggest IVT plus endovascular treatment (EVT) over direct EVT. EVT on top of best medical treatment (BMT) was compared to BMT alone within 6 and 6-24 h from last seen well. In both time windows, we observed a different effect of treatment depending on (a) the region where the patients were treated (Europe vs. Asia), (b) on the proportion of IVT in the BMT arm, and (c) on the initial stroke severity. In case of high proportion of IVT in the BMT group and in patients with NIHSS below 10, EVT plus BMT was not found better than BMT alone. Based on very low certainty of evidence, we suggest EVT + BMT over BMT alone (i.e. based on results of patients with at least 10 NIHSS points and a low proportion of IVT in BMT). For patients with an NIHSS below 10, we found no evidence to recommend EVT over BMT. In fact, BMT was non-significantly better and safer than EVT. Furthermore, we found a stronger treatment effect of EVT + BMT over BMT alone in proximal and middle locations of BAO compared to distal location. While recommendations for patients without extensive early ischaemic changes in the posterior fossa can, in general, follow those of other PICOs, we formulated an Expert Consensus Statement suggesting against reperfusion therapy in those with extensive bilateral and/or brainstem ischaemic changes. Another Expert Consensus suggests reperfusion therapy regardless of collateral scores. Based on limited evidence, we suggest direct aspiration over stent retriever as the first-line strategy of mechanical thrombectomy. As an Expert Consensus, we suggest rescue percutaneous transluminal angioplasty and/or stenting after a failed EVT procedure. Finally, based on very low certainty of evidence, we suggest add-on antithrombotic treatment during EVT or within 24 h after EVT in patients with no concomitant IVT and in whom EVT was complicated (defined as failed or imminent re-occlusion, or need for additional stenting or angioplasty).

Improving acute stroke assessment in non-enhanced computed tomography: automated tool for early ischemic lesion volume detection.

ASPECTs is a widely used marker to identify early stroke signs on non-enhanced computed tomography (NECT), yet it presents interindividual variability and it may be hard to use for non-experts. We introduce an algorithm capable of automatically estimating the NECT volumetric extension of early acute ischemic changes in the 3D space. We compared the power of this marker with ASPECTs evaluated by experienced practitioner in predicting the clinical outcome. We analyzed and processed neuroimaging data of 153 patients admitted with acute ischemic stroke. All patients underwent a NECT at admission and on follow-up. The developed algorithm identifies the early ischemic hypodense region based on an automatic comparison of the gray level in the images of the two hemispheres, assumed to be an approximate mirror image of each other in healthy patients. In the two standard axial slices used to estimate the ASPECTs, the regions identified by the algorithm overlap significantly with those identified by experienced practitioners. However, in many patients, the regions identified automatically extend significantly to other slices. In these cases,the volume marker provides supplementary and independent information.Indeed,theclinical outcome of patients with volume marker = 0 can be distinguished with higher statistical confidence than the outcome of patients with ASPECTs = 10. The volumetric extension and the location of acute ischemic region in the 3D-space, automatically identified by our algorithm, provide data that are mostly in agreement with the ASPECTs value estimated by expert practitioners, and in some cases complementary and independent.

Combining Early Ischemic Change and Collateral Extent for Functional Outcomes After Endovascular Therapy: An Analysis From AcT Trial.

Early ischemic change and collateral extent are colinear with ischemic core volume (ICV). We investigated the relationship between a combined score using the Alberta Stroke Program Early Computed Tomography Score and multiphase computed tomography angiography (mCTA) collateral extent, named mCTA-ACE score, on functional outcomes in endovascular therapy-treated patients. We performed a post hoc analysis of a subset of endovascular therapy-treated patients from the Alteplase Compared to Tenecteplase trial which was conducted between December 2019 and January 2022 at 22 centers across Canada. Ten-point mCTA collateral corresponding to M2 to M6 regions of the Alberta Stroke Program Early Computed Tomography Score grid was evaluated as 0 (poor), 1 (moderate), or 2 (normal) and additively combined with the 10-point Alberta Stroke Program Early Computed Tomography Score to produce a 20-point mCTA-ACE score. We investigated the association of mCTA-ACE score with modified Rankin Scale score ≤2 and return to prestroke level of function at 90 to 120 days using mixed-effects logistic regression. In the subset of patients who underwent baseline computed tomography perfusion imaging, we compared the mCTA-ACE score and ICV for outcome prediction. Among 1577 intention-to-treat population in the trial, 368 (23%; 179 men; median age, 73 years) were included, with Alberta Stroke Program Early Computed Tomography Score, mCTA collateral, and combination of both (mCTA-ACE score: median [interquartile range], 8 [7-10], 9 [8-10], and 17 [16-19], respectively). The probability of modified Rankin Scale score ≤2 and return to prestroke level of function increased for each 1-point increase in mCTA-ACE score (odds ratio, 1.16 [95% CI, 1.06-1.28] and 1.22 [95% CI, 1.06-1.40], respectively). Among 173 patients in whom computed tomography perfusion data was assessable, the mCTA-ACE score was inversely correlated with ICV (ρ=-0.46; P<0.01). The mCTA-ACE score was comparable to ICV to predict a modified Rankin Scale score ≤2 and return to prestroke level of function (C statistics 0.71 versus 0.69 and 0.68 versus 0.64, respectively). The mCTA-ACE score had a significant positive association with functional outcomes after endovascular therapy and had a similar predictive performance as ICV.

Automatic assessment of DWI-ASPECTS for acute ischemic stroke based on deep learning.

Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is a standardized semi-quantitative method for early ischemic changes in acute ischemic stroke. However, ASPECTS is still affected by expert experience and inconsistent results between readers in clinical. This study aims to propose an automatic ASPECTS scoring model based on diffusion-weighted imaging (DWI) mode to help clinicians make accurate treatment plans. Eighty-two patients with stroke were included in the study. First, we designed a new deep learning network for segmenting ASPECTS scoring brain regions. The network is improved based on U-net, which integrates multiple modules. Second, we proposed using hybrid classifiers to classify brain regions. For brain regions with larger areas, we used brain grayscale comparison algorithm to train machine learning classifiers, while using hybrid feature training for brain regions with smaller areas. The average DICE coefficient of the segmented hindbrain area can reach 0.864. With the proposed hybrid classifier, our method performs significantly on both region-level ASPECTS and dichotomous ASPECTS. The sensitivity and accuracy on the test set are 95.51% and 93.43%, respectively. For dichotomous ASPECTS, the intraclass correlation coefficient (ICC) between our automated ASPECTS score and the expert reading was 0.87. This study proposed an automated model for ASPECTS scoring of patients with acute ischemic stroke based on DWI images. Experimental results show that the method of segmentation first and then classification is feasible. Our method has the potential to assist physicians in the Alberta Stroke Program with early CT scoring and clinical stroke diagnosis.

IV Thrombolysis in Basilar Artery Occlusion: Outcomes and Comparison With Endovascular Thrombectomy.

Recanalization is considered a prerequisite for favorable outcome in basilar artery occlusion (BAO). Intravenous thrombolysis (IVT) has been successfully used for eligible patients with BAO well beyond the 4.5-hour time window but has been largely underrepresented in the best medical management arms in recent randomized controlled trials of recanalization therapy in BAO. We aimed to analyze the outcomes of patients with BAO treated with IVT only and to compare IVT with endovascular thrombectomy (EVT). This observational single-center, retrospective cohort study included consecutive patients with BAO treated with IVT and/or EVT up to 48 hours of symptom onset during 1995-2022. The primary outcome was favorable functional outcome (modified Rankin Scale 0-3) at 3 months collected by a stroke physician by phone. In the first part, we described the outcomes and factors associated with functional outcome in the IVT-only cohort during 1995-2022. In the second part, we used doubly robust inverse probability-weighted regression adjustment models to compare functional outcome of patients treated with IVT vs EVT+/-IVT during 2010-2022. In the whole cohort of 376 patients with acute BAO treated with recanalization therapy, 245 (65.2%) received only IVT. In the IVT-only cohort, most patients had moderate-to-severe clinical presentation (median NIH Stroke Scale 18) but no extensive early ischemic changes in the posterior circulation on admission. Half of them had onset-to-treatment time over 6 hours. 46.5% of the IVT-treated patients achieved 3-month favorable functional outcome, whereas mortality was 35.9%. sICH occurred in 11.1%. In a multivariable analysis, younger age, milder symptom severity, and less baseline ischemic changes predicted favorable functional outcome. In the 2010-2022 cohort, when compared with patients treated with EVT+/-IVT (n = 121), the IVT-only cohort (n = 122) had higher odds for favorable functional outcome (IVT 58.2% vs EVT 43.0% (aOR 2.82 [95% CI 1.31-6.05]). IVT alone produced outcomes comparable with those in recent trials of endovascular BAO recanalization. Furthermore, in head-to-head comparison in our cohort, the IVT-only approach was more often associated with favorable outcome than EVT+/-IVT. Thus, it should not be overlooked as the first-line recanalization therapy in acute BAO, even in longer time windows. This study provides Class IV evidence that tPA is as effective as thrombectomy for basilar artery thrombosis.

Baseline clinical and neuroradiological predictors of outcome in patients with large ischemic core undergoing mechanical thrombectomy: A retrospective multicenter study.

Recent randomized trials have shown the benefit of mechanical thrombectomy (MT) also in patients with an established large ischemic core. The purpose of this study was to define baseline predictors of clinical outcome in patients with large vessel occlusion (LVO) in the anterior circulation and an Alberta Stroke Program Early CT score (ASPECTS) ⩽ 5, undergoing MT. The databases of 16 comprehensive stroke centers were retrospectively screened for patients with LVO and ASPECTS ⩽5 that received MT. Baseline clinical and neuroradiological features, including the differential contribution of all ASPECTS regions to the composite score, were collected. Primary clinical outcome measure was a 90-day modified Rankin Scale (mRS) score of 0-2. Statistical analysis used a logistic regression model and random forest algorithm. A total of 408 patients were available for analysis. In multivariate model, among baseline features, lower age (odd ratio (OR) = 0.962, 95% confidence interval (CI) = 0.943-0.982) and lower National Institute of Health Stroke Scale (NIHSS) score (OR = 0.911, 95% CI = 0.862-0.963) were associated with the mRS score 0-2. Involvement of the M2 (OR = 0.398, 95% CI = 0.206-0.770) or M4 (OR = 0.496, 95% CI = 0.260-0.945) ASPECTS regions was associated with an unfavorable outcome. Random forest analysis confirmed that age and baseline NIHSS score are the most important variables influencing clinical outcome, whereas involvement of cortical regions M5, M4, M2, and M1 can have a negative impact. Our retrospective analysis shows that, along with age and baseline clinical impairment, presence of early ischemic changes involving cortical areas has a role in clinical outcome in patients with large ischemic core undergoing MT. The data that support the findings of this study are available upon reasonable request.

Factors associated with decreasing diffusion-weighted imaging-positive area volume after mechanical thrombectomy in patients with large early ischemic changes.

This study aimed to evaluate the factors associated with decreasing diffusion-weighted imaging (DWI) positive areas in patients with large early ischemic changes after mechanical thrombectomy (MT). This retrospective single-center clinical study was conducted between January 2013 and December 2022. We included consecutive patients who underwent MT for acute large-vessel occlusion of the anterior circulation with low pretreatment DWI-Alberta Stroke Program Early Computed Tomography Scores (ASPECTS) (0-5), effective recanalization [thrombolysis in cerebral infarction (TICI) 2b or TICI3], and magnetic resonance imaging (MRI) acquired before and after MT. We measured the DWI-positive area volume before and after MT. The primary endpoint was the after/before-MT DWI-positive area-volume ratio. In total, 28 patients were included in this study. Eight patients (29%) had an after/before-MT DWI-positive area-volume ratio of <1. The median mean apparent diffusion coefficient (ADC) levels of the DWI-positive areas in the groups with a ratio of <1 or >1 were 717 × 10⁶ mm2/s and 637 × 106 mm2/s, respectively (p = 0.011). Multivariate logistic regression analysis showed that ADC level (OR, 1.020 [95% confidence intervals (CIs), 1.001-1.040]; p = 0.040) was an independent predictor of a decreased DWI-positive area after MT. There was a negative correlation between the mean ADC level and the after/before-MT DWI-positive area-volume ratio (p < 0.001, |ρ| = 0.650), and the mean pretreatment ADC cutoff level was 649 × 106 mm2/s (area under the curve (AUC) = 0.806) for predicting a volume ratio of <1. The mean ADC level before-MT correlated with the after/before-MT DWI-positive area-volume ratio. A mean pretreatment ADC cutoff level of 649 × 106 mm2/s predicted a decreased DWI-positive area after MT.

Diagnostic accuracy of computed tomography brain perfusion in the prediction of acute ischemic stroke taking the findings of MRI as gold standard.

Objectives: To determine the diagnostic accuracy of computed tomography brain perfusion to predict acute ischemic stroke taking the findings of MRI as gold standard. Study Design: Cross-sectional Validation study. Setting: Department of Radiology Allied Hospital Faisalabad. Period: 20th May 2022 to 19th November 2022. Material &amp; Methods: A total of 215 individuals, aged between 30 and 70, of both sexes, and exhibiting ischemic stroke symptoms lasting no more than 12 hours, were included. Patients with abnormal renal function tests having renal disease were excluded. The conventional non-contrast CT used in the CT stroke protocol had basal sections that were either 3 mm or 4 mm in thickness and supra tentorial sections that were either 3 mm or 4 mm in thickness. The acquisition parameters were 80kVp and 120mAs. Dynamic CT perfusion was carried out with 4 cm plane coverage. At the seventh day, all patients underwent a follow-up MRI using a 1.5 Tesla Philips MRI scanner. A radiologist examined CTP to look for signs of early ischemic changes. For CT perfusion (CTP), measurements were taken for time to peak (TTP), cerebral blood flow (CBF), and cerebral blood volume (CBV). Results: Overall sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of computed tomography brain perfusion in the prediction of acute ischemic stroke taking the findings of MRI as gold standard was 85.37%, 76.09%, 82.68%, 79.55% and 81.40% respectively. Conclusion: This study led to the conclusion that diagnostic accuracy of computed tomography brain perfusion to predict acute ischemic stroke is quite high.

A deep learning and radiomics based Alberta stroke program early CT score method on CTA to evaluate acute ischemic stroke.

Alberta stroke program early CT score (ASPECTS) is a semi-quantitative evaluation method used to evaluate early ischemic changes in patients with acute ischemic stroke, which can guide physicians in treatment decisions and prognostic judgments. We propose a method combining deep learning and radiomics to alleviate the problem of large inter-observer variance in ASPECTS faced by physicians and assist them to improve the accuracy and comprehensiveness of the ASPECTS. Our study used a brain region segmentation method based on an improved encoding-decoding network. Through the deep convolutional neural network, 10 regions defined for ASPECTS will be obtained. Then, we used Pyradiomics to extract features associated with cerebral infarction and select those significantly associated with stroke to train machine learning classifiers to determine the presence of cerebral infarction in each scored brain region. The experimental results show that the Dice coefficient for brain region segmentation reaches 0.79. Three radioactive features are selected to identify cerebral infarction in brain regions, and the 5-fold cross-validation experiment proves that these 3 features are reliable. The classifier trained based on 3 features reaches prediction performance of AUC = 0.95. Moreover, the intraclass correlation coefficient of ASPECTS between those obtained by the automated ASPECTS method and physicians is 0.86 (95% confidence interval, 0.56-0.96). This study demonstrates advantages of using a deep learning network to replace the traditional template registration for brain region segmentation, which can determine the shape and location of each brain region more precisely. In addition, a new brain region classifier based on radiomics features has potential to assist physicians in clinical stroke detection and improve the consistency of ASPECTS.

Abstract TP204: Performance of Rapidai NCCT Stroke Software in Colombia's Early Stroke System: Preliminary Results

Background: Automated stroke solutions in developing countries have the potential to reduce healthcare gaps. This study assesses the performance of the RAPID NCCT Stroke module compared to local neuroradiologists’ evaluation of acute stroke. Methods: Rapid NCCT stroke is a new multi-module AI tool that simultaneously evaluates non-contrast CT scans (NCCT) for ICH (any subtype, volume &gt;0.4 ml), the ASPECT score, and suspicion of LVO (i.e., intracranial ICA or horizontal segment of the MCA). The software determines suspicion of LVO based on an algorithm that evaluates the hyperdense MCA sign and early ischemic changes in the MCA territory. Consensus readings were defined by three blinded neuroradiologists based on a subset of Non-contrast CTs obtained between January 2013 to December 2018 at Fundacion Santa Fe De Bogota University Hospital. The overall diagnostic performance of the RAPID NCCT was compared to the assessments made by the neuroradiologists. Results: 179 total stroke cases with technically adequate NCCT scans were identified. Based on the consensus of the neuroradiologists, these cases included 151 ischemic strokes, 27 ICHs &gt;0.4 ml, 1 ICH &lt;0.4 ml, and 28 LVO cases (verified by CT angiography). The Rapid NCCT Stroke module demonstrated high specificity (96%), NPV (98%), and accuracy (95%) for the detection of ICH. For determining the ASPECT score, the software had a specificity of 93% and an NPV of 76%. Seventy percent of the CTA-verified LVOs were detected from NCCT alone with a specificity and NPV of 82%. Conclusions: The RAPID NCCT Stroke software displayed promising results for the early identification of ICH and characterization of ischemic strokes. The software identified 70% of the LVOs from NCCT alone. This tool can potentially enhance patient outcomes by bridging healthcare gaps in evolving stroke systems. Multicenter studies in additional Latin American countries are needed for further validation.

Mediation of Age and Thrombectomy Outcome by Neuroimaging Markers of Frailty in Patients With Stroke

Age is a leading predictor of poor outcomes after brain injuries like stroke. The extent to which age is associated with preexisting burdens of brain changes, visible on neuroimaging but rarely considered in acute decision-making or trials, is unknown. To explore the mediation of age on functional outcome by neuroimaging markers of frailty (hereinafter neuroimaging frailty) in patients with acute ischemic stroke receiving endovascular thrombectomy (EVT). This cohort study was a post hoc analysis of the Safety and Efficacy of Nerinetide (NA-1) in Subjects Undergoing Endovascular Thrombectomy for Stroke (ESCAPE-NA1) randomized clinical trial, which investigated intravenous (IV) nerinetide in patients who underwent EVT within a 12-hour treatment window. Patients from 48 acute care hospitals in 8 countries (Canada, US, Germany, Korea, Australia, Ireland, UK, and Sweden) were enrolled between March 1, 2017, and August 12, 2019. Markers of brain frailty (brain atrophy [subcortical or cortical], white matter disease [periventricular or deep], and the number of lacunes and chronic infarctions) were retrospectively assessed while reviewers were blinded to other imaging (eg, computed tomography angiography, computed tomography perfusion) or outcome variables. All analyses were done between December 1, 2022, and January 31, 2023. All patients received EVT and were randomized to IV nerinetide (2.6 mg/kg of body weight) and alteplase (if indicated) treatment vs best medical management. The primary outcome was the proportion of the total effect of age on 90-day outcome, mediated by neuroimaging frailty. A combined mediation was also examined by clinical features associated with frailty and neuroimaging markers (total frailty). Structural equation modeling was used to create latent variables as potential mediators, adjusting for baseline, early ischemic changes; stroke severity; onset-to-puncture time; nerinetide treatment; and alteplase treatment. Among a total of 1105 patients enrolled in the study, 1102 (median age, 71 years [IQR, 61-80 years]; 554 [50.3%] male) had interpretable imaging at baseline. Of these participants, 549 (49.8%) were treated with IV nerinetide. The indirect effect of age on 90-day outcome, mediated by neuroimaging frailty, was associated with 85.1% of the total effect (β coefficient, 0.04 per year [95% CI, 0.02-0.06 per year]; P < .001). When including both frailty constructs, the indirect pathway was associated with essentially 100% of the total effect (β coefficient, 0.07 per year [95% CI, 0.03-0.10 per year]; P = .001). In this cohort study, a secondary analysis of the ESCAPE-NA1 trial, most of the association between age and 90-day outcome was mediated by neuroimaging frailty, underscoring the importance of features like brain atrophy and small vessel disease, as opposed to chronological age alone, in predicting poststroke outcomes. Future trials could include such frailty features to stratify randomization or improve adjustment in outcome analyses.

Contribution to an Advanced Clinical Aided Tool Dedicated to Explore ASPECTS Score of Ischemic Stroke

The Alberta Stroke Program Early CT Score (ASPECTS) is a simple and reliable systematic method used to quantify and explore acute ischemic stroke. It was initially developed to standardize the assessment of the early ischemic changes’ extent within the Middle Cerebral Artery (MCA). The ASPECTS assessment has been increasingly incorporated into treatment decision-making and has been used in several randomized clinical trials for endovascular treatment decision-making. The e-ASPECTS software is a tool for the automated use of ASPECTS. The purpose of this paper is twofold: The first objective is to present an advanced clinical that streamlines the extraction of ASPECTS regions of interest. This tool aids neuro-physicians by automating the segmentation Department process through preprocessing steps involving skull bone stripping, edge detection, and thresholding. The second objective is to propose an automated semi-quantitative method using Non-Contrast Computed Tomography (NCCT), enabling neuro-physicians to accurately diagnose and evaluate acute ischemic stroke. This comprehensive approach improves the exploration, diagnosis, and evaluation of acute ischemic stroke, bolstering clinical decision-making and treatment strategies. Experimental results were promising and depicted an interesting accuracy level ranging from 0.81 (internal capsule) to 0.98 (caudate), with a greater agreement for cortical areas. The proposed automated ASPECTS method presents an independent predictor for clinical practice and ischemic core judgment and treatment selection.

Recanalization status and temporal evolution of early ischemic changes following stroke thrombectomy.

Present-day computer tomography (CT) scanners have excellent spatial resolution and signal-to-noise ratio and are instrumental detecting early ischemic changes (EIC) in brain. We assessed the temporal changes of EIC based on the recanalization status after thrombectomy. The cohort comprises consecutive patients with acute ischemic stroke in anterior circulation treated with thrombectomy in tertiary referral hospital. All baseline and follow-up scans were screened for any ischemic changes and further classified using Alberta Stroke Program Early CT Score (ASPECTS). Generalized linear mixed models were used to analyze the impact of recanalization status using modified Thrombolysis in Cerebral Infarction (mTICI) on temporal evolution of ischemic changes. We included 614 patients with ICA, M1, or M2 occlusions. Median ASPECTS score was 9 (IQR 7-10) at baseline and 7 (5-8) at approximately 24 h. mTICI 3 was achieved in 207 (33.8%), 2B 241 (39.3%), 2A in 77 (12.6%), and 0-1 in 88 (14.3%) patients. Compared to patients with mTICI 3, those with mTICI 0-1 and 2A had less favorable temporal changes of ASPECTS (p < 0.001). Effect of recanalization was noted in the cortical regions of ICA/M1 patients, but not in their deep structures or patients with M2 occlusions. All ischemic changes detected at baseline were also present at all follow-up images, regardless of the recanalization status. Temporal evolution of the ischemic changes and ASPECTS are related to the success of the recanalization therapy in cortical regions of ICA/M1 patients, but not in their deep brain structures or M2 patients. In none of the patients did EIC revert in any brain region after successful recanalization.

Efficacy of levosimendan vs its combination with magnesium sulphate on spinal cord protection in infants undergoing coarctectomy: A randomized controlled study

ABSTRACT Background and Objective Spinal cord ischemia with subsequent paraplegia secondary to aortic coarctation repair procedures is rare, but it has serious consequences that can affect quality of life. Infrared spectroscopy (NIRS) is used for non invasive spinal cord oxygenation monitoring to estimate cord perfusion and detect early cord ischemic changes. Several pharmacological agents have been used to improve cord perfusion, the main action of these agents is to improve regional/systemic perfusion and decrease ICP. In the current study, we studied magnesium sulphate and levosimendan for their vasodilating effect that might improve spinal cord perfusion as part of spinal cord protection. Methods Forty two infants undergoing aortic coarctectomy under general anaesthesia were registered in double blinded randomized controlled study, three groups were included; group C received i.v. saline, group L received levosimendan in loading dose 6ug/kg i.v. for 15 minutes then maintenance dose 0.1 ug/kg/min till end of surgery and group M received levosimendan in loading dose 6 ug/kg i.v. for 15 minutes then maintenance dose 0.1 ug/kg/min in combination with magnesium sulphate in loading dose 25 mg/kg i.v. for 15 minutes then maintenance dose 10 mg/kg/hr till the end of surgery. The vital signs and NIRS values assessed before, during and after clamping of aorta. Results All baseline demographic data were comparable among all groups except for height (cm), which was significantly lower in Group L compared to Group C (p = 0.013). NIRS values were comparable among the three groups throughout experimental protocol except after cross clamp at 20 minutes, where Group M was significantly higher compared to group C (P = 0.007).Heart rate, mean arterial blood pressure, total fluid intake, urine output, aortic cross clamp time and surgical time was comparable among all groups, were comparable among 3 studied groups. Conclusion Adding magnesium sulphate to levosimendan has showed improvement in spinal cord perfusion during cross clamping as monitored by NIRS when compared to use of levosimendan alone or placebo in coarctectomy operations without affecting hemodynamics.

Abstract 096: Hypoperfusion Intensity Ratio Suggests Collateral Status, Stroke Mechanism, and Clinical Stability in Large Vessel Occlusion

Introduction Hypoperfusion Intensity Ratio (HIR), defined by the ratio of Tmax &gt;10s/Tmax &gt;6s on perfusion imaging, has been directly correlated with collateral status, stroke mechanism, and clinical outcomes in patients with acute large vessel occlusions [1,2]. We report a case of a patient with mild neurological symptoms despite an acute MCA M1 occlusion in which a very favorable HIR may have predicted clinical stability, extensive atherosclerotic burden, and compensatory leptomeningeal collaterals. Our aim was to provide support of the utility of HIR in quantifying collateral status and possibly predicting the underlying stroke mechanism and stroke progression of patients with acute large vessel occlusions. Methods Case report. Results A 61‐year‐old woman with a history of hypertension and hyperlipidemia, who is an active smoker with a known right extracranial carotid stenosis presented with acute left facial droop (NIHSS 1) upon awakening. CT head did not demonstrate early ischemic changes. CT angiogram demonstrated a right MCA M1 occlusion, marked narrowing of the right common carotid artery, and severe narrowing of the proximal innominate artery (Figure 1, Image A). CT perfusion demonstrated a Tmax &gt;6s delay of 41mL and HIR of 0, suggestive of robust collaterals (Figure 1, Image B). The patient was out of the window for tenecteplase administration. Thrombectomy was deferred due to a low NIHSS. MRI showed a right putamen and corona radiata infarct. DSA demonstrated crossed collateralization across the anterior communicating artery and robust right ACA‐MCA and PCA‐MCA leptomeningeal collaterals and retrograde filling of the brachiocephalic and right common carotid artery via the right vertebral artery. These findings were supported by quantitative MRA, which showed decreased blood flow in the right ICA, increased blood flow in right A2, increased blood flow in left A1, and retrograde right vertebral flow indicative of a brachiocephalic steal phenomenon. Her neurological exam remained stable upon discharge. She will be evaluated for brachiocephalic revascularization as an outpatient. Conclusion We present a patient with very mild symptoms due to an acute large vessel occlusion who remained clinically stable despite an acute MCA M1 occlusion, which was likely caused by ischemic conditioning related to chronic hypoperfusion secondary to severe brachiocephalic and right common carotid artery stenosis. Favorable HIR on perfusion imaging was predictive of robust collaterals, the underlying stroke mechanism, and the stable clinical course. Since clinical equipoise exists regarding the treatment of patients with low NIHSS in the setting of an acute large vessel occlusion, individualized selection remains paramount. HIR may serve as a quantitative radiographic marker to rapidly quantify collateral status and assist in decision‐making. Future studies exploring the role of HIR in predicting stroke progression are warranted.

Abstract 212: Percutaneous Carotid access in Mechanical Thrombectomy ‐ a safe alternative to transfemoral approach

Introduction Emergent percutaneous carotid artery MER approach for acute ischemic large vessel strokes are rare given the risk of complications and seldom reported. Methods 75‐year‐old left‐handed functional male (mRs:0) with past medical history of HTN, HLD presented to ED after being found on the floor by his family with slurred speech, new onset right sided weakness, with a last known well of 17 hours. NIHSS on arrival was 14 for expressive aphasia, right visual field defect, right facial weakness, significant dysarthria, right hemiparesis, and sensory defect. CT Head demonstrated left MCA territory early ischemic changes. CTA head/neck demonstrated left M1 occlusion with large penumbra. Perfusion data demonstrated no area of core infarct with area of ischemic penumbra in the left MCA territory involving the left frontal, temporal and parietal lobes measuring 161 ml. ASPECT score 5‐6. The patient was deemed a candidate for mechanical endovascular thrombectomy (MER). The procedure was initiated via ultrasound‐guided right common femoral access. After multiple attempts using a wide range of techniques and wire/catheter combinations in order to establish left intracranial access and given extreme angulation/tortuosity/elongation in the proximal left common carotid artery, it was decided to proceed with the catheter position in the left common carotid or the left internal carotid artery that would allow for subsequent catheterization of the intracranial circulation for MER. Results Near complete revascularization with minimal distal thrombus material beyond endovascular reach corresponding to a TICI 2C degree of revascularization was achieved. Closure of the femoral puncture site was performed using an Angio seal femoral closure device. Surgical closure of the puncture site was performed by vascular surgery. The patient was eventually discharged to short term acute rehabilitation and continues to follow up outpatient with the Stroke clinic. Conclusion Older patients with ischemic stroke commonly have tortuous vessels or peripheral vascular disease. As a result, they may greatly benefit from emergent direct carotid access, as the trans‐femoral approach often poses challenges in accessing the thrombus. For patients with complex and unfavorable vascular anatomy for mechanical endo‐vascularization, direct percutaneous carotid puncture can be advantageous, effectively reducing the aforementioned difficulties. When opting for such an approach it is vital to factor in the aortic arch appearance and its branches.