Amide proton transfer imaging in stroke.

Amide proton transfer (APT) imaging, a variant of chemical exchange saturation transfer MRI, has shown promise in detecting ischemic tissue acidosis following impaired aerobic metabolism in animal models and in human stroke patients due to the sensitivity of the amide proton exchange rate to changes in pH within the physiological range. Recent studies have demonstrated the possibility of using APT-MRI to detect acidosis of the ischemic penumbra, enabling the assessment of stroke severity and risk of progression, monitoring of treatment progress, and prognostication of clinical outcome. This paper reviews current APT imaging methods actively used in ischemic stroke research and explores the clinical aspects of ischemic stroke and future applications for these methods.

Quantitative chemical exchange saturation transfer imaging of nuclear overhauser effects in acute ischemic stroke.

PURPOSE: In chemical exchange saturation transfer imaging, saturation effects between - 2 to - 5 ppm (nuclear Overhauser effects, NOEs) have been shown to exhibit contrast in preclinical stroke models. Our previous work on NOEs in human stroke used an analysis model that combined NOEs and semisolid MT; however their combination might feasibly have reduced sensitivity to changes in NOEs. The aim of this study was to explore the information a 4-pool Bloch-McConnell model provides about the NOE contribution in ischemic stroke, contrasting that with an intentionally approximate 3-pool model. METHODS: MRI data from 12 patients presenting with ischemic stroke were retrospectively analyzed, as well as from six animals induced with an ischemic lesion. Two Bloch-McConnell models (4 pools, and a 3-pool approximation) were compared for their ability to distinguish pathological tissue in acute stroke. The association of NOEs with pH was also explored, using pH phantoms that mimic the intracellular environment of naïve mouse brain. RESULTS: The 4-pool measure of NOEs exhibited a different association with tissue outcome compared to 3-pool approximation in the ischemic core and in tissue that underwent delayed infarction. In the ischemic core, the 4-pool measure was elevated in patient white matter ( 1.20±0.20 ) and in animals ( 1.27±0.20 ). In the naïve brain pH phantoms, significant positive correlation between the NOE and pH was observed. CONCLUSION: Associations of NOEs with tissue pathology were found using the 4-pool metric that were not observed using the 3-pool approximation. The 4-pool model more adequately captured in vivo changes in NOEs and revealed trends depending on tissue pathology in stroke.

Noncontrast Computed Tomography e-Stroke Infarct Volume Is Similar to RAPID Computed Tomography Perfusion in Estimating Postreperfusion Infarct Volumes.

BACKGROUND AND PURPOSE: The e-Stroke Suite software (Brainomix, Oxford, United Kingdom) is a tool designed for the automated quantification of The Alberta Stroke Program Early CT Score and ischemic core volumes on noncontrast computed tomography (NCCT). We sought to compare the prediction of postreperfusion infarct volumes and the clinical outcomes across NCCT e-Stroke software versus RAPID (IschemaView, Menlo Park, CA) computed tomography perfusion measurements. METHODS: All consecutive patients with anterior circulation large vessel occlusion stroke presenting at a tertiary care center between September 2010 and November 2018 who had available baseline infarct volumes on both NCCT e-Stroke Suite software and RAPID CTP as well as final infarct volume (FIV) measurements and achieved complete reperfusion (modified Thrombolysis in Cerebral Infarction scale 2c-3) post-thrombectomy were included. The associations between estimated baseline ischemic core volumes and FIV as well as 90-day functional outcomes were assessed. RESULTS: Four hundred seventy-nine patients met inclusion criteria. Median age was 64 years (55-75), median e-Stroke and computed tomography perfusion ischemic core volumes were 38.4 (21.8-58) and 5 (0-17.7) mL, respectively, whereas median FIV was 22.2 (9.1-56.2) mL. The correlation between e-Stroke and CTP ischemic core volumes was moderate (R=0.44; P<0.001). Similarly, moderate correlations were observed between e-Stroke software ischemic core and FIV (R=0.52; P<0.001) and CTP core and FIV (R=0.43; P<0.001). Subgroup analysis showed that e-Stroke software and CTP performance was similar in the early and late (>6 hours) treatment windows. Multivariate analysis showed that both e-Stroke software NCCT baseline ischemic core volume (adjusted odds ratio, 0.98 [95% CI, 0.97-0.99]) and RAPID CTP ischemic core volume (adjusted odds ratio, 0.98 [95% CI, 0.97-0.99]) were independently and comparably associated with good outcome (modified Rankin Scale score of 0-2) at 90 days. CONCLUSIONS: NCCT e-Stroke Suite software performed similarly to RAPID CTP in assessing postreperfusion FIV and functional outcomes for both early- and late-presenting patients. NCCT e-Stroke volumes seems to represent a viable alternative in centers where access to advanced imaging is limited. Moreover, the future development of fusion maps of NCCT and CTP ischemic core estimates may improve upon the current performance of these tools as applied in isolation.

Prospects for investigating brain oxygenation in acute stroke: Experience with a non-contrast quantitative BOLD based approach.

Metabolic markers of baseline brain oxygenation and tissue perfusion have an important role to play in the early identification of ischaemic tissue in acute stroke. Although well established MRI techniques exist for mapping brain perfusion, quantitative imaging of brain oxygenation is poorly served. Streamlined-qBOLD (sqBOLD) is a recently developed technique for mapping oxygenation that is well suited to the challenge of investigating acute stroke. In this study a noninvasive serial imaging protocol was implemented, incorporating sqBOLD and arterial spin labelling to map blood oxygenation and perfusion, respectively. The utility of these parameters was investigated using imaging based definitions of tissue outcome (ischaemic core, infarct growth and contralateral tissue). Voxel wise analysis revealed significant differences between all tissue outcomes using pairwise comparisons for the transverse reversible relaxation rate (R 2 '), deoxygenated blood volume (DBV) and deoxyghaemoglobin concentration ([dHb]; p < 0.01 in all cases). At the patient level (n = 9), a significant difference was observed for [dHb] between ischaemic core and contralateral tissue. Furthermore, serial analysis at the patient level (n = 6) revealed significant changes in R 2 ' between the presentation and 1 week scans for both ischaemic core (p < 0.01) and infarct growth (p < 0.05). In conclusion, this study presents evidence supporting the potential of sqBOLD for imaging oxygenation in stroke.

Collateral Automation for Triage in Stroke: Evaluating Automated Scoring of Collaterals in Acute Stroke on Computed Tomography Scans.

Computed tomography angiography (CTA) collateral scoring can identify patients most likely to benefit from mechanical thrombectomy and those more likely to have good outcomes and ranges from 0 (no collaterals) to 3 (complete collaterals). In this study, we used a machine learning approach to categorise the degree of collateral flow in 98 patients who were eligible for mechanical thrombectomy and generate an e-CTA collateral score (CTA-CS) for each patient (e-STROKE SUITE, Brainomix Ltd., Oxford, UK). Three experienced neuroradiologists (NRs) independently estimated the CTA-CS, first without and then with knowledge of the e-CTA output, before finally agreeing on a consensus score. Addition of the e-CTA improved the intraclass correlation coefficient (ICC) between NRs from 0.58 (0.46-0.67) to 0.77 (0.66-0.85, p = 0.003). Automated e-CTA, without NR input, agreed with the consensus score in 90% of scans with the remaining 10% within 1 point of the consensus (ICC 0.93, 0.90-0.95). Sensitivity and specificity for identifying favourable collateral flow (collateral score 2-3) were 0.99 (0.93-1.00) and 0.94 (0.70-1.00), respectively. e-CTA correlated with the Alberta Stroke Programme Early CT Score (Spearman correlation 0.46, p < 0.001) highlighting the value of good collateral flow in maintaining tissue viability prior to reperfusion. In conclusion, -e-CTA provides a real-time and fully automated approach to collateral scoring with the potential to improve consistency of image interpretation and to independently quantify collateral scores even without expert rater input.

Quantifying Infarct Growth and Secondary Injury Volumes: Comparing Multimodal Image Registration Measures.

BACKGROUND AND PURPOSE: Lesion expansion in the week after acute stroke involves both infarct growth (IG) and anatomic distortion (AD) because of edema and hemorrhage. Enabling separate quantification would allow clinical trials targeting these distinct pathological processes. We developed an objective and automated approach to quantify these processes at 24 hours and 1 week. METHODS: Patients with acute ischemic stroke were scanned at presentation, 24 hours, and 1 week in a magnetic resonance imaging (MRI) cohort study. IG and AD were calculated from follow-up lesion masks after linear and nonlinear registration to a presenting MRI scan. Performance of IG and AD was compared with edema quantified using cerebrospinal fluid displacement. The use of alternative reference images to define AD, including template MRI, mirrored MRI, and presenting computed tomographic scan, was explored. RESULTS: Thirty-seven patients with nonlacunar stroke were included. AD was responsible for 20% and 36% of lesion expansion at 24 hours (n=30) and 1 week (n=28). Registration-defined IG and AD compared favorably with edema quantified using cerebrospinal fluid displacement, particularly at smaller infarct volumes. Presenting computed tomographic imaging was the preferred alternative reference image to presenting MRI for measuring AD. CONCLUSIONS: The contributions of IG and AD to lesion expansion can be measured separately over time through the use of image registration. This approach can be used to combine imaging outcome data from computed tomography and MRI.

Quantification of Serial Cerebral Blood Flow in Acute Stroke Using Arterial Spin Labeling.

BACKGROUND AND PURPOSE: Perfusion-weighted imaging is used to select patients with acute ischemic stroke for intervention, but knowledge of cerebral perfusion can also inform the understanding of ischemic injury. Arterial spin labeling allows repeated measurement of absolute cerebral blood flow (CBF) without the need for exogenous contrast. The aim of this study was to explore the relationship between dynamic CBF and tissue outcome in the month after stroke onset. METHODS: Patients with nonlacunar ischemic stroke underwent ≤5 repeated magnetic resonance imaging scans at presentation, 2 hours, 1 day, 1 week, and 1 month. Imaging included vessel-encoded pseudocontinuous arterial spin labeling using multiple postlabeling delays to quantify CBF in gray matter regions of interest. Receiver-operator characteristic curves were used to predict tissue outcome using CBF. Repeatability was assessed in 6 healthy volunteers and compared with contralateral regions of patients. Diffusion-weighted and T2-weighted fluid attenuated inversion recovery imaging were used to define tissue outcome. RESULTS: Forty patients were included. In contralateral regions of patients, there was significant variation of CBF between individuals, but not between scan times (mean±SD: 53±42 mL/100 g/min). Within ischemic regions, mean CBF was lowest in ischemic core (17±23 mL/100 g/min), followed by regions of early (21±26 mL/100 g/min) and late infarct growth (25±35 mL/100 g/min; ANOVA P<0.0001). Between patients, there was marked overlap in presenting and serial CBF values. CONCLUSIONS: Knowledge of perfusion dynamics partially explained tissue fate. Factors such as metabolism and tissue susceptibility are also likely to influence tissue outcome.

Identifying the ischaemic penumbra using pH-weighted magnetic resonance imaging.

The original concept of the ischaemic penumbra suggested imaging of regional cerebral blood flow and metabolism would be required to identify tissue that may benefit from intervention. Amide proton transfer magnetic resonance imaging, a chemical exchange saturation transfer technique, has been used to derive cerebral intracellular pH in preclinical stroke models and has been proposed as a metabolic marker of ischaemic penumbra. In this proof of principle clinical study, we explored the potential of this pH-weighted magnetic resonance imaging technique at tissue-level. Detailed voxel-wise analysis was performed on data from a prospective cohort of 12 patients with acute ischaemic stroke. Voxels within ischaemic core had a more severe intracellular acidosis than hypoperfused tissue recruited to the final infarct (P < 0.0001), which in turn was more acidotic than hypoperfused tissue that survived (P < 0.0001). In addition, when confined to the grey matter perfusion deficit, intracellular pH (P < 0.0001), but not cerebral blood flow (P = 0.31), differed between tissue that infarcted and tissue that survived. Within the presenting apparent diffusion coefficient lesion, intracellular pH differed between tissue with early apparent diffusion lesion pseudonormalization and tissue with true radiographic recovery. These findings support the need for further investigation of pH-weighted imaging in patients with acute ischaemic stroke.

Quantification of amide proton transfer effect pre- and post-gadolinium contrast agent administration.

PURPOSE: To compare quantification of the amide proton transfer (APT) effect pre- and post-gadolinium contrast agent (Gd) administration in order to establish to what extent Gd alters quantification of the APT effect. MATERIALS AND METHODS: Four patients with internal carotid stenosis were recruited. APT imaging was acquired pre- and post-contrast in two sessions (before and after surgery) to assess the extent of relaxation time, T1 , change on APT effect calculated using magnetization transfer ratio asymmetry analysis at offsets of ±3.5 ppm relative to water resonance. Statistical and modeling evaluations were performed on the pre- and post-contrast APT effect to study the sensitivity to contrast administration. RESULTS: Before surgery, the post-contrast T1 was estimated to drop <10% of the pre-value for the majority of the patients. After surgery, higher post-contrast T1 reductions were observed in all the patients (maximum decrease was about 20% of the pre-value). Consistent differences between pre- and post-contrast were seen in the APT effect quantified using the asymmetry measure in most regions of the brain, with significant differences found in the white matter at the group level and in 25% of the individual patient results. CONCLUSION: APT imaging should be performed prior to Gd administration to avoid potential misinterpretation of the APT effect.

Posterior circulation ischaemic stroke diagnosis and management.

This narrative review provides an overview of the posterior circulation and the clinical features of common posterior circulation stroke (PCS) syndromes in the posterior arterial territories and how to distinguish them from mimics. We outline the hyperacute management of patients with suspected PCS with emphasis on how to identify those who are likely to benefit from intervention based on imaging findings. Finally, we review advances in treatment options, including developments in endovascular thrombectomy (EVT) and intravenous thrombolysis (IVT), and the principles of medical management and indications for neurosurgery. Observational and randomised clinical trial data have been equivocal regarding EVT in PCS, but more recent studies strongly support its efficacy. There have been concomitant advances in imaging of posterior stroke to guide optimal patient selection for thrombectomy. Recent evidence suggests that clinicians should have a heightened suspicion of posterior circulation events with the resultant implementation of timely, evidence-based management.

Artificial intelligence-based decision support software to improve the efficacy of acute stroke pathway in the NHS: an observational study.

Introduction: In a drip-and-ship model for endovascular thrombectomy (EVT), early identification of large vessel occlusion (LVO) and timely referral to a comprehensive center (CSC) are crucial when patients are admitted to an acute stroke center (ASC). Several artificial intelligence (AI) decision-aid tools are increasingly being used to facilitate the rapid identification of LVO. This retrospective cohort study aimed to evaluate the impact of deploying e-Stroke AI decision support software in the hyperacute stroke pathway on process metrics and patient outcomes at an ASC in the United Kingdom. Methods: Except for the deployment of e-Stroke on 01 March 2020, there were no significant changes made to the stroke pathway at the ASC. The data were obtained from a prospective stroke registry between 01 January 2019 and 31 March 2021. The outcomes were compared between the 14 months before and 12 months after the deployment of AI (pre-e-Stroke cohort vs. post-e-Stroke cohort) on 01 March 2020. Time window analyses were performed using Welch's t-test. Cochran-Mantel-Haenszel test was used to compare changes in disability at 3 months assessed by modified Rankin Score (mRS) ordinal shift analysis, and Fisher's exact test was used for dichotomised mRS analysis. Results: In the pre-e-Stroke cohort, 19 of 22 patients referred received EVT. In the post-e-Stroke cohort, 21 of the 25 patients referred were treated. The mean door-in-door-out (DIDO) and door-to-referral times in pre-e-Stroke vs. post-e-Stroke cohorts were 141 vs. 79 min (difference 62 min, 95% CI 96.9-26.8 min, p < 0.001) and 71 vs. 44 min (difference 27 min, 95% CI 47.4-5.4 min, p = 0.01), respectively. The adjusted odds ratio (age and NIHSS) for mRS ordinal shift analysis at 3 months was 3.14 (95% CI 0.99-10.51, p = 0.06) and the dichotomized mRS 0-2 at 3 months was 16% vs. 48% (p = 0.04) in the pre- vs. post-e-Stroke cohorts, respectively. Conclusion: In this single-center study in the United Kingdom, the DIDO time significantly decreased since the introduction of e-Stroke decision support software into an ASC hyperacute stroke pathway. The reduction in door-in to referral time indicates faster image interpretation and referral for EVT. There was an indication of an increased proportion of patients regaining independent function after EVT. However, this should be interpreted with caution given the small sample size. Larger, prospective studies and further systematic real-world evaluation are needed to demonstrate the widespread generalisability of these findings.

Reduced Left Atrial Rotational Flow Is Independently Associated With Embolic Brain Infarcts.

BACKGROUND: Up to 25% of embolic strokes occur in individuals without atrial fibrillation (AF) or other identifiable mechanisms. OBJECTIVES: This study aims to assess whether left atrial (LA) blood flow characteristics are associated with embolic brain infarcts, independently of AF. METHODS: The authors recruited 134 patients: 44 with a history of ischemic stroke and 90 with no history of stroke but CHA2DS2VASc score ≥1. Cardiac magnetic resonance (CMR) evaluated cardiac function and LA 4-dimensional flow parameters, including velocity and vorticity (a measure of rotational flow), and brain magnetic resonance imaging (MRI) was performed to detect large noncortical or cortical infarcts (LNCCIs) (likely embolic), or nonembolic lacunar infarcts. RESULTS: Patients (41% female; age 70 ± 9 years) had moderate stroke risk (median CHA2DS2VASc = 3, Q1-Q3: 2-4). Sixty-eight (51%) had diagnosed AF, of whom 58 (43%) were in AF during CMR. Thirty-nine (29%) had ≥1 LNCCI, 20 (15%) had ≥1 lacunar infarct without LNCCI, and 75 (56%) had no infarct. Lower LA vorticity was significantly associated with prevalent LNCCIs after adjustment for AF during CMR, history of AF, CHA2DS2VASc score, LA emptying fraction, LA indexed maximum volume, left ventricular ejection fraction, and indexed left ventricular mass (OR: 2.06 [95% CI: 1.08-3.92 per SD]; P = 0.027). By contrast, LA flow peak velocity was not significantly associated with LNCCIs (P = 0.21). No LA parameter was associated with lacunar infarcts (all P > 0.05). CONCLUSIONS: Reduced LA flow vorticity is significantly and independently associated with embolic brain infarcts. Imaging LA flow characteristics may aid identification of individuals who would benefit from anticoagulation for embolic stroke prevention, regardless of heart rhythm.

Automated CT angiography collateral scoring in anterior large vessel occlusion stroke: A multireader study.

BACKGROUND: Computed tomography (CT) angiography collateral score (CTA-CS) is an important clinical outcome predictor following mechanical thrombectomy for ischemic stroke with large vessel occlusion (LVO). The present multireader study aimed to evaluate the performance of e-CTA software for automated assistance in CTA-CS scoring. MATERIALS AND METHODS: Brain CTA images of 56 patients with anterior LVO were retrospectively processed. Twelve readers of various clinical training, including junior neuroradiologists, senior neuroradiologists, and neurologists graded collateral flow using visual CTA-CS scale in two sessions separated by a washout period. Reference standard was the consensus of three expert readers. Duration of reading time, inter-rater reliability, and statistical comparison of readers' performance metrics were analyzed between the e-CTA assisted and unassisted sessions. RESULTS: e-CTA assistance resulted in significant increase in mean accuracy (58.6% to 67.5%, p = 0.003), mean F1 score (0.574 to 0.676, p = 0.002), mean precision (58.8% to 68%, p = 0.007), and mean recall (58.7% to 69.9%, p = 0.002), especially with slight filling deficit (CTA-CS 2 and 3). Mean reading time was reduced across all readers (103.4 to 59.7 s, p = 0.001), and inter-rater agreement in CTA-CS assessment was increased (Krippendorff's alpha 0.366 to 0.676). Optimized occlusion laterality detection was also noted with mean accuracy (92.9% to 96.8%, p = 0.009). CONCLUSION: Automated assistance for CTA-CS using e-CTA software provided helpful decision support for readers in terms of improving scoring accuracy and reading efficiency for physicians with a range of experience and training backgrounds and leading to significant improvements in inter-rater agreement.

Investigation of relayed nuclear Overhauser enhancement effect at -1.6 ppm in an ischemic stroke model.

Background: When an ischemic stroke happens, it triggers a complex signalling cascade that may eventually lead to neuronal cell death if no reperfusion. Recently, the relayed nuclear Overhauser enhancement effect at -1.6 ppm [NOE(-1.6 ppm)] has been postulated may allow for a more in-depth analysis of the ischemic injury. This study assessed the potential utility of NOE(-1.6 ppm) in an ischemic stroke model. Methods: Diffusion-weighted imaging, perfusion-weighted imaging, and chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) data were acquired from five rats that underwent scans at 9.4 T after middle cerebral artery occlusion. Results: The apparent diffusion coefficient (ADC), cerebral blood flow (CBF), and apparent exchange-dependent relaxations (AREX) at 3.5 ppm and NOE(-1.6 ppm) were quantified. AREX(3.5 ppm) and NOE(-1.6 ppm) were found to be hypointense and exhibited different signal patterns within the ischemic tissue. The NOE(-1.6 ppm) deficit areas were equal to or larger than the ADC deficit areas, but smaller than the AREX(3.5 ppm) deficit areas. This suggested that NOE(-1.6 ppm) might further delineate the acidotic tissue estimated using AREX(3.5 ppm). Since NOE(-1.6 ppm) is closely related to membrane phospholipids, NOE(-1.6 ppm) potentially highlighted at-risk tissue affected by lipid peroxidation and membrane damage. Altogether, the ADC/NOE(-1.6 ppm)/AREX(3.5 ppm)/CBF mismatches revealed four zones of increasing sizes within the ischemic tissue, potentially reflecting different pathophysiological information. Conclusions: Using CEST coupled with ADC and CBF, the ischemic tissue may thus potentially be separated into four zones to better understand the pathophysiology after stroke and improve ischemic tissue fate definition. Further verification of the potential utility of NOE(-1.6 ppm) may therefore lead to a more precise diagnosis.

Impact of e-ASPECTS software on the performance of physicians compared to a consensus ground truth: a multi-reader, multi-case study.

Background: The Alberta Stroke Program Early CT Score (ASPECTS) is used to quantify the extent of injury to the brain following acute ischemic stroke (AIS) and to inform treatment decisions. The e-ASPECTS software uses artificial intelligence methods to automatically process non-contrast CT (NCCT) brain scans from patients with AIS affecting the middle cerebral artery (MCA) territory and generate an ASPECTS. This study aimed to evaluate the impact of e-ASPECTS (Brainomix, Oxford, UK) on the performance of US physicians compared to a consensus ground truth. Methods: The study used a multi-reader, multi-case design. A total of 10 US board-certified physicians (neurologists and neuroradiologists) scored 54 NCCT brain scans of patients with AIS affecting the MCA territory. Each reader scored each scan on two occasions: once with and once without reference to the e-ASPECTS software, in random order. Agreement with a reference standard (expert consensus read with reference to follow-up imaging) was evaluated with and without software support. Results: A comparison of the area under the curve (AUC) for each reader showed a significant improvement from 0.81 to 0.83 (p = 0.028) with the support of the e-ASPECTS tool. The agreement of reader ASPECTS scoring with the reference standard was improved with e-ASPECTS compared to unassisted reading of scans: Cohen's kappa improved from 0.60 to 0.65, and the case-based weighted Kappa improved from 0.70 to 0.81. Conclusion: Decision support with the e-ASPECTS software significantly improves the accuracy of ASPECTS scoring, even by expert US neurologists and neuroradiologists.

Interpretable Machine Learning Modeling for Ischemic Stroke Outcome Prediction.

Background and Purpose: Mechanical thrombectomy greatly improves stroke outcomes. Nonetheless, some patients fall short of full recovery despite good reperfusion. The purpose of this study was to develop machine learning (ML) models for the pre-interventional prediction of functional outcome at 3 months of thrombectomy in acute ischemic stroke (AIS), using clinical and auto-extractable radiological information consistently available upon first emergency evaluation. Materials and Methods: A two-center retrospective cohort of 293 patients with AIS who underwent thrombectomy was analyzed. ML models were developed to predict dichotomized modified Rankin score at 90 days (mRS-90) using clinical and imaging features, both separately and combined. Conventional and experimental imaging biomarkers were quantified using automated image-processing software from non-contract computed tomography (CT) and computed tomography angiography (CTA). Shapley Additive Explanation (SHAP) was applied for model interpretability and predictor importance analysis of the optimal model. Results: Merging clinical and imaging features returned the best results for mRS-90 prediction. The best performing classifier was Extreme Gradient Boosting (XGB) with an area under the receiver operating characteristic curve (AUC) = 84% using selected features. The most important classifying features were age, baseline National Institutes of Health Stroke Scale (NIHSS), occlusion side, degree of brain atrophy [primarily represented by cortical cerebrospinal fluid (CSF) volume and lateral ventricle volume], early ischemic core [primarily represented by e-Alberta Stroke Program Early CT Score (ASPECTS)], and collateral circulation deficit volume on CTA. Conclusion: Machine learning that is applied to quantifiable image features from CT and CTA alongside basic clinical characteristics constitutes a promising automated method in the pre-interventional prediction of stroke prognosis. Interpretable models allow for exploring which initial features contribute the most to post-thrombectomy outcome prediction overall and for each individual patient outcome.

Improved Stroke Care in a Primary Stroke Centre Using AI-Decision Support.

BACKGROUND: Patient selection for reperfusion therapies requires significant expertise in neuroimaging. Increasingly, machine learning-based analysis is used for faster and standardized patient selection. However, there is little information on how such software influences real-world patient management. AIMS: We evaluated changes in thrombolysis and thrombectomy delivery following implementation of automated analysis at a high volume primary stroke centre. METHODS: We retrospectively collected data on consecutive stroke patients admitted to a large university stroke centre from two identical 7-month periods in 2017 and 2018 between which the e-Stroke Suite (Brainomix, Oxford, UK) was implemented to analyse non-contrast CT and CT angiography results. Delivery of stroke care was otherwise unchanged. Patients were transferred to a hub for thrombectomy. We collected the number of patients receiving intravenous thrombolysis and/or thrombectomy, the time to treatment; and outcome at 90 days for thrombectomy. RESULTS: 399 patients from 2017 and 398 from 2018 were included in the study. From 2017 to 2018, thrombolysis rates increased from 11.5% to 18.1% with a similar trend for thrombectomy (2.8-4.8%). There was a trend towards shorter door-to-needle times (44-42 min) and CT-to-groin puncture times (174-145 min). There was a non-significant trend towards improved outcomes with thrombectomy. Qualitatively, physician feedback suggested that e-Stroke Suite increased decision-making confidence and improved patient flow. CONCLUSIONS: Use of artificial intelligence decision support in a hyperacute stroke pathway facilitates decision-making and can improve rate and time of reperfusion therapies in a hub-and-spoke system of care.

Efficacy of Cerebrolysin Treatment as an Add-On Therapy to Mechanical Thrombectomy in Patients With Acute Ischemic Stroke Due to Large Vessel Occlusion: Study Protocol for a Prospective, Open Label, Single-Center Study With 12 Months of Follow-Up.

This study is designed to determine the efficacy of Cerebrolysin treatment as an add-on therapy to mechanical thrombectomy (MT) in reducing global disability in subjects with acute ischemic stroke (AIS). We have planned a single center, prospective, open-label, single-arm study with a 12-month follow-up of 50 patients with moderate to severe AIS, with a small established infarct core and with good collateral circulation who achieve significant reperfusion following MT and who receive additional Cerebrolysin within 8 h of stroke onset compared to 50 historical controls treated with MT alone, matched for age, clinical severity, occlusion location, baseline perfusion lesion volume, onset to reperfusion time, and use of iv thrombolytic therapy. The primary outcome measure will be the overall proportion of subjects receiving Cerebrolysin compared to the control group experiencing a favorable functional outcome (by modified Rankin Scale 0-2) at 90 days, following stroke onset. The secondary objectives are to determine the efficacy of Cerebrolysin as compared to the control group in reducing the risk of symptomatic secondary hemorrhagic transformation, improving neurological outcomes (NIHSS 0-2 at day 7, day 30, and 90), reducing mortality rates (over the 90-day and 12 months study period), and improving: activities of daily living (by Barthel Index), health-related quality of life (EQ-5D-5L) assessed at day 30, 90, and at 12 months. The other measures of efficacy in the Cerebrolysin group will include: assessment of final stroke volume and penumbral salvage (measured by CT/CTP at 30 days) and its change compared to baseline volume, changes over time in language function (by the 15-item Boston Naming Test), hemispatial neglect (by line bisection test), global cognitive function (by The Montreal Cognitive Assessment), and depression (by Hamilton Depression Rating Scale) between day 30 and day 90 assessments). The patients will receive 30 ml of Cerebrolysin within 8 h of AIS stroke onset and continue treatment once daily until day 21 (first cycle) and they will receive a second cycle of treatment (30 ml/d for 21 days given in the Outpatient Department or Neurorehabilitation Clinic) from day 69 to 90.