Medicine (RMH) - Research Publications

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    Basilar artery occlusion management: Specialist perspectives from an international survey
    Edwards, C ; Drumm, B ; Siegler, JE ; Schonewille, WJ ; Klein, P ; Huo, X ; Chen, Y ; Abdalkader, M ; Qureshi, MM ; Strbian, D ; Liu, X ; Hu, W ; Ji, X ; Li, C ; Fischer, U ; Nagel, S ; Puetz, V ; Michel, P ; Alemseged, F ; Sacco, S ; Yamagami, H ; Yaghi, S ; Strambo, D ; Kristoffersen, ES ; Sandset, EC ; Mikulik, R ; Tsivgoulis, G ; Masoud, HE ; de Sousa, DA ; Marto, JP ; Lobotesis, K ; Roi, D ; Berberich, A ; Demeestere, J ; Meinel, TR ; Rivera, R ; Poli, S ; Ton, MD ; Zhu, Y ; Li, F ; Sang, H ; Thomalla, G ; Parsons, M ; Campbell, BCV ; Zaidat, OO ; Chen, H-S ; Field, TS ; Raymond, J ; Kaesmacher, J ; Nogueira, RG ; Jovin, TG ; Sun, D ; Liu, R ; Qureshi, AI ; Qiu, Z ; Miao, Z ; Banerjee, S ; Nguyen, TN (Wiley, 2023-05)
    BACKGROUND AND PURPOSE: Two early basilar artery occlusion (BAO) randomized controlled trials did not establish the superiority of endovascular thrombectomy (EVT) over medical management. While many providers continue to recommend EVT for acute BAO, perceptions of equipoise in randomizing patients with BAO to EVT versus medical management may differ between clinician specialties. METHODS: We conducted an international survey (January 18, 2022 to March 31, 2022) regarding management strategies in acute BAO prior to the announcement of two trials indicating the superiority of EVT, and compared responses between interventionalists (INTs) and non-interventionalists (nINTs). Selection practices for routine EVT and perceptions of equipoise regarding randomizing to medical management based on neuroimaging and clinical features were compared between the two groups using descriptive statistics. RESULTS: Among the 1245 respondents (nINTs = 702), INTs more commonly believed that EVT was superior to medical management in acute BAO (98.5% vs. 95.1%, p < .01). A similar proportion of INTs and nINTs responded that they would not randomize a patient with BAO to EVT (29.4% vs. 26.7%), or that they would only under specific clinical circumstances (p = .45). Among respondents who would recommend EVT for BAO, there was no difference in the maximum prestroke disability, minimum stroke severity, or infarct burden on computed tomography between the two groups (p > .05), although nINTs more commonly preferred perfusion imaging (24.2% vs. 19.7%, p = .04). Among respondents who indicated they would randomize to medical management, INTs were more likely to randomize when the National Institutes of Health Stroke Scale was ≥10 (15.9% vs. 6.9%, p < .01). CONCLUSIONS: Following the publication of two neutral clinical trials in BAO EVT, most stroke providers believed EVT to be superior to medical management in carefully selected patients, with most indicating they would not randomize a BAO patient to medical treatment. There were small differences in preference for advanced neuroimaging for patient selection, although these preferences were unsupported by clinical trial data at the time of the survey.
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    Benchmark dataset for clot detection in ischemic stroke vessel-based imaging: CODEC-IV
    Werdiger, F ; Visser, M ; Bivard, A ; Li, X ; Gotla, S ; Sharobeam, A ; Valente, M ; Beharry, J ; Yogendrakumar, V ; Parsons, MW (ACADEMIC PRESS INC ELSEVIER SCIENCE, 2023-05-01)
    We present an annotated dataset for the purposes of creating a benchmark in Artificial Intelligence for automated clot detection. While there are commercial tools available for automated clot detection on computed tomographic (CT) angiographs, they have not been compared in a standardized manner whereby accuracy is reported on a publicly available benchmark dataset. Furthermore, there are known difficulties in automated clot detection - namely, cases where there is robust collateral flow, or residual flow and occlusions of the smaller vessels - and it is necessary to drive an initiative to overcome these challenges. Our dataset contains 159 multiphase CTA patient datasets, derived from CTP and annotated by expert stroke neurologists. In addition to images where the clot is marked, the expert neurologists have provided information about clot location, hemisphere and the degree of collateral flow. The data is available on request by researchers via an online form, and we will host a leaderboard where the results of clot detection algorithms on the dataset will be displayed. Participants are invited to submit an algorithm to us for evaluation using the evaluation tool, which is made available at together with the form at https://github.com/MBC-Neuroimaging/ClotDetectEval.
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    Prospective analysis of stroke recognition, stroke risk factors, thrombolysis rates and outcomes in Indigenous Australians from a large rural referral hospital
    Dos Santos, A ; Mohr, K ; Jude, M ; Simon, NG ; Parsons, M ; Eades, S ; Burchill, L ; Davis, S ; Donnan, G ; Churliov, L ; Delcourt, C (WILEY, 2022-03)
    BACKGROUND: Cardiovascular disease is the most common cause of death and disability in indigenous communities but limited prospective data exist about stroke. AIMS: To estimate the difference in stroke recognition, risk factors, treatment rates and outcomes between indigenous and non-indigenous peoples admitted to the Wagga Wagga Rural Referral Hospital (WWRRH) over a 5-year period with a suspected acute stroke. METHODS: All suspected strokes presenting to the 33 peripheral hospitals within the Murrumbidgee Local Health District (MLHD) were transferred to the WWRRH and prospectively assessed over a 5-year period from 1 January 2012 to 31 December 2017. Actions at stroke onset, risks factors, stroke type, treatment and outcomes were analysed. RESULTS: A total of 1843 patients were included. Of these, 45 (2.5%) patients were indigenous. Only 26.6% of indigenous and 34% of non-indigenous patients knew of the face, arm, speech, time (FAST) acronym. Indigenous patients were younger (mean age 62.0 years vs 74.4 years) and more likely to have diabetes (risk difference (RD) 22.3% (95% CI: 3%, 41.7%)), dyslipidaemia (RD 19.4% (95% CI: 21.%, 36.7%)), and be ever smokers (RD 24.9% (95% CI: 9.5%, 40.3%)). Stroke types were similar except lacunar infarcts were more common (19.2% vs 8.4%). Treatment rates and outcomes were similar between the two groups. CONCLUSIONS: Indigenous Australians with stroke are a decade younger and have a higher prevalence of important, modifiable stroke-risk factors. Delayed presentation to hospital is more common, due in part to stroke symptoms being underrecognised. When admitted to a specialised stroke unit, treatment rates and outcomes are comparable.
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    Association of Endovascular Thrombectomy With Functional Outcome in Patients With Acute Stroke With a Large Ischemic Core
    Garcia-Esperon, C ; Bivard, A ; Johns, H ; Chen, C ; Churilov, L ; Lin, L ; Butcher, K ; Kleinig, TJ ; Choi, PMC ; Cheng, X ; Dong, Q ; Aviv, R ; Miteff, F ; Spratt, NJ ; Levi, CR ; Parsons, MW (LIPPINCOTT WILLIAMS & WILKINS, 2022-09-27)
    BACKGROUND AND OBJECTIVES: Endovascular thrombectomy (EVT) is effective for patients with large vessel occlusion (LVO) stroke with smaller volumes of CT perfusion (CTP)-defined ischemic core. However, the benefit of EVT is unclear in those with a core volume >70 mL. We aimed to compare outcomes of EVT and non-EVT patients with an ischemic core volume ≥70 mL, hypothesizing that there would be a benefit from EVT for fair outcome (3-month modified Rankin scale [mRS] 0-3) after stroke. METHODS: A retrospective analysis of patients enrolled into a multicenter (Australia, China, and Canada) registry (2012-2020) who underwent CTP within 24 hours of stroke onset and had a baseline ischemic core volume ≥70 mL was performed. The primary outcome was the estimation of the association of EVT in patients with core volume ≥70 mL and within 70-100 and ≥100 mL subgroups with fair outcome. RESULTS: Of the 3,283 patients in the registry, 299 had CTP core volume ≥70 mL and 269 complete data (135 had core volume between 70 and 100 mL and 134 had core volume ≥100 mL). EVT was performed in 121 (45%) patients. EVT-treated patients were younger (median 69 vs 75 years; p = 0.011), had lower prestroke mRS, and smaller median core volumes (92 [79-116.5] mL vs 105.5 [85.75-138] mL, p = 0.004). EVT-treated patients had higher odds of achieving fair outcome in adjusted analysis (30% vs 13.9% in the non-EVT group; adjusted odds ratio [aOR] 2.1, 95% CI 1-4.2, p = 0.038). The benefit was seen predominantly in those with 70-100 mL core volume (71/135 [52.6%] EVT-treated), with 54.3% in the EVT-treated vs 21% in the non-EVT group achieving a fair outcome (aOR 2.5, 95% CI 1-6.2, p = 0.005). Of those with a core volume ≥100 mL, 50 of the 134 (37.3%) underwent EVT. Proportions of fair outcome were very low in both groups (8.1% vs 8.7%; p = 0.908). DISCUSSION: We found a positive association of EVT with the 3-month outcome after stroke in patients with a baseline CTP ischemic core volume 70-100 mL but not in those with core volume ≥100 mL. Randomized data to confirm these findings are required. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that EVT is associated with better motor outcomes 3 months after CTP-defined ischemic stroke with a core volume of 70-100 mL.
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    Prevalence and Significance of Impaired Microvascular Tissue Reperfusion Despite Macrovascular Angiographic Reperfusion (No-Reflow)
    Ng, FC ; Churilov, L ; Yassi, N ; Kleinig, TJ ; Thijs, V ; Wu, T ; Shah, D ; Dewey, H ; Sharma, G ; Desmond, P ; Yan, B ; Parsons, M ; Donnan, G ; Davis, S ; Mitchell, P ; Campbell, B (LIPPINCOTT WILLIAMS & WILKINS, 2022-02-22)
    BACKGROUND AND OBJECTIVES: The relevance of impaired microvascular tissue-level reperfusion despite complete upstream macrovascular angiographic reperfusion (no-reflow) in human stroke remains controversial. We investigated the prevalence and clinical-radiologic features of this phenomenon and its associations with outcomes in 3 international randomized controlled thrombectomy trials with prespecified follow-up perfusion imaging. METHODS: In a pooled analysis of the Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial (EXTEND-IA; ClinicalTrials.gov NCT01492725), Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke (EXTEND-IA TNK; NCT02388061), and Determining the Optimal Dose of Tenecteplase Before Endovascular Therapy for Ischaemic Stroke (EXTEND-IA TNK Part 2; NCT03340493) trials, patients undergoing thrombectomy with final angiographic expanded Treatment in Cerebral Infarction score of 2c to 3 score for anterior circulation large vessel occlusion and 24-hour follow-up CT or MRI perfusion imaging were included. No-reflow was defined as regions of visually demonstrable persistent hypoperfusion on relative cerebral blood volume or flow maps within the infarct and verified quantitatively by >15% asymmetry compared to a mirror homolog in the absence of carotid stenosis or reocclusion. RESULTS: Regions of no-reflow were identified in 33 of 130 patients (25.3%), encompassed a median of 60.2% (interquartile range 47.8%-70.7%) of the infarct volume, and involved both subcortical (n = 26 of 33, 78.8%) and cortical (n = 10 of 33, 30.3%) regions. Patients with no-reflow had a median 25.2% (interquartile range 16.4%-32.2%, p < 0.00001) relative cerebral blood volume interside reduction and 19.1% (interquartile range 3.9%-28.3%, p = 0.00011) relative cerebral blood flow reduction but similar mean transit time (median -3.3%, interquartile range -11.9% to 24.4%, p = 0.24) within the infarcted region. Baseline characteristics were similar between patients with and those without no-reflow. The presence of no-reflow was associated with hemorrhagic transformation (adjusted odds ratio [aOR] 1.79, 95% confidence interval [CI] 2.32-15.57, p = 0.0002), greater infarct growth (β = 11.00, 95% CI 5.22-16.78, p = 0.00027), reduced NIH Stroke Scale score improvement at 24 hours (β = -4.06, 95% CI 6.78-1.34, p = 0.004) and being dependent or dead at 90 days as assessed by the modified Rankin Scale (aOR 3.72, 95% CI 1.35-10.20, p = 0.011) in multivariable analysis. DISCUSSION: Cerebral no-reflow in humans is common, can be detected by its characteristic perfusion imaging profile using readily available sequences in the clinical setting, and is associated with posttreatment complications and being dependent or dead. Further studies evaluating the role of no-reflow in secondary injury after angiographic reperfusion are warranted. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that cerebral no-reflow on CT/MRI perfusion imaging at 24 hours is associated with posttreatment complications and poor 3-month functional outcome.
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    Endovascular Thrombectomy Versus Medical Management in Isolated M2 Occlusions: Pooled Patient-Level Analysis from the EXTEND-IA Trials, INSPIRE, and SELECT Studies
    Sarraj, A ; Parsons, M ; Bivard, A ; Hassan, AE ; Abraham, MG ; Wu, T ; Kleinig, T ; Lin, L ; Chen, C ; Levi, C ; Dong, Q ; Cheng, X ; Butcher, KS ; Choi, P ; Yassi, N ; Shah, D ; Sharma, G ; Pujara, D ; Shaker, F ; Blackburn, S ; Dewey, H ; Thijs, V ; Sitton, CW ; Donnan, GA ; Mitchell, PJ ; Yan, B ; Grotta, JG ; Albers, GW ; Davis, SM ; Campbell, B (WILEY, 2022-05)
    OBJECTIVE: The objective of this study was to evaluate functional and safety outcomes of endovascular thrombectomy (EVT) versus medical management (MM) in patients with M2 occlusion and examine their association with perfusion imaging mismatch and stroke severity. METHODS: In a pooled, patient-level analysis of 3 randomized controlled trials (EXTEND-IA, EXTEND-and IA-TNK parts 1 and 2) and 2 prospective nonrandomized studies (INSPIRE and SELECT), we evaluated EVT association with 90-day functional independence (modified Rankin Scale [mRS] = 0-2) in isolated M2 occlusions as compared to medical management overall and in subgroups by mismatch profile status and stroke severity. RESULTS: We included 517 patients (EVT = 195 and MM = 322), baseline median (interquartile range [IQR]) National Institutes of Health Stroke Scale (NIHSS) was 13 (8-19) in EVT versus 10 (6-15) in MM, p < 0.001. Pretreatment ischemic core did not differ (EVT = 10 [0-24] ml vs MM = 9 [3-21] ml, p = 0.59). Compared to MM, EVT was more frequently associated with functional independence (68.3 vs 61.6%, adjusted odds ratio [aOR] = 2.42, 95% confidence interval [CI] = 1.25-4.67, p = 0.008, inverse probability of treatment weights [IPTW]-OR = 1.75, 95% CI = 1.00-3.75, p = 0.05) with a shift toward better mRS outcomes (adjusted cOR = 2.02, 95% CI:1.23-3.29, p = 0.005), and lower mortality (5 vs 10%, aOR = 0.32, 95% CI = 0.12-0.87, p = 0.025). EVT was associated with higher functional independence in patients with a perfusion mismatch profile (EVT = 70.7% vs MM = 61.3%, aOR = 2.29, 95% CI = 1.09-4.79, p = 0.029, IPTW-OR = 2.02, 1.08-3.78, p = 0.029), whereas no difference was found in those without mismatch (EVT = 43.8% vs MM = 62.7%, p = 0.17, IPTW-OR: 0.71, 95% CI = 0.18-2.78, p = 0.62). Functional independence was more frequent with EVT in patients with moderate or severe strokes, as defined by baseline NIHSS above any thresholds from 6 to 10, whereas there was no difference between groups with milder strokes below these thresholds. INTERPRETATION: In patients with M2 occlusion, EVT was associated with improved clinical outcomes when compared to MM. This association was primarily observed in patients with a mismatch profile and those with higher stroke severity. ANN NEUROL 2022;91:629-639.
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    CT vascular territory mapping: a novel method to identify large vessel occlusion collateral.
    Valente, M ; Bivard, A ; Cheung, A ; Manning, NW ; Parsons, MW (Springer Science and Business Media LLC, 2023-01)
    INTRODUCTION: This descriptive study explores typical patterns of vascular territory mapping (VTM) in ischaemic stroke patients with proximal vessel occlusion. VTM is a novel process using CT perfusion that can identify the source and extent of collateral blood flow in patients with vessel occlusion. It functions by determining which vessel provides dominant blood flow to a brain voxel. METHODS: A total of 167 consecutive patients were analysed from INSPIRE (International Stroke Perfusion Imaging Registry) with their CT perfusion reprocessed through VTM software. We explored the typical territory maps generated by this software relating to common large vessel occlusion location sites (ACA/MCA/PCA). RESULTS/CONCLUSION: In the presence of occlusion, VTM demonstrated a reciprocal increase in collateral vessel territories.
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    Automated CT Perfusion Detection of the Acute Infarct Core in Ischemic Stroke: A Systematic Review and Meta-Analysis
    Lim, NE ; Chia, B ; Bulsara, MK ; Parsons, M ; Hankey, GJ ; Bivard, A (KARGER, 2023-01)
    INTRODUCTION: In patients with acute ischemic stroke, the location and volume of an irreversible infarct core determine prognosis and treatment. We aimed to determine if automated CT perfusion (CTP) is non-inferior to diffusion-weighted imaging (DWI) or fluid-attenuated inversion recovery (FLAIR) in predicting the acute infarct core. METHODS: In this systematic review and meta-analysis, we searched MEDLINE and EMBASE from 1960 to December 2020. Five outcome measures were examined: volumetric difference, volumetric correlation, sensitivity and specificity at the patient level, Dice coefficient, and sensitivity and specificity at the voxel level. A random-effects meta-analysis was performed for volumetric difference and correlation. RESULTS: From 3,986 studies retrieved, 48 studies met our inclusion criteria with 46 studies on anterior circulation, one study on posterior circulation, and one study on lacunar infarct strokes. In anterior circulation stroke, there were no significant mean volumetric differences between CTP and acute DWI (cerebral blood flow [CBF] 0.52 mL, 95% CI [-0.07, 1.11], I2 0.0%; relative CBF [rCBF] 3.01 mL, 95% CI [-0.46, 6.48], I2 82.6%; relative cerebral blood volume [rCBV] -12.84 mL, 95% CI [-38.56, 12.88], I2 96.2%) and between CTP and delayed DWI or FLAIR (rCBF -1.29 mL, 95% CI [-6.49, 3.92], I2 91.8%; rCBV -5.80 mL, 95% CI [-16.20, 4.60], I2 84.2%). Mean correlation between CTP and acute DWI was 0.90 (95% CI [0.80, 0.95], I2 60.0%) for rCBF and 0.84 (95% CI [0.58, 0.94], I2 93.5%) for rCBV. Mean correlation between CTP and delayed DWI or FLAIR was 0.74 (95% CI [0.57, 0.85], I2 94.6%) for rCBF and 0.90 (95% CI [0.69, 0.97], I2 93.1%) for rCBV. Sensitivity and specificity at the patient level were reported by three studies and Dice coefficient by four studies. Statistical analysis could not be performed for sensitivity and specificity at the voxel level. Limited evidence was available for posterior circulation or lacunar infarct strokes. CONCLUSION: Due to significant heterogeneity and insufficient high-quality studies reporting each outcome, there is insufficient evidence to reliably determine the accuracy of CTP prediction of the infarct core compared to DWI or FLAIR.
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    Endovascular Treatment of ICAS Patients: Targeting Reperfusion Rather than Residual Stenosis.
    Yi, T ; Zhan, A ; Wu, Y ; Li, Y ; Zheng, X ; Lin, D ; Lin, X ; Pan, Z ; Chen, R ; Parsons, M ; Chen, W ; Lin, L (MDPI AG, 2022-07-22)
    BACKGROUND AND PURPOSE: Previous studies showed that acute reocclusion after endovascular therapy is related to residual stenosis. However, we observed that reperfusion status but not residual stenosis severity is related to acute reocclusion. This study aimed to assess which factor mention above is more likely to be associated with artery reocclusion after endovascular treatment. METHODS: This study included 86 acute ischemic stroke patients who had middle cerebral artery (MCA) atherosclerotic occlusions and received endovascular treatment within 24 h of a stroke. The primary outcomes included intraprocedural reocclusion assessed during endovascular treatment and delayed reocclusion assessed through follow-up angiography. RESULTS: Of the 86 patients, the intraprocedural reocclusion rate was 7.0% (6/86) and the delayed reocclusion rate was 2.3% (2/86). Regarding intraprocedural occlusion, for patients with severe residual stenosis, patients with successful thrombectomy reperfusion showed a significantly lower rate than unsuccessful thrombectomy reperfusion (0/30 vs. 6/31, p = 0.003); on the other hand, for patients with successful thrombectomy reperfusion, patients with severe residual stenosis showed no difference from those with mild to moderate residual stenosis in terms of intraprocedural occlusion (0/30 vs. 0/25, p = 1.00). In addition, after endovascular treatment, all patients achieved successful reperfusion. There was no significant difference in the delayed reocclusion rate between patients with severe residual stenosis and those with mild to moderate residual stenosis (2/25 vs. 0/61, p = 0.085). CONCLUSION: Reperfusion status rather than residual stenosis severity is associated with artery reocclusion after endovascular treatment. Once successful reperfusion was achieved, the reocclusion occurrence was fairly low in MCA atherosclerosis stroke patients, even with severe residual stenosis.
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    Net water uptake, a neuroimaging marker of early brain edema, as a predictor of symptomatic intracranial hemorrhage after acute ischemic stroke.
    Xu, T ; Yang, J ; Han, Q ; Wu, Y ; Gao, X ; Xu, Y ; Huang, Y ; Wang, A ; Parsons, MW ; Lin, L (Frontiers Media SA, 2022)
    OBJECTIVE: We hypothesized that quantitative net water uptake (NWU), a novel neuroimaging marker of early brain edema, can predict symptomatic intracranial hemorrhage (sICH) after acute ischemic stroke (AIS). METHODS: We enrolled patients with AIS who completed admission multimodal computed tomography (CT) within 24 h after stroke onset. NWU within the ischemic core and penumbra was calculated based on admission CT, namely NWU-core and NWU-penumbra. sICH was defined as the presence of ICH in the infarct area within 7 days after stroke onset, accompanied by clinical deterioration. The predictive value of NWU-core and NWU-penumbra on sICH was evaluated by logistic regression analyses and the receiver operating characteristic (ROC) curve. A pure neuroimaging prediction model was built considering imaging markers, which has the potential to be automatically quantified with an artificial algorithm on image workstation. RESULTS: 154 patients were included, of which 93 underwent mechanical thrombectomy (MT). The median time from symptom onset to admission CT was 262 min (interquartile range, 198-368). In patients with MT, NWU-penumbra (OR =1.442; 95% CI = 1.177-1.766; P < 0.001) and NWU-core (OR = 1.155; 95% CI = 1.027-1.299; P = 0.016) were independently associated with sICH with adjustments for age, sex, time from symptom onset to CT, hypertension, lesion volume, and admission National Institutes of Health Stroke Scale (NIHSS) score. ROC curve showed that NWU-penumbra had better predictive performance than NWU-core on sICH [area under the curve (AUC): 0.773 vs. 0.673]. The diagnostic efficiency of the predictive model was improved with the containing of NWU-penumbra (AUC: 0.853 vs. 0.760). A pure imaging model also presented stable predictive power (AUC = 0.812). In patients without MT, however, only admission NIHSS score (OR = 1.440; 95% CI = 1.055-1.965; P = 0.022) showed significance in predicting sICH in multivariate analyses. CONCLUSIONS: NWU-penumbra may have better predictive performance than NWU-core on sICH after MT. A pure imaging model showed potential value to automatically screen patients with sICH risk by image recognition, which may optimize treatment strategy.