Reperfusion Is a More Accurate Predictor of Follow-Up Infarct Volume Than Recanalization: A Proof of Concept Using CT in Acute Ischemic Stroke Patients

Introduction: Revascularization is a robust therapy for acute ischemic stroke, but animal studies suggest that reperfusion edema may attenuate its beneficial effects. In stroke patients, early reperfusion consistently reduces infarct volume and improves long-term functional outcome, but there is little clinical data available regarding reperfusion edema. We sought to elucidate the relationship between reperfusion and brain edema in a patient cohort of moderate to severe stroke. Methods: Seventy-one patients enrolled in the Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET) with serial brain magnetic resonance imaging and perfusion-weighted imaging (PWI) were analyzed. Reperfusion percentage was calculated based on the difference in PWI lesion volume at baseline and follow-up (day 3-5). Midline shift (MLS) was measured on the day 3-5 fluid attenuated inversion recovery (FLAIR) sequence. Swelling volume and infarct growth volume were assessed using region-of-interest analysis on the baseline and follow-up DWI scans based on our prior methods. Results: Greater percentage of reperfusion was associated with less MLS (Spearman ρ = -0.46; P <0.0001) and reduced swelling volume (Spearman ρ = -0.56; P <0.0001). In multivariate analysis, reperfusion was an independent predictor of less MLS ( P <0.006) and decreased swelling volume ( P <0.0054), after adjusting for age, baseline NIHSS, admission blood glucose, baseline DWI volume, and IV tPA treatment. Conclusions: Reperfusion is associated with reduced brain edema as measured by MLS and swelling volume. While our data do not exclude the possibility of reperfusion edema in certain circumstances, in stroke patients, reperfusion following acute stroke is predominantly linked to less brain swelling.

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Abstract P538: A Detailed Analysis of Intracranial Hemorrhage After Endovascular Treatment in Acute Ischemic Stroke Due to Large Vessel Occlusion in the Escape-NA1 Trial

Stroke ◽

10.1161/str.52.suppl_1.p538 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Johanna Ospel ◽

Michael D Hill ◽

Nima Kashani ◽

Arnuv Mayank ◽

Nishita Singh ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Intracranial Hemorrhage ◽

Intraventricular Hemorrhage ◽

Infarct Volume ◽

Prognostic Impact ◽

Vessel Occlusion ◽

Good Outcome

Purpose: We investigated the prevalence and prognostic impact on outcome of any intracranial hemorrhage, hemorrhage morphology, type and volume in acute ischemic stroke patients undergoing mechanical thrombectomy. Methods: Prevalence of intracranial hemorrhage, hemorrhage type, morphology and volume was determined on 24h follow-up imaging (non contrast head CT or gradient-echo/susceptibility-weighted MRI). Proportions of good outcome (mRS 0-2 at 90 days) were reported for patients with vs. without any intracranial hemorrhage. Multivariable logistic regression with adjustment for key minimization variables and total infarct volume was performed to obtain adjusted effect size estimates for hemorrhage type and volume on good outcome. Results: Hemorrhage on follow up-imaging was seen in 372/1097 (33.9%) patients, among them 126 (33.9%) with hemorrhagic infarction (HI) type 1, 108 (29.0%) with HI-2, 72 /19.4%) with parenchymal hematoma (PH) type 1, 37 (10.0) with PH2, 8 (2.2%) with remote PH and 21 (5.7%) with extra-parenchymal/intraventricular hemorrhage. Good outcomes were less often achieved by patients with hemorrhage on follow-up imaging (164/369 [44.4%] vs. 500/720 [69.4%]). Any type of intracranial hemorrhage was strongly associated with decreased chances of good outcome ( adj OR 0.62 [CI 95 0.44 - 0.87]). The effect of hemorrhage was driven by both PH hemorrhage sub-type [PH-1 ( adj OR 0.39 [CI 95 0.21 - 0.72]), PH-2 ( adj OR 0.15 [CI 95 0.05 - 0.50])] and extra-parenchymal/intraventricular hemorrhage ( adj OR 0.60 (0.20-1.78) Petechial hemorrhages (HI-1 and HI-2) were not associated with poorer outcomes. Hemorrhage volume ( adj OR 0.97 [CI 95 0.05 - 0.99] per ml increase) was significantly associated with decreased chances of good outcome. Conclusion: Presence of any hemorrhage on follow-up imaging was seen in one third of patients and strongly associated with decreased chances of good outcome.

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Abstract 176: Long Term Mortality in Acute Ischemic Stroke Patients with Nonvalvular Atrial Fibrillation According to Location and Burden of Cerebral Microbleeds

Stroke ◽

10.1161/str.45.suppl_1.176 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Tae-Jin Song ◽

Jinkwon Kim ◽

Dongbeom Song ◽

Yong-Jae Kim ◽

Hyo Suk Nam ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Hemorrhagic Stroke ◽

Independent Predictor ◽

Stroke Patients ◽

Risk Of Death ◽

Long Term Mortality

Background: Cerebral microbleeds (CMBs) were predictive of mortality in elderly and considered as a putative marker for risk of intracranial hemorrhage. Stroke patients with non valvular atrial fibrillation (NVAF) require anticoagulation, which increases the risk of hemorrhages. We investigated association of CMBs with the long term mortality in acute ischemic stroke patients with NVAF. Methods: During 6 years , consecutive ischemic stroke patients who had NVAF and who had undergone brain MRI with a gradient-recalled echo sequence were enrolled. Long-term mortality and causes of death were identified using data from Korean National Statistical Office. Survival analysis was performed whether the presence, number and location of CMBs were related with all causes, cardiovascular, and cerebrovascular mortality during follow-up. Results: Total 506 patients were enrolled during the study period and were followed up for median 2.5 years. CMBs were found in 30.8% of patients (156/506). Oral anticoagulation with warfarin was prescribed at discharge in 477 (82.7%) patients. During follow up, 177 (35%) patients died and cerebrovascular death was noted in 93 patients (81 ischemic stroke and 12 hemorrhagic stroke). After adjusting age, sex and significant variables in univariate analysis (p<0.1), multiple CMBs (≥5) were the independent predictor for all-cause, cardiovascular and ischemic stroke mortalities. The strictly lobar CMBs were associated with hemorrhagic stroke mortality in multivariate Cox regression analysis (HR 4.776, p=0.032) (Figure 1). Conclusions: Multiple CMBs were the independent predictor for the long term mortality in stroke patients with NVAF. Among them, patients with strictly lobar CMBs had a high risk of death due to hemorrhagic stroke. Our findings suggest that detection of CMBs in stroke patients with NVAF are of clinical relevance for predicting long term outcome and that particular concern is necessary in those with strictly lobar CMBs for their increased risk of death due to hemorrhagic stroke. Figure 1.

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Abstract MP86: Effects of Immediate Blood Pressure Reduction on Death and Major Disability in Acute Ischemic Stroke Patients by History of Hypertension and Use of Antihypertensive Medications

Circulation ◽

10.1161/circ.131.suppl_1.mp86 ◽

2015 ◽

Vol 131 (suppl_1) ◽

Author(s):

Tan Xu ◽

Yonghong Zhang ◽

Yingxian Sun ◽

Chung-Shiuan Chen ◽

Jing Chen ◽

...

Keyword(s):

Ischemic Stroke ◽

Treatment Group ◽

Acute Ischemic Stroke ◽

Hospital Discharge ◽

Odds Ratio ◽

Recurrent Stroke ◽

Stroke Patients ◽

Antihypertensive Medications ◽

History Of

Introduction: The effects of blood pressure (BP) reduction on clinical outcomes among acute stroke patient remain uncertain. Hypothesis: We tested the effects of immediate BP reduction on death and major disability at 14 days or hospital discharge and 3-month follow-up in acute ischemic stroke patients with and without a previous history of hypertension or use of antihypertensive medications. Methods: The China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) randomly assigned patients with ischemic stroke within 48 hours of onset and elevated systolic BP (SBP) to receive antihypertensive treatment (N=2,038) or to discontinue all antihypertensive medications (N=2,033) during hospitalization. Randomization was stratified by participating hospitals and use of antihypertensive medications. Study outcomes were assessed at 14 days or hospital discharge and 3-month post-treatment follow-up. The primary outcome was death and major disability (modified Rankin Scale score≥3), and secondary outcomes included recurrent stroke and vascular events. Results: Mean SBP was reduced 12.7% in the treatment group and 7.2% in the control group within 24 hours after randomization (P<0.001). Mean SBP was 137.3 mmHg in the treatment group and 146.5 in the control group at day 7 after randomization (P<0.001). At 14 days or hospital discharge, the primary and secondary outcomes were not significantly different between the treatment and control groups by subgroups. At the 3-month follow-up, recurrent stroke was significantly reduced in the antihypertensive treatment group among patients with a history of hypertension (odds ratio 0.43, 95% CI 0.24-0.75, P=0.003) and among patients with a history of use of antihypertensive medications (odds ratio 0.41, 95% CI 0.20-0.84, P=0.01). All-cause mortality (odds ratio 2.84, 95% CI 1.11-7.27, P=0.03) was increased among patients without a history of hypertension. Conclusion: Immediate BP reduction lowers recurrent stroke among acute ischemic stroke patients with a previous history of hypertension or use of antihypertensive medications at 3 months. On the other hand, BP reduction increases all-cause mortality among patients without a history of hypertension.

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Abstract 3681: Early Anticoagulation Is Not Associated With Hemorrhagic Transformation Of Ischemic Stroke In Patients With Atrial Fibrillation

Stroke ◽

10.1161/str.43.suppl_1.a3681 ◽

2012 ◽

Vol 43 (suppl_1) ◽

Author(s):

H. B Brouwers ◽

Svetlana Lorenzano ◽

Lyndsey H Starks ◽

David M Greer ◽

Steven K Feske ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Clinical Data ◽

Infarct Volume ◽

Hemorrhagic Transformation ◽

P Value ◽

Long Term Outcome ◽

Nihss Score

Purpose: Hemorrhagic transformation (HT) is a common and potentially devastating complication of ischemic stroke, however its prevalence, predictors, and outcome remain unclear. Early anticoagulation is thought to be a risk factor for HT which raises the clinical question when to (re)start anticoagulation in ischemic stroke patients who have a compelling indication, such as atrial fibrillation. We conducted a prospective cohort study to address this question and to identify association of hemorrhagic transformation with outcome measures in patients with atrial fibrillation in the setting of acute ischemic stroke. Materials and Methods: We performed a prospective study which enrolled consecutive patients admitted with acute ischemic stroke presenting to a single center over a three-year period. As part of the observational study, baseline clinical data and stroke characteristics as well as 3 month functional outcome were collected. For this sub-study, we restricted the analysis to subjects diagnosed with atrial fibrillation. CT and MRI scans were reviewed by experienced readers, blinded to clinical data, to assess for hemorrhagic transformation (using ECASS 2 criteria), microbleeds and infarct volumes in both admission and follow-up scans. Clinical and outcome data were analyzed for association with hemorrhagic transformation. Results: Of 94 patients, 63 had a history of atrial fibrillation (67.0%) and 31 had newly discovered atrial fibrillation (33.0%). We identified HT in 3 of 94 baseline scans (3.2%) and 22 of 48 follow-up scans (45.8%) obtained a median of 3 days post-stroke. In-hospital initiation of either anti-platelet (n = 36; OR 0.34 [95% CI 0.10-1.16], p-value = 0.09) or anticoagulation with unfractionated intravenous heparin or low molecular weight heparin (n = 72; OR 0.25 [95% CI 0.06-1.15], p-value = 0.08) was not associated with HT. Initial NIH Stroke Scale (NIHSS) score (median 13.0 [IQR 15.0] vs. 7.0 [IQR 10.0], p-value = 0.029) and baseline infarct volume (median 17 [IQR 42.03] vs. 5 [IQR 10.95], p-value = 0.011) were significantly higher in patients with HT compared to those without. Hemorrhagic transformation was associated with a significantly higher 48-hour median NIHSS score (20 [IQR 3.0] vs. 2 [IQR 3.25], p-value = 0.007) and larger final infarct volume (81.40 [IQR 82.75] vs. 9.95 [IQR 19.73], p-value < 0.001). Finally, we found a trend towards poorer 3-month modified Rankin Scale scores in subjects with HT (OR 11.25 [95% CI 0.97-130.22], p-value = 0.05). Conclusion: In patients with atrial fibrillation, initial NIHSS score and baseline infarct volume are associated with hemorrhagic transformation in acute ischemic stroke. Early initiation of antithrombotic therapy was not associated with hemorrhagic transformation. Patients with hemorrhagic transformation were found to have a poorer short and long term outcome and larger final infarct volumes.

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Abstract P12: Alteplase Reduces Mortality in Patients With Ischemic Stroke and Atrial Fibrillation: Analysis of the IAC Study

Stroke ◽

10.1161/str.52.suppl_1.p12 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Shadi Yaghi ◽

Eva Mistry ◽

Adam H De Havenon ◽

Christopher Leon Guerrero ◽

Amre Nouh ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Infarct Volume ◽

Intravenous Thrombolysis ◽

The United States ◽

Hemorrhagic Transformation ◽

Stroke Patients ◽

Increased Risk ◽

Significant Difference

Background and Purpose: Multiple studies have established that intravenous thrombolysis with alteplase improves outcome after acute ischemic stroke. However, assessment of thrombolysis’ efficacy in stroke patients with atrial fibrillation (AF) has yielded mixed results. We sought to determine the association of alteplase with mortality, hemorrhagic transformation (HT), infarct volume, and mortality in patients with AF and acute ischemic stroke. Methods: We retrospectively analyzed consecutive acute ischemic stroke patients with AF included in the Initiation of Anticoagulation after Cardioembolic stroke (IAC) study, which pooled data from 8 comprehensive stroke centers in the United States. 1889 (90.6%) had available 90-day follow up data and were included. For our primary analysis we used a cohort of 1367/1889 (72.4%) patients who did not undergo mechanical thrombectomy (MT). Secondary analyses were repeated in the patients that underwent MT (n=522). Binary logistic regression was used to determine whether alteplase use was independently associated with risk of HT, final infarct volume, and 90-day mortality, respectively, adjusting for potential confounders. Results: In our primary analyses we found that alteplase use was independently associated with an increased risk for HT (adjusted OR 2.14, 95% CI 1.49 - 3.07, p <0.001) but overall reduced risk of 90-day mortality (adjusted OR 0.58, 95% CI 0.39 - 0.87, p = 0.009). Among patients undergoing MT, alteplase use was associated with a trend towards a reduction in 90-day mortality (adjusted OR 0.68 95% CI 0.45 - 1.04, p = 0.077). In the subgroup of patients prescribed DOAC treatment (n = 327; 24 received alteplase), alteplase treatment was associated with a trend towards smaller infarct size (< 10 mL), (adjusted OR 0.40, 95% CI 0.15 - 1.12, p = 0.082) without a significant difference in the odds of 90-day mortality (adjusted OR 0.51, 95% CI 0.12 - 2.13, p = 0.357) or hemorrhagic transformation (adjusted OR 0.27, 95% CI 0.03 - 2.07, p = 0.206). Conclusion: Thrombolysis with intravenous alteplase was associated with reduced 90-day mortality in AF patients with acute ischemic stroke not undergoing MT. Further study is required to assess the safety and efficacy of alteplase in AF patients undergoing MT and those on DOACs.

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Abstract TP315: D-dimer is Associated With 30-day Mortality in Acute Ischemic Stroke With Active Cancer

Stroke ◽

10.1161/str.48.suppl_1.tp315 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Ki Woong Nam ◽

Chi Kyung Kim ◽

Tae Jung Kim ◽

Sang Joon An ◽

Kyungmi Oh ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Infarct Volume ◽

Hemorrhagic Transformation ◽

Stroke Patients ◽

Nihss Score ◽

Patients With Cancer ◽

Advanced Stages ◽

D Dimer ◽

Active Cancer

Background: Stroke in cancer patients is not rare, but is a devastating event with high mortality. However, the predictors of mortality in stroke patients with cancer have not been well addressed. D-dimer could be a useful predictor because it can reflect both thromboembolic events and advanced stages of cancer. In this study, we evaluate the possibility of D-dimer as a predictor of 30-day mortality in stroke patients with active cancer. Methods: We included 210 ischemic stroke patients with active cancer. The data of 30-day mortality were collected by reviewing medical records. We also collected follow-up D-dimer levels in 106 (50%) participants to evaluate the effects of treatment response on D-dimer levels. Results: Of the 210 participants, 30-day mortality occurred in 28 (13%) patients. Higher initial NIHSS score, D-dimer levels, CRP levels, frequent cryptogenic mechanism, systemic metastasis, multiple vascular territory lesion, hemorrhagic transformation, and larger infarct volume were related to 30-day mortality. In the multivariate analysis, D-dimer [adjusted OR (aOR) = 2.19; 95% CI, 1.46-3.28, P < 0.001] predicted 30-day mortality after adjusting for confounders. Initial NIHSS score (aOR = 1.07; 95% CI, 1.00-1.14, P = 0.043) and hemorrhagic transformation (aOR = 3.02; 95% CI, 1.10-8.29, P = 0.032) were also significant independently from D-dimer levels. In the analysis of D-dimer changes after treatment, the mortality group showed no significant decrease of D-dimer levels, despite treatment, while the survivor group showed opposite responses. Conclusions: D-dimer levels may predict 30-day mortality in acute ischemic stroke patients with active cancer.

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Erratum to: Serum levels of cytokines and C-reactive protein in acute ischemic stroke patients, and their relationship to stroke lateralization, type, and infarct volume

Journal of Neurology ◽

10.1007/s00415-011-6333-1 ◽

2011 ◽

Vol 259 (2) ◽

pp. 400-400 ◽

Cited By ~ 1

Author(s):

Heidi Ormstad ◽

Hans Christian Dalsbotten Aass ◽

Niels Lund-Sørensen ◽

Karl-Friedrich Amthor ◽

Leif Sandvik

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Infarct Volume ◽

Serum Levels ◽

C Reactive Protein ◽

Stroke Patients ◽

Reactive Protein

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Nitroglycerin Is Not Associated with Improved Cerebral Perfusion in Acute Ischemic Stroke

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2020.179 ◽

2020 ◽

pp. 1-9

Author(s):

Mahesh Kate ◽

Laura Gioia ◽

Negar Asdaghi ◽

Thomas Jeerakathil ◽

Ashfaq Shuaib ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Cerebral Perfusion ◽

Primary Outcome ◽

Infarct Volume ◽

Univariate Analysis ◽

Primary Outcome Measure ◽

Untreated Group ◽

Stroke Patients ◽

The Mean

ABSTRACT: Objective: The study was conducted to test the hypothesis that nitroglycerin (NTG) increases cerebral perfusion focally and globally in acute ischemic stroke patients, using serial perfusion-weighted imaging (PWI) magnetic resonance imaging measurements. Patients and methods: Thirty-five patients underwent PWI immediately before and 72 h after administration of a transdermal NTG patch or no treatment. Patients with baseline mean arterial pressure (MAP) > 100 mmHg (NTG group, n = 20) were treated with transdermal NTG (0.2 mg/h) for 72 h, without a nitrate-free interval. Patients with MAP ≤ 100 mmHg (untreated group, n = 15) were not treated. The primary outcome measure was absolute cerebral blood flow (CBF) in the hypoperfused region at 72 h. Results: The mean baseline absolute CBF in the hypoperfused region was similar in the NTG group (33.3 ± 10.2 ml/100 g/min) and untreated (32.7 ± 8.4 ml/100 g/min, p = 0.4) groups. The median (IQR) baseline infarct volume was 10.4 (2.5–49.3) ml in the NTG group and 32.6 (8.6–96.7) ml in the untreated group (p = 0.09). MAP change in the NTG group was 1.2 ± 12.6 and 8 ± 20.7 mmHg at 2 h and 72 h, respectively. Mean absolute CBF in the hypoperfused region at 72 h was similar in the NTG (29.9 ± 12 ml/100 g/min) and untreated groups (24.1 ± 10 ml/100 g/min, p = 0.8). The median infarct volume increased in untreated (11.8 (5.7–44.2) ml) than the NTG group (3.2 (0.5–16.5) ml; p = 0.033) on univariate analysis, however, there was no difference on regression analysis. Conclusion: NTG was not associated with improvement in cerebral perfusion in acute ischemic stroke patients.

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Computed Tomography Perfusion–Based Machine Learning Model Better Predicts Follow-Up Infarction in Patients With Acute Ischemic Stroke

Stroke ◽

10.1161/strokeaha.120.030092 ◽

2021 ◽

Vol 52 (1) ◽

pp. 223-231

Author(s):

Hulin Kuang ◽

Wu Qiu ◽

Anna M. Boers ◽

Scott Brown ◽

Keith Muir ◽

...

Keyword(s):

Computed Tomography ◽

Blood Flow ◽

Cerebral Blood Flow ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Infarct Volume ◽

Interquartile Range ◽

Time Dependent ◽

Computed Tomography Perfusion

Background and Purpose: Prediction of infarct extent among patients with acute ischemic stroke using computed tomography perfusion is defined by predefined discrete computed tomography perfusion thresholds. Our objective is to develop a threshold-free computed tomography perfusion–based machine learning (ML) model to predict follow-up infarct in patients with acute ischemic stroke. Methods: Sixty-eight patients from the PRoveIT study (Measuring Collaterals With Multi-Phase CT Angiography in Patients With Ischemic Stroke) were used to derive a ML model using random forest to predict follow-up infarction voxel by voxel, and 137 patients from the HERMES study (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) were used to test the derived ML model. Average map, T max , cerebral blood flow, cerebral blood volume, and time variables including stroke onset-to-imaging and imaging-to-reperfusion time, were used as features to train the ML model. Spatial and volumetric agreement between the ML model predicted follow-up infarct and actual follow-up infarct were assessed. Relative cerebral blood flow <0.3 threshold using RAPID software and time-dependent T max thresholds were compared with the ML model. Results: In the test cohort (137 patients), median follow-up infarct volume predicted by the ML model was 30.9 mL (interquartile range, 16.4–54.3 mL), compared with a median 29.6 mL (interquartile range, 11.1–70.9 mL) of actual follow-up infarct volume. The Pearson correlation coefficient between 2 measurements was 0.80 (95% CI, 0.74–0.86, P <0.001) while the volumetric difference was −3.2 mL (interquartile range, −16.7 to 6.1 mL). Volumetric difference with the ML model was smaller versus the relative cerebral blood flow <0.3 threshold and the time-dependent T max threshold ( P <0.001). Conclusions: A ML using computed tomography perfusion data and time estimates follow-up infarction in patients with acute ischemic stroke better than current methods.

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