The association between telomere length and ischemic stroke risk and phenotype

AbstractThe chronological age of a person is a key determinant of etiology and prognosis in the setting of ischemic stroke. Telomere length, an indicator of biological aging, progressively shortens with every cell cycle. Herein, we determined telomere length from peripheral blood leukocytes by Southern blot analyses in a prospective cohort of ischemic stroke patients (n = 163) and equal number of non-stroke controls and evaluated its association with various ischemic stroke features including etiology, severity, and outcome. A shorter telomere length (i.e. lowest quartile; ≤ 5.5 kb) was significantly associated with ischemic stroke (OR 2.95, 95% CI 1.70–5.13). This significant relationship persisted for all stroke etiologies, except for other rare causes of stroke. No significant association was present between admission lesion volume and telomere length; however, patients with shorter telomeres had higher admission National Institutes of Health Stroke Scale scores when adjusted for chronological age, risk factors, etiology, and infarct volume (p = 0.046). On the other hand, chronological age, but not telomere length, was associated with unfavorable outcome (modified Rankin scale > 2) and mortality at 90 days follow-up. The association between shorter telomere length and more severe clinical phenotype at the time of admission, might reflect reduced resilience of cerebral tissue to ischemia as part of biological aging.

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Abstract WP47: Reperfusion Following Ischemic Stroke is Associated with Reduced Brain Edema

Stroke ◽

10.1161/str.48.suppl_1.wp47 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Hannah J Irvine ◽

Thomas W Battey ◽

Ann-Christin Ostwaldt ◽

Bruce C Campbell ◽

Stephen M Davis ◽

...

Keyword(s):

Ischemic Stroke ◽

Brain Edema ◽

Infarct Volume ◽

Brain Magnetic Resonance Imaging ◽

Lesion Volume ◽

Stroke Patients ◽

Early Reperfusion ◽

Echoplanar Imaging ◽

Swelling Volume

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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Dynamic Change of Eosinophil and Acute Ischemic Stroke

10.21203/rs.3.rs-38803/v1 ◽

2020 ◽

Author(s):

Huimin Zhao ◽

QinRong Xu ◽

Hongxuan Feng ◽

XiaoXia Hou ◽

ZhongMin Wen ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Eosinophil Count ◽

Infarct Volume ◽

Dynamic Change ◽

Characteristic Analysis ◽

Stroke Patients ◽

Poor Outcome ◽

Scale Scores ◽

Time Of Admission

Abstract Background: Eosinopenia has been shown to be a predicative factor for the infection and mortality in ischemic stroke patients which mainly focused on static eosinophil count. This study aimed to explore the relationship between dynamic change of eosinophil count and short-term prognosis of acute ischemic stroke (AIS).Methods: A total of 174 patients with AIS were respectively enrolled. Blood samples for blood routine examination were obtained at admission before any treatments and the next day. Eosinopenia was defined as the continuous decrease of the count of eosinophil from the first day to the second. Infarct volume was measured by diffusion-weighted MR imaging volume. 90-day modified Rankin Scale scores were collected to assess the prognosis of patients with AIS.Results: Patients were divided into two groups according to whether they have eosinopenia. Patients with eosinopenia were more likely to have large infarct volume (3.2 [0.6-39.9] cm3 vs 1.1 [0.3-6.0] cm3, P =.004). Receiver operating characteristic analysis demonstrated that the eosinophil count on the second day was more accurate than the time of admission to identify the large cerebral infarction (LCI) (0.866 vs 0.603, P ＜.001). Logistic regression analysis revealed that eosinopenia was independently associated with LCI (P =.015) and poor outcome (P =.011), and patients with eosinopenia had a 4.05-fold greater risk for LCL (95% CI 1.31-12.51) and a 4.29-fold greater risk for worse clinical outcomes (95% CI 1.27-14.51) than patients without.Conclusion： Eosinophil is a dynamic variable, and its variation is associated with poor outcome in acute ischemic stroke patients.

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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 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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Diffusion imaging of cerebral diaschisis in childhood arterial ischemic stroke

International Journal of Stroke ◽

10.1177/1747493016666089 ◽

2016 ◽

Vol 11 (9) ◽

pp. 1028-1035 ◽

Cited By ~ 10

Author(s):

Adam Kirton ◽

Elizabeth Williams ◽

Michael Dowling ◽

Sarah Mah ◽

Jacquie Hodge ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Ischemic Stroke ◽

Magnetic Resonance ◽

Diffusion Weighted Imaging ◽

Infarct Volume ◽

Resonance Imaging ◽

Arterial Ischemic Stroke ◽

Diffusion Weighted ◽

Motor Outcome

Background Diffusion-weighted imaging magnetic resonance imaging may detect changes in brain structures remote but connected to stroke consistent with neuropathological descriptions of diaschisis. Early diffusion-weighted imaging demonstrates restriction in corticospinal pathways after arterial ischemic stroke of all ages that correlates with motor outcome. Aim/hypothesis We hypothesized that cerebral diaschisis is measurable in childhood arterial ischemic stroke and explored associations with outcome. Methods This sub-study of the validation of the Pediatric NIH Stroke Scale study prospectively enrolled children with acute arterial ischemic stroke and both acute and early follow-up (5–14 days) diffusion-weighted imaging. Inclusion criteria were (1) unilateral middle cerebral artery arterial ischemic stroke, (2) acute and subacute diffusion-weighted imaging ( b = 1000), and (3) 12 month neurological follow-up (Pediatric Stroke Outcome Measure). A validated method using ImageJ software quantified diffusion-weighted imaging diaschisis in anatomically connected structures. Diaschisis measures were corrected for infarct volume, compared to age, imaging timing, and outcomes (Chi square/Fisher, Mann–Whitney test). Results Nineteen children (53% male, median 8.1 years) had magnetic resonance imaging at medians of 21 and 168 h post-stroke onset. Diaschisis was common and evolved over time, observed in one (5%) on acute but eight (42%) by follow-up diffusion-weighted imaging. Thalamic and callosal diaschisis were most common (5, 26%). Estimates of perilesional diaschisis varied (54 ± 18% of infarct volume). Children with diaschisis tended to be younger (7.02 ± 5.4 vs. 11.82 ± 4.3 years, p = 0.08). Total diaschisis score was associated with poor cognitive outcomes ( p = 0.03). Corticospinal tract diaschisis was associated with motor outcome ( p = 0.004). Method reliability was excellent. Conclusions Diffusion-weighted imaging diaschisis occurs in childhood arterial ischemic stroke. Mistaking diaschisis for new areas of infarction carries important clinical implications. Improved recognition and study are required to establish clinical relevance.

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Abstract TMP57: The Influence of Telomere Length on Ischemic Stroke Risk and Phenotype

Stroke ◽

10.1161/str.51.suppl_1.tmp57 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Ezgi Yetim ◽

Mehmet A Topcuoglu ◽

Nuket Yurur Kutlay ◽

Ajlan Tukun ◽

Kader K Oguz ◽

...

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Telomere Length ◽

Significant Relationship ◽

Stroke Risk ◽

Prior History ◽

Lesion Volume ◽

Nihss Score ◽

Stroke Etiology ◽

Age Related

Background: Telomeres are specific nucleotide repeats that play a central role in control of DNA damage related to cell division and aging. The degree of telomere shortening that occurs as part of aging is associated with age-related non-cancer diseases like hypertension, diabetes mellitus and coronary artery disease. Although a number of studies have highlighted that a similar relationship might exist with ischemic stroke, contradictory reports are also present in the literature. In this study we investigated the association between telomere length and ischemic stroke, not only in terms of stroke risk in general, but also from the perspective of stroke etiology and severity. Methods: In a Caucasian cohort, telomere length was determined by Southern blot from peripheral blood leukocytes in 163 consecutive ischemic stroke patients, and 210 controls without any prior history of ischemic stroke. Univariate and multivariate analyses were performed to determine the contribution of telomere length to stroke risk, stroke etiology, admission NIHSS score and DWI lesion volume. Results: The median (interquartile range) telomere length was 7.0 (5.5-9.0) kb in the overall population. Expectedly, telomere length was negatively correlated with aging (r=-0.23; p<0.001). A short telomere length (i.e. lowest quartile; ≤5.5 kb) was significantly associated with ischemic stroke (OR 3.0, 95%CI 1.8-5.1) when adjusted for age, gender and cardiovascular risk factors. This significant relationship persisted for all stroke etiologies, except for other rare causes of stroke. There was no significant relationship between admission lesion volume and telomere length; however, patients with short telomeres presented with more severe strokes (NIHSS score ≥16) when adjusted for age, risk factors, stroke etiology and infarct volume (OR 7.0; 95%CI 1.7-28.7). Conclusion: Almost all etiologic subtypes of ischemic stroke are related to shortened telomere length, irrespective of the age of the subject. Furthermore, presence of short telomeres negatively influences the tolerance of brain to ischemia, thereby causing more severe clinical phenotypes in these patients in the setting of ischemic stroke.

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COMPARABILITY OF BIOLOGICAL AGING MEASURES IN THE NATIONAL HEALTH AND NUTRITION EXAMINATION STUDY, 1999-2002

Innovation in Aging ◽

10.1093/geroni/igz038.1783 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S479-S479

Author(s):

Waylon J Hastings ◽

Daniel Belsky ◽

Idan Shalev

Keyword(s):

Risk Factors ◽

Telomere Length ◽

Cellular Level ◽

Biological Age ◽

Effect Sizes ◽

Chronological Age ◽

Biological Aging ◽

Patient Level ◽

Age Related ◽

Level Information

Abstract Biological processes of aging are thought to be modifiable causes of many chronic diseases. Measures of biological aging could provide sensitive endpoints for studies of risk factors hypothesized to shorten healthy lifespan and/or interventions that extend it. However, uncertainty remains about how to measure biological aging and if proposed measures assess the same thing. We tested four proposed measures of biological aging with available data from NHANES 1999-2002: Klemera-Doubal method (KDM) Biological Age, homeostatic dysregulation, Levine Method (LM) Biological Age, and leukocyte telomere length. All measures of biological aging were correlated with chronological age. KDM Biological Age, homeostatic dysregulation, and LM Biological Age were all significantly associated with each other, but were each not associated with telomere length. NHANES participants with older biological ages performed worse on tests of physical, cognitive, perceptual, and subjective functions known to decline with advancing chronological age and thought to mediate age-related disability. Further, NHANES participants with higher levels of exposure to life-course risk factors were measured as having older biological ages. In both sets of analyses, effect-sizes tended to be larger for KDM Biological Age, homeostatic dysregulation, and LM Biological Age as compared to telomere length. Composite measures combining cellular- and patient-level information tended to have the largest effect-sizes. The cellular-level aging biomarker telomere length may measure different aspects of the aging process relative to the patient-level physiological measures. Studies aiming to test if risk factors accelerate aging or if interventions may slow aging should not treat proposed measures of biological aging as interchangeable.

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Thrombolysis Outcomes in Acute Ischemic Stroke by Fluid-Attenuated Inversion Recovery Hyperintense Arteries

Stroke ◽

10.1161/strokeaha.119.028550 ◽

2020 ◽

Vol 51 (7) ◽

pp. 2240-2243

Author(s):

Zien Zhou ◽

Sohei Yoshimura ◽

Candice Delcourt ◽

Richard I. Lindley ◽

Shoujiang You ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Ischemic Stroke ◽

Magnetic Resonance ◽

Acute Ischemic Stroke ◽

Infarct Volume ◽

Inversion Recovery ◽

Modified Rankin Scale ◽

Resonance Imaging ◽

Scale Scores ◽

Fluid Attenuated Inversion Recovery

Background and Purpose: To determine factors associated with fluid-attenuated inversion recovery (FLAIR) hyperintense arteries (FLAIR-HAs) on magnetic resonance imaging and their prognostic significance in thrombolysis-treated patients with acute ischemic stroke from the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study) trial alteplase-dose arm. Methods: Patients with acute ischemic stroke (N=293) with brain magnetic resonance imaging (FLAIR and diffusion-weighted imaging sequences) scanned <4.5 hours of symptom onset were assessed for location and extent (score) of FLAIR-HAs, infarct volume, large vessel occlusion (LVO), and other ischemic signs. Logistic regression models were used to determine predictors of FLAIR-HAs and the association of FLAIR-HAs with 90-day outcomes: favorable functional outcome (primary; modified Rankin Scale scores, 0–1), other modified Rankin Scale scores, and intracerebral hemorrhage. Results: Prior atrial fibrillation, LVO, large infarct volume, and anterior circulation infarction were independently associated with FLAIR-HAs. The rate of modified Rankin Scale scores 0 to 1 was numerically lower in patients with FLAIR-HAs versus without (69/152 [45.4%] versus 75/131 [57.3%]), as was the subset of LVO (37/93 [39.8%] versus 9/16 [56.3%]), but not in those without LVO (25/36 [69.4%] versus 60/106 [56.6%]). After adjustment for covariables, FLAIR-HAs were independently associated with increased primary outcome (adjusted odds ratio [95% CI]: overall 4.14 [1.63–10.50]; with LVO 4.92 [0.87–27.86]; no LVO 6.16 [1.57–24.14]) despite an increased risk of hemorrhagic infarct (4.77 [1.12–20.26]). Conclusions: FLAIR-HAs are more frequent in acute ischemic stroke with cardioembolic features and indicate potential for a favorable prognosis in thrombolysis-treated patients possibly mediated by LVO. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01422616.

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The Safety and Feasibility of Mechanical Thrombectomy for Mild Acute Ischemic Stroke With Large Vessel Occlusion

Neurosurgery ◽

10.1093/neuros/nyz354 ◽

2019 ◽

Vol 86 (6) ◽

pp. 802-807 ◽

Cited By ~ 1

Author(s):

Gabor Toth ◽

Santiago Ortega-Gutierrez ◽

Jenny P Tsai ◽

Russell Cerejo ◽

Sami Al Kasab ◽

...

Keyword(s):

Ischemic Stroke ◽

Mechanical Thrombectomy ◽

Infarct Volume ◽

Invasive Procedure ◽

Large Vessel ◽

Large Vessel Occlusion ◽

Vessel Occlusion ◽

Symptomatic Intracerebral Hemorrhage ◽

Significant Difference

Abstract BACKGROUND Prospective evidence to support mechanical thrombectomy (MT) for mild ischemic stroke with large vessel occlusion (LVO) is lacking. There is uncertainty about using an invasive procedure in patients with mild symptoms. OBJECTIVE To evaluate the safety and feasibility of MT in patients with mild symptoms and LVO. METHODS Our single-arm prospective pilot study recruited patients with LVO and initial National Institute of Health Stroke Scale (NIHSS) <6, who underwent standard MT. Primary safety endpoints were symptomatic intracerebral hemorrhage (sICH), and/or worsening NIHSS by ≥4 points. Secondary endpoints included angiographic recanalization, NIHSS change, final infarct volume, and modified Rankin score (mRS). RESULTS We enrolled 20 patients (mean age 65.6 ± 12.3 yr; 45% females). Thrombolysis in Cerebral Ischemia 2B/3 thrombectomy was achieved in 95%. No patients suffered sICH. One patient (5%) had neurologic worsening within 24 h because of underlying intracranial stenosis. No other complications or safety concerns were identified. Median NIHSS was significantly better at discharge (0.5, P = .007) and at last follow-up (0, P < .001) than before treatment (3). Mean post vs preintervention infarct volumes were small without significant difference (1.2 ml, P = .434). Most patients (85%) were discharged directly home. Excellent clinical outcome (mRS 0-1) at last follow-up was seen in 95% of patients. CONCLUSION This is one of the first specifically designed prospective studies showing that MT is safe and feasible in patients with low NIHSS and LVO. Chronic underlying vasculopathy may be a challenging dilemma. We observed excellent clinical and radiographic outcomes, but randomized controlled trials are needed to demonstrate the efficacy of MT in this unique cohort.

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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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