Does variability in automated perfusion software outputs for acute ischemic stroke matter? Reanalysis of EXTEND perfusion imaging

Aims We reprocessed the Extending the time for Thrombolysis in Emergency Neurological Deficits (EXTEND) perfusion imaging with a different automated software with the aim of comparing mismatch eligibility and outcomes. Methods EXTEND baseline perfusion imaging data were reprocessed using autoMIStar software to identify patients who were eligible based on the same target mismatch criteria as per the original trial. Results From the 225 patients fulfilling RAPID-based mismatch criteria randomized in the EXTEND study, 196 (87%) patients met the revised mismatch criteria. Most common reasons for not meeting revised criteria were core >70 ml (n = 9), and no perfusion lesion/lack of penumbral tissue (n = 20). The revised perfusion lesion volumes were significantly smaller compared to the original RAPID volumes (median 68 ml IQR 34-102 ml vs. 42 ml 16-92 ml, p = 0.036). Of the patients who met the revised mismatch criteria, 40% receiving alteplase had modified Rankin Scale (mRS) 0-1 at 3-month compared to 28% with placebo (Adjusted Odds Ratio (OR) = 2.23, CI 1.08-4.58, p = 0.028). In contrast, in the original mismatch cohort, 35% receiving alteplase had mRS 0-1 at 3-month compared to 30% with placebo (adjusted OR = 1.88, p = 0.056). Conclusions These data reinforce the benefit of alteplase in the later time window, and suggest that differences in automated perfusion imaging software outputs may be clinically relevant.Peer reviewe

Comparing mismatch strategies for patients being considered for ischemic stroke tenecteplase trials

Background: Currently there are multiple variations of imaging-based patient selection mismatch methods in ischemic stroke. In the present study, we sought to compare the two most common mismatch methods and identify if there were different effects on the outcome of a randomized clinical trial depending on the mismatch method used. Aims: Investigate the effect of clinical and imaging-based mismatch criteria on patient outcomes of a pooled cohort from randomized trials of intravenous tenecteplase versus alteplase. Methods: Baseline clinical and imaging scores were used to categorize patients as meeting either the DAWN mismatch (baseline NIHSS ≥ 10, and age cut-offs for ischemic core volume) or DEFUSE 2 mismatch criteria (mismatch volume > 15 mL, mismatch ratio > 1.8 and ischemic core < 70 mL). We then investigated whether tenecteplase-treated patients had favorable odds of less disability (on modified Rankin scale, mRS) compared to those treated with alteplase, for clinical and imaging mismatch, respectively. Results: From 146 pooled patients, 71 received alteplase and 75 received tenecteplase. The overall pooled group did not show improved patient outcomes when treated with tenecteplase (mRS 0-1 OR 1.77, 95% CI 0.89–3.51, p = 0.102) compared with alteplase. A total of 39 (27%) patients met both clinical and imaging mismatch criteria, 25 (17%) patients met only imaging criteria, 36 (25%) met only clinical mismatch criteria and, finally, 46 (31%) did not meet either of imaging or mismatch criteria. Patients treated with tenecteplase had more favorable outcomes when they met either imaging mismatch (mRS 0–1, OR 2.33, 95% CI 1.13–5.94, p = 0.032) or clinical mismatch criteria (mRS 0–1, OR 2.15, 95% CI 1.142, 8.732, p = 0.027) but with differing proportions. Conclusion: Target mismatch selection was more inclusive and exhibited in a larger treatment effect between tenecteplase and alteplase

Thresholds for infarction vary between gray matter and white matter in acute ischemic stroke : a CT perfusion study

We aimed to investigate optimal perfusion thresholds defining ischemic core and penumbra for hemispheric-cortical gray matter (GM) and subcortical white matter (WM). A total of 65 sub-6 h ischemic stroke patients were assessed, who underwent acute computed tomography perfusion (CTP) and acute magnetic resonance imaging. CTP maps were generated by both standard singular value deconvolution (sSVD) and SVD with delay and dispersion correction (ddSVD). Analyses were undertaken to calculate sensitivity, specificity, and area under the curve (AUC) for each CTP threshold for core and penumbra in GM and WM. With sSVD, the core was best defined in GM by cerebral blood flow (CBF) < 30% (AUC: 0.73) and in WM by CBF < 20% (AUC: 0.67). With ddSVD, GM core was best defined by CBF < 35% (AUC: 0.75) and in WM by CBF < 25% (AUC: 0.68). A combined GM/WM threshold overestimated core compared to diffusion-weighted imaging, CBF < 25% from sSVD (1.88 ml, P = 0.007) and CBF < 30% from ddSVD (1.27 ml, P = 0.011). The perfusion lesion was best defined by T max > 5 s (AUC: 0.80) in GM and T max > 7 s (AUC: 0.75) in WM. With sSVD, a delay time (DT) > 3 s from ddSVD was the optimal for both GM (AUC: 0.78) and WM (AUC: 0.75). Using tissue-specific thresholds for GM/WM provides more accurate estimation of acute ischemic core

Association of collateral status and ischemic core growth in patients with acute ischemic stroke

OBJECTIVE: To test the hypothesis that patients with acute ischemic stroke with poorer collaterals would have faster ischemic core growth, we included 2 cohorts in the study: cohort 1 of 342 patients for derivation and cohort 2 of 414 patients for validation. METHODS: Patients with acute ischemic stroke with large vessel occlusion were included. Core growth rate was calculated by the following equation: core growth rate = acute core volume on CT perfusion (CTP)/time from stroke onset to CTP. Collateral status was assessed by the ratio of severe hypoperfusion volume within the hypoperfusion region of CTP. The CTP collateral index was categorized in tertiles; for each tertile, core growth rate was summarized as median and interquartile range. Simple linear regressions were then performed to measure the predictive power of CTP collateral index in core growth rate. RESULTS: For patients allocated to good collateral on CTP (tertile 1 of collateral index), moderate collateral (tertile 2), and poor collateral (tertile 3), the median core growth rate was 2.93 mL/h (1.10-7.94), 8.65 mL/h (4.53-18.13), and 25.41 mL/h (12.83-45.07), respectively. Increments in the collateral index by 1% resulted in an increase of core growth by 0.57 mL/h (coefficient 0.57, 95% confidence interval [0.46, 0.68], p < 0.001). The relationship of core growth and CTP collateral index was validated in cohort 2. An increment in collateral index by 1% resulted in an increase of core growth by 0.59 mL/h (coefficient 0.59 [0.48-0.71], p < 0.001) in cohort 2. CONCLUSION: Collateral status is a major determinant of ischemic core growth

Endovascular Thrombectomy versus Medical Management in Isolated M2 Occlusions: Pooled Patient-Level Analysis from the EXTEND-IA Trials, INSPIRE and SELECT Studies

Objective: To evaluate functional and safety outcomes of Endovascular thrombectomy(EVT) vs 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-IA-TNK part 1&2) and 2 prospective non-randomized studies(INSPIRE&SELECT), we evaluated EVT association with 90-day functional independence(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, MM=322), baseline median(IQR) NIHSS was 13(8-19) in EVT vs 10(6-15) in MM, p Interpretation: In patients with M2 occlusion, EVT was associated with improved clinical outcomes when compared to medical management. This association was primarily observed in patients with a mismatch profile and those with higher stroke severity. This article is protected by copyright. All rights reserved

Exploring the relationship between ischemic core volume and clinical outcomes after thrombectomy or thrombolysis

ObjectiveTo assess whether complete reperfusion after IV thrombolysis (IVT-R) would result in similar clinical outcomes compared to complete reperfusion after endovascular thrombectomy (EVT-R) in patients with a large vessel occlusion (LVO).MethodsEVT-R patients were matched by age, clinical severity, occlusion location, and baseline perfusion lesion volume to IVT-R patients from the International Stroke Perfusion Imaging Registry (INSPIRE). Only patients with complete reperfusion on follow-up imaging were included. The excellent clinical outcome rates at day 90 on the modified Rankin Scale (mRS) were compared between EVT-R vs IVT-R patients within quintiles of increasing baseline ischemic core and penumbral volumes.ResultsFrom INSPIRE, there were 141 EVT-R patients and 141 matched controls (IVT-R) who met the eligibility criteria. In patients with a baseline core 30 mL (internal carotid artery and mostly proximal M1 occlusions), EVT-R increased the odds of patients achieving an excellent clinical outcome (day 90 mRS 0-1 odds ratio 1.61, p 30 mL (20% vs 3% in EVT-R, p = 0.008).ConclusionFrom this observational cohort, LVO patients with larger baseline ischemic cores and proximal LVO, with poorer collaterals, clearly benefited from EVT-R compared to IVT-R alone. However, for distal LVO patients, with smaller ischemic cores and better collaterals, EVT-R was associated with a lower odds of favorable outcome compared to IVT-R alone

Influence of penumbral reperfusion on clinical outcome depends on baseline ischemic core volume

Background and Purpose: In alteplase-treated patients with acute ischemic stroke, we investigated the relationship between penumbral reperfusion at 24 hours and clinical outcomes, with and without adjustment for baseline ischemic core volume. Methods: Data were collected from consecutive acute ischemic stroke patients with baseline and follow-up perfusion imaging presenting to hospital within 4.5 hours of symptom onset at 7 hospitals. Logistic regression models were used for predicting the effect of the reperfused penumbral volume on the dichotomized modified Rankin Scale (MRS) at 90 days and improvement of National Institutes of Health Stroke Scale at 24 hours, both adjusted for baseline ischemic core volume. Results: This study included 1507 patients. Reperfused penumbral volume had moderate ability to predict 90-day MRS 0 to 1 (area under the curve, 0.77; R2, 0.28; P&lt;0.0001). However, after adjusting for baseline ischemic core volume, the reperfused penumbral volume was a strong predictor of good functional outcome (area under the curve, 0.946; R2, 0.55; P&lt;0.0001). For every 1% increase in penumbral reperfusion, the odds of achieving MRS 0 to 1 at day 90 increased by 7.4%. Improvement in acute 24-hour National Institutes of Health Stroke Scale was also significantly related to the degree of reperfused penumbra (R2, 0.31; P&lt;0.0001). This association was again stronger after adjustment for baseline ischemic core volume (R2, 0.41; P&lt;0.0001). For each 1% of penumbra that was reperfused, the 24-hour National Institutes of Health Stroke Scale decreased by 0.069 compared with baseline. Conclusions: In patients treated with alteplase, the extent of the penumbra that is reperfused is a powerful predictor of early and late clinical outcomes, particularly when baseline ischemic core is taken into account. © 2017 American Heart Association, Inc

Stroke patients with faster core growth have greater benefit from endovascular therapy

BACKGROUND AND PURPOSE: This study aimed to explore whether the therapeutic benefit of endovascular thrombectomy (EVT) was mediated by core growth rate. METHODS: This retrospective cohort study identified acute ischemic stroke patients with large vessel occlusion and receiving reperfusion treatment, either EVT or intravenous thrombolysis (IVT), within 4.5 hours of stroke onset. Patients were divided into 2 groups: EVT versus IVT only patients (who had no access to EVT). Core growth rate was estimated by the acute core volume on perfusion computed tomography divided by the time from stroke onset to perfusion computed tomography. The primary clinical outcome was good outcome defined by 3-month modified Rankin Scale score of 0–2. Tissue outcome was the final infarction volume. RESULTS: A total of 806 patients were included, 429 in the EVT group (recanalization rate of 61.6%) and 377 in the IVT only group (recanalization rate of 44.7%). The treatment effect of EVT versus IVT only was mediated by core growth rate, showing a significant interaction between EVT treatment and core growth rate in predicting good clinical outcome (interaction odds ratio=1.03 [1.01–1.05], P=0.007) and final infarct volume (interaction odds ratio=-0.44 [-0.87 to -0.01], P=0.047). For patients with fast core growth of >25 mL/h, EVT treatment (compared with IVT only) increased the odds of good clinical outcome (adjusted odds ratio=3.62 [1.21–10.76], P=0.021) and resulted in smaller final infarction volume (37.5 versus 73.9 mL, P=0.012). For patients with slow core growth of <15 mL/h, there were no significant differences between the EVT and the IVT only group in either good clinical outcome (adjusted odds ratio=1.44 [0.97–2.14], P=0.070) or final infarction volume (22.6 versus 21.9 mL, P=0.551). CONCLUSIONS: Fast core growth was associated with greater benefit from EVT compared with IVT in the early <4.5-hour time window

Table_5_Intravenous Thrombolysis May Not Improve Clinical Outcome of Acute Ischemic Stroke Patients Without a Baseline Vessel Occlusion.docx

<p>Background and Purpose: The benefit of thrombolysis in ischemic stroke patients without a visible vessel occlusion still requires investigation. This study tested the hypothesis that non-lacunar stroke patients with no visible vessel occlusion on baseline imaging would have a favorable outcome regardless of treatment with alteplase.</p><p>Methods: We utilized a prospectively collected registry of ischemic stroke patients [the International Stroke Perfusion Imaging Registry (INSPIRE)] who had baseline computed tomographic perfusion and computed tomographic angiography. The rates of patients achieving modified Rankin Scale (mRS) 0–1 were compared between alteplase treated and untreated patients using logistic regression to generate odds ratios.</p><p>Results: Of 1569 patients in the INSPIRE registry, 1,277 were eligible for inclusion. Of these, 306 (24%) had no identifiable occlusion and were eligible for alteplase, with 141 (46%) of these patients receiving thrombolysis. The treated and untreated groups had significantly different median baseline National Institutes of Health Stroke Scale (NIHSS) [alteplase 8, interquartile range (IQR) 5–10, untreated 6, IQR 4–8, P < 0.001] and median volume of baseline perfusion lesion [alteplase 5.6 mL, IQR 1.3–17.7 mL, untreated 2.6 mL, IQR 0–6.7 mL, P < 0.001]. After propensity analysis, alteplase treated patients without a vessel occlusion were less likely to have an excellent outcome (mRS 0–1; 56%) than untreated (78.8%, OR, 0.42, 95% confidence interval, 0.24–0.75, P = 0.003).</p><p>Conclusions: In this non-randomized comparison, alteplase treatment in patients without an identifiable vessel occlusion did not result in higher rates of favorable outcome compared to untreated. However, treated patients displayed less favorable baseline prognostic factors than the untreated group. Further studies may be required to confirm this data.</p

Table_4_Intravenous Thrombolysis May Not Improve Clinical Outcome of Acute Ischemic Stroke Patients Without a Baseline Vessel Occlusion.DOCX

<p>Background and Purpose: The benefit of thrombolysis in ischemic stroke patients without a visible vessel occlusion still requires investigation. This study tested the hypothesis that non-lacunar stroke patients with no visible vessel occlusion on baseline imaging would have a favorable outcome regardless of treatment with alteplase.</p><p>Methods: We utilized a prospectively collected registry of ischemic stroke patients [the International Stroke Perfusion Imaging Registry (INSPIRE)] who had baseline computed tomographic perfusion and computed tomographic angiography. The rates of patients achieving modified Rankin Scale (mRS) 0–1 were compared between alteplase treated and untreated patients using logistic regression to generate odds ratios.</p><p>Results: Of 1569 patients in the INSPIRE registry, 1,277 were eligible for inclusion. Of these, 306 (24%) had no identifiable occlusion and were eligible for alteplase, with 141 (46%) of these patients receiving thrombolysis. The treated and untreated groups had significantly different median baseline National Institutes of Health Stroke Scale (NIHSS) [alteplase 8, interquartile range (IQR) 5–10, untreated 6, IQR 4–8, P < 0.001] and median volume of baseline perfusion lesion [alteplase 5.6 mL, IQR 1.3–17.7 mL, untreated 2.6 mL, IQR 0–6.7 mL, P < 0.001]. After propensity analysis, alteplase treated patients without a vessel occlusion were less likely to have an excellent outcome (mRS 0–1; 56%) than untreated (78.8%, OR, 0.42, 95% confidence interval, 0.24–0.75, P = 0.003).</p><p>Conclusions: In this non-randomized comparison, alteplase treatment in patients without an identifiable vessel occlusion did not result in higher rates of favorable outcome compared to untreated. However, treated patients displayed less favorable baseline prognostic factors than the untreated group. Further studies may be required to confirm this data.</p