Baseline Ischemic Core Volume Research Articles

Abstract WP56: The Hypoperfusion Intensity Ratio is a Poor Discriminator of Infarct Growth in Fully Reperfused Patients

Background and Purpose: The hypoperfusion intensity ratio (HIR) is a perfusion-weighted imaging parameter defined as the ratio of Tmax>10 seconds : Tmax>6 seconds volume and is believed to be reflective of collateral strength and consequently influence infarct growth. We sought to assess the utility of the HIR in predicting infarct growth in patients undergoing thrombectomy at a comprehensive stroke center (CSC). Methods: Consecutive acute ischemic stroke patients transferred to our CSC from 09/2010-11/2018 were identified and included if the following criteria were met: 1)computed tomography perfusion (CTP) imaging enabling assessment of baseline ischemic core volume and HIR 2) follow-up neuroimaging for assessment of final infarct volumes and 3)modified Thrombolysis In Cerebral Infarction scale (mTICI) 2c status or greater post-thrombectomy. Infarct growth rate (IGR) was calculated as the difference between infarct volume on follow-up imaging and the acute DWI lesion volume, divided by time from CTP to reperfusion in hours. Results: 461 patients (median age, 64 [55-75] years, median baseline NIHSS, 16 [12-21]) were eligible for this analysis. HIR poorly correlated with IGR (Spearman’s rho=0.001, p=0.89). An HIR cut-off of 0.5 was not able to discriminate ‘fast progressors’ (IGR>5 mL/hr) (AUC 0.42, sensitivity 40%, specificity 51%), or IGR at thresholds of either 2.5 or 10 mL/hr (AUC 0.44 and 0.49 respectively, with 95% confidence intervals [0.35-0.52] and [0.41-0.57], respectively). Similarly, an HIR of 0.5 only weakly distinguished ‘fast progression’ in patients reperfused beyond 120 min from imaging and patients with early CTP (last known well to CTP<6 hrs) (AUC 0.59, sensitivity 43%, specificity 68% and AUC 0.50, sensitivity 45%, specificity 55%). On multiple regression analysis, HIR was not predictive of infarct growth (regression equation=18.09+8.48x, F=2.46, p=0.11, R 2 =0.13) but was predictive of ‘fast progression’ (OR 0.22, 95% CI [0.09-0.60], p=0.003, pseudo-R 2 =0.16). Conclusions: Though predictive of fast progression, the HIR is a poor discriminator of infarct growth in successfully reperfused thrombectomy patients who undergo perfusion imaging at a CSC, and thus should not be factored into treatment decision-making.

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

To 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). EVT-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. From 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, EVT-R resulted in a lower odds of achieving an excellent outcome at day 90 compared to IVT-R (day 90 mRS 0-1 odds ratio 0.01, p < 0.001). The group with a baseline core <30 mL contained mostly patients with distal M1 or M2 occlusions, and good collaterals (p = 0.01). In patients with a baseline ischemic core volume >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 < 0.001) and there was increased symptomatic intracranial hemorrhage in the IVT-R group with core >30 mL (20% vs 3% in EVT-R, p = 0.008). From 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.

Ischemic Core and Hypoperfusion Volumes Correlate With Infarct Size 24 Hours After Randomization in DEFUSE 3.

Background and Purpose- Accurate prediction of the subsequent infarct volume early after stroke onset helps determine appropriate interventions and prognosis. In the DEFUSE 3 trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke), we evaluated the accuracy of baseline ischemic core and hypoperfusion volumes for predicting infarct volume 24 hours after randomization to endovascular thrombectomy versus medical management. We also assessed if the union of baseline ischemic core and the volume of persistent hypoperfusion at 24 hours after randomization predicts infarct volume. Methods- Patients in DEFUSE 3 with computed tomography perfusion imaging or magnetic resonance diffusion weighted imaging/perfusion imaging acquired at baseline and at 24 hours after randomization were included. Ischemic core and Tmax >6s hypoperfusion volumes at baseline and follow-up were calculated using RAPID software and compared with the infarct volumes obtained 24 hours after randomization. Patients were stratified by reperfusion status for analyses. Results- Of 125 eligible patients, 59 patients with >90% reperfusion had a strong correlation between baseline ischemic core volume and infarct volume 24 hours postrandomization ( r=0.83; P<0.0001), and 14 patients with <10% reperfusion had a strong correlation between baseline Tmax >6s volume and infarct volume 24 hours postrandomization ( r=0.77; P<0.001). In the 52 patients with 10% to 90% reperfusion, as well as in all 125 patients, the union of the baseline ischemic core and the follow-up Tmax >6s perfusion volume was highly correlated with infarct volume 24 hours postrandomization (for N=125; r=0.83; P<0.0001), with a median absolute difference of 21.3 mL between observed and predicted infarct volumes. Conclusions- The union of the irreversibly injured ischemic core and persistently hypoperfused tissue volumes, as identified by computed tomography perfusion or magnetic resonance diffusion weighted imaging/perfusion, predicted infarct volume at 24 hours after randomization in DEFUSE 3 patients. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02586415.

Results From DEFUSE 3: Good Collaterals Are Associated With Reduced Ischemic Core Growth but Not Neurologic Outcome

Background and Purpose- The effect of leptomeningeal collaterals for acute ischemic stroke patients with large vessel occlusion in the late window (>6 hours from last known normal) remains unknown. We sought to determine if collateral status on baseline computed tomography angiography impacted neurological outcome, ischemic core growth, and moderated the effect of endovascular thrombectomy in the late window. Methods- This is a prespecified analysis of DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke). We included patients with computed tomography angiography as their baseline imaging and rated collateral status using the validated scales described by Tan and Maas. The primary outcome is functional independence (modified Rankin Scale score of ≤2). Additional outcomes include the full range of the modified Rankin Scale, baseline ischemic core volume, change from baseline in the ischemic core volume at 24 hours, and death at 90 days. Results- Of the 130 patients in our cohort, 33 (25%) had poor collaterals and 97 (75%) had good collaterals. There was no difference in the rate of functional independence with good versus poor collaterals in unadjusted analysis (30% versus 39%; P=0.3) or after adjustment for treatment arm (odds ratio [95% CI], 0.61 [0.26-1.45]). Good collaterals were associated with significantly smaller ischemic core volume and less ischemic core growth. The difference in the treatment effect of endovascular thrombectomy was not significant ( P=0.8). Collateral status also did not affect the rate of stroke-related death (n [%], good versus poor collaterals, 18/97 [19%] versus 8/33 [24%], P=0.5]. Conclusions- In DEFUSE 3 patients, good leptomeningeal collaterals on single phase computed tomography angiography were not predictive of functional independence or death and did not impact the treatment effect of endovascular thrombectomy. These unexpected findings require further study to confirm their validity and to better understand the role of collaterals for stroke patients with anterior circulation large vessel occlusion in the late therapeutic window. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02586415.

Abstract WP61: Union of Ischemic Core and Hypoperfusion Volume Correlates With 24-hour Infarct Size in DEFUSE 3

Background and Purpose: Accurate prediction of 24-hour infarct volume early after stroke onset helps determine appropriate interventions and prognosis. In the Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke (DEFUSE 3) trial, we evaluated the accuracy of early ischemic core and hypoperfusion volumes for predicting infarct volume 24 hours after randomization to endovascular thrombectomy vs. medical management. We also assessed if the volume of persistent hypoperfusion at 24 hours predicts infarct volume. Methods: Patients in DEFUSE 3 with CT or MRI DWI/perfusion imaging acquired at baseline and at 24 hours after randomization were included. Ischemic core and Tmax&gt;6s hypoperfusion volumes at baseline and 24 hours were calculated using RAPID software and compared with the 24-hour infarct volumes. Patients were stratified by reperfusion status for analyses. Results: Of 125 eligible patients, 59 patients with &gt;90% reperfusion had a strong correlation between baseline ischemic core volumes and 24-hour infarct volume (r = 0.83; p &lt; 0.0001), and 14 patients with &lt;10% reperfusion had a strong correlation between baseline Tmax&gt;6s volume and 24-hour infarct volume (r = 0.77; p &lt; 0.001). In the 52 patients with 10-90% reperfusion, as well as in all 125 patients, the union of the baseline ischemic core and the Tmax&gt;6s perfusion volume at 24 hours was highly correlated with 24-hour infarct volume (for N=125, r = 0.83; p &lt; 0.0001), with a median absolute difference of 21.3 ml between observed and predicted infarct volumes. Conclusions: The union of the irreversibly injured ischemic core and critically hypoperfused tissue volumes, as identified by CT perfusion or MR DWI/perfusion, predicted infarct volume at 24 hours in DEFUSE 3 patients. Clinical Trial Registration - URL: http://www.clinicaltrials.gov. Unique identifier: NCT02586415

Abstract TP66: Optimizing CT Perfusion Thresholds for Identification of Ischemic Core in Hyperacute Stroke

Objective: CT perfusion (CTP) estimates of infarct core are typically based on identifying regions of very low CBF (typically &lt;30% of normal). These thresholds were optimized in patient populations that typically did not include patients scanned in the hyper-acute phase (&lt; 60 minutes from stroke onset). Our aim was to determine if these thresholds apply to the hyper-acute phase. Methods: We conducted a retrospective review (2012 to 2017) of patients who met the following inclusion criteria: acute ischemic stroke due to an ICA or M1 occlusion, baseline CTP core (rCBF &lt;30%) &gt;20ml, and underwent endovascular therapy with TICI2b/3 reperfusion. Baseline ischemic core volumes were compared to final infarct volumes, measured on follow-up CT or MRI obtained &gt;24 hours after stroke onset. Results: In 7 of 21 included patients, the ischemic core assessed on baseline CTP overestimated the final infarct by at least 10 ml. Five of these patients had witnessed onset and two were unwitnessed. The mean time from stroke onset to CTP was 0.96 hours for the seven patients with core overestimation and 3.4 hours in the 14 patients without core overcall. 6 of the 7 patients with core overcall had good outcomes (mRS of 0 to 2 at 90 days) compared to 4/14 without core overcall (p-value 0.01). For patients with core overcall, 2 additional CTP thresholds (rCBF &lt;20% and &lt;15%) were assessed. rCBF&lt;20% produced core volume estimates that most closely matched the final infarct volume and did not overcall the final infarct volume. The median difference between baseline core and final infarct volume with the &lt;20% threshold was 27 ml compared to 35 ml with &lt;30%. Conclusion: A rCBF threshold of &lt;30% tends to overestimate the ischemic core in patients imaged within 60 minutes of symptom onset. A threshold of &lt;20% may be more appropriate for patients imaged in the hyper-acute phase of stroke.

Abstract 159: Baseline Perfusion Imaging Collateral Scores Predict Infarct Growth in DEFUSE 3

Background: High relative cerebral blood volume (rCBV) within the ischemic lesion and a low hypoperfusion intensity ratio (HIR) predict good collateral vessel status and correlate with infarct growth and functional outcome in early window patients with large vessel anterior circulation occlusions. Their performance in predicting clinical and radiologic outcome has not been assessed in late presenting patients. We hypothesized that favorable baseline HIR and rCBV profiles would predict less infarct growth at 24 hours in late presenting (6-16h), non-reperfused patients in DEFUSE 3. Methods: Non-reperfused patients in both arms of DEFUSE 3 were included. Baseline ischemic core, Tmax &gt;6s, and Tmax &gt;10s perfusion lesion volumes were calculated with RAPID software; 24h infarct volumes were manually determined from DWI or CT. Substantial infarct growth was defined as a &gt;25mL increase between baseline ischemic core and 24h infarct volume. HIR was defined as the proportion of the Tmax &gt;6s lesion with Tmax &gt;10s delay; rCBV was calculated by RAPID from the mean CBV values within the Tmax &gt;6s lesion compared to regions of normal CBV. Functional independence was defined as a modified Rankin score of 0-2. Results: Eighty-four patients with baseline perfusion imaging were included. ROC analysis showed that HIR &gt;0.34 (AUC=0.68) and rCBV &lt;0.74 (AUC=0.72) optimally predicted substantial infarct growth at 24h. Median growth was 23.4 versus 73.2mL with the HIR threshold of 0.34 (p=0.005), and 24.3 versus 58.7mL with the rCBV threshold of 0.74 (p=0.004). If baseline HIR and rCBV were both favorable, median growth was 21.7mL, 40.9mL if one was favorable, and 108.2mL if both were unfavorable (p=&lt;0.001). Baseline HIR and rCBV were not associated with functional outcome at 90 days, though baseline Tmax &gt;10s volume was significantly smaller in functionally independent patients (p=0.04). Conclusion: Perfusion collateral scores (HIR and rCBV) forecast infarct growth in late presenting, non-reperfused ischemic stroke patients. These parameters may be useful for guiding transfer decisions, such as need for repeat imaging on arrival to a thrombectomy center, and may help identify slow progressing patients more likely to have persistent salvageable ischemic tissue beyond 24 hours.

Influence of Penumbral Reperfusion on Clinical Outcome Depends on Baseline Ischemic Core Volume.

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. 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. 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<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<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<0.0001). This association was again stronger after adjustment for baseline ischemic core volume (R2, 0.41; P<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. 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.

Abstract WP248: Pre-treatment Perfusion CT in Stroke Thrombolysis Can Predict Disability-free Life

Introduction: Stroke shortens an individual’s disability-free life. We aimed to assess the relative prognostic influence of pre- and post-treatment perfusion CT imaging variables (e.g. ischemic core and penumbral volumes) compared to standard clinical predictors (such as onset-to-treatment time) on long-term stroke disability in patients undergoing thrombolysis. Methods: We used data from a prospectively collected international, multicenter, observational registry of acute ischemic stroke patients who had perfusion CT and CT angiography before treatment with intravenous alteplase. Baseline perfusion CT and follow-up MRI were analysed to derive the baseline penumbra volume, baseline ischemic core volume, and penumbra salvaged from infarction. The primary outcome measure was the effect of imaging and clinical variables on disability-adjusted life years (DALY). Clinical variables were age, sex, NIHSS score, and onset-to-treatment time. Age, sex, country, and 3-month modified Rankin Scale were extracted from the registry to calculate DALY due to stroke, such that one year of DALY equates to 1 year of healthy life lost due to stroke. Results: Seven hundred seventy two patients were treated with alteplase therapy. 17.5 DALY-days were lost per 1 mL of baseline ischemic core volume (95%CI, 13.2 - 21.9 days, p &lt; 0.001). For every mL of penumbra salvaged, 7.2 days of DALY-days were saved (95%CI, 4.1 - 10.4 days, p &lt; 0.001). Each minute of earlier onset-to-treatment time resulted in a saving of 4.4 disability-free days after stroke (1.3 - 7.5 days, p = 0.006). However, after adjustment for imaging variables, onset-to-treatment time was not significantly associated with savings in DALY-days. Conclusions: Pre-treatment perfusion CT scan defined penumbra (independently of clinical variables) predict significant gains, or loss, of disability-free life in patients undergoing reperfusion therapy for stroke. The effect of earlier treatment on disability-free life appears explained by salvage of penumbra.

Abstract 31: The Association Between Baseline Ischemic Core Volume and Benefit of Endovascular Thrombectomy in Pooled Data from Six Randomized Trials

Background and purpose: Patients estimated to have a large irreversibly injured ischemic core are sometimes excluded from reperfusion therapies. We examined the association between estimated core volume and thrombectomy outcomes. Methods: Patient-level CT perfusion (CTP) and clinical data were pooled from trials comparing endovascular thrombectomy with standard care in anterior circulation ischemic stroke: MR CLEAN, EXTEND IA, ESCAPE, SWIFT PRIME, REVASCAT and PISTE. Ischemic core volume was estimated using relative cerebral blood flow &lt;30% of normal brain (RAPID automated software, IschemaView). The primary outcome was the 90 day modified Rankin scale (mRS), adjusted for baseline prognostic variables. To account for between-trial variance we used mixed-effects modeling with a random effect for trial incorporated in all models. Results: Of 1352 patients, pre-treatment CTP was assessable in 539 after exclusion of 27 patients (12 severe motion, 2 no lesion within coverage, 2 contrast bolus failure, 11 data corruption during transfer from site). There were 264 allocated to endovascular thrombectomy and 275 to control. Baseline characteristics were similar between endovascular and control patients with CTP, median core 9.6 mL (IQR 2.4-26 mL) and with the overall trial demographics. Larger estimated core volume was associated with lower probability of independent outcome (mRS 0-2) in endovascular (OR 0.87 95%CI 0.80-0.95) and control patients (OR 0.85 95%CI 0.77-0.93, core*treatment interaction p=0.62) and increased disability: utility scores derived from mRS reduced by 2% (95%CI 1-4%) per 10mL increase in core volume for both endovascular and control patients (core*treatment interaction p=0.79). However, patients with &gt;70mL core (median 100 mL, IQR 82-144mL) still benefitted from thrombectomy: ordinal mRS cOR 7.0 (2.6 -18.9) and the number needed to treat (NNT) remained stable across the spectrum of core volumes (point estimate NNT&lt;10 for mRS 0-2 and NNT&lt;3 for improvement in at least 1 mRS level). Conclusions: Increasing estimated core volume was independently associated with worse outcome but endovascular thrombectomy remained effective versus standard care even in patients with large core who otherwise met eligibility for these trials.

Endovascular Treatment for Patients With Acute Stroke Who Have a Large Ischemic Core and Large Mismatch Imaging Profile

Endovascular therapy (ET) is typically not considered for patients with large baseline ischemic cores (irreversibly injured tissue). Computed tomographic perfusion (CTP) imaging may identify a subset of patients with large ischemic cores who remain at risk for significant infarct expansion and thus could still benefit from reperfusion to reduce their degree of disability. To compare the outcomes of patients with large baseline ischemic cores on CTP undergoing ET with the outcomes of matched controls who had medical care alone. A matched case-control study of patients with proximal occlusion after stroke (intracranial internal carotid artery and/or middle cerebral artery M1 and/or M2) on computed tomographic angiography and baseline ischemic core greater than 50 mL on CTP at a tertiary care center from May 1, 2011, through October 31, 2015. Patients receiving ET and controls receiving medical treatment alone were matched for age, baseline ischemic core volume on CTP, and glucose levels. Baseline characteristics and outcomes were compared. The primary outcome measure was the shift in the degree of disability among the treatment and control groups as measured by the modified Rankin Scale (mRS) (with scores ranging from 0 [fully independent] to 6 [dead]) at 90 days. Fifty-six patients were matched across 2 equally distributed groups (mean [SD] age, 62.25 [13.92] years for cases and 58.32 [14.79] years for controls; male, 13 cases [46%] and 14 controls [50%]). Endovascular therapy was significantly associated with a favorable shift in the overall distribution of 90-day mRS scores (odds ratio, 2.56; 95% CI, 2.50-8.47; P = .04), higher rates of independent outcomes (90-day mRS scores of 0-2, 25% vs 0%; P = .04), and smaller final infarct volumes (mean [SD], 87 [77] vs 242 [120] mL; P < .001). One control (4%) and 2 treatment patients (7%) developed a parenchymal hematoma type 2 (P > .99). The rates of hemicraniectomy (2 [7%] vs 6 [21%]; P = .10) and 90-day mortality (7 [29%] vs 11 [48%]; P = .75) were numerically lower in the intervention arm. Sensitivity analysis for patients with a baseline ischemic core greater than 70 mL (12 pairs) revealed a significant reduction in final infarct volumes (mean [SD], 110 [65] vs 319 [147] mL; P < .001) but only a nonsignificant improvement in the overall distribution of mRS scores favoring the treatment group (P = .18). All 11 patients older than 75 years had poor outcomes (mRS score >3) at 90 days. In properly selected patients, ET appears to benefit patients with large core and large mismatch profiles. Future prospective studies are warranted.

Automated CT Perfusion for Ischemic Core Volume Prediction in Tandem Anterior Circulation Occlusions

Background/Aim: CT perfusion (CTP) predicts ischemic core volumes in acute ischemic stroke (AIS); however, assumptions made within the pharmacokinetic model may engender errors by the presence of tracer delay or dispersion. We aimed to evaluate the impact of hemodynamic disturbance due to extracranial anterior circulation occlusions upon the accuracy of ischemic core volume estimation with an automated perfusion analysis tool (RAPID) among AIS patients with large-vessel occlusions. Methods: A prospectively collected, interventional database was retrospectively reviewed for all cases of endovascular treatment of AIS between September 2010 and March 2015 for patients with anterior circulation occlusions with baseline CTP and full reperfusion (mTICI3). Results: Out of 685 treated patients, 114 fit the inclusion criteria. Comparison between tandem (n = 21) and nontandem groups (n = 93) revealed similar baseline ischemic core (20 ± 19 vs. 19 ± 25 cm³; p = 0.8), T_max >6 s (175 ± 109 vs. 162 ± 118 cm³; p = 0.6), T_max >10 s (90 ± 84 vs. 90 ± 91 cm³; p = 0.9), and final infarct volumes (45 ± 47 vs. 37 ± 45 cm³; p = 0.5). Baseline core volumes were found to correlate with final infarct volumes for the tandem (r = 0.49; p = 0.02) and nontandem (r = 0.44; p < 0.01) groups. The mean absolute difference between estimated core and final infarct volume was similar between patients with and those without (24 ± 41 vs. 17 ± 41 cm³; p = 0.5) tandem lesions. Conclusions: The prediction of baseline ischemic core volumes through an optimized CTP analysis employing rigorous normalization, thresholding, and voxel-wise analysis is not significantly influenced by the presence of underlying extracranial carotid steno-occlusive disease in large-vessel AIS.

Abstract WP34: Associations Between CTP Ischemic Core Volume, ASPECTS Scores and Clinical Outcomes After Endovascular Reperfusion

Introduction: ASPECTS and CT perfusion (CTP) lesion volumes have been used to triage patients with large artery occlusions to endovascular therapy. Specifically, ASPECTS ≤5 and CTP infarct core &gt;50 mL excluded patients from some recent endovascular trials. It is unclear how well these criteria select patients who will have poor functional outcomes despite reperfusion and if the criteria are interchangeable. Hypothesis: ASPECTS and CTP infarct volumes are correlated and both predict clinical outcome. Methods: Patients with anterior circulation strokes were enrolled in a prospective multi-center study (CRISP) if CTP could be obtained &lt;90 minutes before endovascular treatment, and intervention performed &lt;18h from onset. Reperfusion was defined as &gt;50% reduction from baseline Tmax&gt;6s volume on early follow-up MRI (&lt;36h from baseline CT) or final TICI 2b/3 if follow-up MRI unavailable. A single blinded reader at the core imaging facility determined ASPECTS on baseline CT. Baseline ischemic core volumes were assessed using automated software (RAPID). Good outcome was defined as mRS 0-2 and poor outcome as mRS 5-6. Results: This analysis includes 165 patients with reperfusion after endovascular therapy. Baseline ASPECTS and infarct core volume are inversely associated (p=0.009). Lower ASPECTS and larger infarct core were associated with a lower chance of good outcome in univariate analysis: OR for good outcome was 0.8 (95% CI 0.7-1.0) per point decrease in ASPECTS and 0.8 (95% CI 0.6-0.9) per 10mL increase in infarct core. Adjusted for baseline NIHSS and age, core remained a predictor of good outcomes (p=0.025) while ASPECTS showed a strong trend (p=0.072). The PPV for poor outcome despite reperfusion was 38% (5/13) for infarct core &gt;50 mL and 0% (0/7) for ASPECTS ≤5 (p=0.1 for difference in PPV). No patient met both criteria. Conclusions: The ASPECTS and ischemic core volume criteria used to exclude patients from some endovascular therapy trials, did not agree in identifying patients with presumed poor outcomes. Neither criterion had a high specificity for identifying patients destined to have a poor outcome despite reperfusion. Randomized trials are warranted to assess the efficacy of endovascular therapy in patients with ischemic core lesions &gt;50 ml and ASPECTS ≤5.

Ischemic core and hypoperfusion volumes predict infarct size in SWIFT PRIME.

Within the context of a prospective randomized trial (SWIFT PRIME), we assessed whether early imaging of stroke patients, primarily with computed tomography (CT) perfusion, can estimate the size of the irreversibly injured ischemic core and the volume of critically hypoperfused tissue. We also evaluated the accuracy of ischemic core and hypoperfusion volumes for predicting infarct volume in patients with the target mismatch profile. Baseline ischemic core and hypoperfusion volumes were assessed prior to randomized treatment with intravenous (IV) tissue plasminogen activator (tPA) alone versus IV tPA + endovascular therapy (Solitaire stent-retriever) using RAPID automated postprocessing software. Reperfusion was assessed with angiographic Thrombolysis in Cerebral Infarction scores at the end of the procedure (endovascular group) and Tmax > 6-second volumes at 27 hours (both groups). Infarct volume was assessed at 27 hours on noncontrast CT or magnetic resonance imaging (MRI). A total of 151 patients with baseline imaging with CT perfusion (79%) or multimodal MRI (21%) were included. The median baseline ischemic core volume was 6 ml (interquartile range= 0-16). Ischemic core volumes correlated with 27-hour infarct volumes in patients who achieved reperfusion (r = 0.58, p < 0.0001). In patients who did not reperfuse (<10% reperfusion), baseline Tmax > 6-second lesion volumes correlated with 27-hour infarct volume (r = 0.78, p = 0.005). In target mismatch patients, the union of baseline core and early follow-up Tmax > 6-second volume (ie, predicted infarct volume) correlated with the 27-hour infarct volume (r = 0.73, p < 0.0001); the median absolute difference between the observed and predicted volume was 13 ml. Ischemic core and hypoperfusion volumes, obtained primarily from CT perfusion scans, predict 27-hour infarct volume in acute stroke patients who were treated with reperfusion therapies.