Infarct Growth Rate Research Articles

Abstract P492: 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.

Abstract TP40: Time From Stroke Onset to Reperfusion is Associated With Worse Functional Outcomes in Patients With Rapidly Progressing Infarcts

Introduction: Recent trials have demonstrated the benefit of endovascular therapy (EVT) beyond 6 hours of symptom onset. However, the importance of time to reperfusion (TTR) in the extended time window has recently been questioned. Given the variability of infarct growth rate (IGR), the time delay until reperfusion may have greater consequences for those with rapidly progressing infarcts, and identifying such patients is essential for improving outcomes. We tested the hypothesis that TTR is more closely associated with functional outcome in patients with rapidly progressing infarcts compared to their slow-progressing counterparts. Methods: We retrospectively identified 106 patients at our center’s prospectively collected stroke database with anterior circulation large-vessel occlusion stroke and known time of symptom onset. Patients underwent initial CT perfusion imaging (CTP), EVT and and follow-up MRI at 24 hours. Core infarct volumes at presentation (CBF<30%) were estimated using RAPID software. The time between symptom onset and CTP was used to estimate IGR and to categorize patients as fast (≥5 mL/hour) or slow (<5 mL/hour) progressors. Alternatively, final infarct volume (FIV) was measured on MRI and used to calculate IGR in the absence of CTP. Functional outcome was assessed using the modified Rankin scale (mRS) at discharge and 90 days. Associations were computed using ordinal regression adjusting for age, ASPECTS, and TICI. Results: 35 fast progressors (age 71±14, 17 F, TTR 288±91 minutes, mean IGR 21±24 mL/hour) and 71 slow progressors (age 71±17, 48 F, TTR 374±211 minutes, mean IGR 1.0±1.5 mL/hour) were identified. Fast progressors had higher admission NIHSS scores (18±6 vs 13±7, p<0.001) and significantly larger FIV (101±77 vs 47±65 mL, p<0.001). After adjusting for baseline factors, TTR was significantly associated with worse functional outcome at 90 days in fast progressors (p=0.026, aOR 1.13 per 10 minutes, 95% CI 1.02-1.28), but not for slow progressors (p=0.708). Conclusions: In patients with rapidly progressing infarcts (≥5 mL/hour), TTR was associated with worse functional outcomes at 90 days compared to slow progressors. Identifying such patients may be critical for appropriate triage and rapid delivery of acute stroke care.

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.

Abstract WMP5: CT Perfusion Profiles of Infarct Growth in Large Vessel Occlusion Acute Stroke Patients Sensitive to Decreases in Blood Pressure

The growth of a final infarct volume largely depends on cerebral perfusion after a large vessel occlusion (LVO) stroke. Decreases of blood pressure (BP) before recanalization are associated with larger infarct and worse functional outcome. It is uncertain whether an intervention to elevate BP improves outcome, particularly if susceptibility to the BP beneficial effect varies by individual factors such as the collateral vessel status. We aim to define the association of BP, infarct growth and perfusion patterns of potential vulnerable patients. We retrospectively studied patients with anterior LVOs who underwent mechanical thrombectomy (MT) at two comprehensive stroke centers. Only patients with TICI score ≥2b and admission CTP and 24 hours MRI were included. Infarct growth was calculated as 620 ADC volume subtracted from CBF <30% in the ischemic hemisphere using the Automatic Rapid Software. Hypoperfusion intensity ratio (HIR) was calculated as the ratio of the Tmax >10s volume to the Tmax >6s volume with a lower value indicating a more favorable ratio. Intra-procedural BP was continuously monitored using a non-invasive cuff or intraarterial catheter. Systolic BP (SBP) and mean arterial pressure (MAP) were averaged at various time points throughout MT. We analyzed 199 patients from 317 MT. A quantile regression with quantile τ = 0.25, 0.5 and 0.75 was fitted to study how Infarct Growth Rate (IGR) is affected by BP change. At 0.25 and 0.5 quantiles, one unit change in MAP did not lead to a significant change for IGR. At the 0.75 quantile (quartile 3), one unit change in MAP resulted in 0.79 unit change in IGR (95% CI: -0.11, 1.69; p= 0.09). Hence, we identified patients whose IGR is above the 0.75 quantile as the vulnerable subgroup. The vulnerable subgroup had significant larger median volumes of Tmax in all sequences when compared to the non-vulnerable subgroup: Tmax10 (67.8cc vs 40.0cc, p= 0.004), Tmax8 (92.9cc vs 62.0cc, p= 0.003), Tmax6 (134cc vs 98.7cc, p =0.003), Tmax4 (228.6cc vs 184.3cc, p= 0.016). The median HIR was also significantly higher (0.4 vs 0.3, p= 0.026) in the BP vulnerable population. Admission perfusion patterns of collaterals evaluated may help to identify the most vulnerable population to increase their infarct growth when facing decrease in BP.

Abstract WP52: Defining and Predicting Fast Progression of Infarct Growth in Large Vessel Occlusion Strokes

Background and Purpose: Identification of patients with failing collaterals and rapid progression of infarct growth (fast progressors) is crucial when assessing patients for potential transfer from primary to comprehensive stroke centers endovascular therapy (ET). Methods: Review of a prospectively collected database of endovascular patients with anterior circulation Large vessel occlusion strokes from 09/2010-11/2018. Patients with adequate CTP maps and follow-up final infarct volume (FIV) measurements who achieved full reperfusion (mTICI 2c-3) were included.Infarct growth rate was calculated as the difference between FIV and the acute CTP core volume, divided by time from CTP to reperfusion in hours. Receiver operating characteristic analysis was used to identify the optimal infarct growth rate that better discriminated 90-day good outcome(mRS 0-2). Fast progression was defined as having an infarct growth rate above the identified threshold. Results: 461 patients qualified for the study. The optimal infarct growth rate threshold to predict good outcome was 3.9 ml/h (sensitivity 79%, specificity 47%). 286 (62%) were subsequently categorized as fast progressors. There were no differences in baseline characteristics between fast and slow progressors except for higher NIHSS(16[12-21]vs16[11-21],p=0.02), longer Last known normal to CT times (367 mins [219-679]vs 269.5[111.5-570],p<0.001) and smaller CTP core volumes (3.8cc[0-20] vs 8[0-25.5],p=0.02). Fast progressors had larger FIV (36.7[18.6-66.9] vs 7[3.5-16],p<0.001), lower rates of good outcome (52.8% vs 77.4%, p<0.001), higher mortality rates (17.5% vs 6%,p=0.02). There was a trend toward higher rates of parenchymal hematomas in fast progressors (5.1% vs 1.7%,p=0.07). On multivariate analysis, only ASPECTS was an independent predictor of fast progression (aOR 0.7 95%CI[0.54-0.91,p=0.007) while CTP parameters did not reach statistical significance. Conclusions: Fast progression of infarct growth is associated with poorer clinical outcomes. ASPECTS may help triage transfers when assessing patients for ET. Larger studies are warranted.

Factors influencing infarct growth including collateral status assessed using computed tomography in acute stroke patients with large artery occlusion.

In major ischemic stroke caused by a large artery occlusion, neuronal loss varies considerably across individuals without revascularization. This study aims to identify which patient characteristics are most highly associated with this variability. Demographic and clinical information were retrospectively collected on a registry of 878 patients. Imaging biomarkers including Alberta Stroke Program Early CT score, noncontrast head computed tomography infarct volume, perfusion computed tomography infarct core and penumbra, occlusion site, collateral score, and recanalization status were evaluated on the baseline and early follow-up computed tomography images. Infarct growth rates were calculated by dividing infarct volumes by the time elapsed between the computed tomography scan and the symptom onset. Collateral score was graded into four levels (0, 1, 2, and 3) in comparison with the normal side. Correlation of perfusion computed tomography and noncontrast head computed tomography infarct volumes and infarct growth rates were estimated with the nonparametric Spearman's rank correlation. Conditional inference trees were used to identify the clinical and imaging biomarkers that were most highly associated with the infarct growth rate and modified Rankin Scale at 90 days. Two hundred and thirty-two patients met the inclusion criteria for this study. The median infarct growth rates for perfusion computed tomography and noncontrast head computed tomography were 11.2 and 6.2 ml/log(min) in logarithmic model, and 18.9 and 10.4 ml/h in linear model, respectively. Noncontrast head computed tomography and perfusion computed tomography infarct volumes and infarct growth rates were significantly correlated (rho=0.53; P < 0.001). Collateral status was the strongest predictor for infarct growth rates. For collateral=0, the perfusion computed tomography and noncontrast head computed tomography infarct growth rate were 31.56 and 16.86 ml/log(min), respectively. Patients who had collateral >0 and penumbra volumes>92 ml had the lowest predicted perfusion computed tomography infarct growth rates (6.61 ml/log(min)). Collateral status was closely related to the diversity of infarct growth rates, poor collaterals were associated with a faster infarct growth rates and vice versa.

Abstract TP72: Should Hypoperfusion Intensity Ratio Influence Patient Selection for Mechanical Thrombectomy?

Background: Current data utilizes clinical-radiographic mismatch (core and mismatch ratio) as patient selection criteria for mechanical thrombectomy in LVO. High HIR (Hypoperfusion Intensity Ratio) is known to correlate with core size, infarct growth and outcome though influence on patient selection has not been yet determined. Hypothesis: Patients with High HIR and malignant profile (Tmax &gt;10s greater than 50% of penumbra) indicative of fast growing infarct may influence final clinical outcome irrespective of reperfusion. Methods: We retrospectively identified all AIS patients with LVO who underwent CTP imaging between January and June2018 within 24 hours from symptom onset. Demographics, CTP imaging variables, reperfusion status and outcomes (discharge NIHSS and mRS) were analyzed. HIR was dichotomized by proportion of greater and less than 0.5 into malignant vs favorable profile. Association with core size, infarct growth velocity, reperfusion (defined as TICI 2b or 3) and impact on outcomes was analyzed using Wilcoxon Ranked Sum tests for the (skewed) continuous and ordinal variables; chi-square test of proportion were used for categorical variables. The independent contribution of HIR and reperfusion predicting the major outcomes was assessed with logistic regression. Results: A total of 67 patients with LVO were identified with a median age of 78 (IQR 62-87), NIHSS of 16 (IQR 11-21) and time from last seen normal to CT 404 minutes (IQR 113-734). Five patients were excluded due inadequate CTP data. Patients with high HIR (n=23) had a higher core size (median 39 cc; IQR 16-73) compared to 0 cc (IQR 0-12) than patients with low HIR (n=39; median 0; IQR 0-12) (p=&lt;0.001) and faster Infarct growth rate 14.8 cc/hr (IQR 3.6-29.7) vs. 0 cc/hr (IQR 0-1.12) (p=&lt;0.001). After adjusting for reperfusion, median discharge NIHSS was not significantly different (p=0.22) in groups with low vs high HIR, however in-hospital mortality differed (p=0.02). Conclusion: Higher HIR and malignant profile is associated with larger index core size and faster growth rate. However, the influence of this profile on clinical outcomes after recanalization is yet to be established. Ongoing studies evaluating the utility of HIR on patient selection for thrombectomy are needed.

Abstract TP67: Acute Blood Pressure Changes Aggravate Ischemic Lesion Growth After Large Vessel Occlusion

Backgrounds: Penumbral perfusion dynamically changes with alterations of collateral flow and systemic blood pressure. We investigated the association between acute changes of systolic blood pressures and infarct growth within penumbral area. Method: We included ischemic stroke patients &lt;24h after onset from Jan 2015 to Mar 2018 with the following criteria; initial NIHSS score ≥ 6-point, internal carotid or middle cerebral artery occlusion, no recanalization treatment, baseline penumbral volume &gt;15 mL, and mismatch ratio &gt;1.8. Perfusion quantification, 3D voxel-registration and image segmentation were done by Olea 3.0 and Analyze 12.0. Penumbra was defined as Tmax &gt;6s lesion without infarct. Infarct growth within penumbra was defined by the infarct volume at a follow-up image. Hypoperfusion intensity ratio (HIR) was defined by the proportion of Tmax &gt;10s within penumbra. Blood pressure change integral (BPCI) was defined by an integration of SBP initial - SBP trajectory over 24 h (Figure A). BP dropmax was defined by a maximum decrease of SBP between successive measurements. Results: Among 25 patients included (age, 71.3±13.5; male, 56%), median baseline NIHSS score was 13 (interquartile range [IQR], 8-18). Median volume of initial infarct within Tmax &gt;6s was 16 mL (IQR, 6-58), penumbra was 80 mL (IQR, 29-138), HIR was 46% (IQR, 31-63), and infarct growth within penumbra was 26% (IQR, 11-48). Median BPCI was 157.4 mmHg·h (IQR, -76.8-566.2) and BP dropmax was 34 mmHg (IQR, 25-43). Median infarct growth was linearly associated with BPCI (β=0.022; p -value=0.03; Figure B), BP dropmax (β=0.77; p -value=0.048; Figure C), and HIR (β=0.69; p -value&lt;0.01). High dichotomized BPCI and BP dropmax increased infarct growth rate (Figure D). Conclusions: Acute decline of systemic blood pressure may aggravates penumbral perfusion and thus increase infarct growth within penumbral tissue in emergent large vessel occlusion patients without recanalization.

Abstract 164: Early Infarct Growth Correlates With Both Collateral Status and Clinical Outcomes After Thrombecomy

Background: We assessed the correlation between early infarct growth rate (EIGR), collaterals and clinical outcomes following endovascular thrombectomy (EVT). Methods: In a prospective multicenter cohort study of imaging selection for EVT (SELECT), consecutive patients with large vessel occlusion (ICA, M1, M2) presenting up to 24 hr from last known well (LKW) were enrolled at 9 centers. CT perfusion was obtained prior to EVT. EIGR was defined as CTP ischemic core volume (rCBF&lt;30%) divided by the time from LKW to baseline CTP. The optimal EIGR cutoff was identified by maximizing the sum of the sensitivity and specificity to predict favorable outcome (90 day mRS 0-2). Slow progressors were defined as having an EIGR below the cutoff. Good collaterals were defined on CTP as a hypoperfusion intensity ratio (HIR) &lt;0.4 and on CTA as collateral score &gt; 2. Results: Of 445 enrolled, 284 received EVT. The optimal EIGR was &lt;10 ml/hr; 199 were slow and 85 fast progressors. Fast progressors had higher median NIHSS (19 vs. 15, P&lt; 0.001), earlier median LKW to puncture 180 vs. 266 min, P&lt; 0.001,. Slow progressors had better collaterals on both CTP and CTAs: HIR aOR 4.97 (2.3-10.7), p&lt;0.001; CTA collaterals 3.02 (1.6-5.7), p=0.001. EIGR was an independent predictor of good outcome after adjusting for age NIHSS, LKW to puncture, mTICI and tPA aOR 0.73 (95% CI 0.61-0.89, p=0.001). Slow progressors were 3.5 times more likely to achieve mRS 0-2 after EVT aOR 3.51 (95% CI 1.8-6.7, p&lt;0.001). Fast progressors had substantially worse clinical outcomes both in early and late time window (Table 1). The odds of good outcome decreased by 14% for each 5 ml/hour increase in EIGR, OR:0.87(0.80-0.94), p&lt;0.001 and the probability of good outcome declined more rapidly in fast progressors (Figure 1). Conclusion: The early infarct growth strongly correlates with both collateral status and clinical outcomes after EVT. Fast progressors have a much more rapid decline in favorable outcomes at late treatment times.

High Variability in Neuronal Loss.

Background and Purpose- In the setting of acute ischemic stroke because of large-vessel occlusion (LVO) there is progressive loss of brain tissue which occurs in a time-dependent fashion previously quantified to be ≈1.9 million neurons per minute. However, this number represents an average and accumulating evidence suggests large individual variation. In this study, we aim to quantify the distribution and range in the rate of loss brain tissue across the entire spectrum of clinical phenotypes of anterior circulation LVO strokes encountered in clinical practice. Methods- Retrospective review of a prospectively acquired database of consecutive patients with anterior circulation stroke because of proximal LVO and appropriate ischemic core imaging was performed. Ischemic core volume was measured using automated software processing and time from last known well to imaging was recorded. Applying previously published methodology for brain loss quantification, we computed rate of brain tissue elements loss in proximal LVO stroke patients. Results- We studied 415 patients with internal carotid artery or middle cerebral artery (M1 segment) occlusion. Mean ischemic core volume was 50.4 mL and mean time to imaging from time from last known well (TLKW) was 8.7 hours, which is similar to previously published data, translates into a mean loss per minute of 2.03 million neurons, 14.8 billion synapses, and 12.8 km of myelinated fibers. However, the distribution of neuron loss was highly variable, ranging from <35 000 to >27 million cells per minute. Conclusions- Widely spread rates of infarct growth are observed in acute ischemic stroke because of proximal LVO with rate of neuron loss per minute ranging from <35 000 per minute in slow progressors to >27 million per minute in fast progressors, with a mean and median of 2 million and 0.9 million, respectively.

Hypoperfusion ratio predicts infarct growth during transfer for thrombectomy.

We hypothesized that automated assessment of collaterals on computed tomography perfusion can predict the rate of infarct growth during transfer from a primary to a comprehensive stroke center for endovascular stroke treatment. We identified consecutive patients (N = 28) and assessed their collaterals based on the hypoperfusion intensity ratio (HIR) prior to transfer. Infarct growth rate was strongly correlated with HIR (r = 0.78, p < 0.001). Receiver operating characteristic analysis identified HIR ≥ 0.5 as optimal for predicting infarct growth. Patients with HIR ≥ 0.5 had a median infarct growth rate of 10.1ml/h (interquartile range [IQR] = 6.4-18.4) compared with 0.9ml/h (IQR = 0-2.8; p < 0.001) in patients with HIR < 0.5. Patients with HIR ≥ 0.5 had an 83% probability of significant core growth, whereas patients with HIR < 0.5 had an 88% probability of core stability. These preliminary data have the potential to guide decision making regarding whether repeat brain imaging should be performed after transfer to a comprehensive stroke center. Ann Neurol 2018;84:616-620.

Endovascular Treatment in the DEFUSE 3 Study.

Background and Purpose- Endovascular therapy in an extended time window has been shown to be beneficial in selected patients. This study correlated angiographic outcomes of patients randomized to endovascular therapy with clinical and imaging outcomes in the DEFUSE 3 study (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3). Methods- Angiograms were assessed for the primary arterial occlusive lesion and the modified Thrombolysis in Cerebral Infarction (TICI) score at baseline and the final modified TICI score. Clinical outcomes were assessed using an ordinal analysis of 90-day modified Rankin Scale and a dichotomous analysis for functional independence (modified Rankin Scale score of 0-2). TICI scores were correlated with outcome, types of device used for thrombectomy, and 24-hour follow-up imaging. Results- TICI 2B-3 reperfusion was achieved in 70 of 92 patients (76%). TICI 2B-3 reperfusion showed a more favorable distribution of Rankin scores compared with TICI 0-2A; odds ratio, 2.77; 95% confidence interval, 1.17-6.56; P=0.019. Good functional outcome (90-day modified Rankin Scale score of 0-2) increased with better TICI scores ( P=0.0028). There was less disability comparing TICI 3 patients to TICI 2B patients ( P=0.037). Successful reperfusion (TICI 2B-3) was independent of the device used, the site of occlusion (internal carotid artery or M1) or adjunctive use of carotid angioplasty and stenting. Significantly less infarct growth at 24 hours was seen in TICI 3 patients compared with TICI 0-2A ( P=0.0015) and TICI 2B ( P=0.0002) patients. Conclusions- Thrombectomy in an extended time window demonstrates similar rates of TICI 2B-3 reperfusion to earlier time window studies. Successful reperfusion was independent of the device used, the site of occlusion or adjunctive use of carotid angioplasty and stenting. TICI 3 reperfusion was more likely to result in low rates of infarct growth at 24 hours and good functional outcome at 90 days. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT02586415.

Time Is Brain: The Stroke Theory of Relativity

Since the introduction of the philosophical tenet "Time is Brain!," multiple lines of research have demonstrated that other factors contribute to the degree of ischemic injury at any one point in time, and it is now clear that the therapeutic window of acute ischemic stroke is more protracted than it was first suspected. To define a more realistic relationship between time and the ischemic process, we used computational modeling to assess how these 2 variables are affected by collateral circulatory competence. Starting from the premise that the expression "Time=Brain" is mathematically false, we reviewed the existing literature on the attributes of cerebral ischemia over time, with particular attention to relevant clinical parameters, and the effect of different variables, particularly collateral circulation, on the time-ischemia relationship. We used this information to construct a theoretical computational model and applied it to categorically different yet abnormal cerebral perfusion scenarios, allowing comparison of their behavior both overall (i.e., final infarct volume) and in real-time (i.e., instantaneous infarct growth rate). Optimal collateral circulatory competence was predictably associated with slower infarct growth rates and prolongation of therapeutic window. Modeling of identifiable specific types of perfusion maps allows forecasting of the fate of the ischemic process over time. Distinct cerebral perfusion map patterns can be readily identified in patients with acute ischemic stroke. These patterns have inherently different behaviors relative to the time-ischemia construct, allowing the possibility of improving parsing and treatment allocation. It is clearly evident that the effect of time on the ischemic process is relative.

Predictors of decompressive hemicraniectomy in malignant middle cerebral artery stroke.

Identification of factors in malignant middle cerebral artery (MMCA) stroke patients that may be useful in selecting patients for DHC. This study was a retrospective multicenter study of patients referred for DHC based on the criteria of the randomized control trials of DHC in MMCA stroke. Demographic, clinical, and radiology data were analyzed. Patients who underwent DHC were compared to those who survived without surgery. Two hundred three patients with MMCA strokes were identified: 137 underwent DHC, 47 survived without DHC, and 19 refused surgery and died. Multivariate analysis identified the following factors determining DHC in MMCA stroke: age < 55years (OR 8.5, 95% CI 3.3-22.1, P < 0.001), MCA with involvement of additional vascular territories (anterior cerebral artery, posterior cerebral artery (OR 4.8, 95% CI 1.5-14.9, P = 0.007), septum pellucidum displacement ≥ 7.5mm (OR 4.8, 95% CI 1.9-11.7, P = 0.001), diabetes (OR 3.7, 95% CI 1.3-10.6, P = 0.012), infarct growth rate (IGR) ml/h (OR 1.11, 95% CI 1.02-1.2, P = 0.015), and temporal lobe involvement (OR 2.5, 95% CI 1.01-6.1, P = 0.048). The internal validation of the multivariate logistic regression model using bootstrapping analysis showed marginal bias. Among patients with MMCA infarctions, an increased possibility of DHC is associated with younger age, MCA with additional infarction, septum pellucidum deviation of > 7.5mm, diabetes, IGR, and temporal lobe involvement. The presence of these risk factors identifies those MMCA stroke patients who may require DHC. Bootstrapping analysis indicated the model is good enough to predict the outcome in general population.

Factors that Can Help Select the Timing for Decompressive Hemicraniectomy for Malignant MCA Stroke.

In patients with malignant middle cerebral artery (MMCA) stroke, a vital clinically relevant question is determination of the speed with which infarction evolves to select the time for decompressive hemicraniectomy [DHC]. A retrospective, multicenter cross-sectional study of patients referred for DHC, based on the criteria of randomized controlled trials, was undertaken to identify factors for selecting the timing of DHC in MMCA stroke, stratified by time [< 48, 48-72, > 72h]. Infarction volume and infarct growth rate [IGR] were measured on all CT scans. One hundred eighty-two patients [135 underwent DHC and 47 survived without DHC] were included in the analysis. After multivariate adjustment, factors showing the strongest independent association with DHC were patients < 55years of age, septum pellucidum deviation, temporal lobe involvement, MCA with additional infarcts, and IGR on second CT. Of the five factors identified, different combinations of determining factors were observed in each subgroup. Both first and second IGRs were highest in the < 48, 48-< 72, and > 72h [p < 0.001]. Patients who survived without surgery had the slowest IGRs. There was no association between time to DHC and infarct volume, although infarct volume was lower in patients who survived without DHC compared to the DHC subgroups. We identify the major risk factors associated with DHC in time-stratified subgroups of patients with MMCA. Evaluation of IGRs between the first and second scan and when possible second and third scan can help in selecting the timing of hemicraniectomy.

Abstract TP12: Distribution and Incidence of Fast versus Slow Progressors of Infarct Growth in Large Vessel Occlusion Stroke

Background and Purpose: Fast and slow progressors of infarct growth due to a large vessel occlusion (LVO) are commonly observed when patients are considered for acute endovascular therapy. However, the incidence of these clinical phenotypes has not been formally quantified. We aimed to measure the frequency and distribution of fast versus slow infarct growth in LVO patients in different time strata after stroke onset. Methods: Retrospective study of consecutive patients with acute LVO admitted to our comprehensive stroke center. Inclusion criteria were: 1. CTA or MRA evidence of intracranial ICA and/or MCA(M1) occlusion, with or without extracranial ICA occlusion. 2. Baseline CTP or MRI DWI before reperfusion therapy and within 25 hours of time of last seen well/stroke onset. Automated core volume measurements were performed using RAPID software (iSchemaView). Fast progressors were defined as having core volumes &gt; 70 cc at early time quantiles (0 - 8 hours). Slow progressors were defined as having core volumes &lt; 10 cc at later time quantiles (&gt; 8 hours). Infarct growth rate was computed using ischemic core volume divided by time from stroke onset to core imaging. Descriptive statistics and univariate analysis were performed. Results: A total of 115 patients were included with mean age 69+/-15.5 and NIHSS 16.5+/-7; 66% were females. Patients had MCA occlusion in 81% and intracranial ICA occlusion in 19% of cases. The median time from stroke onset to baseline core imaging was 9.1 hours (IQR, 4 - 14.7) and 53 patients were imaged before 8 hours. The median core volume was 10 (range 0 - 405 ml). In the early time epoch (&lt; 8 hrs), 5/13 patients (38%) had core &gt; 70ml by 3.65 hours (fast progressors). In the later time epoch (&gt; 8 hrs), 29/62 patients (46%) had ischemic cores &lt; 10ml at 25 hours from stroke onset. The median infarct growth rate was 2.6 ml/hr (0 - 14.6) in patients imaged before 8 hours and 1.2 ml/hr (0 - 5.48) in the later time epoch. Conclusions: The incidence of fast and slow progressors of LVO stroke may be higher than previously anticipated depending on different time quantiles of stroke onset to imaging.

Abstract 178: Infarct Growth Rate Depends on Collateral Status in Acute Ischemic Stroke Patients

Introduction and Hypothesis: Multiple studies have demonstrated no statistically significant association between time after stroke onset and initial infarct volume. Factors other than time may play a role in infarct growth. We sought to investigate association between collateral status and infarct growth rate in acute ischemic stroke (AIS) patients. Methods: We included 130 consecutive patients with CTA showing ICA and/or proximal MCA occlusions who had DWI within 8 hours of stroke onset. Collateral status was categorized into three groups: poor (none or minimal), intermediate (present but &lt; contralateral side) and good (≥ contralateral side). DWI lesion volumes were measured and infarct growth rate was calculated using MRI time after stroke onset. Mann-Whitney test and correlation coefficient were used for statistical analysis. Results: In our 130 patients, 62 female (48%), the average values (mean±SD) were: age 70 ± 17 years, NIHSS 16 ± 6, DWI volume 59 ± 65 mL, time after stroke onset 4 ± 2 hours, and infarct growth rate 17 ± 23 mL/hour. 19 (14.6%) had poor, 75 (57.7%) had intermediate, and 36 (27.7%) had good collaterals. Infarct growth rate and DWI lesion volume were significantly increased with decreased collateral quality (p&lt;0.0004 for all group comparisons). Patients with good collaterals were younger (p=0.004 and p=0.018 compared to poor and intermediate groups respectively) and had lower NIHSS scores (p&lt; 0.001). Time after stroke onset, gender, or occlusion site (ICA vs MCA) were not significantly different among different collateral groups. There was no correlation between time and DWI volume (r2=0.02, p=0.8) or collateral status (r2=0.05, p=0.6). There was significant correlation between collateral status and infarct growth (r2=-0.6,p&lt;0.0001). Conclusion: AIS patients with good collaterals have small initial DWI lesion volumes and slower infarct growth rates. These patients may be candidates for treatment options outside traditional time windows.

Abstract TP135: Late Decompressive Hemicraniectomy for Malignant Middle Cerebral Artery Stroke: Role of Infarct Growth

Objective: The purpose of this multi-institutional pooled data analyses from three countries was to determine the impact of DHC timing on the functional outcomes in patients operated beyond 48 hours in comparison with DHC under 48 hours. In addition factors leading to early or late DHC were also identified. Methods: Retrospective, multicenter cross-sectional study to measure outcome following DHC &lt;48 or &gt;48 hours using the modified Rankin Scale [mRS] and dichotomized as favorable ≤4 or unfavorable &gt;4, at three months. Results: In total 137 patients underwent DHC. There was no significant difference in the functional outcome [P=0.140] and mortality [P=0.975] but with a trend towards better outcome in patients operated over 48 hours. Multivariate analysis showed age ≥ 55, MCA with additional infarction, septum pellucidum deviation ≥1cm, and uncal herniation was independent predictor of poor functional outcome at three months. In the ‘‘best’’ multivariate model IGR &gt;7.5ml/hr, MCA with additional infarction, and patients with temporal lobe involvement were independently associated with surgery under 48 hours. Both first infarct growth rate [IGR1] [DHC&lt;48 hours, 15.2± 8.1ml/hr vs. &gt;48 hours, 7.1 ± 5.03ml/hr] [P&lt;0.001] and second infarct growth rate [IGR2] [DHC 48 13.64 ±8.76 ml/hr, &gt; 48 hours 7.15 ±6.23 ml/hr [P&lt;0.001] were nearly double in patients with early surgery [&lt;48 hours]. Conclusions: There was no significant difference in the functional outcome and mortality in patients operated &gt;48 hours of stroke onset compared to early [&lt;48 hours]. Time to surgery had no impact on functional outcome. Our data identifies IGR, temporal lobe involvement and MCA with additional infarct were independent predictors of early surgery.

Abstract TP62: To Determine the Evolution of Stroke Volume Overtime Using ANFIS

Background: There is limited information on evolution of temporal lesion volumetric changes in acute ischemia. Though infarct evolves in natural logarithmic or linear pattern in acute phase [24 hrs] both fail to predict the lesion volume in later phase [48,96,200 hours]. Maximum infarct volume [MIV] measured by these methods don’t reach a plateau at the infinite point in time, not true in clinical medicine. Instead of probability based statistical methods we used Adaptive Neuro-Fuzzy Inference System [ANFIS]. ANFIS utilizes features of human brain fundamental to the learning process, pattern modeling and perceptive inference. The purpose is to identify the best method to predict stroke volume at various time intervals. Methods: We used pooled hemicraniectomy database to select patients with three CT scans. Measurement of the infarct volume [IV] was done using ABC/2 method. Maximum infarct volume [MIV] was calculated using last CT before DHC. Time was measured from stroke onset to CT. Mean measured MIV was used as standard to compare the outcome by various methods. A Pseudo-Monte-Carlo scheme was utilized in improving the accuracy of the classification. Results: There were 66 patients with 3 CT-scans. We used MATLAB-2015 with Fuzzy Logic Toolbox functions to determine the pattern of infarct growth [Linear, Logarithmic, Exponential and ANFIS] and to determine the best predictive method at various time intervals. Of the measured IV on CT 1 and 2, 40 patients [60%] data set was used for training the ANFIS system while remaining 26 [40%] was used for testing. Mean measured MIV was 332±112.21 cm 3 [min 112.86 cm 3 , max 650 cm 3 ] at mean time 67.75±67.39 hour [min 21.30 hours, max 350 hours]. Mean MIV measured by ANFIS 319.05±94.58 cm 3 [p=0.32], Linear 251.77±154.46 cm 3 [p=0.01], Logarithmic 259.68±88.76 cm 3 [p=0.00], and Exponential 157.80±84.05 cm 3 Conclusion: ANFIS predicted the third infarct volume with high degree of accuracy across various time intervals. ANFIS method can provide an excellent model for forecasting infarct volume and growth rate, characterizing the evolution of lesion and pathological stages for mechanistic studies and therapeutic interventions of stroke disease.

Impact of Computed Tomography Perfusion Imaging on the Response to Tenecteplase in Ischemic Stroke: Analysis of 2 Randomized Controlled Trials.

We pooled 2 clinical trials of tenecteplase compared with alteplase for the treatment of acute ischemic stroke, 1 that demonstrated superiority of tenecteplase and the other that showed no difference between the treatments in patient clinical outcomes. We tested the hypotheses that reperfusion therapy with tenecteplase would be superior to alteplase in improving functional outcomes in the group of patients with target mismatch as identified with advanced imaging. We investigated whether tenecteplase-treated patients had a different 24-hour reduction in the National Institutes of Health Stroke Scale and a favorable odds ratio of a modified Rankin scale score of 0 to 1 versus 2 to 6 compared with alteplase-treated patients using linear regression to generate odds ratios. Imaging outcomes included rates of vessel recanalization and infarct growth at 24 hours and occurrence of large parenchymal hematoma. Baseline computed tomography perfusion was analyzed to assess whether patients met the target mismatch criteria (absolute mismatch volume >15 mL, mismatch ratio >1.8, baseline ischemic core <70 mL, and volume of severely hypoperfused tissue <100 mL). Patients meeting target mismatch criteria were analyzed as a subgroup to identify whether they had different treatment responses from the pooled group. Of 146 pooled patients, 71 received alteplase and 75 received tenecteplase. Tenecteplase-treated patients had greater early clinical improvement (median National Institutes of Health Stroke Scale score change: tenecteplase, 7; alteplase, 2; P=0.018) and less parenchymal hematoma (2 of 75 versus 10 of 71; P=0.02). The pooled group did not show improved patient outcomes when treated with tenecteplase (modified Rankin scale score 0-1: odds ratio, 1.77; 95% confidence interval, 0.89-3.51; P=0.102) compared with alteplase therapy. However, in patients with target mismatch (33 tenecteplase, 35 alteplase), treatment with tenecteplase was associated with greater early clinical improvement (median National Institutes of Health Stroke Scale score change: tenecteplase, 6; alteplase, 1; P<0.001) and better late independent recovery (modified Rankin scale score 0-1: odds ratio, 2.33; 95% confidence interval, 1.13-5.94; P=0.032) than those treated with alteplase. Tenecteplase may offer an improved efficacy and safety profile compared with alteplase, benefits possibly exaggerated in patients with baseline computed tomography perfusion-defined target mismatch. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01472926. URL: https://www.anzctr.org.au. Unique identifier: ACTRN12608000466347.