DWI Volume Research Articles

Interleukin-10 facilitates the selection of patients for systemic thrombolysis

BackgroundClinical-Diffusion mismatch (CDM; NIHSS score ≥8 & DWI lesion volume ≤25 mL) and Perfusion-Diffusion mismatch (PDM; difference >20% between initial DWI and MTT lesion volumes) have been proposed as surrogates for ischemic brains that are at risk of infarction. However, their utility to improve the selection of patients for thrombolytic treatment remains controversial. Our aim was to identify molecular biomarkers that can be used with neuroimaging to facilitate the selection of ischemic stroke patients for systemic thrombolysis.MethodsWe prospectively studied 595 patients with ischemic stroke within 12 h of the stroke onset. A total of 184 patients received thrombolytic treatment according to the SITS-MOST criteria. DWI and MTT volumes were measured at admission. The main outcome variable was good functional outcome at 3 months (modified Rankin scale <3). Serum levels of glutamate (Glu), IL-10, TNF-α, IL-6, NSE, and active MMP-9 also were determined at admission.ResultsPatients treated with t-PA who presented with PDM had higher IL-10 levels at admission (p < 0.0001). In contrast, patients with CDM had higher levels of IL-10 (p < 0.0001) as well as Glu and TNF-α (all p < 0.05) and lower levels of NSE and active MMP-9 (all p < 0.0001). IL-10 ≥ 30 pg/mL predicts good functional outcome at 3 months with a specificity of 88% and a sensitibity of 86%. IL-10 levels ≥30 pg/mL independently in both patients with PDM (OR, 18.9) and CDM (OR, 7.5), after an adjustment for covariates.ConclusionsSerum levels of IL-10 facilitate the selection of ischemic stroke patients with CDM and PDM for systemic thrombolysis.

Stroke Mismatch Volume with the Use of ABC/2 Is Equivalent to Planimetric Stroke Mismatch Volume

In the clinical setting, there is a need to perform mismatch measurements quickly and easily on the MR imaging scanner to determine the specific amount of treatable penumbra. The objective of this study was to quantify the agreement of the ABC/2 method with the established planimetric method. Patients (n = 193) were selected from the NINDS Natural History Stroke Registry if they 1) were treated with standard intravenous rtPA, 2) had a pretreatment MR imaging with evaluable DWI and PWI, and 3) had an acute ischemic stroke lesion. A rater placed the linear diameters to measure the largest DWI and MTT lesion areas in 3 perpendicular axes-A, B, and C-and then used the ABC/2 formula to calculate lesion volumes. A separate rater measured the planimetric volumes. Multiple mismatch thresholds were used, including MTT volume - DWI volume ≥50 mL versus ≥60 mL and (MTT volume - DWI volume)/MTT volume ≥20% versus MTT/DWI = 1.8. Compared with the planimetric method, the ABC/2 method had high sensitivity (0.91), specificity (0.90), accuracy (0.91), PPV (0.90), and NPV (0.91) to quantify mismatch by use of the ≥50 mL definition. The Spearman correlation coefficients were 0.846 and 0.876, respectively, for the DWI and MTT measurements. The inter-rater Bland-Altman plots demonstrated 95%, 95%, and 97% agreement for the DWI, MTT, and mismatch measurements. The ABC/2 method is highly reliable and accurate for quantifying the specific amount of MR imaging-determined mismatch and therefore is a potential tool to quickly calculate a treatable mismatch pattern.

Abstract WMP13: The Predictive Value of Volumetric MRI Profiles in Stroke Patients Receiving IV tPA in the 3-Hour Time Window

Background: Recent studies have detected a population of acute ischemic stroke patients whose MRI profile is associated with intracranial hemorrhage (ICH) when treated beyond 3 hours. This so-called malignant profile (MP) supports MRI based selection of patients for treatment. Purpose: To test the hypothesis that there is an MRI based volumetric profile that identifies patients at increased risk of ICH when treated with IV tPA within 3 hours Methods: An analysis was performed on a database of stroke patients provided by the STIR and VISTA Imaging Investigators. 75 patients were identified who had DWI, PWI, and GRE images prior to IV tPA and follow-up imaging to assess for parenchymal hematoma (PH). The pre-tPA MRI scans were analyzed using Matlab software to calculate DWI and PWI volumes. DWI lesions were defined by an ADC threshold of 600. PWI lesions were defined by a time-to-peak threshold of an 8 seconds delay. Follow-up GRE images were reviewed for evidence of PH. ROC curves were generated using thresholds from 1-300mL. Results: 44 of the 75 patients were women with a mean ± stdev age of 70±17. The mean NIHSS was 12±9. The mean time from stroke onset to tPA administration was 147±30 minutes. For the entire cohort, mean lesion volumes were 22±41mL for DWI and 41±42 mL for PWI. 9 patients developed PH. For the PH group, mean lesion volumes were 24±20 mL for DWI and 48±40 mL for PWI. The ROC curves are shown in Figure 1. The areas under the curves are 0.68 for DWI volumes and 0.60 for PWI volumes. The optimal thresholds for predicting PH were 13 mL for DWI with a sensitivity of 0.67 and a specificity of 0.66 and 21 mL for PWI with a sensitivity of 0.78 and a specificity of 0.46. Conclusions: Although DWI volume performed better than PWI volume in predicting PH, neither served as a robust predictor in this population. Although further studies are needed, these results suggest that an MRI profile defined by DWI and PWI volumes in the 0-3 hour window may not be able to reliably guide clinical management.

Abstract TMP8: Post-thrombolysis Changes in DWI Lesion Volume and Correlation with Good Clinical Outcome

Objectives and Hypothesis: Studies investigating the change of the DWI volume after thrombolysis have not demonstrated a consistent correlation with clinical outcome. Our objective was to quantify the DWI change at 2 hours and compare to the change in NIHSS in a large homogeneous stroke patient population. Our hypothesis is that patients with a decrease in DWI volume at 2 hours have a better clinical outcome compared to patients with no decrease. Methods: Patients were selected from the Lesion Evolution of Stroke and Ischemia On Neuroimaging (LESION) Project if they: had a pre-treatment MRI with evaluable DWI, were treated with standard IV-tPA, and had post-treatment MRI with evaluable DWI at 2 and 24 hours. A reader measured the DWI volumes using a validated technique. A vascular neurologist scored the NIHSS at pre-treatment, 2 and 24 hours and the mRS at discharge, 5, 30 and 90 days. The Chi-Squared, independent samples median and Mann-Whitney U tests were used to demonstrate differences between groups. Results: Seventy-one patients met the study criteria with a mean (±SD) age of 71.6 (±16.4) years, 58% women (n=41), median baseline NIHSS of 9 (IQR25-75: 4-18), median onset of 45 minutes (30-65) and median first MRI to start of thrombolysis of 47 minutes (39-59). The median pre-treatment and 2 hour DWI volumes were 8.4 ml (2.1-51.5) and 11.4 (3.6-54.7). Sixteen patients (23%) had a decrease in DWI volume &gt; 2 ml at 2 hours versus 55 (77%) had an increase or no change at 2 hours (p=0.000). Of the 16 patients with a decrease in DWI volume &gt; 2 ml at 2 hours, 10 (63%) had a mRS=0 or 1, while 20 (36%) of the 55 patients with no decrease had a mRS=0 or 1 (p=0.192). Limiting the analysis to the 43 patients with a pre-treatment DWI lesion ≥ 5 ml, there was a significant difference in mRS between the 15 patients with a decrease in DWI volume &gt; 2 ml at 2 hours versus the 28 patients with no decrease, median of 1 versus 4, (p=0.014). There was also a significant difference in mRS distribution between these groups, (0-3 versus 2-6, p=0.008). Conclusions: In patients with a substantial pre-treatment DWI lesion volume, the decrease of DWI volume at 2 hours post-thrombolysis is a significant predictor of good clinical outcome.

Abstract TP21: Impact Of Complete Recanalization On The Relationships Between Pretreatment Dwi Volume And Clinical Outcome In Patients Treated By Endovascular Treatment.

Objectives: To evaluate the relationships between pre-treatment DWI volume and clinical outcome following endovascular therapy. Methods: Patients from the REcanalisation using Combined intravenous Alteplase and Neurointerventional ALgorithm for acute Ischemic StrokE (RECANALISE) study who suffered an acute hemispheric infarction with a large vessel occlusion and underwent DWI before endovascular treatment were enrolled. DWI volumes were automatically calculated by the RAPID software. Recanalization was graded using the TIMI scale. Outcomes assessed were favorable outcome (mRS 0-2) and death at 90 days. Findings: 66% (138/210) of the patients were eligible for this substudy. Mean age was 69.6 years (+/-17.6), median NIHSS 16 (IQR: 10-21) median time to MRI 110 min (IQR 77-178), and median time to treatment 149 min (IQR: 115-250). Median DWI volume was 14mL (IQR: 5 to 43) and was categorized into tertiles.Median volume per tertile were: Small: 3mL(IQR:1-5); Moderate 14mL(IQR:10-20) and Large 60mL(IQR:43-104)including 19 patients with a very large DWI lesion (&gt;70mL). TIMI 3 was achieved in 47%[median delay 238 min, (IQR, 206 to 285)]and TIMI 2 in 38%; [median delay 269 min, (IQR, 219 to 350)]. Overall, the rate of favorable outcome decreased and the death rate increased gradually with DWI volume.( cf Table) After adjustment for age and NIHSS, complete recanalization was associated with a higher rate of favorable outcome and decreased death rate in the moderate and large DWI volume tertiles.(cf table)This relationship was not observed in patients with very large (&gt;70 mL) or small DWI volumes. Conclusion: In patients undergoing endovascular treatment, our results demonstrate that increasing DWI volumes were associated with a worse outcome while a complete recanalization was associated with a significant better clinical outcome in patients with a moderate to large DWI lesion. This relationship was not observed in small or very large DWI lesion volume (&gt;70 mL). /&gt;

Abstract 35: Early Diffusion Weighted Imaging and Perfusion Weighted Imaging Lesion Volumes Forecast Final Infarct Size in DEFUSE 2

Background: It is hypothesized that early DWI lesions accurately estimate the size of the irreversibly injured ischemic core and that appropriately thresholded PWI lesions (Tmax &gt; 6 seconds) approximate the volume of critically hypoperfused tissue. With incomplete reperfusion, the union of baseline DWI and post-treatment PWI is hypothesized to predict infarct volume. Methods: This is a substudy of DEFUSE 2; all patients who had technically adequate MRI scans at 3 time points were included: just prior to endovascular therapy, within 12 hours post-therapy, and at 5 days. Baseline DWI and early follow-up PWI lesion volumes were determined by the RAPID software program and manually adjusted by the DEFUSE 2 core lab if needed. Final infarct volumes were assessed on the Day 5 FLAIR and corrected for edema. Reperfusion was defined based on the reduction in PWI lesion volume between baseline and early follow-up MRI. DWI and PWI volumes were correlated with final infarct volumes. Results: Seventy-eight patients were eligible; the 28 patients with &gt;90% reperfusion show a high correlation between early DWI volume and final infarct volume (r = 0.81, p &lt; 0.001) with a slope of 0.95. Twelve patients with &lt;10% reperfusion have a high correlation between baseline PWI (Tmax &gt;6 sec) volume and final infarct volume with a slope of 1.17 (r = 0.93, p &lt; 0.001). Using all 78 patients, the union of baseline DWI with early follow-up PWI is highly correlated with final volume (r = 0.86, p &lt; 0.001) with a slope of 1.01. The median absolute difference between observed and predicted final volume is 15 ml (IQR, 4.8-32.8). Conclusions: Early DWI and PWI (Tmax &gt; 6 sec) volumes provide a reasonable approximation of final infarct volume following endovascular therapy.

Abstract WMP11: The Association between Endovascular Reperfusion and Favorable Clinical Response Is Similar in Older and Younger Stroke Patients

Background: Older stroke patients generally have poorer clinical outcomes than younger stroke patients. We aimed to determine if the clinical response following endovascular reperfusion differs between older and younger patients with the Target Mismatch profile. Methods: Stroke patients enrolled in the DEFUSE 2 study underwent MRI diffusion (DWI) and perfusion (PWI) weighted imaging prior to endovascular treatment. Target Mismatch was defined as a ratio of PWI (Tmax &gt;6s) over DWI volume &gt;1.8, DWI volume &lt;70ml, and a PWI (Tmax &gt;10s) volume &lt;100ml. Favorable clinical response was defined as a &gt;8 point improvement on the NIHSS or an NIHSS score of 0-1 at 30 days. The relationship between baseline clinical and neuroimaging variables and favorable clinical response, was assessed using logistic regression. In addition, we evaluated the interaction of age and reperfusion on favorable clinical response and compared the effect of reperfusion between younger (age ≤ 80 years) and older (age &gt; 80 years) patients. Results: Seventy-eight patients had a Target Mismatch and forty-two patients had a favorable clinical response. Age (p&lt;0.01), reperfusion status (p&lt;0.01), baseline DWI volume (p=0.07), hypertension (p&lt;0.01) and history of stroke or TIA (p&lt;0.01) were associated with favorable clinical response in univariate analyses. In multivariate analysis, age (p&lt;0.05), reperfusion (p&lt;0.01) and baseline DWI volume (p&lt;0.05) were independent predictors of favorable clinical response. The age by reperfusion status interaction was not significant in the multivariate model (p = 0.3). Additionally, there was no significant difference between the odds ratio for favorable clinical response with reperfusion in patients ≤80 years (n = 58; OR = 6.2, 95% CI = 1.7 - 24.4) and those above 80 years (n = 20; OR = 2.1, 95% CI = 0.2 - 21.1) (p = 0.3 for the difference between the odds ratios). Conclusion: Target Mismatch patients who are younger have overall better clinical outcomes than older patients with the Target Mismatch. The association between endovascular reperfusion and favorable clinical response did, however, not differ between younger and older stroke patients. These results argue against the use of an age cutoff for endovascular stroke therapy.

Abstract 179: Patient Selection for Endovascular Stroke Therapy: Can MRA substitute for PWI?

Background: The DEFUSE 2 study demonstrated that in acute ischemic stroke patients, the perfusion-diffusion mismatch profile, termed Target Mismatch (TMM), is associated with favorable clinical outcomes following endovascular reperfusion; no association was present for patients without TMM. Perfusion imaging,however, may not be feasible in various clinical settings. We examined whether a combination of magnetic resonance angiography (MRA) and DWI could be used as an alternative to PWI/DWI. Methods: We assessed agreement between the MRA/DWI mismatch and TMM profiles. MRA/DWI Mismatch was defined as an ICA or MCA-M1 occlusion with a DWI volume &lt;25 ml, or a distal MCA occlusion with a DWI volume &lt;15 ml. The TMM was defined as a PWI (Tmax &gt;6 sec) / DWI &gt;1.8, DWI &lt;70 ml and PWI (Tmax &gt;10 sec) &lt;100 mL. Favorable Clinical Response was defined as an improvement of ≥8 points on the NIHSS between day 0 and day 30, or an NIHSS score of ≤1 at day 30. The response to reperfusion was assessed in patients with MRA/DWI mismatch and no MRA/DWI mismatch, and similarly, in patients with TMM and no TMM. Results: In DEFUSE 2, 58 of 94 patients had MRA/DWI mismatch (61.7%) and 76 had TMM (80.9%). The MRA/DWI mismatch model correctly identified 71% of the TMM patients (54/76). It had a high positive predictive value for identifying TMM (54/58; 93.1%), but relatively low sensitivity (54/76; 71%). There was a differential response to reperfusion according to a patient’s TMM status (p=0.03), but not according to their MRA/DWI mismatch status (p=0.5; see figure). Conclusions: The MRA/DWI mismatch model has high specificity for identifying TMM but lacks sensitivity.Consequently, patient selection based on MRA/DWI criteria may exclude a substantial proportion of patients from treatment who have the potential to respond favorably to reperfusion.

Abstract 65: Malignant Emboli On Trans Cranial Doppler During Carotid Stenting Predict Post Procedural DWI Lesions And Are Most Common During Stent And Distal Protection Device Deployment

BACKGOUND: We evaluated the safety of the steps during carotid stenting. METHODS: This was a prospective single-arm study. Cases were monitored by TCD during the stenting procedure. The time of each of 11 steps was recorded and noted during TCD interpretation. Post stenting MRI was done in all patients. Emboli on TCD were classified based on the relative energy index of microemboli (REIM) method into microemboli (REIM ≤ 1) or malignant (REIM &gt;1). Medians were compared using Mann-Whitney test. A negative binomial model was used to investigate the predictive value of TCD findings on new DWI hits. RESULTS: We enrolled 30 subjects. The median age was 70.5 years and 23.3% were asymptomatic. The median count of embolic signals was 212.5 (108 microemboli, 80 malignant). Stent deployment had the highest median count 58 (31 microemboli, 20 malignant) followed by protection device deployment 30 (21 microemboli, 10 malignant, (p value 0.0006)) “Figure”. On post stenting MRI, 80% had new DWI hits. The median DWI count was 4 (range 0-33). The median volume of DWI hits was 0.4 ml (range 0 - 6.1 ml). 63% of patients had a total volume under 1 ml. Only 2 patients (6.7%) had new deficits post stenting. The median DWI volume in those patients was 3.0 ml compared to 0.6 ml in asymptomatic cases (p 0.037). Median emboli count in those with vs. without new deficits was not different (p 0.87) Total TCD emboli count did not predict DWI hits, adjusting for age and symptoms’ status (p 0.25). Malignant emboli predicted new DWI hits (p 0.044). For every malignant embolus, the expected count of DWI hits increases by 1% (CI95 0-2%). There was no relation between total or malignant emboli with the DWI volume. CONCLUSIONS: In this prospective study, we observed a high incidence of emboli on TCD during stenting, especially when stent and protection device were deployed. Most patients developed new DWI hits but only 6.7% had new deficits. The combined DWI volume was less than 1.0 ml in most cases. Only malignant emboli predicted new DWI hits.

Abstract WP7: Leukoaraiosis And Outcomes After Intra-arterial Therapy In Acute Ischemic Stroke

Background: Selecting patients most likely to benefit (MLTB) from intra-arterial therapy (IAT) is essential to assure favorable outcomes after intervention for acute ischemic stroke (AIS). Leukoaraiosis (LA) has been linked to infarct growth, risk of hemorrhage after IV rt-PA, and poor post-stroke outcomes. We investigated whether LA severity is associated with AIS outcomes after IAT. Methods: We analyzed consecutive AIS subjects from our institutional GWTG-Stroke database enrolled between 01/01/2007-06/30/2009, who met our pre-specified criteria for MLTB: CTA and MRI within 6 hours from last known well, NIHSS score ≥8, baseline DWI volume (DWIv) ≤ 100 cc, and proximal artery occlusion and were treated with IAT. LA volume (LAv) was assessed on FLAIR using validated, semi-automated protocols. We analyzed CTA to assess collateral grade; post-IAT angiogram for recanalization status (TICI score ≥2B); and the 24-hour CT for symptomatic ICH (sICH). Logistic regression was used to determine independent predictors of good functional outcome (mRS≤ 2) and mortality at 90 days post-stroke. Results: There were 48 AIS subjects in this analysis (mean age 69.2, SD±13.8; 55% male; median LAv 4cc, IQR 2.2-8.8cc; median NIHSS 15, IQR 13-19; median DWIv 15.4cc, IQR 9.2-20.3cc). Of these, 34 (72%) received IV rt-PA; 3 (6%) had sICH; 21 (44.7%) recanalized; and 23 (50%) had collateral grade ≥3. At 90 days, 15/48 (36.6%) were deceased and 15/48 had mRS≤ 2. In univariate analysis, recanalization (OR 6.2, 95%CI 1.5-25.5), NIHSS (OR 0.8 per point, 95%CI 0.64-0.95), age (OR 0.95 per yr, 95%CI 0.89-0.99) were associated with good outcome, whereas age (OR 1.1, 95%CI 1.01-1.14) and HTN (OR 5.6, 95%CI 1.04-29.8) were associated with mortality. In multivariable analysis including age, NIHSS, recanalization, collateral grade, and LAv, only recanalization independently predicted good functional outcome (OR 21.3, 95%CI 2.3-199.9) and reduced mortality (OR 0.15, 95%CI 0.02-1.12) after IAT. Conclusions: LA severity is not associated with poor outcome in patients selected MLTB for IAT. Among AIS patients considered likely to benefit from IAT, only recanalization independently predicted good functional outcome and decreased mortality.

Abstract TMP11: Leptomeningeal Collaterals Predict Infarct Growth And 90 Day Clinical Outcome In Acute Ischemic Strokes Given Intra Arterial Therapy.

Introduction: We tried to explore the role of lepto meningeal collaterals, baseline imaging to recanalization time in predicting infarct growth and final clinical outcome in acute ischemic strokes. Methods: Data is from a prospective study of consecutive acute stroke patients (2005-2009) from Keimyung University, Daegu,South Korea analysed at University of Calgary. Only patients with M1 MCA+/- intracranial ICA on baseline CT-angio, known stroke onset time with MR DWI at baseline and follow-up were included for analyses. Baseline infarct volume on DWI was calculated using Quantomo, a validated in house software. Infarct growth was calculated as difference in DWI volume between 24 hrs and baseline. Lepto meningeal collaterals at baseline CT-angio assesed using a previously published scale. Results: Of the 264 patients analysed 84 patients were eligible for the study. Of 84 patients [mean age 65.2 +/- 13 yrs, 52.4% male, median NIHSS 14 IQR=8.5, median time from onset of stroke symptom to baseline MR 164 mins, IQR 100.5) in the study, 59.5% achieved TIMI 2-3 recanalization and 35.7% good clinical outcome (mRS 0-2). Median baseline DWI volume was 31.6 ml (IQR 75); median infarct growth 29.8 ml (IQR 64.1). We noted significant correlation (spearman’s r=-0.68, p&lt;0.001) between baseline DWI volume and collateral status and between infarct growth and collateral status (r=-0.38, p&lt;0.01). No correlation (r=0.1, p=0.34) was noted between infarct growth and baseline MR to recanalization time. In patients with baseline DWI volume &lt;=18 ml (group 1), 61.3% of patients achieved good clinical outcome when compared to 26.7% in patients with volume 18-80 ml (group 2) and 13% with volume &gt;80 ml (group 3). Median infarct growth was lowest in group 1 (5.9 ml, IQR 52.7) followed by group 2 (30.5 ml, IQR 70.6) and group 3 (63 ml, IQR 108.1). Conclusion: Leptomeningeal collateral status determines baseline infarct volume and the extent of infarct growth until recanalization is achieved

Abstract WP35: An ASL Collateral Score Can Identify Improved Quantitative Cerebral Blood Flow in Acute Stroke Patients

Objective: To measure quantitative hemodynamic parameters in acute stroke patients using a tomographic collateral assessment based on arterial spin labeling (ASL) [1]. Methods: Patients were retrospectively identified who met these criteria: symptom onset &lt;27 hrs, DWI volume &gt;=10 ml, and ASL and bolus contrast PWI, 1.5T. Pseudocontinuous 3D fast spin echo ASL was performed with the parameters: TR/TE/label time/post-label delay 5500/9.5/1500/2000 ms. PWI was performed using 0.1 mmol Gd and single-shot EPI with the parameters: TR/TE 1800/40 ms. Automated software (RAPID) was used to measure relative CBF, CBV, and time to peak of the residue function (Tmax) [2]. The combined ASL and DSC method was used to determine quantitative CBF and CBV [3]. A four point collateral score (CS) (0=poor, 1=intermediate, 2=good, 3=antegrade perfusion) [4] was determined based on ASL arterial transit artifact (ATA) in 20 ASPECTS ROI’s in each patient [1]. Tests for significant relationships between CS and each parameter was performed. Findings: 13 patients were identified (4 M, 63±13 yrs, 17±7 hrs from symptom onset, DWI size 61±52 ml, PWI Tmax&gt;6 sec size 84±65 ml). CBF increased with increasing CS, with the highest CBF in the antegrade perfused regions. CBV also increased with CS, but there was no difference between good collateral and antegrade regions. Tmax decreased significantly as CS increased. Acute stroke patients with good and poor collaterals are shown in the Figure (yellow arrows = collaterals). Conclusions: Collaterals are important because they supply CBF. ASL is able to predict the quality of collaterals in acute stroke, as was shown previously in Moyamoya disease [1]. This non-contrast assessment of collaterals on MRI may improve patient selection for stroke therapy.

Abstract WMP9: Impact of Collateral Blood Flow on Clinical Presentation, Diffusion and Perfusion Imaging, Infarct Growth and Clinical Outcome in the DEFUSE 2 Trial

Objective: To determine the relationships between angiographic collaterals and diffusion/perfusion imaging, subsequent infarct growth and clinical outcomes in DEFUSE 2 study patients. Methods: Patients undergoing endovascular therapy within 12 hours of stroke onset were prospectively enrolled. Only patients with a TICI score of 0, 1 and ICA/M1 occlusion at baseline were included in this analysis. A blinded reader assigned a collateral score using a previously described 5 point scale, from 0 (no collateral flow) to 4 (complete/rapid collaterals to entire ischemic territory). Analysis was dichotomized to poor flow (0-2) versus good flow (3-4). Collateral score was correlated with baseline NIHSS, DWI volume, PWI volume (Tmax &gt; 6), TICI reperfusion, infarct growth and mRS at day 90. Results: Sixty patients had TICI 0, 1 ICA/M1 occlusions and adequate angiographic images to evaluate collaterals. Baseline NIHSS correlated with collateral score (p=0.002). Median NIHSS for patients with poor collateral flow (0-2) was 18 (IQR, 13-22) versus 14 (10-17) for those with good flow (3-4), p=0.025. Baseline T max &gt; 6 volume correlated with collateral score (p=0.002). Median volume of tissue at risk (T max &gt; 6) in those with poor collateral flow was 115 ml (IQR, 74-136) versus 82 (51-109) with good flow, p=0.012. Collateral score did not correlate with baseline DWI volume. TICI reperfusion (0-3) correlated with collateral score (p=0.027). Patients with poor collateral flow had 29% TICI 2b-3 reperfusion versus 65.5% with good flow, p=0.009. Those with poor reperfusion (TICI 0-2a) showed a trend to more infarct growth with poor collaterals, 92 ml (52-194) [mean (IQR)] versus 36 ml (14-106) with good collaterals, p=0.06. Patients with poor collaterals who reperfused (TICI 2b-3) were still likely to have a mRS 0-2 at 90 days compared to those without reperfusion; OR 12 (95% CI, 1.6-98). Conclusion: Collaterals correlate with baseline clinical stroke severity and the PWI volume. In addition, good collaterals correlate with higher rates of reperfusion (TICI 2b-3). When patients do not reperfuse, good collaterals appear to limit infarct growth.

Abstract WP22: A Scoring System Based on Age and DWI Volume Predicts Poor Functional Outcome Following Endovascular Treatment for Acute Ischemic Stroke

Background: The Houston IAT (HIAT) score predicts poor outcome following endovascular stroke therapy based on clinical variables (age, serum glucose, and NIHSS score). We aimed to validate the HIAT score in an independent cohort of patients treated with endovascular therapy (DEFUSE 2) and determine if prediction of poor outcome could be improved by including neuroimaging variables in the prediction score. Methods: Patients enrolled in the DEFUSE 2 study had a clinical diagnosis of acute ischemic stroke and underwent MRI prior to endovascular treatment. Poor functional outcome was defined as a modified Rankin Scale score of 4 to 6 at day 90. The relationship between baseline clinical and neuroimaging variables and poor functional outcome was assessed using univariate and multivariate logistic regression. Statistically significant variables in the multivariate model were used to create a new scoring system. We evaluated the new scoring system and the HIAT score using ROC analysis. Results: One hundred and ten patients were included in the analysis; forty-two patients had a poor functional outcome. Validation of the HIAT score demonstrated similar ROC properties in the DEFUSE 2 cohort (AUC=0.69) compared to the Houston derivation cohort (AUC=0.73). In DEFUSE 2, age (p=0.001), baseline DWI volume (p=0.09), baseline NIHSS score (p=0.03) and hypertension (p=0.003) were associated with poor functional outcome in univariate analysis. In multivariate analysis, age (p&lt;0.001) and baseline DWI volume (p=0.03) were independent predictors of poor functional outcome. Based on this we developed a new scoring system with a maximum of 3 points awarded for age (0 points, &lt; 55; 1 point, 56-69; 2 points, 70-79; 3 points, ≥ 80) and a maximum of 1 point awarded for baseline DWI volume (0 points, volume ≤ 15 cc; 1 point, volume &gt;15 cc). The percentage of patients with poor functional outcomes increased with the number of points awarded (0% poor outcomes in patients with 0 points, 25% with 1 point, 30% with 2 points, 75% with 3 points, and 89% with 4 points). The AUC for the new scoring system was 0.82. Conclusion: The new scoring system that incorporates baseline DWI volume and age predicts poor outcome more accurately than a scoring system based on clinical variables alone.

Abstract WMP17: Early DWI Reversal Following Endovascular Reperfusion Is Typically Transient

Background and Purpose: There are conflicting reports regarding the incidence and prognostic significance of DWI reversal following reperfusion therapy. The aim of this study was to assess the frequency and extent of early DWI reversal following endovascular therapy and to determine if early reversal is sustained or transient. Methods: This is a substudy of the DEFUSE 2. MRI with DWI and PWI was performed before (DWI 1) and within 12 hours after (DWI 2) endovascular stroke treatment and again at 5 days. Acute DWI lesions were outlined and quantified using mipav software (http://mipav.cit.nih.gov/). Ischemic lesion volumes were outlined on the Day 5 FLAIR then corrected for edema using a validated technique to determine the final infarct volume. Early DWI reversal was defined as (DWI 1 - DWI 2) &gt;3 ml and permanent DWI reversal was defined (DWI 1 - final infarct volume) &gt; 1 ml. Reperfusion was defined as a &gt;50% reduction in PWI volume (Tmax &gt;6 sec) on the MRI performed after endovascular therapy. The prognostic significance of early reversal was assessed in a regression model. Results: 104 patients had a technically adequate DWI and PWI prior to endovascular therapy (performed 4.4 [3.0-6.0] hours after symptom onset). Of these, 77 had an acute DWI lesion &gt;3 ml and a follow-up MRI (156 min [72-342] after completion of endovascular therapy) and a 5 day MRI. Seventeen percent (13/77) of the patients had early DWI reversal representing a median (IQR) of 42.4% (25.0-57.6) of the initial DWI lesion (median volume 10.9 ml [IQR 7.3-18.2]). The incidence of early DWI reversal was 21% (11/52) following reperfusion vs. 8% (2/25) in patients who did not reperfuse (p=0.20). Of the 13 patients with early DWI reversal, permanent DWI reversal occurred in only 2 (volume of permanent DWI reversal 6.9 ml and 4.7 ml). Early DWI reversal was not an independent predictor of clinical outcome. Conclusion: Early DWI reversal occurs in about 15-20% of patients following endovascular therapy and can involve a substantial percentage of the initial DWI volume. However, early DWI reversal is usually transient and does not appear to signify tissue salvage.

Abstract TP195: Tobacco And Stroke Among Active and Prior Cocaine Users: An Avenue For Prevention.

Background: We characterized stroke mechanisms and risk factors in a cohort of cocaine users across a broad range of socioeconomic status to inform stroke management and prevention efforts. Methods: Cases were consecutive patients ≥ 18 years with acute ischemic stroke (AIS) and enrolled into a prospective registry, with history or laboratory confirmed cocaine use. Non-cocaine user AIS controls matched for age, sex, and race were derived from the same study population (2:1 ratio). Demographic, risk factor, and clinical data were collected prospectively. TOAST subtypes were assigned. Admission brain MRIs were used to assess infarct size and location. Multivariate logistic regression model for variables showing univariate association with cocaine use at p &lt;0.2 was used to identify independent predictors of cocaine-associated AIS. Results: Between 2007-2010, we identified 91 cases and 182 controls (mean age 50.1±10.4 years; 73.6% male). Cases did not statistically differ from controls by income ($49,499 ±15,494 vs. $51,818±16,776), occupation (52% in “service/clerical”), or educational level (42.5% high-school graduates)(all p&gt;0.5). Stroke severity was similar in both groups (median NIHSS 5, IQR 1-8 vs. 5.7, IQR 1-8, p=0.3) as was acute DWI volume (median 33.6cc, IQR 5-20 vs. 21.2cc, IQR 5-20; p=0.5), and proportion of patients treated with IV tPA (12% vs. 17%, p=0.4). Active tobacco use was significantly greater in cocaine-associated AIS (84% vs. 6%, p&lt; 0.001). In multivariable analysis, tobacco use (OR 3.9, 95% CI 2.0-7.5), history of migraine (OR 2.5, 95% CI 1.1-5.9), and cardioembolic stroke subtype (OR 2.52, 95% CI 0.6-0.9) were independent predictors of cocaine-associated AIS. Subset analysis of toxicology confirmed (“active”) cocaine users (n=29) with AIS compared to non-cocaine using controls (n=58) from the same population. Association between cardioembolic stroke subtype (p&lt;0.004) persisted. Active tobacco use emerged as a robust predictor of cocaine-associated stroke (OR 12.9, 95%CI 3.7-44.4) in this subset. Conclusions: Active tobacco use is an independent predictor of stroke among both active and past cocaine users. Stroke prevention campaigns should target broader audiences for smoking cessation and cocaine use prevention.

Abstract TMP10: A 4D Patient-specific Metamorphosis-based Method to Model Ischemic Stroke Lesion Evolution from Acute Diffusion-weighted to Final T2-defined Outcome

There is considerable interest in how well acute DWI can predict the infarct on final T2-w imaging at &gt;1month after stroke. We estimated the 4D dynamic change, from the acute DWI to the final T2-w lesion, to assess DWI predictive ability. Our model dynamically simulates the evolution of uni- or multi-component lesions. We applied a 4D metamorphosis, modeling the morphogenesis of the acute (&lt;6hr) DWI lesion boundary into that of the final (90 day) T2-w in 10 representative patients, dividing the 90 days into 10 equal intervals. We estimated the mean contraction and expansion deformation velocities that drive change in the acute DWI to the final T2-w boundary, focusing on areas where the DWI volume differed from the final T2-w volume (DWI\T2). In DWI\T2, over the 10 patients, time-evolving contraction velocity values show a rapid decrease from 0.206+/-0.0091 (mean over time, mm/9days +/- sd) to 0.00097+/-0.001 with time, indicating that contracting DWI\T2 areas were very dynamic acutely and rapidly slowed. Expansion areas displayed a rapid and quasi-monotonic fall from 0.025+/-0.01 to 0.00075+/-0.00028 showing that some parts of DWI tissue had an early high expansion velocity which slowed with time, leading to appearance of newly infarcted areas not present in the acute DWI. A high correlation index (r=0.72, p&lt;0.001) between contraction (also expansion) velocity curves of all patients shows that the 4D evolution patterns of DWI\T2 were similar between patients. Our imaging derived 4D model of acute DWI-final T2-W lesion evolution shows a consistent pattern, with both ‘recovery’ and ‘new’ infarct happening rapidly at early time points. This confirms that a) acute DWI lesion includes salvageable tissue and is not all statically dead, b) acute DWI lesion does not include all final T2-w dead tissue and c) the method can accurately assess and quantify early treatment response, eg in clinical trials.

Abstract TMP16: Hypoperfusion Severity Is Associated With Poor Collaterals And Progresses Over Time

Background: We hypothesized that cerebral perfusion deficits are more severe in acute stroke patients with poor collaterals and that the severity would increase over time if reperfusion does not occur. Methods: This is a substudy of DEFUSE 2. Collaterals were assessed on conventional angiography and dichotomized as poor vs. good flow. DWI and PWI were performed before and within 12 hrs after endovascular therapy; PWI lesion volumes were determined using a Tmax&gt;6sec threshold. The hypoperfusion ratio (HR) was calculated by determining the proportion of the PWI lesion that had severe Tmax delay (&gt;10sec). Acute lesion growth was defined as the difference between the baseline and follow-up DWI volume. Part 1: In patients with an ICA or M1 occlusion we compared the HR to the collateral score. An ROC curve assessed whether the HR predicts the collateral score. Part 2: Among patients who did not experience early reperfusion, the difference between the baseline and follow-up HR was assessed and correlated with early infarct growth. Results: Part 1: Fifty six patients were eligible. Poor collateral flow was associated with larger baseline PWI lesion volume, p=0.012 and a higher HR compared to patients with good flow [median HR 45% (IQR: 35-52%) vs. 34% (IQR 14-41), p=0.003]. A HR &gt; 41% predicted poor collateral flow with an AUC=0.73 (sensitivity 65%, specificity 78%, p=0.003). Part 2: Thirty two patients who did not achieve reperfusion were included; PWI Tmax &gt;6sec lesions volumes at baseline and follow-up were similar (median volume 75 mL at both time points). The median HR at follow-up was significantly higher than baseline [46% IQR (34-65) vs. 40% (24-48), p=0.007; median difference = 13% (IQR: 3.5-17)]. Patients who had worsening of their HR between baseline and follow-up were more likely to experience early ischemic lesion growth (R=0.53, p=0.002). Conclusion: The size and severity of Tmax lesions are associated with angiographic collateral scores. Patients who have a high percentage of their PWI lesion comprised of severe Tmax delays are likely to have poor collaterals. When early reperfusion is not achieved, the severity of hypoperfusion progresses and this progression is associated with early infarct growth.

Abstract TP33: Early DWI Changes in the Thrombolysis Time Window: From DWI-Negative to Malignant Stroke in More than 300 Cases

Background: Thrombolysis for acute stroke is routinely based on time from last known well (TLKW) as the extent of ischemic injury during early epochs is assumed to be minimal. DWI is extremely sensitive, yet rarely acquired prior to thrombolysis and the nature of DWI lesions is largely unknown during this time window. Large or malignant strokes on DWI, however, result in poor outcome after thrombolysis. We retrospectively analyzed a large cohort of DWI acquired as part of a standard MRI protocol for triage of patients at a single center over 8 years. Methods: Consecutive patients with discharge diagnosis of ischemic stroke and documented time last known well to DWI MRI acquisition &lt; 4.5 hours were identified. An imaging expert outlined DWI lesions on every axial slice for all MRIs to calculate corresponding lesion volumes as often-subtle changes may evade automated detection. Total DWI volumes were analyzed with respect to age, gender, TLKW and time of day. Results: 307 stroke patients (mean age 69±17 years, 51% female) from 2004-2012 had DWI with TLKW &lt; 4.5 hours (mean 147±62 min). DWI lesion volume (median 3.67cc) in each case varied extensively (TLKW-DWI &lt; 1 hour (n=8) 0.40cc (0-93cc), 1-2 hours (n=126) 3.02 (0-265), 2-3 hours (n=78) 2.18 (0-103), 3-4.5 hours (n=95) 6.96 (0-227)). Only slight or negligible correlation (r=0.175, p=0.002) was noted between DWI lesion volume and TLKW-DWI time duration. DWI-negative findings &lt; 4.5 hours occurred in 8.5% of stroke cases. Malignant strokes (&gt;70cc) were noted in 7.5%. Older age was associated with DWI-negative strokes (mean 77 vs. 68 years, p=0.013). TLKW-DWI time duration was unrelated to DWI-negative strokes, yet malignant stroke was more common later (p=0.009). Interestingly, the majority of malignant strokes on DWI had TLKW during the daytime. Conclusions: DWI changes are extremely variable within 4.5 hours. Most lesions are small, yet malignant strokes are not uncommon. Further work should delineate the clinical determinants of these early malignant strokes to optimize outcomes in acute ischemic stroke.

Rapid identification of a major diffusion/perfusion mismatch in distal internal carotid artery or middle cerebral artery ischemic stroke

BackgroundWe tested the hypothesis that in patients with occlusion of the terminal internal carotid artery and/or the proximal middle cerebral artery, a diffusion abnormality of 70 ml or less is accompanied by a diffusion/perfusion mismatch of at least 100%.MethodsSixty-eight consecutive patients with terminal ICA and/or proximal MCA occlusions and who underwent diffusion/perfusion MRI within 24 hours of stroke onset were retrospectively identified. DWI and mean transit time (MTT) volumes were measured. Prospectively, 48 consecutive patients were identified with the same inclusion criteria. DWI and time to peak (TTP) lesion volumes were measured. A large mismatch volume was defined as an MTT or TTP abnormality at least twice the DWI lesion volume.ResultsIn the retrospective study, 49 of 68 patients had a DWI lesion volume ≤ 70 ml (mean 20.2 ml; SEM 2.9 ml). A DWI/MTT mismatch of > 100% was observed in all 49 patients (P < .0001). In the prospective study, there were 35/48 patients with DWI volumes ≤ 70 ml (mean 18.7 ml; SEM 3.0 ml). A mismatch > 100% was present in all 35 (P < .0001).ConclusionsAcute stroke patients with major anterior circulation artery occlusion are exceedingly likely to have a major diffusion/perfusion mismatch if the diffusion lesion volume is 70 ml or less. This suggests that physiology-based patient assessments may be made using only vessel imaging and diffusion MRI as a simple alternative to perfusion imaging.