Follow-up Infarct Research Articles

Assessment of Collateral Circulation Using Perfusion CT in Middle Cerebral Artery Thrombectomy-Treated Patients

Introduction: The prognostic value of leptomeningeal collateral circulation in thrombectomy-treated patients remains unclear. We evaluated the construct validity of assessing leptomeningeal collateral circulation using a new regional perfusion CT source image-based approach, the Perfusion Acquisition for THrombectomy Scale (PATHS). We also compared the prognostic value of PATHS with a further 6 scales based on various techniques: CT-angiography, perfusion CT, and digital subtraction angiography. Additionally, we studied the relationship between the scores for the different scales. Patients and Methods: We performed a retrospective study of consecutive patients with stroke and M1/terminal carotid occlusion treated with thrombectomy in our center. Leptomeningeal collateral circulation was prospectively evaluated using 7 scales: Tan and Miteff (CT Angiography); Calleja, Cao, American Society of Intervention and Therapeutic Neuroradiology/Society of Interventional Radiology, and PATHS (perfusion); and Christoforidis (Digital Subtraction Angiography). Correlations were studied using the Spearman method. Results: The study population comprised 108 patients. All scales predicted the modified Rankin Scale at 3 months (P ≤ .02) and all but 1 (Christoforidis) correlated with 24-hour brain infarct volume (P ≤ .02). These correlations were higher with PATHS (rho = −0.47, P < .001 for 3-month modified Rankin Scale; rho = −0.35, P < .001 for follow-up infarct volume). The multivariate analysis showed PATHS to be an independent predictor of modified Rankin Scale at 3 months less than equal to 2. A crosscorrelation analysis revealed a better correlation between scales that used the same techniques. Conclusions: PATHS can be used to assess leptomeningeal collateral circulation. PATHS had better prognostic value than other scales; therefore, it might be considered for assessment of leptomeningeal collateral circulation in candidates for thrombectomy. The moderate correlation between scales suggests that scores are not interchangeable.

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&lt;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&lt;0.001), lower rates of good outcome (52.8% vs 77.4%, p&lt;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.

Abstract 75: Hemorrhagic Transformation After Acute Ischemic Stroke Due to a Large Vessel Occlusion is Associated With Less Treatment Benefit

Introduction: Intracranial hemorrhage after acute ischemic stroke patients manifests as natural progression or as a complication of treatment with potential subsequent neurological deterioration. Currently it is unclear whether these hemorrhagic transformations (HT) contribute to the poorer functional outcomes observed in patients with large infarcts. The purpose of this study is to assess the association of HT with follow-up infarct volume (FIV) and functional outcome at 90 days after AIS. Additionally, we determined whether the development of HT was associated with a diminished endovascular therapy (EVT) effect. Methods: All patients from the HERMES collaboration with follow-up imaging were included. HERMES is pooled data from seven randomized controlled trials that assessed the efficacy and safety of EVT compared to usual care. Patients with HT were identified according to the ECASS classification and FIV was assessed on CT or MRI. Infarct and hemorrhage were included in the FIV. We assessed functional outcome using the modified Rankin Scale 90 days after stroke onset. Ordinal logistic regression with adjustment for potential confounders was used to determine the association of HT and FIV with functional outcome. Results: Of all included patients with follow-up imaging (n=1665), 42% had HT (n=698). Before and after adjustment for confounders HT and FIV were associated with a shift in the direction of poorer functional outcome (aOR:0.71,95%CI:0.58-0.86 and aOR:0.99,95%CI:0.99-0.99). EVT was beneficial in patients with and without HT, but effect was greater in patients without (aOR:1.70,95%CI:1.27-2.28 vs. aOR:2.51,95%CI:1.97-3.20)(figure 1.) Conclusions: In this analysis, patients with HT after AIS were less likely to have good functional outcome compared to those without HT, independent of the FIV. While the EVT effect was slightly diminished in patients who developed HT, EVT was always of significant benefit.

Abstract WP15: Correlation of 24-Hour Infarct Volumes and Imaging Reperfusion With Functional Independence in DEFUSE 3

Background: In DEFUSE 3, infarct volumes 24 hours after randomization did not significantly differ in EVT vs. medical management only (MM) groups. We hypothesized that this lack of difference was due underestimation of the final infarct volume among patients who had persistent penumbral tissue 24 hours after randomization that subsequently progressed to infarction. In this substudy, we evaluated if the 24 hr post-randomization DWI volumes correlated with functional independence. Methods: We correlated the 24-hr post-randomization DWI volumes and penumbral profiles with 90-day functional independence. Results: 182 patients, 92 were randomized to EVT, 90 to MM. 24 hr post-randomization Tmax and DWI volume were assessable for 75 EVT and 69 MM. Infarct volumes at 24 hr follow-up did not differ between EVT and MM median (IQR) ml 35.0 (17.6-81.6) vs 41.0(25.4-106.2), P=0.185. Still, 24 hr infarct volumes independently correlated with 90 day functional independence: median (IQR) 30.3 ml (9.0-55.6) vs. 47.5 ml (25.4-132.3), aOR=0.93 (95%CI=0.89-0.98, P=0.004) for achieving functional independence vs. disability for each additional 5 ml of infarct volume after adjustment for baseline NIHSS, age, glucose, and treatment, figure 1. EVT resulted in higher rates of reperfusion (&gt;90% reduction in Tmax&gt;6 seconds at 24 hrs in 79% of EVT vs. 18% of MM, P&lt;0.001). Patients who achieved successful reperfusion with no evidence of remaining penumbra had smaller 24- hr infarct volumes: 32.9 (17.6-67.0) vs. 59.3 (24.7-126.3), P=0.007), figure 2 and a higher odds of functional independence aOR=10.9, 95%CI 3.6-39.8, P&lt;0.001, compared to those who had remaining penumbral tissue, figure 3. Conclusion: 24 hr- post randomization infarct volumes independently correlated with functional independence in DEFUSE 3. Patients who had complete reperfusion had smaller follow-up infarct volumes and a higher odds of functional independence as compared to those with persistent penumbral mismatch.

Abstract TP91: Unfavorable Baseline Hypoperfusion Intensity Ratio is Associated With Infarct Growth and Poor Outcome in Patients With Distal MCA Occlusions

Background: A low hypoperfusion intensity ratio (HIR) predicts good collateral vessel status and correlates with infarct growth and functional outcome in early window patients with proximal large vessel anterior circulation occlusions. Its performance in predicting clinical and radiologic outcome has not been assessed in patients with more distal occlusions. In this retrospective analysis of the CT Perfusion to Predict Response to Recanalization in Ischemic Stroke (CRISP) study, we hypothesized that a favorable baseline HIR would predict less infarct growth in patients with distal middle cerebral artery (MCA) occlusions. Methodology: Patients with occlusions of an M2 or M3 branch of the MCA on catheter angiography were included; all patients underwent mechanical thrombectomy with TICI2B/3 reperfusion. Baseline ischemic core volume and HIR (Tmax &gt;10s / Tmax &gt;6s) were assessed with RAPID software; late follow-up infarct volumes (&gt;36 hours from initial CT perfusion) were manually determined from DWI MRI. Excellent functional outcome was defined as a modified Rankin score of 0-1. Results: Fourteen patients with baseline perfusion and late follow-up imaging were included; nine patients presented with M2 occlusions, and 5 with M3 occlusions. The mean baseline HIR of 0.48 was used to dichotomize patients into favorable or unfavorable baseline profiles. Patients with a favorable baseline HIR had significantly smaller baseline ischemic core volumes (0 mL [IQR 0-3.3] vs. 14.0 mL [IQR 8.7-22.1], p=0.01), smaller final infarct volumes (16.1 mL [IQR 12.7-41.2] vs. 71.4 mL [IQR 43.8-113.5], p=0.01) and less infarct growth (16.1 mL [IQR 9.4-31.9] vs. 49.0 mL [IQR 31.1-100.8], p=0.03). Excellent functional outcome was achieved in 6/6 (100%) of those with favorable baseline HIR, versus 3/8 (37.5%) with unfavorable baseline profile (p=0.03). Conclusion: In patients with distal MCA occlusions, poor collateral status at baseline as demonstrated by a high HIR score is associated with more infarct growth and worse clinical outcomes. HIR may be helpful for guiding thrombectomy decisions in patients with distal occlusions and warrants further prospective study in this population.

Abstract WMP19: Pattern of Internal Carotid Artery Calcification Modifies the Effect of Intravenous Thrombolysis

Introduction: The pattern of intracranial internal carotid artery calcification (ICAC) has been identified as an effect modifier of endovascular treatment in patients with acute ischemic stroke, but it is unclear whether it modifies the effect of intravenous thrombolysis. We evaluated the association between intravenous thrombolysis and 90-day clinical outcome, follow-up infarct volume and recanalization across different patterns of ICAC. Methods: Three groups from the Dutch acute stroke study, a prospective multicentre observational cohort study, were analyzed: patients with ischemic stroke, a subgroup (1) of patients with intracranial anterior circulation occlusions and a subgroup (2) of patients with M1 occlusions. ICAC pattern was determined on admission thin-slice non-contrast CT and categorized as absent, intimal, medial or indistinguishable. The primary outcome was 90-day modified Rankin scale. Other outcomes included follow-up infarct volume, recanalization and collateral status. Associations were quantified with regression analyses and stratified by ICAC pattern. Odds ratios (OR) and 95% confidence intervals (CI) were adjusted for demographics, cardiovascular risk factors, stroke severity, occlusion site and collateral status. Results: Of the 982 patients 609 (62%) received intravenous thrombolysis and 381 (39%) had unfavorable clinical outcome. Intravenous thrombolysis was associated with a lower modified Rankin scale in the groups without ICAC (adjusted OR 0.3; 95% CI 0.1-0.9) and with a medial ICAC pattern (adjusted OR 0.5; 95% CI 0.3-0.8), but not in the groups with an intimal (adjusted OR 0.9;95%-CI:0.5-1.5) or indistinguishable pattern (adjusted OR 0.6; 95% CI 0.2-1.8). In subgroup 1 (n=220), intravenous thrombolysis was associated with recanalization only in the group with a medial ICAC pattern (adjusted OR 3.5; 95% CI 1.2-11.0). In subgroup 2 (n=148), compared to an intimal ICAC pattern a medial ICAC pattern was associated with good collateral status (adjusted OR 2.6; 95% CI 1.1-6.0). Conclusions: Intravenous thrombolysis was significantly related to favorable clinical outcome and recanalization in the group with a medial ICAC pattern, but not in the groups with other ICAC patterns.

Computed Tomography Perfusion-Based Machine Learning Model Better Predicts Follow-Up Infarction in Patients With Acute Ischemic Stroke.

Prediction of infarct extent among patients with acute ischemic stroke using computed tomography perfusion is defined by predefined discrete computed tomography perfusion thresholds. Our objective is to develop a threshold-free computed tomography perfusion-based machine learning (ML) model to predict follow-up infarct in patients with acute ischemic stroke. Sixty-eight patients from the PRoveIT study (Measuring Collaterals With Multi-Phase CT Angiography in Patients With Ischemic Stroke) were used to derive a ML model using random forest to predict follow-up infarction voxel by voxel, and 137 patients from the HERMES study (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) were used to test the derived ML model. Average map, Tmax, cerebral blood flow, cerebral blood volume, and time variables including stroke onset-to-imaging and imaging-to-reperfusion time, were used as features to train the ML model. Spatial and volumetric agreement between the ML model predicted follow-up infarct and actual follow-up infarct were assessed. Relative cerebral blood flow <0.3 threshold using RAPID software and time-dependent Tmax thresholds were compared with the ML model. In the test cohort (137 patients), median follow-up infarct volume predicted by the ML model was 30.9 mL (interquartile range, 16.4-54.3 mL), compared with a median 29.6 mL (interquartile range, 11.1-70.9 mL) of actual follow-up infarct volume. The Pearson correlation coefficient between 2 measurements was 0.80 (95% CI, 0.74-0.86, P<0.001) while the volumetric difference was -3.2 mL (interquartile range, -16.7 to 6.1 mL). Volumetric difference with the ML model was smaller versus the relative cerebral blood flow <0.3 threshold and the time-dependent Tmax threshold (P<0.001). A ML using computed tomography perfusion data and time estimates follow-up infarction in patients with acute ischemic stroke better than current methods.

Development of a Routinely Applicable Imaging Protocol for Fast and Precise Middle Cerebral Artery Occlusion Assessment and Perfusion Deficit Measure in an Ovine Stroke Model: A Case Study.

Temporary middle cerebral artery occlusion (MCAO) in sheep allows modeling of acute large vessel occlusion stroke and subsequent vessel recanalization. However, rapid and precise imaging-based assessment of vessel occlusion and the resulting perfusion deficit during MCAO still represents an experimental challenge. Here, we tested feasibility and suitability of a strategy for MCAO verification and perfusion deficit assessment. We also compared the extent of the initial perfusion deficit and subsequent lesion size for different MCAO durations. The rete mirabile prevents reliable vascular imaging investigation of middle cerebral artery filling status. Hence, computed tomography perfusion imaging was chosen for indirect confirmation of MCAO. Follow-up infarct size evaluation by diffusion-weighted magnetic resonance imaging revealed fluctuating results, with no apparent relationship of lesion size with MCAO at occlusion times below 4 h, potentially related to the variable collateralization of the MCA territory. This underlines the need for intra-ischemic perfusion assessment and future studies focusing on the correlation between perfusion deficit, MCAO duration, and final infarct volume. Temporary MCAO and intra-ischemic perfusion imaging nevertheless has the potential to be applied for the simulation of novel recanalization therapies, particularly those that aim for a fast reperfusion effect in combination with mechanical thrombectomy in a clinically realistic scenario.

P121918F-FDG perfusion-metabolism mismatch 3 days after acute myocardial infarction predicts worse outcome: molecular glucose steel phenomenon visualized by hybrid PET-MRI images

Abstract Background The disturbance of cardiac energy substrate metabolism has a decisive role in the pathogenesis of adverse cardiac remodeling and heart failure. Under normoxic conditions, the free fatty acid metabolism is the predominant pathway by providing the highest energy per substrate molecule. Severe myocardial hypoxia leads to a switch from beta-oxidation to glucose metabolism to increase the ATP production per oxygen molecule. This metabolic disorder appears as perfusion-metabolism mismatch in 18F-fluorodeoxyglucose (18F-FDG) PET images, as increased 18F-FDG uptake in the under-perfused hypoxic myocardial area. Purpose The aim of our study was to evaluate the simultaneous perfusion, metabolism and function of the ischemic heart by hybrid 18F-FDG-PET-cMRI with late enhancement images in a translation animal model of heart failure. Methods Under general anesthesia, closed chest reperfused acute myocardial infarction (AMI) was induced in 36 domestic pigs by 90 min occlusion of the mid left anterior descending artery with a percutaneous intracoronary balloon, followed by reperfusion. Three days and 1 month after AMI, after 12h fasting, 18F-FDG-PET-cMRI were performed by using standardized acquisition protocols (n=30). Cardiac functional parameter, such as ejection fraction (EF), end-diastolic volume (EDV), infarct size, and mean tracer uptake of the infarcted area were quantitatively assessed. Six animals were euthanized after the 3-day 18F-FDG-PET-cMRI images to elaborate the differences in gene expression patterns in animals with perfusion-metabolic mismatch by using next generation sequencing (NGS) and pathway network analyses. Results Eight (group Mismatch) of the 30 animals (group Match) with 1-month follow-up showed high 18F-FDG uptake in the infarcted area (perfusion-metabolism mismatch) at the 3-day 18F-FDG-PET-cMRI-LE images (Figure). The animals in the Mismatch group had significantly lower EF at 3 days (34±8.8 vs 42±3%) and at the 1-month follow-up (35.8±6 vs 43±6.6%) and larger infarct size at day 3 (26.6±6.6 vs 22.1±4.4%) and 1 month (28±5.4 vs 20.3±4.3%) with higher EDV at 1 month. Mean tracer uptake of the infarcted area was significantly reduced in the Mismatch group at 1 month (56±23.1 vs 64.7±13.2%). NGS revealed downregulation of the cholesterol metabolism pathway, and upregulation of carbohydrate derivative catabolism pathway with highly activated innate immune system and genes responsible for cytokine activation in the infarcted area 3 days post-AMI in the Mismatch group, which explains the paradox high 18F-FDG tracer uptake in the infarction zone. Accordingly, the high energy demand of the severe hypoxic area led to “glucose steel phenomenon” at the molecular level, subtracting the 18F-FDG from the normally perfused non-ischemic myocardial regions. Conclusions 18F-FDG-glucose perfusion-metabolism mismatch early after AMI visualized by hybrid 18F-FDG-PET-MRI images predict development of LV adverse remodeling. Acknowledgement/Funding Fibrotarget EU Grant Nr 602904

Blood Pressure Drop and Penumbral Tissue Loss in Nonrecanalized Emergent Large Vessel Occlusion.

Background and Purpose- For patients with emergent large vessel occlusion who may not benefit from timely recanalization treatment, maintaining adequate cerebral perfusion to prevent penumbral tissue loss is a key therapeutic strategy. Cerebral perfusion should be proportional to systemic blood pressure (BP) due to the loss of autoregulation properties in ischemic brain tissue. We hypothesized that acute fluctuations in BP would lead to aggravated penumbral tissue loss in persistent large vessel occlusion. Methods- A total of 80 patients with persistent large vessel occlusion of internal carotid artery or middle cerebral artery admitted within 24 hours after onset, and with a baseline, National Institutes of Health Stroke Scale score ≥4-point were included. Baseline and follow-up (median 88 hours) magnetic resonance images were analyzed, and penumbra was defined as the Tmax>6 s region excluding baseline infarction. The hypoperfusion intensity ratio (Tmax>10 s/Tmax>6 s) was calculated within the penumbra. Penumbral tissue loss (%) was defined as the proportion of follow-up infarct in the penumbra. With serial BP measurements in the first 24 hours (median 29, interquartile range 26-35), BP and BP variability parameters, including BPdropmax (change from local maxima to minima), were calculated and compared. Generalized linear models were applied to examine the association between BP parameters and the penumbral tissue loss. Results- The median penumbral volume was 79.3 mL (interquartile range, 38.2-129.6) and median penumbral tissue loss was 36.7% (interquartile range, 12.0-56.1). In a multivariable analysis, systolic BP (SBP) SBPdropmax (β±SE of fourth quartile, 17.82±6.58; P value, 0.01) and diastolic BP (DBP) DBPdropmax (β±SE of fourth quartile, 14.04±6.38; P value, 0.01) were associated with increasing penumbral tissue loss, independently of age, baseline infarction and hypoperfusion intensity ratio. DBPincmax, SBPmax, DBPmax, SBPmax-min, DBPmax-min, and most of the DBP variability indices were associated with penumbral tissue loss. Conclusions- BP fluctuations, even a brief and drastic BP drop in the first 24 hours, significantly contributed to penumbral tissue loss irrespective of baseline hypoperfusion.

Intravenous fibrinolysis plus endovascular thrombectomy versus direct endovascular thrombectomy for anterior circulation acute ischemic stroke: clinical and infarct volume results

Backgroundendovascular therapy (ET) is the standard of care for anterior circulation acute ischemic stroke (AIS) caused by large vessel occlusion (LVO). The role of adjunctive intravenous thrombolysis (IVT) in these patients remains unclear. The present study aims to investigate whether IVT followed by ET (CoT, combined therapy) provides additional benefits over direct ET for anterior circulation AIS with LVO.Methodswe achieved a single center retrospective study of patients with AIS caused by anterior circulation LVO, referred to our center between January 2014 and January 2017 and treated with ET. Functional recovery (modified Rankin at 3-months follow-up), recanalization rate (thrombolysis in cerebral infarction [TICI] score) and time, early follow-up brain CT scan infarct volume (EFIV) (for recanalized patients only), symptomatic intracerebral hemorrhage (sICH) and 3-month mortality were the outcomes of interests. Independent predictors of the outcomes were explored with multivariable logistic regression.Results145 subjects were included in the study, of whom 70 underwent direct ET and 75 were treated with CoT. Functional independence at 3-months was more frequent in CoT subjects compared to patients who received direct ET (mRS score 0–1: 48.5% vs 18.6%; P < 0.001. mRS score 0–2: 67.1% vs 37.3%; P < 0.001); CoT patients had also higher first-pass success rate (62.7% vs 38.6%, P < 0.05), higher recanalization rate (84.3% vs 65.3%; P = 0.009) and, in recanalized subjects, smaller EFIV (16.4 ml vs 62.3 ml; P = 0.003). Mortality and intracranial bleeding did not differ between the two groups. In multivariable regression analysis, low baseline NIHSS score (P < 0.05), vessel recanalization (P = 0.05) and CoT (P = 0.03) were independent predictors of favorable outcome at three months.ConclusionsCoT appears more effective than ET alone for anterior circulation AIS with LVO, with similar safety profile.

Abstract TP85: Accuracy of “At Risk” Tissue Predictions Using CT Perfusion in Acute Large Vessel Occlusions

Accuracy of “At Risk” Tissue Predictions using CT Perfusion in Acute Large Vessel Occlusions Songmi Lee, Albert J. Yoo, Olvert A. Berkhemer, Charles B. Majoie, Diederik W.J. Dippel, Sunil A. Sheth, for the MR CLEAN Investigators. Background: CT Perfusion (CTP) determinations of salvageable tissue are increasingly used in patient selection for endovascular stroke therapy (EST). However, the validity of CTP predictions of expected infarction volume without rapid recanalization from EST (“at risk” tissue) remains poorly characterized. Methods: From the multicenter randomized MR CLEAN trial, we included patients who underwent CTP without successful recanalization (randomized to medical therapy or to EST with failed reperfusion). “At risk” volumes were based on Tmax &gt; 6 seconds and infarct core on relative CBF &lt; 30 (Olea Sphere, Le Ciotat, France). Primary outcomes were follow-up infarct volume (FIV) on CT at 1 to 5 days, and 90-day mRS. Data are presented as median [IQR] or OR [95% CI] unless otherwise specified. Results: Among 37 patients that met criteria for this study, 14 (38%) were women and age was 61 years [IQR 52-69]. NIHSS was 19 [IQR 15-21], ASPECTS 8 [IQR 7-9], and time from onset to presentation 160 minutes [IQR 39-200]. Occlusion location was M1 for 22 (59%), ICA-T in 11 (30%), and M2 in 4 (11%). “At risk” volume was 85 mL [IQR 71-115], infarct core was 7 mL [IQR 0.2-23] and mismatch was 79 mL [IQR 51-95]. FIV of &lt; 60 mL was predicted in 7 patients, among whom 4 (57%) had &gt; 90 mL FIV. In univariate analysis, “at risk” volume correlated poorly with FIV (r=0.08, p=0.65). In linear regression adjusted for age, onset to presentation and occlusion location, presentation NIHSS but not “at risk” volume predicted FIV (Coef 12, p&lt;0.05; Coef -0.15, p=0.8). In similarly adjusted logistic regression, presentation NIHSS but not “at risk” volume predicted mRS 0-2 at 90 days (OR 0.7 [0.5-0.99]; OR 1.02 [0.99 - 1.05]). Conclusion: Predictions of “at-risk” tissue using CTP may underestimate the natural history of infarction from acute large vessel occlusions. An NIHSS-ischemic core mismatch may perform better as a predictor of clinical outcomes in patients without rapid recanalization.

Accuracy of "At Risk" Tissue Predictions Using CT Perfusion in Acute Large Vessel Occlusions.

The validity of CT perfusion (CTP) predictions of expected infarction volume ("at risk" tissue) without rapid recanalization remains poorly characterized. From the MR CLEAN trial, we included patients who underwent CTP without successful recanalization. "At risk" volume was defined as Tmax > 6 seconds and ischemic core as relative CBF < 30 (Olea Sphere). Coprimary outcomes were follow-up infarct volume (FIV) on CT at 1-5 days and 90-day mRS. Data are presented as median [IQR] or OR [95% CI] unless otherwise specified. Among 37 patients who met criteria, 14 (38%) were women, median age was 61 years [52-69], NIHSS was 19 [15-21], ASPECTS was 8 [7-9], and onset to imaging was 160 minutes [39-200]. Occlusion location was M1 for 22 (59%), ICA-T in 10 (27%), and M2 in 4 (11%). In univariable analysis, "at risk" volume correlated poorly with FIV (r = .06, P = .77). Among patients with predicted "at risk" volume < 100 mL, 36% had FIV > 200 mL. In adjusted linear regression, NIHSS but not "at risk" volume was associated with FIV (Coef 12, P = .045; Coef -.15, P = .8). In adjusted logistic regression, NIHSS but not "at risk" volume was associated with mRS 0-2 at 90 days (OR .7 [.5-.99]; OR 1.0 [.99-1.04]). Predictions of "at-risk" tissue using CTP may underestimate the natural history of infarction from acute large vessel occlusions. NIHSS may perform better as a predictor of clinical outcomes in patients without rapid recanalization.

Mediation of the Relationship Between Endovascular Therapy and Functional Outcome by Follow-up Infarct Volume in Patients With Acute Ischemic Stroke

The positive treatment effect of endovascular therapy (EVT) is assumed to be caused by the preservation of brain tissue. It remains unclear to what extent the treatment-related reduction in follow-up infarct volume (FIV) explains the improved functional outcome after EVT in patients with acute ischemic stroke. To study whether FIV mediates the relationship between EVT and functional outcome in patients with acute ischemic stroke. Patient data from 7 randomized multicenter trials were pooled. These trials were conducted between December 2010 and April 2015 and included 1764 patients randomly assigned to receive either EVT or standard care (control). Follow-up infarct volume was assessed on computed tomography or magnetic resonance imaging after stroke onset. Mediation analysis was performed to examine the potential causal chain in which FIV may mediate the relationship between EVT and functional outcome. A total of 1690 patients met the inclusion criteria. Twenty-five additional patients were excluded, resulting in a total of 1665 patients, including 821 (49.3%) in the EVT group and 844 (50.7%) in the control group. Data were analyzed from January to June 2017. The 90-day functional outcome via the modified Rankin Scale (mRS). Among 1665 patients, the median (interquartile range [IQR]) age was 68 (57-76) years, and 781 (46.9%) were female. The median (IQR) time to FIV measurement was 30 (24-237) hours. The median (IQR) FIV was 41 (14-120) mL. Patients in the EVT group had significantly smaller FIVs compared with patients in the control group (median [IQR] FIV, 33 [11-99] vs 51 [18-134] mL; P = .007) and lower mRS scores at 90 days (median [IQR] score, 3 [1-4] vs 4 [2-5]). Follow-up infarct volume was a predictor of functional outcome (adjusted common odds ratio, 0.46; 95% CI, 0.39-0.54; P < .001). Follow-up infarct volume partially mediated the relationship between treatment type with mRS score, as EVT was still significantly associated with functional outcome after adjustment for FIV (adjusted common odds ratio, 2.22; 95% CI, 1.52-3.21; P < .001). Treatment-reduced FIV explained 12% (95% CI, 1-19) of the relationship between EVT and functional outcome. In this analysis, follow-up infarct volume predicted functional outcome; however, a reduced infarct volume after treatment with EVT only explained 12% of the treatment benefit. Follow-up infarct volume as measured on computed tomography and magnetic resonance imaging is not a valid proxy for estimating treatment effect in phase II and III trials of acute ischemic stroke.

Subacute Infarct Volume With Edema Correction in Computed Tomography Is Equivalent to Final Infarct Volume After Ischemic Stroke: Improving the Comparability of Infarct Imaging Endpoints in Clinical Trials.

Final infarct volume is regularly used as an end point of tissue outcome in stroke trials; however, the reported volumes are most commonly derived from early follow-up imaging. Those volumes are significantly impaired by ischemic edema, which causes an overestimation of the true final lesion volume. As net water uptake within ischemic brain can be quantified densitometrically in computed tomography (CT) as recently described, we hypothesized that the final lesion volume can be better estimated by correcting the lesion volume in early follow-up for the corresponding proportion of edema. After retrospective consecutive screening of the local registry, 20 patients with acute middle cerebral artery large vessel occlusion met the inclusion criteria with early and late follow-up CT; the latter acquired at least 4 weeks after admission. In early follow-up imaging 24 hours after onset, the proportion of edema contributing to the infarct lesion was calculated by quantifying the total volume of ischemic net water uptake. Edema volume was then subtracted from the total lesion volume to obtain edema-corrected lesion volumes. Finally, these corrected lesion volumes were compared with the final lesion volume on late follow-up serving as ground truth. The median lesion volume in the early follow-up was 115.1 mL (range, 21.9-539.9 mL) and significantly exceeded the median final lesion volume in the late follow-up CT, which was 86.6 mL (range, 11.2-399.0 mL; p < 0.001). The calculated mean proportion of edema within the early lesion volume was 25.8% (±5.9%; range, 11.1%-35.9%. The median edema-corrected lesion volume measured after 24 hours was 87.1 mL (range, 18.2-376.3 mL). The estimation of final lesion volume in the early follow-up CT was therefore improved by a mean of 31.4% (±2.1%) when correcting for the proportion of edema and did not differ significantly from the true final infarct volume (p = 0.2). Edema-corrected volumes of early follow-up infarct lesion in CT were in close agreement with the actual final infarct volumes. Computed tomography-based edema correction of subacute infarct lesions improves the estimation of final tissue outcome. This could especially improve the comparability of imaging end points and facilitate patient recruitment in clinical trials.

Follow-up infarct volume as a mediator of endovascular treatment effect on functional outcome in ischaemic stroke

ObjectiveThe putative mechanism for the favourable effect of endovascular treatment (EVT) on functional outcome after acute ischaemic stroke is preventing follow-up infarct volume (FIV) progression. We aimed to assess to what extent difference in FIV explains the effect of EVT on functional outcome in a randomised trial of EVT versus no EVT (MR CLEAN).MethodsFIV was assessed on non-contrast CT scan 5–7 days after stroke. Functional outcome was the score on the modified Rankin Scale at 3 months. We tested the causal pathway from intervention, via FIV to functional outcome with a mediation model, using linear and ordinal regression, adjusted for relevant baseline covariates, including stroke severity. Explained effect was assessed by taking the ratio of the log odds ratios of treatment with and without adjustment for FIV.ResultsOf the 500 patients included in MR CLEAN, 60 died and four patients underwent hemicraniectomy before FIV was assessed, leaving 436 patients for analysis. Patients in the intervention group had better functional outcomes (adjusted common odds ratio (acOR) 2.30 (95% CI 1.62–3.26) than controls and smaller FIV (median 53 vs. 81 ml) (difference 28 ml; 95% CI 13–41). Smaller FIV was associated with better outcome (acOR per 10 ml 0.60, 95% CI 0.52–0.68). After adjustment for FIV the effect of intervention on functional outcome decreased but remained substantial (acOR 2.05, 95% CI 1.44–2.91). This implies that preventing FIV progression explains 14% (95% CI 0–34) of the beneficial effect of EVT on outcome.ConclusionThe effect of EVT on FIV explains only part of the treatment effect on functional outcome.Key Points• Endovascular treatment in acute ischaemic stroke patients prevents progression of follow-up infarct volume on non-contrast CT at 5–7 days.• Follow-up infarct volume was related to functional outcome, but only explained a modest part of the effect of intervention on functional outcome.• A large proportion of treatment effect on functional outcome remains unexplained, suggesting FIV alone cannot be used as an early surrogate imaging marker of functional outcome.

Value of Quantitative Collateral Scoring on CT Angiography in Patients with Acute Ischemic Stroke.

Many studies have emphasized the relevance of collateral flow in patients presenting with acute ischemic stroke. Our aim was to evaluate the relationship of the quantitative collateral score on baseline CTA with the outcome of patients with acute ischemic stroke and test whether the timing of the CTA acquisition influences this relationship. From the Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN) data base, all baseline thin-slice CTA images of patients with acute ischemic stroke with intracranial large-vessel occlusion were retrospectively collected. The quantitative collateral score was calculated as the ratio of the vascular appearance of both hemispheres and was compared with the visual collateral score. Primary outcomes were 90-day mRS score and follow-up infarct volume. The relation with outcome and the association with treatment effect were estimated. The influence of the CTA acquisition phase on the relation of collateral scores with outcome was determined. A total of 442 patients were included. The quantitative collateral score strongly correlated with the visual collateral score (ρ = 0.75) and was an independent predictor of mRS (adjusted odds ratio = 0.81; 95% CI, .77-.86) and follow-up infarct volume (exponent β = 0.88; P < .001) per 10% increase. The quantitative collateral score showed areas under the curve of 0.71 and 0.69 for predicting functional independence (mRS 0-2) and follow-up infarct volume of >90 mL, respectively. We found significant interaction of the quantitative collateral score with the endovascular therapy effect in unadjusted analysis on the full ordinal mRS scale (P = .048) and on functional independence (P = .049). Modification of the quantitative collateral score by acquisition phase on outcome was significant (mRS: P = .004; follow-up infarct volume: P < .001) in adjusted analysis. Automated quantitative collateral scoring in patients with acute ischemic stroke is a reliable and user-independent measure of the collateral capacity on baseline CTA and has the potential to augment the triage of patients with acute stroke for endovascular therapy.

Association of follow-up infarct volume with functional outcome in acute ischemic stroke: a pooled analysis of seven randomized trials

BackgroundFollow-up infarct volume (FIV) has been recommended as an early indicator of treatment efficacy in patients with acute ischemic stroke. Questions remain about the optimal imaging approach for FIV measurement.ObjectiveTo...

Abstract WP54: Early Alterations in Neurite Orientation Dispersion and Density After Acute Ischemic Stroke

Background: Advanced diffusion imaging approaches that model intracellular and extracellular diffusion components such as neurite orientation dispersion and density imaging (NODDI) may provide additional insight into evolution of acute ischemic stroke (AIS) injury over standard diffusion tensor imaging approaches (DTI). Methods: NODDI was acquired at discharge in a prospective study of acute ischemic stroke patients with advanced white matter disease (N=36). Neurite density (ND), and orientation dispersion (OD) were calculated along with model-free diffusion parameters: mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD) and fractional anisotropy (FA). Follow-up (FU) infarct volumes were drawn on discharge FLAIR. MD, AD, RD, FA, MK, AK, RK, OD and ND values were compared (1-way ANOVA) in infarct core (abnormal acute DWI), Growth (normal acute DWI, abnormal FU) and normal contralateral gray matter (nGM) and white matter (nWM). Results: Patient characteristics were: mean±SD age 69±10 y, median [IQR] initial NIH SS score 6 [3-11], time-to-acute MRI 7.3±5.3 h, time-to-FU MRI 2.8±1.2 days, acute DWI lesion 3.1 [0.5-18.8] cm 3 , FU lesion 8.1 [1.2-45.4] cm 3 and 61% men. Figure A shows examples of maps from a single subject. Core and growth values differed significantly (P&lt;0.0001) from nGM and nWM for MD AD, RD, FA, MK, AK, RK, OD and ND. Within the lesion MD, AD, RD and FA were decreased while MK, AK and RK were increased. OD and ND were also increased within the lesion. Discussion: Increased OD is expected with tissue infarction due to loss of structural integrity. In contrast, increased ND in the subacute time-frame is paradoxical. One possible mechanism could be that hyperacute ischemia-induced cellular swelling increases tortuosity of water diffusion paths, imposing direction-dependent restrictions upon diffusion, increasing intracellular and extracellular diffusion.

In patients with suspected acute stroke, CT perfusion-based cerebral blood flow maps cannot substitute for DWI in measuring the ischemic core.

BackgroundNeuroimaging may guide acute stroke treatment by measuring the volume of brain tissue in the irreversibly injured “ischemic core.” The most widely accepted core volume measurement technique is diffusion-weighted MRI (DWI). However, some claim that measuring regional cerebral blood flow (CBF) with CT perfusion imaging (CTP), and labeling tissue below some threshold as the core, provides equivalent estimates. We tested whether any threshold allows reliable substitution of CBF for DWI.Methods58 patients with suspected stroke underwent DWI and CTP within six hours of symptom onset. A neuroradiologist outlined DWI lesions. In CBF maps, core pixels were defined by thresholds ranging from 0%-100% of normal, in 1% increments. Replicating prior studies, we used receiver operating characteristic (ROC) curves to select thresholds that optimized sensitivity and specificity in predicting DWI-positive pixels, first using only pixels on the side of the brain where infarction was clinically suspected (“unilateral” method), then including both sides (“bilateral”). We quantified each method and threshold’s accuracy in estimating DWI volumes, using sums of squared errors (SSE). For the 23 patients with follow-up studies, we assessed whether CBF-derived volumes inaccurately exceeded follow-up infarct volumes.ResultsThe areas under the ROC curves were 0.89 (unilateral) and 0.90 (bilateral). Various metrics selected optimum CBF thresholds ranging from 29%-32%, with sensitivities of 0.79–0.81, and specificities of 0.83–0.85. However, for the unilateral and bilateral methods respectively, volume estimates derived from all CBF thresholds above 28% and 22% were less accurate than disregarding imaging and presuming every patient’s core volume to be zero. The unilateral method with a 30% threshold, which recent clinical trials have employed, produced a mean core overestimation of 65 mL (range: –82–191), and exceeded follow-up volumes for 83% of patients, by up to 191 mL.ConclusionCTP-derived CBF maps cannot substitute for DWI in measuring the ischemic core.