Abstract only Background: TICI scores are routinely used to measure reperfusion on angiography after endovascular therapies for acute stroke. Reperfusion may also be quantified by Tmax parameter ...changes on serial perfusion MRI before and after treatment. Such definitions of reperfusion used in trials may vary and we therefore investigated the correlation between TICI and quantification of Tmax changes on serial MRI in proximal middle cerebral artery (MCA) stroke cases treated with endovascular therapy. Methods: Consecutive acute ischemic stroke patients treated with endovascular therapy for proximal or M1 MCA occlusions with serial perfusion MRI at baseline and 3-6 hours after treatment were analyzed. TICI scores were noted for reperfusion on angiography. Reperfusion on serial MRI was separately defined as interval volume of Tmax>6s lesion size, dichotomous change by > 70% reduction in Tmax>6s, and voxel-wise changes across all Tmax values. Results: 57 stroke patients (mean age 64±20 years, 68% female) with M1 MCA occlusions imaged with perfusion MRI both before and after treatment with endovascular therapy were studied. TICI angiographic outcomes included 8 TICI 0, 4 TICI 1, 22 TICI 2a, 22 TICI 2b and 1 TICI 3. Both the interval volume of Tmax>6s lesion size and voxel-wise changes across all Tmax values varied extensively. Dichotomous reduction in Tmax>6s lesion volume by 70% was noted in only 12.9% of cases, with reduction by 60% in 19.4%, and by 50% in 30.6%. TICI reperfusion did not correlate with either: interval volume of Tmax>6s lesion size, dichotomous change by > 70% reduction in Tmax>6s, or voxel-wise changes across all Tmax values. Even when only TICI 2a/2b/3 or TICI 2b/3 cases were analyzed, no correlation could be established between the TICI angiographic measure of reperfusion at post-procedure with the change in Tmax lesion from baseline to 3-6 hours after revascularization. Conclusions: Reperfusion measured by TICI at angiography and changes in Tmax on serial perfusion MRI provide distinct information, likely reflecting heterogeneity and different vascular phases (arterial vs. microcirculation). Determining the clinical impact of such reperfusion measures on recovery after stroke remains paramount.
Abstract only Background: Perfusion MRI may be used to reveal permeability changes reflective of blood-brain barrier derangements that predate hemorrhagic transformation (HT) in acute ischemic ...stroke. We conducted a multicenter observational study to compare and validate these novel T2*-permeability MRI measures as predictors of hemorrhage, deriving a predictive model for use with acute stroke therapies. Methods: Dynamic T2*-weighted perfusion MRI source images routinely obtained in the setting of acute ischemic stroke were collected from four academic medical centers. Post-processing was used to generate six previously described permeability parameters including contrast slope (CS), final contrast (FC), maximum peak bolus concentration (MPB), peak bolus area (PB), relative recirculation (rR), and %Recovery (%R). Clinical data including baseline demographics, medical history, lab values and treatment details were utilized to develop a predictive model for HT, combined with these novel permeability measures. The multivariate predictive model was evaluated using a 10-fold cross-validation to measure its generalization power on new patients. Results: Among 263 acute ischemic stroke patients analyzed in this large, multicenter collaborative imaging study, mean age was 69±15 years, 58.2% were women and baseline median NIHSS was 10 (range, 0-40). T2*-MRI sequences were acquired as part of routine imaging evaluation at a median of 214 minutes (range, 33-1440) from symptom onset. Treatments included IV tPA alone in 49%, endovascular recanalization therapies alone in 21.2%, and both in 10.4%. Overall, HT on GRE at 24 hours was observed in 84 (31.9%), including 34 HI1, 30 HI2, 9 PH1 and 11 PH2. More severe baseline NIHSS (r= 0.25, p<0.01) predicted HT at 24 hours. Individual T2*-permeability parameters exhibited positive predictive values (PPV) for HT ranging from 79-82% with negative predictive values (NPV) ranging from 70-78%. An automated predictive model integrating clinical data and all 6 multiparametric permeability measures exhibited PPV of 80% and NPV of 73% for HT at 24 hours. Conclusions: Permeability indices on dynamic T2*-weighted MRI routinely acquired for perfusion imaging in acute ischemic stroke can accurately predict HT using an automated predictive model. This novel automated predictive model may be used to refine treatment decisions in acute stroke.
Abstract only Background: Leptomeningeal collaterals and associated cortical perfusion downstream from a proximal arterial occlusion or stenosis are potent predictors of outcome in acute stroke. ...Arterial spin-labeled (ASL) MRI may depict delayed arterial transit effects (DATE) of these collaterals and cerebral blood flow (CBF), utilizing noninvasive techniques without the use of contrast. We conducted a prospective validation study of ASL DATE and CBF as biomarkers of leptomeningeal collateral perfusion compared to digital subtraction angiography (DSA) and dynamic susceptibility contrast (DSC) perfusion MRI in acute ischemic stroke. Methods: Consecutive anterior circulation acute ischemic stroke patients admitted during a 1-year period were evaluated with pseudo-continuous ASL, DSA and DSC perfusion MRI within 12 hours of symptom onset. ASL DATE extent was scored using a 3-point scale and angiographic collaterals on the DSA graded using the ASITN/SIR collateral score. ASL CBF and DSC CBF maps were co-registered to derive comparative ROI statistics on perfusion in the symptomatic territory. ASL CBF lesions < 15 mL/100 g/min were used to measure DSC CBF values within coregistered ROIs. Results: Among 39 patients meeting entry criteria, mean age was 66±19 years and 51% were male. All 39 patients were imaged with ASL and DSA, with DSC perfusion MRI in a subset of 27. Sites of vascular occlusion or stenosis were: terminal ICA - 10, M1 MCA - 20, M2 MCA - 5 and more distal MCA - 4. ASL DATE scores ranged from 0-2, with a median of 1. DSA collateral grade ranged from 0-4, with a median of 2. Overall, there was strong correlation (r=0.702, p<0.001) between the ASL and DSA measures of leptomeningeal collateral supply. In the downstream territory from these leptomeningeal collaterals, ASL CBF and DSC CBF maps both revealed hypoperfusion in regions that closely matched. Only limited correlation, however, was noted between exact ASL CBF and DSC CBF values within the co-registered ROIs. Conclusions: ASL MRI provides an accurate, noninvasive measure of leptomeningeal collateral perfusion in acute ischemic stroke due to anterior circulation stenosis or occlusion. ASL CBF measures of collateral perfusion likely are arterially weighted, like DSA collateral grades, and unlike conventional DSC perfusion MRI CBF values.
ABSTRACT
BACKGROUND
Reperfusion of penumbral tissue is a promising strategy for treatment of acute cerebral ischemia more than 3 hours from symptom onset. However, there has been only sparse direct ...evidence that reperfusion after 3 hours prevents infarct growth.
METHODS
We analyzed clinical and serial magnetic resonance imaging (MRI) data on patients who received endovascular recanalization therapy 3‐12 hours after last known well time. Multimodal MRIs were acquired pretreatment, early (1‐20 hours), and late (2‐7 days) after treatment. Degree of recanalization was assessed on end of procedure catheter angiogram, degree of reperfusion on early posttreatment perfusion MRI, and infarct growth by analysis of diffusion lesion volumes on pretreatment and late MRIs.
RESULTS
Twenty‐seven (12 men, 15 women) underwent endovascular recanalization procedures at 6.0 ± 2.1 hours (range, 3.0‐11.5 hours) after last known well time. Immediate posttreatment perfusion lesion (Tmax ≥4 seconds) volume correlated strongly with infarct growth (r= .951, P < .001), exceeding the correlations of vessel recanalization score (r=−.198, P= .446) and pretreatment diffusion‐perfusion mismatch volume (r= .518, P= .033). Without reperfusion, enlargement of DWI lesion volume was observed in all patients, and extent of enlargement depended on volume of immediate posttreatment perfusion defects.
CONCLUSION
Our data indicate that posttreatment reperfusion is the major determinant of threatened tissue outcome, and suggest reperfusion even after 3 hours of symptom onset can alter tissue fate over a wide range of mismatch volumes.
Abstract only Background: Arterial spin-labeled (ASL) MRI facilitates repeated noninvasive evaluation of cerebral blood flow without the use of contrast. Hyperperfusion may be readily detected with ...ASL and serial imaging may therefore chronicle the dynamics of territorial perfusion from acute to chronic phases after stroke. We characterized hyperperfusion on ASL in a prospective series of acute ischemic stroke patients, describing the clinical correlates, time course and association with reperfusion hemorrhage. Methods: A consecutive series of acute ischemic stroke patients admitted during a 1-year period were evaluated with pseudo-continuous ASL with background suppressed 3D GRASE (delay=2s, matrix=64x64; 26 slices, resolution 3.4x3.4x5mm, scan time 4min). Post-processed ASL CBF maps were visually inspected for detection of hyperperfusion. DSA measures of collaterals and reperfusion were scored when available and hemorrhagic transformation (HT) was graded on GRE in all 198 cases. Univariate and multivariate statistical analyses delineated clinical correlates, timing and other imaging features of hyperperfusion. Results: Among 198 patients, mean age was 69.4±15.7 years and 48.5% were women. Among 77 with serial ASL MRI, interval from initial to follow-up MRI was median 25.0 (IQR 10.3-53.9) hours. Hyperperfusion was detected in 15/198 (7.6%) patients at baseline and 30/77 (39.0%) at follow-up. Trajectories included 7/77 (9.1%) with hyperperfusion at both baseline and follow-up and 38/77 (49.4%) showing hyperperfusion at any timepoint during admission. Hyperperfusion correlated with achievement of reperfusion among patients undergoing endovascular therapy (OR 6.5, 95% CI 1.82-23.25, p=0.018) and history of atrial fibrillation (OR 4.4, 95% CI 1.9-10.6, p<0.001). Analysis of the 42 cases with DSA revealed that hyperperfusion was most common in patients with poor collateral grade followed by more complete TICI reperfusion scores. Overall, HT affected 57/198 (28.8%), including 35/198 (17.7%) HI1, 11/198 (5.6%) HI2, 8/198 (4.1%) PH1 and 3/198 (1.5%) PH2. Multivariate analyses revealed that hyperperfusion at any timepoint was a potent predictor of HT (OR 52.6, 95%CI 12.4-222.6, p<0.001). Conclusions: Hyperperfusion in acute ischemic stroke is frequently demonstrated by ASL MRI, providing novel insight on the dynamics of reperfusion and HT. Hyperperfusion increases the risk of HT 50-fold, likely due to autoregulatory loss. Poor collaterals and sudden reperfusion in vulnerable cases such as those with atrial fibrillation may herald hyperperfusion and HT.
Rapid implementation of multimodal MR imaging, including diffusion-perfusion imaging before and following endovascular therapies for treatment of acute ischemic stroke, has yielded novel observations ...and expanded contemporary knowledge of acute stroke pathophysiology. For more than a decade at the University of California at Los Angeles, an intensive imaging strategy has been used to establish stroke diagnosis, delineate early patterns of cerebral ischemia, and monitor response to various reperfusion techniques. Angiographic findings before thrombolysis have substantiated stroke subtype, and documentation of concomitant recanalization has provided considerable insight regarding the vascular and imaging correlates of intra-arterial therapies. MR imaging studies have progressively characterized the complex pathophysiology of acute ischemic stroke, providing imaging strategies and models that may be used to optimize acute stroke care. The ensuing review emphasizes salient aspects of these neuroimaging studies, addressing numerous facets of acute stroke pathophysiology.
12 Introduction: Hemorrhagic transformation is a major limitation of thrombolytic therapy for the treatment of acute ischemic stroke. A method to identify patients at high risk for hemorrhage would ...be of substantial value for selecting the best candidates for treatment. Methods: Diffusion-perfusion MRIs were obtained prior to treatment and at 7 days post-treatment in patients with large vessel anterior circulation occlusions treated with intra-arterial (IA) thrombolysis. Patients received either combined IV/IA tPA or only IA thrombolytics (tPA or urokinase) within 6 hours of symptom onset. CT scans were performed immediately following the angiographic procedure and at 24 hours. Regions of hemorrhagic transformation were outlined on the post-treatment scans, which were then co-registered to the pretreatment MRI. A stepwise discriminant analysis was performed using pretreatment apparent diffusion coefficient (ADC) and mean transit time (MTT) measures to identify voxels that developed hemorrhage. Results: Eighteen patients were studied with mean age 73, 12 females / 5 males, median NIHSS score 14. Five patients (29%) developed regions of hemorrhagic transformation following therapy. There were no significant differences in time to pretreatment MRI or time to completion of thrombolysis between patients who developed hemorrhage vs. those that did not. For regions that developed hemorrhage, mean ADC was 583 um2/sec and mean MTT was 38 secs, vs. 746 and 25 for regions that went on to infarction, vs. 874 and 17 for regions that were salvaged (p<0.05 for all mean comparisons by ANOVA). A discriminant model employing pretreatment ADC and MTT variables correctly classified tissue fate (hemorrhage vs. non-hemorrhage) with overall accuracy 85%. Conclusions: In humans undergoing intra-arterial thrombolysis, pretreatment MRI ADC values are significantly lower and MTT values significantly higher in regions that develop hemorrhagic transformation compared to regions that are salvaged or develop ischemic infarction. Using these variables, a discriminant model can correctly classify tissue fate with overall accuracy of 85%.
8 Background: Late secondary injury following vessel recanalization, recently observed in animal stroke models, may limit the benefit of reperfusion therapy. The frequency and clinical correlates of ...secondary injury in humans have not been previously characterized. Methods: Diffusion-perfusion MRIs were performed prior to treatment, early after recanalization (median 4 hrs), and at day 7 in patients undergoing vessel recanalization with intra-arterial (IA) thrombolytics. Post-treatment MRIs were co-registered to the pretreatment scan to allow a voxel-by-voxel analysis of tissue fate over time. Results: Eighteen patients (13 females, 5 males) were studied. Mean age was 71 and median entry NIHSS score 13. Early after recanalization, partial or complete normalization of DWI abnormalities occurred in 8/18 (44%) patients, and of apparent diffusion coefficient (ADC) abnormalities in 13/18 (72%). Among the 8 patients with early DWI reversal, late secondary injury on day 7 (on DWI or T2W sequences) occurred in 5 (63%), and sustained normalization of all reversed tissue in 3 (38%). Across all patients, of tissues showing pretreatment DWI abnormality, 41% of voxels showed no early reversal, 33% early reversal with sustained normalization at day 7, and 18% early reversal but late secondary injury. Pretreatment ADC values were lowest in regions experiencing no reversal (mean ADC 624 um2/sec), intermediate in regions with reversal and secondary decline (641), and highest in regions with sustained reversal (677). Evolution of neurologic deficit (NIHSS) did not differ in patients with secondary injury vs. those with sustained reversal, nor did age, time to recanalization, degree of recanalization, or presence of post-ischemic hyperperfusion. Conclusions: Following vessel recanalization with IA thrombolysis, partial or complete reversal of initial DWI abnormality occurs in ∼40% of patients. A late, secondary signature of injury compromising some or all of the initially normalized tissue occurs in over 50% of these patients, but is not associated with clinical worsening.
PDF
