Abstract only Background: The pace of ischemic injury due to stroke may vary due to collaterals and degree of reperfusion. Previous linear models that estimate time is brain have not incorporated ...individual patient data from advanced imaging such as diffusion-weighted imaging (DWI) and angiographic assessment of collateral grade or reperfusion. We developed a realistic model of ischemic injury using detailed imaging data in a homogenous cohort of isolated M1 middle cerebral artery occlusions. Methods: Retrospective analysis of a consecutive series of isolated M1 occlusions was conducted at an expert core lab. ASITN collateral grade was assessed at baseline and extent of reperfusion after endovascular therapy (EVT) was scored with 3 distinct versions of TICI. A separate imaging expert measured DWI lesion volumes on serial MRI acquired from admission to discharge. Graphical analyses illustrated curves demarcating extent of injury over time, based on both collateral grade and extent of reperfusion. Results: 126 patients (median age 73; 88 women; median NIHSS 17; median time to 1 st DWI, 4h08min) with acute stroke due to M1 occlusion (61 proximal, 65 distal) underwent EVT during a 6-year period. Median collateral grade was 2 (range 0-4) and median TICI, 2B (range 0-3). mTICI scores were 0 (n=18), 1 (6), 2A (25), 2B (73), and 3 (4) with 24 TICI 2C scores when evaluated in detail. Total number of DWI scans was 323, with mean 2.5 per patient. Collateral grade strongly influenced pace of development of initial tissue injury (ASITN 0, 0.445 cc/min; 1, 0.276 cc/min; 2, 0.178 cc/min; 3, 0.106 cc/min; 4, 0.031 cc/min). The relationship between time and DWI lesion growth was not linear, but best fit logarithmically (R 2 = 0.985, RMSE 2.1 for log fit; R 2 = 0.757, RMSE 8.1 for linear fit). Individual lesion growth varied markedly with both collateral grade (ANOVA p<0.001) and the degree (TICI 2B/3 vs. 0,1,2A) of reperfusion (ANOVA p=0.013). Conclusions: Collateral grade and the degree of reperfusion strongly dictate the timecourse of ischemic injury in the brain after stroke onset. Advanced imaging and angiographic assessment of collaterals and reperfusion confirm a logarithmic, not linear, model that can be used to differentiate stroke patients and streamline therapeutic strategies.
Abstract only Background: The MR RESCUE trial failed to show a benefit of endovascular therapy over standard medical care for first generation thrombectomy devices within 8 hours of onset of acute ...ischemic stroke. We now report a subset analysis of patients enrolled with MRI, employing DEFUSE 2 criteria to define favorable penumbral pattern (target mismatch) which differed from MR RESCUE penumbral prediction criteria. Methods: Patients with large vessel, anterior circulation strokes were randomized to mechanical embolectomy (Merci Retriever or Penumbra System) or standard care. Patients were categorized as having a favorable penumbral or non-penumbral pattern employing the DEFUSE 2 criteria for target mismatch (Tmax > 6s / thresholded ADC < 600 х 10 −6 mm 2 /s > 1.8, thresholded ADC < 70 cc, and Tmax > 10 s < 100 cc). Results: Among 118 total patients, 94 qualified for this analysis. Mean age was 65.8, mean time to enrollment 5.6 hours, median NIHSS 17, and 47% had target mismatch. Predicted core volume using DEFUSE 2 criteria (thresholded ADC volume < 600 х 10 −6 mm 2 /s) was 18.8 cc (target mismatch) and 64.3 cc (non-target mismatch; p<0.001). Revascularization in the embolectomy group was achieved in 62% (TICI 2a-3), and 21% (TICI 2b-3). Among all patients, mean 90-day mRS scores did not differ between embolectomy and standard care (3.8 vs 3.8; p=0.92). In patients with target mismatch, embolectomy was not superior to standard care (mean mRS 3.5 vs 3.3, p=0.78). Similarly, in patients without target mismatch, embolectomy was not superior (4.1 vs 4.3, p=0.67). Furthermore, there was no interaction between pretreatment penumbral imaging pattern employing DEFUSE 2 target mismatch criteria and treatment assignment in these 90-day mRS scores (p=0.11). Conclusions: In this analysis MR RESCUE patients enrolled with pretreatment MRI, use of the DEFUSE 2 criteria for target mismatch as a definition of penumbral pattern failed to identify a subset of patients with improved outcomes when treated with embolectomy. Further randomized, controlled studies employing new generation thrombectomy devices are needed to validate target mismatch as a selection criterion for acute stroke treatments.
Cerebral microbleeds (CMB) detected on gradient-echo T2*-weighted MRI have been associated with cognitive impairment and the potential for increased risk of intracranial hemorrhage. We evaluated risk ...factors for these microangiopathic lesions in a cohort of stroke and transient ischemic attack patients.
Presence and number of CMB in consecutive acute stroke patients admitted to a university hospital stroke service over an 18-month period were rated. Multivariate models were generated to determine the contribution of 21 demographic and clinical variables to the frequency and number of CMB.
Of 164 patients (mean age 71 years, 52% female), 57 (35%) had CMB evident on gradient-echo T2*-weighted MRI. CMB were more commonly noted among patients with small vessel disease ischemic stroke mechanism (47%) than large vessel atherothromboembolic (12%) or cardioembolic (18%, p = 0.0001). In univariate analysis, patients with CMB were older, (p = 0.008), more likely to have been on >1 antihypertensive prior to admission (p = 0.024) than those without CMB. In multivariate logistic regression analyses, presumed small vessel stroke subtype, history of atrial fibrillation, being on >1 antihypertensive prior to admission, and smoking were independent factors increasing the risk of CMB. Logistic regression analysis by number of CMB showed almost similar findings.
CMB are more frequently noted in hospitalized stroke and transient ischemic attack patients with small vessel ischemia, as well as those with important modifiable vascular risk factors like atrial fibrillation and smoking.
Recently, the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) and the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) trialists suggested that ...diffusion-perfusion magnetic resonance imaging (MRI) can classify patients into 4 subgroups likely to differentially experience benefit or harm from reperfusion therapies. However, there is a lack of data comparing MR mismatch profiles between different race-ethnic groups. In addition, clinical factors affecting MR mismatch profiles are not well described.
We analyzed clinical and pretreatment MRI data of patients from 2 geographically and ethnically distinct study populations (Seoul, South Korea, and Los Angeles, Calif., USA) who are eligible for recanalization therapy. Diffusion-perfusion mismatch regions were classified among the 4 DEFUSE MR profiles: target mismatch, no mismatch, small lesion and malignant.
A total of 147 South Korean and 162 Southern Californian subjects (64.2% Whites) were included. Pretreatment MRIs revealed that the MR mismatch profiles were different in the 2 study populations (p < 0.001). Target mismatch was more prevalent in Southern Californian subjects (67.9%) compared with South Korean subjects (58.5%), whereas the small lesion pattern was more prevalent in the latter (9.9 vs. 23.1%). After adjusting for covariables, 3 features independently decreased the likelihood of presence of target mismatch: history of diabetes (OR 0.369, 95% CI 0.196-0.694), small versus large arterial occlusion (OR 0.052, 95% CI 0.01-0.255) and largest size (highest tertile) of diffusion-weighted imaging (DWI) lesion volume (OR 0.516, 95% CI 0.266-0.999). The one feature independently increasing target mismatch likelihood was intermediate size (middle tertile) DWI volume (OR 2.977, 95% CI 1.431-6.195).
Target mismatch profiles are present in 55-70% of patients. Target mismatch is less common in patients with diabetes, small vessel occlusion, Asian ethnicity and extensive DWI lesions, and more common in patients with DWI lesions of intermediate size.
Abstract only Background: Hemodynamic interventions, such as blood pressure (BP) manipulation, are often utilized to optimize perfusion of the ischemic territory. Scant data support theoretical ...effects of permissive hypertension or BP reduction, yet arterial-spin labeled (ASL) MRI may chronicle quantitative cerebral blood flow (CBF) changes. We used serial ASL to measure CBF changes associated with hemodynamic interventions, based on arterial occlusion site and collaterals. Methods: Serial ASL acquired in 148 consecutive cases of acute ischemic stroke at a single center during a 3-year period. A pseudo-continuous ASL pulse sequence with background suppressed 3D GRASE (gradient and spin echo) readout with 4 post-labeling delays was used, with normalization of quantitative CBF on a standard neurovascular template. CBF values and relative changes were measured in the affected hemisphere and in discrete regions of infarct core and collateral territories. Results: 148 cases (median age 68 years (IQR 62-82), 73 women) were studied. Overall, CBF (ml/100g/min) was related to age (r=-0.40, p<0.001) but not gender (male: 39±9.7, female: 40.6±8.2; r=.05, p=NS). Serial studies were obtained in 126 cases, including 2 studies in 91, 3 in 32, and 4 in 3. Median time to 1 st , 2 nd , 3 rd , and 4 th ASL study was 11.3, 39.7, 140.7, and 121.3 hrs and median CBF at these timepoints was 39.9 (IQR 28-48); 42.2 (IQR 29-52); 47.1 (IQR 36-56); and 35.6 (IQR 34-41). Average changes in CBF from study 1 to 2, 2 to 3, 3 to 4 were +2.2; +3.4; -14.8. Average CBF ratio between leptomeningeal and perforating MCA regions was 1.1. The correlation of initial delta CBF (study 1 to 2) with initial delta BP (1 to 2) was r=-0.1, p=NS. Average delta CBF/delta mmHg SBP was 0.25. At studies 1 and 2, lower BP was related to higher CBF (r=-0.148, p=0.102). Overall, delta BP was not linked with CBF (r=0.002, p=NS) or delta CBF (r=-0.108, p=NS). For those with low initial CBF (<40), positive delta BP was strongly associated with lower CBF at study 2 (r=-0.552, p=0.006). Conclusions: Blood pressure modification, permissive or interventional, may differentially affect CBF in the ischemic core and collateral regions. ASL provides a novel method for non-invasive mapping of serial changes in absolute CBF quantification in the ICU and beyond.
Background
The influence of lesion size and laterality on each component of the National Institutes of Health Stroke Scale has not been delineated. The objective of this study was to use ...perfusion-weighted imaging to characterize the association of ischaemic volume and laterality on each component item and the total score of the <National Institutes of Health Stroke Scale.
Methods
We analysed consecutive right-handed patients with first-ever supratentorial acute ischaemic strokes who underwent acute perfusion-weighted imaging at a single centre. Perfusion deficits were defined as mean transit time > 10 s. Ordinal regression was used to clarify the relationship between ischaemic volume, laterality, and <National Institutes of Health Stroke Scale scores.
Results
Among 111 patients, 58 were left-hemisphere stroke, and 53 right-hemisphere stroke. Median ischaemic volume was 53 ml in left-hand stroke and 65 ml in right-hand stroke and median total National Institutes of Health Stroke Scale was 10 in left-hand stroke and eight in right-hand stroke. For individual National Institutes of Health Stroke Scale items, ischaemic volume correlated most closely with commands and visual field and most weakly with ataxia and neglect. Left-hand stroke predicted higher scores of total National Institutes of Health Stroke Scale and National Institutes of Health Stroke Scale items of questions, commands, right limb weakness, and language. Right-hand stroke predicted higher scores of left limb weakness and extinction.
Conclusions
Larger perfusion defects contribute to higher scores on the total and most individual items of the National Institutes of Health Stroke Scale. However, lesion laterality contributes substantially to half the item scores, with greater association of left than right-brain side. These findings indicate that imaging-deficit correlations will be improved by designating lesions into an atlas, taking into account side in addition to size.
Abstract only Introduction: Collateral status may predict outcomes after endovascular therapy, yet a reliable noninvasive technique prior to angiography is needed. We developed a novel method for ...projection of perfusion imaging data and validated it with respect to DSA acquired immediately afterwards. Methods: Consecutive acute ischemic stroke patients with M1 MCA occlusions with perfusion MR imaging prior to endovascular revascularization therapy were included. Collateral status on DSA was graded with the ASITN/SIR scale (0-4). 4-D dynamic susceptibility contrast concentration time images were constructed and projected in 2-D axial and sagittal planes at each time point. Independent review of the resulting MRI-based collateral sequences was conducted to generate a score analogous to the ASITN/SIR scale, followed by correlation studies between the two techniques. Results: 47 patients were included with mean age 68.5 ± 16.3, 76.5% were female, baseline NIHSS was median 14 (range 3-31), and mean time from MRI to groin puncture was 109 min ± 95.5. DSA collateral grade was (0 (n=3); 1 (n=9); 2 (n=12); 3 (n=21); 4 (n=2)) with MRI collateral grade (0 (n=2); 1 (n=11); 2 (n=13); 3 (n=18); 4 (n=2)). MRI and DSA collateral scores were closely correlated, Spearman's rho = 0.91, weighted kappa = 0.82 (P <0.00001). Poor collateral status on MRI showed correlations with moderate to severe NIHSS (Spearman's rho = -0.31 (p< 0.039)). Figure depicts a panel version of MRI-based collateral sequences from a patient with a left M1 occlusion with a MR collateral grade of 1. Conclusions: Novel post-processing of noninvasive MRI perfusion data based on routine acquisitions can reliably measure the degree of collaterals on DSA.
Abstract only Background: The degree of reperfusion in acute stroke is a key predictor of clinical outcome, yet validation of a noninvasive imaging technique such as arterial spin-labeled MRI (ASL) ...that can quantify both hypo- and hyperperfusion is needed. Methods: Consecutive series of endovascular therapy for acute stroke and ASL-MRI within 36 hours after treatment start during a 3-year period were analyzed. Reperfusion on DSA was scored with TICI and mTICI (2b definitions of 2/3 and ½, respectively). ASL cerebral blood flow was graded with a scale analogous to mTICI (0=none, 1=< ½, 2=>½, 3=complete) separately for hypo- and hyperperfusion based on occlusion site, yet blinded to TICI/mTICI results. Results: 64 patients (mean age 67.7 ± 13.9 years; 53% women; median baseline NIHSS 15 (2-38)) had ASL acquired within 36 hours (median 7.07 hours (2.69-33.08)) from start of IV thrombolysis or thrombectomy over a 3-year period. 31/64 (48%) patients received IV tPA before endovascular therapy. DSA revealed 32 M1, 18 ICA, 10 M2, and 4 basilar occlusions. After endovascular treatment, TICI0/mTICI0 (6%), TICI1/mTICI1 (2%), TICI2a/mTICI2a (30%), TICI2a/mTICI2b (22%), TICI2b/mTICI2b (39%) and TICI3/mTICI3 (2%) results were noted. ASL revealed hypoperfusion (0 (19%); 1 (59%); 2 (14%); 3 (8%)) and hyperperfusion (0 (69%); 1 (27%); 3 (5%)). 7 combined patterns of hypo- and hyperperfusion were noted on ASL, all unrelated to baseline clinical variables. ASL mTICI hypoperfusion strongly correlated with DSA mTICI (R=-0.77, p<0.001) and TICI (R=-0.71, p<0.001). ASL hyperperfusion was noted only with TICI2a/mTICI2a (9%), TICI2a/mTICI2b (14%), TICI2b/mTICI2b (9%) and was more common with increased time from DSA to ASL (p=0.017). Conclusions: ASL hypoperfusion within 36 hours of acute stroke therapy strongly correlates with reperfusion scores on DSA, providing a novel means to accurately quantify degree of reperfusion. ASL hyperperfusion, concomitant with hypoperfusion, affects a substantial number of cases, predominantly affecting the TICI2a/mTICI2b reperfusion category on DSA.
Abstract only Background: Arterial spin-labeled (ASL) perfusion MRI can measure cerebral blood flow (CBF), yet the prolonged delays of collateral perfusion in acute ischemic stroke may impose ...limitations. Multiparametric maps of perfusion, including transit times and cerebral blood volume (CBV), may reveal important hemodynamic features before CBF collapse. We implemented a novel multi-delay ASL sequence to investigate multiparametric perfusion changes in acute stroke. Methods: Consecutive acute ischemic stroke patients admitted during an 8-month period were evaluated with pseudo-continuous ASL on Siemens 1.5 T and 3 T scanners within 12 hours of symptom onset. ASL was acquired using a 4-delay pCASL protocol with background suppressed 3D GRASE (postlabeling delay (PLD)=1.5/2/2.5/3s, FOV=22cm, matrix=64x64, 16x8mm slices, rate-2 GRAPPA, TE=22ms, 8 pairs of tag and control for each delay, total scan time 4min). After motion correction, arterial transit time (ATT), CBF, and arterial CBV (aCBV) maps were generated from the 4 PLDs. Results: A total of 161 ASL multi-delay perfusion MRI studies were performed in 130 acute ischemic stroke patients (mean age was 71±18 years and 56% were female). Repeated multi-delay ASL or serial studies were acquired in 19 cases, including 11 cases with 2 MRIs, 7 with 3, and 1 with 6 MRIs, depicting multiparametric blood flow changes after treatment. Correlation of multi-delay ASL (4 PLDs) and DSC MRI CBF asymmetry measures in MCA stroke patients (when available) was r=0.785 (p<0.001) and r=0.683 (p=0.003) for CBV measures with limited correlation for ATT. Conclusions: Multidelay ASL with 4 PLDs is feasible in the setting of acute stroke, providing multiparametric perfusion measures (CBF, CBV, ATT) of blood flow changes with treatment.
Abstract only 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 < 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 < 4.5 hours (mean 147±62 min). DWI lesion volume (median 3.67cc) in each case varied extensively (TLKW-DWI < 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 < 4.5 hours occurred in 8.5% of stroke cases. Malignant strokes (>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.
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