Hypoperfusion Volume Research Articles

MR Perfusion to Determine the Status of Collaterals in Patients with Acute Ischemic Stroke: A Look Beyond Time Maps.

Patients with acute stroke with robust collateral flow have better clinical outcomes and may benefit from endovascular treatment throughout an extended time window. Using a multiparametric approach, we aimed to identify MR perfusion parameters that can represent the extent of collaterals, approximating DSA. Patients with anterior circulation proximal arterial occlusion who had baseline MR perfusion and DSA were evaluated. The volume of arterial tissue delay (ATD) at thresholds of 2-6 seconds (ATD2-6 seconds) and >6 seconds (ATD>6 seconds) in addition to corresponding values of normalized CBV and CBF was calculated using VOI analysis. The association of MR perfusion parameters and the status of collaterals on DSA were assessed by multivariate analyses. Receiver operating characteristic analysis was performed. Of 108 patients reviewed, 39 met our inclusion criteria. On DSA, 22/39 (56%) patients had good collaterals. Patients with good collaterals had significantly smaller baseline and final infarct volumes, smaller volumes of severe hypoperfusion (ATD>6 seconds), larger volumes of moderate hypoperfusion (ATD2-6 seconds), and higher relative CBF and relative CBV values than patients with insufficient collaterals. Combining the 2 parameters into a Perfusion Collateral Index (volume of ATD2-6 seconds × relative CBV2-6 seconds) yielded the highest accuracy for predicting collateral status: At a threshold of 61.7, this index identified 15/17 (88%) patients with insufficient collaterals and 22/22 (100%) patients with good collaterals, for an overall accuracy of 94.1%. The Perfusion Collateral Index can predict the baseline collateral status with 94% diagnostic accuracy compared with DSA.

Early-phase 18F-AV-45 PET Imaging can Detect Crossed Cerebellar Diaschisis Following Carotid Artery Stenosis and Cerebral Hypoperfusion.

Carotid artery stenosis (CAS) may induce cerebral hypoperfusion. Early-phase 18F-Florbetapir (AV-45/Amyvid, 18F-AV-45) positron emission tomography (PET) imaging can provide perfusion-like property (pAV-45) for the estimation of cerebral blood flow (CBF). Supra-tentorial lesions may cause decreased blood flow and metabolism in the contralateral cerebellum known as crossed cerebellar diaschisis (CCD). The aim was to study the occurrence of CCD after CAS using pAV-45 PET. Eleven healthy controls and 21 patients with unilateral CAS were studied. All subjects underwent 18F-AV-45 PET imaging and arterial spin labeling (ASL) CBF magnetic resonance perfusion imaging. The pAV-45 and ASL CBF values were first correlated. Then, cerebral and cerebellar hypoperfusion volume was analyzed. The cerebral and cerebellar perfusion asymmetry indices (AIs) were calculated from the pAV-45 standard uptake value ratios (SUVRs) of bilateral cerebral and cerebellar cortices, respectively. We found that pAV-45 SUVR was significantly correlated to ASL CBF (p<0.0001, r=0.5731). The AI of cerebellar perfusion was negatively correlated to that of cerebral perfusion (p<0.0001, r=-0.8751). Multiple linear regression showed the cerebral AI (p<0.0001) and hypoperfusion volume (p=0.02) but not the infarction severity and CAS degree significantly correlated to cerebellar AI. If the lower limit of 95% confidence interval of cerebellar AI in healthy controls was set as cut-off for positive CCD, the occurrence of CCD correlated to infarction severity in CAS patients (p=0.03). Our results suggest pAV-45 is reliable to study CBF change. Under unilateral CAS, cerebral AI and hypoperfusion severity may determine the occurrence of CCD.

Validation of the cingulate island sign with optimized ratios for discriminating dementia with Lewy bodies from Alzheimer\u2019s disease using brain perfusion SPECT

ObjectiveDementia with Lewy bodies (DLB) is often cited as the second most common dementia after Alzheimer’s disease (AD). It is clinically important to distinguish DLB from AD because specific side effects of antipsychotic drugs are limited to DLB. The relative preservation of cingulate glucose metabolism in the posterior cingulate gyri versus that in the precuni, known as the cingulate island sign (CIS), in patients with DLB compared with AD is supposed to be highly specific for diagnosing DLB. In a previous study, using brain perfusion SPECT, the largest value (0.873) for the area under the receiver operating characteristic (ROC) curve (AUC) for differentiating DLB from AD was obtained with the ratio of the posterior cingulate gyri from an early Alzheimer’s disease-specific hypoperfusion volume of interest (VOI) versus the medial occipital lobe. Two purposes of this study are as follows: one is optimization of VOI setting for calculating CIS values and the other is to evaluate their accuracy and simultaneously to retest the method described in our previous paper.MethodsWe conducted a retest of this SPECT method with another cohort of 13 patients with DLB and 13 patients with AD. Furthermore, we optimized VOIs using contrast images obtained from group comparisons of DLB and normal controls; the same 18 patients with DLB and 18 normal controls examined in our previous study. We obtained DLB-specific VOIs from areas where brain perfusion was significantly decreased in DLB. As the numerators of these ratios, early Alzheimer’s disease-specific VOIs were used after subtracting DLB-specific VOIs. The DLB-specific VOIs were used as the denominator.ResultsIn retest, the obtained AUC was 0.858 and the accuracy, sensitivity, and specificity were 84.6, 84.6, and 84.6%, respectively. The ROC curve analysis with these optimized VOIs yielded a higher AUC of 0.882; and the accuracy, sensitivity, and specificity of these new CIS ratios were 84.6, 92.3, and 76.9%, respectively, with a threshold value of 0.281.ConclusionOptimized CISs using brain perfusion SPECT are clinically useful for differentiating DLB from AD.

Classification of hemodynamically significant stenoses from dynamic CT perfusion and CTA myocardial territories.

Myocardial blood flow (MBF) obtained by dynamic CT perfusion (CTP) has been recently introduced to assess hemodynamic significance of coronary stenosis in coronary artery disease. The diagnostic performance of dynamic CTP MBF is limited due to subjective interpretation of MBF maps and MBF variations caused by physiological, methodological, and technical issues. In this paper, we introduce a novel method to quantify the hypoperfused volume (HPV) in myocardial territories derived from CT angiography (CTA) to overcome the limitations of current dynamic CTP MBF analysis methods. The diagnostic performance of HPV in classifying significant stenoses was evaluated on 22 patients (57 vessels) that underwent CTA, CTP and invasive fractional flow reserve (FFR). FFR was used as the standard of reference to determine stenosis significance. The diagnostic performance was compared to that of the mean MBF computed in regions manually annotated by an expert (MA-MBF). HPV was derived by thresholding the MBF in myocardial territories constructed from CTA by locating the closest artery. Diagnostic performance was evaluated using leave-one-case out cross-validation. Inter-observer reproducibility was assessed by performing annotations of coronary seeds (HPV) and manual regions (MA-MBF) with two users. In addition, the influence of different parameter settings on the diagnostic performance of HPV was assessed. Leave-one-case out cross-validation showed that HPV has an accuracy of 72% (58-83%) with sensitivity of 72% (47-90%) and specificity of 72% (58-83%). The accuracy of MA-MBF was 70% (57-82%) with a sensitivity of 50% (26-74%) and a specificity of 79% (64-91%). The Spearman correlation and the kappa statistic was (ρ = 0.94, κ = 0.86) for HPV and (ρ = 0.72, κ = 0.82) for MA-MBF. The influence of parameter settings on HPV based diagnostic performance was not significant. The proposed HPV accurately classifies hemodynamically significant stenoses with a level of accuracy comparable to the mean MBF in regions annotated by an expert. HPV improves inter-observer reproducibility as compared to MA-MBF by providing a more objective criterion to associate the stenotic coronary with the supplied myocardial territory.

Abstract WP136: Perfusion and Plaque Evaluation in Symptomatic Middle Cerebral Arterial Athrosclerotic Stenosis: Characterization With Multimodel MRI

Objevtive: We investigated the baseline demographics of patients with severe unilateral middle cerebral artery(MCA) athrosclerotic stenosis using multimodel MRI and tired to find out the hemodynamic and plaque features of patients who had recurrent stroke. Methods: This retrospective study had recruited consecutive patients with severe unilateral MCA athrosclerotic stenosis at 2 centers. All patients were performed arterial spin labeling(ASL) with post labeling delay(PLD) of 1.5s and 2.5s, MR angiography and high-resolution MRI. Hypoerfusion volume ratio (HVR) was calculated as [hypoperfusion volume at 2.5s / hypoperfusion volume at 1.5s X 100%]. Plaques enhancement at maximal lumen narrowing were graded from 0(none enhancement) to 3(signal intensity as high as post-contrast pituitary). In patients who had conducted conventional angiography, Spearman correlation was analyzed between collateral grades and HVR. Baseline characteristics were compared between patients with 1 year follow up ischemic events(event+) and without(event-), then multivariable logistic analysis was performed. Results: Thirty-seven patients (47.1±11.8 years; 25 men) were included in this study. HVR was with a mean of 24.9±23.6% and ranged from 0% to 93%. In 17 patients (50.47±7.23 years; 12 men) who had underwent conventional angiography, HVR was significantly correlated with collateral grading (r=-0.40, p=0.0493). In 1 year follow up, 7 patients had recurrent events in the same territory. NIHSS, HVR was significantly higher in Event+ group(p<0.05) and no significantly difference was detected in plaque enhancement grade as well as age, risk factors, qualifying event and time from symptom onset to imaging. In multivariable analysis, HVR >50% was significantly associated with recurrent stroke(OR=13.714, 95% confidence interval: 1.061-177.320, p=0.045) after adjusted by NIHSS and plaque enhancement grade. Conclusion: Multimodel MRI may be a promising approach to explore the mechanism of ischemic stroke in patients with intracranial artery stenosis. HVR obtained from 2 PLD ASL is associated with collateral circulation and may be predictable for recurrent stroke.This work was supported by the National Natural Science Foundation of China (Grant number: 81471390).

Abstract TMP5: The Smoking-Thrombolysis Paradox in Large Vessel Occlusion Acute Ischemic Stroke Undergoing Endovascular Therapy

Background and Purpose: The smoking-thrombolysis paradox has been well described in myocardial infarction. However, its existence in the stroke population remains elusive. In the past decade, several studies have investigated the phenomenon with mixed results. We sought to determine whether clinical outcomes differ between smokers and non-smokers with acute ischemic stroke undergoing endovascular therapy. Methods: We reviewed our prospectively collected endovascular database at a tertiary care academic institution. All patients who underwent endovascular therapy for acute large vessel occlusion acute ischemic stroke were categorized into current smokers and non-smokers. Baseline characteristics, procedural radiological as well as outcome parameters where compared. Results: A total of 968 patients qualified for the study of which 189 (19.5%) were current smokers. Smokers were younger (60.78±11.95 vs. 66.41±15.05 years, p<0.001), had higher rates of dyslipidemia (49.7% vs 31.7%, p<0.001) and posterior circulation strokes (13.2% vs 7.8%, p=0.02,) and lower rates of atrial fibrillation (21.1% vs 37.9%, p<0.001). There were no statistically significant differences between groups in terms of stroke severity (as assessed by NIHSS), baseline CT perfusion core and hypoperfusion volumes, CT angiogram collateral scores as well as procedural variables. On univariate analysis, smokers had higher rates of good outcomes at 90 days (modified Rankin scale, mRS 0-2: 53.8% vs 42.8%, p=0.01) and similar rates of successful reperfusion (mTICI 2b-3) (92.1% vs 87.7%, p=0.09), parenchymal hematomas (4.2% vs 4%, p=0.84) and mortality at 90 days (20.2% vs 25.7%, p=0.14). Multivariate analysis showed that smoking was not independently associated with good outcomes. Stratifying for (1) stroke etiology and (2) anterior vs. posterior circulation topology yielded similar results. Conclusion: In stroke patients treated with mechanical thrombectomy, smoking does not seem to be associated with outcomes regardless of stroke subtype or location.

Body Temperature Modulates Infarction Growth following Endovascular Reperfusion.

The neuronal substrate is highly sensitive to temperature elevation; however, its impact on the fate of the ischemic penumbra has not been established. We analyzed interactions between temperature and penumbral expansion among successfully reperfused patients with acute ischemic stroke, hypothesizing infarction growth and worse outcomes among patients with fever who achieve full reperfusion. Data from 129 successfully reperfused (modified TICI 2b/3) patients (mean age, 65 ± 15 years) presenting within 12 hours of onset were examined from a prospectively collected acute ischemic stroke registry. CT perfusion was analyzed to produce infarct core, hypoperfusion, and penumbral mismatch volumes. Final DWI infarction volumes were measured, and relative infarction growth was computed. Systemic temperatures were recorded throughout hospitalization. Correlational and logistic regression analyses assessed the associations between fever (>37.5°C) and both relative infarction growth and favorable clinical outcome (90-day mRS of ≤2), corrected for NIHSS score, reperfusion times, and age. An optimized model for outcome prediction was computed by using the Akaike Information Criterion. The median presentation NIHSS score was 18 (interquartile range, 14-22). Median (interquartile range) CTP-derived volumes were: core = 9.6 mL (1.5-25.3 mL); hypoperfusion = 133 mL (84.2-204 mL); and final infarct volume = 9.6 mL (8.3-45.2 mL). Highly significant correlations were observed between temperature of >37.5°C and relative infarction growth (Kendall τ correlation coefficient = 0.24, P = .002). Odds ratios for favorable clinical outcome suggested a trend toward significance for fever in predicting a 90-day mRS of ≤2 (OR = 0.31, P = .05). The optimized predictive model for favorable outcomes included age, NIHSS score, procedure time to reperfusion, and fever. Likelihood ratios confirmed the superiority of fever inclusion (P < .05). Baseline temperature, range, and maximum temperature did not meet statistical significance. These findings suggest that imaging and clinical outcomes may be affected by systemic temperature elevations, promoting infarction growth despite reperfusion.

The cingulate island sign within early Alzheimer’s disease-specific hypoperfusion volumes of interest is useful for differentiating Alzheimer’s disease from dementia with Lewy bodies

BackgroundIn addition to occipital hypoperfusion, preserved metabolism of the posterior cingulate gyri (PCG) relative to the precunei is known as the cingulate island sign (CIS) in the patients with dementia with Lewy bodies (DLB). CIS has been detected using [18F]fluorodeoxyglucose positron emission tomography but not using brain perfusion single-photon emission computed tomography (SPECT). The purpose of this study was to optimize brain perfusion SPECT to enable differentiation of DLB from Alzheimer’s disease (AD) using CIS and occipital hypoperfusion.Eighteen patients with probable DLB and 17 age-matched Pittsburgh compound B-positive patients with AD underwent technetium-99m ethyl cysteinate dimer SPECT. SPECT Z-score maps were generated using the easy Z-score imaging system (eZIS) analysis software (Matsuda H, Mizumura S, Nagao T, Ota T, Iizuka T, Nemoto K, Takemura N, Arai H, Homma A, AJNR Am J Neuroradiol 28(4):731–6, 2007), which included volumes of interest (VOIs) in which a group comparison between patients with AD and cognitively normal subjects revealed significant relative hypoperfusion. We used the Montreal Neurological Institute (MNI) space anatomical border to divide the bilateral PCG to precunei VOIs into two parts, the PCG and precunei. Z-scores in the PCG, precunei, and occipital areas and ratios were analysed and compared with receiver operating characteristic (ROC) curve analyses.ResultsThe largest area under the curve (AUC) value for use in differentiating DLB from AD with the ratio of PCG to medial occipital was 0.87; the accuracy, sensitivity, and specificity were 85.7, 88.9, and 82.4 %, respectively. The AUC with the ratio of PCG to the precuneus was smaller, and it was 0.85, though no significant difference was observed between these two AUCs.ConclusionsThe Z-score ratio of the PCG within the early-AD-specific VOI to medial-occipital area is clinically useful in discriminating demented patients with DLB from those with AD.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-016-0224-5) contains supplementary material, which is available to authorized users.

Comparison of Perfusion CT Software to Predict the Final Infarct Volume After Thrombectomy

Computed tomographic perfusion represents an interesting physiological imaging modality to select patients for reperfusion therapy in acute ischemic stroke. The purpose of our study was to determine the accuracy of different commercial perfusion CT software packages (Philips (A), Siemens (B), and RAPID (C)) to predict the final infarct volume (FIV) after mechanical thrombectomy. Single-institutional computed tomographic perfusion data from 147 mechanically recanalized acute ischemic stroke patients were postprocessed. Ischemic core and FIV were compared about thrombolysis in cerebral infarction (TICI) score and time interval to reperfusion. FIV was measured at follow-up imaging between days 1 and 8 after stroke. In 118 successfully recanalized patients (TICI 2b/3), a moderately to strongly positive correlation was observed between ischemic core and FIV. The highest accuracy and best correlation are shown in early and fully recanalized patients (Pearson r for A=0.42, B=0.64, and C=0.83; P<0.001). Bland-Altman plots and boxplots demonstrate smaller ranges in package C than in A and B. Significant differences were found between the packages about over- and underestimation of the ischemic core. Package A, compared with B and C, estimated more than twice as many patients with a malignant stroke profile (P<0.001). Package C best predicted hypoperfusion volume in nonsuccessfully recanalized patients. Our study demonstrates best accuracy and approximation between the results of a fully automated software (RAPID) and FIV, especially in early and fully recanalized patients. Furthermore, this software package overestimated the FIV to a significantly lower degree and estimated a malignant mismatch profile less often than other software.

Abstract WMP11: Arterial Occlusive Lesion Location Does Not Impact Functional Outcome in Patients with Endovascular Reperfusion

Introduction: The relationship between clinical outcome and arterial occlusive lesion (AOL) location in patients after endovascular therapy is not fully determined. We aimed to investigate if the location of the arterial occlusive lesion (AOL) is an independent predictor of good functional outcome. Hypothesis: AOL location impacts clinical outcome with distal lesions having higher rates of good functional outcome (GFO) in reperfused patients. Methods: Using data from the CTP to predict Response to recanalization in Ischemic Stroke Project (CRISP), a multi-center, NIH-sponsored prospective cohort study, we analyzed the effect of AOL location on clinical outcome. Patients were included if they had documented reperfusion on early follow-up MR or CT perfusion imaging (&gt;50% reduction in Tmax&gt;6s lesion volume) or on angiography (TICI 2b or 3). Good functional outcome was defined as mRS score 0-2 at day 90. AOL location was categorized as proximal ICA, distal ICA, MCA-M1, or MCA-M2. Fully automated perfusion software (RAPID) was used to calculate CTP infarct core volume (rCBF&lt;30%) and critically hypoperfused tissue volume (Tmax&gt;6s). We assessed whether age, NIHSS score, infarct core, critically hypoperfused tissue, and AOL are associated with GFO using univariate and multivariate analyses. Results: The analysis included 167 of 201 patients (proximal ICA=21, distal ICA=32, M1=99, M2=15). Median NIHSS score (IQR) for groups were respectively: 18(14-22), 18(15-23), 17(11-20), 15( 13-19). Mean core volumes (mL) (IQR) were: 24.2(1.1-22.9), 13.0(0.0-17.7), 16.5(0.0-26.2), 10.6(1.1-13.0). Significant independent predictors of GFO were age (OR 0.82 for every 5 year increment, 95% CI 0.72-0.94), NIHSS score (OR 0.86, 95% CI 0.79-0.93), and core volume (OR 0.78 for every 10 mL increase, 95% CI 0.62-0.94), whereas AOL location (p=0.8-0.9) and the volume of critically hypoperfused tissue (p=0.5) were not significant in univariate and multivariate analyses. Conclusion: Baseline symptom severity, infarct core volume, and age drive functional outcomes in stroke patients with successful endovascular reperfusion. These variables, but not AOL location and volume of critically hypoperfused tissue, should be used for prognostication in the acute setting.

Abstract TP73: Lower Prehospital Blood Pressure Is Not Associated with Larger Infarct Volumes in Non-lacunar Ischemic Stroke Patients

Background: Although prehospital blood pressure (BP)-lowering trials in acute stroke have begun, concerns persist that hypotension may exacerbate hypoperfusion and increase infarct volumes, particularly in non-lacunar stroke. We tested the hypothesis that lower prehospital BP is associated with larger infarct volumes in non-lacunar ischemic stroke. Methods: We conducted a retrospective study of consecutive patients with suspected stroke transported by Emergency Medical Services (EMS) during an 18-month period. Serial prehospital BP data were obtained from a centralized EMS database. Hospital charts and neuroimaging were reviewed. Stroke etiology was classified using TOAST criteria. Infarct volumes were measured on follow-up MRI or CT using semi-automated thresholding planimetric techniques by two independent raters, blinded to prehospital BP. Results: Of a total 960 patients transported by EMS, 367 had a final diagnosis of ischemic stroke. Stroke etiology was large artery disease in 51 patients, cardioembolic in 140, lacunar in 44, other determined etiology in 22, and cryptogenic in 110 patients. Follow-up imaging was available in 315 patients (163 MR, 152 CT) at a median (IQR) 1(1) days. The overall median non-lacunar infarct volume was 16.5 (49.6) ml, median NIHSS was 7(10), and mean prehospital SBP was 153 ± 25 mmHg. Mean prehospital SBP was lower in patients with other determined etiology (133.2 ± 26.1 mmHg, p&lt;0.01) than cardioembolic (150.9 ± 25.5 mmHg), large artery disease (157.1 ± 26.1 mmHg) and cryptogenic stroke (157.7 ± 22.9 mmHg). Median infarct volume was similar across categories of stroke etiology (large artery disease (16.3 (60.3) ml), cardioembolic (19.9 (76.2) ml), other determined etiology (23.9 (33.6) ml), and cryptogenic stroke (11.5 (35.9) ml), p=0.12). There was no correlation between mean prehospital SBP and mean infarct volume (r =-0.06, p=0.33). NIHSS score was correlated with mean infarct volume (r=0.6, p&lt;0.001), but not mean prehospital SBP (r=-0.07, p=0.24). Conclusion: These data provide no evidence to suggest that lower prehospital BP is associated with larger infarct volumes in patients with non-lacunar ischemic stroke. The effect of BP reduction on infarct volumes should be assessed as part of randomized trials.

Ischemic core and hypoperfusion volumes predict infarct size in SWIFT PRIME.

Within the context of a prospective randomized trial (SWIFT PRIME), we assessed whether early imaging of stroke patients, primarily with computed tomography (CT) perfusion, can estimate the size of the irreversibly injured ischemic core and the volume of critically hypoperfused tissue. We also evaluated the accuracy of ischemic core and hypoperfusion volumes for predicting infarct volume in patients with the target mismatch profile. Baseline ischemic core and hypoperfusion volumes were assessed prior to randomized treatment with intravenous (IV) tissue plasminogen activator (tPA) alone versus IV tPA + endovascular therapy (Solitaire stent-retriever) using RAPID automated postprocessing software. Reperfusion was assessed with angiographic Thrombolysis in Cerebral Infarction scores at the end of the procedure (endovascular group) and Tmax > 6-second volumes at 27 hours (both groups). Infarct volume was assessed at 27 hours on noncontrast CT or magnetic resonance imaging (MRI). A total of 151 patients with baseline imaging with CT perfusion (79%) or multimodal MRI (21%) were included. The median baseline ischemic core volume was 6 ml (interquartile range= 0-16). Ischemic core volumes correlated with 27-hour infarct volumes in patients who achieved reperfusion (r = 0.58, p < 0.0001). In patients who did not reperfuse (<10% reperfusion), baseline Tmax > 6-second lesion volumes correlated with 27-hour infarct volume (r = 0.78, p = 0.005). In target mismatch patients, the union of baseline core and early follow-up Tmax > 6-second volume (ie, predicted infarct volume) correlated with the 27-hour infarct volume (r = 0.73, p < 0.0001); the median absolute difference between the observed and predicted volume was 13 ml. Ischemic core and hypoperfusion volumes, obtained primarily from CT perfusion scans, predict 27-hour infarct volume in acute stroke patients who were treated with reperfusion therapies.

Crossed cerebellar diaschisis in patients with acute middle cerebral artery infarction: Occurrence and perfusion characteristics

We aimed to investigate the overall prevalence and possible factors influencing the occurrence of crossed cerebellar diaschisis after acute middle cerebral artery infarction using whole-brain CT perfusion. A total of 156 patients with unilateral hypoperfusion of the middle cerebral artery territory formed the study cohort; 352 patients without hypoperfusion served as controls. We performed blinded reading of different perfusion maps for the presence of crossed cerebellar diaschisis and determined the relative supratentorial and cerebellar perfusion reduction. Moreover, imaging patterns (location and volume of hypoperfusion) and clinical factors (age, sex, time from symptom onset) resulting in crossed cerebellar diaschisis were analysed. Crossed cerebellar diaschisis was detected in 35.3% of the patients with middle cerebral artery infarction. Crossed cerebellar diaschisis was significantly associated with hypoperfusion involving the left hemisphere, the frontal lobe and the thalamus. The degree of the relative supratentorial perfusion reduction was significantly more pronounced in crossed cerebellar diaschisis-positive patients but did not correlate with the relative cerebellar perfusion reduction. Our data suggest that (i) crossed cerebellar diaschisis is a common feature after middle cerebral artery infarction which can robustly be detected using whole-brain CT perfusion, (ii) its occurrence is influenced by location and degree of the supratentorial perfusion reduction rather than infarct volume (iii) other clinical factors (age, sex and time from symptom onset) did not affect the occurrence of crossed cerebellar diaschisis.

Large Volumes of Critically Hypoperfused Penumbral Tissue Do Not Preclude Good Outcomes After Complete Endovascular Reperfusion

Acute ischemic stroke patients with large volumes of severe hypoperfusion (Tmax>10 s>100 mL) on magnetic resonance imaging have a higher likelihood of intracranial hemorrhage and poor outcomes after reperfusion. We aim to evaluate the impact of the extent of Tmax>10 s CTP lesions in patients undergoing successful treatment. Retrospective database review of endovascular acute ischemic stroke treatment between September 2010 and March 2015 for patients with anterior circulation occlusions with baseline RAPID CTP and full reperfusion (mTICI 3). The primary outcome was the impact of the Tmax>10 s lesion spectrum on infarct growth. Secondary safety and efficacy outcomes included parenchymal hematomas and good clinical outcomes (90-day modified Rankin Scale score, 0-2). Of 684 treated patients, 113 patients fit the inclusion criteria. Tmax>10 s>100 mL patients (n=37) had significantly higher baseline National Institutes of Health Stroke Scale (20.7±3.8 versus 17.0±5.9; P<0.01), more internal carotid artery terminus occlusions (29% versus 9%; P=0.02), and larger baseline (38.6±29.6 versus 11.7±15.8 mL; P<0.01) and final (60.7±60.0 versus 29.4±33.9 mL; P<0.01) infarct volumes when compared with patients without Tmax>10 s>100 mL (n=76); however, the 2 groups were otherwise well balanced. There were no significant differences in infarct growth (22.1±51.6 versus 17.8±32.4 mL; P=0.78), severe intracranial hemorrhage (PH2: 2% versus 4%; P=0.73), good outcomes (90-day mRS score, 0-2: 56% versus 59%; P=0.83), or 90-day mortality (16% versus 7%; P=0.28). On multivariate analysis, only baseline National Institutes of Health Stroke Scale (odds ratio, 1.19; 95% confidence interval, 1.06-1.34; P<0.01) and baseline infarct core volume (odds ratio, 1.05; 95% confidence interval, 1.02-1.08; P<0.01) were independently associated with Tmax>10 s>100 mL. There was no association between Tmax>10 s>100 mL with any PH, good outcome, or infarct growth. In the setting of limited baseline ischemic cores, large Tmax>10 s lesions on computed tomographic perfusion do not seem to be associated with a higher risk of parenchymal hematomas and do not preclude good outcomes in patients undergoing endovascular reperfusion with contemporary technology.

Predicting Collateral Status With Magnetic Resonance Perfusion Parameters: Probabilistic Approach With a Tmax-Derived Prediction Model.

Good collateral flow is an important predictor for favorable responses to recanalization therapy and successful outcomes after acute ischemic stroke. Magnetic resonance perfusion-weighted imaging (MRP) is widely used in patients with stroke. However, it is unclear whether the perfusion parameters and thresholds would predict collateral status. The present study evaluated the relationship between hypoperfusion severity and collateral status to develop a predictive model for good collaterals using MRP parameters. Patients who were eligible for recanalization therapy that underwent both serial diffusion-weighted imaging and serial MRP were enrolled into the study. A collateral flow map derived from MRP source data was generated through automatic postprocessing. Hypoperfusion severity, presented as proportions of every 2-s Tmax strata to the entire hypoperfusion volume (Tmax≥2 s), was compared between patients with good and poor collaterals. Prediction models for good collaterals were developed with each Tmax strata proportion and cerebral blood volumes. Among 66 patients, 53 showed good collaterals based on MRP-based collateral grading. Although no difference was noted in delays within 16 s, more severe Tmax delays (Tmax16-18 s, Tmax18-22 s, Tmax22-24 s, and Tmax>24 s) were associated with poor collaterals. The probability equation model using Tmax strata proportion demonstrated high predictive power in a receiver operating characteristic analysis (area under the curve=0.9303; 95% confidence interval, 0.8682-0.9924). The probability score was negatively correlated with the volume of infarct growth (P=0.030). Collateral status is associated with more severe Tmax delays than previously defined. The present Tmax severity-weighted model can determine good collaterals and subsequent infarct growth.

National Institutes of Health Stroke Scale score is an unreliable predictor of perfusion deficits in acute stroke.

Perfusion-weighted magnetic resonance imaging is not routinely used to investigate stroke/transient ischemic attack. Many clinicians use perfusion-weighted magnetic resonance imaging selectively in patients with more severe neurological deficits, but optimal selection criteria have never been identified. We tested the hypothesis that a National Institutes of Health Stroke Scale score threshold can be used to predict the presence of perfusion-weighted magnetic resonance imaging deficits in patients with acute ischemic stroke/transient ischemic attack. National Institutes of Health Stroke Scale scores were prospectively assessed in 131 acute stroke/transient ischemic attack patients followed by magnetic resonance imaging, including perfusion-weighted magnetic resonance imaging within 72 h of symptom onset. Patients were dichotomized based on the presence or absence of perfusion deficits using a threshold of Tmax (time to peak maps after the impulse response) delay ≥four-seconds and a hypoperfused tissue volume of ≥1 ml. Patients with perfusion deficits (77/131, 59%) had higher median (interquartile range) National Institutes of Health Stroke Scale scores (8 [12]) than those without perfusion deficits (3 [4], P < 0.001). A receiver operator characteristic analysis indicated poor to moderate sensitivity of National Institutes of Health Stroke Scale scores for predicting perfusion deficits (area under the curve = 0.787). A National Institutes of Health Stroke Scale score of ≥6 was associated with specificity of 85%, but sensitivity of only 69%. No National Institutes of Health Stroke Scale score threshold identified all cases of perfusion-weighted magnetic resonance imaging deficits with sensitivity >94%. Although higher National Institutes of Health Stroke Scale scores are predictive of perfusion deficits, many patients with no clinically detectable signs have persisting cerebral blood flow changes. A National Institutes of Health Stroke Scale score threshold should therefore not be used to select patients for perfusion-weighted magnetic resonance imaging. Perfusion-weighted magnetic resonance imaging should be considered in all patients presenting with acute focal neurological deficits, even if these deficits are transient.

Diffusion-perfusion mismatch: an opportunity for improvement in cortical function.

Objective: There has been controversy over whether diffusion–perfusion mismatch provides a biomarker for the ischemic penumbra. In the context of clinical stroke trials, regions of the diffusion–perfusion mismatch that do not progress to infarct in the absence of reperfusion are considered to represent “benign oligemia.” However, at least in some cases (particularly large vessel stenosis), some of this hypoperfused tissue may remain dysfunctional for a prolonged period without progressing to infarct and may recover function if eventually reperfused. We hypothesized that patients with persistent diffusion–perfusion mismatch using a hypoperfusion threshold of 4–5.9 s delay on time-to-peak (TTP) maps at least sometimes have persistent cognitive deficits relative to those who show some reperfusion of this hypoperfused tissue.Methods: We tested this hypothesis in 38 patients with acute ischemic stroke who had simple cognitive tests (naming or line cancelation) and MRI with diffusion and perfusion imaging within 24 h of onset and again within 10 days, most of whom had large vessel stenosis or occlusion.Results: A persistent perfusion deficit of 4–5.9 s delay in TTP on follow up MRI was associated with a persistent cognitive deficit at that time point (p < 0.001). When we evaluated only patients who did not have infarct growth (n = 14), persistent hypoperfusion (persistent mismatch) was associated with a lack of cognitive improvement compared with those who had reperfused. The initial volume of hypoperfusion did not correlate with the later infarct volume (progression to infarct), but change in volume of hypoperfusion correlated with change in cognitive performance (p = 0.0001). Moreover, multivariable regression showed that the change in volume of hypoperfused tissue of 4–5.9 s delay (p = 0.002), and change in volume of ischemic tissue on diffusion weighted imaging (p = 0.02) were independently associated with change in cognitive function.Conclusion: Our results provide additional evidence that non-infarcted tissue with a TTP delay of 4–5.9 s may be associated with persistent deficits, even if it does not always result in imminent progression to infarct. This tissue may represent the occasional opportunity to intervene to improve function even days after onset of symptoms.

Abstract 189: STAR: CT and MR Perfusion Imaging and Good Outcomes in Endovascular Stroke Treatment

Background: Perfusion imaging may be used to select stroke patients for endovascular treatment, although few data are available on studies of CT and MRI, as used in Solitaire Flow Restoration Thrombectomy for Acute Revascularization (STAR), a prospective, multicenter, single-arm trial. Methods: The CT/MRI core lab processed available CT and MR perfusion source images with Olea Sphere 2.2 to measure volumes of infarct core and hypoperfusion. Established definitions for CT and MRI (core: rCBF &lt; 31% (CT); ADC &lt; 600х10 -6 mm 2 /s (MRI); hypoperfusion: Tmax &gt; 6s (CT and MRI)) were used to provide equivalent measures. Core and hypoperfusion volumes, mismatch ratio and DEFUSE-2 categories of target and malignant profile were used to define the relationship of perfusion imaging with clinical outcomes. Results: 87 of 202 cases in STAR (mean age 68.7 ± 12.5 years; 57% women; median baseline NIHSS 15 (8-25)) had CT (60/87 or 69%) or MRI (27/87 or 31%) perfusion imaging processed. This cohort was similar to other STAR cases with mean time to treatment of 263 ± 95 min and IV tPA before thrombectomy in 55%. Infarct core volume was mean 11.2 ± 19.7 (0-116.9) cc with hypoperfusion volume of mean 70.6 ± 46.0 (0-182.2) cc. Mismatch ratio was mean 17.8 ± 53.7. 75/87 (86%) cases were categorized as target mismatch and only 5/87 (6%) as malignant profile. 58/87 patients (67%) had a mRS of 0, 1, or 2 at 90 days and 39/87 (45%) with a mRS of 0 or 1. Multivariate logistic regression identified that age (OR 0.91, p=0.010), time to treatment (OR 0.23, p=0.001), and Tmax &gt; 10 s volume (OR 0.96, p=0.003) were associated with good outcomes (mRS 0-2 at 90 days). Only 2/87 (2.3%) patients had symptomatic ICH. Target mismatch exhibited a trend for good outcomes (p=0.149). Conclusions: STAR enrolled subjects with small infarct cores and extensive mismatch, achieving good clinical outcomes in a majority of cases treated with endovascular therapy. Randomized trials using CT and MR perfusion imaging are warranted to assess the impact of current endovascular stroke treatments.

Utility of Early Post-treatment Single-Photon Emission Computed Tomography Imaging to Predict Outcome in Stroke Patients Treated with Intravenous Tissue Plasminogen Activator

It is important to predict the outcome of tissue plasminogen activator (tPA)-treated patients early after the treatment for considering the post-tPA treatment option. We assessed cerebral blood flow (CBF) of tPA-treated patients with single-photon emission computed tomography (SPECT) 1 hour after tPA infusion to predict the patient outcome. Technetium-99m-hexamethylpropyleneamine oxime SPECT was performed in 35 consecutive tPA-treated patients. Asymmetry index, a contralateral-to-ipsilateral ratio of CBF, was calculated to analyze CBF quantitatively. Hypoperfusion or hyperperfusion was defined as a decrease of 25% or more or a increase of 25% or more in asymmetry index, respectively. Of all 35 patients, 23 had only hypoperfusion, 8 had both hypoperfusion and hyperperfusion, 2 had only hyperperfusion, and 2 had no perfusion abnormality. When evaluating the association between hypoperfusion and outcome, hypoperfusion volumes were significantly correlated with the modified Rankin Scale at 3months (r=.634, P<.001). Hyperperfusion was observed in 10 patients (28.6%) and they showed a marked National Institutes of Health Stroke Scale score improvement in the first 24-hour period, which were significantly greater than those of 25 patients without hyperperfusion (P=.033). Eight patients (22.9%) with intracerebral hemorrhage (ICH) were all asymptomatic. Most ICHs were located in hypoperfusion areas, and no ICH was related to hyperperfusion. The results of the present study demonstrated that hypoperfusion volume was associated with poor outcome, whereas the presence of hyperperfusion seemed to be predictive of symptom improvement but not of development of ICH. Taken together, early post-treatment SPECT imaging seems to be a useful biomarker of outcome in tPA-treated patients.

Quantitative Analysis of Hypoperfusion in Acute Stroke

This study compares the concordance between arterial spin labeling (ASL) and dynamic susceptibility contrast (DSC) for the identification of regional hypoperfusion and diffusion-perfusion mismatch tissue classification using a quantitative method. The inclusion criteria for this retrospective study were as follows: patients with acute ischemic syndrome with symptom onset <24 hours and acquisition of both ASL and DSC MR perfusion. The volumes of infarction and hypoperfused lesions were calculated on ASL and DSC multi-parametric maps. Patients were classified into reperfused, matched, or mismatch groups using time to maximum >6 sec as the reference. In a subset of patients who were successfully recanalized, the identical analysis was performed and the infarction and hypoperfused lesion volumes were used for paired pre- and posttreatment comparisons. Forty-one patients met our inclusion criteria. Twenty patients underwent successful endovascular revascularization (TICI>2a), resulting in a total of 61 ASL-DSC data pairs for comparison. The hypoperfusion volume on ASL-cerebral blood flow best approximated the DSC-time to peak volume (r=0.83) in pretreatment group and time to maximum (r=0.46) after recanalization. Both ASL-cerebral blood flow and DSC-TTP overestimated the hypoperfusion volume compared with time to maximum volume in pretreatment (F=27.41, P<0.0001) and recanalized patients (F=8.78, P<0.0001). ASL-cerebral blood flow overestimates the DSC time to maximum hypoperfusion volume and mismatch classification in patients with acute ischemic syndrome. Continued overestimation of hypoperfused volume after recanalization suggests flow pattern and velocity changes in addition to arterial transit delay can affects the performance of ASL.