Perfusion In Acute Ischemic Stroke Research Articles

HMGB1: A New Target for Ischemic Stroke and Hemorrhagic Transformation.

Stroke in China is distinguished by its high rates of morbidity, recurrence, disability, and mortality. The ultra-early administration of rtPA is essential for restoring perfusion in acute ischemic stroke, though it concurrently elevates the risk of hemorrhagic transformation. High-mobility group box 1 (HMGB1) emerges as a pivotal player in neuroinflammation after brain ischemia and ischemia-reperfusion. Released passively by necrotic cells and actively secreted, including direct secretion of HMGB1 into the extracellular space and packaging of HMGB1 into intracellular vesicles by immune cells, glial cells, platelets, and endothelial cells, HMGB1 represents a prototypical damage-associated molecular pattern (DAMP). It is intricately involved in the pathogenesis of atherosclerosis, thromboembolism, and detrimental inflammation during the early phases of ischemic stroke. Moreover, HMGB1 significantly contributes to neurovascular remodeling and functional recovery in later stages. Significantly, HMGB1 mediates hemorrhagic transformation by facilitating neuroinflammation, directly compromising the integrity of the blood-brain barrier, and enhancing MMP9 secretion through its interaction with rtPA. As a systemic inflammatory factor, HMGB1 is also implicated in post-stroke depression and an elevated risk of stroke-associated pneumonia. The role of HMGB1 extends to influencing the pathogenesis of ischemia by polarizing various subtypes of immune and glial cells. This includes mediating excitotoxicity due to excitatory amino acids, autophagy, MMP9 release, NET formation, and autocrine trophic pathways. Given its multifaceted role, HMGB1 is recognized as a crucial therapeutic target and prognostic marker for ischemic stroke and hemorrhagic transformation. In this review, we summarize the structure and redox properties, secretion and pathways, regulation of immune cell activity, the role of pathophysiological mechanisms in stroke, and hemorrhage transformation for HMGB1, which will pave the way for developing new neuroprotective drugs, reduction of post-stroke neuroinflammation, and expansion of thrombolysis time window.

Use of the SONAS Ultrasound Device for the Assessment of Cerebral Perfusion in Acute Ischemic Stroke

Background Early recognition of large‐vessel occlusion in acute ischemic stroke is pivotal to ensuring timely and effective treatment. However, current prehospital evaluation strategies largely rely on stroke scales that lack sensitivity and specificity. Recently, a novel, portable, noninvasive brain perfusion ultrasound device (SONAS) was developed as a diagnostic aid and demonstrated robust correlation with magnetic resonance imaging–based brain perfusion imaging. The present study aimed to investigate the feasibility and diagnostic performance of the SONAS device in identifying alterations in cerebral blood flow in patients with acute ischemic stroke with suspected or known perfusion deficits. Methods We performed a phase II, single‐arm, prospective study using SONAS in a close timely relation to computed tomography perfusion imaging in subjects diagnosed with acute ischemic stroke and suspected or known large‐vessel pathology, presenting within 24 hours of symptom onset between April 2019 through December 2019. Performance end points included successful measurement of time‐to‐peak in each hemisphere and comparison of perfusion deficits measured by SONAS to the reference standard computed tomography perfusion imaging. Safety end points included frequency, severity, and outcome of adverse events. Results A total of 20 subjects were enrolled. Eighteen subjects (90%) had microbubble signals successfully detected on initial assessment by SONAS. The diagnostic accuracy of the SONAS device in identifying a perfusion deficit was 88.9%. The sensitivity was 14 of 15 (93.3%), and the specificity was 2 of 3 (66.7%). No adverse events were reported secondary to SONAS or the contrast agent used. Conclusion In this clinical study, we demonstrated that the SONAS system is a safe tool that can aid in identifying cerebral perfusion deficits in this selected population of patients with acute ischemic stroke with suspected or known perfusion deficits. Future studies should assess the efficacy and impact on clinical outcomes of using SONAS in a real‐world “in the field” setting on a large subset of patients with suspected stroke and in addition to prehospital stroke scales.

A 3D Multi-task Regression and Ordinal Regression Deep Neural Network for Collateral Imaging from Dynamic Susceptibility Contrast-Enhanced MR perfusion in Acute Ischemic Stroke

Background and ObjectiveCerebral collaterals have been identified as one of the primary determinants for treatment options in acute ischemic stroke. Several works have been proposed, but these have not been adopted for a routine clinical usage due to their manual and heuristic nature as well as inconsistency and instability of the assessment. Herein, we present an advanced deep learning-based method that can automatically generate a multiphase collateral imaging (collateral map) derived from dynamic susceptibility contrast-enhanced MR perfusion (DSC-MRP) in an accurate and robust manner. MethodsWe develop a 3D multi-task regression and ordinal regression deep neural network for generating collateral maps from DSC-MRP, which formulates the prediction of collateral maps as both a regression task and an ordinal regression task. For an ordinal regression task, we introduce a spacing-decreasing discretization (SDD) strategy to represent the intensity of the collateral status on a discrete, ordinal scale. We also devise loss functions to achieve effective and efficient multi-task learning. ResultsWe systematically evaluated the performance of the proposed network using DSC-MRP from 802 patients. On average, the proposed network achieved ≥0.900 squared correlation coefficient (R-Squared), ≥0.916 Tanimoto measure (TM), ≥0.0913 structural similarity index measure (SSIM), and ≤0.564 × 10−1 mean absolute error (MAE), outperforming eight competing models that have been recently developed in medical imaging and computer vision. We also found that the proposed network could provide an improved contrast between the low and high intensity regions in the collateral maps, which is a key to an accurate evaluation of the collateral status. ConclusionsThe experimental results demonstrate that the proposed network is able to generate collateral maps with high accuracy, facilitating a timely and prompt assessment of the collateral status in clinlcs. The future study will entail the optimization of the proposed network and its clinical evalution in a prospective manner.

Whole blood viscosity is associated with baseline cerebral perfusion in acute ischemic stroke

Whole blood viscosity (WBV) is the intrinsic resistance to flow developed due to the frictional force between adjacent layers of flowing blood. Elevated WBV is an independent risk factor for stroke. Poor microcirculation due to elevated WBV can prevent adequate perfusion of the brain and might act as an important secondary factor for hypoperfusion in acute ischaemic stroke. In the present study, we examined the association of WBV with basal cerebral perfusion assessed by CT perfusion in acute ischaemic stroke. Confirmed acute ischemic stroke patients (n = 82) presenting in hours were recruited from the single centre. Patients underwent baseline multimodal CT (non-contrast CT, CT angiography and CT perfusion). Where clinically warranted, patients also underwent follow-up DWI. WBV was measured in duplicate within 2 h after sampling from 5-mL EDTA blood sample. WBV was significantly correlated with CT perfusion parameters such as perfusion lesion volume, ischemic core volume and mismatch ratio; DWI volume and baseline NIHSS. In a multivariate linear regression model, WBV significantly predicted acute perfusion lesion volume, core volume and mismatch ratio after adjusting for the effect of occlusion site and collateral status. Association of WBV with hypoperfusion (increased perfusion lesion volume, ischaemic core volume and mismatch ratio) suggest the role of erythrocyte rheology in cerebral haemodynamic of acute ischemic stroke. The present findings open new possibilities for therapeutic strategies targeting erythrocyte rheology to improve cerebral microcirculation in stroke.

Nitroglycerin Is Not Associated with Improved Cerebral Perfusion in Acute Ischemic Stroke

The study was conducted to test the hypothesis that nitroglycerin (NTG) increases cerebral perfusion focally and globally in acute ischemic stroke patients, using serial perfusion-weighted imaging (PWI) magnetic resonance imaging measurements. Thirty-five patients underwent PWI immediately before and 72 h after administration of a transdermal NTG patch or no treatment. Patients with baseline mean arterial pressure (MAP) > 100 mmHg (NTG group, n = 20) were treated with transdermal NTG (0.2 mg/h) for 72 h, without a nitrate-free interval. Patients with MAP ≤ 100 mmHg (untreated group, n = 15) were not treated. The primary outcome measure was absolute cerebral blood flow (CBF) in the hypoperfused region at 72 h. The mean baseline absolute CBF in the hypoperfused region was similar in the NTG group (33.3 ± 10.2 ml/100 g/min) and untreated (32.7 ± 8.4 ml/100 g/min, p = 0.4) groups. The median (IQR) baseline infarct volume was 10.4 (2.5-49.3) ml in the NTG group and 32.6 (8.6-96.7) ml in the untreated group (p = 0.09). MAP change in the NTG group was 1.2 ± 12.6 and 8 ± 20.7 mmHg at 2 h and 72 h, respectively. Mean absolute CBF in the hypoperfused region at 72 h was similar in the NTG (29.9 ± 12 ml/100 g/min) and untreated groups (24.1 ± 10 ml/100 g/min, p = 0.8). The median infarct volume increased in untreated (11.8 (5.7-44.2) ml) than the NTG group (3.2 (0.5-16.5) ml; p = 0.033) on univariate analysis, however, there was no difference on regression analysis. NTG was not associated with improvement in cerebral perfusion in acute ischemic stroke patients.

Deep regression neural networks for collateral imaging from dynamic susceptibility contrast-enhanced magnetic resonance perfusion in acute ischemic stroke.

Acute ischemic stroke is one of the primary causes of death worldwide. Recent studies have shown that the assessment of collateral status could aid in improving the treatment for patients with acute ischemic stroke. We present a 3D deep regression neural network to automatically generate the collateral images from dynamic susceptibility contrast-enhanced magnetic resonance perfusion (DSC-MRP) in acute ischemic stroke. This retrospective study includes 144 subjects with acute ischemic stroke (stroke cases) and 201 subjects without acute ischemic stroke (controls). DSC-MRP images of these subjects were manually inspected for collateral assessment in arterial, capillary, early and late venous, and delay phases. The proposed network was trained on 205 subjects, and the optimal model was chosen using the validation set of 64 subjects. The predictive power of the network was assessed on the test set of 76 subjects using the squared correlation coefficient (R-squared), mean absolute error (MAE), Tanimoto measure (TM), and structural similarity index (SSIM). The proposed network was able to predict the five phase maps with high accuracy. On average, 0.897 R-squared, 0.581 × 10-1 MAE, 0.946 TM, and 0.846 SSIM were achieved for the five phase maps. No statistically significant difference was, in general, found between controls and stroke cases. The performance of the proposed network was lower in the arterial and venous phases than the other three phases. The results suggested that the proposed network performs equally well for both control and acute ischemic stroke groups. The proposed network could help automate the assessment of collateral status in an efficient and effective manner and improve the quality and yield of diagnosis of acute ischemic stroke. The follow-up study will entail the clinical evaluation of the collateral images that are generated by the proposed network.

Ultrasonic quantification of cerebral perfusion in acute anterior circulation occlusive stroke-A comparative challenge of the refill- and the bolus-kinetics approach.

PurposeTo prospectively evaluate the potential of semi-quantitative evaluation of cerebral perfusion in acute ischemic stroke by comparing two established ultrasound approaches.Materials and methodsConsecutive inclusion of patients with acute occlusion of middle cerebral artery (MCA) confirmed by either magnetic resonance imaging (MRI) or computed tomography (CT) perfusion imaging qualifying for interventional therapy. Comparison of bilateral high mechanical index (MI) bolus-kinetics (HighMiB) and unilateral low MI refill-kinetics (LowMiR) performed before specific treatment.ResultsIn 16/31 patients HighMiB was eligible, in 8/31 patients LowMiR was eligible. In six out of these eight patients both HighMiB and LowMiR were eligible for direct comparison. In MR/CT perfusion imaging of the 16 patients eligible for HighMiB, 29/48 cortical regions of interest (ROIs) (60%) displayed hypoperfusion or ischemia, areas inadequately accessible by LowMiR. These ROIs made up 49% of the 59 ROIs displaying hypoperfusion or ischemia, altogether. Matching of parameters in normal and impaired ROIs between LowMiR and MRI/CT perfusion imaging was significantly poorer than in HighMiB.ConclusionLowMiR using refill-kinetics potentially has the advantage of real time imaging and better resolution. The diagnostic impact, however, proves inferior to HighMiB both with respect to imaging quality and semi-quantitative evaluation.

Microthrombus-Targeting Micelles for Neurovascular Remodeling and Enhanced Microcirculatory Perfusion in Acute Ischemic Stroke.

Reperfusion injury exists as the major obstacle to full recovery of neuron functions after ischemic stroke onset and clinical thrombolytic therapies. Complex cellular cascades including oxidative stress, neuroinflammation, and brain vascular impairment occur within neurovascular units, leading to microthrombus formation and ultimate neuron death. In this work, a multitarget micelle system is developed to simultaneously modulate various cell types involved in these events. Briefly, rapamycin is encapsulated in self-assembled micelles that are consisted of reactive oxygen species (ROS)-responsive and fibrin-binding polymers to achieve micelle retention and controlled drug release within the ischemic lesion. Neuron survival is reinforced by the combination of micelle facilitated ROS elimination and antistress signaling pathway interference under ischemia conditions. In vivo results demonstrate an overall remodeling of neurovascular unit through micelle polarized M2 microglia repair and blood-brain barrier preservation, leading to enhanced neuroprotection and blood perfusion. This strategy gives a proof of concept that neurovascular units can serve as an integrated target for ischemic stroke treatment with nanomedicines.

Abstract 177: The Association of Blood Pressure and Pretreatment Arterial Collaterals in Acute Ischemic Stroke

Introduction: Leptomeningeal collaterals maintain arterial perfusion in acute arterial occlusion but may fluctuate subject to arterial blood pressure (ABP). We aim to investigate the relationship between ABP and collaterals as assessed by CT perfusion in acute ischemic stroke. Methods: We retrospectively analyzed acute anterior circulation ischemic stroke patients with CT perfusion from 2009 to 2014. Collateral status using relative filling time delay (rFTD) determined by time delay of collateral-derived contrast opacification within the Sylvian fissure, from 0 seconds to unlimited count. The data were analyzed by zero-inflated negative binomial regression model including an appropriate interaction examining in the model in terms of occlusion location and onset-to-CT time (OCT). Results: Two hundred and seventy patients were included. We found that increment of 10mm Hg in BP, the odds that a patient would have rFTD equal to 0 seconds increased by 27.9% in SBP (P=0.001), by 73.9% in diastolic blood pressure (DBP) (P<0.001) and by 68.5% in mean blood pressure (MBP) (P<0.001). For patients with rFTD not necessarily equal to 0 seconds, every 10mm Hg increase in BP, there was a 7% decrease in expected count of seconds for rFTD in SBP (P=0.002), 10% decrease for rFTD in DBP and 11% decrease for rFTD in MBP. The arterial occlusion location and OCT showed no significant interaction in the BP-rFTD relationship (P>0.05). Conclusions: In acute ischemic stroke, higher ABP is associated with improved leptomeningeal collaterals as identified by decreased rFTD.

Contrast-Enhanced Ultrasound Imaging in Detection of Changes in Cerebral Perfusion

Contrast-enhanced ultrasonography (CEU) is a non-invasive imaging technique that provides real-time, bedside information on changes in global and segmental organ perfusion. Currently, there is a lack of data concerning changes in the distribution of segmental brain perfusion in acute ischemic stroke treated by decompressive craniectomy. The aim of our case series was to assess the role of CEU after decompressive craniectomy in patients with acute ischemic stroke. CEU was performed in 12 patients at baseline and after any one of the following interventions was performed as dictated by the patient's clinical condition: vasoactive drug administration (in order to achieve cerebral perfusion pressure ≥70 mm Hg and mean arterial pressure <100 mm Hg for management of arterial blood pressure) and mild hyperventilation (carbon dioxide arterial pressure = 30–35 mm Hg). CEU was able to detect a significant variation in cerebral contrast distribution in both normal and pathologic hemispheres after induced hyperventilation (difference in time to peak [dTTP] = −38.4%), vasodilation (dTTP = −6.6%) and vasoconstriction (dTTP = +31.2%) (p < 0.05). CEU can be useful in assessing real-time cerebral perfusion changes in neurocritical care patients.

Abstract TP58: A Comparison of Automated and Manual Volumetric Analysis of CT Perfusion in Acute Ischemic Stroke Patients

Background: Manual volumetric analysis of CT perfusion (CTP) in acute ischemic stroke (AIS) patients using the OsiriX software is an established and accurate technique. Hypothesis: Automated software will produce accurate measurements compared to manual volumetric measurements. Methods: We reviewed 120 inpatients from 2010-2014 with AIS and a CTP from the acute setting. We used the automated Olea Sphere software to generate perfusion maps with oscillation index singular value decomposition (oSVD) and Bayesian probabilistic deconvolution. We used the manual OsiriX software to draw regions-of-interest delineating the stroke core on cerebral blood volume (CBV) and penumbra on cerebral blood flow (CBF) maps of the original CTP. For Bayesian analysis we defined stroke core as relative CBF2 seconds, and penumbra as relative mean transit time &gt;135%. For oSVD we defined stroke core as relative CBF2 seconds, and penumbra as absolute Tmax &gt;6 seconds. We compared techniques with a Pearson correlation coefficient and linear regression. Results: Both automated techniques had excellent correlation and agreement with the manual measurements (Table 1), but Bayesian deconvolution yielded superior agreement for CBV (Figure 1). Conclusion: Automated CTP volumetric analysis in AIS patients is reliable and accurate. Bayesian deconvolution has superior agreement with manual measurements of stroke core. Automated volumetric methods have an inherent appeal in the acute stroke setting given their efficiency.

Abstract WMP81: Collaterals and the Severity of Hypoperfusion in Acute Ischemic Stroke are Independent of Dehydration or Volume Status

Background: Systemic hemodynamic factors may affect blood flow to the brain, yet the influence of volume status and the use of fluid administration to improve perfusion in acute ischemic stroke remains unproven. We correlated the presence of dehydration and volume status defined by initial lab values with perfusion MRI and collaterals at angiography in middle cerebral artery (MCA) stroke patients. Methods: Retrospective analysis of a consecutive series of isolated M1 MCA occlusions was conducted at an expert core lab to quantify acute Tmax volumes, Tmax hypoperfusion severity ratios and ASITN collateral grade on digital subtraction angiography (DSA). Blood urea nitrogen (BUN) and creatinine (Cr) measured during triage were correlated with hypoperfusion and ASITN/SIR grade. Statistical methods included correlations and ANOVA. Results: 95 patients (median age 74 (24-101) years; 71 women; median NIHSS 16; median time to MRI, 4h06min) with acute stroke due to M1 occlusion (52 proximal, 43 distal) had contemporaneous BUN/Cr, perfusion MRI and DSA during a 6-year period. Dehydration was noted in 38% (BUN/Cr&gt;20) and 71% (BUN/Cr&gt;15) of patients. Tmax&gt;6sec volumes were median 197 cc (IQR 102-347), with Tmax hypoperfusion severity ratios of 10/6 (median 0.80 (IQR 0.72-0.87)). DSA collateral grade was median 2 (IQR 2-3). Volume status or BUN/Cr was distinct from Tmax hypoperfusion severity at all thresholds, including Tmax&gt;6s (r=0.143, p=0.166), Tmax 10/6 (r=0.114, p=0.271). Direct correlation between BUN/Cr and DSA collateral grade was also unapparent (r=0.034, p=0.744). Conclusions: Dehydration and the degree of volume depletion may be common, but are not associated with the severity of collateral perfusion in acute M1 MCA occlusion. Collateral grade defined by DSA and the associated severity of hypoperfusion in the brain is unrelated to intravascular volume status.

The Prognostic Value of CT Angiography and CT Perfusion in Acute Ischemic Stroke

Background: CT angiography (CTA) and CT perfusion (CTP) are important diagnostic tools in acute ischemic stroke. We investigated the prognostic value of CTA and CTP for clinical outcome and determined whether they have additional prognostic value over patient characteristics and non-contrast CT (NCCT). Methods: We included 1,374 patients with suspected acute ischemic stroke in the prospective multicenter Dutch acute stroke study. Sixty percent of the cohort was used for deriving the predictors and the remaining 40% for validating them. We calculated the predictive values of CTA and CTP predictors for poor clinical outcome (modified Rankin Scale score 3-6). Associations between CTA and CTP predictors and poor clinical outcome were assessed with odds ratios (OR). Multivariable logistic regression models were developed based on patient characteristics and NCCT predictors, and subsequently CTA and CTP predictors were added. The increase in area under the curve (AUC) value was determined to assess the additional prognostic value of CTA and CTP. Model validation was performed by assessing discrimination and calibration. Results: Poor outcome occurred in 501 patients (36.5%). Each of the evaluated CTA measures strongly predicted outcome in univariable analyses: the positive predictive value (PPV) was 59% for Alberta Stroke Program Early CT Score (ASPECTS) ≤7 on CTA source images (OR 3.3; 95% CI 2.3-4.8), 63% for presence of a proximal intracranial occlusion (OR 5.1; 95% CI 3.7-7.1), 66% for poor leptomeningeal collaterals (OR 4.3; 95% CI 2.8-6.6), and 58% for a >70% carotid or vertebrobasilar stenosis/occlusion (OR 3.2; 95% CI 2.2-4.6). The same applied to the CTP measures, as the PPVs were 65% for ASPECTS ≤7 on cerebral blood volume maps (OR 5.1; 95% CI 3.7-7.2) and 53% for ASPECTS ≤7 on mean transit time maps (OR 3.9; 95% CI 2.9-5.3). The prognostic model based on patient characteristics and NCCT measures was highly predictive for poor clinical outcome (AUC 0.84; 95% CI 0.81-0.86). Adding CTA and CTP predictors to this model did not improve the predictive value (AUC 0.85; 95% CI 0.83-0.88). In the validation cohort, the AUC values were 0.78 (95% CI 0.73-0.82) and 0.79 (95% CI 0.75-0.83), respectively. Calibration of the models was satisfactory. Conclusions: In patients with suspected acute ischemic stroke, admission CTA and CTP parameters are strong predictors of poor outcome and can be used to predict long-term clinical outcome. In multivariable prediction models, however, their additional prognostic value over patient characteristics and NCCT is limited in an unselected stroke population.

Computed Tomography Perfusion in Acute Ischemic Stroke: Is It Ready for Prime Time?

### David S. Liebeskind, Mark W. Parsons, and Max Wintermark Computed tomography perfusion (CTP) is beyond prime time, ready for use to select patients with acute ischemic stroke for intravenous and endovascular reperfusion therapies in routine clinical practice. After 2 decades of fervent stroke research using advanced imaging and revascularization techniques, recent stroke trials astutely combined imaging and therapeutic expertise, likely the recipe for their resounding success. Multimodal CT, including CTP, was a key element in these trials that selected individuals with favorable collateral profiles and resultant improved outcomes after effective reperfusion.1 Academic discourse about optimal thresholds of ischemic core and mismatch volumes comprise late news, beyond prime time. Literature of only a few years ago aptly predicted the pivotal role of CTP.2 Lev2 eloquently noted the impact of collateral perfusion, critical data from a snapshot of hemodynamics, and the essential imaging goals of delineating core to avert hemorrhage while measuring salvageable tissue at-risk that need not be perfect. Prior trials failed to leverage advanced imaging or alternatively, entwined imaging and reperfusion inefficiently. In 2015 and beyond, triage of acute ischemic stroke for potential reperfusion should rapidly and efficiently identify optimal candidates for thrombolysis and thrombectomy across the broadest population. Multimodal imaging can swiftly address ischemic injury in the brain, arterial occlusion, collateral status, and the topography of perfusion that map the risk of hemorrhagic transformation and nutritive reperfusion. As noted by Lev,2 multimodal imaging is brain and may improve outcomes and optimize costs. The stroke community has historically been polarized between minimalists and extremists regarding the role and nature of imaging for acute stroke evaluation. Minimalists have argued that noncontrast CT may suffice; yet this approach will no longer work in the endovascular era when presence/absence and location of arterial occlusion and collateral profile are pivotal. In addition, telemedicine supplant refutes the minimalists’ argument that …

Early Basal Ganglia Hyperperfusion on CT Perfusion in Acute Ischemic Stroke: A Marker of Irreversible Damage?

CT perfusion scans are often used in acute stroke evaluations. We aimed to assess the outcome of areas of basal ganglia hyperperfusion on CTP in patients with acute ischemic stroke. We retrospectively reviewed the medical records and brain imaging of 139 patients presenting with acute stroke who underwent CTP for consideration of endovascular recanalization. Hyperperfusion was assessed qualitatively and defined as a matched region of increased cerebral blood flow and cerebral blood volume. CTA was used to locate arterial occlusion. Follow-up imaging was used to determine whether regions of hyperperfusion at baseline became infarcted or developed hemorrhage. Angiographic imaging was assessed to determine the presence or absence of early venous opacification. Six patients (4.3%) demonstrated hyperperfusion in the basal ganglia of the affected side (4 in the lenticular nucleus and 2 in the caudate). In all cases, the area of hyperperfusion ultimately proved to be infarcted. All patients had received intravenous thrombolysis before the CTP. CTA at the time of CTP showed middle or distal M1 occlusion but patency of the proximal M1 and A1 segments. Intracranial hemorrhage was noted in 2 of these 6 patients at follow-up. Acute basal ganglia hyperperfusion in patients with stroke may indicate nonviable parenchyma and risk of hemorrhagic conversion.

ASPECTS is a predictor of favorable CT perfusion in acute ischemic stroke

Computed tomography perfusion (CTP) is used by some stroke centers to stratify stroke patients who may potentially benefit from endovascular treatment. Our aim is to identify predictors of a favorable CTP in acute ischemic stroke patients evaluated within 8h from symptoms onset for possible endovascular treatment. We reviewed records of patients who had CTP studies between August 2010 and September 2012. We included all patients with anterior circulation strokes with evidence of large vessel disease. All patients had CT head and CT angiography head and neck as part of our protocol. Favorable CTP was defined as core infarct size less than one third the middle cerebral artery distribution and penumbra>20% of infarct size. The patients were divided into two groups based on favorable CTP or not. Baseline characteristics, time parameters, laboratory data and radiological data were compared between both groups. For statistical analysis, we used independent and Fisher's exact tests and a multivariate logistic regression model. During this period, 60 patients met the inclusion criteria. Patients with favorable CTP were likely to be ≥ 80 years (33% vs 9%, P = 0.026), have Alberta Stroke Program early CT score (ASPECTS) > 7 (81% v. 21%, P ≤ 0.001) and lower mean time from symptom onset to CTP (234 ± 91 vs 305 ± 122, P = 0.015). On regression analysis, ASPECTS was the only independent predictor of a favorable CTP (OR = 16.2, CI: 4.3-62.2, P < 0.001). ASPECT score may be used as a tool to predict a favorable CTP. Larger studies are needed to confirm our findings.

Trials of endovascular therapies or collaterals?

Several landmark clinical trials of endovascular therapy for acute ischemic stroke have recently jolted the concerted multidisciplinary efforts to develop effective revascularization strategies. Further consideration of these four endovascular stroke trials published in the last year suggests a more fundamental question: are these trials of specific treatments or have the results simply reflected the importance of underlying pathophysiology? Data from IMS III, MR RESCUE, SWIFT and TREVO2 consistently demonstrate the dramatic impact of collateral perfusion in acute ischemic stroke. Such collateral, or parallel, trials of the underlying pathophysiology in stroke reveal that diagnosis or selection of optimal candidates may be paramount to the specific drug or device therapy. Future trials of endovascular therapies may harness the influential role of collaterals as critical selection criteria for intervention, with triage based on imaging rather than time alone. Treating the optimal patient may be more important than chasing an elusive magical therapy.

Abstract TP237: Simulation: A Novel Modality for Improving Physician Knowledge and Confidence with recombinant tissue-type Plasminogen Activator for Acute Ischemic Stroke

Background: Intravenous recombinant tissue-type plasminogen activator (rtPA) is the only FDA approved non-invasive medical treatment for restoring brain perfusion in acute ischemic stroke (AIS) patients, however many neurology residents will graduate with little or no experience in its use. rtPA for AIS is underutilized, in part, due to lack of physician experience and training. Inappropriate use of rtPA leads to more frequent, potentially deadly complications. Simulation is an ideal educational modality for increasing physician knowledge, skill, and experience with the management of AIS without risk to patients. Methods: 23 physicians (13 neurology, 10 emergency medicine) were interviewed to identify and prioritize learning objectives for AIS management with respect to intravenous rtPA use. A comprehensive curriculum consisting of case discussions, a standardized patient encounter, and both high and low fidelity simulated patient scenarios were designed around these objectives in the format of a half-day simulation workshop. A pilot workshop was used to refine the curriculum. Entrance and exit surveys were administered to measure changes in knowledge, skills, and attitudes. The use of rtPA for AIS was tracked before and after the intervention. Results: To date, 17 neurology and emergency medicine residents have completed the workshop. All trainees reported significantly increased confidence in AIS patient selection and management with rtPA, including its potential complications. Intravenous rtPA use increased by 75% in the 7 months after residents began participating in the workshop (no protocol violations). This increase has persisted at 13 months after the initial simulation. Conclusions: Medical simulation is an effective educational modality for the training of physicians in management of AIS and shows great promise to favorably impact physician practice and AIS patient outcome.

Abstract TP41: Arterial Spin-Labeled Perfusion MRI with Multi-Delay: Expanding Beyond CBF in Acute Ischemic Stroke

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&lt;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 1901: Perfusion Augmentation with the NeuroFlo Device in the SENTIS Trial: Cerebral Blood Volume Gradients Improve on Serial MRI

Background: Partial aortic occlusion may increase global cerebral blood volume (CBV) to enhance collateral perfusion in acute ischemic stroke. Therapeutic CBV changes in the ischemic territory may be difficult to detect with standard techniques if superimposed on global CBV alterations. We used CBV gradient maps to evaluate perfusion augmentation in the ischemic territory on serial MRI from baseline to 6 hours follow-up in subjects randomized to medical therapy with or without NeuroFlo treatment in the SENTIS trial. Methods: Perfusion MRI datasets in 54 subjects acquired at both baseline and 6 hours were prospectively collected at the core lab. Post-processing yielded CBV images and corresponding CBV gradient maps that depict regional variation of this perfusion parameter. Blinded imaging expert review was conducted to document presence, location, and other features of CBV gradients, with description of serial changes. Serial changes in CBV gradient maps were analyzed with respect to baseline demographics, medical history, treatment arm, and clinical outcomes (modified Rankin Scale, mRS) at day 90. Results: CBV gradient maps could be generated in 51 subjects with paired perfusion MRIs. CBV gradients were evident in 33/51 subjects (64.7%) at baseline, predominantly involving peripheral regions of the MCA territory. The presence of CBV gradients at baseline did not differ based on demographics, medical history, or treatment allocation. Overall, 12.1% revealed unchanged CBV gradients from baseline to 6 hours, with worsening in 18.2% and improvements in 69.7%. Alterations of CBV gradients on serial MRI were not related to baseline demographics or medical history in this cohort. Device therapy, however, was significantly associated with improvement of CBV gradients (p=0.005). Such early improvement in perfusion immediately post-procedure did not translate into statistically improved clinical outcomes (mRS 0-2) at day 90. Conclusions: CBV gradient maps can depict evolution of ischemia in acute stroke and therapeutic interventions such as perfusion augmentation. Treatment with the NeuroFlo device may improve perfusion in acute stroke, although other factors may subsequently influence clinical outcomes at day 90.