Perfusion-diffusion Mismatch Research Articles

Diffusion‐Weighted Imaging Volume as the Best Predictor of the Diffusion–Perfusion Mismatch in Acute Stroke Patients within 8 Hours of Onset

Diagnostic accuracies of standard NCCT, CTA, CTA-SI, FLAIR, and DWI to detect the diffusion-perfusion mismatch (DPM) were compared. Stroke patients considered for endovascular therapy within 8 hours of onset were enrolled. DPM was defined as at least 160% mismatch between DWI and PWI volume. DPM was seen in 35 (71%) of 49 patients. ASPECTS on NCCT, CTA-SI, and DWI was 9 (8-9), 8 (6-9), and 7 (5-9) in mismatch group, and 6 (4-9), 6 (2-7), 5 (2-6) in nonmismatch group, respectively (P = .027, .006, and .001). Ischemic volume on CTA-SI and DWI was 4.6 (.2-13.0) cm(3) and 21.5 (9.7-44.0) cm(3) in mismatch group, and 61.5 (6.6-101.1) cm(3) and 94.9 (45.7-139.8) cm(3) in nonmismatch group (P = .003 and <.001). Significant collateralization on CTA-SI and FLAIR was seen in 80% and 88% in mismatch group, and 42% and 58% in nonmismatch group (P = .026 and .039). Odds ratios (95% CI) of DWI volume of ≤ 70 cm(3) to predict the mismatch was 30.17 (2.06-442.41) after adjusting for ASPECTSs on NCCT, CTA-SI, and DWI, 44.90 (2.75-732.73) for ischemic volume on CTA-SI, and 42.80 (3.05-601.41) for significant collateralization on CTA-SI and FLAIR (P = .013, .008, and .005). DWI volume was the best predictor of DPM.

Abstract W P40: Assessing Criteria for Intra-Arterial Therapy: Inter-Rater Reliability of Clinical-Diffusion Mismatch Among Stroke Clinicians

Background: Optimal patient selection strategy for intra-arterial therapy (IAT) in acute ischemic stroke remains uncertain. Clinical-diffusion mismatch (CDM) and perfusion-diffusion mismatch (PDM) on MRI are two selection methods used in practice. PDM can be radiologically defined and its analysis automated but this requires additional time and contrast administration. CDM is less technically challenging, however, there is variation in its definition and its inter-rater reliability has not been reported. Hypothesis: CDM has a higher inter-rater variability than PDM among vascular neurologists. Methods: Fellowship-trained vascular neurologists from our high-volume stroke center were surveyed on ten cases. For each case, they were first shown diffusion-weighted and apparent diffusion coefficient imaging and NIHSS score components and were asked if they felt a CDM existed. Based on the CDM alone, they were next asked if they would pursue IAT in the presence of a persistent large vessel occlusion. A perfusion image was then shown and the participants were asked if they felt a PDM existed. A final slide was shown giving the age, co-morbidities and pre-morbid disability, and location of arterial occlusion, after which they were again asked if they would pursue IAT. Kappa statistics were used to assess agreement. Results: Ten vascular neurologists participated in this study. The average inter-rater kappa for CDM was 0.35, 95% CI (0.28, 0.43) across the 10 cases. The average inter-rater kappa to take a patient for IAT based on CDM alone was 0.37, 95% CI (0.28, 0.46). The average inter-rater kappa for PDM was 0.61, 95% CI (0.53, 0.69). The average inter-rater kappa for final decision to take the patient to IAT was 0.30, 95% CI(0.22,0.37). The rate of IAT over the 10 cases varied from 10% to 70% among the vascular neurologists. Conclusions: This study suggests that vascular neurologists have a marginal inter-rater reliability for determining CDM. Inter-rater reliability for PDM was good although this did not have an effect on the reliability of final decision to take a patient for IAT. Further multi-center studies are needed to assess the variability of decision making for IA therapy.

Arterial spin labeling magnetic resonance perfusion imaging in cerebral ischemia

Arterial spin labeling (ASL) is a noninvasive magnetic resonance perfusion imaging method for visualizing and quantifying whole-brain perfusion that does not require exogenous contrast agents. The goal of this review article is to explain the principles of ASL perfusion imaging and review the strengths and limitations of different ASL methods. There are several different approaches that vary mainly on the basis of the technique that is used to label the inflowing arterial blood. These methods can be used to assess perfusion at brain tissue level or the perfusion territories of the brain feeding arteries. In patients with acute ischemic stroke, ASL can be of clinical value by detecting brain regions with hypoperfusion and perfusion-diffusion mismatch. ASL has been used to detect decreased perfusion, delayed arrival of the arterial blood bolus and assessment of collateral blood flow in patients with extracranial large artery disease and moyamoya disease. Recent evidence indicates that perfusion and territorial perfusion imaging of the brain feeding arteries with ASL can help to assess the extent of hemodynamic compromise and to customize medicinal and surgical treatment, both in patients with acute and with chronic cerebrovascular disease.

Abstract 117: A Six Minute MRI Protocol for Evaluation of Acute Ischemic Stroke: Pushing the Boundaries

Purpose: Multimodal cerebrovascular CT and MR can now provide information about tissue viability, site of occlusion, and collateral status in patients with acute ischemic stroke (AIS). If MRI is to compete with CT for evaluation of AIS, there is need for further improvements in acquisition speed. The purpose of this study was to establish the feasibility of a fast MR protocol with a 6 minute acquisition time for evaluation of AIS. Methods: Patients with suspicion of AIS and absence of MRI contraindications were prospectively enrolled. A combination of echo-planar imaging (EPI) and parallel acquisition technique were used on a 3T MR scanner to accelerate the acquisition time. The imaging protocol included: DWI (1 min), EPI-FLAIR (52 sec), EPI-GRE (50 sec), contrast-enhanced MR angiography (CE-MRA) of the entire supra-aortic arteries (20 sec), and DSC perfusion (2 min). Using a modified 2-phase contrast injection scheme, high spatial resolution CE-MRA of the supra-aortic arteries was performed just before DSC perfusion without the need for additional contrast. Image analysis was performed independently by two neuroradiologists and interobserver agreement was calculated using Kappa test. Results: A total of 50 patients were included. Diagnostic image quality was achieved in 100% of DWI, 96% EPI-FLAIR, 98% EPI-GRE, 90% neck MRA, 96% of brain MRA, and 94% of DSC perfusion scans. Thirty eight patients (76%) had acute infarction. Using Tmax perfusion maps and applying DEFUSE criteria, 42% of patients had perfusion-diffusion mismatch with interobserver agreement of k=0.90. The mean of the signal-intensity-ratio values of the infarction on EPI-FLAIR was 1.08 for patients presenting &lt; 4.5 hours (n=16) and 1.35 for patients presenting &gt; 4.5 hours (n=22) from the time of imaging. Three patients had evidence of intracranial hemorrhage detected on EPI-GRE and confirmed by non-contrast CT. CE-MRA showed 27 segmental stenoses of the extra-cranial arteries and 24 segmental stenoses of the intracranial arteries with interobserver agreement of k= 0.82 and 0.74 respectively. Conclusion: Described multimodal MR protocol is feasible for evaluation of patients with AIS and can result in significant reduction in scan time rivaling that of the multimodal CT protocol.

Abstract 116: Migraineurs Are More Susceptible to Infarct Growth in Acute Stroke

Epidemiological data indicate that migraine is an independent stroke risk factor. Recent data suggest that migraine mutations increase brain vulnerability to ischemia via excitatory mechanisms (Circulation 2012; 125:335). Migraine mutant mice developed higher number of ischemic depolarizations and accelerated infarct growth during hyperacute stroke, with worse tissue and neurological outcomes. Here, we retrospectively assessed acute stroke evolution in patients with a reliably documented migraine history. In a blinded fashion, we analyzed the lesion volume on diffusion-weighted imaging (DWI), and the volume of perfusion defect on perfusion-weighted imaging (PWI) using mean transit time (MTT), from consecutive patients during the years 2003-2012 in the Massachusetts General Hospital stroke database. DWI-PWI mismatch was calculated on spatially co-registered DWI and MTT maps, as a marker for viable tissue at risk for infarction. A total of 155 stroke patients had reliably documented presence or absence of a migraine history. Stroke patients with a history of migraine were younger and more often female, compared to stroke patients who never suffered from migraine. Migraineurs less frequently had coronary artery disease or diabetes. The frequency of posterior circulation lesions was significantly higher in migraineurs. Otherwise, groups were comparable. In migraineurs with aura, a larger proportion of the perfusion defect showed DWI changes, resulting in smaller DWI/PWI mismatches. A significantly larger proportion of migraineurs with aura showed no mismatch (i.e., DWI/PWI&gt;0.9), indicating that the entire perfusion defect was already infarcted (Table). Our data show that a history of migraine, particularly with aura, is associated with accelerated acute infarct growth, consistent with data obtained in migraine mutant mice. [Table. Diffusion-perfusion mismatch. *p=0.011 migraine vs no migraine, † p=0.002 migraine with aura vs no migraine]

Abstract T P88: Angiographic Steno-Occlusive Lesion and Collateral Circulation in Cerebral Vascular Reservoir in Acute Ischemic Stroke and Transent Ischemic Attack

Background: : Atherosclerotic intra- or extra- cranial steno-occlusive disease is one of the risk factors of ischemic stroke. While best medial treatment, some patients with these lesions still have hypoperfusion and may need an intervention for proper perfusion. In the real world of clinical practice, it is difficult to perform all kinds of studies such as digital subtraction angiography (DSA), MR perfusion, SPECT with Diamox challenig for assessment of perfusion status and cerebral vascular reservoir (CVR). We selected patients who undergone those methods and evaluated the correlations beween the collateral pattern and perfusion status and clinical manifestation and short term outcome. Methods: From a cohort of patients consecutively admitted for stroke or transient ischemic attack (TIA), we selected patients with symptomatic large artery steno-occlusive lesion confirmed by DSA. Cerebral angiogram was graded systematically in a blinded fashion for collateral flow, using Theraupeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) grading. We also evaluated diffusion-perfusion mismatch in MRI studies and CVR by Diamox SPECT. Demographic and clnical variables, initial NIHSS score and modified Rankin scale (mRS) scores at discharge were collcted. We divided thse patients in two groups according to cerebral vascalar reservoir pattern and compared clnical and imaging status. Results: A total of 21 patient were selected. Men was 14(67%) and mean age was 64.3(range of 40 to 84). Eleven patients had ICA steno-occlusive (7 with occlusion), 8 had MCA steno-occlusive lesions(4 with occlusion) and remaning 2 had tandem lesions. In Diamox SPECT, 6 patients showed preserved CVR. Patients with preserved CVR more had stenotic lesion while those with reduced CVR had occlusive lesion (p=0.001) and ASITN/SIR grading was differently distributed between two groups (p=0.046). Conclusion: DSA is still most important in evaluating steno-occlusive lesion and collateral status as shown previous studies. The status of the steno-occlusive lesion may have an effect on CVR. And the pattern of collateral flows may have a certain relation to vascular reserve capacity. But there are needed longer follow up in much larger populations.

Abstract W P244: Effect of Remote Limb Ischemic Conditioning on CBF as Measured by Arterial Spin Labeling in Human Stroke

Background: Remote limb ischemic conditioning (RLIC) is a promising treatment for ischemic stroke. We have previously shown that RLIC increases cerebral blood flow, reduces infarct size, and improves outcome in a murine thromboembolic stroke model (Hoda N et al. Stroke. 2012; 43:2794). We hypothesized that RLIC will increase CBF in hypoperfused areas in acute stroke patients as detected by MRI Arterial Spin Labeling (ASL) Methods: Patients with an acute ischemic stroke within 14 days and with a persistent mismatch defined by a perfusion defect measured by ASL that was at least 20% larger than the area of infarction as measured by diffusion weighted imaging (DWI) were eligible. Patients underwent 4 cycles of blood pressure cuff inflation (x200 mm Hg) for 5 minutes and deflation for 5 minutes on the leg or arm, 1- 2 times per day. MRI ASL, DWI, and 3D T1-weighted Fast Spoiled Gradient-Echo (FSPGR) images were taken before and 60 minutes after the last cycle of RLIC to measure CBF. Two neuroradiologists analyzed the images. Results: After 3 of 4 RLIC sessions, the CBF improved and the mismatch decreased by at least 15%. In the one patient without a reduction in mismatch, the RLIC was performed on the arm and not the leg. Conclusions: 1.) RLIC increased CBF as measured by ASL in stroke patients with a persistent diffusion-perfusion mismatch. 2.) Since it can be repeated multiple times on the same patient, ASL may be a useful biomarker of the conditioning response in humans. 3.) Further work in a larger sample of patients is needed to define the optimal regimen of RLIC and to determine the utility of ASL as a biomarker.

ANTONIA perfusion and stroke. A software tool for the multi-purpose analysis of MR perfusion-weighted datasets and quantitative ischemic stroke assessment.

The objective of this work is to present the software tool ANTONIA, which has been developed to facilitate a quantitative analysis of perfusion-weighted MRI (PWI) datasets in general as well as the subsequent multi-parametric analysis of additional datasets for the specific purpose of acute ischemic stroke patient dataset evaluation. Three different methods for the analysis of DSC or DCE PWI datasets are currently implemented in ANTONIA, which can be case-specifically selected based on the study protocol. These methods comprise a curve fitting method as well as a deconvolution-based and deconvolution-free method integrating a previously defined arterial input function. The perfusion analysis is extended for the purpose of acute ischemic stroke analysis by additional methods that enable an automatic atlas-based selection of the arterial input function, an analysis of the perfusion-diffusion and DWI-FLAIR mismatch as well as segmentation-based volumetric analyses. For reliability evaluation, the described software tool was used by two observers for quantitative analysis of 15 datasets from acute ischemic stroke patients to extract the acute lesion core volume, FLAIR ratio, perfusion-diffusion mismatch volume with manually as well as automatically selected arterial input functions, and follow-up lesion volume. The results of this evaluation revealed that the described software tool leads to highly reproducible results for all parameters if the automatic arterial input function selection method is used. Due to the broad selection of processing methods that are available in the software tool, ANTONIA is especially helpful to support image-based perfusion and acute ischemic stroke research projects.

Sphenoid Ridge Meningioma Presenting as Acute Cerebral Infarction

A previously healthy 52-year-old man presented to the emergency room with acute onset left hemiparesis and dysarthria. Brain computed tomography and magnetic resonance examinations revealed acute cerebral infarction in the right middle cerebral artery territory and a sphenoid ridge meningioma encasing the right carotid artery terminus. Cerebral angiography demonstrated complete occlusion of the right proximal M1 portion. A computed tomography perfusion study showed a wide area of perfusion-diffusion mismatch. Over the ensuing 48 hours, left sided weakness deteriorated despite medical treatment. Emergency extracranial-intracranial bypass was performed using a double-barrel technique, leaving the tumor as it was, and subsequently his neurological function was improved dramatically. We present a rare case of sphenoid ridge meningioma causing acute cerebral infarction as a result of middle cerebral artery compression.

Magnetic resonance imaging in acute ischemic stroke treatment.

Although intravenous administration of tissue plasminogen activator is the only proven treatment after acute ischemic stroke, there is always a concern of hemorrhagic risk after thrombolysis. Therefore, selection of patients with potential benefits in overcoming potential harms of thrombolysis is of great importance. Despite the practical issues in using magnetic resonance imaging (MRI) for acute stroke treatment, multimodal MRI can provide useful information for accurate diagnosis of stroke, evaluation of the risks and benefits of thrombolysis, and prediction of outcomes. For example, the high sensitivity and specificity of diffusion-weighted image (DWI) can help distinguish acute ischemic stroke from stroke-mimics. Additionally, the lesion mismatch between perfusion-weighted image (PWI) and DWI is thought to represent potential salvageable tissue by reperfusion therapy. However, the optimal threshold to discriminate between benign oligemic areas and the penumbra is still debatable. Signal changes of fluid-attenuated inversion recovery image within DWI lesions may be a surrogate marker for ischemic lesion age and might indicate risks of hemorrhage after thrombolysis. Clot sign on gradient echo image may reflect the nature of clot, and their location, length and morphology may provide predictive information on recanalization by reperfusion therapy. However, previous clinical trials which solely or mainly relied on perfusion-diffusion mismatch for patient selection, failed to show benefits of MRI-based thrombolysis. Therefore, understanding the clinical implication of various useful MRI findings and comprehensively incorporating those variables into therapeutic decision-making may be a more reasonable approach for expanding the indication of acute stroke thrombolysis.

Patients with Single Distal MCA Perfusion Lesions Have a High Rate of Good Outcome with or without Reperfusion

Reperfusion is associated with good functional outcome after stroke. However, minimal data are available regarding the effect of reperfusion on clinical outcome and infarct growth in patients with distal MCA branch occlusions. The aim of this study was to evaluate this association and to determine the impact of the perfusion-diffusion mismatch. Individual patient data from three stroke studies (EPITHET, DEFUSE and DEFUSE 2) with baseline MRI profiles and reperfusion status were pooled. Patients were included if they had a single cortical perfusion lesion on their baseline MRI that was consistent with a distal MCA branch occlusion. Good functional outcome was defined as a score of 0-2 on the modified Rankin Scale at day 90 and infarct growth was defined as change in lesion volume between the baseline DWI and the final T2/FLAIR. Thirty patients met inclusion criteria. Eighteen (60%) had a good functional outcome and twenty (67%) had reperfusion. Reperfusion was not associated with good functional outcome in the overall cohort (OR: 1·0, 95% CI 0·2-4·7) and also not in the subset of patients with a PWI-DWI mismatch (n = 17; OR: 0·7, 95% CI 0·1-5·5). Median infarct growth was modest and not significantly different between patients with (0 ml) and without reperfusion (6 ml); P = 0·2. The overall high rate of good outcomes in patients with distal MCA perfusion lesions might obscure a potential benefit from reperfusion in this population. A larger pooled analysis evaluating the effect of reperfusion in patients with distal MCA branch occlusions is warranted as confirmation of our results could have implications for the design of future stroke trials.

Translational Perspectives on Perfusion–Diffusion Mismatch in Ischemic Stroke

Magnetic resonance imaging has tremendous potential to illuminate ischemic stroke pathophysiology and guide rational treatment decisions. Clinical applications to date have been largely limited to trials. However, recent analyses of the major clinical studies have led to refinements in selection criteria and improved understanding of the potential implications for the risk vs. benefit of thrombolytic therapy. In parallel, preclinical studies have provided complementary information on the evolution of stroke that is difficult to obtain in humans due to the requirement for continuous or repeated imaging and pathological verification. We review the clinical and preclinical advances that have led to perfusion-diffusion mismatch being applied in phase 3 randomized trials and, potentially, future routine clinical practice.

Remote Ischemic Perconditioning as an Adjunct Therapy to Thrombolysis in Patients With Acute Ischemic Stroke

Remote ischemic preconditioning is neuroprotective in models of acute cerebral ischemia. We tested the effect of prehospital rPerC as an adjunct to treatment with intravenous alteplase in patients with acute ischemic stroke. Open-label blinded outcome proof-of-concept study of prehospital, paramedic-administered rPerC at a 1:1 ratio in consecutive patients with suspected acute stroke. After neurological examination and MRI, patients with verified stroke receiving alteplase treatment were included and received MRI at 24 hours and 1 month and clinical re-examination after 3 months. The primary end point was penumbral salvage, defined as the volume of the perfusion-diffusion mismatch not progressing to infarction after 1 month. Four hundred forty-three patients were randomized after provisional consent, 247 received rPerC and 196 received standard treatment. Patients with a nonstroke diagnosis (n=105) were excluded from further examinations. The remaining patients had transient ischemic attack (n=58), acute ischemic stroke (n=240), or hemorrhagic stroke (n=37). Transient ischemic attack was more frequent (P=0.006), and National Institutes of Health Stroke Scale score on admission was lower (P=0.016) in the intervention group compared with controls. Penumbral salvage, final infarct size at 1 month, infarct growth between baseline and 1 month, and clinical outcome after 3 months did not differ among groups. After adjustment for baseline perfusion and diffusion lesion severity, voxelwise analysis showed that rPerC reduced tissue risk of infarction (P=0.0003). Although the overall results were neutral, a tissue survival analysis suggests that prehospital rPerC may have immediate neuroprotective effects. Future clinical trials should take such immediate effects, and their duration, into account. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00975962.

Effects of Cerebral Ischemic and Reperfusion on T2∗-Weighted MRI Responses to Brief Oxygen Challenge

This study characterized the effects of cerebral ischemia and reperfusion on T2*-weighted magnetic resonance image (MRI) responses to brief oxygen challenge (OC) in transient (60 minutes) cerebral ischemia in rats. During occlusion, the ischemic core tissue showed no significant OC response, whereas the perfusion-diffusion mismatch tissue showed markedly higher percent changes relative to normal tissue. After reperfusion, much of the pixels with initial exaggerated OC responses showed normal OC responses, and the majority of these tissues were salvaged as defined by endpoint T2 MRI. The initial core pixels showed exaggerated OC responses after reperfusion, but the majority of the core pixels eventually became infarct, suggesting exaggerated OC responses do not necessarily reflect salvageable tissue. Twenty-four hours after stroke, basal T1 increased in the ischemic core. Oxygen challenge decreased T1 significantly in the core, indicative of the substantial increases in dissolved oxygen in the core as the result of hyperperfusion. We concluded that exaggerated T2*-weighted MRI responses to OC offer useful insight in ischemic tissue fates. However, exaggerated OC pixels are not all salvageable, and they exhibited complex dynamics depending on reperfusion status, hyperperfusion, and edema effects.

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.

Perfusion MR Predicts Outcome in High-Risk Transient Ischemic Attack/Minor Stroke

Transient or minor ischemic stroke is associated with an early risk of deterioration. Baseline perfusion-diffusion mismatch may predict clinical deterioration and infarct growth in this population. High-risk transient ischemic attack and minor stroke (National Institutes of Health Stroke Scale ≤3) subjects were prospectively enrolled and imaged with MRI within 24 hours of symptom onset as part of sequential derivation and validation cohorts. Baseline diffusion-weighted imaging, perfusion-weighted imaging (Tmax≥4 s), mismatch (Tmax≥4 s-diffusion-weighted imaging), and follow-up fluid-attenuated inversion recovery infarct volumes were measured. Primary outcome was infarct growth on fluid-attenuated inversion recovery, and secondary outcome was symptom progression. One hundred thirty-seven and 281 subjects were included in the derivation and validation cohorts, respectively. Infarct growth occurred in 18.5% of the derivation and 5.5% of the validation cohorts. Symptom progression occurred in 9.5% of the derivation and 4.5% of the validation cohorts. In the derivation cohort, subjects with baseline mismatch were significantly more likely to show infarct growth on fluid-attenuated inversion recovery (relative risk [RR], 13.5; 95% confidence interval [CI], 4.2-38.9) and symptom progression (RR, 7.0; 95% CI, 2.0-7.3). A baseline mismatch volume of 10 mL in the derivation cohort was the optimal threshold to predict infarct growth (area under the curve, 0.89; 95% CI, 0.80-0.98). This threshold was highly predictive of infarct growth in the validation cohort (P=0.001). Baseline mismatch was associated with clinical deterioration in the derivation (area under the curve, 0.81; 95% CI, 0.67-0.96) and validation cohorts (area under the curve, 0.66; 95% CI, 0.46-0.85). Among subjects with high-risk transient ischemic attack and minor stroke, diffusion-weighted imaging-perfusion-weighted imaging mismatch predicts infarct growth and clinical deterioration. These findings suggest that reperfusion strategies would be beneficial in this population.

Total mismatch in anterior circulation stroke patients before thrombolysis

Our aim was to estimate the prevalence of negative diffusion-weighted imaging (DWI) with total perfusion-diffusion mismatch in a large series of anterior circulation stroke patients treated with thrombolysis and to describe the characteristics of these patients. From January 2006 to December 2010, a retrospective search was made for total perfusion-diffusion (PWI-DWI) mismatch patterns on pretreatment 1.5-T MRI scans of 166 consecutive thrombolyzed patients taken<4.5 h after onset of anterior stroke. A total mismatch profile corresponded to an absence of initial DWI signal changes with hypoperfusion (T(max)>6 s) on PWI. Clinical and MRI characteristics were compared between DWI+ and DWI- patients. Five (3%) patients had a normal initial DWI. All had stable substantial clinical deficits (NIHSS scores ≥ 6) and large perfusion abnormalities - in other words, 'total mismatch' - and infarcts in the acutely hypoperfused area on follow-up imaging. While DWI- and DWI+ patients did not significantly differ in any of the pretreatment imaging or clinical variables except for the extent of PWI-DWI mismatch, DWI- patients had lower NIHSS scores at 24 h, and were more likely to show early neurological improvement (Δ0-24 h NIHSS ≥ 8) and good outcomes (mRS ≤ 2) at the time of hospital discharge. Total mismatch i.e. failure of DWI to reveal any ischemic tissue despite a large perfusion defect, can be observed before thrombolysis even in stroke patients with stable substantial neurological deficits. However, this rare MRI profile is associated with a favorable outcome after thrombolysis.

Interleukin-10 facilitates the selection of patients for systemic thrombolysis

BackgroundClinical-Diffusion mismatch (CDM; NIHSS score ≥8 & DWI lesion volume ≤25 mL) and Perfusion-Diffusion mismatch (PDM; difference >20% between initial DWI and MTT lesion volumes) have been proposed as surrogates for ischemic brains that are at risk of infarction. However, their utility to improve the selection of patients for thrombolytic treatment remains controversial. Our aim was to identify molecular biomarkers that can be used with neuroimaging to facilitate the selection of ischemic stroke patients for systemic thrombolysis.MethodsWe prospectively studied 595 patients with ischemic stroke within 12 h of the stroke onset. A total of 184 patients received thrombolytic treatment according to the SITS-MOST criteria. DWI and MTT volumes were measured at admission. The main outcome variable was good functional outcome at 3 months (modified Rankin scale <3). Serum levels of glutamate (Glu), IL-10, TNF-α, IL-6, NSE, and active MMP-9 also were determined at admission.ResultsPatients treated with t-PA who presented with PDM had higher IL-10 levels at admission (p < 0.0001). In contrast, patients with CDM had higher levels of IL-10 (p < 0.0001) as well as Glu and TNF-α (all p < 0.05) and lower levels of NSE and active MMP-9 (all p < 0.0001). IL-10 ≥ 30 pg/mL predicts good functional outcome at 3 months with a specificity of 88% and a sensitibity of 86%. IL-10 levels ≥30 pg/mL independently in both patients with PDM (OR, 18.9) and CDM (OR, 7.5), after an adjustment for covariates.ConclusionsSerum levels of IL-10 facilitate the selection of ischemic stroke patients with CDM and PDM for systemic thrombolysis.

Early Anticipation of Candidacy for Intra-Arterial Reperfusion Therapy Based on Baseline Clinical Stroke Subtypes: Comparison with Multiparametric MRI Taken within 4.5 Hours from Stroke Onset

Background: The decision to proceed with intra-arterial (IA) reperfusion therapy is typically made late in the course of in-hospital treatment for acute ischemic stroke. Early anticipation of candidacy for IA reperfusion therapy based on clinical stroke subtypes would be useful for guiding stroke management. The aim of this study was to investigate the relationship between the clinical Oxfordshire Community Stroke Project (OCSP) classification and MRI results taken within a 4.5-hour time window from stroke onset, with the hypothesis that the persistence of major arterial occlusion and extended ischemic penumbra, key criteria for proceeding with IA reperfusion therapy, would be distinctive between the clinical stroke subtypes. Methods: A total of 161 patients with acute ischemic stroke in the anterior circulation were included in this study. All patients were treated with intravenous alteplase, and MRI scans were performed following alteplase initiation. Prior to treatment, the patients were categorized, based on the OCSP classification scheme, as having total anterior circulation infarcts (TACI), partial anterior circulation infarcts (PACI), or lacunar infarcts (LACI). The relationship between OCSP subtypes, MRI parameters, and clinical variables was analyzed. Results: Overall, 40/161 patients (24.8%) were candidates for IA rescue reperfusion. With respect to the classification, 30/69 TACI (43.5%), 6/33 PACI (18.2%), and 4/59 LACI patients (6.8%) were candidates (p < 0.001). Major arterial occlusion was found in 56/161 patients (34.8%), and 46/69 TACI (66.7%), 6/33 PACI (18.2%), and 4/59 LACI patients (6.8%) had a major arterial occlusion (p < 0.001). A perfusion-diffusion mismatch greater than 20% was found in 85/161 patients (52.8%). More specifically, 40/69 TACI (58.0%), 25/33 PACI (75.8%), and 20/59 LACI patients (33.9%) had a perfusion-diffusion mismatch (p < 0.001). However, in terms of the total area of mismatch, 66.0% of patients with ASPECTS_DWI-PWI ≥2 (Alberta Stroke Program Early CT Score) were classified as TACI patients (p < 0.001) and of the patients with ASPECTS_DWI-PWI ≥3, 74.3% were classified as TACI patients (p < 0.001). Relative to candidates for IA rescue reperfusion, the clinical TACI group showed 75.0% sensitivity, 67.8% specificity, a positive predictive value of 43.5%, and a negative predictive value of 89.1%. Conclusions: In this study, patients classified as having clinical TACI were significantly more likely to be candidates for IA rescue reperfusion. Additionally, they incurred a higher incidence of persistent major arterial occlusion and had a penumbra area that was significantly larger than normal. Therefore, clinical OCSP can be used as an ‘early warning system' for IA reperfusion candidacy, which can allow for advanced preparation of IA therapy and theoretically shorten treatment time and reduce infarction.

Magnetic resonance imaging of perfusion–diffusion mismatch in rodent and non-human primate stroke models

Stroke is a leading cause of death and long-term disability. Non-invasive magnetic resonance imaging (MRI) has been widely used for the early detection of ischemic stroke and the longitudinal monitoring of novel treatment strategies. Recent advances in MRI techniques have enabled improved sensitivity and specificity to detecting ischemic brain injury and monitoring functional recovery. This review describes recent progresses in the development and application of multimodal MRI and image analysis techniques to study experimental stroke in rats and non-human primates.