Penumbral Pattern Research Articles

Ischemic Lesion Growth in Patients with a Persistent Target Mismatch After Large Vessel Occlusion

BackgroundFailure to reperfuse a cerebral occlusion resulting in a persistent penumbral pattern has not been fully described.MethodsWe retrospectively reviewed patients with anterior large vessel occlusion who did not receive reperfusion, and underwent repeated perfusion imaging, with baseline imaging < 6 h after onset and follow-up scans from 16–168 h. A persistent target mismatch (PTM) was defined as core volume of < 100 mL, mismatch ratio > 1.2, and mismatch volume > 10 mL on follow-up imaging. Patients were divided into PTM or non-PTM groups. Ischemic core and penumbral volumes were compared between baseline and follow-up imaging between the two groups, and collateral flow status assessed using CT perfusion collateral index.ResultsA total of 25 patients (14 PTM and 11 non-PTM) were enrolled in the study. Median core volumes increased slightly in the PTM group, from 22 to 36 ml. There was a much greater increase in the non-PTM group, from 57 to 190 ml. Penumbral volumes were stable in the PTM group from a median of 79 ml at baseline to 88 ml at follow-up, whereas penumbra was reduced in the non-PTM group, from 120 to 0 ml. Collateral flow status was also better in the PTM group and the median collateral index was 33% compared with 44% in the non-PTM group (p = 0.043).ConclusionMultiple patients were identified with limited core growth and large penumbra (persistent target mismatch) > 16 h after stroke onset, likely due to more favorable collateral flow.

Advances of MRI in stroke

The imaging of stroke has several potential objectives: 1. Differentiation of stroke from non-stroke. 2. Classification of stroke sub-types. 3. Identification of patients likely to benefit from acute interventions. 4. Identification of patients at risk from stroke treatment. 5. Guidance of in-patient management. 6. Selection of appropriate secondary prevention strategies. 7. Research to improve understanding of stroke pathology, the effect in interventions, and the development and testing of new treatments. For most indications, MRI offers advantages over CT scanning. The two modalities are equivalently sensitive to detection of acute intracranial hemorrhage, but MRI is more sensitive to and more precisely delineates a variety of brain pathologies. In particular, MRI is superior for the detection of the earlier and smaller regions of ischemic changes using diffusion weighted imaging (DWI), and for the presence of chronic microhemorrhages, which are indicative of future risk of intracranial hemorrhage. The most important recent therapeutic advances in imaging-based acute stroke intervention have expanded the time window for treatable ischemic stroke. Clinical trials proved the benefit of intravenous alteplase for ischemic stroke in patients who wake-up with stroke symptoms or otherwise present later than the standard time from last known well, if MRI shows a positive DWI but negative FLAIR, indicative of early stroke, or shows a diffusion-perfusion mismatch indicative of ischemic penumbra. A penumbral pattern on MRI in the presence of acute occlusion of the internal carotid or middle cerebral artery identifies patients who benefit from mechanical thrombectomy 6-24 hours from time last known well.

Acute imaging for evidence-based treatment of ischemic stroke.

Until recently, intravenous thrombolysis and mechanical thrombectomy for acute stroke treatment relied on reported information on the known time of symptom onset and was limited to treatment within a narrow time window. New trials have provided evidence for imaging-based effective reperfusion treatment in an extended time window and unknown-onset stroke. This review summarizes evidence from recent clinical trials and suggests a simple algorithm for the choice of imaging modalities to guide evidence-based reperfusion treatment of acute stroke. Two trials have provided evidence for benefit of mechanical thombectomy in patients with stroke from large vessel occlusion up to 24 h after symptom onset or with unknown symptom onset who have a small infarct core but large perfusion lesion or severe clinical deficit (DAWN, DEFUSE-3). An MRI-based trial has demonstrated the benefit of intravenous thrombolysis with alteplase in patients with unknown onset stroke who present with MRI findings of DWI-FLAIR mismatch (WAKE-UP). Another trial demonstrated benefit of intravenous alteplase in an extended or unknown time-window in patients with penumbral pattern on MRI or CT perfusion (EXTEND). In stroke patients with unknown symptom onset or known symptom onset up to 24 h, advanced imaging with MRI or with CT perfusion can guide effective acute reperfusion treatment with mechanical thrombectomy and intravenous alteplase.

Computed Tomographic Perfusion Predicts Poor Outcomes in a Randomized Trial of Endovascular Therapy.

In the ESCAPE trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times), patients with large vessel occlusions and small infarct cores identified with computed tomography (CT)/CT angiography were randomized to endovascular therapy or standard of care. CT perfusion (CTP) was obtained in some cases but was not used to select patients. We tested the hypothesis that patients with penumbral CTP patterns have higher rates of good clinical outcome. All CTP data acquired in ESCAPE patients were analyzed centrally using a semiautomated perfusion threshold-based approach. A penumbral pattern was defined as an infarct core <70 mL, penumbral volume >15 mL, and a total hypoperfused volume:core volume ratio of >1.8. The primary outcome was good functional outcome at 90 days (modified Rankin Scale score, 0-2). CTP was acquired in 138 of 316 ESCAPE patients. Penumbral patterns were present in 116 of 128 (90.6%) of patients with interpretable CTP data. The rate of good functional outcome in penumbral pattern patients (53 of 114; 46%) was higher than that in nonpenumbral patients (2 of 12; 17%; P=0.041). In penumbral patients, endovascular therapy increased the likelihood of a good clinical outcome (34 of 58; 57%) compared with those in the control group (19 of 58; 33%; odds ratio, 2.68; 95% confidence interval, 1.25-5.76; P=0.011). Only 3 of 12 nonpenumbral patients were randomized to the endovascular group, preventing an analysis of treatment effect. The majority of patients with CTP imaging in the ESCAPE trial had penumbral patterns, which were associated with better outcomes overall. Patients with penumbra treated with endovascular therapy had the greatest odds of good functional outcome. Nonpenumbral patients were much less likely to achieve good outcomes.

Abstract 115: CT Perfusion Identifies Patients with Poor Outcomes in The Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times (ESCAPE) Trial

Background: In the ESCAPE trial, patients with large vessel occlusions and small infarct cores identified with CT/CT angiography were randomized to endovascular therapy or standard of care. CT Perfusion (CTP) was obtained in some cases, but was not utilized to select patients. We tested the hypothesis that patients with penumbral CTP patterns have higher rates of good clinical outcome. Methods: All CTP data acquired in ESCAPE patients was analyzed centrally using a semi-automated perfusion threshold based approach. A penumbral pattern was defined as an infarct core&lt;70 mL, penumbral volume &gt;15 mL, and a total hypoperfused volume:core volume ratio of &gt;1.8. The primary outcome was a good functional outcome at 90 days (mRS 0-2). Results: CTP was acquired in 138 of 316 ESCAPE patients. Motion degraded CTP images from 9 patients were excluded. Penumbral patterns were present in 110/129 (85.3%) of patients. The rate of good functional outcome in penumbral pattern patients (53/108; 49.1%) was higher than that in non-penumbral patients (3/19; 15.8%, p=0.011). In penumbral patients, endovascular therapy increased the likelihood of good outcome (35/58; 60.3%) over those in the control group (18/50; 36%, OR=2.71, p=0.013). Only 4 of 19 non-penumbral patients were randomized to the endovascular group, preventing an analysis of treatment effect. Conclusion: The majority of patients with CTP imaging in the ESCAPE trial had penumbral patterns, which were associated with better outcomes overall. Patients with penumbra treated with endovascular therapy had the greatest odds of good functional outcome. Non-penumbral patients were much less likely to achieve good outcomes.

Abstract WP55: Low Predictive Value of Multiphase CT Angiography for CT Perfusion Defined Ischemic Penumbra

Introduction: Multiphase CT angiography (mCTA) has been proposed as an alternative to CT Perfusion (CTP) for identification of acute stroke patients with the potential for salvage after reperfusion therapy. We tested the hypothesis that poor collateral patterns on mCTA are predictive of large CTP defined ischemic cores. Methods: Multiphase CTA was generated from CTP source images (peak arterial, +8 and +16 s). Two expert raters assessed the collateral pattern on mCTA (absent/moderate/good). An Alberta Stroke Program Early CT (ASPECT) score was also assessed on the first and last phase of the mCTA as well as the non-contrast CT (NCCT). Hypoperfused regions were defined as those without vessel enhancement on the first phase. Core regions were defined as those without vessel enhancement on the final phase and/or NCCT changes. An ASPECTS mismatch score was calculated as a penumbral estimate. Penumbral tissue on CTP was defined as regions with a Delay Time (DT) &gt;3 seconds, and ischemic core was defined as a combination of DT&gt;3 seconds and relative CBF&lt;40% of the contralateral hemisphere. Results: Of 141 patients, 79(56%) had penumbral patterns on CTP. Of these, 71(90%) had moderate/good collaterals. The mean penumbral volume in all patients was 20.8±26.6 ml and that in patients with large vessel occlusions (LVO; n=40) was 44.0±30.5 ml. At an ASPECTS mismatch score threshold of 2, mCTA predicted CTP defined penumbral patterns with a sensitivity of 77% and specificity of only 10%. The positive and negative predictive values were 57.7% and 61.5% respectively. In large vessel occlusion patients, mCTA predicted penumbra with 95.8% sensitivity and 43.8% specificity. The positive predictive value for penumbral patterns was 71.7%, and the negative predictive value was 87.5%. Eight patients were found to have a large core (&gt;70 ml) on CTP, 3 of whom had moderate/good collaterals and 2 of whom also had a NCCT ASPECTS&gt;5. Four large core patients had a mCTA penumbral score ≥ 2. Discussion: mCTA predicts penumbra with relatively high sensitivity, particularly in LVO patients. In some patients, however, mCTA can incorrectly classify penumbral patterns despite the presence of large cores on CTP. In non-LVO patients, mCTA is neither sensitive, nor specific for penumbral patterns.

Abstract WP46: Sex Differences in Therapeutic Targets in Ischemic Stroke

Sex differences exist in stroke epidemiology, acute presentation, treatment, and post-stroke clinical outcome. Neuroimaging can objectively identify potential pathological therapeutic targets and is reflective clinical observations. MCA occlusion (MCAO) is measurable by angiography and the presence of penumbra by diffusion-perfusion mismatch. We present evaluation of sex differences in the Lesion Evolution in Stroke and Ischemia On Neuroimaging (LESION) Project to determine if the probability of MCAO and penumbra depend on sex. We hypothesize imaging-based evidence is consistent with clinical observations of sex differences in severity and interactions with age and race. Methods: Patients included in the LESION study were diagnosed with acute ischemic cerebrovascular syndrome, had a brain MRI obtained within 24 hours from last known well and NIHSS&gt;3 or were treated with acute intervention with a pre-treatment MRI. MR imaging included DWI, FLAIR, MRA and PWI, which were co-localized over the entire brain. Patients with M1 or M2 abnormalities were graded as MCAO. The probability of having an MCAO or measurable pathological target was qualitatively evaluated as a function of sex with adjustment for age and race. Results: Women were more likely than men (all p&lt;0.05) to have a measurable of MCAO (OR [CI’s]) = (1.43 [1.08-1.89]), perfusion defect (1.42 [1.02-2.0]), or a diffusion-perfusion mismatch (1.35 [1.02-1.80]) (Table). This sex difference remained after adjusting for time from onset, NIHSS and age. Women over 70 years are most likely to have a measurable therapeutic target and white women are more likely to have a penumbral pattern than men or non-white women (p&lt;0.05). Conclusion: This preliminary imaging-based evidence is encouraging that sex differences in imaging biomarkers exist in a representative sample of acute stroke patients. This study shows that sex differences exist not only in the clinical phenotype, but in presence of a biological target.

Impact of the Penumbral Pattern on Clinical Outcome in Patients with Successful Endovascular Revascularization

In patients with acute ischemic stroke, the impact of penumbral patterns on clinical outcomes after endovascular treatment (EVT) remains controversial. We aimed to establish whether penumbral patterns are associated with clinical outcome after successful recanalization with EVT while adjusting for onset to revascularization time. Using a web-based, multicenter, prospective stroke registry database, we identified patients with acute ischemic stroke who underwent perfusion and diffusion magnetic resonance imaging (MRI) before EVT, had anterior circulation stroke, received EVT within 12 hours of symptom onset, and had successful revascularization confirmed during EVT. Based on pretreatment MRI, patients were stratified as having a favorable or nonfavorable penumbral pattern. Onset to revascularization time was dichotomized by median value. Primary outcome was functional independence (modified Rankin Scale score ≤2) at 90 days. Among 121 eligible patients from three university hospitals, 104 (86.0%) had a favorable penumbral pattern, and the median time to revascularization was 271 minutes (interquartile range, 196-371). The functionally independent patient proportion was higher in those with a favorable penumbral pattern than in those without (53.8% versus 5.9%; P <.001), but was not different between early and late revascularization groups (49.2% versus 45.0%; P = .65). The favorable penumbral pattern was associated with functional independence after adjusting confounders (odds ratio, 23.25; 95% confidence interval: 1.58-341.99; P = .02). Time to revascularization did not modify the association (P for interaction, .53). A favorable penumbral pattern is associated with improved functional independence in patients with endovascular revascularization, and the association was not time-dependent.

Good Clinical and Radiological Correlation from Standard Perfusion Computed Tomography Accurately Identifies Salvageable Tissue in Ischemic Stroke

It has been debated whether the penumbral pattern, as identified using multimodal imaging, is a specific marker of tissue viability in ischemic stroke. We assessed whether perfusion computed tomography (PCT) accurately identifies salvageable tissue and helps predict postreperfusion outcomes. A retrospective study of patients with anterior circulation stroke undergoing reperfusion therapies who had a PCT before treatment and an assessment of vessel recanalization post treatment was conducted. Tissue at risk was considered as that with reduced cerebral blood flow, whereas the infarct core was the region of reduced cerebral blood volume, the mismatch region being salvageable tissue. The volume of hypodensity in slices corresponding to perfusion acquisition cage in 24-hour computed tomography (partial lesion volume [PLV]) was measured. Outcome variables were the amount of preserved tissue, that is, the difference between volumes of tissue at risk and PLV expressed as a percentage, and the modified Rankin Scale (mRS) score at 3 months. Patients (n = 34) meeting the inclusion criteria were included. Vessel recanalization was associated with a larger amount of tissue at risk preserved from definite lesion (89% [interquartile range {IQR}: 76-94] versus 46% [IQR: 23-86], P < .005). The amount of preserved tissue correlated with clinical outcome at 24 hours: for each 10% of preserved tissue, the National Institutes of Health Stroke Scale score improved by 3 points (95% confidence interval [CI]: -4.9 to -.8, P = .007) and was the only predictor of independency (mRS score 0-2) following adjustment for covariates (odds ratio 1.15, 95% CI: 1.04-1.28, P = .005). PCT provides accurate markers of viability of tissue in acute ischemic stroke and could help predict the degree of improvement following reperfusion.

Abstract W MP31: Penumbral Imaging-Based Thrombolysis with Tenecteplase is Feasible Up to 24 Hours After Symptom Onset

Introduction: Penumbral imaging-based selection of patients for thrombolysis with tenecteplase (TNK) has been shown to be feasible up to 6 h after onset. We aimed to demonstrate the feasibility and safety of thrombolysis in ischemic stroke patients with penumbral patterns presenting 4.5-24 h after symptom onset. Methods: We conducted an open label single arm trial. Acute ischemic stroke patients presenting between 4.5-24 h after symptom onset were assessed with perfusion imaging. Patients with pretreatment perfusion CT/MRI that demonstrated a perfusion deficit volume &gt;15 ml and penumbra volume &gt;20% of the infarct core were eligible for TNK treatment. They received 0.25 mg/kg IV TNK. The primary outcome was symptomatic hemorrhagic transformation. Patients screened with perfusion CT/MRI who met trial criteria, but were not enrolled in the study, formed a parallel cohort. Results: A total of 26 patients were screened with perfusion CT/MRI. Thirteen patients received TNK (mean±SD age = 62±12 y). The 13 parallel cohort patients were of similar age (55±18 y, p=0.257). Median (IQR) baseline NIHSS in TNK treated patients (13(9)) was similar to that in the parallel cohort (14(10), p=1.00). Median time to TNK treatment was 8.7 h(range: 5.1-23.3). Reperfusion and recanalization occurred in 54.5% and 50% of TNK treated patients at 24 h, respectively. Infarct growth at 24 h was attenuated in TNK treated patients (8.7 (31.3) ml) relative to the parallel cohort (53.0 (91.5) ml, p=0.017). Penumbral salvage volume was greater in TNK treated patients (51.7 (58.2) ml) than parallel cohort patients (-16.7 (112.2) ml, p=0.001). There was one symptomatic hemorrhage in the TNK group (ECASS grade PH1). Two other TNK treated patients developed asymptomatic hemorrhages (ECASS grade PH1). The rate of good functional outcome (modified Rankin Score ≤2) at day 90 was greater in TNK patients (8/12, 66.7%) than in the parallel cohort (2/13, 15.3%, p=0.015). Conclusion: Thrombolysis with TNK treatment in appropriately selected patients is feasible even up to 24 hours after onset. Randomized studies of penumbral imaging-based selection of TNK candidates in an extended therapeutic time window are warranted.

Abstract T P8: Outcomes of Endovascular Treatment Using Solitaire Devices in Acute Ischemic Stroke With Favorable Penumbral Imaging Pattern

Introduction: Through emerging of novel devices and elaborated patient selection, endovascular treatment against acute ischemic stroke is gaining popularity. We investigated factors influencing outcomes after endovascular treatment in highly applicable patients. Methods: We enrolled consecutive 72 patients with favorable penumbral pattern, who underwent endovascular treatment with Solitaire from 2010 through 2013 in three hospitals of Korea. Inclusion criteria were these: the NIHSS and age were between 6 and 29, and 18 and 85, respectively, and endovascular procedures could begin within 8 h from onset. A favorable penumbral pattern was defined as a mismatch ratio ≥ 1.43 between hypoperfusion by Tmax &gt; 6 s and infarction core by DWI which should be &lt; 90 mL. The good outcome was defined as mRS ≤ 2 at 3 Mo. The recanalization was evaluated by TICI grading and successful recanalization was defined as grade 2b or 3. Results: Among 72 patients, 44 (61%) underwent combined treatment with intravenous (IV) and endovascular treatments, and 28 (39%) were treated by endovascular thrombectomy only. The overall recanalization rate was 82%, and the proportion of good outcome was 55.6%. Younger age and recanalization were associated with good outcome, but onset to treatment time and the combined IV thrombolysis was not related to good outcome. After propensity score matching to balance possible confounders between combined and endovascular-only treatment groups, combined treatment did not have beneficial effects than endovascular-only (OR, 0.8; 95% CI, 0.1-2.6). The successful recanalization after endovascular treatment was an independent predictor for good outcome (adjusted OR, 6.8; 95% CI, 1.3-34.5), after controlling age, sex, stroke severity, onset to treatment time, the combined IV therapy, and risk factors. Conclusion: In patients with discrete diffusion-perfusion mismatch, the recanalization after thrombectomy is the most important predictor for good outcomes.

Acute ischemic stroke with tandem/terminal ICA occlusion - CT perfusion based case selection for mechanical recanalization

Rapid reperfusion in a patient with a favorable penumbral pattern is crucial to achieving a good outcome in acute ischemic stroke. Recanalization rates for tandem and terminal internal carotid artery (ICA) occlusion are better with endovascular management as compared with intravenous tissue plasminogen activator (IV-tPA) alone. We hypothesize that tissue-based selection would enable the identification of the ideal patient most suited for reperfusion therapy. We present our series of patients who developed tandem or terminal ICA occlusion and were selected for endovascular management based on their computed tomography (CT) perfusion (CTP) imaging. In this prospective study, 14 (29.16%) of the 48 patients treated by endovascular intervention between January 2011 and March 2014 had either tandem or terminal ICA occlusion. In the tandem group, thrombolysis in cerebral infarction (TICI) 2b/3 reperfusion and a good outcome was observed in five (71.42%, n = 7) and six patients (85.71%, n = 6), respectively. Among the terminal ICA occlusion group, TICI 2b/3 reperfusion and a good outcome was observed in three (42.8%, n = 7) and two patients (28.5%, n = 7), respectively. In patients with early reperfusion, a strong correlation with a median difference of one, in cerebral blood volume (CBV) Alberta Stroke Program Early CT Score (ASPECTS) on CBV map and post-procedure 24-h non-contrast CT, was noted. The median imaging-to-puncture and puncture-to -meaningful reperfusion time was 70 and 68.5 min, respectively, and, overall, good outcomes were seen in 57.1% of the patients. The cerebral blood volume (CBV) core estimation reliably predicted the final infarct volume. The key reasons for the significantly better outcomes seen in our cohort were the stringent perfusion imaging-based patient selection and the rapid reperfusion.

A review of current clinical studies leading to improved outcomes in patients treated with newer-generation thrombectomy devices

Treatment with endovascular treatment in conjunction with intra-venous Tissue Plasminogen Activator (IV tPA) under specific clinical situations leads to improved functional outcomes in patients. This review addresses the efficacy of endovascular stroke treatment in patients selected under ideal inclusion criteria and treated with the most up to date embolectomy devices. Recent trials such as ESCAPE, MR CLEAN, EXTEND IA and SWIFT PRIME showed that demonstration of proximal vessel occlusion in CT scans, stratification of penumbral patterns, along with expedient recanalization with the most up to date embolectomy devices leads to a statistically significant improvement in function, NIHSS scores, and mortality in patients treated with endovascular tPA. SWIFT PRIME, in particular, demonstrated that patients demonstrated a 4.5 point improvement in NIHSS scores 27 hours after treatment and decreased mortality along with an increased number of patients with a Rankin score of 1-2 90 days after therapy. Evidence shows that endovascular stroke treatment leads to improved outcomes in patients who are selected based on refined CT guided inclusion criteria and rapid revascularization by newer generation embolectomy devices in conjunct with IA tPA.

A comparison of two methods for MRI classification of at-risk tissue and core infarction.

Objective: To compare how at-risk tissue and core infarction were defined in two major trials that tested the use of MRI in selecting acute stroke patients for endovascular recanalization therapy.Methods: MRIs from 12 patients evaluated for possible endovascular therapy were processed using the methods published from two major trials, MR RESCUE and DEFUSE 2. Specifically, volumes of at-risk tissue and core infarction were generated from each patient’s MRI. MRIs were then classified as whether or not they met criteria for salvageable tissue: “penumbral pattern” for MR RESCUE and/or “target profile” for DEFUSE 2 as defined by each trial.Results: Volumes of at-risk tissue measured by the two definitions were correlated (p = 0.017) while the volumes of core infarct were not (p = 0.059). The volume of at-risk tissue was consistently larger when defined by the penumbral pattern than the target profile while the volume of core infarct was consistently larger when defined by the target profile than the penumbral pattern. When these volumes were used to classify the MRI scans, 9 out of 12 patients (75%) were classified as having a penumbral pattern, while only 4 out of 12 patients (33%) were classified as having a target profile. Of the 9 patients classified as penumbral pattern, 5 (55%) were classified differently by the target profile.Interpretation: Our analysis found that the MR RESCUE trial defined salvageable tissue in a way that made it more likely for patients be labeled as favorable for treatment. For the cohort of patients examined in this study, had they been enrolled in both trials, most of the patients identified as having salvageable tissue by the MR RESCUE trial would not have been considered to have salvageable tissue in the DEFUSE 2 trial. Caution should be taken in concluding that MRI selection for endovascular therapy is not effective as imaging selection criteria were substantially different between the two trials.

Penumbra pattern assessment in acute stroke patients: comparison of quantitative and non-quantitative methods in whole brain CT perfusion.

Background And PurposeWhile penumbra assessment has become an important part of the clinical decision making for acute stroke patients, there is a lack of studies measuring the reliability and reproducibility of defined assessment techniques in the clinical setting. Our aim was to determine reliability and reproducibility of different types of three-dimensional penumbra assessment methods in stroke patients who underwent whole brain CT perfusion imaging (WB-CTP).Materials And MethodsWe included 29 patients with a confirmed MCA infarction who underwent initial WB-CTP with a scan coverage of 100 mm in the z-axis. Two blinded and experienced readers assessed the flow-volume-mismatch twice and in two quantitative ways: Performing a volumetric mismatch analysis using OsiriX imaging software (MMVOL) and visual estimation of mismatch (MMEST). Complementarily, the semiquantitative Alberta Stroke Programme Early CT Score for CT perfusion was used to define mismatch (MMASPECTS). A favorable penumbral pattern was defined by a mismatch of ≥30% in combination with a cerebral blood flow deficit of ≤90 ml and an MMASPECTS score of ≥1, respectively. Inter- and intrareader agreement was determined by Kappa-values and ICCs.ResultsOverall, MMVOL showed considerably higher inter-/intrareader agreement (ICCs: 0.751/0.843) compared to MMEST (0.292/0.749). In the subgroup of large (≥50 mL) perfusion deficits, inter- and intrareader agreement of MMVOL was excellent (ICCs: 0.961/0.942), while MMEST interreader agreement was poor (0.415) and intrareader agreement was good (0.919). With respect to penumbra classification, MMVOL showed the highest agreement (interreader agreement: 25 agreements/4 non-agreements/κ: 0.595; intrareader agreement 27/2/0.833), followed by MMEST (22/7/0.471; 23/6/0.577), and MMASPECTS (18/11/0.133; 21/8/0.340).ConclusionThe evaluated approach of volumetric mismatch assessment is superior to pure visual and ASPECTS penumbra pattern assessment in WB-CTP and helps to precisely judge the extent of 3-dimensional mismatch in acute stroke patients.

Abstract T MP9: Analysis of MR RESCUE Dataset Employing DEFUSE 2 Target Mismatch Criteria for Defining Penumbra

Background: The MR RESCUE trial failed to show a benefit of endovascular therapy over standard medical care for first generation thrombectomy devices within 8 hours of onset of acute ischemic stroke. We now report a subset analysis of patients enrolled with MRI, employing DEFUSE 2 criteria to define favorable penumbral pattern (target mismatch) which differed from MR RESCUE penumbral prediction criteria. Methods: Patients with large vessel, anterior circulation strokes were randomized to mechanical embolectomy (Merci Retriever or Penumbra System) or standard care. Patients were categorized as having a favorable penumbral or non-penumbral pattern employing the DEFUSE 2 criteria for target mismatch ([Tmax &gt; 6s / thresholded ADC &lt; 600 х 10 −6 mm 2 /s] &gt; 1.8, thresholded ADC &lt; 70 cc, and Tmax &gt; 10 s &lt; 100 cc). Results: Among 118 total patients, 94 qualified for this analysis. Mean age was 65.8, mean time to enrollment 5.6 hours, median NIHSS 17, and 47% had target mismatch. Predicted core volume using DEFUSE 2 criteria (thresholded ADC volume &lt; 600 х 10 −6 mm 2 /s) was 18.8 cc (target mismatch) and 64.3 cc (non-target mismatch; p&lt;0.001). Revascularization in the embolectomy group was achieved in 62% (TICI 2a-3), and 21% (TICI 2b-3). Among all patients, mean 90-day mRS scores did not differ between embolectomy and standard care (3.8 vs 3.8; p=0.92). In patients with target mismatch, embolectomy was not superior to standard care (mean mRS 3.5 vs 3.3, p=0.78). Similarly, in patients without target mismatch, embolectomy was not superior (4.1 vs 4.3, p=0.67). Furthermore, there was no interaction between pretreatment penumbral imaging pattern employing DEFUSE 2 target mismatch criteria and treatment assignment in these 90-day mRS scores (p=0.11). Conclusions: In this analysis MR RESCUE patients enrolled with pretreatment MRI, use of the DEFUSE 2 criteria for target mismatch as a definition of penumbral pattern failed to identify a subset of patients with improved outcomes when treated with embolectomy. Further randomized, controlled studies employing new generation thrombectomy devices are needed to validate target mismatch as a selection criterion for acute stroke treatments.

DWI Reversal Is Associated with Small Infarct Volume in Patients with TIA and Minor Stroke

More than half of patients with TIA/minor stroke have ischemic lesions on early DWI, which represent irreversibly damaged tissue. The presence and volume of DWI lesions predict early deterioration in this population. We aimed to study the rate and implications of DWI reversal in patients with TIA/minor stroke. Patients with TIA/minor stroke were prospectively enrolled and imaged within 24 hours of onset. Patients were followed for 3 months with repeat MR imaging either at day 30 or 90. Baseline DWI/PWI and follow-up FLAIR final infarct volumes were measured. Of 418 patients included, 55.5% had DWI and 37% had PWI (time-to-peak of the impulse response ≥2 seconds' delay) lesions at baseline. The median time from symptom onset to baseline and follow-up imaging was 13.4 (interquartile range, 12.7) and 78.73 hours (interquartile range, 60.2), respectively. DWI reversal occurred in 5.7% of patients. The median DWI lesion volume was significantly smaller in those with reversal (0.26 mL, interquartile range = 0.58 mL) compared with those without (1.29 mL, interquartile range = 3.6 mL, P = .002); 72.7% of DWI reversal occurred in cortically based lesions. Concurrent tissue hypoperfusion (time-to-peak of the impulse response ≥2 seconds) was seen in 36.4% of those with DWI reversal versus 62.4% without (P = .08). DWI reversal occurred in 3.3% of patients with penumbral patterns (time-to-peak of the impulse response ≥6 seconds - DWI) > 0 and in 6.8% of those without penumbral patterns (P = .3). The severity of hypoperfusion, defined as greater prolongation of time-to-peak of the impulse response (≥2, ≥4, ≥6, ≥8 seconds), did not affect the likelihood of DWI reversal (linear trend, P = .147). No patient with DWI reversal had an mRS score of ≥2 at 90 days versus 18.2% of those without reversal (P = .02). DWI reversal is uncommon in patients with TIA/minor stroke and is more likely to occur in those with smaller baseline lesions. DWI reversal should not have a significant effect on the accuracy of penumbra definition.

Stroke: new horizons in treatment

Intra-arterial therapy (IAT) has been used for three decades to promote recanalisation after stroke. Whereas results of the Prolyse in Acute Cerebral Thromboembolism-II trial (PROACT-II) 1 Furlan A Higashida R Wechsler L et al. Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism. JAMA. 1999; 282: 2003-2011 Crossref PubMed Scopus (2720) Google Scholar showed significant improvement in clinical outcome with intra-arterial fibrinolysis, the stroke specialty received some disturbing news in 2013. Results of the Interventional Management of Stroke-III (IMS-III), 2 Broderick JP Palesch YY Demchuk AM et al. for the Interventional Management of Stroke (IMS) III InvestigatorsEndovascular therapy after intravenous t-PA vs t-PA alone for stroke. N Engl J Med. 2013; 368: 893-903 Crossref PubMed Scopus (1421) Google Scholar SYNTHESIS, 3 Ciccone A Valvassori L Nichelatti M et al. for the SYNTHESIS Expansion InvestigatorsEndovascular treatment for acute ischemic stroke. N Engl J Med. 2013; 368: 904-913 Crossref PubMed Scopus (357) Google Scholar and Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE) 4 Kidwell CS Jahan R Gornbein J et al. for the MR RESCUE InvestigatorsA trial of imaging selection and endovascular treatment for ischemic stroke. N Engl J Med. 2013; 368: 914-923 Crossref PubMed Scopus (1091) Google Scholar studies failed to show an increased benefit for IAT compared with intravenous alteplase (t-PA) or as an adjunctive approach to intravenous alteplase. All three studies were randomised controlled trials: IMS-III assessed the adjunctive benefit of IAT with intravenous alteplase, SYNTHESIS tested IAT efficacy against intravenous alteplase, and MR RESCUE tried to identify patients most likely to benefit from IAT on the basis of a favourable imaging profile showing a penumbral pattern. IAT advocates have pointed out that newer devices than those used in these studies might achieve more rapid and complete recanalisation and better outcomes. A post-hoc analysis from IMS-III showed that patients treated within 4 h from symptom onset have potential to benefit most from IAT. Furthermore, new data showing improved reperfusion rates and times with the introduction of stent retrievers could result in improved clinical outcomes. 5 Saver JL Jahan R Levy EI et al. for the SWIFT TrialistsSolitaire flow restoration device versus the Merci Retriever in patients with acute ischaemic stroke (SWIFT): a randomised, parallel-group, non-inferiority trial. Lancet. 2012; 380: 1241-1249 Summary Full Text Full Text PDF PubMed Scopus (1051) Google Scholar , 6 Nogueira RG Lutsep HL Gupta R et al. for the TREVO2 trialistsTrevo versus Merci retrievers for thrombectomy revascularisation of large vessel occlusions in acute ischaemic stroke (TREVO 2): a randomised trial. Lancet. 2012; 380: 1231-1240 Summary Full Text Full Text PDF PubMed Scopus (889) Google Scholar

Commentary

Commentary

MR RESCUE

The timely concurrent publication of Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE) with the International Management of Stroke Trial III and the Local Versus Systemic Thrombolysis for Acute Ischemic Stroke (SYNTHESIS) Expansion trials confirmed that endovascular therapy was not superior to standard care for patients with acute ischemic stroke.1–3 The novel conclusion from MR RESCUE was that, …a favorable penumbral pattern on neuroimaging did not identify patients who would differentially benefit from endovascular Some have interpreted this finding to support a pessimistic (glass half-empty) view of advanced imaging selection for acute reperfusion therapy. We disagree with this viewpoint and argue that the results of MR RESCUE should not dampen enthusiasm for the concept of imaging-based selection. Key limitations of MR RESCUE that hinder the generalizability of the conclusions of the study include enrollment bias, with a preponderance of patients having large infarct cores, and late times to endovascular therapy combined with very low rates of adequate early reperfusion. Lessons learned from this important study should help guide future trials. MR RESCUE was a phase IIb randomized, controlled, open-label, blinded outcome, multicenter study. Patients were assigned within 8 hours after the onset of large-vessel anterior circulation stroke to undergo embolectomy (with the first-generation Merci or Penumbra devices) or standard care (37% of patients received IV recombinant tissue plasminogen activator). Based on MRI (80%) or multimodal computed tomography, randomization was stratified according to whether the patient had a favorable penumbral pattern (infarct core <90 mL and substantial salvageable tissue) or a nonpenumbral pattern (large core and small or absent penumbra). Notably, only 118 patients eligible for the primary analyses were enrolled across 22 high-volume North American Stroke Centers over nearly a decade (2004–2011). The median predicted infarct core volume at the time of baseline …