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Reperfusion therapy is highly beneficial for ischemic stroke. Reduction in both infarct growth and edema are plausible mediators of clinical benefit with reperfusion. We aimed to quantify these mediators and their interrelationship.In a pooled, patient-level analysis of EXTEND-IA trials and SELECT study, we employed a mediation analysis framework to quantify infarct growth and cerebral edema(midline shift) mediation effect on successful reperfusion(mTICI≥2b) association with functional outcome(mRS distribution). Further, we evaluated an additional pathway to the original hypothesis, where infarct growth mediated successful reperfusion effect on midline shift.542/665(81.5%) eligible patients achieved successful reperfusion. Baseline clinical and imaging characteristics were largely similar between those achieving successful vs unsuccessful reperfusion. Median(IQR) infarct growth was 12.3(1.8-48.4)ml and median(IQR) midline shift was 0(0,2.2)mm. Of 249(37%) demonstrating a midline shift of ≥1mm, median(IQR) shift was 2.75(1.89, 4.21)mm). Successful reperfusion was associated with reductions in both predefined mediators; infarct growth (β, -1.19; 95%CI, -1.51to-0.88;p0.001) and midline shift (aOR:0.36,95%CI:0.23-0.57,p0.001). Successful reperfusion association with improved functional outcome (acOR:2.68; 95%CI:1.86-3.88,p0.001), became insignificant (acOR:1.39, 95%CI:0.95-2.04,p=0.094) when infarct growth and midline shift were added to the regression model. Infarct growth and midline shift explained 45% and 34% of successful reperfusion effect. Analysis considering alternative hypothesis demonstrated consistent results.In this mediation analysis from a pooled, patient-level cohort, a significant proportion(~80%) of successful reperfusion effect on functional outcome was mediated through reduction in infarct growth and cerebral edema. Further studies are required to confirm our findings, detect additional mediators to explain successful reperfusion residual effect and identify novel therapeutic targets to further enhance reperfusion benefits. This article is protected by copyright. All rights reserved.

Objective: We propose a novel measure, the PSI, to evaluate procedural success and prognostication after EVT and compare its prognostic ability with successful reperfusion (mTICI ≥2b). Methods: SELECT EVT patients with adequate follow-up MR DWI imaging were stratified based on PSI [ratio of salvaged tissue volume (Tmax >6s volume at baseline – f/up DWI infarct volume) to the Tmax >6s volume at baseline] into good (PSI≥50%) and poor penumbral salvage (PSI Results: 142/206(69%) had good penumbral salvage, with better CT ASPECTS (Good PSI: 9(7-10) vs Poor PSI: 7(6-9),p6s volume (aOR: 1.01, 95%CI: 1.00-1.02, p=0.003) and mTICI≥2b (aOR: 8.84, 95%CI: 3.16-24.71, p Conclusion: Good penumbral salvage is associated with higher odds of functional independence, and has a better predictive value than successful reperfusion on cerebral angiogram after EVT. Prospective studies are needed to confirm the predictive utility of the PSI.

Introduction: Improvement in NIH stroke scale scores on 24h follow-up is considered a key prognostic element after endovascular thrombectomy (EVT). We aimed to evaluate the proportion of effect of 24h NIHSS improvement on mRS 0-2 at 90d mediated through improvement in motor and language domains. Methods: From SELECT study, EVT patients with detailed NIHSS components on presentation and 24h follow-up as well as complete mRS on discharge and 90d were selected. Motor improvement was defined as ≥2 point in cumulative arms and legs score or 0 score at 24h and language improvement was defined as ≥1 point in cumulative aphasia and dysarthria scores at 24h. Mediation analysis framework using 4-step method (Figure 1a) was used to evaluate the effect of 24h NIHSS improvement mediated through improvement in motor and language scores. Results: Of 192 eligible EVT patients, 176 demonstrated motor deficits and 187 demonstrated language deficits. 24h NIHSS improvement was significantly associated with mRS 0-2 (aOR:1.15[1.07-1.23], p Conclusions: Almost all (~95%) of the effect of 24h NIHSS improvement on functional independence (mRS 0-2) was mediated through specific improvement in motor and language domains, suggesting a large role of improvement in motor and language domains in achieving better functional independence. Further studies are needed to confirm the findings.

Objective: To serially quantify the blood coagulation within hematoma of patients with hyper-acute intracerebral hemorrhagic (ICH) stroke using non-invasive quantitative susceptibility mapping (QSM) MRI. Introduction: A blood clot is a combination of aggregated red blood cells, fibrin, platelets, hemosiderin, and other cell debris. An accurate evaluation of clot formation within hematoma could advance the clinical management of hematoma expansion, blood pressure management, and reversal of anticoagulants. Post-ICH hemolysis changes the heme iron oxidation state from oxy to deoxyhemoglobin (deoxy-Hb) resulting in unpaired iron electrons on aggregated RBC’s deoxy-Hb inducing magnetic susceptibility (χ). Therefore, a region with a higher number of aggregated RBC deoxy-Hb molecules, the dominant component of clots, will exhibit a higher positive χ susceptibility. We hypothesized that coagulated blood within hematoma will exhibit a higher positive χ in comparison to the non-clotted which can be quantified using quantitative susceptibility mapping (QSM), which is an advanced MRI image-processing algorithm. Methods: For proof of concept, we measured susceptibilities of 5 human blood phantoms with various percentages of the clot. Twenty-four patients with acute spontaneous ICH were enrolled and serially imaged 3 times within 12-24 (T1), 36-48 (T2), and 60-72(T3) hours of last known well (LNW). A 3D anatomical and multi-echo gradient echo images were obtained using a 3T MRI system. Hematoma and edema volumes were segmented and used as a region of interest (ROI). The rate of coagulation was assessed by measuring the change in susceptibilities within the hematoma. Results: The blood phantom exhibited a linear relationship between the percent coagulation and χ (R 2 =0.91). The QSM maps showed a significant increased in hematoma susceptibility over time (T1=0.29 ± 0.04, T2=0.36 ± 0.04, T3= 0.45 ± 0.04 ppm, p Conclusion: In conclusion, we present novel surrogate imaging markers of coagulation within the hematoma of ICH.

Bone marrow mononuclear cells (MNCs) attenuate secondary degeneration and enhance recovery in stroke animal models. In a nonrandomized clinical trial, we imaged 37 patients with stroke: 17 patients treated with MNCs (treated) and 20 patients who received standard of care (nontreated) at 1, 3, and 12 months onset of stroke on 3.0T MRI system. Three‐dimensional anatomical and diffusion tensor images were obtained. The integrity of the corticospinal tract was assessed by measuring absolute and relative fractional anisotropy (FA) and mean diffusivity (MD) in the rostral pons (RP), posterior limb of the internal capsule, and corona radiata by drawing regions of interest. Infarct volume and stroke severity, which was assessed via the NIH Stroke Scale (NIHSS), were higher in the MNC group compared with the nontreated patients, which is a major limitation. Overall, the relative FA (rFA) of the nontreated patients exhibited continued reduction and an increase in relative MD (rMD) from 1 to 12 months, whereas despite larger infarcts and higher severity, treated patients displayed an increase in rFA from 3 to 12 months and no change in rMD. Contrary to the nontreated group, the treated patients' rFA was also significantly correlated (P, Autologous bone‐marrow mononuclear cells were intravenously administered in patients with acute ischemic stroke as procedure outline in panel (A). The nontreated patients were recruited separately. Both groups were imaged three times over year and neuroimaging biomarkers were developed. Integrity of the ipsilesional and contralesional cortical spinal tracts (CST) were evaluated via diffusion tensor imaging (DTI), in the rostral pons (RP), posterior limb of internal capsule (PLIC), and corona radiata (CR) as illustrated in panel (B). The relative fractional anisotropy (rFA), an imaging marker of white matter integrity, was serially quantified in these three regions in each group as shown in panel (C1), (C2), and (C3). Despite larger infarct size and severity of the treated group, the rFA either increased or stabilized as compared to the nontreated patients.

We thank the Editors of JNIS for alerting us in advance to the concerns about SELECT2 raised by Jadhav1 and colleagues and appreciate the opportunity to explain the rationale for the study design and clarify the benefits of including perfusion imaging-based selection criteria. We are confident that SELECT2 will provide high-level, reliable data regarding the safety and efficacy of endovascular thrombectomy (EVT) for large core patients. The choice of imaging modality for identifying large core in acute ischemic stroke remains an area of considerable debate. Magnetic resonance imaging (MRI) diffusion-weighted imaging (DWI), computed tomography (CT) or MR perfusion imaging and Alberta Stroke Program Early CT Score (ASPECTS) have all been proposed and studied. At present, there is no clear consensus on which imaging modality is best for identifying patients with large core. It is important to recognize that the early window randomized EVT trials used a broad range of imaging selection criteria. The imaging selection criteria for the initial five pivotal trials ranged from allowing patients to be enrolled regardless of the degree of early infarct signs,2 to studies that required a specific ASPECTS score range in addition to other imaging criteria,3–5 to EXTEND IA6 where the ASPECTS score was not considered, and CT perfusion (CTP) mismatch with a maximum estimated core size was required. All five trials were successful but with substantial variability in the treatment effect, leaving uncertainty as to the optimal imaging approach as well as whether there are patient subgroups who do not benefit. In fact, those utilizing perfusion mismatch criteria (EXTEND-IA, SWIFT PRIME) had higher rates of modified Rankin Scale (mRS) scores 0–2 and larger treatment effects, compared with other trials.2–6 Even if a treatment has a clear benefit in most patients, there can be important subgroups that do not …

ObjectiveTo evaluate the comparative safety and efficacy of direct endovascular thrombectomy (dEVT) compared to bridging therapy (BT; IV tissue plasminogen activator + EVT) and to assess whether BT potential benefit relates to stroke severity, size, and initial presentation to EVT vs non-EVT center.MethodsIn a prospective multicenter cohort study of imaging selection for endovascular thrombectomy (Optimizing Patient Selection for Endovascular Treatment in Acute Ischemic Stroke [SELECT]), patients with anterior circulation large vessel occlusion (LVO) presenting to EVT-capable centers within 4.5 hours from last known well were stratified into BT vs dEVT. The primary outcome was 90-day functional independence (modified Rankin Scale [mRS] score 0–2). Secondary outcomes included a shift across 90-day mRS grades, mortality, and symptomatic intracranial hemorrhage. We also performed subgroup analyses according to initial presentation to EVT-capable center (direct vs transfer), stroke severity, and baseline infarct core volume.ResultsWe identified 226 LVOs (54% men, mean age 65.6 ± 14.6 years, median NIH Stroke Scale [NIHSS] score 17, 28% received dEVT). Median time from arrival to groin puncture did not differ in patients with BT when presenting directly (dEVT 1.43 [interquartile range (IQR) 1.13–1.90] hours vs BT 1.58 [IQR 1.27–2.02] hours, p = 0.40) or transferred to EVT-capable centers (dEVT 1.17 [IQR 0.90–1.48] hours vs BT 1.27 [IQR 0.97–1.87] hours, p = 0.24). BT was associated with higher odds of 90-day functional independence (57% vs 44%, adjusted odds ratio [aOR] 2.02, 95% confidence interval [CI] 1.01–4.03, p = 0.046) and functional improvement (adjusted common OR 2.06, 95% CI 1.18–3.60, p = 0.011) and lower likelihood of 90-day mortality (11% vs 23%, aOR 0.20, 95% CI 0.07–0.58, p = 0.003). No differences in any other outcomes were detected. In subgroup analyses, patients with BT with baseline NIHSS scores p = 0.006); this association was not evident for patients with NIHSS scores ≥15 (aOR 1.05, 95% CI 0.40–2.74, p = 0.92). Similarly, functional outcomes improvements with BT were detected in patients with core volume strata (ischemic core 3: aOR 2.10, 95% CI 1.02–4.33, p = 0.044 vs ischemic core ≥50 cm3: aOR 0.41, 95% CI 0.01–16.02, p = 0.64) and transfer status (transferred: aOR 2.21, 95% CI 0.93–9.65, p = 0.29 vs direct to EVT center: aOR 1.84, 95% CI 0.80–4.23, p = 0.15).ConclusionsBT appears to be associated with better clinical outcomes, especially with milder NIHSS scores, smaller presentation core volumes, and those who were “dripped and shipped.” We did not observe any potential benefit of BT in patients with more severe strokes.Trial Registration InformationClinicalTrials.gov Identifier: NCT02446587.Classification of EvidenceThis study provides Class III evidence that for patients with ischemic stroke from anterior circulation LVO within 4.5 hours from last known well, BT compared to dEVT leads to better 90-day functional outcomes.

BackgroundIt is unknown whether endovascular thrombectomy (EVT) is cost effective in large ischemic core infarcts.MethodsIn the prospective, multicenter, cohort study of imaging selection study (SELECT), large core was defined as computed tomography (CT) ASPECTSResultsFrom 361 patients enrolled in SELECT, 105 had large core on CT or CTP (EVT 62, MM 43). 19 (31%) EVT vs 6 (14%) MM patients achieved modified Rankin Scale (mRS) score 0–2 (OR 3.27, 95% CI 1.11 to 9.62, P=0.03) with a shift towards better mRS (cOR 2.12, 95% CI 1.05 to 4.31, P=0.04). Over the projected lifetime of patients presenting with large core, EVT led to incremental costs of $33 094 and a gain of 1.34 QALYs per patient, resulting in ICER of $24 665 per QALY. EVT has a higher NMB compared with MM at lower (EVT -$42 747, MM -$76 740) and upper (EVT $155 041, MM $57 134) WTP thresholds. PSA confirmed the results and CEAC showed 77% and 92% acceptability of EVT at the WTP of $50 000 and $100 000, respectively. EVT was associated with an increment of $29 225 in societal costs. The pivotal EVT trials (HERMES, DAWN, DEFUSE 3) were dominant in a sensitivity analysis at the same inputs, with societal cost-savings of $37 901, $86 164 and $22 501 and a gain of 1.62, 2.36 and 2.21 QALYs, respectively.ConclusionsIn a non-randomized prospective cohort study, EVT resulted in better outcomes in large core patients with higher QALYs, NMB and high cost-effectiveness acceptability rates at current WTP thresholds. Randomized trials are needed to confirm these results.Clinical trial registrationNCT02446587

Objective This study was undertaken to evaluate functional and safety outcomes for endovascular thrombectomy (EVT) versus medical management (MM) in patients with large vessel occlusion (LVO) and mild neurological deficits, stratified by perfusion imaging mismatch. Methods The pooled cohort consisted of patients with National Institutes of Health Stroke Scale (NIHSS) < 6 and internal carotid artery (ICA), M1, or M2 occlusions from the Extending the Time for Thrombolysis in Emergecy Neurological Deficits - Intra-Arterial (EXTEND-IA) Trial, Tenecteplase vs Alteplase before Endovascular Thrombectomy in Ischemic Stroke (EXTEND-IA TNK) trials Part I/II and prospective data from 15 EVT centers from October 2010 to April 2020. RAPID software estimated ischemic core and mismatch. Patients receiving primary EVT (EVTpri) were compared to those who received primary MM (MMpri), including those who deteriorated and received rescue EVT, in overall and propensity score (PS)-matched cohorts. Patients were stratified by target mismatch (mismatch ratio >= 1.8 and mismatch volume >= 15ml). Primary outcome was functional independence (90-day modified Rankin Scale = 0-2). Secondary outcomes included safety (symptomatic intracerebral hemorrhage [sICH], neurological worsening, and mortality). Results Of 540 patients, 286 (53%) received EVTpri and demonstrated larger critically hypoperfused tissue (Tmax > 6 seconds) volumes (median [IQR]: 64 [26-96] ml vs MMpri: 40 [14-76] ml, p < 0.001) and higher presentation NIHSS (median [IQR]: 4 [2-5] vs MMpri: 3 [2-4], p < 0.001). Functional independence was similar (EVTpri: 77.4% vs MMpri: 75.6%, adjusted odds ratio [aOR] = 1.29, 95% confidence interval [CI] = 0.82-2.03, p = 0.27). EVT had worse safety regarding sICH (EVTpri: 16.3% vs MMpri: 1.3%, p < 0.001) and neurological worsening (EVTpri: 19.6% vs MMpri: 6.7%, p < 0.001). In 414 subjects (76.7%) with target mismatch, EVT was associated with improved functional independence (EVTpri: 77.4% vs MMpri: 72.7%, aOR = 1.68, 95% CI = 1.01-2.81, p = 0.048), whereas there was a trend toward less favorable outcomes with primary EVT (EVTpri: 77.4% vs MMpri: 83.3%, aOR = 0.39, 95% CI = 0.12-1.34, p = 0.13) without target mismatch (p(interaction) = 0.06). Similar findings were observed in a propensity score-matched subpopulation. Interpretation Overall, EVT was not associated with improved clinical outcomes in mild strokes due to LVO, and sICH was increased. However, in patients with target mismatch profile, EVT was associated with increased functional independence. Perfusion imaging may be helpful to select mild stroke patients for EVT. ANN NEUROL 2022

This meeting abstract was removed due to the OA licensing requirements of this journal. The full abstract is listed here : https://www.svin.org/files/SVIN_2021_Abstracts_for_Web.pdf

Rationale Randomized evidence for endovascular thrombectomy safety and efficacy in patients with large core strokes is lacking. Aims To demonstrate endovascular thrombectomy efficacy and safety in patients with large core on non-contrast CT or perfusion imaging (CT/MR) and determine if there is heterogeneity of treatment effect in large cores based on the imaging modality. Design SELECT2 is a prospective, randomized, multi-center, assessor-blinded controlled trial with adaptive enrichment design, enrolling up to 560 patients. Procedure Patients who meet the clinical criteria and have anterior circulation large vessel occlusions with large core on either NCCT (ASPECTS 3–5) or perfusion imaging (CTP [rCBF Study outcomes The distribution of 90-day mRS scores is the primary outcome. Functional independence (mRS = 0–2) rate is a secondary outcome. Other secondary outcomes include safety (symptomatic ICH, neurological worsening, mortality) and imaging outcomes. Analysis A normal approximation of the Wilcoxon-Mann-Whitney test (the generalized likelihood ratio test) to assess the primary outcome. Functional independence rates, safety and imaging outcomes will also be compared. Discussion The SELECT2 trial will evaluate endovascular thrombectomy safety and efficacy in large cores on either CT or perfusion imaging and may provide randomized evidence to extend endovascular thrombectomy eligibility to larger population. Registration: ClinicalTrials.gov–NCT03876457

Ischemic strokes in young adults are devastatingly debilitating and increasingly frequent. Stroke remains the leading cause of serious disability in the United States. The consequences of this familiar disease in this atypical age group are especially detrimental and long lasting. Ischemic stroke in young adults is now emerging as a public health issue, one in which radiologists can play a key role. The incidence of ischemic infarction in young adults has risen over the past couple of decades. Increased public awareness, increased use of MRI and angiography, and more accurate diagnosis may in part explain the increased detection of stroke in young adults. The increased prevalence of stroke risk factors in young adults (especially sedentary lifestyle and hypertension) may also contribute. However, compared with older adults, young adults have fewer ischemic infarcts related to the standard cardiovascular risk factors and large- or small-vessel disease. Instead, their infarcts most commonly result from cardioembolic disease and other demonstrated causes (ie, dissection). Thus, radiologists must expand their differential diagnoses to appropriately diagnose ischemic strokes and identify their causes in the young adult population. From the more frequent cardioembolism and dissection to the less common vasculitis, drug-related, CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), moyamoya, and hypercoagulable state-related infarcts, this article covers a wide breadth of causes and imaging findings of ischemic stroke in young adults. ©RSNA, 2019.

Background: Acute ischemic strokes outcomes may be less favorable in elderly patients. Whether transferring octogenarians with large vessel occlusion (LVO) for endovascular thrombectomy (EVT) results in similar outcomes to younger patients is uncertain. Methods: A pooled cohort from 6 centers (Europe, US) from 1/2014 to 5/2020 of pts with (ICA, M1, M2) LVO transferred for EVT ≤ 24 hrs from LKW. Patients were stratified into < 80 vs ≥ 80 years old. We compared 90 day functional independence and safety outcomes and assessed for predictors of good outcome (mRS 0-2) and profound disability (mRS 5-6). Results: Of 1176 pts received EVT as transfers, 216 (18%) were octogenarians. Baseline NIHSS was higher in octogenarians [19 (14, 22) vs 17 (12, 21), p Milder strokes (aOR 0.88, 95%CI 0.86-0.91, p Conclusion: EVT may be associated with lower independence rates in transferred octogenarians with LVO. Milder stroke severity, earlier presentation and IV thrombolysis increased the odds of good outcomes in octogenarians. Severe strokes and later treatment were associated with profound disability. Optimized selection and workflow is warranted in transferring elderly patients for EVT.

Background: Efficacy and safety of endovascular thrombectomy (EVT) in large vessel occlusion (LVO) patients with mild deficits is unclear. Methods: Pooled cohort of pts with mild deficits (NIHSS Results: Of 371 pts, 189 (51%) had EVT. Time LKW to EVT center: EVT 165 (70- 416) vs MM 200 (72-564) min, p=0.35 were similar. EVT pts had larger perfusion lesions (51 cc (23-86) vs 30.1 (5, 65), p0.99, neuro-worsening 17% vs 6%, p=0.30) and mortality 5% vs 3%, p>0.99). Without target profile, excellent outcomes were similar without a shift, Fig 1C. Safety was worse with EVT: sICH 8% vs 0%, p=0.001; neuro-worsening 20% vs 3%, p Conclusion: EVT was not associated with improved outcomes in patients with mild deficits; safety was worse. However, EVT was safe and associated with improved outcomes in target profile patients.

Background: The accuracy of CT perfusion imaging for estimating the ischemic core has been questioned. Methods: In SELECT, a prospective cohort study of imaging selection, pts who achieved complete reperfusion after EVT were stratified on time from LKW to imaging acquisition and time from imaging to reperfusion. The difference between baseline CTP core volume and f/up infarct volume (on DWI after EVT) was classified as over-estimation (core >10 cc larger than infarct), adequate, or under-estimation (≥ 25 cc smaller). F/up DWI lesion was outlined using a semiautomated algorithm and co-registered to CTP. Results: Of 361 enrolled, 117 achieved TICI 3. F/up MRIs were acquired at 21 (13-30) hrs from EVT with median infarct volume of 16.4 cc, median 8.1 cc larger than baseline core. Median (IQR) time from imaging acquisition to groin puncture (GP) was 70 (50-95) min. Reperfusion was achieved at 35 (25-54) min of GP. The frequency of overestimation decreased as time LKW to imaging increased: < 90 min 6 (14%), 90 – 270 min 3 (6%) and > 270 min 1 (4%), and adequate estimation increased (< 90 min 21 (50%), 90 – 270 min 32 (65%) and > 270min 19 (73%), p for trend 0.048) Fig 1. Overestimation primarily occurred in pts imaged within 90 min who had short imaging to reperfusion times Fig 2. Volumetric correlation between pre-procedure and f/up imaging improved as LKW time to imaging acquisition increased; Spearman’s ρ: 270 min: 0.79 (p Conclusion: In patients who achieve reperfusion, the correlation between baseline CTP ischemic core volume and f/up DWI volume improved as time LKW to imaging increased. Core estimation accuracy improved by using the < 20% CBF threshold for patients imaged within 90 minutes of LKW.

Background: Direct To Angio (DTA) for transferred large vessel occlusions (LVO) lowers time to endovascular thrombectomy (EVT), reperfusion and potentially improves outcomes. Safety and efficacy of DTA in late time window and on-call hours is unknown. Methods: Pooled cohort from 6 centers (EU, US) from 1/14-5/20 (ICA, M1, M2) LVO pts transferred for EVT≤24 hrs from LKW. Pts stratified into with repeat imaging (RI) (CT+/- CTA/CTP) and without RI (DTA). We compared time metrics, good outcome (90 day mRS 0-2), safety (sICH, mortality) and assessed the impact of arrival for EVT; regular (M-F, 8am-5pm) vs on-call hrs. Propensity matched analysis was done. Results: Of 1178 EVT transfers, 334 (28%) were DTA. DTA pts had more tPA (61% vs 51%, p=0.002), trended to lower NIHSS 17 (12, 20) vs 17 (13, 21), p=0.07 and lower LKW to arrival 268 (190, 430) min vs 280 (190, 518), p=0.097. Groin puncture (GP) was faster with DTA (p6-24, p=0.88 for interaction). In propensity matched 75 pairs, DTA had shorter time to EVT (19 min vs 52, p Conclusion: In pooled, non-randomized data DTA may result in faster treatment, safe and better functional outcomes, during all hours and treatment windows. Repeat imaging may be reasonable with prolonged transfer times. Optimal EVT workflow in transfers may result in faster, safe reperfusion with higher good outcomes.

Background and Purpose: Time elapsed from last-known well (LKW) and baseline imaging results are influential on endovascular thrombectomy (EVT) outcomes. Methods: In a prospective multicenter cohort study of imaging selection for endovascular thrombectomy (SELECT [Optimizing Patient’s Selection for Endovascular Treatment in Acute Ischemic Stroke], the early infarct growth rate (EIGR) was defined as ischemic core volume on perfusion imaging (relative cerebral blood flow2. The primary outcome was 90-day functional independence (modified Rankin Scale score =0–2). Results: Of 445 consented, 361 (285 EVT, 76 medical management only) patients met the study inclusion criteria. The optimal EIGR was P P P P =0.001). EIGR independently correlated with functional independence after EVT, adjusting for age, National Institutes of Health Stroke Scale, time LKW to groin puncture, reperfusion (modified Thrombolysis in Cerebral Infarction score of ≥2b), IV-tPA (intravenous tissue-type plasminogen activator), and transfer status (aOR: 0.78 [0.65–0.94], P =0.01). Slow progressors had higher functional independence rates (121 [61%] versus 30 [35%], P P =0.001) as compared to fast progressors, who had substantially worse clinical outcomes both in early and late time window. The odds of good outcome decreased by 14% for each 5 mL/h increase in EIGR (aOR, 0.87 [0.80–0.94], P Conclusions: The EIGR strongly correlates with both collateral status and clinical outcomes after EVT. Fast progressors demonstrated worse outcomes when receiving EVT beyond 6 hours of stroke onset as compared to those who received EVT within 6 hours. Registration: URL: https://clinicaltrials.gov . Unique identifier: NCT02446587.

Background: The effect of anesthesia choice on endovascular thrombectomy (EVT) outcomes is unclear. Methods: In the prospective multicenter cohort study of imaging selection for EVT (SELECT), patients were stratified based on their anesthesia type into general anesthesia (GA) and conscious sedation (CS). EVT times and outcomes were compared. Further we assessed the impact of ischemic core size (rCBF Results: Of 361 enrolled, 285 received EVT. 129 (45%%) received GA and 156 (54%) CS. The baseline characteristics were similar, except for presentation NIHSS (GA 17(13-21), CS 15(11-20), p=0.027) and ischemic core volume (GA 14.1 cc (0-38) vs CS 6.3(0-26.1), p=0.034). GA was associated with numerically longer arrival to GP times 92 (68—115) vs. 85(60-117) mins, p=0.58. After adjustment for baseline imbalances, patients who received CS had a shift toward better outcome (adj cOR 1.72, 95% CI=1.08-2.75, p=0.022) with higher functional independence rates 56.8% vs 48.8%, p=0.75. Furthermore, GA was associated with higher mortality rates (19% vs 9%, p=0.017), figure 1A. In patients with core volume ≥ 50 cc, there was a trend for a shift towards better outcomes (adj cOR=5.84, 95%CI= 0.90-38.00, P=0.065), figure 1B while there was no difference in patients with core volume < 50 cc (adj cOR=1.01 (95%CI 0.53-1.94, P=0.96), figure 1C. There was an interaction between core volume size and anesthesia type on functional outcome (p=0.042). For every 10cc increase in the core volume, the odds of attaining better functional outcome decreased by 29% (adjusted cOR: 0.71, 95% CI=0.61-0.83, p Conclusion: Conscious sedation was associated with a shift towards better EVT outcomes. This effect was driven by patients with larger ischemic core volumes and has implications for randomized trials of conscious sedation vs general anesthesia.

Introduction: Whether reperfusion therapy is safe and efficacious in acute ischemic strokes (AIS) due to posterior circulation large vessel occlusions (PCLVO) beyond 4.5 hrs is unknown. Methods: A retrospective analysis of AIS due to PCLVO presenting to a comprehensive stroke center up to 24 hrs from last known well. Patients were stratified based on the treatment received into reperfusion therapy (IV-tPA and/or endovascular thrombectomy) and no reperfusion therapy. All patients received CT/CTA and CT perfusion with RAPID mismatch determination. Functional independence (90 day mRS 0-2) and sICH were primary and secondary outcomes. The two groups were compared in the overall cohort in an ordinal logistic regression and in a propensity matched analyses. Results: Between 8/2017 and 5/2019, 52 patients were included [reperfusion = 23(44%) vs no-reperfusion=29(56%)]. Reperfusion rate beyond 4.5 hours was 26% (6/23). The two groups were similar at baseline except for larger perfusion delays (Tmax>6s) volume [median (IQR), 16 (0, 46) vs. 0 (0, 25) cc, p=0.03], and higher presentation NIHSS [median (IQR), 10 (5, 21) vs. 4 (1, 8), p=0.004] in the reperfusion group. Reperfusion was associated with higher functional independence rates 10 (43%) vs. 8 (28%), p=0.23 (fig 1), and a trend for a shift towards better outcomes adj cOR 1.89, 95% CI=0.59-6.13, p=0.29. There was no difference in sICH rates 9% vs. 0%, P=0.19. In a propensity matched analysis on NIHSS and perfusion deficit of 14 pairs, reperfusion was associated with statistically significant higher mRS 0-2 rates 9 (64%) vs. 1 (7%), p=0.004 (fig 2). Functional independence rates did not differ in the reperfusion group in relation to time (47% Conclusion: PCLVOs with more severe strokes and large perfusion deficits were more likely to receive reperfusion which was associated with a shift towards better outcomes both earlier and beyond 4.5 hours without worsening safety outcomes.

Background: Whether IV tPA has adjunctive benefit to endovascular thrombectomy (EVT) is unclear. Methods: In a prospective multicenter cohort study of imaging selection for EVT (SELECT), patients who received IV tPA vs. no IV tPA were compared stratified by stroke severity and ischemic core size (rCBF Results: Of 361 enrolled, 285 received EVT; 226 presented within 4.5 hrs, 162 (72%) received IV tPA. IV tPA patients had lower median ASPECTS (8 vs 9, p=0.007) and larger ischemic core size (11.4 (1.5-37) vs 3.9 (0-32.15), p=0.042, otherwise similar at baseline. There were no delays in EVT delivery associated with tPA: median time (IQR) from arrival to groin puncture 95.0 min (66.0, 118.0) tPA vs 81.5 (63.5, 107.5) no tPA, p=0.21. IV tPA use was associated with higher mRS 0-2 rates (57% vs 44%), aOR 2.02 (95% CI 1.01-4.03, p=0.046) after adjustment for baseline differences with a shift towards better outcomes on all mRS levels (cOR 2.06, 95% CI 1.18-3.59, p=0.01) with lower mortality (11% vs 22%, p=0.026) and similar sICH rates (and 6% vs 6%, p=1.0). In patients with NIHSS Conclusion: IV tPA did not result in thrombectomy delivery delays and may result in better outcomes. Patients with less severe strokes and smaller infarct size had a stronger association between the use of IV tPA and favorable outcomes.

Introduction: Many cell-based therapies attenuate secondary degeneration after initial ischemic injury and enhance repair. We serially compared over time the integrity of the corticospinal tract (CST) in ischemic stroke (IS) patients treated with autologous bone marrow cells versus a prospectively collected, comparable stroke patient population not treated with cells (controls). Methods: We imaged 37 IS patients (17=treated, 20=control) at 1, 3, and 12 mo after stroke on a 3T MRI. A maximum of 10 million cells/kg were administered IV within 72 hrs of stroke. 3D anatomical and DTI images were obtained. CST integrity was assessed by relative (ipsilesional/contralesional) rFA in the rostral pons (RP). A mixed model was used for statistical analysis. Results: Infarct size of controls was 26.4 ±27 mL and the treated group was 64.7 ± 40.3 mL. The rFA in the rostral pons (RP) of controls decreased from 0.91 ± 0.1 to 0.86 ± 0.1 over 12 months. In the cell treated group, rFA in the RP decreased initially from 0.73 ±0.1 to 0.69 ±0.1 between 1 and 3 months but then increased to 0.76 ± 0.1 at 12 months. Qualitative and quantitative results are summarized (fig). The rFA in the RP was significantly correlated (p Conclusion: Despite smaller infarct size in controls, CST integrity continued to degenerate and showed no improvement by 12 months after stroke. In contrast, the cell treated patients with initial larger infarcts showed initial degeneration of the CST but then had improved CST integrity by 12 months after stroke. The temporal decrease in rFA in controls and increase in rFA in treated patients suggest a potential treatment effect from the cells. Although the results are generated from a non-randomized trial, the significant correlation between mRS and rFA suggests rFA could be used as a surrogate marker of treatment effect.

Introduction: White matter tract (WMT) injury occurs in patients with acute cerebrovascular disorders. In this study, we elucidate longitudinal differences in mechanism of injury and repair between ischemic stroke (ISC) and intracerebral hemorrhage (ICH). Methods: Twenty patients (10 ISC and ICH) were prospectively imaged at 1, 3, and 12 months of onset on a 3T MRI. 3D anatomical and DTI images were obtained and integrity of the corticospinal tract (CST) assessed at the ipsi and contralesional posterior limb of internal capsule (PLIC). Fractional anisotropy (FA), mean diffusivity (MD) and pixel volume were recorded. A linear regression model was applied for statistical analysis. Results: ISC group had 4 men, 6 women whereas ICH group had 7 men, 3 women, both with average age 52. Baseline NIHSS in ISC was 11 (IQR=4.5-20) and ICH 6 (IQR=2-13). All lesions were unilateral, hemispheric, completely subcortical or with a significant subcortical component. The average lesion and hematoma volume at 1 month was 37 and 39 cc in ISC and ICH, respectively. The MD in the PLIC of the ISC increased from 1 to 3m (P Conclusions: ISC and ICH display unique patterns of WMT changes over one year in which ICH injury reflects a compression of the CST that resolves over time, while in ISC our data show degeneration and microstructural injury. These changes reflect different mechanisms of injury and remodeling on a cellular level. A better understanding of these changes could improve recovery therapies. Larger studies are needed to better characterize long term WMT changes in IS and ICH.

Background: Whether Endovascular Thrombectomy (EVT) is cost-effective in large ischemic core infarcts is unknown. Methods: In the prospective multicenter cohort study of imaging selection study (SELECT), large core was defined as CT ASPECTS < 6 or CTP ischemic core volume (rCBF Results: Of 361 enrolled, 105 had large core on CT or CTP (EVT 62, MM 43). 19 (31%) EVT patients achieved mRS 0-2 vs 6 (14%) MM (aOR: 3.27, 95% CI: 1.11-9.62; P = .03) with a shift towards better mRS (adj cOR: 2.12, 95% CI: 1.05-4.31, P = .04). Over 20 years EVT was associated with $26589 (C.I. $8672- $43978) incremental costs and a gain of 1.18 QALYs (C.I. 0.091- 2.2) per patient. EVT could avert 75 deaths over a theoretical cohort of 1000 patients (MM 861 vs EVT 786) thus the ICER of EVT compared to MM was $22400 per QALY (CI. $10109 - $66140), which is EVT has a higher NMB compared to MM at the lower and upper WTP thresholds (EVT $86,3 and 271,4 million vs MM $53,6-$179,3 million), Tab 2. The PSA confirmed the results (fig 1). The CEAC showed 94% and 97% cost-effectiveness probability of EVT at the lower and upper values respectively of the maximum WTP, fig 2. EVT ICER in SELECT large core ($22400/QALY) was higher but still comparable to those in HERMES ($16882/QALY), DAWN ($7335/QALY) and DEFUSE3 ($14673/QALY), Tab 3. Conclusion: EVT may result in better outcomes and more lives saved in large core patients with higher QALYs, NMB and an acceptable ICER. The results were comparable to other EVT RCTs.

Background: The efficacy of endovascular thrombectomy (EVT) in M2 occlusions is uncertain. Methods: In a prospective multicenter cohort study of imaging selection (SELECT), EVT outcomes were compared to medical managment (MM) in M2 occlusions. Further, we assessed for potential treatment benefit in patients with higher stroke severity (NIHSS) and a larger perfusion deficit on CTP (Tmax > 6 sec - ischemic core volume)The primary outcome was excellent outcome (mRS 0-1). Results: of 361 patients enrolled in SELECT, 87 had isolated M2 occlusion (EVT 59, MM 28). Baseline NIHSS median (IQR) (EVT 14 (10-20), MM 15 (9.5-19.5), p=0.72) and infarct volume rCBF10 had better outcomes with EVT (46%) vs MM (10%), aOR=11.39, 95% CI=1.80-72.11, p=0.01 as shown in figure 1. As perfusion deficit lesion size increased, the odds of achieving excellent outcomes was reduced (for each 10cc by 11%, aOR: 0.89, 95% CI=0.79-1.00, p=0.05). Excellent outcomes declined in patients with MM as perfusion deficit lesion size increased, yet in the EVT they were maintained as shown in figure 2. Similar results were obtained for mRS 0-2. Conclusion: EVT may result in better rates of excellent outcomes in isolated M2 occlusions, especially those with more severe strokes and larger perfusion deficits who are more likely to have worse outcomes without emergent reperfusion.

Nuclear medicine studies have previously been utilized to assess for blockage of cerebrospinal fluid (CSF) flow prior to intraventricular chemotherapy infusions. To assess CSF flow without nuclear medicine studies, we obtained cine phase-contrast MRI sequences that assess CSF flow from the fourth ventricle down to the sacrum. In three clinical trials, 18 patients with recurrent malignant posterior fossa tumors underwent implantation of a ventricular access device (VAD) into the fourth ventricle, either with or without simultaneous tumor resection. Prior to infusing therapeutic agents into the VAD, cine MRI phase-contrast CSF flow sequences of the brain and total spine were performed. Velocity encoding (VENC) of 5 and 10 cm/s was used to confirm CSF flow from the fourth ventricular outlets to the cervical, thoracic, and lumbar spine. Qualitative CSF flow was characterized by neuroradiologists as present or absent. All 18 patients demonstrated CSF flow from the outlets of the fourth ventricle down to the sacrum with no evidence of obstruction. One of these patients, after disease progression, subsequently showed obstruction of CSF flow. No patient required a nuclear medicine study to assess CSF flow prior to initiation of infusions. Fourteen patients have received infusions to date, and none has had neurological toxicity. CSF flow including the fourth ventricle and the total spine can be assessed noninvasively with phase-contrast MRI sequences. Advantages over nuclear medicine studies include avoiding both an invasive procedure and radiation exposure.

IMPORTANCE: A direct to angiography (DTA) treatment paradigm without repeated imaging for transferred patients with large vessel occlusion (LVO) may reduce time to endovascular thrombectomy (EVT). Whether DTA is safe and associated with better outcomes in the late (>6 hours) window is unknown. Also, DTA feasibility and effectiveness in reducing time to EVT during on-call vs regular-work hours and the association of interfacility transfer times with DTA outcomes have not been established. OBJECTIVE: To evaluate the functional and safety outcomes of DTA vs repeated imaging in the different treatment windows and on-call hours vs regular hours. DESIGN, SETTING, AND PARTICIPANTS: This pooled retrospective cohort study at 6 US and European comprehensive stroke centers enrolled adults (aged ≥18 years) with anterior circulation LVO (internal cerebral artery or middle cerebral artery subdivisions M1/M2) and transferred for EVT within 24 hours of the last-known-well time from January 1, 2014, to February 29, 2020. EXPOSURES: Repeated imaging (computed tomography with or without computed tomographic angiography or computed tomography perfusion) before EVT vs DTA. MAIN OUTCOMES AND MEASURES: Functional independence (90-day modified Rankin Scale score, 0-2) was the primary outcome. Symptomatic intracerebral hemorrhage, mortality, and time metrics were also compared between the DTA and repeated imaging groups. RESULTS: A total of 1140 patients with LVO received EVT after transfer, including 327 (28.7%) in the DTA group and 813 (71.3%) in the repeated imaging group. The median age was 69 (interquartile range [IQR], 59-78) years; 529 were female (46.4%) and 609 (53.4%) were male. Patients undergoing DTA had greater use of intravenous alteplase (200 of 327 [61.2%] vs 412 of 808 [51.0%]; P = .002), but otherwise groups were similar. Median time from EVT center arrival to groin puncture was faster with DTA (34 [IQR, 20-62] vs 60 [IQR, 37-95] minutes; P 6 to 24 hours; P = .88 for interaction). Three-month mortality was lower with DTA (53 of 312 [17.0%] vs 186 of 763 [24.4%]; P = .008). A 10-minute increase in EVT-center arrival to groin puncture in the repeated imaging group correlated with 5% reduction in the functional independence odds (aOR, 0.95 [95% CI, 0.91-0.99]; P = .01). The rates of modified Rankin Scale score of 0 to 2 decreased with interfacility transfer times of greater than 3 hours in the DTA group (96 of 161 [59.6%] vs 15 of 42 [35.7%]; P = .006), but not in the repeated imaging group (75 of 208 [36.1%] vs 71 of 192 [37.0%]; P = .85). CONCLUSIONS AND RELEVANCE: The DTA approach may be associated with faster treatment and better functional outcomes during all hours and treatment windows, and repeated imaging may be reasonable with prolonged transfer times. Optimal EVT workflow in transfers may be associated with faster, safe reperfusion with improved outcomes.

OBJECTIVE The primary imaging modalities used to select patients for endovascular thrombectomy (EVT) are noncontrast computed tomography (CT) and CT perfusion (CTP). However, their relative utility is uncertain. We prospectively assessed CT and CTP concordance/discordance and correlated the imaging profiles on both with EVT treatment decisions and clinical outcomes. METHODS A phase 2, multicenter, prospective cohort study of large-vessel occlusions presented up to 24 hours from last known well was conducted. Patients received a unified prespecified imaging evaluation (CT, CT angiography, and CTP with Rapid Processing of Perfusion and Diffusion software mismatch determination). The treatment decision, EVT versus medical management, was nonrandomized and at the treating physicians' discretion. An independent, blinded, neuroimaging core laboratory adjudicated favorable profiles based on predefined criteria (CT:Alberta Stroke Program Early CT Score ≥ 6, CTP:regional cerebral blood flow (

OBJECTIVE For research and risk factor analysis, a reproducible method quantifying atherosclerosis is necessary. Our aim was to develop a computed tomography (CT) angiography grading system to quantify atherosclerotic disease of the head and neck. METHODS Institutional review board-approved, retrospective analysis was performed on 152 patients who underwent head/neck CT angiography. A grading scale was designed to calculate plaque burden at multiple sites with the sum referred to as atherosclerosis score. Three radiologists calculated scores with an overlap of cases to calculate the intraclass correlation coefficient. RESULTS Without any prior training, the intraclass correlation coefficient between readers was considered fair. After a short tutorial, intraclass correlation coefficient was recalculated using separate patients, showing excellent correlation.Statistically significant positive correlation was found between atherosclerosis scale and age, hyperlipidemia, hypertension, and diabetes, but no correlation with sex or smoking status. CONCLUSIONS A simple, visual grading scale for atherosclerosis in head/neck CT angiography was used to standardize reporting and better characterize a patient's risk of stroke.

Purpose: Ongoing post-stroke structural degeneration and neuronal loss preceding neuropsychological symptoms such as cognitive decline and depression are poorly understood. Various substructures of the limbic system have been linked to cognitive impairment. In this longitudinal study, we investigated the post-stroke macro- and micro-structural integrity of the limbic system using structural and diffusion tensor magnetic resonance imaging.Materials and Methods: Nineteen ischemic stroke patients (11 men, 8 women, average age 53.4 ± 12.3, range 18–75 years), with lesions remote from the limbic system, were serially imaged three times over 1 year. Structural and diffusion-tensor images (DTI) were obtained on a 3.0 T MRI system. The cortical thickness, subcortical volume, mean diffusivity (MD), and fractional anisotropy (FA) were measured in eight different regions of the limbic system. The National Institutes of Health Stroke Scale (NIHSS) was used for clinical assessment. A mixed model for multiple factors was used for statistical analysis, and p-values

Purpose: Cell-based therapy offers new opportunities for the development of novel treatments to promote tissue repair, functional restoration, and cerebral metabolic balance. N-acetylasperate (NAA), Choline (Cho), and Creatine (Cr) are three major metabolites seen on proton magnetic resonance spectroscopy (MRS) that play a vital role in balancing the biochemical processes and are suggested as markers of recovery. In this preliminary study, we serially monitored changes in these metabolites in ischemic stroke patients who were treated with autologous bone marrow-derived mononuclear cells (MNCs) using non-invasive MRS.Materials and Methods: A sub-group of nine patients (3 male, 6 female) participated in a serial MRS study, as part of a clinical trial on autologous bone marrow cell therapy in acute ischemic stroke. Seven to ten million mononuclear cells were isolated from the patient's bone marrow and administered intravenously within 72 h of onset of injury. MRS data were obtained at 1, 3, and 6 months using a whole-body 3.0T MRI. Single voxel point-resolved spectroscopy (PRESS) was obtained within the lesion and contralesional gray matter. Spectral analysis was done using TARQUIN software and absolute concentration of NAA, Cho, and Cr was determined. National Institute of Health Stroke Scale (NIHSS) was serially recoreded. Two-way analysis of variance was performed and p < 0.05 considered statistically significant.Results: All metabolites showed statistically significant or clear trends toward lower ipsilesional concentrations compared to the contralesional side at all time points. Statistically significant reductions were found in ipsilesional NAA at 1M and 3M, Cho at 6M, and Cr at 1M and 6M (p < 0.03), compared to the contralesional side. Temporally, ipsilesional NAA increased between 3M and 6M (p < 0.01). On the other hand, ipsilesional Cho showed continued decline till 6M (p < 0.01). Ipsilesional Cr was stable over time. Contralesional metabolites were relatively stable over time, with only Cr showing a reduction 3M (p < 0.02). There was a significant (p < 0.03) correlation between ipsilesional NAA and NIHSS at 3M follow-up.Conclusion: Serial changes in metabolites suggest that MRS can be applied to monitor therapeutic changes. Post-treatment increasing trends of NAA concentration and significant correlation with NIHSS support a potential therapeutic effect.

Introduction: Endovascular therapy (EVT) improves clinical outcomes in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). Transfer from a referring hospital (RH) to a comprehensive stroke center (CSC) renders some patients ineligible for EVT due to infarct expansion. We evaluated the association of clinical and imaging factors, and the effect of time on infarct expansion using CT ASPECTS decay, subsequent impact on thrombectomy decision and consequent clinical outcomes. Methods: We retrospectively analyzed data on patients with AIS from LVO transferred for potential EVT from a RH to our comprehensive stroke center (hub) between September 2015 and December 2017. Patients were stratified into two groups, CT decay vs. CT non-decay, where CT ASPECTS decay was defined as deterioration of score from ≥6 at RH to > 6). Baseline characteristics, clinical and imaging variables were assessed for association with decay. Good outcomes (90 day mRS 0-2) were compared between the two groups. Multivariable logistic regression was applied to identify the independent predictors for decay and the adjusted odds ratio (aOR) was calculated. Results: Of a total 154 patients, 32 (21%) had ASPECTS decay. Baseline characteristics were similar in both groups except patients with decay had higher NIHSS [Median (IQR), 21(16, 25) vs. 16 (11, 21); P Conclusion: In patients transferred for potential EVT, severity of stroke at initial presentation and poor collateral circulation had significant impact on ASPECTS deterioration. This information can be employed to develop stroke systems of care to triage patients with LVO to a CSC

Background: Whether bridging therapy with IV tPA delays endovascular thrombectomy (EVT) or alters clinical outcomes is unknown. Methods: In this prospective multicenter cohort study of imaging selection for EVT (SELECT), consecutive patients with anterior circulation (ICA, M1, M2) occlusions who presented within 24 hrs from last known well were enrolled at 9 centers. We stratified patients into those who received IV tPA prior to EVT vs those who did not. Results: Of 445 enrolled, 284 received EVT; 222 (78%) treated within 6 hrs and 62 (22%) >6-24 hrs. 65% received IV tPA. Baseline characteristics were similar between the tPA and no tPA groups. There were no workflow delays associated with IV tPA: arrival to groin puncture, median (IQR) 92 (64-117) min in the tPA group vs. 82 (64-113) no IV tPA, p=0.52. The rate of functional independence (90 day mRS 0-2) was 57% with IV tPA vs. 47% without, aOR 1.7 (95% CI 0.95-3.05), p=0.07. The ordinal analysis showed a significant shift towards better 90 day mRS scores in the tPA group, aOR 1.9, 95% CI: 1.19-3.00, p=0.007. Mortality was 11% (tPA) vs 18% (no tPA), p=0.07 and sICH rates were 7% (tPA) vs. 5% (no tPA), p=0.5. Restricting the analyses to patients presenting directly to EVT centers within 4.5 hours (N=115), no significant delays were evident; arrival to puncture with tPA 95 (76-121) min vs 86 (68-114) without tPA, p=0.4. Functional independence was 62% with tPA vs 51% without, aOR 1.73 (95% CI 0.78-3.83, p=0.18) with a statistically significant shift in favor of tPA on the ordinal analysis, aOR 1.8, 95% CI: 1.08-3.45, p=0.038. Patients with M2 occlusions, smaller baseline infarct core volume, earlier treatment, and milder strokes were most likely to have better outcomes with tPA vs no tPA (Fig 1). Conclusion: IV tPA administration did not result in delays to EVT and was associated with higher rates of good outcome. Randomized trials are required to more definitively establish the efficacy of bridging therapy with tPA prior to EVT.

Background: Large infarct cores on CT or CTP were an exclusion from most trials of Endovascular thrombectomy (EVT). However, large cores may be seen in occasional patients presenting within the early window (0-3 hours) and may not preclude potential benefit from thrombectomy. We studied clinical outcomes with thrombectomy in patients presenting with large cores measured by CT or CTP within 3 hours of last known well (LKW). Methods: From a multicenter prospective cohort study of imaging selection for EVT (SELECT), patients with a large ischemic core (CBF 50cc or ASPECT≤5 presenting within 3 hours from LKW to imaging were identified. All patients received CT and CTP with mismatch determination by RAPID software. A blinded independent core-lab adjudicated all images. Good (90 day mRS 0-2) and safety (sICH and mortality) outcomes were compared between patients who received EVT and those with medical management (MM) only. Results: Of 445 patients enrolled, 54 met criteria for large core and early presentation; 28 had ASPECT≤5 (17 EVT, 11 MM) and 40 had CTP >50 cc (26 EVT, 14 MM) and 14 on both CT and CTP. Median (IQR) age 66 years (60, 75), NIHSS 20 (18, 23), LKW to puncture 162 min (range 69-343). Baseline characteristics were similar between EVT and MM. Patients with large core whether on CT (ASPECT≤5) or CTP (CBF>50cc) had more frequent good outcome with EVT (30% overall, CT 35%, and CTP 27% vs 0% MM, p=0.04, Fig 1) Furthermore, EVT resulted in smaller average final infarcts (77 vs 202 ml, p=0.03), similar mortality (31% vs 29%, p=0.87) and sICH (16% vs 6%,p=0.34). In patients who achieved good outcome with thrombectomy, EVT resulted in smaller infarct growth 31 ml (10-58) vs 111 cc (67-233) in patients who had poor outcome, p=0.01. Outcome rates were similar if large core was defined as >70ml. Conclusion: Patients with large core infarct measured by CT or CTP presenting within 3 hours may benefit from EVT. Time may trump imaging in patients with large core who present early.

Background: It is unknown if repeat imaging of transfer patients for endovascular thrombectomy (EVT) results in better patient selection and improved clinical outcomes or if bypassing repeat imaging and direct transfer to the angiosuite is safe, saves time and improve outcomes. Methods: A multicenter retrospective cohort was pooled from 6 centers (Europe and US) from 1/2014 to 4/2018 of patients with anterior circulation occlusion (ICA, M1, M2) transferred for EVT up to 24 hours from last known well. Patients were divided based on imaging acquisition at the EVT center into those who underwent any repeat imaging (CT+/- CTA, CTP) and those who bypassed imaging and went directly to the angiosuite. We compared good outcome (90 day mRS 0-2) and safety (sICH, mortality) between the two groups. Results: Of 646 patients, 559 received EVT and 87 were excluded for poor imaging profiles. In patients who received EVT, 173 (31%) had no repeat nd 386 (69%) had repeat images. The two groups had similar age and NIHSS. ASPECTS was lower in the repeat images group 8(7-10) when compared to ASPECTS from the outside facility in the non-repeat 9(8-10), p Conclusion: In patients transferred for EVT, repeat imaging resulted in treatment delays without improving good outcome. Direct angio suite access may result in more patients treated safely who achieve good outcome.

Background: While CT ASPECT scores predict clinical outcomes, the association between the scores and ischemic lesion volume is not linear as the subcortical regions involve small volumes while the cortical areas often involve large volumes. We evaluated whether ASPECTS and CTP ischemic core volume, modify each other’s association with clinical outcome in patients undergoing endovascular thrombectomy (EVT). Methods: In a prospective multicenter cohort study of imaging selection (SELECT), anterior circulation large vessel occlusion patients up to 24 hours from last known well were enrolled at 9 centers. All patients received a unified imaging profile (NCCT, CTA, and CTP with ischemic core volume [rCBF Results: Of 445 enrolled, 284 received EVT and are included in this analysis. Median (IQR) ASPECTS was 8 (7-9), median (IQR) ischemic core volume 10 ml (0-33). Both ASPECTS and ischemic core volume independently correlated with good outcome after EVT. For ASPECTS, the probability of good outcome decreased by 14% per point (aOR 1.18, 95% CI 1.01-1.38, p=0.03). For CTP mRS 0-2 probability dropped by 25% for each 10 ml increase in core volume (aOR 0.75, 95% CI 0.67-0.84, P Conclusion: ASPECTS association with clinical outcome after EVT was strongly modified by ischemic core volumes. Favorable outcomes were achieved in patients with small ischemic core volume despite low ASPECTS.

Background: We assessed the correlation between early infarct growth rate (EIGR), collaterals and clinical outcomes following endovascular thrombectomy (EVT). Methods: In a prospective multicenter cohort study of imaging selection for EVT (SELECT), consecutive patients with large vessel occlusion (ICA, M1, M2) presenting up to 24 hr from last known well (LKW) were enrolled at 9 centers. CT perfusion was obtained prior to EVT. EIGR was defined as CTP ischemic core volume (rCBF> 2. Results: Of 445 enrolled, 284 received EVT. The optimal EIGR was Conclusion: The early infarct growth strongly correlates with both collateral status and clinical outcomes after EVT. Fast progressors have a much more rapid decline in favorable outcomes at late treatment times.

Background: Endovascular thrombectomy (EVT) efficacy and safety is not established in patients with large core. We evaluated the clinical and radiologic outcomes following EVT in acute strokes with large ischemic core lesions defined by CT ASPECTS and/or CTP. Methods: From a multicenter prospective cohort study of imaging selection for thrombectomy (SELECT), patients with large ischemic core on CTP (rCBF< 30%) >50 ml and/or ASPECT≤5 up to 24 hrs from last known well were identified at 9 U.S centers. All patients received a baseline CT and CTP with automated ischemic core determination by RAPID. A blinded core lab adjudicated all images. The primary outcome was 90 day mRS 0-2. Safety outcomes were sICH and mortality. Outcomes of EVT patients were compared to those who received medical management (MM) only. Results: Of 445 enrolled, 106 had large core on either CT or CTP: 71 ASPECTS≤5 (EVT 37, MM 34) and 75 CTP core >50 ml (EVT 40, MM 35), 40 on both CT and CTP. Median (IQR) age 66 yr, NIHSS 20 (16-23), time to puncture 224 min (range 69-832), ASPECTS 5 (4-6) and CTP core 72 ml (41-96). Baseline characteristics were similar in EVT vs. MM patients in both CT and CTP definition groups. The EVT group had better mRS 0-2 rates as compared to MM (32 % vs 14%), aOR: 2.9 (95% CI: 1.0-7.9, p=0.041) and a favorable mRS shift on ordinal analysis aOR: 2.0 (95% CI 1.0-4.1, p=0.049), smaller final infarct volume 96 (49-196) vs 175 (127-225) ml, p=0.02, and less infarct growth 44 (0.7-107.6) vs 83 (61-133) ml, p=0.03 with similar mortality 29% EVT, 42% MM, p=0.16 and sICH 13% EVT, 7% MM, p=0.3. EVT patients were more likely to achieve mRS 0-2 if treated early (0-6) vs late (>6-24 hrs) for both CTP defined (27% vs 0%) and CT defined large core (44% vs. 18%). The good outcome declined by 20% for each hr of treatment delay (Fig 1). Conclusion: EVT may be effective and safe for patients with a large core, especially if treated early. RCTs are needed.

Background Endovascular thrombectomy RCTs used different imaging selection modalities and criteria. Early window (0–6 hours) trials mostly used simple CT, while DAWN and DEFUSE3 utilized advanced perfusion images (CTP/MRP) beyond 6 hours. Thus, optimal imaging selection criteria for thrombectomy is unknown. Method In this multicenter prospective cohort study, consecutive anterior-circulation large vessel occlusion patients up-to-24 hours from last-known-normal were enrolled in 9 centers (January/16–February/18). All patients received CT and CTP with mismatch determination using RAPID software. Treating physicians documented imaging selection modality prior to thrombectomy. Patients were divided based on selection modality into CT versus CTP groups. A blinded independent core-lab adjudicated imaging profiles defined a priori (Good CT=ASPECTS≥6, Good CTP=core vol 1.2). The primary outcome (90 day mRS=0–2) was compared between the CT and CTP groups and for different CT and CTP profiles. Results Of 445 patients enrolled, 341 received thrombectomy (figure 1). Median/IQR age=66/57–77, NIHSS=17/12–21, LSN-to-GP=3.8 hours/2.6–5.7 (range=1.2–17.6). 20% had ICA occlusions, 62% M1, and 18% M2. Selection modality was CT in 42% and CTP in 58%, with similar good outcome (CT=53.3% vs 54.3%=CTP, aOR=0.6,95% CI: 0.3 to 1.5, p=0.3, figure 2a). There was no interaction with time, early vs late window, p=0.1. 87% had good CT and 89.6% had good CTP with comparable good outcome (CT=55.7% vs CTP=57.3, aOR=2.2, 95% CI: 0.5 to 10.9, p=0.3, figure 2b). In early window, the good outcome rates were 54.9% for good CT and 58% for good CTP; for late window, they were 58.7% and 57.1%, respectively. There was no interaction with time (p=0.5). 16.8% would have been excluded from thrombectomy based on either CT or CTP only; 40.5% of them had good outcome. Of patients potentially excluded by CT but qualified by CTP, 50% had good outcomes with thrombectomy and 33% with medical management only. Similarly, of those excluded by CTP but treated by CT, 27.8% had good outcomes with and 0% without thrombectomy, respectively (table 1). Furthermore, discordant profiles patients (Good CT-Poor CTP and Poor CT-Good CTP) with good reperfusion (mTICI ≥2b) had higher good outcome rates, compared to mTICI Thrombectomy did not confer good outcomes in patients with Poor CT-Poor CTP. Conclusion Good outcome rates were comparable in patients selected for thrombectomy by CT versus CTP and those with good imaging profiles on either CT or CTP irrespective of the treatment time window, early or late. However, both imaging modalities excluded a similar number of patients who may benefit from the intervention. Our results will be validated in a randomized trial (SELECT2). Disclosures A. Sarraj: 1; C; Principal Investigator of the SELECT and SELECT 2 trials – unrestricted grant from Stryker Neurovascular to UT McGovern-Houston. 2; C; Consultant and Speaker for Stryker Neurovascular, Advisory Board – Stryker Neurovascular. 6; C; UT-Memorial Hermann Center PI for the Trevo Registry and DEFUSE 3 TRIAL, Steering Committee –ASSIST Registry. A. Hassan: None. R. Gupta: None. C. Sitton: None. J. Grotta: None. C. Cai: None. G. Cutter: None. B. Imam: None. S. Reddy: None. K. Parsha: None. N. Vora: None. M. Abraham: None. R. Edgell:None. F. Hellinger: None. D. Haussen: None. H. Kamal: None. L. McCullough: None. M. Lansberg: None. S. Savitz: None. G. Albers: None.

We hypothesize that chemotherapy can be safely administered directly into the fourth ventricle to treat recurrent malignant brain tumors in children. For the first time in humans, methotrexate was infused into the fourth ventricle in children with recurrent, malignant brain tumors. A catheter was surgically placed into the fourth ventricle and attached to a ventricular access device. Cerebrospinal fluid (CSF) flow was confirmed by CINE MRI postoperatively. Each cycle consisted of 4 consecutive daily methotrexate infusions (2 milligrams). Disease response was monitored with serial MRI scans and CSF cytologic analysis. Trough CSF methotrexate levels were sampled. Five patients (3 with medulloblastoma and 2 with ependymoma) received 18, 18, 12, 9, and 3 cycles, respectively. There were no serious adverse events or new neurological deficits attributed to methotrexate. Two additional enrolled patients were withdrawn prior to planned infusions due to rapid disease progression. Median serum methotrexate level 4 h after infusion was 0.04 µmol/L. Range was 0.02-0.13 µmol/L. Median trough CSF methotrexate level 24 h after infusion was 3.18 µmol/L (range 0.53-212.36 µmol/L). All three patients with medulloblastoma had partial response or stable disease until one patient had progressive disease after cycle 18. Both patients with ependymoma had progressive disease after 9 and 3 cycles, respectively. Low-dose methotrexate can be infused into the fourth ventricle without causing neurological toxicity. Some patients with recurrent medulloblastoma experience a beneficial anti-tumor effect both within the fourth ventricle and at distant sites.

Computerized tomography perfusion (CTP) has been widely studied in assessing physiological brain tissue parameters in patients with acute ischemic stroke (AIS). The utility of CTP to predict clinical outcome in patients with AIS treated with intravenous tissue plasminogen activator (IV t-PA) is controversial. We reviewed CTP data in AIS patients treated with IV t-PA to uncover potential predictors of clinical outcome.We retrospectively identified AIS patients from our stroke registry (7/07 to 2/10) who underwent CTP on arrival and then received IV t-PA. A neuroradiologist blinded to outcome performed all CTP parameter measurements on a commercially available Siemens Neuro PCT workstation. Tissue at risk (TAR) was defined as the area of infarct territory with a relative time to peak (rTTP) greater than 4s. Non-viable tissue (NVT) was defined as the area of infarct territory with absolute cerebral blood volume (CBV) less than 2 ml/100g and cerebral blood flow (CBF) less than 12.7 ml/100g/min. Penumbra was defined as the area of (TAR) minus the area of (NVT). Excellent clinical outcome was defined as mRS (0-1), good clinical outcome was defined as mRS (0-2), and poor clinical outcome was defined as mRS (4-6), all measured at hospital discharge and 90 days if available. Recanalization data was obtained when available by comparing pre-thrombolytic CTA data and post-treatment MRA/CTA images by a single blinded radiologist.We identified 61 patients that met our inclusion criteria with a mean age of 68 (29-94), median NIHSS on admission of 13 (1-40), and median discharge mRS of 4 (0-6). Using multivariate logistic regression and ordinal logistic regression controlling for age and admission NIHSS, none of the CTP parameters were statistically associated with excellent or good clinical outcome (mRS2). Using multivariate analysis controlling for age and admission NIHSS, NVT area30 cm(2) (OR=5.12, CI: 0.95-27, p=0.05) was statistically associated with poor clinical outcome at discharge. NVT area ≥ 30 cm(2) was a potential predictor of poor outcome at discharge even when controlling for age and NIHSS.CTP parameters derived from commercially available software and published thresholds yield little predictive value for good clinical outcomes for AIS patients treated with IV t-PA but may be useful in predicting poor clinical outcome especially if the area of non-viable tissue is greater than 30 cm(2).