Portal de Periódicos da CAPES

Collateral Circulation in Ischemic Stroke

2015; Lippincott Williams & Wilkins; Volume: 46; Issue: 11 Linguagem: Inglês

10.1161/strokeaha.115.010508

1524-4628

Oh Young Bang, Mayank Goyal, David S. Liebeskind,

Stroke Rehabilitation and Recovery

HomeStrokeVol. 46, No. 11Collateral Circulation in Ischemic Stroke Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplemental MaterialFree AccessResearch ArticlePDF/EPUBCollateral Circulation in Ischemic StrokeAssessment Tools and Therapeutic Strategies Oh Young Bang, MD, PhD, Mayank Goyal, MD and David S. Liebeskind, MD Oh Young BangOh Young Bang From the Department of Neurology, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea (O.Y.B.); Department of Radiology and Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada (M.G.); and Neurovascular Imaging Research Core and Department of Neurology, Comprehensive Stroke Center, Geffen School of Medicine, University of California, Los Angeles (D.S.L.). , Mayank GoyalMayank Goyal From the Department of Neurology, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea (O.Y.B.); Department of Radiology and Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada (M.G.); and Neurovascular Imaging Research Core and Department of Neurology, Comprehensive Stroke Center, Geffen School of Medicine, University of California, Los Angeles (D.S.L.). and David S. LiebeskindDavid S. Liebeskind From the Department of Neurology, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea (O.Y.B.); Department of Radiology and Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada (M.G.); and Neurovascular Imaging Research Core and Department of Neurology, Comprehensive Stroke Center, Geffen School of Medicine, University of California, Los Angeles (D.S.L.). Originally published8 Oct 2015https://doi.org/10.1161/STROKEAHA.115.010508Stroke. 2015;46:3302–3309Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2015: Previous Version 1 Revascularization encompasses all treatment-related improvements in blood flow, including recanalization of the proximal arterial occlusion and reperfusion of the downstream territory. Recanalization is required for antegrade tissue reperfusion, but recanalization may not necessarily lead to reperfusion in regions where distal emboli or established infarctions are present.1,2 On the contrary, acute reperfusion without recanalization may occur in patients who received or did not received endovascular therapies, and reperfusion ≤6 hours was consistently superior to recanalization in predicting tissue and clinical outcome.3 The cerebral collateral circulation refers to the subsidiary network of vascular channels that stabilize cerebral blood flow when principal conduits fail. Collateral status differs among patients with acute ischemic stroke. Relatively sparse attention has been devoted to the role of baseline collateral circulation in patients with acute ischemic stroke who are candidates for revascularization.The Interventional Management of Stroke (IMS) III,4 Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE),5 and Intra-Arterial Versus Systemic Thrombolysis for Acute Ischemic Stroke (SYNTHESIS EXP) trials6 were 3 multicenter, prospective, randomized controlled trials, which failed to show a benefit from endovascular intervention for acute ischemic stroke. In addition, successful recanalization failed to improve the functional outcome in a significant proportion of patients, ranging from 26% to 49% (futile and dangerous recanalization), stimulating the need to improve the selection of patients based on individual pathophysiology.7,8Among neuroimaging parameters, a large core and poor collaterals are demonstrated to be strong predictors of both response to endovascular therapy and functional outcome,9–13 and excluding patients with large core and poor collateral circulation may improve the therapeutic benefit from endovascular therapy. In the subgroup analysis of the IMS III trial, more robust collateral grade was associated with better clinical outcomes.14 Adequate collateral circulation may contribute to the maintenance of tissue viability in the absence of recanalization. In both intravenous thrombolysis and endovascular trials, shorter time to treatment was associated with better odds for positive outcome.15–17 However, stroke patients presenting at later time points may still benefit from endovascular therapy,18 and the time to treatment was a predictor of outcome only when collaterals were not considered, suggesting the important role of collaterals for the determination of this time window.19 Good pial or leptomeningeal collateral circulation predicts better clinical responses to intra-arterial treatment even 5 hours after the onset of the stroke, suggesting that collateral status could extend the time window for endovascular procedures.20,21 Therefore, collateral flow to penumbral tissue beyond the clot has clinical implications in the setting of acute endovascular therapy (Figure 1).Download figureDownload PowerPointFigure 1. Impact of collateral flow to penumbral tissue and occluding clot. tPA indicates tissue-type plasminogen activator.With the lessons from the aforementioned randomized clinical trials published 2013, the recent phase III randomized control trials have been conducted; the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN),22 Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE),23 Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial (EXTEND-IA),24 Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke (SWIFT PRIME),25 and Endovascular Revascularization With Solitaire Device Versus Best Medical Therapy in Anterior Circulation Stroke Within 8 hours (REVASCAT) trials.26 Most studies addressed the large core (as measured by the ASPECT score <5–7 points) and 1 study (the ESCAPE trial) poor collaterals in their exclusion criteria. In the ESCAPE trial, collateral status was measured in most cases by multiphasic computed tomography (CT) angiography, a dedicated CT technique to exclude patients with absent collateral.23,27 New evidence from these new randomized trials has demonstrated an overwhelming benefit from endovascular intervention, preferably with stent retriever–mediated mechanical thrombectomy, for the treatment of acute ischemic stroke secondary to large arterial occlusion. Beside the endovascular therapy field, the results of recent stroke prevention trials (Warfarin Aspirin Symptomatic Intra-Cranial Disease [WASID] and Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis [SAMMPRIS]) and thrombolysis trials (Desmoteplase in Acute Ischemic Stroke-2 [DIAS-2]) have also emphasized the importance of collateral circulation.28,29Images for Assessment of Collateral Status Using CT or Magnetic Resonance ImagingConventional angiographic evaluation has advantages, including its reliable demonstration of occlusion versus subtotal occlusion, well standardized recanalization grading, and high resolution visualization of leptomeningeal collaterals.1,30 However, it has several limitations. First, because conventional angiography is invasive, it requires more expertise and time to perform and carries a small risk of thrombotic events. Second, the results of angiographic collateral studies would mostly be incomplete (eg, not including the venous phase, no contralateral or vertebrobasilar view), especially in acute setting. In addition, it is not possible to simultaneously examine both anterior and poster circulation-derived collaterals (Figure 1). Finally, the information obtained about the effect of collateral status on the anterior and lateral views in conventional angiography cannot easily be correlated with axial images typically used to depict CT or magnetic resonance imaging (MRI) of ischemic injury. Various efforts have been made to visualize collateral flow using CT or MRI (Figure 2).Download figureDownload PowerPointFigure 2. Various neuroimaging parameters representing the infarcted area and collateral status. Arrow indicates the distal hyperintense vessels. ASL indicates arterial spin labeling; CBF, cerebral blood flow; CBV, cerebral blood volume; CT, computed tomography; DWI, diffusion weighted imaging; ESCAPE, Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times; FLAIR, Fluid Attenuation Inversion Recovery; and MRP, magnetic resonance perfusion. *Based on the contralateral side.Alberta Stroke Program Early CT ScoreThe Alberta Stroke Program Early CT Score (ASPECTS) on baseline imaging is an established predictor of acute ischemic stroke outcome. Both nonenhanced CT and contrast-enhanced CT ASPECTS showed a good correlation with leptomeningeal collateral grade on conventional angiography.31 Hypoattenuation on noncontrast CT is caused by a shift in brain tissue water content secondary to ischemia, and this process is dependent on the time and the degree of ischemia. To increase the interrater reliability of nonenhanced CT ASPECTS, especially in early phase of infarction, ASEPCTS on CT angiography source image has been developed that is less time dependent.32 The ASPECTS on contrast-enhanced CT or CT angiography source image showed better correlation with baseline stroke severity and infarct growth than nonenhanced CT ASPECTS.33Multiphasic CT and CT AngiographyMultiphasic contrast-enhanced CT collateral grades showed a good correlation with leptomeningeal collateral grade on conventional angiography in acute ischemic stroke34,35 and have been used as a prediction tool for final infarct volume, infarct growth, subsequent brain edema, and clinical response after thrombolysis.36–38 More recently, the ESCAPE trialists developed a 6-point score system for pial arterial filling using multiphasic CT angiography, which showed a good interrater reliability and ability to help determine clinical outcome.27 This technique is a quick and easy-to-use and needs minimal additional radiation and no additional contrast material and no postprocessing.CT PerfusionCT perfusion may provide information of collateral status, as well as core and penumbra. CT perfusion has the advantage of rapidity and wide accessibility in emergency room and can be combined with nonenhanced CT and CT angiographic data, especially in patients with anterior circulation stroke.39,40 One retrospective study showed that the most accurate assessment of the site of occlusion, infarct core, salvageable brain tissue, and collateral circulation in patients suspected of acute stroke is afforded by a combination of CT perfusion and CT angiography.39 CT perfusion and CT angiography provide differential assessment of collateral circulation and functional and anatomic aspects, respectively.41 Cerebral blood volume may be elevated or within the normal range depending on effectiveness of collateral supply. Moreover, virtual CT perfusion can be obtained using CT angiographic information.42 CT perfusion–based selection was used in 2 recent randomized control trials of revascularization therapy (tenecteplase and thrombectomy).24,43 However, more specific CT perfusion criteria for collateral assessment are yet to be determined.Conventional MRIThe diffusion-weighted image lesion volume and pattern are associated with the degree of collateral flow in acute ischemic stroke.44,45 A large lesion volume and cortical lesion pattern (regardless of the lesion volume) on diffusion-weighted image are frequently found in patients with poor collaterals. Fluid attenuation inversion recovery images can also provide information about collateral status. The presence of distal hyperintense vessels or fluid attenuation inversion recovery vascular hyperintensities and the absence of perisylvian sulcal effacement are associated with good collaterals and favorable outcome in patients with acute middle cerebral artery stroke.46,47 Similarly, conspicuous flow voids, deoxygenation seen as hypointensity, or disappearing phase mismapping on gradient echo image may also be clues about the collateral status.48Dynamic Susceptibility Contrast MR PerfusionVarious MR perfusion parameters have been used to measure collateral status. Compared with patients with poor collaterals, those with good collaterals show less severe delays in Tmax and relatively preserved (or even increased) cerebral blood volume within ischemic regions.10 Optimal MR perfusion parameter to predict collateral grade has seldom been reported. In our Tmax severity-weighted probabilistic model, collateral status was determined by the presence of delayed perfusion (Tmax of 16–22 s) rather than by the presence of a shorter delay in perfusion (Tmax ≤10).49 In addition, collateral circulation can be easily visualized by simple postprocessing using the source data of dynamic susceptibility contrast MRI. Christensen et al50 reported the potential use of novel postprocessing and visualization techniques (subtracting the image of the first movement map) for evaluating collaterals using bolus tracking MRI. Campbell et al developed collateral vessel grading using a digitally subtracted perfusion MRI and showed that deterioration in collateral grade correlated with subsequent infarct growth.51 We have applied a simple semiautomatic collateral map technique (Fast Analysis System for Collaterals [FAST-Coll] program) using perfusion scan source data to assess collateral grade in acute ischemic stroke.52 A good correlation was observed between MR- and conventional angiography-based collateral assessment systems. These techniques have an advantage in that the information about collateral status can be directly compared with MR diffusion and perfusion image, and there is no need for additional acquisition of conventional angiography or MRI dedicated for collateral assessment.Arterial Spin Labeling MRIArterial spin labeling (ASL) is a noncontrast perfusion imaging method to measure cerebral blood flow that relies on the magnetic labeling of arterial water. ASL is a promising technique for the assessment of collateral flow that can provide various types of information about collateral status. With ASL, late-arriving flow seems as a serpiginous high ASL signal within cortical vessels, which has been termed arterial transit artifact. Patients with arterial transit artifact had improved outcomes, suggesting that this signal may represent collateral flow.53,54 In addition, flow direction–sensitive phase contrast MR angiography (MRA) and vessel-encoded arterial spin labeling could noninvasively provide information about the origins and distal function of collateral flow comparable with that obtained with conventional angiograms.55,56 Finally, ASL can provide anatomic (ASL MRA) and dynamic blood flow (time-resolved) information in the circle of Willis, similar to that obtained with conventional angiography without the use of exogenous contrast agents.57,58Imaging Techniques to Visualize Collateral ArteriesVarious modalities have been used to noninvasively measure collateral flow, such as transcranial Doppler, CT angiography, or MRA.59 CT or MRA can evaluate the cerebral collateral circulation in the circle of Willis with moderate-to-good diagnostic performance, but has limitation in the evaluation of leptomeningeal collaterals. Recent advances in 7-Tesla MRI have enabled the direct visualization of pial branches in cerebral arterial disease, indicating the possibility of assessing leptomeningeal collaterals with high-resolution MRA.60 However, this technique is not feasible in patients with acute stroke.Advantages and Disadvantages of Various Neuroimaging TechniquesAs shown in Table 1, they differ greatly depending on the technique used in the assessment of collateral status. Although there are various ways to determine collaterals using MRI, these may have limited usefulness in light of (1) recent trials where mostly CT was used; (2) further overwhelming data for the need for speed. It is unlikely that in the near future, MRI images can be obtained at the same efficiency as CT-based imaging. MRI techniques for collateral status deserve further investigation but are not yet ready for implementation as a valid predicting neurological biomarker in stroke reperfusion trials for the following aspects.Table 1. Advantages and Disadvantages of Various Neuroimaging Techniques for Collateral AssessmentImagesA Good Correlation With Conventional Angiographic Collateral GradeClinical TrialsAdvantagesDisadvantagesConventional angiographyNoneReference standardInvasiveASPECTS scoreASPECTS on contrast-enhanced than nonenhanced CT31ESCAPE23SWIFT PRIME,25 REVASCAT26Easy-to-useRoutine studyRelatively low interrater reliability61Collaterals not visualizedMultiphasic CTMultiphasic perfusion CT collateral grades34,35ESCAPE23Easy-to-useRadiationNeeds contrast dyeDiffusion-weighted imageInfarct volume44Infarct pattern45BRASIL62DEFUSE63Routine MRI studyMany confoundersCollaterals not visualizedFLAIR and gradient echo imageDistal hyperintense vessel on FLAIR46Observational studiesRoutine MRI studyPoor visualizationMR or CT perfusionTmax severity10,49DEFUSE63EPITHET64MR RESCUE5EXTEND-IA24SWIFT PRIME25Quantitative and good visualizationNeeds postprocessingNeeds contrast dyeMore specific criteria for collateral assessment are neededMR-based collateral imageCollateral map using DSC PWI source data52Observational studiesGood visualizationSimple postprocessing performed at workstationsCovers the entire vascular phaseNeeds validationArterial spin labelingVessel-encoded ASL55,56Arterial transit artifact53iCASOther ongoing studies*Vessel selective informationNo contrast dyeContamination from the partial labeling of the nearby vessels or antegrade flowT1 decay of the label may limit the extent to which slow inflows can be imagedASL indicates arterial spin labeling; ASPECTS, Alberta Stroke Program Early CT Score; BRASIL, Bleeding Risk Analysis in Stroke; CT, computed tomography; DEFUSE, Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Imaging Before Thrombolysis; EPITHET, the Echoplanar Imaging Thrombolysis Evaluation Trial; ESCAPE, Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times; EXTEND-IA, Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial; FLAIR, Fluid Attenuation Inversion Recovery; iCAS, imaging collaterals in acute stroke; MRI, magnetic resonance imaging; MR RESCUE, Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy; REVASCAT, Endovascular Revascularization With Solitaire Device Versus Best Medical Therapy in Anterior Circulation Stroke Within 8 hours; and SWIFT PRIME, Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke.*Quantifying collateral perfusion in cerebrovascular disease–Moyamoya disease and patients with stroke (NCT01419275), acute MRI in transient ischemic attack (NCT01531946), and a longitudinal study of multimodal resonance imaging in patients with stroke (NCT02024503).Availability and Scan TimeCT-based collateral assessment is faster and more accessible than MRI-based techniques. However, the great potential for improving feasibility and accuracy of MR-based collateral assessment exists. For example, a 6-minute multimodal MRI protocol was proposed recently, which showed a good diagnostic quality and a significant reduction in scan time rivaling that of multimodal CT protocol.65VisualizationThe ASPECTS scoring system imperfectly accounts for brain eloquence is limited to the middle cerebral artery territory, is dependent on attention to scan quality and technique, and takes practice to learn and use well. MRI-based or multimodal CT-based collateral techniques may provide better quantitative and good visualization than simple nonenhanced CT techniques.EvidencesAlthough CT-based collateral assessments have been used in large randomized controlled trials, no studies have been focused on MRI-based collateral assessments versus standard CT in patient selection for revascularization therapy. Randomized trials are needed to show the same kind of efficiency at CT.Strategies to Enhance Collateral CirculationSeveral conditions might adversely affect collateral status, including systemic illness (cardiac or pulmonary illness, dehydration, vascular risk factors, etc), medications that inhibit physiological augmentation of blood pressure (ie, high-dose antihypertensives or wide fluctuation in blood pressure), and cerebral vascular status (widespread cerebral atherosclerosis or incomplete circle of illness).66 Optimization of these factors could help to minimize the risk of collateral failure. Beside, nonmodifiable factors, such as aging and genetic factors, may also influence on the collateral development and rarefaction.67,68Collateral enhancing strategies are important ways to restore blood flow within ischemic regions, particularly in patients who are ineligible for revascularization therapy, such as those outside the therapeutic time window for intravenous thrombolysis (4.5 hours) or endovascular therapy (6–8 hours), or those having poor collaterals in whom unfavorable response to revascularization therapy is expected. Collateral enhancing strategies for hemodynamic manipulations include induced hypertension, lying flat head position, volume expansion, external counterpulsation, partial aortic obstruction diverting splanchnic blood flow to the upper body and brain, and sphenopalatine ganglion stimulation (Table 2).66,69 In the field of neurosurgery, emergent bypass surgery has been applied for patients with acute ischemic stroke.70,71 Application of nitric oxide,72 albumin,73 and tumor necrosis factor-α inhibitor74 have been shown to increase arteriogenesis (collateral formation from preexisting channels) in animal model of stroke. In addition, preclinical and clinical studies have showed that various pharmacological therapies may enhance angiogenesis (capillary formation from preexisting vessels) and vasculogenesis (de novo capillary formation),66,75,76 which includes sildenafil and phosphodiesterase type 5 inhibitors,77,78 erythropoietin/trophic factors,79–81 and statins with or without cell therapy.82–85 Large, randomized trials in patients with acute stroke have seldom been performed and showed negative results.86–89 The potential reasons for these failures include inadequate patient selection and lack of assessment of the effects of such interventions on collateral blood vessels and collateral flow. Further studies are needed with optimal patient selection and rigorous assessment of the therapeutic values of collateral enhancing strategies using advanced imaging techniques for collateral flow. There are currently several ongoing clinical trials using various strategies (Table 2).Table 2. Therapeutic Strategies for Enhancing Collateral Circulation via Arteriogenesis and Angiogenesis/VasculogenesisArteriogenesisClinical TrialsAngiogenesis/VasculogenesisClinical TrialsInduced hypertensionSETIN-Hypertension (O)ErythropoietinEPO stroke (C)Head positionHeadPoST (O)Trophic factors…Volume expansion…Statins…Partial aortic occlusionSENTIS (C), FASTFlo-tPA (C), Flo24 (C)PDE5 inhibitorsSildenafil treatment of subacute ischemic stroke (C)SPG stimulationImpACT-24 (O)Stem/progenitor cells…External counter pulsationCUFFS (C), EULIPCCS (O)Bypass surgery…AlbuminALIAS (C)Nitric oxideENOS (C)TNF-α inhibitor…ALIAS indicates Albumin in Acute Ischemic Stroke trial; C, completed trials; CUFFS, Safety Study of External Counterpulsation as a Treatment for Acute Ischemic Stroke; ENOS, Efficacy of Nitric Oxide in Stroke; EPO stroke, Multicenter Efficacy Study of Recombinant Human Erythropoietin in Acute Ischemic Stroke; EULIPCCS, Effects of Upper Limb Ischemic Postconditioning on Collateral Circulation After Stroke; FASTFlot-tPA, Feasibility and Safety of NeuroFlo in Stroke Patients Receiving Tissue-Type Plasminogen Activator; Flo24, Safety and Efficacy of NeuroFlo in 8 to 24-h Stroke Patients; HeadPoST, Head Position in Stroke Trial; ImpACT-24, Implant for Augmentation of Cerebral Blood Flow Trial, Effectiveness and Safety in a 24-h Window; O, ongoing trials; PDE5, phosphodiesterase type 5 inhibitors; SENTIS, Safety and Efficacy of NeuroFlo Technology in Ischemic Stroke; SETIN-Hypertension, Safety and Efficacy of Therapeutic Induced Hypertension in Acute Noncardioembolic Ischemic Stroke; SPG, sphenopalatine ganglion; and TNF-α, tumor necrosis factor-α.Conclusions and PerspectivesIn patients with acute stroke, reperfusion after cerebral ischemia can be achieved via collaterals or through arterial revascularization. Relatively little attention has been paid to the patient's collateral status or therapeutic strategies for collateral enhancement. Growing evidence has demonstrated that it is important to reestimate the risk benefits of stroke therapy, such as endovascular therapy for acute ischemic stroke, in consideration of collateral status. Neuroimaging techniques for the assessment of collaterals are rapidly developing and may provide insight on the perfusion of collaterals in patients who may not otherwise be candidates for conventional angiography. Continuous efforts are needed to develop collateral enhancing strategies, and large randomized trials are needed with monitoring their effects using imaging modalities for collateral assessment.Sources of FundingThis study was supported by the Korea Health Technology R&D Project, the Ministry of Health & Welfare (HI14C1624) to Dr Bang. Dr Liebeskind has received a research grant from the NIH-NINDS (K24NS072272 and R13NS089280), and Dr Goyal has received a research support from Covidien.DisclosuresDr Goyal has received honoraria from Covidien and remuneration from GE Healthcare. The other authors report no conflicts.FootnotesGuest Editor for this article was Stephen M. Davis, MD.Correspondence to Oh Young Bang, MD, PhD, Department of Neurology, Samsung Medical Center, Sungkyunkwan University, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, South Korea. E-mail [email protected]References1. Zaidat OO, Yoo AJ, Khatri P, Tomsick TA, von Kummer R, Saver JL, et al; Cerebral Angiographic Revascularization Grading (CARG) Collaborators; STIR Revascularization working group; STIR Thrombolysis in Cerebral Infarction (TICI) Task Force. Recommendations on angiographic revascularization grading standards for acute ischemic stroke: a consensus statement.Stroke. 2013; 44:2650–2663. doi: 10.1161/STROKEAHA.113.001972.LinkGoogle Scholar2. Soares BP, Chien JD, Wintermark M.MR and CT monitoring of recanalization, reperfusion, and penumbra salvage: everything that recanalizes does not necessarily reperfuse!Stroke. 2009; 40(3 suppl):S24–S27. doi: 10.1161/STROKEAHA.108.526814.LinkGoogle Scholar3. Cho TH, Nighoghossian N, Mikkelsen IK, Derex L, Hermier M, Pedraza S, et al. Reperfusion within 6 hours outperforms recanalization in predicting penumbra salvage, lesion growth, final infarct, and clinical outcome.Stroke. 2015; 46:1582–1589. doi: 10.1161/STROKEAHA.114.007964.LinkGoogle Scholar4. Broderick JP, Palesch YY, Demchuk AM, Yeatts SD, Khatri P, Hill MD, et al; Interventional Management of Stroke (IMS) III Investigators. Endovascular therapy after intravenous t-PA versus t-PA alone for stroke.N Engl J Med. 2013; 368:893–903. doi: 10.1056/NEJMoa1214300.CrossrefMedlineGoogle Scholar5. Kidwell CS, Jahan R, Gornbein J, Alger JR, Nenov V, Ajani Z, et al; MR RESCUE Investigators. A trial of imaging selection and endovascular treatment for ischemic stroke.N Engl J Med. 2013; 368:914–923. doi: 10.1056/NEJMoa1212793.CrossrefMedlineGoogle Scholar6. Ciccone A, Valvassori L, Nichelatti M, Sgoifo A, Ponzio M, Sterzi R, et al; SYNTHESIS Expansion Investigators. Endovascular treatment for acute ischemic stroke.N Engl J Med. 2013; 368:904–913. doi: 10.1056/NEJMoa1213701.Google Scholar7. Molina CA.Futile recanalization in mechanical embolectomy trials: a call to improve selection of patients for revascularization.Stroke. 2010; 41:842–843. doi: 10.1161/STROKEAHA.110.580266.LinkGoogle Scholar8. Shi ZS, Liebeskind DS, Xiang B, Ge SG, Feng L, Albers GW, et al; Multi MERCI, TREVO, and TREVO 2 Investigators. Predictors of functional dependence despite successful revascularization in large-vessel occlusion strokes.Stroke. 2014; 45:1977–1984. doi: 10.1161/STROKEAHA.114.005603.LinkGoogle Scholar9. Hill MD, Demchuk AM, Goyal M, Jovin TG, Foster LD, Tomsick TA, et al; IMS3 Investigators. Alberta Stroke Program early computed tomography score to select patients for endovascular treatment: Interventional Management of Stroke (IMS)-III Trial.Stroke. 2014; 45:444–449. doi: 10.1161/STROKEAHA.113.003580.LinkGoogle Scholar10. Bang OY, Saver JL, Buck BH, Alger JR, Starkman S, Ovbiagele B, et al; UCLA Collateral Investigators. Impact of collateral flow on tissue fate in acute ischaemic stroke.J Neurol Neurosurg Psychiatry. 2008; 79:625–629. doi: 10.1136/jnnp.2007.132100.CrossrefMedlineGoogle Scholar11. Bang OY, Saver JL, Kim SJ, Kim GM, Chung CS, Ovbiagele B, et al. Collateral flow predicts response to endovascular therapy for acute ischemic stroke.Stroke. 2011; 42:693–699. doi: 10.1161/STROKEAHA.110.595256.LinkGoogle Scholar12. Bang OY, Saver JL, Kim SJ, Kim GM, Chung CS, Ovbiagele B, et al; UCLA-Samsung Stroke Collaborators. Collateral flow averts hemorrhagic transformation after endovascular therapy for acute ischemic stroke.Stroke. 2011; 42:2235–2239. doi: 10.1161/STROKEAHA.110.604603.