Multi-modality Imaging-based Strategies For Reperfusion Therapy In Acute Ischemic Stroke Patients

Vascular stenosis or occlusion during ischemic strokeleadstodecreased blood perfusion and brain cells necrosis occurs within a few minutes.The distribution regionof these cells is called infarct core and hypoperfusion areaaround the core is called ischemic penumbra.Openingthe occlusion vessels to get the ischemic penumbra reperfusion in time can protect the penumbra from infarction.However,if the occlusion continues,ischemic penumbra will progress and expanseintoa larger infarct core.Therefore,revascularization of the occlusion vascular to rescue the ischemic penumbra is the main target of acute ischemic stroke treatment.At present,clinical practice of reperfusion therapy decision is still based on CT scan home and abroad.However non-contrast CT scanning of the majority of patients did not change within 6 hours after the stroke occurred.So it is not possible to identify the pathophysiologicalchanges of brain tissue.The development of imaging provides an opportunity for us to observe the pathophysiological changes of brain tissue in vivo.Recently,studies have shown that multimodal images can reflect penumbra and core.Combined with that information,therapeutic window of reperfusion therapy of some individuals can be extended effectively.Multi-modality imaging can also provide important information on intracranial blood vessels,including the level of intracranial collateral circulation and venous drainage,and thus complete brain-vein network assessment to provide a more complete evaluation systemfor reperfusion therapy.However,there is an urgent need for these new imaging technologies to transforminto clinical practice.Therefore,our studyintends tomake a series of in-depth analysisof the imaging features of perfusion,arterial collateral and venous drainage of the ischemic brain tissue,by using the multi-modality imaging of acute ischemic patients,so as to clarify the imaging features of the population that could benefit from reperfusion therapy.The aimof this study is to increasethe benefit-risk of reperfusion therapy and optimize the strategies for reperfusion therapy.Part OneThe safety and efficacy of mismatch-based thrombolysis with extended time-window in acute ischemic strokeAimsThe aim of this study was to validate the safety and efficacy of the target mismatch standard that was applied in thrombolysis with extended time window.MethodsWe retrospectively reviewed our prospectively collected database of acute ischemic stroke patients(AIS)who received intravenous thrombolysis(IVT)within 9 hours of stroke onset.Patients were classified into the within-time-window(WT)group(onset to needle time less than 4.5 hours)and the beyond-time-window(BT)group(onset to needle time over 4.5 hours with target mismatch).Target mismatch was defined as hypoperfusion/ischemic core ratio>1.2,and baseline hypoperfusion volume>10 mL.Hypoperfusion was defined as peak time>6s.Hemorrhagic transformation(HT)was defined according to European-Australasian Acute Stroke Study(ECASS)criteria.HI hemorrhage was defined as a punctate hemorrhage seen on the 24-hour image.Modified Rankin scale(mRS)score was used to define clinical outcome at 3 months.Good outcome was mRS score≤2and poor outcome was mRS score>2.ResultA total of 747 patients were enrolled,including 447 patients(59.8%)with complete baseline imaging data.The rates of hemorrhagic transformation(HT)(32.3%vs 34.4%,p=0.650)and symptomatic HT(4.3%vs 5.1%,p=0.492)at 24 hours after thrombolysis were similar between WT(n=625)and BT(n=122)patients.Even among patients with target mismatch(n=433),the rate of HT(40.2%vs 34.4%,p=0.267),poor outcome(49.5%vs 55.7%,p=0.244)and death(12.5%vs 15.6%,p=0.404)in BT group(n=122)were comparable to that in WT group(n=311).Compared with WT patients(n= 14)without target mismatch,BT patients(n= 122)had a much lower rate of hemorrhagic infarction(23.0%vs 50.0%,p=0.028),and a trendy lower rate of poor outcome(55.7%vs 78.6%,p=0.101).ConclusionThe safety and efficacy of mismatch-based thrombolysis in AIS patients with extended time window is comparable to that in WT patients,indicating that target mismatch can optimize the selection criteria forreperfusion therapy within 9 hours after onset.Part TwoThe prognostic value of collateral status based on perfusion imaging in acute ischemic stroke1 The velocity of collateral filling predicts recanalization in acute ischemic stroke after intravenous thrombolysisAims:The aim of this study was to evaluate the impact of pretreatment quality of collaterals,involving velocity and extent of collateral filling,on recanalization after intravenous thrombolysis(IVT).Methods:A retrospective analysis was performed of 66 patients with acute middle cerebral artery(MCA)Ml segment occlusion who underwent MR perfusion-weighted(PWI)imaging before IVT.The velocity of collateral filling was defined as arrival time delay(ATD)of contrast bolus to Sylvian fissure between the normal and the affected hemisphere.The extent of collateral filling was assessed according to the Alberta Stroke Program Early CT(ASPECT)score on temporally fused maximum intensity projections(tMIP).Arterial occlusive lesion(AOL)scorewas used to assess the degree of arterial recanalization.AOL score of 2 or 3 was defined as recanalization,and the 24-hour hemorrhagic transformation was evaluated according to the ECASS criteria.Results:ATD(the velocity of collateral filling)(OR=0.775,95%CI=0.626-0.9605,p=0.020),but not tMIP-ASPECT score(theextent of collateral filling)(OR=1.073,95%CI=0.820-1.405,p=0.607),was independently associated with recanalization(AOL score of 2 and 3)at 24 hours after IVT.When recanalization was achieved,hemorrhagic transformation(HT)occurred more frequently in patients with slow collaterals(ATD≥2.3 seconds)than those with rapid collaterals(ATD<2.3 seconds)(88.9%vs 38.1%,p=0.011).Conclusion:The velocity of collaterals related to recanalization,which may guide the decision-making of revascularization therapy in acute ischemic stroke.2The prognostic value of a four-dimensional CT angiography-based collateral grading scale for reperfusion therapy in acute ischemic stroke patientsAimsWe sought to develop a comprehensive rating system to integrate thevelocityand extent of collateral flow on 4D CTA,and investigate its prognostic value for reperfusion therapy in acute ischemic stroke(AIS)patients.MethodsWe retrospectively studied 101 patients with M1±internal carotid artery(ICA)occlusion who had baseline CTP before intravenous thrombolysis.The velocity and extent of collaterals were evaluated by regional leptomeningeal collateral score on peak phase(rLMC-P)and temporally fused intensity projections(tMIP)(rLMC-M)on 4D CTA,respectively.The cutoffs of rLMC-P and rLMC-M score for predicting good outcome(mRS score≤2)were integrated to develop the collateral grading scale(CGS)(rating from 0-2).ResultsThe CGS score was correlated with 3-months mRS score(non-recanalizers:p=-0.535,<0.001;recanalizers:p =-0.446,p<0.001).Patients with intermediate or good collaterals(CGS score of 1 and 2)who recanalized(51%vs 0%,p= 0.019)were more likely to have good outcome than those without recanalization(73.9%vs 37.5%,p=0.048),while there was no significant difference in outcome in patients with poor collaterals(CGS score of 0)stratified by recanalization(13.0%vs 0%,p = 0.227).ConclusionsIdentification of collaterals based on CGS may help to select good responders to reperfusion therapy in patients with large artery occlusion.Part ThreeAbsent filling of ipsilateral superficial middle cerebral vein is associated with poor outcome after reperfusion therapyAims:Our aim was to study the effect of drainage of cortical veins,including the superficial middle cerebral vein(SMCV),vein of Trolard(VOT),and vein of Labb6(VOL)on neurological outcomes after reperfusion therapy.Methods:Consecutive ischemic stroke patients who underwent pretreatment CT perfusion(CTP)and 24-hour CTP or MR perfusion after intravenous thrombolysis were included.FourdimensionalCT angiography(4D CTA)was originated from CT perfusion(CTP).We defined "absent filling of ipsilateral cortical vein"(e.g.SMCV-,VOT-and VOL-)as no contrast filling of the vein across the whole venous phase on 4D CTAin the ischemic hemisphere.Reperfusion was defined as reperfusion of more than 80%of the hypoperfusion area from the baseline to 24-hour.The degree of brain edema was assessed according to Wardlaw’s method.The poor prognosis was defined as the 3-month modified Rankin score>2.Results:Of 228 patients,SMCV-,VOT-and VOL-were observed in 51(22.4%),27(11.8%),and 32(14.0%)patients,respectively.Only SMCV-independently predicted poor outcome(3-month modified Rankin Scale score>2)(OR=2.710,p=0.040).No difference was found in reperfusion rate after treatment between patients with and without SMCV-(42.9%vs 46.0%,p=0.754).In patients achieving major reperfusion(≥80%),there was no difference in 24-hour infarct volume,or rate of poor outcome between patients with and without SMCV-(all p>0.05).However,in those without major reperfusion,patients with SMCV-had larger 24-hour infarct volume(118.0±112.7 mL vs 49.0±58.6 mL,p=0.011),higher rate of poor outcome(95%vs 66.0%,p=0.012),and death(25.0%vs 6.4%,p=0.032),compared to those with SMCV filling.SMCV-was significantly associated with brain edema at 24 hours(p=0.037)which,in turn,was associated with poor 3-month outcome(p=0.002).Conclusions:Lack of SMCV filling contributed to poor outcome after thrombolysis,and it may be related to brain edema progress.