Ruiting Zhang

Overestimation of Susceptibility Vessel Sign: A Predictive Marker of Stroke Cause.

Background and Purpose— The extent of blooming artifact may reflect the amount of paramagnetic material. We thus assessed the overestimation ratio of susceptibility vessel sign (SVS) on susceptibility-weighted imaging, defined as the extent of SVS width beyond the lumen and examined its value for predicting the stroke cause in acute ischemic stroke patients. Methods— We included consecutive acute ischemic stroke patients with proximal large artery occlusion who underwent both susceptibility-weighted imaging and time-of-flight magnetic resonance angiography within 8 hours poststroke onset. We calculated the length, width, and overestimation ratio of SVS on susceptibility-weighted imaging and then investigated their values for predicting the stroke cause, respectively. Results— One-hundred eleven consecutive patients (72 female; mean age, 66.6±13.4 years) were enrolled, among whom 39 (35.1%) were diagnosed with cardiogenic embolism, 43 (38.7%) with large artery atherosclerosis, and 29 (26.1%) with undetermined cause. The presence, length, width, and overestimation ratio of SVS were all independently associated with the cause of cardiogenic embolism after adjusting for baseline National Institute of Health Stroke Scale and infarct volume. After excluded patients with undetermined cause, the sensitivity and specificity of overestimation ratio of SVS for cardiogenic embolism were 0.971 and 0.913; for the length of SVS, they were 0.629 and 0.739; for the width of SVS, they were 0.829 and 0.826, respectively. Conclusions— The overestimation ratio of SVS can predict cardiogenic embolism, with both high sensitivity and specificity, which can be helpful for the management of acute ischemic stroke patients in hyperacute stage.

Rationale and design of combination of an immune modulator Fingolimod with Alteplase bridging with Mechanical Thrombectomy in Acute Ischemic Stroke (FAMTAIS) trial.

Rationale In acute ischemic stroke patients with large vessel occlusion, although reperfusion within 6 h after stroke onset using combined intravenous alteplase and mechanical thrombectomy (bridging therapy) can improve functional outcome, still approximately 50% patients suffer disability which may result from reperfusion injury. Proof-of-concept clinical trials have indicated that the sphingosine-1-phosphate receptor modulator fingolimod may be efficacious in attenuating brain inflammation and improving clinical outcomes in acute ischemic stroke patients as a single therapy beyond 4.5 h of disease onset, or in combination with alteplase within 4.5 h of disease onset. Aim To assess whether the treatment of fingolimod combined with bridging therapy in large vessel occlusion acute ischemic stroke patients is effective and safe. Design and sample size estimates Fingolimod with Alteplase bridging with Mechanical Thrombectomy in Acute Ischemic Stroke (FAMTAIS) study is a randomized, open-label, multiple central trial. This study includes 98 patients with anterior circulation large vessel occlusion acute ischemic stroke who are eligible for bridging therapy, providing 80% power to reject the null hypothesis that, combined with fingolimod, the bridging therapy has an at least 15% higher penumbra tissue salvage index than receiving bridging therapy alone. Study outcomes The primary outcome is the penumbra tissue salvage index. Key secondary outcomes focus on: infarct growth and extent of clinical improvement from day 1 to day 7, frequency of parenchymal hemorrhage at day 1. Discussion If the hypothesis of FAMTAIS is confirmed, combination of fingolimod with bridging therapy is effective in attenuating reperfusion injury in patients with large vessel occlusion treated with 6 h of stroke onset.

Better Correlation of Cognitive Function to White Matter Integrity than to Blood Supply in Subjects with Leukoaraiosis

Leukoaraiosis is associated with increased risk of cognitive impairment, but its pathophysiological pathway is unclear. The aim of the present study was to determine whether brain structural damage or cerebral blood supply better correlated with the global cognitive outcome in subjects with leukoaraiosis. Seventy-five subjects with leukoaraiosis were included in present study, with age ranged from 43 to 85 years, with mean white matter hyperintensities (WMH) volume 30.69 ± 24.35 mL. Among them, 19(25.33%) subjects presented with cerebral microbleeds (CMB) and 40 (53.33%) subjects presented with lacunes. These participants received arterial spin labeling perfusion MRI, diffusion-tensor imaging (DTI) and diffusion Kurtosis imaging. We analyzed the cerebral blood flow (CBF) by dividing the brain tissue into three regions: WMH, normal appearing white matter (NAWM) and cortex. After adjusting for age and gender, the CBF of NAWM was significantly correlated with fractional anisotropy (FA) (r = 0.336, p = 0.004) and mean diffusion (MD) (r = -0.271, p = 0.020) of NAWM, while there lacked of association between CBF of cortex and mean kurtosis (MK) of cortex (r = -0.015, p = 0.912). Meanwhile, both NAWM-FA (r = -0.443, p < 0.001) and NAWM-MD (r = 0.293, p = 0.012), as well as cortex-MK (r = -0.341, p = 0.012) was significantly correlated with WMH volume. Univariate regression analysis demonstrated that global cognitive function was significantly associated with mean FA or MD of both WMH and NAWM, and cortex-CBF, but neither with the cortex-MK, nor the presences of CMB or lacunes. Finally, multiple linear regression analysis revealed that global cognitive function was independently associated with NAWM-FA (standardized β = 0.403, p < 0.001) and WMH-FA (Standardized β = 0.211, p = 0.017), but not with the cortex-CBF. A model that contained NAWM-FA, WMH-FA and years of education explained 49% of the variance of global cognitive function. Cerebral perfusion status might have a significant impact on the maintenance of white matter integrity in subjects with leukoaraiosis. Global cognitive function was more strongly associated with white matter integrity than with blood supply. DTI parameters, especially FA could serve as a potent imaging indicator for detecting the invisible alteration of white matter integrity and implying its potential cognitive relevance.

Impact of perfusion lesion in corticospinal tract on response to reperfusion

ObjectivesWe aimed to examine the impact of corticospinal tract (CST) involvement in acute ischaemic stroke (AIS) patients on functional outcome and the interaction with reperfusion.MethodsWe retrospectively examined data in consecutive anterior circulation AIS patients undergoing thrombolysis. MR perfusion (time to maximum of tissue residue function, Tmax) and apparent diffusion coefficient (ADC) images were transformed into standard space and the volumes of CST involvement by Tmax > 6 s (CST-Tmax) and ADC < 620 × 10−6 mm2/s (CST-ADC) lesions were calculated. Good outcome was defined as modified Rankin scale ≤ 2 at 3 months. Reperfusion was defined as a reduction in Tmax > 6 s lesion volume of ≥70% between baseline and 24 h.Results82 patients were included. Binary logistic regression revealed that both CST-Tmax and CST-ADC volume at baseline were significantly associated with poor outcome (p < 0.05). The 24-h CST-ADC volume was correlated with baseline CST-ADC volume in patients with reperfusion (r = 0.79, p < 0.001) and baseline CST-Tmax volume in patients without reperfusion (r = 0.67, p < 0.001). In patients with CST-Tmax volume > 0 mL and CST-ADC volume < 3 mL, the rate of good outcome was higher in patients with reperfusion than those without (70.4% vs 38.1%, p = 0.04).ConclusionsThe use of CST-Tmax in combination with CST-ADC provides prognostic information in patients considered for reperfusion therapies.Key Points• Examine the impact of corticospinal tract involvement in acute ischaemic stroke patients.• Spatially registered Tmax images can identify corticospinal tract hypoperfusion injury.• Corticospinal tract salvage through reperfusion is associated with improved outcome.

Reperfusion facilitates reversible disruption of the human blood–brain barrier following acute ischaemic stroke

AbstractObjectivesWe aimed to detect early changes of the blood–brain barrier permeability (BBBP) in acute ischaemic stroke (AIS), with or without reperfusion, and find out whether BBBP can predict clinical outcomes.MethodsConsecutive AIS patients imaged with computed tomographic perfusion (CTP) before and 24 h after treatment were included. The relative permeability–surface area product (rPS) was calculated within the hypoperfused region (rPShypo-i), non-hypoperfused region of ischaemic hemisphere (rPSnonhypo-i) and their contralateral mirror regions (rPShypo-c and rPSnonhypo-c). The changes of rPS were analysed using analysis of variance (ANOVA) with repeated measures. Logistic regression was used to identify independent predictors of unfavourable outcome.ResultsFifty-six patients were included in the analysis, median age was 76 (IQR 62–81) years and 28 (50%) were female. From baseline to 24 h after treatment, rPShypo-i, rPSnonhypo-i and rPShypo-c all decreased significantly. The decreases in rPShypo-i and rPShypo-c were larger in the reperfusion group than non-reperfusion group. The rPShypo-i at follow-up was a predictor for unfavourable outcome (OR 1.131; 95% CI 1.018–1.256; P = 0.022).ConclusionEarly disruption of BBB in AIS is reversible, particularly when greater reperfusion is achieved. Elevated BBBP at 24 h after treatment, not the pretreatment BBBP, predicts unfavourable outcome.Key points• Early disruption of blood–brain barrier (BBB) in stroke is reversible after treatment. • The reversibility of BBB permeability is associated with reperfusion. • Unfavourable outcome is associated with BBB permeability at 24 h after treatment. • Contralateral non-ischaemic hemisphere is not ‘normal’ during an acute stroke.

Pseudo-Occlusion of the Internal Carotid Artery Predicts Poor Outcome After Reperfusion Therapy

Background and Purpose— This study aimed to evaluate the occurrence rate of the internal carotid artery pseudo-occlusion (ICA-PO) on 4-dimensional–computed tomography angiography and to investigate its relationship with clinical outcome after reperfusion therapy. Methods— In this case–control study, we retrospectively reviewed our prospectively collected database for consecutive acute ischemic stroke patients who received reperfusion therapy between June 2009 and February 2017. ICA-PO was defined when the arterial segment was not opacified on peak arterial phase yet was subsequently patent after artery peak phase on 4-dimensional–computed tomography angiography. Poor outcome was defined as 3-month modified Rankin Scale of 4 to 6. Binary logistic regression was used to investigate the relationship of ICA-PO with poor outcome and the rate of reperfusion, respectively. Results— A total of 143 patients with isolated middle cerebral artery occlusion were included and 30 (21.0%) had ICA-PO. Patients with ICA-PO were more likely to have poor outcome (80.0% versus 37.2%; P<0.001) and a lower rate of reperfusion (45.8% versus 69.0%; P=0.033) than those without. Binary logistic regression revealed that ICA-PO was independently associated with poor outcome (odds ratio, 7.957; 95% confidence interval, 1.655–34.869; P=0.009) and reperfusion at 24 hours (odds ratio, 0.150; 95% confidence interval, 0.045–0.500; P=0.002) after adjustment. Among patients with no reperfusion, all ICA-PO patients obtained poor outcome, whereas only 45.2% non-PO patients underwent poor outcome (P=0.001). Conclusions— Four dimensional-computed tomography angiography is a useful noninvasive technique to identify ICA-PO. Patients with ICA-PO are prone to undergo poor outcome from reperfusion therapy, especially when reperfusion is not achieved.

Increased blood-brain barrier permeability in contralateral hemisphere predicts worse outcome in acute ischemic stroke after reperfusion therapy

Aims We sought to investigate the risk factors of blood-brain barrier (BBB) disruption, and its potential impact on 90-day clinical outcome in acute ischemic stroke (AIS) patients after reperfusion therapy. Methods Consecutive acute anterior circulation AIS patients imaged with computed tomographic perfusion (CTP) before reperfusion therapy were included. Tmax >6 s was used for the volumetric measurement of the hypoperfusion area. BBB permeability (BBBP) was calculated as the average relative permeability-surface area product (rPS) within the hypoperfusion region (rPShypo-i) and its contralateral mirror region (rPShypo-c) on CTP-derived PS color maps. Modified Rankin Scale (mRS) score was obtained at 90-day post-stroke. Results A total of 187 patients were included, among whom the median age was 73 (61–80) years and 76 (40.6%) were women. Median baseline NIHSS score was 12 (7– 16). Ninety-eight (52.4%) patients had mRS score >2. Increased rPShypo-i and rPShypo-c were both independently associated with males and large infarct volume. The increased rPShypo-i was also independently associated with a history of atrial fibrillation and high NIHSS score. Multivariable analysis showed higher rPShypo-c was independently associated with higher mRS (OR: 1.064, 95% CI 1.011 to 1.121; P=0.018). Conclusion BBBP in both the hypoperfusion region and its contralateral mirror region are associated with stroke severity, but only increased BBBP in the contralateral mirror hypoperfusion region relates to worse outcome after reperfusion therapy.

Corrigendum: Novel Prehospital Prediction Model of Large Vessel Occlusion Using Artificial Neural Network

[This corrects the article DOI: 10.3389/fnagi.2018.00181.].

Novel Prehospital Prediction Model of Large Vessel Occlusion Using Artificial Neural Network

Background: Identifying large vessel occlusion (LVO) patients in the prehospital triage stage to avoid unnecessary and costly delays is important but still challenging. We aim to develop an artificial neural network (ANN) algorithm to predict LVO using prehospital accessible data including demographics, National Institutes of Health Stroke Scale (NIHSS) items and vascular risk factors. Methods: Consecutive acute ischemic stroke patients who underwent CT angiography (CTA) or time of flight MR angiography (TOF-MRA) and received reperfusion therapy within 8 h from symptom onset were included. The diagnosis of LVO was defined as occlusion of the intracranial internal carotid artery (ICA), M1 and M2 segments of the middle cerebral artery (MCA) and basilar artery on CTA or TOF-MRA before treatment. Patients with and without LVO were randomly selected at a 1:1 ratio. The ANN model was developed using backpropagation algorithm, and 10-fold cross-validation was used to validate the model. The comparison of diagnostic parameters between the ANN model and previously established prehospital prediction scales were performed. Results: Finally, 300 LVO and 300 non-LVO patients were randomly selected for the training and validation of the ANN model. The mean Youden index, sensitivity, specificity and accuracy of the ANN model based on the 10-fold cross-validation analysis were 0.640, 0.807, 0.833 and 0.820, respectively. The area under the curve (AUC), Youden index and accuracy of the ANN model were all higher than other prehospital prediction scales. Conclusions: The ANN can be an effective tool for the recognition of LVO in the prehospital triage stage.

Thrombus Permeability on Dynamic CTA Predicts Good Outcome after Reperfusion Therapy

BACKGROUND AND PURPOSE: Thrombus permeability assessed on conventional CTA is associated with neurologic outcome in patients with acute ischemic stroke. We aimed to investigate whether dynamic CTA can improve the accuracy of thrombus permeability assessment and its predictive value for outcome. MATERIALS AND METHODS: We reviewed consecutive patients with acute ischemic stroke who had occlusion of the M1 segment of the middle artery cerebral artery and underwent pretreatment perfusion CT. Thrombus permeability, determined by thrombus attenuation increase (TAI), was assessed on 26-phase dynamic CTA derived from perfusion CT. TAImax was defined as the maximum TAI among phases; TAIpeak, as TAI of peak arterial phase; TAIcon, as TAI on phase 13. Good outcome was defined as a 3-month mRS score of ≤2. RESULTS: One hundred four patients were enrolled in the final analysis. The median TAImax, TAIpeak, and TAIcon were 30.1 HU (interquartile range, 13.0–50.2 HU), 9.5 HU (interquartile range, −1.6–28.7 HU), and 6.6 HU (interquartile range, −5.1–24.4 HU), respectively. Multivariable regression analyses showed that TAImax (OR = 1.027; 95% CI, 1.007–1.048; P = .008), TAIpeak (OR = 1.029; 95% CI, 1.005–1.054; P = .020), and TAIcon (OR = 1.026; 95% CI, 1.002–1.051; P = .037) were independently associated with good outcome. The areas under the ROC curve of TAImax, TAIpeak, and TAIcon in predicting good outcome were 0.734, 0.701, and 0.658, respectively. CONCLUSIONS: Thrombus permeability assessed on dynamic CTA could be a better predictor of outcome after reperfusion therapy than that assessed on conventional single-phase CTA.