Impact of leukoaraiosis on the infarct growth rate and clinical outcome in acute large vessel occlusion stroke after endovascular thrombectomy.

INTRODUCTION: As a marker of chronic cerebral small vessel disease, leukoaraiosis (LA) was reported to impact the recruitment of collaterals in acute ischemic stroke (AIS). We intended to explore the impact of LA on the infarct growth rate (IGR) and clinical outcome by impaired collateral development in AIS patients with large vessel occlusion (LVO) who underwent endovascular thrombectomy (EVT). PATIENTS AND METHODS: Two hundred thirty-six AIS patients who underwent EVT were retrospectively reviewed. The severity of LA was graded using the Fazekas scale with non-contrast CT. IGR was calculated by the acute core volume on CT perfusion divided by the time from stroke onset to imaging. The collateral status after LVO was assessed using the ASITN/SIR collateral scale. The clinical outcomes after EVT were evaluated using a modified Rankin Scale (mRS). The Alberta stroke program early CT score (ASPECTS), the National Institutes of Health Stroke Scale (NIHSS) score at admission, and the modified treatment in cerebral infarction (mTICI) score after EVT were also included. Correlations between those factors were analyzed. RESULTS: Patients with severe LA had significantly larger core volume on CTP (p = 0.022) and lower collateral grade (p < 0.001). Faster IGR was significantly associated with higher LA severity (adjusted odds ratio [aOR]: 1.53; 95% CI: 1.02-2.33; p = 0.046), higher NIHSS (aOR: 1.04; 95% CI: 1.00-1.09; p = 0.032) and impaired collaterals (aOR: 2.26; 95% CI: 1.27-4.03; p = 0.005). In mediation analysis, collaterals explained 33% of the effect of LA on fast IGR. There was correlation between the severity of LA and mRS (p = 0.007). DISCUSSION AND CONCLUSION: The increasing severity of LA is associated with impaired collateral status and fast infarct growth. These findings suggest that LA may become a predictive imaging biomarker for the likelihood of progression of tissue injury and clinical outcome after EVT in acute large vessel occlusion stroke.

Core overestimation of CT perfusion in patients with cardiac insufficiency who had a stroke is mediated by impaired collaterals.

BACKGROUND: We hypothesized that left ventricular systolic dysfunction (LVSD) would lead to an ischemic core overestimation in patients with acute ischemic stroke (AIS), and impaired collateral status might partly mediate this effect. OBJECTIVE: A pixel-based analysis of CT perfusion (CTP) and follow-up CT was undertaken to investigate the optimum CTP thresholds for the ischemic core if overestimation was found. METHODS: A total of 208 consecutive patients with AIS with large vessel occlusion in the anterior circulation, who received initial CTP evaluation and successful reperfusion, were retrospectively analyzed and divided into an LVSD (left ventricular ejection fraction (LVEF) ratio <50%; n=40) and a normal cardiac function (LVEF≥50%; n=168) group. Ischemic core overestimation was considered when the CTP-derived core was larger than the final infarct volume. We investigated the relationship between cardiac function, probability for core overestimation, and collateral scores using mediation analysis. A pixel-based analysis was undertaken to define the optimum CTP thresholds for ischemic core. RESULTS: LVSD was independently associated with impaired collaterals (aOR=4.28, 95% CI 2.01 to 9.80, P<0.001) and core overestimation (aOR=2.52, 95% CI 1.07 to 5.72, P=0.030). In mediation analysis, the total effect on core overestimation is composed of the direct effect of LVSD (+17%, P=0.034) and the mediated indirect effect of collateral status (+6%, P=0.020). Collaterals explained 26% of the effect of LVSD on core overestimation. Compared with relative cerebral blood flow (rCBF) thresholds of <35%, <30%, and <20%, a rCBF <25% cut-off point had the highest correlation (r=0.91) and best agreement (mean difference 3.2±7.3 mL) with the final infarct volume to determine the CTP-derived ischemic core in patients with LVSD. CONCLUSIONS: LVSD increased the possibility of ischemic core overestimation on baseline CTP, partly due to impaired collateral status, and a stricter rCBF threshold should be considered.

Thrombus Enhancement Sign May Differentiate Embolism From Arteriosclerosis-Related Large Vessel Occlusion.

BACKGROUND AND PURPOSE: To evaluate whether the thrombus enhancement sign (TES) can be used to differentiate embolic large vessel occlusion (LVO) from in situ intracranial atherosclerotic stenosis (ICAS)-related LVO in the anterior circulation of patients with acute ischemic stroke (AIS). METHODS: Patients with LVO in the anterior circulation who underwent both non-contrast computed tomography (CT) and CT angiography and mechanical thrombectomy were retrospectively enrolled. Both embolic LVO (embo-LVO) and in situ ICAS-related LVO (ICAS-LVO) were confirmed by two neurointerventional radiologists after reviewing the medical and imaging data. TES was assessed to predict embo-LVO or ICAS-LVO. The associations between occlusion type and TES, along with clinical and interventional parameters, were investigated using logistic regression analysis and a receiver operating characteristic curve. RESULTS: A total of 288 patients with AIS were included and divided into an embo-LVO group (n=235) and an ICAS-LVO group (n=53). TES was identified in 205 (71.2%) patients and was more frequently observed in those with embo-LVO, with a sensitivity of 83.8%, specificity of 84.9%, and area under the curve (AUC) of 0.844. Multivariate analysis showed that TES (odds ratio [OR], 22.2; 95% confidence interval [CI], 9.4-53.8; P<0.001) and atrial fibrillation (OR, 6.6; 95% CI, 2.8-15.8; P<0.001) were independent predictors of embolic occlusion. A predictive model that included both TES and atrial fibrillation yielded a higher diagnostic ability for embo-LVO, with an AUC of 0.899. CONCLUSION: TES is an imaging marker with high predictive value for identifying embo- and ICAS-LVO in AIS and provides guidance for endovascular reperfusion therapy.

Prediction of cerebral aneurysm rupture using a point cloud neural network.

OBJECTIVE: Accurate prediction of cerebral aneurysm (CA) rupture is of great significance. We intended to evaluate the accuracy of the point cloud neural network (PC-NN) in predicting CA rupture using MR angiography (MRA) and CT angiography (CTA) data. METHODS: 418 CAs in 411 consecutive patients confirmed by CTA (n=180) or MRA (n=238) in a single hospital were retrospectively analyzed. A PC-NN aneurysm model with/without parent artery involvement was used for CA rupture prediction and compared with ridge regression, support vector machine (SVM) and neural network (NN) models based on radiomics features. Furthermore, the performance of the trained PC-NN and radiomics-based models was prospectively evaluated in 258 CAs of 254 patients from five external centers. RESULTS: In the internal test data, the area under the curve (AUC) of the PC-NN model trained with parent artery (AUC=0.913) was significantly higher than that of the PC-NN model trained without parent artery (AUC=0.851; p=0.041) and of the ridge regression (AUC=0.803; p=0.019), SVM (AUC=0.788; p=0.013) and NN (AUC=0.805; p=0.023) radiomics-based models. Additionally, the PC-NN model trained with MRA source data achieved a higher prediction accuracy (AUC=0.936) than that trained with CTA source data (AUC=0.824; p=0.043). In external data of prospective cohort patients, the AUC of PC-NN was 0.835, significantly higher than ridge regression (0.692; p<0.001), SVM (0.701; p<0.001) and NN (0.681; p<0.001) models. CONCLUSION: PC-NNs can achieve more accurate CA rupture prediction than traditional radiomics-based models. Furthermore, the performance of the PC-NN model trained with MRA data was superior to that trained with CTA data.

Thrombus enhancement sign on CT angiography is associated with the first pass effect of stent retrievers.

BACKGROUND: The thrombus enhancement sign (TES) is thought to be associated with the source of the stroke and thrombus composition. We investigated whether this imaging sign along with other thrombus characteristics could be used to predict the successful first pass effect (FPE) of mechanical thrombectomy. METHODS: 246 consecutive patients with acute ischemic stroke in the anterior circulation with large vessel occlusion who underwent thrombectomy with a stent retriever and clot collection were included. Patients were divided into FPE (modified Thrombolysis in Cerebral Infarction (mTICI) grade 2c or 3)/non-FPE (mTICI 0-2b) and modified FPE (mFPE) (mTICI 2b-3)/non-mFPE (mTICI 0-2a) groups based on flow restoration after the first pass. TES presence, thrombus density, thrombus length, clot burden score, and thrombus composition were compared. The association between FPE and imaging biomarkers, along with clinical and interventional parameters, was investigated by univariate and multivariate analysis. RESULTS: FPE was achieved in 85 (34.6%) patients. TES presence was significantly lower in the FPE group (64.7% vs 80.7% in the non-FPE group, p=0.008) and mFPE group (69.1% vs 81.0% in the non-mFPE group, p=0.039). Histopathological examination revealed that TES (+) thrombi contained a higher fibrin/platelet proportion (50.9% vs 46.9% in TES (-) thrombi, p=0.029) and fewer erythrocytes (43.3% vs 47.3% in TES (-) thrombi, p=0.030). Thrombus characteristics, namely shorter thrombus length (p=0.032), higher erythrocyte proportions (p=0.026), and less fibrin/platelets (p=0.014), were confirmed in patients with FPE. In multivariable analysis, TES was the only independent predictor of FPE failure (OR 0.51, 95% CI 0.28 to 0.94; p=0.031). CONCLUSIONS: TES was independently associated with first pass angiographic failure in patients treated with a stent retriever.

Advances in cerebral perfusion imaging techniques in acute ischemic stroke.

The application of cerebral perfusion imaging has demonstrated significant assessment benefits and an ability to establish an appropriate triage of patients with acute ischemic stroke (AIS) and large artery occlusion (LAO) in the extended time window. Computed tomography perfusion (CTP) and magnetic resonance imaging (MRI) are routinely used to determine the ischemic core, as well as the tissue at risk, to aid in therapeutic decision-making. However, the time required to transport patients to imaging extends the door-to-reperfusion time. C-arm cone-beam CT (CBCT) is a novel tomography technology that combines 2D radiography and 3D CT imaging based on the digital subtraction angiography platform. In comparison with CT or MRI perfusion techniques, CBCT combined with catheterized angiogram or therapy can serve as a "one-stop-shop" for the diagnosis and treatment of AIS, and greatly reduce the door to reperfusion time. Here, we review the current evidence on the efficacy and theoretical basis of CBCT, as well as other perfusion techniques, with the purpose to assist clinicians to establish an effective and repaid workflow for patients with AIS and LAO in clinical practice.

Design and optimization of three-dimensional composite multilayer cylindrical pentamode metamaterials for controlling low frequency acoustic waves.

For three-dimensional pentamode metamaterials, it is of great significance to realize underwater low frequency acoustic wave control. Therefore, in order to compare with traditional double-cone pentamode metamaterials, two multilayer composite cylindrical three-dimensional pentamode metamaterials with low frequency and broad band gaps are proposed in this paper. By using pentamode metamaterials with lattice constants on the order of centimeters, the phononic band gaps below 60 Hz and the single-mode area below 30 Hz can be obtained. In addition, compared with asymmetrical double-cone locally resonant pentamode metamaterials, the lower edge frequency, relative bandwidth and figure of merit of the first phononic band gap can be reduced by up to 61.4%, 10.3% and 40.6%, respectively. It will provide reference and guidance for the engineering application of pentamode metamaterials in controlling the ultra-low frequency broadband acoustic waves, vibration and noise reduction.

Diagnostic Performance of MRA for UnrupturedAneurysms at the Distal ICA.

PURPOSE: Unruptured intracranial aneurysms (UIAs) at the distal internal carotid artery (ICA) (segments C5-C7) are difficult to accurately display on computed tomography angiography (CTA) due to the influences of bone structures and vessel curvature. We investigated the utility of three-dimensional time-of-flight magnetic resonance angiography (3D-TOF-MRA) at 3.0­T for the detection of morphologic features compared to digital subtraction angiography (DSA). METHODS: This retrospective study included 2398 patients between January 2015 and May 2020 who underwent 3D-TOF-MRA and DSA within 3 months. Morphologic features including aneurysm size, neck width, shape and relation to adjacent arteries and other diagnostic parameters were recorded. Three observers blinded to the clinical and DSA results independently analyzed MRA data sets. The statistical difference of each aneurysm-specific variable was performed using χ2-tests and multivariate logistic regression analysis. RESULTS: A total of 551 aneurysms in 514 patients were confirmed at the distal ICA by DSA. Patient-based, aneurysm-based and location-based evaluations with 3D-TOF-MRA yielded high diagnostic accuracy in the detection of target UIAs. The accuracy of displayed morphologic features was 94.9% for size, 97.2% for neck width, 92.6% for shape, and 96.4% for relationship to adjacent vessels. Multivariate logistic regression showed that tiny (P < 0.001) or giant (P = 0.039) size and a lobulated shape (P = 0.006) significantly affected the morphologic assessment on 3D-TOF-MRA. CONCLUSION: Three-dimensional TOF-MRA can accurately depict and display morphologic features of distal ICA UIAs. Tiny or giant-sized distal ICA aneurysms and with lobulation tend to carry a great risk of misdiagnosis in morphologic assessments.

Mechanical thrombectomy injury to the arterial wall: A comparison between catheter aspiration and stent retriever.

PURPOSE: To compare the extent of arterial wall damage when SR and CA were used for treatment of AIS models to evaluate their efficacy and safety. METHODS: A thrombin-induced thrombus was pre-injected into the right distal external carotid-maxillary artery (ECMA) in 12 dogs to create an acute thrombus occlusion model and were randomly divided into the SR group (n = 6; received SR treatment) and CA group (n = 6; received CA treatment). Device safety was also assessed by five passages through the normal left ECMA using each device. Device manipulation-related damage to arterial walls, final flow restoration, recanalization time and complications were recorded. RESULTS: Sixteen retriever and 10 aspiration attempts were performed in the SR and CA groups. Reperfusion time was significantly reduced in the CA group (17.83 ±â€¯1.96 vs. 28.33 ±â€¯3.26 in the SR group; P = 0.02). Stent retriever thrombectomy resulted in an increased risk of endothelium denudation (1.17 ±â€¯0.24 in SR group vs. 0.42 ±â€¯0.15 in CA group; P = 0.01) and reduced frequency of vessel vasospasm (0.67 ±â€¯0.14 in SR group vs. 0.25 ±â€¯0.13 in CA group; P = 0.04). Injury score and thrombus deposition were similar between the two groups (P > 0.05). TICI 2b/3 flow restoration values of the right ECMA were 100 % in both groups. Device-related complications, including dissection (P = 0.21), side branch influence (P = 0.24), and distal thromboembolism (P = 1.00), did not differ between the two groups. CONCLUSION: Both devices had similar efficacy and caused minimal arterial wall damage in our dog models. SR was more likely to cause endothelium denudation, while CA had a greater risk of vasospasm.

Advances in imaging acute ischemic stroke: evaluation before thrombectomy.

Recent advances in neuroimaging have demonstrated significant assessment benefits and appropriate triage of patients based on specific clinical and radiological features in the acute stroke setting. Endovascular thrombectomy is arguably the most important aspect of acute stroke management with an extended time window. Imaging-based physiological information may potentially shift the treatment paradigm from a rigid time-based model to a more flexible and individualized, tissue-based approach, increasing the proportion of patients amenable to treatment. Various imaging modalities are routinely used in the diagnosis and management of acute ischemic stroke, including multimodal computed tomography (CT) and magnetic resonance imaging (MRI). Therefore, these imaging methods should provide information beyond the presence or absence of intracranial hemorrhage as well as the presence and extent of the ischemic core, collateral circulation and penumbra in patients with neurological symptoms. Target mismatch may optimize selection of patients with late or unknown symptom onset who would potentially be eligible for revascularization therapy. The purpose of this study was to provide a comprehensive review of the current evidence about efficacy and theoretical basis of present imaging modalities, and explores future directions for imaging in the management of acute ischemic stroke.

Arterial wall injury and miRNA expression induced by stent retriever thrombectomy under stenotic conditions in a dog model.

BACKGROUND: Acute ischemic stroke can be caused by in situ stenotic vessel occlusion. In the present study, we compared the extent of arterial wall damage and miRNA expression following stent retriever use under normal and stenotic conditions. METHODS: The stent retriever procedure was simulated in three dogs by the creation of four stenoses on each side of the common carotid artery (CCA) to allow five stent passages. Device safety was also assessed in normal control models by five passages through both CCAs. Device manipulation-related damage to the arterial walls was evaluated and compared between groups by angiography and pathological analysis. Real-time PCR was used to evaluate the differences in the expression of miRNAs between the two groups. RESULTS: Twenty-four stenoses were created in three model dogs, and the mean stenosis rate was 65.58%±18.95%. Angiography revealed greater vasospasm in the stenotic group than in the non-stenotic group (1.17±0.17 vs 0.5±0.23; P=0.04). Pathological examination revealed that SR passage through the stenotic lumen caused higher injury scores (1.63±0.19 vs 0.25±0.09 for the non-stenotic lumen; P<0.001), more endothelial denudation (1.79±0.13 vs 0.58±0.13 for the non-stenotic lumen; P<0.001), and increased thrombus deposition (0.71±0.14 vs 0±0 for the non-stenotic lumen; P<0.001). miR21-3p, miR29-3p, and miR26a were upregulated in stenotic vessels compared with non-stenotic vessels after SR thrombectomy (P<0.001). CONCLUSION: In our model dogs, SR thrombectomy resulted in more severe tissue damage to the arterial wall under stenotic conditions than under non-stenotic conditions. The damage may have resulted from upregulation of miR21-3p, miR29-3p, and miR26a expression.

Mono antiplatelet therapy for cardioembolic and undetermined etiological stroke after receiving successful mechanical thrombectomy.

BACKGROUND: Recent studies indicated that majority of stroke with undetermined etiology (SUE) showed strong overlap with cardioembolic stroke (CE). We intended to determine the efficacy of the mono antiplatelet (MA) therapy in both stroke types after receiving successful mechanical thrombectomy (MT) recanalization in the acute stage. METHODS: 178 consecutive stroke patients who received MT treatment were retrospectively analyzed. For CE and SUE type stroke patients, aspirin 100 mg or clopidogrel 75 mg was added immediate for those didn`t received IV-rtPA and after 24 h for those received IV-rtPA if symptomatic intracranial hemorrhage (sICH) was not found. MA treatment outcomes included recanalized artery patency, subsequent sICH and functional independence (mRS score 0-2) were compared between two stroke types. RESULTS: 75 CE and 50 SUE patients were included into final analysis. Target artery was confirmed 100 % patency in the CE group and 97.5 % in the SUE group at 7 days after recanalization. Hemorrhagic transformation after 24 h was found in 10 % patients in the SUE group and in 12 % patients in the CE group (P > 0.05). sICH was confirmed in 1 patient in the SUE group and in 2 patients in the CE group. At 90 days, 45.8 % in the SUE group and 46.5 % in the CE group of patients had achieved good outcomes (P = 1.00). However, accumulative death was higher in the CE group than in the SUE group (21 % vs. 15 %; P = 0.47). CONCLUSION: For patients considered CE or SUE stroke types, mono antiplatelet therapy after good flow restoration by thrombectomy is safe and effective.