Baixue Jia

Functional assessment of cerebral artery stenosis: A pilot study based on computational fluid dynamics

The fractional pressure ratio is introduced to quantitatively assess the hemodynamic significance of severe intracranial stenosis. A computational fluid dynamics-based method is proposed to non-invasively compute the FPRCFD and compared against fractional pressure ratio measured by an invasive technique. Eleven patients with severe intracranial stenosis considered for endovascular intervention were recruited and an invasive procedure was performed to measure the distal and the aortic pressure (Pd and Pa). The fractional pressure ratio was calculated as P d / P a . The computed tomography angiography was used to reconstruct three-dimensional (3D) arteries for each patient. Cerebral hemodynamics was then computed for the arteries using a mathematical model governed by Navier–Stokes equations and with the outflow conditions imposed by a model of distal resistance and compliance. The non-invasive P d - CFD , P a - CFD , and FPRCFD were then obtained from the computational fluid dynamics calculation using a 16-core parallel computer. The invasive and non-invasive parameters were tested by statistical analysis. For this group of patients, the computational fluid dynamics method achieved comparable results with the invasive measurements. The fractional pressure ratio and FPRCFD are very close and highly correlated, but not linearly proportional, with the percentage of stenosis. The proposed computational fluid dynamics method can potentially be useful in assessing the functional alteration of cerebral stenosis.

Fractional Flow Assessment for the Evaluation of Intracranial Atherosclerosis: A Feasibility Study

Purpose: Current studies on endovascular intervention for intracranial atherosclerosis select patients based on luminal stenosis. Coronary studies demonstrated that fractional flow measurements assess ischemia better than anatomical stenosis and can guide patient selection for intervention. We similarly postulated that fractional flow can be used to assess ischemic stroke risk. Methods: This was a feasibility study to assess the technical use and safety of applying a pressure guidewire to measure fractional flow across intracranial stenoses. Twenty patients with severe intracranial stenosis were recruited. The percentage of luminal stenosis, distal to proximal pressure ratios (fractional flow) and the fractional flow gradients across the stenosis were measured. Procedural success rate and safety outcomes were documented. Results: All 20 patients had successful crossing of stenosis by the pressure guidewire. Ten patients underwent angioplasty, and 5 had stenting performed. There was one perforator stroke, but not related to the use of the pressure wire. For the 13 patients with complete pre- and postintervention data, the mean preintervention stenosis, fractional flow and translesional pressure gradient were 76.2%, 0.66 and 29.9 mm Hg, whilst the corresponding postintervention measurements were 24.7%, 0.88 and 10.9 mm Hg, respectively. Fractional flow (r = -0.530, p = 0.001) and the translesional pressure gradient (r = 0.501, p = 0.002) only had a modest correlation with the luminal stenosis. Conclusion: Fractional flow measurement by floating a pressure guidewire across the intracranial stenosis was technically feasible and safe in this study. Further studies are needed to validate its use for ischemic stroke risk assessment.

Multimodal CT techniques for cerebrovascular and hemodynamic evaluation of ischemic stroke: occlusion, collaterals, and perfusion

ABSTRACT Neuroimaging of cerebrovascular status and hemodynamics has vastly improved our understanding of stroke mechanisms and provided information for therapeutic decision-making. CT techniques are the most commonly used techniques due to wide availability, rapid acquisition and acceptable tolerance. Numerous multimodal CT techniques have been developed in the last few years. We summarize and explain the various multimodal CT acquisition techniques within three categories based on the scanning mode, namely static mode (single-phase CTA), multiple static mode (multi-phase CTA) and continuous mode (CT perfusion and dynamic CTA). Post-processing methods based on different acquisition modes are also introduced in an easy manner by focusing on the information extracted and products generated. We also describe the applications for these techniques along with their advantages and disadvantages.

Performance of computed tomography angiography to determine anterograde and collateral blood flow status in patients with symptomatic middle cerebral artery stenosis

Background The purpose of this study was to determine the performance of computed tomography angiography (CTA) by using a scoring system to predict anterograde and collateral blood flow status in patients with symptomatic middle cerebral artery (MCA) stenosis with use of conventional angiography as standard reference. Methods We retrospectively identified all consecutive patients with unilateral symptomatic MCA stenosis in our center who underwent conventional angiography and CTA within 1 month. The anterograde and collateral blood flow (AnCo) scoring system consisted of anterograde score (AnS) and collateral score (CoS). Evaluation of the CTA images was done independently by two readers, based on the AnCo scoring system. The conventional angiography was assessed by using the Thrombolysis in Cerebral Infarction (TICI) and American Society of Interventional and Therapeutic Neuroradiology (ASITN/SIR) scoring system to determine the status of anterograde and collateral blood flow. Diagnostic performance of AnCo was evaluated by using the area under the receiver operating characteristic (ROC) curve. Results A total of 61 patients were included in the analysis with mean age of 53.4 ± 11.0 years. AnS demonstrated a strong correlation with TICI with statistical significance (r = 0.786; p < 0.001). CoS had a modest yet statistically significant correlation with ASITN/SIR (r = 0.574; p < 0.001). The ROC curve analysis for AnS demonstrated an area under the curve (AUC) of 0.894 (p < 0.001) and the ROC curve analysis for CoS showed an AUC of 0.824 (p < 0.001). Conclusions CTA was a potential method to evaluate anterograde and collateral blood flow status in patients with symptomatic unilateral MCA stenosis.

Mechanical thrombectomy and rescue therapy for intracranial large artery occlusion with underlying atherosclerosis

Objective To investigate the safety and efficacy of mechanical thrombectomy plus rescue therapy for intracranial large artery occlusion (ILAO) with underlying intracranial atherosclerosis (ICAS). Methods Patients enrolled in the intervention group of EAST (Endovascular Therapy for Acute ischemic Stroke Trial) were analyzed. For underlying ICAS identified during the stent retrieval procedure, rescue treatment was required for those with (1) a degree of arterial stenosis >70% or (2) any degree of arterial with blood flow impairment or (3) evidence of re-occlusion. Outcomes were compared between the ICAS group and the embolic group. Multivariate logistic regression was performed to determine independent predictors of functional independence at 90 days. Results Among the 140 patients included in the analysis, underlying ICAS was identified in 47 (34%), and 30 patients (21.4%) were considered to be eligible to receive rescue treatment. Of the 30 patients, 27 (90%) actually received rescue therapy. Recanalization rate (95.7% vs 96.8%, P=0.757) and functional independence at 90 days (63.8% vs 51.6%, P=0.169) were comparable between the ICAS group and the embolic group. No significant difference in symptomatic hemorrhage (4.3% vs 4.3%, P=1.000) or death (12.8% vs 12.9%, P=0.982) was found between the two groups. National Institutes of Health Stroke Scale score at presentation (OR=0.865, 95% CI 0.795 to 0.941; P=0.001) and modified Thrombolysis in Cerebral Infarction after the procedure (OR=2.864, 95% CI 1.018 to 8.061; P=0.046) were independently associated with functional independence at 90 days. Conclusions Mechanical thrombectomy is safe in patients with ILAO with underlying ICAS. By employing a standard rescue therapy, favorable outcomes could be achieved in such patients. Clinical trial registration NCT02350283 (Post-results).

Collateral circulation alters downstream hemodynamic stress caused by intracranial atherosclerotic stenosis

Abstract Objectives: Fractional flow reserve (FFR) accurately predicts the degree of stenosis and is now widely used to identify clinically significant severe coronary artery lesions. In the current study, we utilized a similar indicator, fractional flow (FF), to determine the hemodynamic impact of symptomatic intracranial atherosclerotic stenosis (ICAS) and to assess the correlation of FF with the severity of stenosis and collateral circulation. Methods: Patients with symptomatic ICAS (70–99% stenosis) confirmed on digital subtraction angiography (DSA) were consecutively recruited. FF was obtained during DSA examination with the use of pressure sensors and was measured as a ratio, comparing measurements distal to an ICAS lesion (Pd) and within the aorta (Pa). The degree of leptomeningeal collateralization was graded from zero (absent) to four (complete compensatory). The correlation between FF, anatomical stenosis, and collateral status was then analyzed. Results: Twenty-five patients with a mean age of 55.6 years were analyzed. The median percentage of stenosis and median FF were 82.3 and 0.68%, respectively. Eleven patients were found to have poor collateralization (grade 0-2), and fourteen patients were identified with good collateral circulation (grade 3-4). Overall, the hemodynamic impact of an atherosclerotic lesions worsened (decreased FF) as the percentage of stenosis increased, although this did not reach statistical significance (r = −0.398, p = 0.06). However, the status of collateralization significantly altered this correlation, worsening the hemodynamic impact in patients with poor collateral circulation (r = −0.677, p = 0.032). There was no difference in patients with good collateral circulation (r = −0.279, p = 0.356). Conclusion: An anatomically severe (70–99%) symptomatic ICAS lesion may generate significant hemodynamic stress downstream as assessed by the indicator FF, particularly in patients with poor collateral circulation. Further, good collateralization may mitigate this hemodynamic impact, partially explaining the protective effect of collateral circulation against recurrent stroke in such patients.

Factors associated with perforator stroke after selective basilar artery angioplasty or stenting

Background and purpose Perforator stroke is one of the most common complications of elective intracranial angioplasty and/or stenting, particularly in the basilar artery. Factors associated with the risk of post-procedural perforator stroke remain unexplored. We investigated factors affecting the risk of perforator stroke after basilar artery angioplasty and/or stenting. Materials and methods Consecutive patients undergoing basilar artery angioplasty and/or stenting due to symptomatic atherosclerotic stenosis were retrospectively included in this single-center study. Analyzed variables including demographic data, risk factors of atherosclerosis, symptoms, characteristics of imaging, and procedure factors were extracted from electronic health records or imaging data. The main outcome was perforator stroke associated with the procedure. Multivariate analysis that correlated factors with the occurrence of perforator stroke in these patients was performed. Results A total of 255 patients were included in the study. Perforator stroke associated with angioplasty and/or stenting was identified in 13 patients (5.1%). Variables with significant correlation with post-procedural perforator stroke included diabetes (OR 6.496; 95% CI 1.741 to 24.241; p=0.005), time from last symptom to procedure <18 days (OR 5.669; 95% CI 1.174 to 27.371; p=0.031), and pre-procedure stenosis percentage <88.4% (OR 5.882; 95% CI 1.465 to 23.608; p=0.012). Conclusions Diabetes, time from last symptom to procedure, and pre-procedure stenosis percentage may be factors affecting the risk of perforator stroke associated with basilar artery angioplasty and/or stenting. These factors should be considered in planning of potential basilar artery angioplasty and/or stenting and prospectively evaluated in future multicenter trials.

Deposition of BACE-1 Protein in the Brains of APP/PS1 Double Transgenic Mice

The main causes of Alzheimers disease remain elusive. Previous data have implicated the BACE-1 protein as a central player in the pathogenesis of Alzheimers disease. However, many inhibitors of BACE-1 have failed during preclinical and clinical trials for AD treatment. Therefore, uncovering the exact role of BACE-1 in AD may have significant impact on the future development of therapeutic agents. Three- and six-month-old female APP/PS1 double transgenic mice were used to study abnormal accumulation of BACE-1 protein in brains of mice here. Immunofluorescence, immunohistochemistry, and western blot were performed to measure the distributing pattern and expression level of BACE-1. We found obvious BACE-1 protein accumulation in 3-month-old APP/PS1 mice, which had increased by the time of 6 months. Coimmunostaining results showed BACE-1 surrounded amyloid plaques in brain sections. The abnormal protein expression might not be attributable to the upregulation of BACE-1 protein, as no significant difference of protein expression was observed between wild-type and APP/PS1 mice. With antibodies against BACE-1 and CD31, we found a high immunoreactive density of BACE-1 protein on the outer layer of brain blood vessels. The aberrant distribution of BACE-1 in APP/PS1 mice suggests BACE-1 may be involved in the microvascular abnormality of AD.

Tyrosol attenuates pro-inflammatory cytokines from cultured astrocytes and NF-κB activation in in vitro oxygen glucose deprivation

ABSTRACT Subsequent inflammation in stroke plays an important role in the damage of neurons in the perilesional area. Therapeutic intervention targeting inflammation may be a promising complementary strategy to current treatments of stroke. Here, we explored the possible beneficial effects of tyrosol, a derivative of phenethyl alcohol and natural antioxidant, playing an anti‐inflammatory role in astrocyte culture and in vitro oxygen glucose deprivation (OGD) model. MTT, western blot, ELISA and EMSA assays were carried out to investigate cell viability, protein expression level, cytokine expression and NF‐&kgr;B activity. We found tyrosol protected cultured astrocytes against OGD‐induced cell viability loss in MTT test. Meanwhile, tyrosol attenuated the released TNF‐&agr; and IL‐6 level from astrocyte via regulating Janus N‐terminal kinase (JNK). The reduction of cytokines from astrocyte might be due to its inhibition of astrocyte activation and regulation of STAT3 signaling pathway since tyrosol attenuated the expression level of GFAP (glial fibrillary acidic protein) and the phosphorylation of STAT3. Additionally, we demonstrated that tyrosol prevented the degradation of I&kgr;B&agr; and the increase of I&kgr;B&agr; phosphorylation in astrocytes exposed to OGD, which led to the suppression of NF‐&kgr;B function during ischemia. Collectively, our results showed that tyrosol may be a promising complementary treatment compound for stroke via modulating the inflammatory response in astrocytes during ischemia. HighlightsOGD induces the release of cytokines from astrocytes.Tyrosol attenuates the neuroinflammation of astrocytes.Tyrosol suppresses NF‐&kgr;B function of astrocytes under OGD.Tyrosol may be a promising supplementary treatment compound for stroke.