Added Clinical Value of Intraplaque Neovascularization Detection to Color Doppler Ultrasound for Assessing Ischemic Stroke Risk.

Purpose: Intraplaque neovascularization, assessed using contrast-enhanced ultrasound (CEUS), is associated with ischemic stroke. It remains unclear whether detection of intraplaque neovascularization combined with color Doppler ultrasound (CDUS) provides additional value compared with CDUS alone in assessing ischemic stroke risk. Therefore, we investigated the clinical value of combined CEUS, CDUS, and clinical features for ischemic stroke risk stratification. Patients and Methods: We recruited 360 patients with ≥50% carotid stenosis between January 2019 and September 2022. Patients were examined using CDUS and CEUS. Covariates associated with ischemic stroke were identified using multivariate logistic regression analysis. The discrimination and calibration were verified using the C-statistic and Hosmer-Lemeshow test. The incremental value of intraplaque neovascularization in the assessment of ischemic stroke was analyzed using the Delong test. Results: We analyzed the data of 162 symptomatic and 159 asymptomatic patients who satisfied the inclusion and exclusion criteria, respectively. Based on multivariate logistic regression analysis, we constructed a nomogram using intraplaque neovascularization, degree of carotid stenosis, plaque hypoechoicity, and smoking status, with a C-statistic of 0.719 (95% confidence interval [CI]: 0.666-0.768) and a Hosmer-Lemeshow test p value of 0.261. The net reclassification index of the nomogram was 0.249 (95% CI: 0.138-0.359), and the integrated discrimination improvement was 0.053 (95% CI: 0.029-0.079). Adding intraplaque neovascularization to the combination of CDUS and clinical features (0.672; 95% CI: 0.617-0.723) increased the C-statistics (p=0.028). Conclusion: Further assessment of intraplaque neovascularization after CDUS may help more accurately identify patients at risk of ischemic stroke. Combining multiparametric carotid ultrasound and clinical features may help improve the risk stratification of patients with ischemic stroke with ≥50% carotid stenosis.

We studied whether using contrast-enhanced ultrasound (CEUS) to detect intraplaque neovascularization could help better determine the risk of ischemic stroke. We compared the combined use of color Doppler ultrasound (CDUS) and CEUS with CDUS alone in patients with more than 50% carotid narrowing. Our findings showed that combining clinical details, CDUS, and CEUS was more effective (0.719 vs 0.672). This means that CEUS provides extra insight when gauging ischemic stroke risk compared with CDUS alone. This could help in accurately identifying patients at high risk of stroke. However, more extensive studies are needed to fully understand the role of these tests in the evaluation of stroke risk.

Comparable dynamic cerebral autoregulation and neurovascular coupling of the posterior cerebral artery between healthy men and women.

AIMS: Most studies focus on dynamic cerebral autoregulation (dCA) in the middle cerebral artery (MCA), and few studies investigated neurovascular coupling (NVC) and dCA in the posterior cerebral artery (PCA). We investigated NVC and dCA of the PCA in healthy volunteers to identify sex differences. METHODS: Thirty men and 30 age-matched women completed dCA and NCV assessments. The cerebral blood flow velocity (CBFV) and mean arterial pressure were evaluated using transcranial Doppler ultrasound and a servo-controlled plethysmograph, respectively. The dCA parameters were analyzed using transfer function analysis. The NCV was evaluated by eyes-open and eyes-closed (24 s each) periodically based on voice prompts. The eyes-open visual stimulation comprised silent reading of Beijing-related tourist information. RESULTS: The PCA gain was lower than that of the MCA in all frequency ranges (all p < 0.05). Phase was consistent across the cerebrovascular territories. The cerebrovascular conductance index (CVCi) and mean CBFV (MV) of the PCA were significantly higher during the eyes-open than eyes-closed period (CVCi: 0.50 ± 0.12 vs. 0.38 ± 0.10; MV: 42.89 ± 8.49 vs. 32.98 ± 7.25, both p < 0.001). The PCA dCA and NVC were similar between the sexes. CONCLUSION: We assessed two major mechanisms that maintain cerebral hemodynamic stability in healthy men and women. The visual stimulation-evoked CBFV of the PCA was significantly increased compared to that during rest, confirming the activation of NVC. Men and women have similar functions in PCA dCA and NCV.

Impaired Dynamic Cerebral Autoregulation in Patients With Cerebral Venous Sinus Thrombosis: Evaluation Using Transcranial Doppler and Silent Reading Stimulation.

OBJECTIVE: Cerebral venous sinus thrombosis (CVST) may impair dynamic cerebral autoregulation (dCA) of the middle cerebral artery (MCA). However, most studies have focused on dCA of the MCA; a few studies are based on the posterior cerebral artery (PCA) during silent reading and neurovascular coupling (NVC). This study explored the effects of CVST on dCA of the MCA and PCA during silent reading and NVC. METHODS: From January 2021 to August 2022, 60 CVST patients and 30 controls were enrolled in this study. Non-invasive continuous beat-to-beat blood pressure, cerebral blood flow velocity and other associated information on the MCA and PCA during silent reading were collected using a transcranial Doppler. NVC assessment was performed by opening and closing the eyes periodically based on voice prompts, and eye-opening visual stimulation was achieved by silently reading Chinese tourism materials. Visual stimulation signals can selectively activate Brodmann's areas 17, 18, and 19 of the occipital when reading silently with open eyes, prompting them to release neurotransmitters and dilate PCA. dCA was determined by transfer function analysis. RESULTS: In dCA of the PCA during silent reading, the CVST group's very low frequency phase was lower than that of the control group (p = 0.047). In NVC, the difference in the indexes of the cerebrovascular conductance and visually evoked flow response of the CVST group were lower than those of the control group (p = 0.017 and p = 0.019, respectively). CONCLUSION: Compared with the control group, dCA and NVC of the PCA during silent reading were impaired in CVST patients.

Intraplaque neovascularisation is associated with ischaemic events after carotid artery stenting: an observational prospective study.

Background: Intraplaque neovascularisation (IPN) is a component of vulnerable atherosclerotic plaque, which is a biomarker of cardiovascular events. However, the identification of patients with high probability of ischaemic events after carotid artery stenting (CAS) is mainly based on vascular risk factors. Prospective studies on the development of plaques are lacking. Objectives: The purpose of this study was to investigate whether IPN detected by contrast-enhanced ultrasound is related to the occurrence of ischaemic events after CAS. Methods: Sixty consecutive patients receiving CAS were prospectively enrolled in our centre. The patients were evaluated using contrast-enhanced ultrasound before CAS. According to the degree of microbubble enhancement, IPN was graded from 0 to 2. Endpoint events, including ischaemic stroke and other cardiovascular events, were recorded during follow-up. Kaplan-Meier survival curves and Cox proportional-hazards models were used to evaluate the risk factors for endpoint events. At a median follow-up of 30 months, 13 patients (28.9%) experienced endpoint events. Kaplan-Meier survival curves showed that patients with grade 2 IPN had a higher risk of future ischaemic events than those with grade 0 or 1 IPN (p < 0.05). Cox proportional-hazards models showed that grade 2 IPN [adjusted hazard ratio (HR), 4.049; 95% confidence interval (CI), 1.078-15.202] was a significant predictor of endpoint events (p < 0.05). Conclusion: Grade 2 IPN evaluated by contrast-enhanced ultrasound has predictive value for ischaemic events in patients after CAS and may help clinicians identify high-risk patients who need close follow-up. Plain Language Summary: Neovascularisation and carotid artery stenting Introduction: Introduction: It is unclear whether intraplaque neovascularisation (IPN) can be used as an biomarker of high probability ischemic events after carotid artery stenting (CAS).Materials and methods: We enrolled 60 patients who underwent CAS, all of whom underwent CEUS before CAS. We recorded ischaemic events during follow-up. Cox proportional-hazards models were used to evaluate the risk factors for ischaemic events.Results: We found that grade 2 IPN was an independent predictor (hazard ratio, 4.049; 95% confidence interval, 1.078-15.202; p < 0.05) of ischaemic events in patients after CAS.Conclusion: This may help clinicians identify high-risk patients who need close follow-up.

Carotid Intraplaque Neovascularization and Future Vascular Events in Patients With Asymptomatic Carotid Stenosis.

Objective: Intraplaque neovascularization is a marker of plaque vulnerability and is used to predict the risk of future vascular events in patients with symptomatic carotid stenosis; however, its association with asymptomatic carotid stenosis has not been prospectively evaluated. Therefore, this study aimed to explore the association between intraplaque neovascularization assessed using contrast-enhanced ultrasound and the occurrence of future ischemic events in asymptomatic patients diagnosed with carotid stenosis. Methods: We recruited patients with asymptomatic carotid stenosis from our center. Contrast-enhanced ultrasound was performed at baseline. The outcomes were ischemic stroke and cardiovascular events. We plotted Kaplan-Meier survival curves and performed a log-rank test to compare endpoint event probability in patients with and without grade 2 intraplaque neovascularization. Univariate and multivariate Cox proportional hazards models were used to assess predictors of future vascular events. Results: The data of 50 participants were included in the analysis (median follow-up, 43.7 months). Endpoint events occurred in 12 participants (24%). The Kaplan-Meier survival curves showed that patients with grade 2 intraplaque neovascularization had a higher probability of future vascular events than those with grades 0 and 1 (p < .05). Grade 2 intraplaque neovascularization (hazard ratio: 4.530, 95% confidence interval, 1.337-15.343, p < .05) was an independent predictor of future vascular events in patients with asymptomatic carotid stenosis. Conclusion: Grade 2 intraplaque neovascularization assessed using contrast-enhanced ultrasound independently predicted future ischemic events in patients with asymptomatic carotid stenosis, and contrast-enhanced ultrasound may be an effective screening method to identify high-risk subgroups of patients with asymptomatic carotid stenosis.

The Potential Role of Hypoxia-Inducible Factor-1 in the Progression and Therapy of Central Nervous System Diseases.

Hypoxia-inducible factor-1 (HIF-1) is a heterodimer protein composed of an oxygenregulated functional subunit, HIF-1α, and a structural subunit, HIF-1ß, belonging to the basic helixloop- helix family. Strict regulation of HIF-1 protein stability and subsequent transcriptional activity involves various molecular interactions and is primarily controlled by post-transcriptional modifications. Hypoxia, owing to impaired cerebral blood flow, has been implicated in a range of central nervous system (CNS) diseases by exerting a deleterious effect on brain function. As a master oxygen- sensitive transcription regulator, HIF-1 is responsible for upregulating a wide spectrum of target genes involved in glucose metabolism, angiogenesis, and erythropoiesis to generate the adaptive response to avoid, or at least minimize, hypoxic brain injury. However, prolonged, severe oxygen deprivation may directly contribute to the role-conversion of HIF-1, namely, from neuroprotection to the promotion of cell death. Currently, an increasing number of studies support the fact HIF-1 is involved in a variety of CNS-related diseases, such as intracranial atherosclerosis, stroke, and neurodegenerative diseases. This review article chiefly focuses on the effect of HIF-1 on the pathogenesis and mechanism of progression of numerous CNS-related disorders by mediating the expression of various downstream genes and extensive biological functional events and presents robust evidence that HIF-1 may represent a potential therapeutic target for CNS-related diseases.

Carotid intraplaque neovascularisation as a predictive factor for future vascular events in patients with mild and moderate carotid stenosis: an observational prospective study.

BACKGROUND: Intraplaque neovascularisation (IPN) increases the vulnerability of plaques, which makes them more likely to rupture and increases the risk of vascular events. However, it is unclear whether IPN can predict future vascular events (stroke recurrence and cardiovascular events). Previous studies on IPN have focused on patients with severe stenosis but overlooked patients with mild and moderate stenosis. This study aimed to investigate whether IPN assessed by contrast-enhanced ultrasonography (CEUS) in patients with mild and moderate degrees of stenosis is associated with future vascular events. METHODS: One hundred and twenty-one patients participated in this study. 76 patients who met the inclusion and exclusion criteria were included in the final dataset of the study. IPN was graded from 0 to 2 according to the extent of the microbubbles assessed using CEUS. The degree of carotid stenosis was graded as mild, moderate, or severe. We recorded future vascular events during the follow-up. Univariate and multivariate logistic regression analyses were used to evaluate risk factors for future vascular events. RESULTS: After a follow-up period of 30 ± 6 months, 30 patients (39.5%) experienced subsequent vascular events. Compared with the 'non-recurrent' group, the 'recurrent' group showed a higher proportion of grade 2 neovascularisation (p < 0.05), and it was an independent predictor of subsequent vascular events (odds ratio 6.066, 95% confidence interval 1.565-23.512, p < 0.05). Furthermore, in patients with mild and moderate stenosis, future vascular events occurred in an unexpectedly high proportion (up to 42.9%). In the 'recurrent' group, 55% of patients with mild and moderate stenosis had grade 2 neovascularisation. CONCLUSION: IPN by CEUS was an independent predictor of future vascular events in patients with recent ischemic stroke, and the high proportion of neovascularisation in patients with mild and moderate stenosis requires more attention.