Regional Cerebral Blood Flow Research Articles

Paying Homage to Microvessel Remodeling and Small Vessel Disease in Neurodegeneration: Implications for the Development of Late-Onset Alzheimer’s Disease

The microvessel neurovascular unit, with its brain endothelial cells (BEC) and blood–brain barrier remodeling, is important in the development of impaired cognition in sporadic or late-onset Alzheimer’s disease (LOAD), which is associated with aging and is highly prevalent in older populations (≥65 years of age). It is also linked with vascular dementia and vascular contributions to cognitive impairment and dementia, including cerebral amyloid angiopathy in neurodegeneration. LOAD is considered to be the number one cause of dementia globally; however, when one considers the role of mixed dementia (MD)—the combination of both the amyloid cascade hypothesis and the vascular hypothesis of LOAD—it becomes apparent that MD is the number one cause. Microvessel BECs are the first cells in the brain to be exposed to peripheral neurotoxins from the systemic circulation and are therefore the brain cells at the highest risk for early and chronic injury. Therefore, these cells are the first to undergo injury, followed by excessive and recurrent wound healing and remodeling processes in aging and other age-related diseases such as cerebrocardiovascular disease, hypertension, type 2 diabetes mellitus, and Parkinson’s disease. This narrative review explores the intricate relationship between microvessel remodeling, cerebral small vessel disease (SVD), and neurodegeneration in LOAD. It also discusses the current understanding of how microvessel dysfunction, disruption, and pathology contribute to the pathogenesis of LOAD and highlights potential avenues for therapeutic intervention.

Association of early perioperative stroke after cardiothoracic surgery with intraoperative regional cerebral oxygenation using near-infrared spectroscopy: an observational cohort study comparing affected versus non-affected hemispheres.

Patients undergoing cardiothoracic surgery are at risk of developing perioperative stroke, but residual effects of anesthesia may hamper timely detection. This study aims to determine if there is an association between intraoperative regional cerebral oxygenation (ScO2) monitoring using near-infrared spectroscopy (NIRS) and the occurrence of early perioperative stroke within three days after cardiothoracic surgery. We performed a single-center retrospective observational cohort study including all consecutive cardiothoracic surgery patients with routinely perioperative ScO2 monitoring admitted postoperatively to the Intensive Care Unit (ICU) between 2008 and 2017. Patients with a confirmed stroke in the anterior cerebral circulation on brain imaging were included in the analysis. Intraoperative area under the curve (AUC), duration, and total ScO2 excursions below predefined thresholds (< 50% ScO2 or > 20% reduction below baseline) were calculated for each hemisphere. Stroke-affected and non-affected hemispheres were compared using logistic regression analyses to investigate a potential association between ScO2 values and stroke. Of the 2454 cardiothoracic surgery patients with perioperative ScO2 monitoring, 39 had a anterior stroke on brain imaging. ScO2 readings of 44 affected hemispheres were compared to 34 non-affected hemispheres. Only the duration of ScO2 < 50% or a > 20% drop from baseline were significantly associated with global ischemia (OR 1.30 (0.95%CI; 1.09-2.30)) when comparing affected (72 [5 to 33] min.) versus non-affected (28 [4 to 44] min.) hemispheres. The duration of ScO2 values < 50% or a drop > 20% from baseline were associated with the occurrence of early perioperative global cerebral ischemia within three days after cardiothoracic surgery.

Angiotensin-II drives changes in microglia–vascular interactions in rats with heart failure

Activation of microglia, the resident immune cells of the central nervous system, leading to the subsequent release of pro-inflammatory cytokines, has been linked to cardiac remodeling, autonomic disbalance, and cognitive deficits in heart failure (HF). While previous studies emphasized the role of hippocampal Angiotensin II (AngII) signaling in HF-induced microglial activation, unanswered mechanistic questions persist. Evidence suggests significant interactions between microglia and local microvasculature, potentially affecting blood–brain barrier integrity and cerebral blood flow regulation. Still, whether the microglial-vascular interface is affected in the brain during HF remains unknown. Using a well-established ischemic HF rat model, we demonstrate the increased abundance of vessel-associated microglia (VAM) in HF rat hippocampi, along with an increased expression of AngII AT1a receptors. Acute AngII administration to sham rats induced microglia recruitment to brain capillaries, along with increased expression of TNFα. Conversely, administering an AT1aR blocker to HF rats prevented the recruitment of microglia to blood vessels, normalizing their levels to those in healthy rats. These results highlight the critical importance of a rather understudied phenomenon (i.e., microglia-vascular interactions in the brain) in the context of the pathophysiology of a highly prevalent cardiovascular disease, and unveil novel potential therapeutic avenues aimed at mitigating neuroinflammation in cardiovascular diseases.

Assessing stroke recurrence in sICAS: a study on mCSVD score and culprit plaque magnetic resonance characteristics.

Recurrent ischemic stroke in patients with symptomatic intracranial atherosclerotic stenosis (sICAS) can be attributed to two main causes: intracranial atherosclerotic stenosis (ICAS) and cerebral small vessel disease (CSVD). This study investigates the potential associations between stroke recurrence and the modified cerebral small vessel disease (mCSVD) burden score, as well as the characteristics of culprit plaques related to intracranial artery high-resolution vessel wall imaging (HR-VWI). A total of 145 patients presenting sICAS underwent intracranial artery HR-VWI and routine cranial MRI at two large Chinese hospitals from December 2019-2022 were participants of this retrospective analysis. Standard MRI scans were used to calculate the mCSVD score. Following a 12-month observation period, the patients were categorized into two distinct groups depending on whether or not they experienced a subsequent stroke. Within 12 months, 32 patients experienced stroke recurrence. The recurrence group's mCSVD score was higher compared to the non-recurrence group (p < 0.001). Their luminal stenosis and culprit plaque thickness and burden were also higher (p < 0.05). Additionally, higher rates of diabetes, T1WI hyperintensity of culprit plaques, and significant plaque enhancement were observed in the recurrence group (p < 0.05). The adjusted Cox regression model indicated that the mCSVD score (HR = 1.730, 95% CI 1.021-2.933, p = 0.042) and T1WI hyperintensity of the culprit plaque (HR = 6.568, 95% CI 1.104-39.059, p = 0.039) remained significantly independent risk variables. The combination of the mCSVD score and T1WI hyperintensity of the culprit plaque demonstrated the highest efficacy in predicting stroke recurrence (z = 2.678, p < 0.05). The mCSVD score, associated with T1WI hyperintensity of culprit plaque, effectively predicts stroke recurrence and can be easily obtained, offering high clinical value.

Association between intercellular adhesion molecule-1 to depression and blood-brain barrier penetration in cerebellar vascular disease

BACKGROUND Cerebral small vessel disease (CSVD) is a prevalent cerebrovascular disease in clinical practice that is often associated with macrovascular disease. A clear understanding of the underlying causes of CSVD remains elusive. AIM To explore the association between intercellular adhesion molecule-1 (ICAM-1) and blood-brain barrier (BBB) penetration in CSVD. METHODS This study included patients admitted to Fuyang People’s Hospital and Fuyang Community (Anhui, China) between December 2021 and March 2022. The study population comprised 142 patients, including 80 in the CSVD group and 62 in the control group. Depression was present in 53 out of 80 patients with CSVD. Multisequence magnetic resonance imaging (MRI) and dynamic contrast-enhanced MRI were applied in patients to determine the brain volume, cortical thickness, and cortical area of each brain region. Moreover, neuropsychological tests including the Hamilton depression scale, mini-mental state examination, and Montreal cognitive assessment basic scores were performed. RESULTS The multivariable analysis showed that age [P = 0.011; odds ratio (OR) = 0.930, 95% confidence interval (CI): 0.880-0.983] and ICAM-1 levels (P = 0.023; OR = 1.007, 95%CI: 1.001-1.013) were associated with CSVD. Two regions of interest (ROIs; ROI3 and ROI4) in the white matter showed significant (both P &lt; 0.001; 95%CI: 0.419-0.837 and 0.366-0.878) differences between the two groups, whereas only ROI1 in the gray matter showed significant difference (P = 0.046; 95%CI: 0.007-0.680) between the two groups. ICAM-1 was significantly correlated (all P &lt; 0.05) with cortical thickness in multiple brain regions in the CSVD group. CONCLUSION This study revealed that ICAM-1 levels were independently associated with CSVD. ICAM-1 may be associated with cortical thickness in the brain, predominantly in the white matter, and a significant increase in BBB permeability, proposing the involvement of ICAM-1 in BBB destruction.

Quantitative mapping of cerebrovascular reactivity amplitude and delay with breath-hold BOLD fMRI when end-tidal CO2 quality is low.

Cerebrovascular reactivity (CVR), the ability of cerebral blood vessels to dilate or constrict in order to regulate blood flow, is a clinically useful measure of cerebrovascular health. CVR is often measured using a breath-hold task to modulate blood CO2 levels during an fMRI scan. Measuring end-tidal CO2 (PETCO2) with a nasal cannula during the task allows CVR amplitude to be calculated in standard units (vascular response per unit change in CO2, or %BOLD/mmHg) and CVR delay to be calculated in seconds. The use of standard units allows for normative CVR ranges to be established and for CVR comparisons to be made across subjects and scan sessions. Although breath-holding can be successfully performed by diverse patient populations, obtaining accurate PETCO2 measurements requires additional task compliance; specifically, participants must breathe exclusively through their nose and exhale immediately before and after each breath hold. Meeting these requirements is challenging, even in healthy participants, and this has limited the translational potential of breath-hold fMRI for CVR mapping. Previous work has focused on using alternative regressors such as respiration volume per time (RVT), derived from respiratory belt measurements, to map CVR. Because measuring RVT does not require additional task compliance from participants, it is a more feasible measure than PETCO2. However, using RVT does not produce CVR in standard units. In this work, we explored how to achieve CVR maps, in standard units, when breath-hold task PETCO2 data quality is low. First, we evaluated whether RVT could be scaled to units of mmHg using a subset of PETCO2 data of sufficiently high quality. Second, we explored whether a PETCO2 timeseries predicted from RVT using deep learning allows for more accurate CVR measurements. Using a dense-mapping breath-hold fMRI dataset, we showed that both rescaled RVT and rescaled, predicted PETCO2 can be used to produce maps of CVR amplitude and delay in standard units with strong absolute agreement to ground-truth maps. However, the rescaled, predicted PETCO2 regressor resulted in superior accuracy for both CVR amplitude and delay. In an individual with regions of increased CVR delay due to Moyamoya disease, the predicted PETCO2 regressor also provided greater sensitivity to pathology than RVT. Ultimately, this work will increase the clinical applicability of CVR in populations exhibiting decreased task compliance.

Microglial and Macrophage Plasticity and Regional Cerebral Blood Flow in the Prenatal Brain and Gut Under Vagus Nerve Stimulation.

An intricate relationship exists between the vagus nerve and systemic immune cell regulation, specifically during fetal development. Little is known about the connection between the vagus nerve and the brain's regional circulatory control. In this chapter, we present a methodology for studying the impact of vagus nerve signaling on these connections in the developing fetus using the sheep model for human fetal physiology. First, we present the protocol to study the connection between the vagus nerve physiology and the regional cerebral blood flow (rCBF). Next, we detail the protocol for measuring how vagal signaling alters microglial cell plasticity in gut and brain. In previous work, our team showed that vagotomy results in amplified redistribution of rCBF toward subcortical structures in the fetal brain. Conversely, efferent VNS reduces rCBF to cortical structures while afferent VNS diminishes the rise of rCBF to subcortical structures (independent of cortical rCBF) when compared to controls in the fetal brain. Additionally, our team showed that Iba-1 expression, a marker for microglial cellular signaling activation, rises in a dose-dependent relationship with systemic inflammatory activation in the setting of vagotomy. The findings support existing preclinical and clinical evidence in adult human physiology that vagotomy is neuroprotective for neurodegenerative diseases such as Parkinson's likely via a glial cell-mediated mechanism. Vagus nerve stimulation (VNS) has also been shown to alter rCBF patterns in adults with treatment-resistant depression, underscoring the importance of further investigation of the relationship between the vagus nerve and rCBF as early as in utero. Together, the body of evidence emphasizes that the vagal pathway is an important player in the programming of microglial cell phenotypes within the developing brain. Further study is needed to better understand the significance of these relationships for the development and treatment of early susceptibility to neuroinflammatory and neurodegenerative disorders in later life. Therefore, we present a methodology for assessing rCBF and morphometric features of microglial and macrophage cell activation to allow future teams to expand on the existing body of work and further examine these relationships at a cellular and systems' levels.

Higher Long-Term Visit-to-Visit Blood Pressure Variability Is Associated With Severe Cerebral Small Vessel Disease in the General Population.

Long-term visit-to-visit blood pressure (BP) variability is linked to various diseases, but its impact on cerebral small vessel disease (cSVD) burden, and its features remains uncertain. We analyzed 1284 participants from the Kailuan cohort (2006-2022). Visit-to-visit systolic BP (SBP), diastolic BP (DBP), and pulse pressure (PP) variability were categorized into tertiles (low, middle, high). Magnetic resonance imaging identified white matter hyperintensities (WMH), lacunae of presumed vascular origin (LA), cerebral microbleeds (CMBs), and visible perivascular spaces (PVS). Total cSVD burden was classified as none (0), mild (1), moderate (2), or severe (3-4) based on the presence of these features. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). High SBP variability was associated with moderate cSVD burden (OR = 1.89, 95% CI: 1.09-3.29) and PVS (OR = 1.62, 95% CI: 1.10-2.39). High DBP variability was associated with LA (OR = 1.74, 95% CI: 1.06-2.84). High PP variability showed a significant risk for severe cSVD burden (OR = 2.49, 95% CI: 1.34-4.63). These associations were modified by age and hypertension status. Among young adults (age < 60 years), high PP variability was associated with severe cSVD burden (OR = 3.33, 95% CI: 1.31-8.44), LA (OR = 3.02, 95% CI: 1.31-6.93), and PVS (OR = 1.86, 95% CI: 1.20-2.88). The risk effects of SBP and PP variability on cSVD burden were significant only in participants with hypertension. High long-term visit-to-visit BP variability (BPV), particularly in combination with hypertension, is a significant risk factor for total cSVD. Special attention should be given to PP variability in younger adults.

Cerebral disorders as a complication of whooping cough in a child under one year old

Whooping cough is a widespread infectious disease, the manifestations of which vary from nonspecific cough to life-threatening conditions with the development of apnea, hypoxic damage to the central nervous system, and respiratory failure, especially in young children. Against the background of a severe form of whooping cough, hemorrhages of various types can be observed, including in the brain. The team of authors describes a clinical case of cerebral impairment in a child under one year of age, which is associated with whooping cough. A day after discharge from the infectious diseases hospital, the child developed a generalized convulsive attack. Clinical, instrumental and objective data allowed us to establish a diagnosis: acute disorder of cerebral and spinal circulation of the hemorrhagic type. Subarachnoid hemorrhage. Severe anemia. Convulsive syndrome. Whooping cough. Subsequently, the development of signs of hydrocephalus was observed over time, with the further formation of multiple cysts and hemiatrophy of the right hemisphere of the brain.

Membrane Budding Inspired Biomimetic Nanocarrier Delivers Brain‐derived Neurotrophic Factor to Improve AD Cognition

AbstractNeurotropic factors, crucial for neural cell maturation and proliferation, hold great therapeutic potential for treating neurodegenerative diseases but face challenges in brain delivery. This study introduces a novel membrane budding‐inspired lipoprotein biomimetic nanocarrier for efficient packaging and precise brain delivery of brain‐derived neurotrophic factor (BDNF). The nanocarrier is created by mixing protein‐loaded biomimetic gel with liposomes composed of lipids prone to forming liquid‐disordered and liquid‐ordered phases. This interaction triggers phase separation and lipid membrane rearrangement, enabling effective protein encapsulation. To enhance blood‐brain barrier permeability and target damaged cerebral vasculature in Alzheimer's Disease, the nanocarrier (RAP‐BHP‐rHDL) is functionalized with Apolipoprotein E3 and αRAP peptides. The obtained RAP‐BHP‐rHDL alleviates neuronal damage, promotes neurogenesis, normalizes the cerebral microvasculature, improves the function of neurovascular units, and restores memory function in 5 × FAD mice. This innovative packaging approach and biomimetic nanocarrier design offer a promising strategy for delivering neurotropic factors to the central nervous system, potentially advancing the management of neurodegenerative diseases.

Higher burden of cerebral small vessel disease is associated with risk of incident stroke in community dwelling individuals.

Mild manifestations of individual cerebral small vessel disease (CSVD) markers are common and may not denote increased risk, but high CSVD burden identifies individuals at increased risk of stroke and dementia. Scores incorporating multiple individual CSVD markers may better identify a person's risk. We related a multi-marker CSVD score to risk of incident stroke and compared it with the Framingham Stroke Risk Profile (FSRP) in community-dwelling individuals. Framingham Heart Study participants aged ≥55 years, free of stroke and dementia and with brain magnetic resonance imaging ratings of CSVD markers were included. A multi-marker CSVD score reflecting increasing CSVD burden was used, assigning one point each for presence of cerebral microbleeds, severe perivascular spaces, extensive white matter hyperintensities, covert brain infarcts, and cortical superficial siderosis. Multivariable Cox proportional hazards regression analyses were used to relate CSVD score to incident stroke. Among 1,154 participants (46% male, mean age 70.9±8.7), 92 (8%) developed stroke over a median follow-up of 8.6 years (Q1-Q3: 5.1-12.5). In models adjusting for age, sex, time interval between clinic exam and MRI, FHS cohort, and FSRP, those with three or more markers had increased risk of stroke (HR: 2.62; 95% CI: 1.17-5.88). In comparison, a 5-percent increase in FSRP was also associated with increased risk (aHR: 1.16; 95% CI: 1.04-1.29). The FSRP and CSVD score had similar model discrimination metrics. Higher CSVD burden is associated with increased risk of stroke, beyond the effect explained by risk factors in the FSRP. These findings support consideration of CSVD burden to identify risk of stroke in community-dwelling individuals for early implementation of preventive strategies.

Intracerebral haemorrhage - mechanisms, diagnosis and prospects for treatment and prevention.

Intracerebral haemorrhage (ICH) is a devastating condition associated with high mortality and substantial residual disability among survivors. Effective treatments for the acute stages of ICH are limited. However, promising findings from randomized trials of therapeutic strategies, including acute care bundles that target anticoagulation therapies, blood pressure control and other physiological parameters, and trials of minimally invasive neurosurgical procedures have led to renewed optimism that patient outcomes can be improved. Currently ongoing areas of research for acute treatment include anti-inflammatory and haemostatic treatments. The implementation of effective secondary prevention strategies requires an understanding of the aetiology of ICH, which involves vascular and brain parenchymal imaging; the use of neuroimaging markers of cerebral small vessel disease improves classification with prognostic relevance. Other data underline the importance of preventing not only recurrent ICH but also ischaemic stroke and cardiovascular events in survivors of ICH. Ongoing and planned randomized controlled trials will assess the efficacy of prevention strategies, including antiplatelet agents, oral anticoagulants or left atrial appendage occlusion (in patients with concomitant atrial fibrillation), and optimal management of long-term blood pressure and statin use. Together, these advances herald a new era of improved understanding and effective interventions to reduce the burden of ICH.

Targeted TGF-βR2 Silencing in the Retrotrapezoid Nucleus Mitigates Respiratory Dysfunction and Cognitive Decline in a Mouse Model of Cerebral Amyloid Angiopathy with and without Stroke.

Cerebral amyloid angiopathy (CAA) is characterized by the deposition of amyloid-beta peptides within cerebral blood vessels, leading to neurovascular complications. Ischemic strokes result from acute disruptions in cerebral blood flow, triggering metabolic disturbances and neurodegeneration. Both conditions often co-occur and are associated with respiratory dysfunctions. The retrotrapezoid nucleus (RTN), which is crucial for CO2 sensing and breathing regulation in the brainstem, may play a key role in breathing disorders seen in these conditions. This study aims to investigate the role of Transforming Growth Factor Beta (TGF-β) signaling in the RTN on respiratory and cognitive functions in CAA, both with and without concurrent ischemic stroke.Adult male Tg-SwDI (CAA model) mice and C57BL/6 wild-type controls underwent stereotaxic injections of lentivirus targeting TGF-βR2 in the RTN. Stroke was induced by middle cerebral artery occlusion using a monofilament. Respiratory functions were assessed using whole-body plethysmography, while cognitive functions were evaluated through the Barnes Maze and Novel Object Recognition Test (NORT). Immunohistochemical analysis was conducted to measure TGF-βR2 and GFAP expressions in the RTN.CAA mice exhibited significant respiratory dysfunctions, including reduced respiratory rates and increased apnea frequency, as well as impaired cognitive performance. TGF-βR2 silencing in the RTN improved respiratory functions and cognitive outcomes in CAA mice. In CAA mice with concurrent stroke, TGF-βR2 silencing similarly enhanced respiratory and cognitive functions. Immunohistochemistry confirmed reduced TGF-βR2 and GFAP expressions in the RTN following silencing.Our findings demonstrate that increased TGF-β signaling and gliosis in the RTN contribute to respiratory and cognitive dysfunctions in CAA and CAA with stroke. Targeting TGF-βR2 signaling in the RTN offers a promising therapeutic strategy to mitigate these impairments. This study is the first to report a causal link between brainstem gliosis and both respiratory and cognitive dysfunctions in CAA and stroke models.

The brain and hypertension: how the brain regulates and suffers from blood pressure.

The brain plays several roles in the relationship between blood pressure (BP) and the brain: it acts as the control center for BP regulation, a target organ in hypertension, and a crucial component for cognitive function. This mini-review introduces recent findings on "brain and hypertension" from Hypertension Research and other journals. Activation of the angiotensin II type 1 receptor (AT1R) signaling pathway in the brain causes sympathoexcitation and hypertension. AT1R-associated protein and β-arrestin promote AT1R internalization and suppress AT1R signaling, with brain-specific roles in BP regulation. The brain receives various inputs from the peripheral system, including the heart and kidneys, and controls central sympathetic outflow. The brain mechanism involved in the enhanced cardiac sympathetic afferent reflex and the beneficial effects of renal denervation have been demonstrated. The brain's vulnerability in hypertension includes stroke, with cerebral small vessel disease (SVD) contributing to stroke risk and brain changes. Sex differences and the age of hypertension onset influence these outcomes. High salt intake exacerbates hypertension and stroke risk, with central mechanisms like sympathoexcitation implicated. Hypertension significantly impacts cognitive function, linking to cerebral SVD and cognitive decline. Orthostatic BP regulation abnormalities also emerge as early risk markers for dementia. Improved BP control in hypertensive individuals can significantly reduce the risk of stroke and cognitive decline, as well as cardiovascular disease, enhancing overall brain health and quality of life. Further understanding the brain's role in BP regulation and the pathogenesis of hypertension will facilitate the development of novel hypertension treatments and prevention strategies.

Early Impairment of Face Perception in Post-Stroke Depression: An ERP Study.

Objective: Face recognition is an important cognitive function of the human brain. Post stroke depression (PSD) is a common mental complication after stroke, which has a serious impact on individual physical function recovery and quality of life. This study aims to explore the face perception characteristics of PSD through electrophysiological indicators N170 and VPP, and provide an objective basis for the early evaluation of facial cognitive dysfunction in PSD. Methods: 58 patients in the cerebral small vessel disease (CSVD) with depressive symptoms (PSD) and 188 patients in the pure CSVD (NPSD). At the same time, 30 healthy subjects were selected as the healthy controls (HC). The differences of N170 and VPP components between the three groups were compared under the stimulation of inverted faces and upright faces. Results: PSD patients exhibited significantly longer peak latency and lower amplitude of N170 and VPP under both inverted and upright face stimulation compared to HC and NPSD. These results suggest that PSD patients have defects in early face recognition, there are abnormalities in the early perception and structural encoding of face information, and both the "overall mechanism" and "feature mechanism" of face recognition are damaged. Conclusions: These findings provide neuroelectrophysiological evidence for impaired emotionless face recognition in PSD patients.

Development and Validation of a Flow-Dependent Endothelialized 3D Model of Intracranial Atherosclerotic Disease.

Intracranial atherosclerotic disease (ICAD) is a major cause of stroke globally, with mechanisms presumed to be shared with atherosclerosis in other vascular regions. Due to the scarcity of relevant animal models, testing biological hypotheses specific to ICAD is challenging. We developed a workflow to create patient-specific models of the middle cerebral artery (MCA) from neuroimaging studies, such as CT angiography. These models, which can be endothelialized with human endothelial cells and subjected to flow forces, provide a reproducible ICAD model. Using imaging from the SAMMPRIS clinical trial, we validated this novel model. Computational fluid dynamics flow velocities correlated strongly with particle-derived flow, regardless of stenosis degree. Post-stenotic flow disruption varied with stenosis severity. Single-cell RNA-seq identified flow-dependent endothelial gene expression and specific endothelial subclusters in diseased MCA segments, including upregulated genes linked to atherosclerosis. Confocal microscopy revealed flow-dependent changes in endothelial cell proliferation and morphology in vessel segments related to stenosis. This platform, rooted in the specific anatomy of cerebral circulation, enables detailed modeling of ICAD lesions and pathways. Given the high stroke risk associated with ICAD and the lack of effective treatments, these experimental models are crucial for developing new ICAD-related stroke therapies.

Imaging, biomarkers, and vascular cognitive impairment in China: Rationale and design for the VICA study.

Vascular cognitive impairment (VCI) is highly heterogeneous, with unclear pathogenesis. Individuals with vascular risk factors (VRF), cerebral small vessel disease (CSVD), and stroke are all at risk of developing VCI. To address the growing challenges posed by VCI, the "Vascular, Imaging and Cognition Association of China" (VICA) was established. VICA aims to recruit 10,000 participants, including 2000 with VRF, 3000 with CSVD, and 5000 stroke patients, to form a nationwide multicenter cohort. The study integrates clinical, neuroimaging, and multi-omics data to better understand VCI heterogeneity, improve disease prediction, and ensure timely diagnosis. VICA has screened 2045 eligible VRF participants from six communities in Wuhan, Shanghai, and Taizhou, along with 602 CSVD and 1269 stroke patients from 135 hospitals nationwide. Baseline enrollment and follow-up work are still ongoing. Establishing a high-quality longitudinal cohort is crucial for understanding VCI pathogenesis and developing novel markers for early screening and diagnosis. Establish a large-scale prospective longitudinal cohort comprising 10,000 participants, focusing on the high-risk population of vascular cognitive impairment (VCI) in China. Establish a nationwide three-tier medical network, make full use of resources, and achieve extensive enrollment of patients with cerebral small vessel disease and stroke patients. Utilize multimodal imaging and biomarkers to lay the foundation for constructing more-precise risk models. Introduce eye movement and gait analysis as new methods for assessing cognitive function. Use positron emission tomography to further investigate the interaction between vascular factors and neurodegeneration.

Cerebral Arterial Inflow and Venous Outflow Assessment Using 4D Flow MRI in Adult and Pediatric Patients

Background and Purpose: The cerebral circulation is highly regulated to maintain brain perfusion, keeping an equilibrium between the brain tissue, cerebrospinal fluid (CSF) and blood of the arterial and venous systems. Cerebral venous drainage abnormalities have been implicated in multiple cerebrovascular diseases. The purpose of this study is to evaluate the relationship between the arterial inflow (AI) and the cerebral venous outflow (CVO) and their correlation with the cardiac outflow in healthy adults and children to understand the role of the emissary veins in normal venous drainage. Materials and Methods: A total of 31 healthy volunteers (24 adults (39.5 ± 16.0) and seven children (3.4 ± 2.2)) underwent intracranial 4D flow with full circle of Willis coverage and 2D PC-MRI at the level of the transverse sinus for measurement of the AI and CVO, respectively. The AI was calculated as the sum of the flow values in the bilateral internal carotid and basilar arteries. The CVO was calculated as the sum of the flow values in the bilateral transverse sinuses. The cardiac outflow was measured via 2D PC-MRI with retrospective ECG gating with images acquired at the proximal ascending aorta (AAo) and descending (DAo) aorta. The ratios of the AI/AAo flow and CVO/AI were calculated to characterize the fraction of cerebral arterial inflow in relation to cardiac outflow and venous blood draining through the transverse sinuses, respectively. Results: The AI and CVO were significantly correlated (r = 0.81, p &lt; 0.001). The CVO constituted approximately 60–70% of the AI. The CVO/AI ratio was significantly lower in children versus adults (p = 0.025). In adults, the negative correlation of the AI with age remained strong (r = −0.81, p &lt; 0.001). However, the CVO was not significantly associated with age. Conclusion: The CVO/AI ratio suggests an important role of the emissary veins, accounting for approximately 30–40% of venous drainage. The lower CVO/AI ratio in children, although partially related to decreased AI with age, suggests a greater role of the emissary veins in childhood, which strongly decreases with age.

Current Status and Progress in Integrative Treatment of Acute Ischemic Cerebrovascular Disease

Acute ischemic cerebrovascular disease (AICD) poses a severe threat to human health, characterized by high incidence and disability rates. Western medicine currently offers multiple treatment methods, such as thrombolysis, anticoagulation, and cerebral circulation improvement, while traditional Chinese medicine demonstrates unique advantages in herbal prescriptions, proprietary Chinese medicines, acupuncture, and massage therapies. Integrative treatment approaches combining Chinese and Western medicine have become widespread in clinical practice, yet challenges remain in optimizing specific treatment plans and elucidating mechanisms of action. This paper aims to comprehensively analyze the current status of integrative treatment for AICD, outline its developmental trajectory, and provide insights for enhancing treatment efficacy.

Interictal EEG spikes increase perfusion in low-grade epilepsy-associated tumors: a pediatric arterial spin labeling study.

Arterial spin labeling (ASL), a noninvasive magnetic resonance (MRI) perfusion sequence, holds promise in the presurgical evaluation of pediatric lesional epilepsy patients, including those with low-grade epilepsy-associated tumors (LEATs). The interpretation of ASL-derived perfusion patterns, however, presents challenges. Our study aims to elucidate these perfusion changes in children with LEATs, exploring their correlations with clinical, electroencephalography (EEG), and anatomical MRI findings. Our cohort included 15 children with LEAT-associated focal lesional epilepsy who underwent single-delay pseudo-continuous ASL imaging; eight were imaged under sedation. We assessed perfusion images both qualitatively and quantitatively, focusing on LEAT-related perfusion changes, as indicated by the asymmetry index (AI) and regional cerebral blood flow (rCBF). ASL revealed LEAT-related perfusion changes in all but two patients: 12 LEATs were hypoperfused and one was hyperperfused relative to the contralateral brain parenchyma (CBP). LEATs showed significantly lower perfusion compared to CBP (median: 38.7 vs. 59.1mL/100g/min for LEAT and CBP, respectively; p value = 0.004, Wilcoxon-Mann-Whitney), regardless of sedation. Notably, elevated AI and rCBF values correlated with interictal spikes on EEG (median: -0.008 and 0.84 vs -0.27 and 0.58, respectively), but not to other clinical, EEG, or MRI variables (p value = 0.036, Wilcoxon-Mann-Whitney). By highlighting the connection between LEAT and brain perfusion, and by correlating perfusion characteristics and epileptogenicity, our research enhanced our understanding of pediatric epilepsy associated with LEATs. Also, by proving the robustness of these findings to sedation we confirmed the importance of adding ASL to epilepsy protocols to as a valuable tool to supplement anatomical imaging.