Pasteurella multocida infection induces blood-brain barrier disruption by decreasing tight junctions and adherens junctions between neighbored brain microvascular endothelial cells.

Meningitis induced by Pasteurella multocida has been substantially described in clinical practice in both human and veterinary medicine, but the underlying mechanisms have not been previously reported. In this study, we investigated the influence of P. multocida infection on the permeability of the blood-brain barrier (BBB) using different models. Our in vivo tests in a mouse model and in vitro tests using human brain microvascular endothelial cell (hBMEC) model showed that P. multocida infection increased murine BBB permeability in mice and hBMEC monolayer permeability. Furthermore, we observed that P. multocida infection resulted in decreased expression of tight junctions (ZO1, claudin-5, occludin) and adherens junctions (E-cadherin) between neighboring hBMECs. Subsequent experiments revealed that P. multocida infection promoted the activation of hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor A (VEGFA) signaling and NF-κB signaling, and suppressed the HIF-1α/VEGFA significantly remitted the decrease in ZO1/E-cadherin induced by P. multocida infection (P < 0.001). NF-κB signaling was found to contribute to the production of chemokines such as TNF-1α, IL-ß, and IL-6. Additionally, transmission electron microscopy revealed that paracellular migration might be the strategy employed by P. multocida to cross the BBB. This study provides the first evidence of the migration strategy used by P. multocida to traverse the mammalian BBB. The data presented herein will contribute to a better understanding of the pathogenesis of the zoonotic pathogen P. multocida.

The Unexpected Role of the Endothelial Nitric Oxide Synthase at the Neurovascular Unit: Beyond the Regulation of Cerebral Blood Flow.

Nitric oxide (NO) is a highly versatile gasotransmitter that has first been shown to regulate cardiovascular function and then to exert tight control over a much broader range of processes, including neurotransmitter release, neuronal excitability, and synaptic plasticity. Endothelial NO synthase (eNOS) is usually far from the mind of synaptic neurophysiologists, who have focused most of their attention on neuronal NO synthase (nNOS) as the primary source of NO at the neurovascular unit (NVU). Nevertheless, the available evidence suggests that eNOS could also contribute to generating the burst of NO that, serving as volume intercellular messenger, is produced in response to neuronal activity in the brain parenchyma. Herein, we review the role of eNOS in both the regulation of cerebral blood flow and of synaptic plasticity and discuss the mechanisms by which cerebrovascular endothelial cells may transduce synaptic inputs into a NO signal. We further suggest that eNOS could play a critical role in vascular-to-neuronal communication by integrating signals converging onto cerebrovascular endothelial cells from both the streaming blood and active neurons.

Perfusion MRI in Cerebral Venous and Sinus Thrombosis.

BACKGROUND AND PURPOSE: Cerebral venous and sinus thrombosis (CVST) leads to perfusion abnormality in the brain. Our aim was to assess perfusion abnormalities in the center and periphery of the parenchymal lesion in CVST patients and correlate with the clinical outcome. MATERIALS AND METHODS: Dynamic susceptibility contrast (DSC) perfusion imaging was performed in patients with CVST. Relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), and mean transit time (MTT) values were obtained in the center and periphery of the parenchymal lesion. RESULTS: A total of 30 consecutive patients of CVST were included in the study. Parenchymal lesion was present in 21 (70%) patients. In rest 9, perfusion map was showing some abnormality although conventional MRI was normal. Mean rCBV and MTT were increasing from periphery of the lesion to the center (rCBV 69.93 ± 29.79 at periphery (PL2) to 92.49 ± 32.07 at center of the lesion and 69.19 ± 25.52 at normal appearing contralateral brain parenchyma (NABP). MTT 11.83 ± 3.76 at periphery (PL2) to 15.27 ± 5.49 at center of the lesion and 10.63 ± 3.37 at NABP). rCBV and MTT from abnormal perfusion areas from 9 patients without parenchymal abnormalities are 92.89 ± 17.76 and 15.92 ± 3.66 respectively. CONCLUSION: There is an increasing trend of MTT and rCBV from periphery to center of the parenchymal lesion. MTT is the most consistent parameter to be abnormal in patients of CVST even in patients without parenchymal lesion. Residual neurological deficit was found in patients with increased rCBV and having large hemorrhagic infarct.

A neural cell automated analysis system based on pathological specimens in a gerbil brain ischemia model.

PURPOSE: Amid rising health awareness, natural products which has milder effects than medical drugs are becoming popular. However, only few systems can quantitatively assess their impact on living organisms. Therefore, we developed a deep-learning system to automate the counting of cells in a gerbil model, aiming to assess a natural product's effectiveness against ischemia. METHODS: The image acquired from paraffin blocks containing gerbil brains was analyzed by a deep-learning model (fine-tuned Detectron2). RESULTS: The counting system achieved a 79%-positive predictive value and 85%-sensitivity when visual judgment by an expert was used as ground truth. CONCLUSIONS: Our system evaluated hydrogen water's potential against ischemia and found it potentially useful, which is consistent with expert assessment. Due to natural product's milder effects, large data sets are needed for evaluation, making manual measurement labor-intensive. Hence, our system offers a promising new approach for evaluating natural products.

Fluorescent Pdots Facilitate High-Resolution Mapping of the Intact Meningeal Vascular Network and Eye-Brain Connections.

Meningeal vascular network is significant in neurology and neurosurgery. However, high-resolution imaging of intact meningeal vascular network is lacking. In this work, we develop a practical experimental method to ensure that the intact meninges are morphologically unfolded and fixed in an agarose gel. With the help of high-brightness polymer dots (Pdots) as probe, macroscopic and detailed imaging of the vascular network on the intact dorsal meninges can be performed. Meningeal vessels are symmetrically distributed along the superior sagittal sinus, and the distribution of meningeal vessels had a certain degree of hierarchy. The meninges are thicker blood vessels and capillary networks from the outside to the inside. Moreover, the diameter of the capillaries is 3.96 ± 0.89 µm. Interestingly, meningeal primo vessels in the central nervous system of mice is imaged with the diameter of 4.18 ± 1.18 µm, which has not been reported previously. It is worth mentioning that we found that orthotopic xenografts of brain tumors caused the appearance of corneal neovascularization and morphological changes in optic nerve microvessels. In conclusion, our work provides an effective Pdots-based imaging method for follow-up research on meningeal vascular-related diseases, and illustrates that the eye can serve as a window for the prevention and diagnosis of brain diseases.

Elevated cerebral blood flow proxy with increased beta-amyloid burden in Alzheimer's disease preclinical phase evaluated by dual-phase 18F-florbetaben positron emission tomography.

This study investigated the earliest change of cerebral blood flow (CBF) and its relationship with ß-amyloid (Aß) burden in preclinical Alzheimer's disease (AD) employing dual-phase 18F-florbetaben (FBB) PET. Seventy-one cognitively normal (NC) individuals were classified as Aß negative (Aß-NC) or positive (Aß+NC) based on two different cutoff values: an SUVR of > 1.08 and a Centiloid scale of > 20. The PET scans were acquired in two phases: an early phase (0-10 min, eFBB) and a delayed phase (90-110 min, dFBB), which were averaged to generate single-frame images for each phase. Furthermore, an R1 parametric map was generated from the early phase data using a simplified reference tissue model. We conducted regional and voxel-based analyses to compare the eFBB, dFBB, and R1 images between the Aß positive and negative groups. In addition, the correlations between the CBF proxy R1 and the dFBB SUVR were analyzed. The Aß+NC group showed significantly higher dFBB SUVR in both the global cerebral cortex and target regions compared to the Aß-NC group, while no significant differences were observed in eFBB SUVR between the two groups. Furthermore, the Aß+NC group exhibited significantly higher R1 values, a proxy for cerebral perfusion, in both the global cerebral cortex and target regions compared to the Aß-NC group. Significant positive correlations were observed between R1 and dFBB SUVR in both the global cerebral cortex and target regions, which remained significant after controlling for demographics and cognitive profiles, except for the medial temporal and occipital cortices. The findings reveal increased CBF in preclinical AD and a positive correlation between CBF and amyloid pathology. The positive correlation between R1 and amyloid burden may indicate a compensatory mechanism in the preclinical stage of Alzheimer's disease, but to elucidate this hypothesis, further longitudinal observational studies are necessary.

An end-to-end deep learning pipeline to derive blood input with partial volume corrections for automated parametric brain PET mapping.

Dynamic 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography (dFDG-PET) for human brain imaging has considerable clinical potential, yet its utilization remains limited. A key challenge in the quantitative analysis of dFDG-PET is characterizing a patient-specific blood input function, traditionally reliant on invasive arterial blood sampling. This research introduces a novel approach employing non-invasive deep learning model-based computations from the internal carotid arteries (ICA) with partial volume (PV) corrections, thereby eliminating the need for invasive arterial sampling. We present an end-to-end pipeline incorporating a 3D U-Net based ICA-net for ICA segmentation, alongside a Recurrent Neural Network (RNN) based MCIF-net for the derivation of a model-corrected blood input function (MCIF) with PV corrections. The developed 3D U-Net and RNN was trained and validated using a 5-fold cross-validation approach on 50 human brain FDG PET scans. The ICA-net achieved an average Dice score of 82.18% and an Intersection over Union of 68.54% across all tested scans. Furthermore, the MCIF-net exhibited a minimal root mean squared error of 0.0052. The application of this pipeline to ground truth data for dFDG-PET brain scans resulted in the precise localization of seizure onset regions, which contributed to a successful clinical outcome, with the patient achieving a seizure-free state after treatment. These results underscore the efficacy of the ICA-net and MCIF-net deep learning pipeline in learning the ICA structure's distribution and automating MCIF computation with PV corrections. This advancement marks a significant leap in non-invasive neuroimaging.

Secretome of brain microvascular endothelial cells promotes endothelial barrier tightness and protects against hypoxia-induced vascular leakage.

Cell-based therapeutic strategies have been proposed as an alternative for brain and blood vessels repair after stroke, but their clinical application is hampered by potential adverse effects. We therefore tested the hypothesis that secretome of these cells might be used instead to still focus on cell-based therapeutic strategies. We therefore characterized the composition and the effect of the secretome of brain microvascular endothelial cells (BMECs) on primary in vitro human models of angiogenesis and vascular barrier. Two different secretome batches produced in high scale (scHSP) were analysed by mass spectrometry. Human primary CD34+-derived endothelial cells (CD34+-ECs) were used as well as in vitro models of EC monolayer (CMECs) and blood-brain barrier (BBB). Cells were also exposed to oxygen-glucose deprivation (OGD) conditions and treated with scHSP during reoxygenation. Protein yield and composition of scHSP batches showed good reproducibility. scHSP increased CD34+-EC proliferation, tubulogenesis, and migration. Proteomic analysis of scHSP revealed the presence of growth factors and proteins modulating cell metabolism and inflammatory pathways. scHSP improved the integrity of CMECs, and upregulated the expression of junctional proteins. Such effects were mediated through the activation of the interferon pathway and downregulation of Wnt signalling. Furthermore, OGD altered the permeability of both CMECs and BBB, while scHSP prevented the OGD-induced vascular leakage in both models. These effects were mediated through upregulation of junctional proteins and regulation of MAPK/VEGFR2. Finally, our results highlight the possibility of using secretome from BMECs as a therapeutic alternative to promote brain angiogenesis and to protect from ischemia-induced vascular leakage.

Single-cell atlas of the human brain vasculature across development, adulthood and disease.

A broad range of brain pathologies critically relies on the vasculature, and cerebrovascular disease is a leading cause of death worldwide. However, the cellular and molecular architecture of the human brain vasculature remains incompletely understood1. Here we performed single-cell RNA sequencing analysis of 606,380 freshly isolated endothelial cells, perivascular cells and other tissue-derived cells from 117 samples, from 68 human fetuses and adult patients to construct a molecular atlas of the developing fetal, adult control and diseased human brain vasculature. We identify extensive molecular heterogeneity of the vasculature of healthy fetal and adult human brains and across five vascular-dependent central nervous system (CNS) pathologies, including brain tumours and brain vascular malformations. We identify alteration of arteriovenous differentiation and reactivated fetal as well as conserved dysregulated genes and pathways in the diseased vasculature. Pathological endothelial cells display a loss of CNS-specific properties and reveal an upregulation of MHC class II molecules, indicating atypical features of CNS endothelial cells. Cell-cell interaction analyses predict substantial endothelial-to-perivascular cell ligand-receptor cross-talk, including immune-related and angiogenic pathways, thereby revealing a central role for the endothelium within brain neurovascular unit signalling networks. Our single-cell brain atlas provides insights into the molecular architecture and heterogeneity of the developing, adult/control and diseased human brain vasculature and serves as a powerful reference for future studies.

Simulation-based optimization and experimental comparison of intracranial T2-weighted DANTE-SPACE vessel wall imaging at 3T and 7T.

PURPOSE: T2-weighted DANTE-SPACE (Delay Alternating with Nutation for Tailored Excitation - Sampling Perfection with Application optimized Contrasts using different flip angle Evolution) sequences facilitate non-invasive intracranial vessel wall imaging at 7T through simultaneous suppression of blood and CSF. However, the achieved vessel wall delineation depends closely on the selected sequence parameters, and little information is available about the performance of the sequence using more widely available 3T MRI. Therefore, in this paper a comprehensive DANTE-SPACE simulation framework is used for the optimization and quantitative comparison of T2-weighted DANTE-SPACE at both 7T and 3T. METHODS: Simulations are used to propose optimized sequence parameters at both 3T and 7T. At 7T, an additional protocol which uses a parallel transmission (pTx) shim during the DANTE preparation for improved suppression of inflowing blood is also proposed. Data at both field strengths using optimized and literature protocols are acquired and quantitatively compared in six healthy volunteers. RESULTS: At 7T, more vessel wall signal can be retained while still achieving sufficient CSF suppression by using fewer DANTE pulses than described in previous implementations. The use of a pTx shim during DANTE at 7T provides a modest further improvement to the inner vessel wall delineation. At 3T, aggressive DANTE preparation is required to achieve CSF suppression, resulting in reduced vessel wall signal. As a result, the achievable vessel wall definition at 3T is around half that of 7T. CONCLUSION: Simulation-based optimization of DANTE parameters facilitates improved T2-weighted DANTE-SPACE contrasts at 7T. The improved vessel definition of T2-weighted DANTE-SPACE at 7T makes DANTE preparation more suitable for T2-weighted VWI at 7T than at 3T.

Reduced B0/B1 + sensitivity in velocity-selective inversion arterial spin labeling using adiabatic refocusing pulses.

PURPOSE: To mitigate the B0/B1 + sensitivity of velocity-selective inversion (VSI) pulse trains for velocity-selective arterial spin labeling (VSASL) by implementing adiabatic refocusing. This approach aims to achieve artifact-free VSI-based perfusion imaging through single-pair label-control subtractions, reducing the need for the currently required four-pair dynamic phase-cycling (DPC) technique when using a velocity-insensitive control. METHODS: We introduce a Fourier-transform VSI (FT-VSI) train that incorporates sinc-modulated hard excitation pulses with MLEV-8-modulated adiabatic hyperbolic secant refocusing pairs. We compare performance between this train and the standard composite refocusing train, including with and without DPC, for dual-module VSI VSASL. We evaluate (1) simulated velocity-selective profiles and subtraction fidelity across a broad B0/B1 + range, (2) subtraction fidelity in phantoms, and (3) image quality, artifact presence, and gray-matter perfusion heterogeneity (as measured by the spatial coefficient of variation) in healthy human subjects. RESULTS: Adiabatic refocusing significantly improves FT-VSI robustness to B0/B1 + inhomogeneity for a single label-control subtraction. Subtraction fidelity is dramatically improved in both simulation and phantoms compared with composite refocusing without DPC, and is similar compared with DPC methods. In humans, marked artifacts seen with the non-DPC composite refocusing approach are eliminated, corroborated by significantly reduced gray-matter heterogeneity (via lower spatial coefficient of variation values). CONCLUSION: A novel VSASL labeling train using adiabatic refocusing pulses for VSI was found to reduce artifacts related to B0/B1 + inhomogeneity, thereby providing an alternative to DPC and its associated limitations, which include increased vulnerability to physiological noise and motion, reduced functional MRI applicability, and suboptimal data censoring.

Evaluation of fetal cerebral microvascular status and its relationship with fetal growth and development using microvascular imaging technique.

The study conducted retrospective analysis design, aiming to explore the use of Microvascular Imaging Technique (MVFI) to assess fetal cerebral microcirculation and analyze the relationship between Microvascular Index (MVI) and fetal growth and development. 100 pregnant women who met the criteria for fetal growth restriction (FGR) provided in the Expert Consensus on Fetal Growth Restriction (2019 Edition) and underwent routine prenatal examinations at the Obstetrics and Gynecology Department of Peking University Third Hospital from January 2021 to June 2023 were selected as the study subjects. A normal fetus with a fetal weight less than 10 % can be classified as FGR, Pregnant women with fetal umbilical artery (UA) systolic and diastolic (S/D) values ≥3 were included in the observation group, while 200 pregnant women with normal fetuses were selected as the control group during the same period. The fetuses' change in both groups were measured using color Doppler ultrasound, including bi-parietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL). The cerebral microcirculation of the fetuses in both groups was evaluated using MVFI, and the MVI values were compared. The clinical characteristics of FGR fetuses with umbilical artery S/D ratio ≥ 3 were summarized, and the correlation between fetal cerebral microvascular status and fetal growth and development was analyzed using Pearson correlation analysis. The outcomes told that the BPD, HC, AC, and FL values of the fetuses in the control group were lower the other's value (P < 0.05), and the MVI and peak systolic velocity of the middle cerebral artery (MCA-PSV) values were also lower in the control group (P < 0.05). Pearson correlation analysis revealed a positive correlation between fetal growth and development and MVI and MCA-PSV values in FGR fetuses. In conclusion, MVFI can monitor and quantitatively analyze fetal intracranial microcirculation, visualize slow blood flow in microvascular structures, and this study provides preliminary evidence of the close relationship between fetal cerebral microcirculation and intrauterine growth and development.

Plasma Brain-Derived Tau in Prognosis of Large Vessel Occlusion Ischemic Stroke.

BACKGROUND: Large vessel occlusion acute ischemic stroke prognosis improved following the 2015 endovascular therapy (EVT) trials. Blood-based biomarkers may improve outcome prediction. We aimed to assess plasma brain-derived tau (BD-Tau) performance in predicting post-EVT large vessel occlusion acute ischemic stroke outcomes. METHODS: We included 2 temporally independent prospective cohorts of anterior circulation in patients with large vessel occlusion acute ischemic stroke who successfully recanalized post-EVT. We measured plasma BD-Tau, GFAP (glial-fibrillary-acidic-protein), NfL (neurofilament-light-chain), and total-Tau upon admission, immediately, 24 hours, and 72 hours post-EVT. Twenty-four-hour neuroimaging and 90-day functional outcomes were independently assessed using the Alberta Stroke Program Early Computed Tomography Score (good outcome: >7 or unchanged) and the modified Rankin Scale (favorable outcome <3 or unchanged), respectively. Based on the first cohort (derivation), we built a multivariable logistic regression model to predict a 90-day functional outcome. Model results were evaluated using the second cohort (evaluation). RESULTS: In the derivation cohort (n=78, mean age=72.9 years, 50% women), 62% of patients had a good 24-hour neuroimaging outcome, and 45% had a favorable 90-day functional outcome. GFAP admission-to-EVT rate-of-change was the best predictor for early neuroimaging outcome but not for 90-day functional outcome. At admission, BD-Tau levels presented the highest discriminative performance for 90-day functional outcomes (area under the curve, 0.76 [95% CI, 0.65-0.87]; P<0.001). The model incorporating age, admission BD-Tau, and 24-hour Alberta Stroke Program Early Computed Tomography Score achieved excellent discrimination of 90-day functional outcome (area under the curve, 0.89 [95% CI, 0.82-0.97]; P<0.001). The score's predictive performance was maintained in the evaluation cohort (n=66; area under the curve, 0.82 [95% CI, 0.71-0.92]; P<0.001). CONCLUSIONS: Admission plasma BD-Tau accurately predicted 90-day functional outcomes in patients with large vessel occlusion acute ischemic stroke after successful EVT. The proposed model may predict functional outcomes using objective measures, minimizing human-related biases and serving as a simplified prognostic tool for AIS.

Pia-FLOW: Deciphering hemodynamic maps of the pial vascular connectome and its response to arterial occlusion.

The pial vasculature is the sole source of blood supply to the neocortex. The brain is contained within the skull, a vascularized bone marrow with a unique anatomical connection to the brain meninges. Recent developments in tissue clearing have enabled detailed mapping of the entire pial and calvarial vasculature. However, what are the absolute flow rate values of those vascular networks? This information cannot accurately be retrieved with the commonly used bioimaging methods. Here, we introduce Pia-FLOW, a unique approach based on large-scale transcranial fluorescence localization microscopy, to attain hemodynamic imaging of the whole murine pial and calvarial vasculature at frame rates up to 1,000 Hz and spatial resolution reaching 5.4 µm. Using Pia-FLOW, we provide detailed maps of flow velocity, direction, and vascular diameters which can serve as ground-truth data for further studies, advancing our understanding of brain fluid dynamics. Furthermore, Pia-FLOW revealed that the pial vascular network functions as one unit for robust allocation of blood after stroke.

Blood-brain barrier integrity is linked to cognitive function, but not to cerebral arterial pulsatility, among elderly.

Blood-brain barrier (BBB) disruption may contribute to cognitive decline, but questions remain whether this association is more pronounced for certain brain regions, such as the hippocampus, or represents a whole-brain mechanism. Further, whether human BBB leakage is triggered by excessive vascular pulsatility, as suggested by animal studies, remains unknown. In a prospective cohort (N = 50; 68-84 years), we used contrast-enhanced MRI to estimate the permeability-surface area product (PS) and fractional plasma volume ( v p ), and 4D flow MRI to assess cerebral arterial pulsatility. Cognition was assessed by the Montreal Cognitive Assessment (MoCA) score. We hypothesized that high PS would be associated with high arterial pulsatility, and that links to cognition would be specific to hippocampal PS. For 15 brain regions, PS ranged from 0.38 to 0.85 (·10-3 min-1) and v p from 0.79 to 1.78%. Cognition was related to PS (·10-3 min-1) in hippocampus (ß = - 2.9; p = 0.006), basal ganglia (ß = - 2.3; p = 0.04), white matter (ß = - 2.6; p = 0.04), whole-brain (ß = - 2.7; p = 0.04) and borderline-related for cortex (ß = - 2.7; p = 0.076). Pulsatility was unrelated to PS for all regions (p > 0.19). Our findings suggest PS-cognition links mainly reflect a whole-brain phenomenon with only slightly more pronounced links for the hippocampus, and provide no evidence of excessive pulsatility as a trigger of BBB disruption.

Dual-task improvement of older adults after treadmill walking combined with blood flow restriction of low occlusion pressure: the effect on the heart-brain axis.

OBJECTIVE: This study explored the impact of one session of low-pressure leg blood flow restriction (BFR) during treadmill walking on dual-task performance in older adults using the neurovisceral integration model framework. METHODS: Twenty-seven older adults participated in 20-min treadmill sessions, either with BFR (100 mmHg cuff pressure on both thighs) or without it (NBFR). Dual-task performance, measured through light-pod tapping while standing on foam, and heart rate variability during treadmill walking were compared. RESULTS: Following BFR treadmill walking, the reaction time (p = 0.002) and sway area (p = 0.012) of the posture dual-task were significantly reduced. Participants exhibited a lower mean heart rate (p < 0.001) and higher heart rate variability (p = 0.038) during BFR treadmill walking. Notably, BFR also led to band-specific reductions in regional brain activities (theta, alpha, and beta bands, p < 0.05). The topology of the EEG network in the theta and alpha bands became more star-like in the post-test after BFR treadmill walking (p < 0.005). CONCLUSION: BFR treadmill walking improves dual-task performance in older adults via vagally-mediated network integration with superior neural economy. This approach has the potential to prevent age-related falls by promoting cognitive reserves.

MRI Evaluation of Microstructural and Perfusion Changes in Patients with Hemsensory Neurological Syndromes.

BACKGROUND: Hemisensory syndrome is characterized by a nondermatomal sensory deficit involving one half of the body. With the conventional imaging techniques, researches find low diagnostic yield in this condition; however, with the advancements in MRI imaging, there is hope to find the pathophysiological basis of hemisensory symptoms. OBJECTIVE: To evaluate microstructural and perfusion changes in brain parenchyma in patients with hemisensory syndrome on MRI with diffusion tensor imaging (DTI) and arterial spin labeling (ASL). MATERIAL AND METHODS: A total of 20 patients with hemisensory symptoms and 10 age-matched controls were enrolled and divided in two study groups - a) case vs. control and b) affected vs. nonaffected cerebral hemisphere in cases. Quantification of absolute cerebral blood flow (aCBF), fractional anisotropy (FA), and mean diffusivity (MD) was done in both groups. RESULTS: On ASL, there was significantly increased aCBF in thalamus on the contralateral-affected side. DTI revealed significantly decreased FA in the thalamus and increased FA in corona radiata of the affected side. There was a significant difference for MD of corona radiata between affected and nonaffected hemisphere. The mean value of MD in corona radiata is decreased on the affected side. CONCLUSION: Changes in advanced neuroimaging techniques like ASL and DTI along the pain processing pathway suggest an alteration in neuronal density and activity at the microstructural level. These findings may provide an insight into the etiopathogenesis of pain syndromes.

Perivascular spaces around arteries exceed perivenous spaces in the mouse brain.

The perivascular space (PVS) surrounds cerebral blood vessels and plays an important role in clearing waste products from the brain. Their anatomy and function have been described for arteries, but PVS around veins remain poorly characterized. Using in vivo 2-photon imaging in mice, we determined the size of the PVS around arteries and veins, and their connection with the subarachnoid space. After infusion of 70 kD FITC-dextran into the cerebrospinal fluid via the cisterna magna, labeled PVS were evident around arteries, but veins showed less frequent labeling of the PVS. The size of the PVS correlated with blood vessel size for both pial arteries and veins, but not for penetrating vessels. The PVS around pial arteries and veins was separated from the subarachnoid space by a thin meningeal layer, which did not form a barrier for the tracer. In vivo, FITC-dextran signal was observed adjacent to the vessel wall, but minimally within the wall itself. Post-mortem, there was a significant shift in the tracer's location within the arterial wall, extending into the smooth muscle layer. Taken together, these findings suggest that the PVS around veins has a limited role in the exchange of solutes between CSF and brain parenchyma.