Contractile pericytes determine the direction of blood flow at capillary junctions.

The essential function of the circulatory system is to continuously and efficiently supply the O2 and nutrients necessary to meet the metabolic demands of every cell in the body, a function in which vast capillary networks play a key role. Capillary networks serve an additional important function in the central nervous system: acting as a sensory network, they detect neuronal activity in the form of elevated extracellular K+ and initiate a retrograde, propagating, hyperpolarizing signal that dilates upstream arterioles to rapidly increase local blood flow. Yet, little is known about how blood entering this network is distributed on a branch-to-branch basis to reach specific neurons in need. Here, we demonstrate that capillary-enwrapping projections of junctional, contractile pericytes within a postarteriole transitional region differentially constrict to structurally and dynamically determine the morphology of capillary junctions and thereby regulate branch-specific blood flow. We further found that these contractile pericytes are capable of receiving propagating K+-induced hyperpolarizing signals propagating through the capillary network and dynamically channeling red blood cells toward the initiating signal. By controlling blood flow at junctions, contractile pericytes within a functionally distinct postarteriole transitional region maintain the efficiency and effectiveness of the capillary network, enabling optimal perfusion of the brain.

Intracranial pressure and veins.

This review summarizes the relationship between intracranial pressure and the venous system as far as ultrasound methods are concerned. Although the pressure in cortical veins is tightly and linearly coupled to the intracranial pressure, venous flow velocities in the basal veins are not. However, venous flow velocities reflect better the local cerebral blood flow than measurements in arteries. Therefore, they correlate better with clinical outcome in head trauma and subarachnoid hemorrhage. Transorbital sonography with measurement of the optic nerve sheath diameter and optic disk elevation has evolved to a valuable point of care diagnostic tool in idiopathic intracranial hypertension. In cerebral vein and sinus thrombosis ultrasound is at best a supplementary diagnostic tool, which may have a value in patient follow-up.

A dynamical model of the laminar BOLD response.

High-resolution functional magnetic resonance imaging (fMRI) using blood oxygenation dependent level-dependent (BOLD) signal is an increasingly popular tool to non-invasively examine neuronal processes at the mesoscopic level. However, as the BOLD signal stems from hemodynamic changes, its temporal and spatial properties do not match those of the underlying neuronal activity. In particular, the laminar BOLD response (LBR), commonly measured with gradient-echo (GE) MRI sequence, is confounded by non-local changes in deoxygenated hemoglobin and cerebral blood volume propagated within intracortical ascending veins, leading to a unidirectional blurring of the neuronal activity distribution towards the cortical surface. Here, we present a new cortical depth-dependent model of the BOLD response based on the principle of mass conservation, which takes the effect of ascending (and pial) veins on the cortical BOLD responses explicitly into account. It can be used to dynamically model cortical depth profiles of the BOLD signal as a function of various baseline- and activity-related physiological parameters for any spatiotemporal distribution of neuronal changes. We demonstrate that the commonly observed spatial increase of LBR is mainly due to baseline blood volume increase towards the surface. In contrast, an occasionally observed local maximum in the LBR (i.e. the so-called "bump") is mainly due to spatially inhomogeneous neuronal changes rather than locally higher baseline blood volume. In addition, we show that the GE-BOLD signal laminar point-spread functions, representing the signal leakage towards the surface, depend on several physiological parameters and on the level of neuronal activity. Furthermore, even in the case of simultaneous neuronal changes at each depth, inter-laminar delays of LBR transients are present due to the ascending vein. In summary, the model provides a conceptual framework for the biophysical interpretation of common experimental observations in high-resolution fMRI data. In the future, the model will allow for deconvolution of the spatiotemporal hemodynamic bias of the LBR and provide an estimate of the underlying laminar excitatory and inhibitory neuronal activity.

Does the prone sleeping position affect the intracranial dural venous flow?

PURPOSE: There are few studies documenting the effect of posture on intracranial dural venous flow. The aim of the present study was to explore alterations caused by the prone position using magnetic resonance (MR) venography. METHODS: A total of eight patients (five men and three women) underwent non-contrast MR venography in both supine and prone positions. RESULTS: In the prone position, an increase in intracranial dural venous flow was found in all patients in the non-dominant transverse and sigmoid sinuses. An increase in venous flow to the straight sinus was observed in 75% of the patients. Flow to the superior ophthalmic vein decreased in three patients. No postural flow alterations were observed in any of the patients in the superior sagittal, dominant transverse, and sigmoid sinuses. CONCLUSION: Based on results of the study, in the prone sleeping position, part of the intracranial venous flow may be preferentially drained through the straight and non-dominant transverse sinuses.

Cortical Spreading Depression Closes Paravascular Space and Impairs Glymphatic Flow: Implications for Migraine Headache.

Functioning of the glymphatic system, a network of paravascular tunnels through which cortical interstitial solutes are cleared from the brain, has recently been linked to sleep and traumatic brain injury, both of which can affect the progression of migraine. This led us to investigate the connection between migraine and the glymphatic system. Taking advantage of a novel in vivo method we developed using two-photon microscopy to visualize the paravascular space (PVS) in naive uninjected mice, we show that a single wave of cortical spreading depression (CSD), an animal model of migraine aura, induces a rapid and nearly complete closure of the PVS around surface as well as penetrating cortical arteries and veins lasting several minutes, and gradually recovering over 30 min. A temporal mismatch between the constriction or dilation of the blood vessel lumen and the closure of the PVS suggests that this closure is not likely to result from changes in vessel diameter. We also show that CSD impairs glymphatic flow, as indicated by the reduced rate at which intraparenchymally injected dye was cleared from the cortex to the PVS. This is the first observation of a PVS closure in connection with an abnormal cortical event that underlies a neurological disorder. More specifically, the findings demonstrate a link between the glymphatic system and migraine, and suggest a novel mechanism for regulation of glymphatic flow.SIGNIFICANCE STATEMENT Impairment of brain solute clearance through the recently described glymphatic system has been linked with traumatic brain injury, prolonged wakefulness, and aging. This paper shows that cortical spreading depression, the neural correlate of migraine aura, closes the paravascular space and impairs glymphatic flow. This closure holds the potential to define a novel mechanism for regulation of glymphatic flow. It also implicates the glymphatic system in the altered cortical and endothelial functioning of the migraine brain.

Contribution of systemic vascular effects to fMRI activity in white matter.

To investigate a potential contribution of systemic physiology to recently reported BOLD fMRI signals in white matter, we compared photo-plethysmography (PPG) and whole-brain fMRI signals recorded simultaneously during long resting-state scans from an overnight sleep study. We found that intermittent drops in the amplitude of the PPG signal exhibited strong and widespread correlations with the fMRI signal, both in white matter (WM) and in gray matter (GM). The WM signal pattern resembled that seen in previous resting-state fMRI studies and closely tracked the location of medullary veins. Its temporal cross-correlation with the PPG amplitude was bipolar, with an early negative value. In GM, the correlation was consistently positive. Consistent with previous studies comparing physiological signals with fMRI, these findings point to a systemic vascular contribution to WM fMRI signals. The PPG drops are interpreted as systemic vasoconstrictive events, possibly related to intermittent increases in sympathetic tone related to fluctuations in arousal state. The counter-intuitive polarity of the WM signal is explained by long blood transit times in the medullary vasculature of WM, which cause blood oxygenation loss and a substantial timing mismatch between blood volume and blood oxygenation effects. A similar mechanism may explain previous findings of negative WM signals around large draining veins during both task- and resting-state fMRI.

Spatial distribution of flow and oxygenation in the cerebral venous drainage system.

PURPOSE: To investigate the venous oxygenation and flow in the brain, and determine how they might change under challenged states. MATERIALS AND METHODS: Eight healthy human subjects (24-37 years) were studied. T2 -relaxation under spin tagging (TRUST) magnetic resonance imaging (MRI) and phase-contrast MRI were performed to measure venous oxygenation and venous blood flow, respectively, in the superior sagittal sinus (SSS), the straight sinus (SS), and the internal jugular veins (IJVs). Venous oxygenation was assessed at room air (0.03%CO2 , 21%O2 ) and under hyperoxia (O%CO2 , 95%O2 , and 5%N2 ) conditions. Venous blood flow was assessed at room air and under hypercapnia (5%CO2 , 21%O2 , and 74%N2 ) conditions. Whole-brain blood flow was also measured at the four feeding arteries of the brain using phase-contrast MRI. The changes in venous oxygenation and blood flow from room air to hyperoxia or hypercapnia conditions were tested using paired t-tests. RESULTS: Venous oxygenation in the SSS, the SS, and the IJVs was 61 ± 4%, 64 ± 4%, and 62 ± 4%, respectively, at room air, and increased to 70 ± 3% (P < 0.01 compared to room air), 71 ± 5% (P = 0.59), and 68 ± 5% (P < 0.05) under hyperoxic condition. The SSS, SS, and IJV drained 46 ± 9%, 16 ± 4%, and 79 ± 1% of whole-brain blood flow, respectively, and this flow distribution did not change under hypercapnic condition (P > 0.5). CONCLUSION: The results found in this study provide insight into the venous oxygenation and venous flow distribution and its heterogeneity among different venous structures. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:1091-1098.

Hemodynamics of cerebral bridging veins connecting the superior sagittal sinus based on numerical simulation.

BACKGROUND: The physiological and hemodynamic features of bridging veins involve wall shear stress (WSS) of the cerebral venous system. Based on the data of cadavers and computational fluid dynamics software pack, the hemodynamic physical models of bridging veins (BVs) connecting superior sagittal sinus (SSS) were established. RESULTS: A total of 137 BVs formed two clusters along the SSS: anterior group and posterior group. The diameters of the BVs in posterior group were larger than of the anterior group, and the entry angle was smaller. When the diameter of a BV was greater than 1.2 mm, the WSS decreased in the downstream wall of SSS with entry angle less than 105°, and the WSS also decreased in the upstream wall of BVs with entry angle less than 65°. The minimum WSS in BVs was only 63% of that in SSS. Compared with the BVs in anterior group, the minimum WSS in the posterior group was smaller, and the distance from location of the minimum WSS to the dural entrance was longer. CONCLUSION: The cerebral venous thrombosis occurs more easily when the diameter of a BV is greater than 1.2 mm and the entry angle is less than 65°. The embolus maybe form earlier in the upstream wall of BVs in the posterior part of SSS.

Increased susceptibility of asymmetrically prominent cortical veins correlates with misery perfusion in patients with occlusion of the middle cerebral artery.

OBJECTIVES: To evaluate tissue perfusion and venous susceptibility in ischaemic stroke patients as a means to predict clinical status and early prognosis. METHODS: A retrospective study of 51 ischaemic stroke patients were enrolled in this study. Susceptibility, perfusion and National Institute of Health stroke scale (NIHSS) were compared between patients with and without asymmetrically prominent cortical veins (APCVs). The correlation between susceptibility, perfusion and NIHSS was performed. RESULTS: Compared to patients without APCVs, the age of patients with APCVs was statistically older (p = 0.017). Patients with APCVs at discharge showed clinical deterioration in their NIHSS. Mean transit time (MTT), time to peak (TTP) and cerebral blood flow (CBF) in the stroke hemisphere were statistically delayed/decreased in patients with and without APCVs (all p < 0.05). In patients with APCVs, the changes in susceptibility positively correlated with increases in MTT and TTP (p < 0.05). Susceptibility and TTP positively correlated and CBF negatively correlated with NIHSS both at admission and discharge (p < 0.05). CONCLUSIONS: Patients with APCVs have a tendency of deterioration. The presence of APCVs indicates the tissue has increased oxygen extraction fraction. Increased susceptibility from APCVs positively correlated with the delayed MTT and TTP, which reflects the clinical status at admission and predicts an early prognosis. KEY POINTS: • Patients with and without APCVs have similar misery perfusion. • Patients with APCVs have a tendency of deterioration compared to those without. • The presence of APCVs indicated the tissue has increased oxygen extraction fraction. • Increased susceptibility from APCVs positively correlated with the MTT and TTP. • Increased susceptibility from APCVs reflected the clinical status at admission.

Four-dimensional MRI flow examinations in cerebral and extracerebral vessels - ready for clinical routine?

PURPOSE OF REVIEW: To evaluate the feasibility of 4-dimensional (4D) flow MRI for the clinical assessment of cerebral and extracerebral vascular hemodynamics in patients with neurovascular disease. RECENT FINDINGS: 4D flow MRI has been applied in multiple studies to qualitatively and quantitatively study intracranial aneurysm blood flow for potential risk stratification and to assess treatment efficacy of various neurovascular lesions, including intraaneurysmal and parent artery blood flow after flow diverter stent placement and staged embolizations of arteriovenous malformations and vein of Galen aneurysmal malformations. Recently, the technique has been utilized to characterize age-related changes of normal cerebral hemodynamics in healthy individuals over a broad age range. SUMMARY: 4D flow MRI is a useful tool for the noninvasive, volumetric and quantitative hemodynamic assessment of neurovascular disease without the need for gadolinium contrast agents. Further improvements are warranted to overcome technical limitations before broader clinical implementation. Current developments, such as advanced acceleration techniques (parallel imaging and compressed sensing) for faster data acquisition, dual or multiple velocity encoding strategies for more accurate arterial and venous flow quantification, ultrahigh-field strengths to achieve higher spatial resolution and streamlined postprocessing workflow for more efficient and standardized flow analysis, are promising advancements in 4D flow MRI.

Correction and optimization of a T2-based approach to map blood oxygenation in small cerebral veins.

PURPOSE: Cerebral venous blood oxygenation (Yv ) is an important biomarker in brain physiology and function. The present study proposes a procedure to provide a quantitative map of the brain's intravascular Yv. THEORY AND METHODS: The method is based on a pulse sequence, T2 -Relaxation-Under-Phase-Contrast (TRU-PC) MRI, with postprocessing approaches to correct eddy-current effects. A complete scan protocol consists of four TRU-PC scans sensitized to large and small vessels with anterior-posterior and foot-head flow-encoding directions, and the data are analyzed conjunctively. Eddy-current correction was performed by fitting the tissue phase to a hyperplane, and then subtracting the eddy-current phase from the measured vessel phase. The reproducibility of the Yv-maps was examined in five participants. Sensitivity of the Yv map to a caffeine challenge was studied in another five participants. RESULTS: Removal of eddy-current induced artifact allowed for the correction of T2 measurements, as demonstrated in vivo and with simulation. A Yv-map depicting all vessels in the slice can be obtained with the proposed protocol. Test-retest variability of the Yv -map was 3.7 ± 1.2%. Yv reduction can be reliably detected (P < 0.001) following the caffeine ingestion. CONCLUSION: With the proposed TRU-PC protocol and eddy-current correction procedure, an accurate, vessel-specific Yv map of the human brain can be obtained.

Multisite evaluations of a T2 -relaxation-under-spin-tagging (TRUST) MRI technique to measure brain oxygenation.

PURPOSE: Venous oxygenation (Yv ) is an important index of brain physiology and may be indicative of brain diseases. A T2 -relaxation-under-spin-tagging (TRUST) MRI technique was recently developed to measure Yv . A multisite evaluation of this technique would be an important step toward broader availability and potential clinical utilizations of Yv measures. METHODS: TRUST MRI was performed on a total of 250 healthy subjects, 125 from the developer's site and 25 each from five other sites. All sites were equipped with a 3 Tesla (T) MRI of the same vendor. The estimated Yv and the standard error (SE) of the estimation εYv were compared across sites. RESULTS: The averaged Yv and εYv across six sites were 61.1% ± 1.4% and 1.3% ± 0.2%, respectively. Multivariate regression analysis showed that the estimated Yv was dependent on age (P = 0.009) but not on performance site. In contrast, the SE of the Yv estimation was site-dependent (P = 0.024) but was less than 1.5%. Further analysis revealed that εYv was positively associated with the amount of subject motion (P < 0.001) but negatively associated with blood signal intensity (P < 0.001). CONCLUSION: This work suggests that TRUST MRI can yield equivalent results of Yv estimation across different sites.

Coupling between arterial and venous cerebral blood flow during postural change.

In supine humans the main drainage from the brain is through the internal jugular vein (IJV), but the vertebral veins (VV) become important during orthostatic stress because the IJV is partially collapsed. To identify the effect of this shift in venous drainage from the brain on the cerebral circulation, this study addressed both arterial and venous flow responses in the "anterior" and "posterior" parts of the brain when nine healthy subjects (5 men) were seated and flow was manipulated by hyperventilation and inhalation of 6% carbon dioxide (CO2). From a supine to a seated position, both internal carotid artery (ICA) and IJV blood flow decreased (P = 0.004 and P = 0.002), while vertebral artery (VA) flow did not change (P = 0.348) and VV flow increased (P = 0.024). In both supine and seated positions the ICA response to manipulation of end-tidal CO2 tension was reflected in IJV (r = 0.645 and r = 0.790, P < 0.001) and VV blood flow (r = 0.771 and r = 0.828, P < 0.001). When seated, the decrease in ICA blood flow did not affect venous outflow, but the decrease in IJV blood flow was associated with the increase in VV blood flow (r = 0.479, P = 0.044). In addition, the increase in VV blood flow when seated was reflected in VA blood flow (r = 0.649, P = 0.004), and the two flows were coupled during manipulation of the end-tidal CO2 tension (supine, r = 0.551, P = 0.004; seated, r = 0.612, P < 0001). These results support that VV compensates for the reduction in IJV blood flow when seated and that VV may influence VA blood flow.

The cerebral venous system and the postural regulation of intracranial pressure: implications in the management of patients with cerebrospinal fluid diversion.

Loss of cerebrospinal fluid (CSF) occurs commonly in daily neurosurgical practice. Understanding the altered physiology following CSF loss is important for optimization of patient care and avoidance of complications. There is overwhelming evidence now that the cerebral venous system plays a major role in intracranial pressure (ICP) dynamics especially when one takes into account the effects of postural changes, atmospheric pressure, and gravity on the craniospinal axis as a whole. The CSF and cerebral venous compartments are tightly coupled in two important ways. CSF is resorbed into the venous system, and there is also an evolved mechanism that prevents overdrainage of venous blood with upright positioning known as the Starling resistor. With loss of CSF pressure, this protective mechanism could become nonfunctional which may result in posture-related venous overdrainage through the cranial venous outflow tracts leading to pathologic states. This review article summarizes the relevant anatomic and physiologic basis of the relationship between the craniospinal venous and CSF compartments in the setting of CSF diversion. It is hoped that this article improves our understanding of ICP dynamics after CSF loss, adds a new dimension to our therapeutic methods, stimulates further research into this field, and ultimately improves our care of these patients.

Quantitative separation of arterial and venous cerebral blood volume increases during voluntary locomotion.

Voluntary locomotion is accompanied by large increases in cortical activity and localized increases in cerebral blood volume (CBV). We sought to quantitatively determine the spatial and temporal dynamics of voluntary locomotion-evoked cerebral hemodynamic changes. We measured single vessel dilations using two-photon microscopy and cortex-wide changes in CBV-related signal using intrinsic optical signal (IOS) imaging in head-fixed mice freely locomoting on a spherical treadmill. During bouts of locomotion, arteries dilated rapidly, while veins distended slightly and recovered slowly. The dynamics of diameter changes of both vessel types could be captured using a simple linear convolution model. Using these single vessel measurements, we developed a novel analysis approach to separate out spatially and temporally distinct arterial and venous components of the location-specific hemodynamic response functions (HRF) for IOS. The HRF of each pixel of was well fit by a sum of a fast arterial and a slow venous component. The HRFs of pixels in the limb representations of somatosensory cortex had a large arterial contribution, while in the frontal cortex the arterial contribution to the HRF was negligible. The venous contribution was much less localized, and was substantial in the frontal cortex. The spatial pattern and amplitude of these HRFs in response to locomotion in the cortex were robust across imaging sessions. Separating the more localized arterial component from the diffuse venous signals will be useful for dealing with the dynamic signals generated by naturalistic stimuli.

A new hemodynamic model for the study of cerebral venous outflow.

We developed a mathematical model of the cerebral venous outflow for the simulation of the average blood flows and pressures in the main drainage vessels of the brain. The main features of the model are that it includes a validated model for the simulation of the intracranial circulation and it accounts for the dependence of the hydraulic properties of the jugular veins with respect to the gravity field, which makes it an useful tool for the study of the correlations between extracranial blood redistributions and changes in the intracranial environment. The model is able to simulate the average pressures and flows in different points of the jugular ducts, taking into account the amount of blood coming from the anastomotic connections; simulate how the blood redistribution due to change of posture affects flows and pressures in specific points of the system; and simulate redistributions due to stenotic patterns. Sensitivity analysis to check the robustness of the model was performed. The model reproduces average physiologic behavior of the jugular, vertebral, and cerebral ducts in terms of pressures and flows. In fact, jugular flow drops from ∼11.7 to ∼1.4 ml/s in the passage from supine to standing. At the same time, vertebral flow increases from 0.8 to 3.4 ml/s, while cerebral blood flow, venous sinuses pressure, and intracranial pressure are constant around the average value of 12.5 ml/s, 6 mmHg, and 10 mmHg, respectively. All these values are in agreement with literature data.

In vivo analysis of physiological 3D blood flow of cerebral veins.

OBJECTIVES: To visualize and quantify physiological blood flow of intracranial veins in vivo using time-resolved, 3D phase-contrast MRI (4D flow MRI), and to test measurement accuracy. METHODS: Fifteen healthy volunteers underwent repeated ECG-triggered 4D flow MRI (3 Tesla, 32-channel head coil). Intracranial venous blood flow was analysed using dedicated software allowing for blood flow visualization and quantification in analysis planes at the superior sagittal, straight, and transverse sinuses. MRI was evaluated for intra- and inter-observer agreement and scan-rescan reproducibility. Measurements of the transverse sinuses were compared with transcranial two-dimensional duplex ultrasound. RESULTS: Visualization of 3D blood flow within cerebral sinuses was feasible in 100 % and within at least one deep cerebral vein in 87 % of the volunteers. Blood flow velocity/volume increased along the superior sagittal sinus and was lower in the left compared to the right transverse sinus. Intra- and inter-observer reliability and reproducibility of blood flow velocity (mean difference 0.01/0.02/0.02 m/s) and volume (mean difference 0.0002/-0.0003/0.00003 l/s) were good to excellent. High/low velocities were more pronounced (8 % overestimation/9 % underestimation) in MRI compared to ultrasound. CONCLUSIONS: Four-dimensional flow MRI reliably visualizes and quantifies three-dimensional cerebral venous blood flow in vivo and is promising for studies in patients with sinus thrombosis and related diseases. KEY POINTS: • 4D flow MRI can be used to visualize and quantify physiological cerebral venous haemodynamics • Flow quantification within cerebral sinuses reveals high reliability and accuracy of 4D flow MRI • Blood flow volume and velocity increase along the superior sagittal sinus • Limited spatial resolution currently precludes flow quantification in small cerebral veins.

Validation of a method to differentiate arterial and venous vessels in CT perfusion data using linear combinations of quantitative time-density curve characteristics.

OBJECTIVES: We aimed to develop and evaluate a new method that reliably differentiates between cerebral arteries and veins using voxel-wise CT-perfusion-derived parameters. MATERIALS AND METHODS: Fourteen consecutive patients with suspected stroke but without pathological findings were examined on a multi-detector CT system: 32 dynamic phases (∆t = 1.5 s) during application of 35 mL iomeprol-350 were acquired at 80 kV/200mAs. Three hemodynamic parameters were calculated for 18 arterial and venous vessel segments: A (maximum of the time-density-curve), T (time-to-peak), and W (full-width-at-half-maximum). Using receiver operator characteristic (ROC) curve analysis and Fisher's linear discriminant analysis (FLDA), the performance of every classifier (A, T, W) and of all linear combinations for the differentiation of arterial and venous vessels was determined. RESULTS: A maximum area under the ROC-curve (AUC) of 0.945 (accuracy = 86.8%) was obtained using the FLDA combination of A&T or the triplet FLDA of A&T&W for the classification of venous and arterial vessels. The best single parameter was T with an AUC of 0.871 (accuracy = 79.0%), which performed significantly worse than the combination A&T (p < 0.001). CONCLUSIONS: Arteries and veins can be accurately differentiated based on dynamic CT perfusion data using the maximum of the time-density curve, its time-to-peak, its width, and FLDA combinations of these parameters, which yield accuracies up to 87%. KEY POINTS: • For classification of cerebral vasculature, time-to-peak has the best single-parameter accuracy. • Fisher's linear discriminant analysis improves the performance of the individual classifiers. • Combining signal maximum and time-to-peak parameters significantly increased the classifying potential. • Pre-processing of time-density-curves by Gaussian filtering or fitting can improve diagnostic accuracy.

Recruitment Pattern in a Complete Cerebral Arterial Circle.

Blood flow through a vessel depends upon compliance and resistance. Resistance changes dynamically due to vasoconstriction and vasodilation as a result of metabolic activity, thus allowing for more or less flow to a particular area. The structure responsible for directing blood to the different areas of the brain and supplying the increase flow is the cerebral arterial circle (CAC). A series of 1D equations were utilized to model propagating flow and pressure waves from the left ventricle of the heart to the CAC. The focus of the current research was to understand the collateral capability of the circle. This was done by decreasing the peripheral resistance in each of the efferent arteries, up to 10% both unilaterally and bilaterally. The collateral patterns were then analyzed. After the initial 60 simulations, it became apparent that flow could increase beyond the scope of a 10% reduction and still be within in vivo conditions. Simulations with higher percentage decreases were performed such that the same amount of flow increase would be induced through each of the efferent arteries separately, same flow tests (SFTs), as well as those that were found to allow for the maximum flow increase through the stimulated artery, maximum flow tests (MFTs). The collateral pattern depended upon which efferent artery was stimulation and if the stimulation was unilaterally or bilaterally induced. With the same amount of flow increase through each of the efferent arteries, the MCAs (middle cerebral arteries) had the largest impact on the collateral capability of the circle, both unilaterally and bilaterally.

Effects of the α2-adrenergic receptor agonist dexmedetomidine on neural, vascular and BOLD fMRI responses in the somatosensory cortex.

This article describes the effects of dexmedetomidine (DEX) - the active ingredient of medetomidine, which is the latest popular sedative for functional magnetic resonance imaging (fMRI) in rodents - on multiple unit activity, local field potential (LFP), cerebral blood flow (CBF), pial vessel diameter [indicative of cerebral blood volume (CBV)], and blood oxygenation level-dependent (BOLD) fMRI. These measurements were obtained from the rat somatosensory cortex during 10 s of forepaw stimulation. We found that the continuous intravascular systemic infusion of DEX (50 µg/kg/h, doses typically used in fMRI studies) caused epileptic activities, and that supplemental isoflurane (ISO) administration of ~0.3% helped to suppress the development of epileptic activities and maintained robust neuronal and hemodynamic responses for up to 3 h. Supplemental administration of N(2)O in addition to DEX nearly abolished hemodynamic responses even if neuronal activity remained. Under DEX + ISO anesthesia, spike firing rate and the delta power of LFP increased, whereas beta and gamma power decreased, as compared with ISO-only anesthesia. DEX administration caused pial arteries and veins to constrict nearly equally, resulting in decreases in baseline CBF and CBV. Evoked LFP and CBF responses to forepaw stimulation were largest at a frequency of 8-10 Hz, and a non-linear relationship was observed. Similarly, BOLD fMRI responses measured at 9.4 T were largest at a frequency of 10 Hz. Both pial arteries and veins dilated rapidly (artery, 32.2%; vein, 5.8%), and venous diameter returned to baseline slower than arterial diameter. These results will be useful for designing, conducting and interpreting fMRI experiments under DEX sedation.