Cerebral Venous Blood Research Articles

Wide-area measurement-based supervision of the cerebral venous hemodynamic in a novel rat model

BackgroundTraumatic brain injury (TBI) includes primary and secondary injuries, while monitoring intracranial pressure (ICP) and cerebral blood flow (CBF) is conducive to improve the prognosis of patients. However, the function of cerebral venous in this process is still unclear. New methodAn acute epidural hematoma (AEDH) model was developed by placing a controllable micro balloon in the right epidural space of a rat. The laser speckle contrast imaging (LSCI) system was used to observe CBF in real time, while ICP was monitored simultaneously. And the stability of this model was examined by magnetic resonance imaging (MRI). ResultsThe blood perfusion rate (BPR) of venous was significantly negatively correlated with ICP. In the 100 μ L group, the ipsilateral cerebral venous and microcirculation blood flow significantly decreased. According to the gross observations and pathological results, ischemic brain injury was the most serious on this condition. Comparison with existing method(s)Modeling method is relatively simple, which effectively reduces the cost. The volume of the micro balloon is adjusted to simulate the volume of different size of hematomas. In addition, LSCI, as an advanced blood flow monitoring technology, has high sensitivity to detect subtle changes in CBF. ConclusionThis study successfully developed a stable and reproducible AEDH rat model. Based on this model, it is preliminarily demonstrated that local intracranial hypertension can cause cerebral venous return restriction, which is an indispensable factor leading to the aggravation of secondary brain injury.

Hypoplasia of the ipsilateral internal jugular vein is associated with worse outcome in acute anterior circulation stroke

Background/Aim. Disruption of cerebral venous blood drainage leads to cerebral venous congestion, an increase in intracranial pressure and decrease of the cerebral perfusion pressure. The exact role of the cerebral venous circulation in acute stroke is not yet known. The main blood drainage from the brain and the superficial parts of the face and neck is drained by a paired internal jugular vein (IJV). Congenital anomalies of IJV may disrupt the blood collection from the brain, which leads to congestion of the cerebral venous circulation. The aim of our study was to determine the association between the hypoplastic ipsilateral IJV and clinical outcome of patients with acute ischemic anterior circulation stroke. Methods. This prospective case series study involved the patients with the anterior circulation stroke and ultrasonographic criteria for unilateral hypoplasia of the ipsilateral IJV. Data from the 74 consecutive patients with acute anterior circulation stroke admitted to the Special Hospital for Cerebrovascular Diseases ?Sveti Sava?, Belgrade, from September 2015 to January 2016 were included. Ultrasonography of IJV diameter and the collection of the hemodynamic data were performed in all patients. Neurological deficits on admission were evaluated using the National Institutes of Health Stroke Scale (NIHSS) score. The clinical outcome was assessed using the modified Rankin Scale (mRS) score (from 0 to 6) at 30 days or at discharge, whichever occurred sooner. Good and poor outcomes were defined as an mRS score of 0?2 and 3?6, respectively. Results. Ipsilateral hypoplastic IJV was diagnosed in 13 (17.6%) patients with anterior circulation stroke. In this group, 9 stroke patients (69.2%) had mRS ? 3. Of the remaining 4 patients with mRS ? 2, three had bilateral hypoplasia of IJV and one patient had smaller diameter of the IJV, but did not fulfill the ultrasonographic criteria for hypoplastic venous anomaly. Conclusions. In our case, a series of the patients with anterior circulation stroke with ultrasonographic criteria for unilateral hypoplasia of the ipsilateral IJV (on stroke side) have worse clinical outcome compared with the patients with bilateral hypoplasia.

Quantitative susceptibility mapping in the human fetus to measure blood oxygenation in the superior sagittal sinus.

To present the feasibility of performing quantitative susceptibility mapping (QSM) in the human fetus to evaluate the oxygenation (SvO2) of cerebral venous blood in vivo. Susceptibility weighted imaging (SWI) data were acquired from healthy pregnant subjects (n = 21, median = 31.3 weeks, interquartile range = 8.8 weeks). The susceptibility maps were generated from the SWI-phase images using a modified QSM processing pipeline, optimised for fetal applications. The processing pipeline is as follows: (1) mild high-pass filtering followed by quadratic fitting of the phase images to eliminate background phase variations; (2) manual creation of a fetal brain mask that includes the superior sagittal sinus (SSS); (3) inverse filtering of the resultant masked phase images using a truncated k-space approach with geometric constraint. Further, the magnetic susceptibility, ∆χv and corresponding putative SvO2 of the SSS were quantified from the generated susceptibility maps. Systematic error in the measured SvO2 due to the modified pipeline was also studied through simulations. Simulations showed that the systematic error in SvO2 when using a mask that includes a minimum of 5 voxels around the SSS and five slices remains < 3% for different orientations of the vessel relative to the main magnetic field. The average ∆χv in the SSS quantified across all gestations was 0.42 ± 0.03 ppm. Based on ∆χv, the average putative SvO2 in the SSS across all fetuses was 67% ± 7%, which is in good agreement with published studies. This in vivo study demonstrates the feasibility of using QSM in the human fetal brain to estimate ∆χv and SvO2. • A modified quantitative susceptibility mapping (QSM) processing pipeline is tested and presented for the human fetus. • QSM is feasible in the human fetus for measuring magnetic susceptibility and oxygenation of venous blood in vivo. • Blood magnetic susceptibility values from MR susceptometry and QSM agree with each other in the human fetus.

Effect sizes of BOLD CVR, resting-state signal fluctuations and time delay measures for the assessment of hemodynamic impairment in carotid occlusion patients

Background and purposeThe BOLD signal amplitude as a response to a hypercapnia stimulus is commonly used to assess cerebrovascular reserve. Despite recent advances, the implementation remains cumbersome and alternative ways to assess hemodynamic impairment are desirable. Resting-state BOLD signal fluctuations (rsBOLD) have been proposed however data on its sensitivity and dependence on baseline venous cerebral blood volume (vCBV) is limited. The primary aim of this study was to compare the effect sizes of resting-state and hypercapnia induced BOLD signal changes in the detection of hemodynamic impairment. The second aim of the study was to assess the dependence of BOLD signal variability on vCBV. Materials and methodsFifteen patients with internal carotid artery occlusive disease and 15 matched healthy controls were included in this study. The BOLD signal was derived from a dual-echo gradient-echo echo-planar sequence during hypercapnia (HC) and hyperoxia (HO) gas modulations. BOLD (fractional) amplitude of low frequency fluctuations ((f)ALFF) was compared to HC-BOLD, BOLD response delays derived from time delay analysis and ΔBOLD in response to progressively increasing HC. Effect sizes (i.e. the standard mean difference between patients and controls) were calculated. HO-BOLD was used to estimate vCBV, and its contribution to the variability in rsBOLD signal was evaluated. ResultsThe effect sizes of ALFF and fALFF (0.61 and 0.72) were lower than the effect sizes related to hypercapnia-based hemodynamic assessment analysis; 1.62, 1.56 and 0.90 for HC-BOLD, BOLD response delays and ΔBOLD in response to progressively increasing HC. A moderate relation was found between (f)ALFF and HC-BOLD in controls (R2 of 0.61 and 0.42), but this relation decreased in patients (R2 of 0.33 and 0.15). (f)ALFF did not differ between patients and controls whereas HC-BOLD did (p < 0.005). The ΔBOLD response to progressively increasing HC was significantly different in between patients and controls for ΔEtCO2 values ≥ 2 mmHg (at +2 mmHg F(1, 18) = 5.85, p = 0.026). Up to 31% and 53% of the variance in the ALFF and HC-BOLD spatial distribution could be explained by HO-BOLD. ConclusionALFF and fALFF demonstrated a moderate effect size to detect hemodynamic impairment whereas the effect size was large for methods employing a hypercapnia-based vascular stress stimulus. Based on our analysis of BOLD signal change as a response to a progressively increasing hypercapnia stimulus we can argue that a hypercapnia stimulus of at least 2 mmHg above baseline EtCO2 is necessary to evaluate hemodynamic impairment. We also demonstrated that a substantial amount of information imbedded in the rsBOLD and HC-BOLD was explained by HO-BOLD. HO-BOLD can serve as a proxy for vCBV and this thus indicates that one should be careful when adopting these techniques in disease cases with compromised CBV.

Hypoxia compounds exercise-induced free radical formation in humans; partitioning contributions from the cerebral and femoral circulation

This study examined to what extent the human cerebral and femoral circulation contribute to free radical formation during basal and exercise-induced responses to hypoxia. Healthy participants (5♂, 5♀) were randomly assigned single-blinded to normoxic (21% O2) and hypoxic (10% O2) trials with measurements taken at rest and 30 min after cycling at 70% of maximal power output in hypoxia and equivalent relative and absolute intensities in normoxia. Blood was sampled from the brachial artery (a), internal jugular and femoral veins (v) for non-enzymatic antioxidants (HPLC), ascorbate radical (A•-, electron paramagnetic resonance spectroscopy), lipid hydroperoxides (LOOH) and low density lipoprotein (LDL) oxidation (spectrophotometry). Cerebral and femoral venous blood flow was evaluated by transcranial Doppler ultrasound (CBF) and constant infusion thermodilution (FBF). With 3 participants lost to follow up (final n = 4♂, 3♀), hypoxia increased CBF and FBF (P = 0.041 vs. normoxia) with further elevations in FBF during exercise (P = 0.002 vs. rest). Cerebral and femoral ascorbate and α-tocopherol consumption (v < a) was accompanied by A•-/LOOH formation (v > a) and increased LDL oxidation during hypoxia (P < 0.043–0.049 vs. normoxia) implying free radical-mediated lipid peroxidation subsequent to inadequate antioxidant defense. This was pronounced during exercise across the femoral circulation in proportion to the increase in local O2 uptake (r = −0.397 to −0.459, P = 0.037–0.045) but unrelated to any reduction in PO2. These findings highlight considerable regional heterogeneity in the oxidative stress response to hypoxia that may be more attributable to local differences in O2 flux than to O2 tension.

Biophysics of BOLD fMRI investigated with animal models

The widely-used BOLD fMRI signal depends on various anatomical, physiological, and imaging parameters. Thus, it is important to examine its biophysical and physiological source in order to optimize, model and accurately interpret fMRI. Animal models have been used to investigate these issues to take systematic measurements and combine with conventional invasive approaches. Here, we reviewed and discussed multiple issues, including the echo time-dependent intravascular contribution and extravascular contributions, gradient-echo vs. spin-echo fMRI, the physiological source of BOLD fMRI, arterial vs. venous cerebral blood volume change, cerebral oxygen consumption change, and arterial oxygen saturation change. We then discuss future directions of animal fMRI and translation to human fMRI. Systematic biophysical BOLD fMRI studies provide insight into the modeling and interpretation of BOLD fMRI in animals and humans.

Interleaved quantitative BOLD: Combining extravascular R2ʹ - and intravascular R2-measurements for estimation of deoxygenated blood volume and hemoglobin oxygen saturation

Quantitative BOLD (qBOLD), a non-invasive MRI method for assessment of hemodynamic and metabolic properties of the brain in the baseline state, provides spatial maps of deoxygenated blood volume fraction (DBV) and hemoglobin oxygen saturation (HbO2) by means of an analytical model for the temporal evolution of free-induction-decay signals in the extravascular compartment. However, mutual coupling between DBV and HbO2 in the signal model results in considerable estimation uncertainty precluding achievement of a unique set of solutions. To address this problem, we developed an interleaved qBOLD method (iqBOLD) that combines extravascular R2ʹ and intravascular R2 mapping techniques so as to obtain prior knowledge for the two unknown parameters. To achieve these goals, asymmetric spin echo and velocity-selective spin-labeling (VSSL) modules were interleaved in a single pulse sequence. Prior to VSSL, arterial blood and CSF signals were suppressed to produce reliable estimates for cerebral venous blood volume fraction (CBVv) as well as venous blood R2 (to yield HbO2). Parameter maps derived from the VSSL module were employed to initialize DBV and HbO2 in the qBOLD processing. Numerical simulations and in vivo experiments at 3 T were performed to evaluate the performance of iqBOLD in comparison to the parent qBOLD method. Data obtained in eight healthy subjects yielded plausible values averaging 60.1 ± 3.3% for HbO2 and 3.1 ± 0.5 and 2.0 ± 0.4% for DBV in gray and white matter, respectively. Furthermore, the results show that prior estimates of CBVv and HbO2 from the VSSL component enhance the solution stability in the qBOLD processing, and thus suggest the feasibility of iqBOLD as a promising alternative to the conventional technique for quantifying neurometabolic parameters.

MRI techniques to measure arterial and venous cerebral blood volume

The measurement of cerebral blood volume (CBV) has been the topic of numerous neuroimaging studies. To date, however, most in vivo imaging approaches can only measure CBV summed over all types of blood vessels, including arterial, capillary and venous vessels in the microvasculature (i.e. total CBV or CBVtot). As different types of blood vessels have intrinsically different anatomy, function and physiology, the ability to quantify CBV in different segments of the microvascular tree may furnish information that is not obtainable from CBVtot, and may provide a more sensitive and specific measure for the underlying physiology. This review attempts to summarize major efforts in the development of MRI techniques to measure arterial (CBVa) and venous CBV (CBVv) separately. Advantages and disadvantages of each type of method are discussed. Applications of some of the methods in the investigation of flow-volume coupling in healthy brains, and in the detection of pathophysiological abnormalities in brain diseases such as arterial steno-occlusive disease, brain tumors, schizophrenia, Huntington's disease, Alzheimer's disease, and hypertension are demonstrated. We believe that the continual development of MRI approaches for the measurement of compartment-specific CBV will likely provide essential imaging tools for the advancement and refinement of our knowledge on the exquisite details of the microvasculature in healthy and diseased brains.

Quantitative assessment of cerebral venous blood T2 in mouse at 11.7T: Implementation, optimization, and age effect.

To develop a non-contrast-agent MRI technique to quantify cerebral venous T2 in mice. We implemented and optimized a T2 -relaxation-under-spin-tagging (TRUST) sequence on an 11.7 Tesla animal imaging system. A flow-sensitive-alternating-inversion-recovery (FAIR) module was used to generate control and label images, pair-wise subtraction of which yielded blood signals. Then, a T2 -preparation module was applied to produce T2 -weighted images, from which blood T2 was quantified. We conducted a series of technical studies to optimize the imaging slice position, inversion slab thickness, post-labeling delay (PLD), and repetition time. We also performed three physiological studies to examine the venous T2 dependence on hyperoxia (N = 4), anesthesia (N = 3), and brain aging (N = 5). Our technical studies suggested that, for efficient data acquisition with minimal bias in estimated T2 , a preferred TRUST protocol was to place the imaging slice at the confluence of sagittal sinuses with an inversion-slab thickness of 2.5-mm, a PLD of 1000 ms and a repetition time of 3.5 s. Venous T2 values under normoxia and hyperoxia (inhaling pure oxygen) were 26.9 ± 1.7 and 32.3 ± 2.2 ms, respectively. Moreover, standard isoflurane anesthesia resulted in a higher venous T2 compared with dexmedetomidine anesthesia (N = 3; P = 0.01) which is more commonly used in animal functional MRI studies to preserve brain function. Venous T2 exhibited a decrease with age (N = 5; P < 0.001). We have developed and optimized a noninvasive method to quantify cerebral venous blood T2 in mouse at 11.7 T. This method may prove useful in studies of brain physiology and pathophysiology in animal models. Magn Reson Med 80:521-528, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Imaging putative foetal cerebral blood oxygenation using susceptibility weighted imaging (SWI).

To evaluate the magnetic susceptibility, ∆χ v , as a surrogate marker of venous blood oxygen saturation, S v O 2, in second- and third-trimester normal human foetuses. Thirty-six pregnant women, having a mean gestational age (GA) of 31 2/7 weeks, underwent magnetic resonance imaging (MRI). Susceptibility-weighted imaging (SWI) data from the foetal brain were acquired. ∆χ v of the superior sagittal sinus (SSS) was quantified using MR susceptometry from the intra-vascular phase measurements. Assuming the magnetic property of foetal blood, ∆χ do , is the same as that of adult blood, S v O 2 was derived from the measured Δχ v . The variation of ∆χ v and S v O 2, as a function of GA, was statistically evaluated. The mean ∆χ v in the SSS in the second-trimester (n = 8) and third-trimester foetuses (n = 28) was found to be 0.34± 0.06 ppm and 0.49 ±0.05 ppm, respectively. Correspondingly, the derived S v O 2 values were 69.4% ±3.27% and 62.6% ±3.25%. Although not statistically significant, an increasing trend (p = 0.08) in Δχ v and a decreasing trend (p = 0.22) in S v O 2 with respect to advancing gestation was observed. We report cerebral venous blood magnetic susceptibility and putative oxygen saturation in healthy human foetuses. Cerebral oxygen saturation in healthy human foetuses, despite a slight decreasing trend, does not change significantly with advancing gestation. • Cerebral venous magnetic susceptibility and oxygenation in human foetuses can be quantified. • Cerebral venous oxygenation was not different between second- and third-trimester foetuses. • Foetal cerebral venous oxygenation does not change significantly with advancing gestation.

Measuring changes in arterial and venous cerebral blood volume in human brain at 7T

Measuring changes in arterial and venous cerebral blood volume in human brain at 7T

Determining Excitatory and Inhibitory Neuronal Activity from Multimodal fMRI Data Using a Generative Hemodynamic Model.

Hemodynamic responses, in general, and the blood oxygenation level-dependent (BOLD) fMRI signal, in particular, provide an indirect measure of neuronal activity. There is strong evidence that the BOLD response correlates well with post-synaptic changes, induced by changes in the excitatory and inhibitory (E-I) balance between active neuronal populations. Typical BOLD responses exhibit transients, such as the early-overshoot and post-stimulus undershoot, that can be linked to transients in neuronal activity, but they can also result from vascular uncoupling between cerebral blood flow (CBF) and venous cerebral blood volume (venous CBV). Recently, we have proposed a novel generative hemodynamic model of the BOLD signal within the dynamic causal modeling framework, inspired by physiological observations, called P-DCM (Havlicek et al., 2015). We demonstrated the generative model's ability to more accurately model commonly observed neuronal and vascular transients in single regions but also effective connectivity between multiple brain areas (Havlicek et al., 2017b). In this paper, we additionally demonstrate the versatility of the generative model to jointly explain dynamic relationships between neuronal and hemodynamic physiological variables underlying the BOLD signal using multi-modal data. For this purpose, we utilized three distinct data-sets of experimentally induced responses in the primary visual areas measured in human, cat, and monkey brain, respectively: (1) CBF and BOLD responses; (2) CBF, total CBV, and BOLD responses (Jin and Kim, 2008); and (3) positive and negative neuronal and BOLD responses (Shmuel et al., 2006). By fitting the generative model to the three multi-modal experimental data-sets, we showed that the presence or absence of dynamic features in the BOLD signal is not an unambiguous indication of presence or absence of those features on the neuronal level. Nevertheless, the generative model that takes into account the dynamics of the physiological mechanisms underlying the BOLD response allowed dissociating neuronal from vascular transients and deducing excitatory and inhibitory neuronal activity time-courses from BOLD data alone and from multi-modal data.

Measurement of jugular foramen diameter using MRI in multiple sclerosis patients compared to control subjects

BackgroundMultiple sclerosis (MS) is a chronic disease of the central nervous system. As an association between MS and reduced cerebral venous blood drainage was hypothesised, our aim was to compare the size of the jugular foramina in patients with MS and in control subjects.MethodsEthics committee approval was received for this retrospective case–control study. We collected imaging and clinical data of 53 patients with MS (23 men, mean age 45 ± 9 years) and an age/gender-matched control group of 53 patients without MS (23 men, mean age 46 ± 10 years). The minimal diameter of both jugular foramina was measured on T1-weighted contrast-enhanced axial magnetic resonance images; the two diameters were summed. Student t test and Spearman correlation coefficient were used for analysis. Reproducibility was estimated using the Bland–Altman method.ResultsThe mean diameter of the right foramen in patients with MS (6.3 ± 1.6 mm) was 10% smaller than that of the controls (7.0 ± 1.4 mm) (p = 0.020); the mean diameter of the left foramen in patients with MS (5.6 ± 1.3 mm) was 7% smaller than that of the controls (6.0 ± 1.3 mm) (p = 0.089). The sum of the diameters of both jugular foramina in patients with MS (mean 11.9 ± 2.3 mm) was 8% smaller (p = 0.009) than that of the controls (mean 13.0 ± 2.1 mm). The differences in diameters between patients with relapsing-remitting MS and patients with secondary progressive MS were not significant (p ≥ 0.332). There was no significant correlation between foramen diameters and the expanded disability status scale (p ≥ 0.079). Intra-reader and inter-reader reproducibility were 91% and 88%, respectively.ConclusionsJugular foramen diameter in patients with MS was 7-10% smaller than that in controls, regardless of the MS disease course.

Identification of the Upward Movement of Human CSFIn Vivoand its Relation to the Brain Venous System

CSF flux is involved in the pathophysiology of neurodegenerative diseases and cognitive impairment after traumatic brain injury, all hallmarked by the accumulation of cellular metabolic waste. Its effective disposal via various CSF routes has been demonstrated in animal models. In contrast, the CSF dynamics in humans are still poorly understood. Using novel real-time MRI, forced inspiration has been identified recently as a main driving force of CSF flow in the human brain. Exploiting technical advances toward real-time phase-contrast MRI, the current work analyzed directions, velocities, and volumes of human CSF flow within the brain aqueduct as part of the internal ventricular system and in the spinal canal during respiratory cycles. A consistent upward CSF movement toward the brain in response to forced inspiration was seen in all subjects at the aqueduct, in 11/12 subjects at thoracic level 2, and in 4/12 subjects at thoracic level 5. Concomitant analyses of CSF dynamics and cerebral venous blood flow, that is, in epidural veins at cervical level 3, uniquely demonstrated CSF and venous flow to be closely communicating cerebral fluid systems in which inspiration-induced downward flow of venous blood due to reduced intrathoracic pressure is counterbalanced by an upward movement of CSF. The results extend our understanding of human CSF flux and open important clinical implications, including concepts for drug delivery and new classifications and therapeutic options for various forms of hydrocephalus and idiopathic intracranial hypertension.SIGNIFICANCE STATEMENT Effective disposal of brain cellular waste products via CSF has been demonstrated repeatedly in animal models. However, CSF dynamics in humans are still poorly understood. A novel quantitative real-time MRI technique yielded in vivo CSF flow directions, velocities, and volumes in the human brain and upper spinal canal. CSF moved upward toward the head in response to forced inspiration. Concomitant analysis of brain venous blood flow indicated that CSF and venous flux act as closely communicating systems. The finding of a human CSF-venous network with upward CSF net movement opens new clinical concepts for drug delivery and new classifications and therapeutic options for various forms of hydrocephalus and ideopathic intracranial hypertension.

ОПТИЧЕСКОЕ ПРОСВЕТЛЕНИЕ ЧЕРЕПНОЙ КОСТИ МНОГОКОМПОНЕНТНЫМИ ИММЕРСИОННЫМИ РАСТВОРАМИ И ВИЗУЛИЗАЦИЯ ЦЕРЕБРАЛЬНОГО ВЕНОЗНОГО КРОВОТОКА

ОПТИЧЕСКОЕ ПРОСВЕТЛЕНИЕ ЧЕРЕПНОЙ КОСТИ МНОГОКОМПОНЕНТНЫМИ ИММЕРСИОННЫМИ РАСТВОРАМИ И ВИЗУЛИЗАЦИЯ ЦЕРЕБРАЛЬНОГО ВЕНОЗНОГО КРОВОТОКА

Bedside Monitoring of Cerebral Energy State During Cardiac Surgery—A Novel Approach Utilizing Intravenous Microdialysis

This study investigated whether the lactate-to-pyruvate (LP) ratio obtained by microdialysis (MD) of the cerebral venous outflow reflected a derangement of global cerebral energy state during cardiopulmonary bypass (CPB). Interventional, prospective, randomized study. Single-center, university teaching hospital. The study included 10 patients undergoing primary, elective coronary artery bypass grafting. Patients were randomized blindly to low mean arterial pressure (MAP) (40-60 mmHg; n = 5) or high MAP (60-80 mmHg; n = 5) during CPB. The MD catheters were positioned in a retrograde direction into the jugular bulb, and a reference catheter was inserted into the brachial artery. The correlations among LP ratio, MAP, data obtained from bifrontal near-infrared spectroscopy (NIRS), and postoperative neurologic outcome measures were assessed. The correlated difference between pooled LP ratio (low and high MAP) of the jugular venous and the arterial blood was significant (LParterial 17 [15-20] v LPvenous 26 [23-27]; p = 0.0001). No cerebral desaturations (decrease in rSO2>20% from baseline) were observed in either group during CPB. In each group, 50% of the patients showed significant cognitive decline (mini-mental state examination, 3 points) 2 days after surgery. The LP ratio of cerebral venous blood increased significantly during CPB, indicating compromised cerebral oxidative metabolism. Conventional monitoring of rSO2 by NIRS did not show a corresponding decrease in cerebral oxygenation. As the patients exhibited decreased cognitive functions after CPB, increases in jugular venous LP ratio may be a sensitive indicator of impending cerebral damage.

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.

Field strength dependence of grey matter [formula omitted] on venous oxygenation

The relationship between venous blood oxygenation and change in transverse relaxation rate (ΔR2*) plays a key role in calibrated BOLD fMRI. This relationship, defined by the parameter β, has previously been determined using theoretical simulations and experimental measures. However, these earlier studies have been confounded by the change in venous cerebral blood volume (CBV) in response to functional tasks. This study used a double-echo gradient echo EPI scheme in conjunction with a graded isocapnic hyperoxic sequence to assess quantitatively the relationship between the fractional venous blood oxygenation (1−Yv) and transverse relaxation rate of grey matter (ΔR2⁢GM*), without inducing a change in vCBV.The results demonstrate that the relationship between ΔR2* and fractional venous oxygenation at all magnet field strengths studied was adequately described by a linear relationship. The gradient of this relationship did not increase monotonically with field strength, which may be attributed to the relative contributions of intravascular and extravascular signals which will vary with both field strength and blood oxygenation.

Multiparametric imaging of brain hemodynamics and function using gas-inhalation MRI

Diagnosis and treatment monitoring of cerebrovascular diseases routinely require hemodynamic imaging of the brain. Current methods either only provide part of the desired information or require the injection of multiple exogenous agents. In this study, we developed a multiparametric imaging scheme for the imaging of brain hemodynamics and function using gas-inhalation MRI. The proposed technique uses a single MRI scan to provide simultaneous measurements of baseline venous cerebral blood volume (vCBV), cerebrovascular reactivity (CVR), bolus arrival time (BAT), and resting-state functional connectivity (fcMRI). This was achieved with a novel, concomitant O2 and CO2 gas inhalation paradigm, rapid MRI image acquisition with a 9.3min BOLD sequence, and an advanced algorithm to extract multiple hemodynamic information from the same dataset. In healthy subjects, CVR and vCBV values were 0.23±0.03%/mmHg and 0.0056±0.0006%/mmHg, respectively, with a strong correlation (r=0.96 for CVR and r=0.91 for vCBV) with more conventional, separate acquisitions that take twice the scan time. In patients with Moyamoya syndrome, CVR in the stenosis-affected flow territories (typically anterior-cerebral-artery, ACA, and middle-cerebral-artery, MCA, territories) was significantly lower than that in posterior-cerebral-artery (PCA), which typically has minimal stenosis, flow territories (0.12±0.06%/mmHg vs. 0.21±0.05%/mmHg, p<0.001). BAT of the gas bolus was significantly longer (p=0.008) in ACA/MCA territories, compared to PCA, and the maps were consistent with the conventional contrast-enhanced CT perfusion method. FcMRI networks were robustly identified from the gas-inhalation MRI data after factoring out the influence of CO2 and O2 on the signal time course. The spatial correspondence between the gas-data-derived fcMRI maps and those using a separate, conventional fcMRI scan was excellent, showing a spatial correlation of 0.58±0.17 and 0.64±0.20 for default mode network and primary visual network, respectively. These findings suggest that advanced gas-inhalation MRI provides reliable measurements of multiple hemodynamic parameters within a clinically acceptable imaging time and is suitable for patient examinations.

The Stress and Vascular Catastrophes in Newborn Rats: Mechanisms Preceding and Accompanying the Brain Hemorrhages.

In this study, we analyzed the time-depended scenario of stress response cascade preceding and accompanying brain hemorrhages in newborn rats using an interdisciplinary approach based on: a morphological analysis of brain tissues, coherent-domain optical technologies for visualization of the cerebral blood flow, monitoring of the cerebral oxygenation and the deformability of red blood cells (RBCs). Using a model of stress-induced brain hemorrhages (sound stress, 120 dB, 370 Hz), we studied changes in neonatal brain 2, 4, 6, 8 h after stress (the pre-hemorrhage, latent period) and 24 h after stress (the post-hemorrhage period). We found that latent period of brain hemorrhages is accompanied by gradual pathological changes in systemic, metabolic, and cellular levels of stress. The incidence of brain hemorrhages is characterized by a progression of these changes and the irreversible cell death in the brain areas involved in higher mental functions. These processes are realized via a time-depended reduction of cerebral venous blood flow and oxygenation that was accompanied by an increase in RBCs deformability. The significant depletion of the molecular layer of the prefrontal cortex and the pyramidal neurons, which are crucial for associative learning and attention, is developed as a consequence of homeostasis imbalance. Thus, stress-induced processes preceding and accompanying brain hemorrhages in neonatal period contribute to serious injuries of the brain blood circulation, cerebral metabolic activity and structural elements of cognitive function. These results are an informative platform for further studies of mechanisms underlying stress-induced brain hemorrhages during the first days of life that will improve the future generation's health.