Extracerebral Blood Research Articles

The heartbeat induces local volumetric compression in the healthy human brain: a 7 T magnetic resonance imaging study on brain tissue pulsations.

Intracerebral blood volume changes along the cardiac cycle cause volumetric strain in brain tissue, measurable with displacement encoding with stimulated echoes (DENSE) magnetic resonance imaging. Individual volumetric strain maps show compressing and expanding voxels, raising the question whether systolic compressions reflect a physiological phenomenon. In DENSE data from nine healthy volunteers, voxels were grouped into three clusters according to volumetric strain in a tissue mask excluding extracerebral blood vessels and cerebrospinal fluid using a two-stage clustering approach. To confirm the physiological source of the compressions, data from a patient with a cranial opening was analysed. Spatial patterns of compressing and expanding clusters were matched to high-resolution anatomical scans, acquired in one additional individual. All healthy subjects consistently showed a cluster with compressive volumetric strain during systole, covering 10.2% [7.3-13.1%] (mean [95% confidence interval]) of the tissue mask, besides two expansion clusters. In the patient, no compression was observed. Although the compression cluster did not consistently co-localize with intracerebral veins or perivascular spaces on the anatomical scans, the first-stage clustering results suggested that the distinction between the clusters has a (peri)vascular source. In conclusion, brain tissue shows heartbeat-induced volumetric compressions, possibly indicating compression of porous structures such as intracerebral veins or perivascular spaces.

New Genetic Biomarkers of the Overlap Syndrome Tension-Type Headache and Arterial Hypertension.

Background: Nitric oxide (NO) is an important autocrine and paracrine signaling molecule that plays a crucial role in cardiovascular physiology and pathology regulation. NO is an important molecule involved in regulation of cerebral and extra cerebral cranial blood flow and arterial diameters. Reduced bioavailability of NO in the endothelium is an important precursor for impaired vasodilation and arterial hypertension (AH). Furthermore, NO is involved in nociceptive processing. A NO-induced biphasic response with immediate and a delayed headache is typical for chronic tension-type headaches (TTH) in humans. The aim was to study the association of allelic variants and genotypes of the single nucleotide variant (SNV) rs3782218 of the NOS1 gene with the TTH and AH overlap syndrome development in middle age adults. Materials and Methods: We observed 91 Caucasian participants who resided in Krasnoyarsk city: group 1 (TTH and AH overlap syndrome)—30 patients; group 2 (AH without headache)—30 patients; group 3 (control)—31 healthy volunteers. The diagnosis of AH was based on criteria of the European Society of Cardiology and the European Society of Hypertension (2018) и criteria of the Russian Society of Cardiology (2020). Diagnosis of TTH was based on criteria of the International Classification of Headache Disorders (2018). Real-time polymerase chain reaction was used for the determination of allelic variants and genotypes of the SNV rs3782218 of the NOS1 gene in all groups of participants. Results: The frequency of the minor allele T of rs3782218 was statistically significantly higher by 16.7 times in group 1 (TTH and AH) compared to group 3 (control): 26.7% versus 1.6%, respectively (p-value = 0.000065) and 3.2 times higher in group 1 (TTH and AH) compared to group 2 (AH without headache): 26.7% versus 8.3%, respectively (p-value = 0.008). The frequency of the heterozygous (CT) genotype was statistically significantly higher in group 1 (TTH and AH) compared to group 3 (control): 40.0% versus 3.2% (p-value = 0.000454) and in group 1 (TTH and AH) compared to group 2 (AH without headache): 40.0% versus 16.7% (p-value = 0.045). The minor allele T was statistically significantly associated with a high risk of developing the TTH and AH overlap syndrome compared with the controls (odds ratio (OR) = 22.2 (95% confidential interval (CI): 2.8–173.5)) and compared with AH without headache (OR = 4.0 (95% CI: 1.4–11.8)). Although the frequency of the minor allele T was 5.2 times higher in group 2 (AH without headache) compared with group 3 (control), there were not statistically significantly differences (p-value = 0.086). Conclusion: Thus, the minor allele T of rs3782218 of the NOS1 gene is an important genetic biomarker for a high risk of developing the TTH and AH overlap syndrome in hypertensive patients.

Longitudinal angiographic characterization of the efficacy of combined cerebral revascularization using minimally invasive encephalodurosynangiosis in patients with moyamoya angiopathy

Moyamoya angiopathy (MMA) can be treated using direct, indirect, or combined revascularization procedures. We perform combined revascularization using the STA-MCA bypass and minimally invasive encephalodurosynangiosis (MIS-EDS). Due to lack of systematic analyses to date it remains unclear whether and to which extent this limited EDS serves as a growth source for extracerebral blood vessels into the brain. The objective of the current study is to characterize the extent of angiographic filling of MIS-EDS and STA-MCA bypass development over time and to determine possible predictors of EDS development in adult MMA patients. Single-center retrospective analysis of 81 MMA patients (139 hemispheres) treated with a MIS-EDS and STA-MCA bypass was performed. Angiographic images and clinical/operative data were reviewed and scored. Uni-/ and multivariate Cox regression analyses identified preoperative predictors of good EDS vascularization. At 3–6 months after surgery EDS showed moderate and high angiographic filling in 40% and 5% of hemispheres, respectively. After 12 months moderate and high filling was found in 57% and 4% of hemispheres, respectively. STA-MCA bypass filling was moderate in 47% and high in 7% of hemispheres at 3–6 months and 45% moderate and 9% high after 12 months. High STA-MCA bypass filling on angiography was a negative predictor of EDS development. MIS-EDS is a simple technique and serves as a source of vessel growth into the brain. EDS development lags behind that of STA-MCA bypass and can be recommended as an additive revascularization source when combined with a direct bypass.

Optimization of time domain diffuse correlation spectroscopy parameters for measuring brain blood flow.

.Significance: Time domain diffuse correlation spectroscopy (TD-DCS) can offer increased sensitivity to cerebral hemodynamics and reduced contamination from extracerebral layers by differentiating photons based on their travel time in tissue. We have developed rigorous simulation and evaluation procedures to determine the optimal time gate parameters for monitoring cerebral perfusion considering instrumentation characteristics and realistic measurement noise.Aim: We simulate TD-DCS cerebral perfusion monitoring performance for different instrument response functions (IRFs) in the presence of realistic experimental noise and evaluate metrics of sensitivity to brain blood flow, signal-to-noise ratio (SNR), and ability to reject the influence of extracerebral blood flow across a variety of time gates to determine optimal operating parameters.Approach: Light propagation was modeled on an MRI-derived human head geometry using Monte Carlo simulations for 765- and 1064-nm excitation wavelengths. We use a virtual probe with a source–detector separation of 1 cm placed in the pre-frontal region. Performance metrics described above were evaluated to determine optimal time gate(s) for different IRFs. Validation of simulation noise estimates was done with experiments conducted on an intralipid-based liquid phantom.Results: We find that TD-DCS performance strongly depends on the system IRF. Among Gaussian pulse shapes, pulse length appears to offer the best performance, at wide gates (500 ps and larger) with start times 400 and 600 ps after the peak of the TPSF at 765 and 1064 nm, respectively, for a 1-s integration time at photon detection rates seen experimentally (600 kcps at 765 nm and 4 Mcps at 1064 nm).Conclusions: Our work shows that optimal time gates satisfy competing requirements for sufficient sensitivity and sufficient SNR. The achievable performance is further impacted by system IRF with quasi-Gaussian pulse obtained using electro-optic laser shaping providing the best results.

Transcranial Optical Monitoring of Cerebral Hemodynamics in Acute Stroke Patients during Mechanical Thrombectomy

Introduction: Mechanical thrombectomy is revolutionizing treatment of acute stroke due to large vessel occlusion (LVO). Unfortunately, use of the modified Thrombolysis in Cerebral Infarction score (mTICI) to characterize recanalization of the cerebral vasculature does not address microvascular perfusion of the distal parenchyma, nor provide more than a vascular “snapshot.” Thus, little is known about tissue-level hemodynamic consequences of LVO recanalization. Diffuse correlation spectroscopy (DCS) and diffuse optical spectroscopy (DOS) are promising methods for continuous, noninvasive, contrast-free transcranial monitoring of cerebral microvasculature. Methods: Here, we use a combined DCS/DOS system to monitor frontal lobe hemodynamic changes during endovascular treatment of 2 patients with ischemic stroke due to internal carotid artery (ICA) occlusions. Results and Discussion: The monitoring instrument identified a recanalization-induced increase in ipsilateral cerebral blood flow (CBF) with little or no concurrent change in contralateral CBF and extracerebral blood flow. The results suggest that diffuse optical monitoring is sensitive to intracerebral hemodynamics in patients with ICA occlusion and can measure microvascular responses to mechanical thrombectomy.

Chronic Migraine and Elevated CRP Levels

C-reactive protein (CRP) is a known pro-inflammation biomarker and important predictor of migraine headache. Many studies have detected higher levels of CRP in patients suffering from migraine headache than normal subjects. Etiopathology has been related to ongoing sterile inflammation of intra and extra cerebral blood vessels and the subsequent release of proinflammatory neuropeptides from perivascular nerve endings. The present study was performed on 50 females suffering from chronic migraine (CM) and their CRP levels were compared with normal persons. We intended to find the correlation between CM and CRP levels as such patients are also predisposed to various other associated cardiovascular and cerebrovascular events like stroke and ischemic heart diseases. Therefore, early detection of CRP levels in migraine sufferer may be helpful in treatment of migraine headache and in prevention of cardiovascular and cerebrovascular events. Mean value of C-reactive protein estimation was significantly higher (< 0.001) in patients group as compared to normal controls. On comparing results of sub group A, (migraine with aura) and sub group B (migraine without aura) with control group, differences were significant. On other hand, result of comparison between groups A with B was not significant. Finally, we could conclude that the present study supports that CRP an inflammatory marker was significantly higher in migraineurs in comparison with normal subjects. By these findings, the role of sterile inflammation could explain the cause of onset and progression of migraine headache.

A multiscale model for the simulation of cerebral and extracerebral blood flows and pressures in humans.

Brain hemodynamics is fundamental for the functioning of the human being. Many biophysical factors affect brain circulation, so that a satisfactory understanding of its behavior is challenging. We developed a mathematical model to simulate cerebral and extracerebral flows and pressures in humans. The model is composed of an anatomically informed 1-D arterial network, and two 0-D networks of the cerebral circulation and brain drainage, respectively. It takes into account the pulse-wave transmission properties of the 55 main arteries and the main hydraulic and autoregulation mechanisms ensuring blood supply and drainage to the brain. Proper pressure outputs from the arterial 1-D model are used as input to the 0-D models, together with the contribution to venous pressure due to breathing that simulates the drainage effect of the thoracic pump. The model we developed is able to link the arterial tree with the venous pathways devoted to the brain drainage, and to simulate important factors affecting cerebral circulation both for physiological and pathological conditions, such as breathing and hypo/hypercapnia. Finally, the average value of simulated flows and pressures is in agreement with the available experimental data. The model has the potential to predict important clinical parameters before and after physiological and/or pathological changes.

Effects of ultrasound-guided stellate ganglion block on cervical vascular blood flow: study protocol for a randomized controlled trial

BackgroundThe stellate ganglion block (SGB) can lead to vasodilation of the head and neck. However, controversy remains concerning the changes in extracerebral blood flow. The objective of this study is to assess the effects of SGB on the blood flow to the neck.MethodsA randomized controlled crossover trial with 38 participants will be conducted. Participants who have primary headaches will be assigned to either group A or B. Patients in group A will receive SGB with 6 ml 1% lidocaine, and after a one-week washout period, they will undergo the second SGB with 6 ml normal saline. In contrast, patients in group B will receive the opposite protocol. Data will be collected at baseline (T0) and at 15 min after the first intervention (T1), 15 min before the second intervention (T2), 15 min after the second intervention (T3) and at a 3-week follow up (T4). T1 is the primary time point for the primary outcome analysis. The primary outcomes include the peak systolic velocity (PSV), the end diastolic velocity (EDV), resistance index (RI) and vessel diameter of the common carotid artery (CCA) and vertebral artery (VA). The secondary outcomes include the rate of ptosis, the rate of conjunctival flushing, and the numerical rating scale (NRS) pain score. Additionally, adverse events (AEs) or serious adverse events (SAEs) will be collected at each assessment point.DiscussionThis study will comprehensively investigate the efficacy of SGB in extracerebral blood flow. Our research may also suggest that SGB will be effective in reducing pain in patients with primary headaches.Trial registrationChinese Clinical Trial Registry, identifier ChiCTR-IOR-17011536. Registered on 1 June 2017.

P 16 The implementation of Near-Infrared-Spectroscopy (NIRS) in sports science – a verification of suitability using the compound movement squat

Introduction Near - Infrared Spectroscopy (NIRS) serves as a promising tool to examine cortical activity in a sports-scientific context. The associated feasibility of said method remains to be validated as exercise - induced confounders such as increases in extracerebral blood flow have been postulated ( Tachtsidis and Scholkmann, 2016 ). Additionally, the relationship between force and cortical activity is yet to be investigated in compound movements. Both parameters show a linear relationship in isolated movements ( Shibuya et al., 2014 ) yet it remains unclear whether this relationship applies to compound movements. Here we assessed the feasibility of NIRS for the compound movement barbell squat (BS). Complementarily the relationship between force levels and cortical activity during the squat was examined. We hypothesized that the extracerebral blood flow superimposes the signal and can be eliminated. Furthermore, we hypothesized a linear relationship between force during BS and cortical activity in the leg area of bilateral primary motor cortex (M1). Methods Ten healthy young adults participated in this study (n = 10; age: 25.7 ± 2.214 years). All subjects performed the BS task, five 90° squats per activity block, on three separate days with varying NIRS - configurations to control for and eliminate extracerebral effects. The experimental setup corresponds to a block design with varying force levels (L0%, L20%, L40%) which were individually adjusted in succession to Maximum Strength Tests. Our standard NIRS - configuration (A) covered the cortical motor system. The second configuration (B) additionally covered bilateral auditory cortices, frontopolar areas, as well as primary visual cortex. A third configuration incorporated a short - distance - channel to use this channel in a short separation regression (C). Cortical activation was assumed to be reflected by increased oxyhemoglobin (HbO2) and a corresponding decline or unchanged deoxyhemoglobin (HHb). Results For (A) and (B), HbO2showed a significant increase in the entire detection range when comparing the varying force levels during BS ( p 0.0023 ). For (C), HbO2 showed a significant increase in bilateral superior parietal lobule (SPL) (L20%, L40%) when compared to L0% ( p 0.01 ). HbO2 showed no significant increase when comparing the different force levels to baseline values. HHb showed no regionally consistent, significant decline for all comparisons. Discussion Short separation regression potentially enables the disentanglement of extracerebral blood flow from cerebral blood flow. There is a relationship between force and cortical activity in the squat when comparing force levels, although in bilateral SPL as opposed to M1 as seen in isolated movements. This implies a different modulator for compound movements compared to isolated movements.

Hemodynamic Response Alterations in Sensorimotor Areas as a Function of Barbell Load Levels during Squatting: An fNIRS Study.

Functional near-infrared spectroscopy (fNIRS) serves as a promising tool to examine hemodynamic response alterations in a sports-scientific context. The present study aimed to investigate how brain activity within the human motor system changes its processing in dependency of different barbell load conditions while executing a barbell squat (BS). Additionally, we used different fNIRS probe configurations to identify and subsequently eliminate potential exercise induced systemic confounders such as increases in extracerebral blood flow. Ten healthy, male participants were enrolled in a crossover design. Participants performed a BS task with random barbell load levels (0% 1RM (1 repetition maximum), 20% 1RM and 40% 1RM for a BS) during fNIRS recordings. Initially, we observed global hemodynamic response alterations within and outside the human motor system. However, short distance channel regression of fNIRS data revealed a focalized hemodynamic response alteration within bilateral superior parietal lobe (SPL) for oxygenated hemoglobin (HbO2) and not for deoxygenated hemoglobin (HHb) when comparing different load levels. These findings indicate that the previously observed load/force-brain relationship for simple and isolated movements is also present in complex multi-joint movements such as the BS. Altogether, our results show the feasibility of fNIRS to investigate brain processing in a sports-related context. We suggest for future studies to incorporate short distance channel regression of fNIRS data to reduce the likelihood of false-positive hemodynamic response alterations during complex whole movements.

Erratum to: Age differences in arterial and venous extra-cerebral blood flow in healthy adults: contributions of vascular risk factors and genetic variants.

Sufficient cerebral blood flow (CBF) and venous drainage are critical for normal brain function, and their alterations can affect brain aging. However, to date, most studies focused on arterial CBF (inflow) with little attention paid to the age differences in venous outflow. We measured extra-cerebral arterial and venous blood flow rates with phase-contrast MRI and assessed the influence of vascular risk factors and genetic polymorphisms (ACE insertion/deletion, COMT val158met, and APOEe4) in 73 adults (age 18–74 years). Advanced age, elevated vascular risk, ACE Deletion, and COMT met alleles were linked to lower in- and outflow, with no effects of APOE e4 noted. Lower age-related CBF rate was unrelated to brain volume and was observed only in val homozygotes of COMTval158met. Thus, in a disease-free population, age differences in CBF may be notable only in persons with high vascular risk and carriers of genetic variants associated with vasoconstriction and lower dopamine availability. It remains to be established if treatments targeting alleviation of the mutable factors can improve the course of cerebrovascular aging in spite of the immutable genetic influence.

Age differences in arterial and venous extra-cerebral blood flow in healthy adults: contributions of vascular risk factors and genetic variants.

Sufficient cerebral blood flow (CBF) and venous drainage are critical for normal brain function, and their alterations can affect brain aging. However, to date, most studies focused on arterial CBF (inflow) with little attention paid to the age differences in venous outflow. We measured extra-cerebral arterial and venous blood flow rates with phase-contrast MRI and assessed the influence of vascular risk factors and genetic polymorphisms (ACE insertion/deletion, COMT val158met, and APOEε4) in 73 adults (age 18-74years). Advanced age, elevated vascular risk, ACE Deletion, and COMT met alleles were linked to lower in- and outflow, with no effects of APOE ε4 noted. Lower age-related CBF rate was unrelated to brain volume and was observed only in val homozygotes of COMTval158met. Thus, in a disease-free population, age differences in CBF may be notable only in persons with high vascular risk and carriers of genetic variants associated with vasoconstriction and lower dopamine availability. It remains to be established if treatments targeting alleviation of the mutable factors can improve the course of cerebrovascular aging in spite of the immutable genetic influence.

Validation of a Hemodynamic Model for the Study of the Cerebral Venous Outflow System Using MR Imaging and Echo-Color Doppler Data.

A comprehensive parameter model was developed to investigate correlations between cerebral hemodynamics and alterations in the extracranial venous circulation due to posture changes and/or extracranial venous obstruction (stenosis). The purpose of this work was to validate the simulation results by using MR imaging and echo-color Doppler experimental blood flow data in humans. To validate the model outcomes, we used supine average arterial and venous extracerebral blood flow, obtained by using phase-contrast MR imaging from 49 individuals with stenosis in the acquisition plane at the level of the disc between the second and third vertebrae of the left internal jugular vein, 20 with stenosis in the acquisition plane at the level of the disc between the fifth and sixth vertebrae of the right internal jugular vein, and 38 healthy controls without stenosis. Average data from a second group of 10 healthy volunteers screened with an echo-color Doppler technique were used to evaluate flow variations due to posture change. There was excellent agreement between experimental and simulated supine flows. Every simulated CBF fell inside the standard error from the corresponding average experimental value, as well as most of the simulated extracerebral arterial flow (extracranial blood flow from the head and face, measured at the level of the disc between second and third vertebrae) and venous flows. Simulations of average jugular and vertebral blood flow variations due to a change of posture from supine to upright also matched the experimental data. The good agreement between simulated and experimental results means that the model can correctly reproduce the main factors affecting the extracranial circulation and could be used to study other types of stenotic conditions not represented by the experimental data.

Intermittent hypoxia training protects cerebrovascular function in Alzheimer's disease.

Alzheimer's disease (AD) is a leading cause of death and disability among older adults. Modifiable vascular risk factors for AD (VRF) include obesity, hypertension, type 2 diabetes mellitus, sleep apnea, and metabolic syndrome. Here, interactions between cerebrovascular function and development of AD are reviewed, as are interventions to improve cerebral blood flow and reduce VRF. Atherosclerosis and small vessel cerebral disease impair metabolic regulation of cerebral blood flow and, along with microvascular rarefaction and altered trans-capillary exchange, create conditions favoring AD development. Although currently there are no definitive therapies for treatment or prevention of AD, reduction of VRFs lowers the risk for cognitive decline. There is increasing evidence that brief repeated exposures to moderate hypoxia, i.e. intermittent hypoxic training (IHT), improve cerebral vascular function and reduce VRFs including systemic hypertension, cardiac arrhythmias, and mental stress. In experimental AD, IHT nearly prevented endothelial dysfunction of both cerebral and extra-cerebral blood vessels, rarefaction of the brain vascular network, and the loss of neurons in the brain cortex. Associated with these vasoprotective effects, IHT improved memory and lessened AD pathology. IHT increases endothelial production of nitric oxide (NO), thereby increasing regional cerebral blood flow and augmenting the vaso- and neuroprotective effects of endothelial NO. On the other hand, in AD excessive production of NO in microglia, astrocytes, and cortical neurons generates neurotoxic peroxynitrite. IHT enhances storage of excessive NO in the form of S-nitrosothiols and dinitrosyl iron complexes. Oxidative stress plays a pivotal role in the pathogenesis of AD, and IHT reduces oxidative stress in a number of experimental pathologies. Beneficial effects of IHT in experimental neuropathologies other than AD, including dyscirculatory encephalopathy, ischemic stroke injury, audiogenic epilepsy, spinal cord injury, and alcohol withdrawal stress have also been reported. Further research on the potential benefits of IHT in AD and other brain pathologies is warranted.

Influence Of Lung Volume On Circulatory Function And Arterial Blood Gases During Prolonged Breath Holding In Elite Apnea Divers

Maximal apnea in elite breath hold divers involves the suppression of involuntary breathing movements (IBMs). During apnea at total lung capacity (TLC), stroke volume (SV) is reduced due to compression of the vena cava; however, IBMs are thought to improve apnea time by elevating cardiac output (Q[Combining Dot Above]) and cerebral oxygen delivery (CDO2) via increased venous return. Although not experimentally investigated, this suggests CDO2 is limited by the reduced Q[Combining Dot Above] secondary to lung inflation. The purpose of this study was to investigate whether a higher Q[Combining Dot Above] during apnea at functional residual capacity (FRC) facilitates CDO2 and determine whether IBM onset and apnea end are linked to PaO2, oxygen content (CaO2) or CDO2. Fifteen elite divers (1F; 185 ± 7 cm, 82 ± 12 kg, 29 ± 7 years) completed two maximal apneas at TLC and FRC. Cardiovascular responses were assessed continuously via photoplethysmography. Global extra-cerebral blood flow (gCBF) and intra-cranial velocities were measured via extracranial and transcranial ultrasound, respectively. Arterial blood gases were assessed at IBM onset and apnea end. Maximal apnea was 38% longer at TLC vs. FRC (304 ± 71 vs. 188 ± 44 sec, P<0.001) and IBM onset occurred later (150 ± 44 vs. 113 ± 36 sec, P <0.001). At FRC, SV and Q[Combining Dot Above] did not change from baseline (P>0.05). In contrast, during the TLC trial SV and Q[Combining Dot Above] were decreased until 80% and 40% of apnea duration, respectively, (P<0.05). Consistent with Q[Combining Dot Above], gCBF was significantly lower at 20% apnea during the TLC trial but recovered for the remainder of the apnea. Mean arterial pressure rose progressively in both trials but to a greater extent at TLC. At apnea end, although PaO2 was lower (30 ± 8 vs. 35 ± 11 mmHg, P=0.004) in the FRC trial, CaO2 was the same due to a higher PaCO2 in the TLC trial. IBM onset occurred at the same PaCO2 (43 ± 5 vs. 43 ± 5 mmHg, P=0.60) but a lower PaO2 (46 ± 14 vs. 71 ± 18 mmHg, p<<0.001) during the FRC trial. Lung volume has a profound effect on SV, Q[Combining Dot Above] and gCBF during the early stages of apnea. However, at apnea end, Q[Combining Dot Above], gCBF and CDO2 are the same irrespective of lung volume. A comparable CaO2 despite a lower PaO2 at FRC apnea end highlights the importance of acidosis on the oxygen dissociation curve. In addition, IBMs appear to be governed by PaCO2 rather than PaO2 suggesting any beneficial effect of IBMs on CDO2 to be indirect and secondary to hypercapnia.

Pressure modulation algorithm to separate cerebral hemodynamic signals from extracerebral artifacts.

We introduce and validate a pressure measurement paradigm that reduces extracerebral contamination from superficial tissues in optical monitoring of cerebral blood flow with diffuse correlation spectroscopy (DCS). The scheme determines subject-specific contributions of extracerebral and cerebral tissues to the DCS signal by utilizing probe pressure modulation to induce variations in extracerebral blood flow. For analysis, the head is modeled as a two-layer medium and is probed with long and short source-detector separations. Then a combination of pressure modulation and a modified Beer-Lambert law for flow enables experimenters to linearly relate differential DCS signals to cerebral and extracerebral blood flow variation without a priori anatomical information. We demonstrate the algorithm's ability to isolate cerebral blood flow during a finger-tapping task and during graded scalp ischemia in healthy adults. Finally, we adapt the pressure modulation algorithm to ameliorate extracerebral contamination in monitoring of cerebral blood oxygenation and blood volume by near-infrared spectroscopy.

Neuronal effects of a nickel-piperazine/NO donor complex in rodents

In the brain, NO is a very important molecule in the regulation of cerebral and extra cerebral cranial blood flow and arterial diameters. It is also importantly involved in many neuronal functions and innumerable roles of NO in many brain related disorders including epilepsy, schizophrenia, drug addiction, anxiety, major depression, have been postulated. The present study aimed to explore the neuronal role exerted by the metal-nonoate compound Ni(PipNONO)Cl, a novel NO donor whose vascular protective effects have been recently demonstrated. Ni(PipNONO)Cl showed antidepressant-like properties in the tail suspension test and antiamnesic activity in the passive avoidance test in the absence of any hypernociceptive response to a mechanical stimulus. These effects were related to the NO-releasing properties of the compound within the central nervous system as demonstrated by the increase of iNOS levels in the brain, spinal cord and dura mater. The modulation of neuronal functions appeared after acute and repeated treatment, showing the lack of any tolerance to neuronal effects. At the dose used (10mg/kg i.p.), Ni(PipNONO)Cl did not induce any visible sign of toxicity and experiments were performed in the absence of locomotor impairments. In addition to the NO-related neuronal activities of Ni(PipNONO)Cl, the decomposition control compound Ni(Pip)Cl2 showed anxiogenic-like and procognitive effects. The present findings showed neuronal modulatory activity of Ni(PipNONO)Cl through a NO-mediated mechanism. The activities of the decomposition compound Ni(Pip)Cl2 attributed to Ni(PipNONO)Cl the capability to modulate additional neuronal functions independently from NO releasing properties extending and improving the therapeutic perspectives of the NO donor.

Detection of delayed cerebral ischemia (DCI) in subarachnoid haemorrhage applying near-infrared spectroscopy: elimination of the extracerebral signal by transcutaneous and intraparenchymatous measurements in parallel.

Detection of delayed cerebral ischemia (DCI) in high-grade subarachnoid haemorrhage (SAH) is an unsolved issue. Conventional near-infrared spectroscopy (NIRS) with optodes applied over the skin is controversial because the NIRS signal is contaminated by extracerebral tissue. The objective is to quantify and subtract the contribution from extracerebral tissue from the signal by using measurements in parallel with a NIRS brain tissue probe and conventional NIRS. In a patient with high-grade SAH, two approaches for NIRS were applied. First, a conventional brain tissue probe for intracranial pressure (ICP) monitoring, supplied by optical fibres, was placed into the brain tissue 2 cm deep from the dura. Second, for conventional NIRS, a plaster-based patch carrying optodes (one emitter, two detectors) was attached to the skin. Central venous injections of 0.3 mg/kg body weight (bw) indocyanine green (ICG) were performed. ICG dye dilution curves obtained with the probe and patch were collected simultaneously and analysed for blood flow values. Twelve measurements in parallel with the probe and patch were performed. Mean cerebral blood flow (CBF) for the probe was higher (24.8 ± 9.1 ml/100 g/min) compared with the values obtained with the patch (for detector 1, extra-cerebral blood flow [ECBF] mean 5.1 ± 1.8 ml/100 g/min; p = 0.002; for detector 2, 6.6 ± 2.1 ml/100 g/min; p = 0.002). CBF values obtained with the probe correlated with blood flow values obtained with the patch (for CBF vs. ECBF detector 1, r = 0.72 [p = 0.008]; ECBF detector 2, r = 0.79 [p = 0.002]). Blood flow values obtained with conventional NIRS correlated significantly with absolute CBF values obtained directly within the brain tissue. Simultaneous measurements with the NeMo Probe and NeMo Patch allow quantification and subtraction of the contribution from extracerebral tissues from the signal obtained with conventional NIRS.

A note on arterial to venous oxygen saturation as reference for NIRS-determined frontal lobe oxygen saturation in healthy humans

A note on arterial to venous oxygen saturation as reference for NIRS-determined frontal lobe oxygen saturation in healthy humans

Variance of time-of-flight distribution is sensitive to cerebral blood flow as demonstrated by ICG bolus-tracking measurements in adult pigs

Variance of time-of-flight distributions have been shown to be more sensitive to cerebral blood flow (CBF) during dynamic-contrast enhanced monitoring of neurotrauma patients than attenuation. What is unknown is the degree to which variance is affected by changes in extracerebral blood flow. Furthermore, the importance of acquiring the arterial input function (AIF) on quantitative analysis of the data is not yet clear. This animal study confirms that variance is both sensitive and specific to changes occurring in the brain when measurements are acquired on the surface of the scalp. Furthermore, when the variance data along with the measured AIF is analyzed using a nonparametric deconvolution method, the recovered change in CBF is in good agreement with CT perfusion values.