Cerebral Blood Flow Response Research Articles

Microvascular cerebral blood flow response to intrathecal nicardipine is associated with delayed cerebral ischemia.

One of the common complications of non-traumatic subarachnoid hemorrhage (SAH) is delayed cerebral ischemia (DCI). Intrathecal (IT) administration of nicardipine, a calcium channel blocker (CCB), upon detection of large-artery cerebral vasospasm holds promise as a treatment that reduces the incidence of DCI. In this observational study, we prospectively employed a non-invasive optical modality called diffuse correlation spectroscopy (DCS) to quantify the acute microvascular cerebral blood flow (CBF) response to IT nicardipine (up to 90 min) in 20 patients with medium-high grade non-traumatic SAH. On average, CBF increased significantly with time post-administration. However, the CBF response was heterogeneous across subjects. A latent class mixture model was able to classify 19 out of 20 patients into two distinct classes of CBF response: patients in Class 1 (n = 6) showed no significant change in CBF, while patients in Class 2 (n = 13) showed a pronounced increase in CBF in response to nicardipine. The incidence of DCI was 5 out of 6 in Class 1 and 1 out of 13 in Class 2 (p < 0.001). These results suggest that the acute (<90 min) DCS-measured CBF response to IT nicardipine is associated with intermediate-term (up to 3 weeks) development of DCI.

Cerebral blood flow response to cardiorespiratory oscillations in healthy humans

Dynamic cerebral autoregulation (CA) characterizes the cerebral blood flow (CBF) response to abrupt changes in arterial blood pressure (ABP). CA operates at frequencies below 0.15Hz. ABP regulation and probably CA are modified by autonomic nervous activity. We investigated the CBF response and CA dynamics to mild increase in sympathetic activity. Twelve healthy volunteers underwent oscillatory lower body negative pressure (oLBNP), which induced respiratory-related ABP oscillations at an average of 0.22Hz. We recorded blood velocity in the internal carotid artery (ICA) by Doppler ultrasound and ABP. We quantified variability and peak wavelet power of ABP and ICA blood velocity by wavelet analysis at low frequency (LF, 0.05-0.15Hz) and Mayer waves (0.08-0.12Hz), respectively. CA was quantified by calculation of the wavelet synchronization gamma index for the pair ABP-ICA blood velocity in the LF and Mayer wave band. oLBNP increased ABP peak wavelet power at the Mayer wave frequency. At the Mayer wave, ABP peak wavelet power increased by >70% from rest to oLBNP (p<0.05), while ICA blood flow velocity peak wavelet power was unchanged, and gamma index increased (from 0.49 to 0.69, p<0.05). At LF, variability in both ABP and ICA blood velocity and gamma index were unchanged from rest to oLBNP. Despite an increased gamma index at Mayer wave, ICA blood flow variability was unchanged during increased ABP variability. The increased synchronization during oLBNP did not cause less stable CBF or less active CA. Sympathetic activation seems to improve the mechanisms of CA.

DEPENDENCE ON ANESTHESIOLOGY SUPPORT IN VICTIMS WITH COMBINED MINE-EXPLOSIVE THORACO-ABDOMINAL INJURIES AND PENETRATING HEAD INJURIES AT THE STAGE OF PREPARATION AND CONDUCTING OF AEROMEDICAL EVACUATION

Introduction. Explosive explosive injuries account for more than 50% of all injuries received in military battles, and the proportion of casualties among the civilian population is also increasing [1]. However, only limited research has been conducted on the pathophysiology of blast-induced brain injury, and the effect of changes in cerebral blood flow (CBF) or cerebral vascular reactivity on blast-induced brain injury has not been investigated [2]. Although secondary hypotension and hypoxemia are associated with increased mortality and morbidity after blunt head injury, the effect of secondary injury factors in blast injury is unknown [2]. TBI itself causes cerebral hypoperfusion, reduced oxygen delivery to the brain, excitotoxicity, and disruption of cerebral blood flow autoregulation, which explains the vulnerability of the affected brain to hypoxia and hypotension caused by blood loss [2,3].

Beyond intracranial pressure: monitoring cerebral perfusion and autoregulation in severe traumatic brain injury.

Severe traumatic brain injury (TBI) remains the most prevalent neurological condition worldwide. Observational and interventional studies provide evidence to recommend monitoring of intracranial pressure (ICP) in all severe TBI patients. Existing guidelines focus on treating elevated ICP and optimizing cerebral perfusion pressure (CPP), according to fixed universal thresholds. However, both ICP and CPP, their target thresholds, and their interaction, need to be interpreted in a broader picture of cerebral autoregulation, the natural capacity to adjust cerebrovascular resistance to preserve cerebral blood flow in response to external stimuli. Cerebral autoregulation is often impaired in TBI patients, and monitoring cerebral autoregulation might be useful to develop personalized therapy rather than treatment of one size fits all thresholds and guidelines based on unidimensional static relationships. Today, there is no gold standard available to estimate cerebral autoregulation. Cerebral autoregulation can be triggered by performing a mean arterial pressure (MAP) challenge, in which MAP is increased by 10% for 20 min. The response of ICP (increase or decrease) will estimate the status of cerebral autoregulation and can steer therapy mainly concerning optimizing patient-specific CPP. The role of cerebral metabolic changes and its relationship to cerebral autoregulation is still unclear and awaits further investigation.

Abstract 63: Age-related Changes In Gray Matter Cerebral Metabolism And Vascular Reactivity In Children

Introduction: Metabolic demand changes throughout childhood as the brain develops, peaking in the 2 nd decade of life. Cerebral blood flow (CBF) is dynamic throughout childhood, likely in response to the increased metabolic demand of brain development. Cerebrovascular reactivity (CVR) reflects the ability to further increase CBF in response to a stimulus, such as carbon dioxide (CO 2 ). We hypothesized that gray matter oxygen metabolism (GM CMRO 2 ) is increased in younger children, corresponding to higher GM CBF and lower GM CVR. Methods: CVR was calculated as the proportional change of a subject’s MRI-measured blood oxygen level dependent signal in response to an increase in end-tidal CO 2 administered by the RespirAct® RA-MR™ device. GM CMRO 2 was calculated voxel-by-voxel as the product of GM CBF (arterial spin labeling), GM oxygen extraction fraction (asymmetric spin echo), and arterial oxygen content (= Hb х (oxygen saturation)х1.34). Univariate relationships were tested using Spearman’s correlation coefficient, and corrected for multiple comparisons. Results: GM CVR, CBF, and CMRO 2 were calculated for 15 healthy participants (ages 8-19, 7 male). GM CMRO 2 was highest in young children and decreased with age (ρ=-0.68, P=0.005), as did CBF (ρ =-0.67, P=0.006). CVR was lower in young children, increasing with age (ρ=0.58, P=0.02). However, while GM CVR correlated with CBF (ρ=-0.64, P=0.01) it did not significantly associate with CMRO 2 (ρ=-0.43, P=0.114). Conclusion: Although GM CMRO 2 and CVR both have age-related changes, CVR does not directly correlate with CMRO 2 . Rather, their relationship may be moderated through other influences on CBF, as further study will investigate. Figure: Linear fits and 95% confidence intervals of subject data, including age, GM CBF, and GM CMRO 2 , versus GM CVR. P-values are from Spearman’s test for monotonic correlation.

Anti-malaria drug artesunate prevents development of amyloid-β pathology in mice by upregulating PICALM at the blood-brain barrier

BackgroundPICALM is one of the most significant susceptibility factors for Alzheimer’s disease (AD). In humans and mice, PICALM is highly expressed in brain endothelium. PICALM endothelial levels are reduced in AD brains. PICALM controls several steps in Aβ transcytosis across the blood-brain barrier (BBB). Its loss from brain endothelium in mice diminishes Aβ clearance at the BBB, which worsens Aβ pathology, but is reversible by endothelial PICALM re-expression. Thus, increasing PICALM at the BBB holds potential to slow down development of Aβ pathology.MethodsTo identify a drug that could increase PICALM expression, we screened a library of 2007 FDA-approved drugs in HEK293t cells expressing luciferase driven by a human PICALM promoter, followed by a secondary mRNA screen in human Eahy926 endothelial cell line. In vivo studies with the lead hit were carried out in Picalm-deficient (Picalm+/−) mice, Picalm+/−; 5XFAD mice and Picalmlox/lox; Cdh5-Cre; 5XFAD mice with endothelial-specific Picalm knockout. We studied PICALM expression at the BBB, Aβ pathology and clearance from brain to blood, cerebral blood flow (CBF) responses, BBB integrity and behavior.ResultsOur screen identified anti-malaria drug artesunate as the lead hit. Artesunate elevated PICALM mRNA and protein levels in Eahy926 endothelial cells and in vivo in brain capillaries of Picalm+/− mice by 2–3-fold. Artesunate treatment (32 mg/kg/day for 2 months) of 3-month old Picalm+/−; 5XFAD mice compared to vehicle increased brain capillary PICALM levels by 2-fold, and reduced Aβ42 and Aβ40 levels and Aβ and thioflavin S-load in the cortex and hippocampus, and vascular Aβ load by 34–51%. Artesunate also increased circulating Aβ42 and Aβ40 levels by 2-fold confirming accelerated Aβ clearance from brain to blood. Consistent with reduced Aβ pathology, treatment of Picalm+/−; 5XFAD mice with artesunate improved CBF responses, BBB integrity and behavior on novel object location and recognition, burrowing and nesting. Endothelial-specific knockout of PICALM abolished all beneficial effects of artesunate in 5XFAD mice indicating that endothelial PICALM is required for its therapeutic effects.ConclusionsArtesunate increases PICALM levels and Aβ clearance at the BBB which prevents development of Aβ pathology and functional deficits in mice and holds potential for translation to human AD.

Hemodynamic MRI parameters to predict asymptomatic unilateral carotid artery stenosis with random forest machine learning.

Internal carotid artery stenosis (ICAS) can cause stroke and cognitive decline. Associated hemodynamic impairments, which are most pronounced within individual watershed areas (iWSA) between vascular territories, can be assessed with hemodynamic-oxygenation-sensitive MRI and may help to detect severely affected patients. We aimed to identify the most sensitive parameters and volumes of interest (VOI) to predict high-grade ICAS with random forest machine learning. We hypothesized an increased predictive ability considering iWSAs and a decreased cognitive performance in correctly classified patients. Twenty-four patients with asymptomatic, unilateral, high-grade carotid artery stenosis and 24 age-matched healthy controls underwent MRI comprising pseudo-continuous arterial spin labeling (pCASL), breath-holding functional MRI (BH-fMRI), dynamic susceptibility contrast (DSC), T2 and T2* mapping, MPRAGE and FLAIR. Quantitative maps of eight perfusion, oxygenation and microvascular parameters were obtained. Mean values of respective parameters within and outside of iWSAs split into gray (GM) and white matter (WM) were calculated for both hemispheres and for interhemispheric differences resulting in 96 features. Random forest classifiers were trained on whole GM/WM VOIs, VOIs considering iWSAs and with additional feature selection, respectively. The most sensitive features in decreasing order were time-to-peak (TTP), cerebral blood flow (CBF) and cerebral vascular reactivity (CVR), all of these inside of iWSAs. Applying iWSAs combined with feature selection yielded significantly higher receiver operating characteristics areas under the curve (AUC) than whole GM/WM VOIs (AUC: 0.84 vs. 0.90, p = 0.039). Correctly predicted patients presented with worse cognitive performances than frequently misclassified patients (Trail-making-test B: 152.5s vs. 94.4s, p = 0.034). Random forest classifiers trained on multiparametric MRI data allow identification of the most relevant parameters and VOIs to predict ICAS, which may improve personalized treatments.

Increased cerebral vascular resistance underlies preserved cerebral blood flow in response to orthostasis in humans on a high-salt diet.

Cerebral blood flow autoregulation protects brain tissue from blood pressure variations and maintains cerebral perfusion pressure by changes in vascular resistance. High salt (HS) diet impairs endothelium-dependent vasodilation in many vascular beds, including cerebral microcirculation, and may affect vascular resistance. The aim of present study was to determine if 7-day HS diet affected the reactivity of middle cerebral artery (MCA) to orthostatic challenge in healthy human individuals, and if autoregulatory mechanisms and sympathetic neural regulation were involved in this phenomenon.Twenty-seven persons participated in study (F:21, M:6, age range 19-24). Participants consumed 7-day low-salt (LS) diet (< 2.3g kitchen salt/day) and afterwards 7-day HS diet (> 11.2g kitchen salt/day). Blood and urine analysis and anthropometric measurements were performed after each diet. Arterial blood pressure, heart rate and heart rate variability, and cerebral and systemic hemodynamic parameters were recorded simultaneously with transcranial Doppler ultrasound and The Task Force®Monitor in response to orthostatic test.Participants remained normotensive during HS diet. Following both, the LS and HS dietary protocols, mean cerebral blood flow (CBF), as well as the velocity time integral and diastolic blood pressure decreased, and cerebral pulsatility index increased after rising up. Importantly, cerebrovascular resistance significantly increased in response to orthostasis only after HS diet. Urine concentration of noradrenaline and vanillylmandelic acid, baroreflex sensitivity (BRS), and sympathetic neural control was significantly decreased in HS diet.Results suggest that CBF in response to orthostatic test was preserved in HS condition due to altered vascular reactivity of MCA, with increased cerebrovascular resistance and blunted BRS and sympathetic activity.

Effects of alfaxalone, propofol and isoflurane on cerebral blood flow and cerebrovascular reactivity to carbon dioxide in dogs: A pilot study.

Propofol total intravenous anesthesia is a common choice to anesthetize patients with increased intracranial pressure, reducing cerebral blood flow while maintaining cerebrovascular reactivity to CO2. Propofol and alfaxalone are commonly used for total intravenous anesthesia in dogs, but the effects of alfaxalone on cerebral blood flow and cerebrovascular reactivity to CO2 are unknown. Our hypothesis was that alfaxalone would not be significantly different to propofol, while isoflurane would increase cerebral blood flow and decrease cerebrovascular reactivity to CO2. Six healthy hound dogs were evaluated in this randomized crossover trial. Dogs were anesthetized with 7.5mg/kg propofol, 3mg/kg alfaxalone or 8% sevoflurane, mechanically ventilated and maintained with propofol (400µg/kg/min), alfaxalone (150µg/kg/min) or 1.7% end-tidal isoflurane, respectively, with one week washout between treatments. Cerebral blood flow and cerebrovascular reactivity to CO2 during hypercapnic and hypocapnic challenges were measured using arterial spin labelling and blood oxygen level-dependent magnetic resonance imaging sequences, respectively. Median (interquartile range, IQR) normocapnic cerebral blood flow was significantly lower (P=0.016) with alfaxalone compared to isoflurane, in the whole brain 15.39mL/min/100g (14.90-19.90mL/min/100g) vs. 34.10mL/min/100g (33.35-43.17mL/min/100g), the grey matter 14.57mL/min/100g (13.66-18.72mL/min/100g) vs. 32.37mL/min/100g (31.03-42.99mL/min/100g), the caudal brain 15.47mL/min/100g (13.37-21.45mL/min/100g) vs. 36.85mL/min/100g (32.50-47.18mL/min/100g) and the temporal lobe grey matter 18.80mL/min/100g (15.89-20.84mL/min/100g) vs. 43.32 (36.07-43.58mL/min/100g). Median (IQR) hypocapnic cerebrovascular reactivity to CO2 was significantly higher (P=0.016) for alfaxalone compared to isoflurane 8.85%S/mm Hg (6.92-10.44%S/mm Hg) vs. 3.90%S/mm Hg (3.80-4.33%S/mm Hg). Alfaxalone maintained lower cerebral blood flow and higher hypocapnic cerebrovascular reactivity to CO2 than isoflurane.

Cerebral Blood Flow Monitoring with Piezoeletric Film, Photoplethysmogram and an LSTM Neural Network

To improve monitoring of cerebral blood flow and arterial response to clinical interventions following acute traumatic brain injury, we have created a small sensor suite that can be mounted around the diameter of a typical intracranial catheter. This instrument is driven by the need to prevent subsequent ischemic injury after a traumatic brain injury, due to elevated intracranial pressure and compromised cerebral autoregulation. To minimize effects on clinician workflow, our sensors can be integrated into catheters that are currently being used in accordance with accepted standards of care. This paper describes the use of a combination of thin piezoelectric material, a photoplethysmogram, and a long short-term memory regression network to track cerebral blood flow fluctuations. The results show a correlation (R2 = 0.76) between beat-to-beat waveform features collected using our sensor suite and reference blood flow measurements by ultrasound imaging. This method we introduce may help give medical professionals timely data on patients’ cerebral hemodynamic status and how well patients responded to clinical interventions.

Simultaneous Discrimination of Multiple Chromophores With Frequency Division Multiplexed Four-Color Functional Near-Infrared Spectroscopy

Herein, we implement a four-color functional near-infrared spectroscopy (fNIRS) system using frequency division multiplexing (FDM) to demonstrate simultaneous discrimination of multiple chromophores. The proposed fNIRS system consists of a four-channel flexible patch with two light-emitting diode (LED) modules, four photodiodes, and a control board for FDM. Unlike the conventional time division multiplexing (TDM) method that turns on/off individual LEDs sequentially, the FDM method can simultaneously turn on/off the entire LEDs using different modulation frequencies. Therefore, the sampling rate of FDM can be increased by eight times compared to the case of TDM under the same condition of two light sources with four wavelengths. First, for validation of the developed fNIRS system, we conducted a comparative experiment with a commercial spectrometer using two types of dyes in a customized phantom. By comparing the absorbance spectra for each wavelength using both instruments, we confirmed that the correlation between the absorbance measured by the two instruments was high with an R-square value of up to 0.99662. Second, three chromophores of oxyhemoglobin (HbO), deoxyhemoglobin (HbR), and the oxidation state of cytochrome-c-oxidase (oxCCO) were discriminated in vivo using four wavelengths for the cerebral blood flow response with correlation coefficients and effect size. The average hemodynamic response during cerebral activity clearly presented an increased HbO and a decreased HbR simultaneously. We also confirmed that the strong correlation between oxCCO (directly involved in oxygen metabolism) and hemoglobin difference (cerebral oxygenation) showed a Pearson’s correlation coefficient of 0.7342. These results demonstrate the validity of the FDM-based fNIRS system and the successful acquisition of brain signals. This reveals that FDM can be applied to various bio-engineering applications in the future.

Alterations to Cerebral Perfusion, Metabolite Profiles, and Neuronal Morphology in the Hippocampus and Cortex of Male and Female Mice during Chronic Exposure to a High-Salt Diet.

Excess dietary salt reduces resting cerebral blood flow (CBF) and vascular reactivity, which can limit the fueling of neuronal metabolism. It is hitherto unknown whether metabolic derangements induced by high-salt-diet (HSD) exposure during adulthood are reversed by reducing salt intake. In this study, male and female mice were fed an HSD from 9 to 16 months of age, followed by a normal-salt diet (ND) thereafter until 23 months of age. Controls were continuously fed either ND or HSD. CBF and metabolite profiles were determined longitudinally by arterial spin labeling magnetic resonance imaging and magnetic resonance spectroscopy, respectively. HSD reduced cortical and hippocampal CBF, which recovered after dietary salt normalization, and affected hippocampal but not cortical metabolite profiles. Compared to ND, HSD increased hippocampal glutamine and phosphocreatine levels and decreased creatine and choline levels. Dietary reversal only allowed recovery of glutamine levels. Histology analyses revealed that HSD reduced the dendritic arborization and spine density of cortical and hippocampal neurons, which were not recovered after dietary salt normalization. We conclude that sustained HSD exposure throughout adulthood causes permanent structural and metabolic alterations to the mouse brain that are not fully normalized by lowering dietary salt during aging.

528: CEREBRAL BLOOD FLOW MONITORING PREDICTS RESPONSE TO INTRATHECAL NICARDIPINE TREATMENT FOR VASOSPASM

Introduction: A common complication of subarachnoid hemorrhage is cerebral vasospasm, which is associated with delayed cerebral ischemia, a predictor of poor functional outcome. Intrathecal administration of nicardipine upon detection of vasospasm holds promise as a treatment that reduces the incidence of secondary stroke. Herein, we utilize a novel non-invasive optical measurement of regional microvascular perfusion to determine the effect of intrathecal nicardipine on microvascular cerebral blood flow (CBF). Methods: In this observational study, we prospectively studied 20 patients with non-traumatic subarachnoid hemorrhage who required an external ventricular drain to treat obstructive hydrocephalus and who were treated with intrathecal nicardipine as part of usual care for evolving cerebral vasospasm. Regional microvascular CBF in the frontal cortex was measured with diffuse correlation spectroscopy for up to 90 min after the first treatment dose, and for a subset of patients, on days 2 and 3 of treatment as well. Outcome was assessed as the presence of delayed cerebral ischemia on imaging. Results: CBF increased significantly over the 90 min of monitoring after the first dose (p< 0.001) in the absence of systemic hemodynamic changes. CBF also increased on average in response to repeated doses on days 2 and 3, although the magnitude of this response decreased with successive treatment day. In general, the CBF response was heterogeneous across subjects. Using data from the first dose, a latent class mixture model was used to classify 19/20 patients into two distinct classes of cerebral blood flow response: patients in class 1 (n=6) showed a decrease or no change in CBF, while patients in class 2 (n=13) showed a pronounced increase in CBF in response to nicardipine. The incidence of delayed cerebral ischemia was 5/6 in class 1 and 0/13 in class 2 (p< 0.001). Similar significant differences in CBF response in patients with and without delayed cerebral ischemia were also observed on days 2 and 3 (both p< 0.001). Conclusions: These results suggest that the CBF response to intrathecal nicardipine reaches a therapeutic steady state with successive treatment days. Moreover, the CBF response may provide a valuable biomarker for treatment responsiveness.

Cerebral blood flow regulation is not acutely altered after a typical number of headers in women footballers.

The repeated act of heading has been implicated in the link between football participation and risk of neurodegenerative disease, and acutely alters cerebrovascular outcomes in men. This study assessed whether exposure to a realistic number of headers acutely influences indices of cerebral blood flow regulation in female footballers. Nineteen female players completed a heading trial and seated control trial on two separate days. The heading trial involved six headers in 1 h (one every 10 min), with the ball traveling at 40 ± 5 km/h. Cerebrovascular reactivity to hypercapnia and hypocapnia was determined using serial breath holding and hyperventilation attempts. Dynamic cerebral autoregulation (dCA) was assessed by scrutinizing the relationship between cerebral blood flow and mean arterial blood pressure during 5 min of squat stand maneuvers at 0.05 Hz. Neurovascular coupling (NVC) was quantified as the posterior cerebral artery blood velocity response to a visual search task. These outcomes were assessed before and 1 h after the heading or control trial. No significant time by trial interaction was present for the hypercapnic (P = 0.48, = 0.05) and hypocapnic (P = 0.47, = 0.06) challenge. Similarly, no significant interaction effect was present for any metric of dCA (P > 0.12, < 0.16 for all) or NVC (P > 0.14, < 0.15 for all). The cerebral blood flow response to changes in carbon dioxide, blood pressure and a visual search task were not altered following six headers in female footballers. Further study is needed to observe whether changes are apparent after more prolonged exposure.

Older adults with perivascular spaces exhibit cerebrovascular reactivity deficits

BackgroundPerivascular spaces on brain magnetic resonance imaging (MRI) may indicate poor fluid drainage in the brain and have been associated with numerous neurological conditions. Cerebrovascular reactivity (CVR) is a marker of cerebrovascular function and represents the ability of cerebral blood vessels to regulate cerebral blood flow in response to vasodilatory or vasoconstrictive stimuli. We aimed to examine whether pathological widening of the perivascular space in older adults may be associated with deficits in CVR. MethodsIndependently living older adults free of dementia or clinical stroke were recruited from the community and underwent brain MRI. Pseudo-continuous arterial spin labeling MRI quantified whole brain cerebral perfusion at rest and during CVR to hypercapnia and hypocapnia induced by visually guided breathing exercises. Perivascular spaces were visually scored using existing scales. ResultsThirty-seven independently living older adults (mean age = 66.3 years; SD = 6.8; age range 55–84 years; 29.7% male) were included in the current analysis. Multiple linear regression analysis revealed a significant negative association between burden of perivascular spaces and global CVR to hypercapnia (B = -2.0, 95% CI (-3.6, -0.4), p = .015), adjusting for age and sex. Perivascular spaces were not related to CVR to hypocapnia. DiscussionPerivascular spaces are associated with deficits in cerebrovascular vasodilatory response, but not vasoconstrictive response. Enlargement of perivascular spaces could contribute to, or be influenced by, deficits in CVR. Additional longitudinal studies are warranted to improve our understanding of the relationship between cerebrovascular function and perivascular space enlargement.

Hippocampal blood flow rapidly and preferentially increases after a bout of moderate-intensity exercise in older adults with poor cerebrovascular health.

Over the course of aging, there is an early degradation of cerebrovascular health, which may be attenuated with aerobic exercise training. Yet, the acute cerebrovascular response to a single bout of exercise remains elusive, particularly within key brain regions most affected by age-related disease processes. We investigated the acute global and region-specific cerebral blood flow (CBF) response to 15minutes of moderate-intensity aerobic exercise in older adults (≥65years; n = 60) using arterial spin labeling magnetic resonance imaging. Within 0-6min post-exercise, CBF decreased across all regions, an effect that was attenuated in the hippocampus. The exercise-induced CBF drop was followed by a rebound effect over the 24-minute postexercise assessment period, an effect that was most robust in the hippocampus. Individuals with low baseline perfusion demonstrated the greatest hippocampal-specific CBF effect post-exercise, showing no immediate drop and a rapid increase in CBF that exceeded baseline levels within 6-12minutes postexercise. Gains in domain-specific cognitive performance postexercise were not associated with changes in regional CBF, suggesting dissociable effects of exercise on acute neural and vascular plasticity. Together, the present findings support a precision-medicine framework for the use of exercise to target brain health that carefully considers age-related changes in the cerebrovascular system.

Counter pressure maneuvers for syncope prevention: A semi-systematic review and meta-analysis.

Physical counter pressure maneuvers (CPM) are movements that are recommended to delay or prevent syncope (fainting) by recruiting the skeletal muscle pump to augment cardiovascular control. However, these recommendations are largely based on theoretical benefit, with limited data evaluating the efficacy of CPM to prevent syncope in the real-world setting. We conducted a semi-systematic literature review and meta-analysis to assess CPM efficacy, identify literature gaps, and highlight future research needs. Articles were identified through a literature search (PubMed, April 2022) of peer-reviewed publications evaluating the use of counter pressure or other lower body maneuvers to prevent syncope. Two team members independently screened records for inclusion and extracted data. From 476 unique records identified by the search, 45 met inclusion criteria. Articles considered various syncopal conditions (vasovagal = 12, orthostatic hypotension = 8, postural orthostatic tachycardia syndrome = 1, familial dysautonomia = 2, spinal cord injury = 1, blood donation = 10, healthy controls = 11). Maneuvers assessed included hand gripping, leg fidgeting, stepping, tiptoeing, marching, calf raises, postural sway, tensing (upper, lower, whole body), leg crossing, squatting, “crash” position, and bending foreword. CPM were assessed in laboratory-based studies (N = 28), the community setting (N = 4), both laboratory and community settings (N = 3), and during blood donation (N = 10). CPM improved standing systolic blood pressure (+ 14.8 ± 0.6 mmHg, p < 0.001) and heart rate (+ 1.4 ± 0.5 bpm, p = 0.006), however, responses of total peripheral resistance, stroke volume, or cerebral blood flow were not widely documented. Most patients experienced symptom improvement following CPM use (laboratory: 60 ± 4%, community: 72 ± 9%). The most prominent barrier to employing CPM in daily living was the inability to recognize an impending faint. Patterns of postural sway may also recruit the skeletal muscle pump to enhance cardiovascular control, and its potential as a discrete, proactive CPM needs further evaluation. Physical CPM were successful in improving syncopal symptoms and producing cardiovascular responses that may bolster against syncope; however, practical limitations may restrict applicability for use in daily living.

Cerebral blood flow predicts multiple demand network activity and fluid intelligence across the adult lifespan

The preservation of cognitive function in old age is a public health priority. Cerebral hypoperfusion is a hallmark of dementia but its impact on maintaining cognitive ability across the lifespan is less clear. We investigated the relationship between baseline cerebral blood flow (CBF) and blood oxygenation level-dependent (BOLD) response during a fluid reasoning task in a population-based adult lifespan cohort. As age differences in CBF could lead to non-neuronal contributions to the BOLD signal, we introduced commonality analysis to neuroimaging to dissociate performance-related CBF effects from the physiological confounding effects of CBF on the BOLD response. Accounting for CBF, we confirmed that performance- and age-related differences in BOLD responses in the multiple-demand network were implicated in fluid reasoning. Age differences in CBF explained not only performance-related BOLD responses but also performance-independent BOLD responses. Our results suggest that CBF is important for maintaining cognitive function, while its non-neuronal contributions to BOLD signals reflect an age-related confound. Maintaining perfusion into old age may serve to support brain function and preserve cognitive performance.

Cerebral O2 and CO2 transport in isovolumic haemodilution: Compensation of cerebral delivery of O2 and maintenance of cerebrovascular reactivity to CO2

This study investigated the influence of acute reductions in arterial O2 content (CaO2) via isovolumic haemodilution on global cerebral blood flow (gCBF) and cerebrovascular CO2 reactivity (CVR) in 11 healthy males (age; 28 ± 7 years: body mass index; 23 ± 2 kg/m2). Radial artery and internal jugular vein catheters provided measurement of blood pressure and gases, quantification of cerebral metabolism, cerebral CO2 washout, and trans-cerebral nitrite exchange (ozone based chemiluminescence). Prior to and following haemodilution, the partial pressure of arterial CO2 (PaCO2) was elevated with dynamic end-tidal forcing while gCBF was measured with duplex ultrasound. CVR was determined as the slope of the gCBF response and PaCO2. Replacement of ∼20% of blood volume with an equal volume of 5% human serum albumin (Alburex® 5%) reduced haemoglobin (13.8 ± 0.8 vs. 11.3 ± 0.6 g/dL; P < 0.001) and CaO2 (18.9 ± 1.0 vs 15.0 ± 0.8 mL/dL P < 0.001), elevated gCBF (+18 ± 11%; P = 0.002), preserved cerebral oxygen delivery (P = 0.49), and elevated CO2 washout (+11%; P = 0.01). The net cerebral uptake of nitrite (11.6 ± 14.0 nmol/min; P = 0.027) at baseline was abolished following haemodilution (−3.6 ± 17.9 nmol/min; P = 0.54), perhaps underpinning the conservation of CVR (61.7 ± 19.0 vs. 69.0 ± 19.2 mL/min/mmHg; P = 0.23). These findings demonstrate that the cerebrovascular responses to acute anaemia in healthy humans are sufficient to support the maintenance of CVR.

Analysis and visualization methods for detecting functional activation using laser speckle contrast imaging.

Previous studies have used regional cerebral blood flow (CBF) hemodynamic response to measure brain activities. In this work, we use a laser speckle contrast imaging (LSCI) apparatus to sample the CBF activation in somatosensory cortex (S1BF) with repetitive whisker stimulation. Traditionally, the CBF activations were processed by depicting the change percentage above baseline; however, it is not clear how different methods influence the detection of activations. Thus, in this work we investigate the influence of different methods to detect activations in LSCI. First, principal component analysis (PCA) was performed to denoise the CBF signal. As the signal of the first principal component (PC1) showed the highest correlation with the S1BF CBF response curve, PC1 was used in the subsequent analyses. Then, we used fast Fourier transform (FFT) to evaluate the frequency properties of the LSCI images and the activation map was generated based on the amplitude of the central frequency. Furthermore, Pearson's correlation coefficient (C-C) analysis and a general linear model (GLM) were performed to estimate the S1BF activation based on the time series of PC1. We found that GLM performed better in identifying activation than C-C. Additionally, the activation maps generated by FFT were similar to those obtained by GLM. Particularly, the superficial vein and arterial vessels separated the activation region as segmented activated areas, and the regions with unresolved vessels showed a common activation for whisker stimulation. Our research analyzed the extent to which PCA can extract meaningful information from the signal and we compared the performance for detecting brain functional activation between different methods that rely on LSCI. This can be used as a reference for LSCI researchers on choosing the best method to estimate brain activation.