Biology subjects

Wise, R. G.

Publications and source records attributed to Wise, R. G..

13 recordsLinked to original sources

bioRxiv2026

Human brain cortical oxygen consumption is positively related to soma surface area density.

Evidence from in-silico, ex vivo and invasive animal studies suggested the function of neural tissue to be inextricably linked to its structural and microstructural organization. However, this link has never been assessed non-invasively in humans. Here, we established a simple quantitative framework linking cerebral oxygen metabolism to gray matter microstructural features in healthy humans using advanced non-invasive MRI methods. The cerebral metabolic rate of oxygen consumption (CMRO2) was quantified with calibrated fMRI, whereas microstructural properties were estimated from diffusion MRI data fitted to the Soma and Neurite Density Imaging (SANDI) model, yielding soma radius (R soma) and soma volume fraction (fsoma) metrics, from which we derived maps of soma surface area density (SAD) and soma numerical density (ND) under the assumption of a spherical soma. CMRO2 was positively associated with SAD (r = 0.29, p < 0.01), fsoma (r = 0.28, p < 0.05) and ND (r = 0.25, p < 0.05), and negatively associated with Rsoma (r = -0.23, p < 0.05) across cortical brain regions. These relationships are consistent with predictions from experimental and theoretical studies, providing the first quantitative evidence that cerebral metabolic demand is coupled to microstructure in humans. The positive association of energy consumption with SAD is consistent with the notion that both the number of synapses (energy-demanding structures), and the energy required to maintain a membrane potential, scale with soma surface area. Our findings establish a non-invasive MRI framework for investigating the microstructural determinants of brain energy metabolism in health and potentially in disease.

neuroscience↗

bioRxiv2026

A comparison of continuous-wave fNIRS with quantitative fMRI-derived indices of brain function in the visual cortex

Functional near-infrared spectroscopy (fNIRS) and functional magnetic resonance imaging (fMRI) both rely on the phenomenon of neurovascular coupling (NVC) to probe brain activity through their sensitivity to cerebral blood oxygenation. However, the relationship between fNIRS chromophores (oxy- and deoxyhaemoglobin, HbO and HbR), and fMRI (Blood Oxygen Level Dependent and Arterial Spin Labeling, BOLD and ASL) measurements, and whether this relationship remains consistent across subjects and physiological conditions, has only been partially characterised.. We acquired concurrent continuous-wave fNIRS and gradient-echo (GE) and spin-echo (SE) BOLD-ASL fMRI in healthy adults (n = 10) during visual stimulation. By applying calibrated fMRI methodology, we examined the relationships between fNIRS-derived haemoglobin modulations and fMRI-derived modulations in macrovascular (GE-) and microvascular (SE-) BOLD signals, cerebral blood flow (CBF), and oxygen metabolism (CMRO2). Group-level results showed strong temporal cross-modal agreement, with HbO and HbR tightly mirroring all fMRI signal time-courses (|r| > 0.8). A quantitative analysis of trial-by-trial modulations revealed distinct state-dependent behaviours: HbO maintained a stable relationship with the fMRI-derived metrics across conditions, whereas cross-modal relationships between HbR and fMRI-derived metrics substantially strengthened at higher flow-metabolism coupling (FMC), the ratio of CBF to CMRO2 change, an index of the strength of NVC. Both HbO and HbR were more strongly associated with GE-BOLD than with SE-BOLD. These findings provide a rigorous physiological grounding for fNIRS signal interpretation, demonstrating its utility as a surrogate marker for specific haemodynamic and metabolic parameters.

bioengineering↗

bioRxiv2025

Three-dimensional T1 mapping demonstrates the transfer of oxygen into cerebrospinal fluid during hyperoxia

BackgroundThis study optimised a non-invasive magnetic resonance imaging technique to investigate the transfer of oxygen into cerebrospinal fluid (CSF) across the whole brain of healthy subjects. MethodsA shortening of the T1 (longitudinal relaxation time) of CSF was induced by 100% hyperoxia and measured using a 3D SPACE sequence at 3T in 29 subjects, thereby demonstrating the diffusion of oxygen from blood to CSF. T1 mapping was performed at high resolution (0.9-mm isotropic, taking approximately 16 minutes) to capture anatomical details of the CSF spaces and was also repeated more rapidly at a lower resolution (3-mm isotropic, taking approximately 3.5 minutes) to capture the temporal dynamics of T1 changes. ResultsSignificant region-dependent reductions in T1 were observed, indicating increased oxygen concentration in CSF. These occurred most prominently and rapidly in the cortical subarachnoid space and basilar cisterns, stabilising between 7 and 10 minutes after initiating hyperoxia, suggesting that oxygen diffusion primarily occurs via pial arteries and arteries at the base of the skull, both of which are in proximity to CSF-filled spaces. Over a timescale of 16 minutes, smaller T1 changes, only observed on the high-resolution T1 maps, occurred in the posterior lateral ventricles, where the choroid plexus is found, and the cisterna magna, possibly because of mixing effects with the adjacent basilar cisterns. ConclusionsThis study provides insights into the structure of CSF and dynamics of blood-CSF oxygen exchange, including their regional dependence. Moreover, the methodology presented here could, in the future, offer a valuable tool for characterising the passive diffusion of oxygen across cerebral blood vessel walls (i.e., their oxygen permeability), thereby providing a potential marker of cerebrovascular integrity.

physiology↗

bioRxiv2024

Velocity-selective arterial spin labelling bolus duration measurements: Implications for consensus recommendations

Velocity-selective arterial spin labelling (VSASL) MRI is insensitive to arterial transit time. This is an advantage over other perfusion measurements, where long arterial transit times can lead to bias. Therefore, VSASL can be used to study perfusion in the presence of long arterial transit times, such as in the ageing brain, in vascular pathologies, and cancer, or where arterial transit time changes, such as during measurement of cerebrovascular reactivity (CVR). However, when calculating perfusion (cerebral blood flow, CBF, in the brain) from VSASL signal, it is assumed that images are acquired before the trailing edge of the labelled blood has arrived in the imaging slice. The arrival of the trailing edge of the labelled bolus of blood will cause an underestimation of perfusion. Here we measure bolus duration in young, healthy human brains, both at rest and during elevated CBF. Grey matter bolus duration was 1.61 {+/-} 0.31 s, but there was a large spatial heterogeneity, with bolus duration being lower in anterior brain regions, with some areas having bolus duration < 1.2 s. We place these results in context of recommendations from a recent consensus paper, which recommends imaging 1.4 s after the label, potentially underestimating CBF in anterior regions. Further, we observed a 0.23 {+/-} 0.12 s reduction in grey matter bolus duration with 5% CO2 inhalation. These results can be used to inform the experimental design of future VSASL studies, to avoid underestimating perfusion by imaging after the arrival of the trailing edge of the labelled bolus.

neuroscience↗

bioRxiv2024

Imaging brain vascular function in Cystic Fibrosis: an MRI study of cerebral blood flow and brain oxygenation

Cystic fibrosis (CF) is a progressive inherited disorder that primarily affects the lungs. With recent breakthroughs in effective treatments for CF that increase life-expectancy, a higher prevalence of age-related comorbidities have been reported including cardiovascular disease, stroke and cognitive decline. Despite the known relationship between cardiovascular health and cerebrovascular function, very little is known about brain blood flow and oxygen metabolism in patients with CF (PwCF). In 14 PwCF and 56 healthy age / sex matched controls, we used pseudo-continuous arterial spin labelling (pCASL) to quantify cerebral perfusion in grey-matter and T2-Relaxation-Under-Spin-Tagging (TRUST) to estimate global oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen consumption (CMRO2). Compared to healthy controls, PwCF showed elevated CMRO2 (p = 0.015). There were no significant between-group differences in grey-matter CBF (p = 0.342), or whole brain OEF (p = 0.091). However, regional analysis showed certain areas with higher CBF in PwCF (p < .05, FDR). This is the first study to characterise cerebrovascular function and brain oxygen metabolism in PwCF. Our findings highlight the need for early cardiovascular monitoring procedures to help maintain cerebrovascular function and combat accelerated aging effects in the brains of PwCF.

neuroscience↗

bioRxiv2021

Quantitative mapping of cerebral oxygen metabolism using breath-hold calibrated fMRI

Magnetic resonance imaging (MRI) offers the possibility to non-invasively map the rate of cerebral metabolic oxygen consumption (CMRO2), which is essential for understanding and monitoring neural function in both health and disease. Existing methods of mapping CMRO2, based on respiratory modulation of arterial spin labelling (ASL) and blood oxygen level dependent (BOLD) signals, require lengthy acquisitions and independent modulation of both arterial oxygen and carbon dioxide levels. Here, we present a new simplified method for mapping the rate of cerebral oxygen metabolism that can be performed using a simple breath-holding paradigm. The method incorporates flow-diffusion modelling of oxygen transport and physiological constraints to create a non-linear mapping between the maximum BOLD signal, M, baseline blood flow (CBF0), and CMRO2. A gradient boosted decision tree is used to learn this mapping directly from simulated MRI data. Modelling studies demonstrate that the proposed method is robust to variation in cerebral physiology and metabolism. This new gas-free methodology offers a rapid and pragmatic alternative to existing dual-calibrated methods, removing the need for specialist respiratory equipment and long acquisition times. In-vivo testing of the method, using an 8-minute 45 second protocol of repeated breath-holding, was performed on 15 healthy volunteers, producing quantitative maps of cerebral blood flow (CBF), oxygen extraction fraction (OEF), and CMRO2.

neuroscience↗

bioRxiv2021

Using dual-calibrated functional MRI to map brain oxygen supply and consumption in multiple sclerosis

Evidence suggests that cerebrovascular function and oxygen consumption are altered in multiple sclerosis (MS). Here, we quantified the vascular and oxygen metabolic MRI burden in patients with MS (PwMS) and assessed the relationship between these MRI measures of and metrics of damage and disability. In PwMS and in matched healthy volunteers, we applied a newly developed dual-calibrated fMRI method of acquisition and analysis to map grey matter (GM) cerebral blood flow (CBF), oxygen extraction fraction (OEF), cerebral metabolic rate of oxygen consumption (CMRO2) and effective oxygen diffusivity of the capillary network (DC). We also quantified physical and cognitive function in PwMS and controls. There was no significant difference in GM volume between 22 PwMS and 20 healthy controls (p=0.302). Significant differences in CBF (PwMS vs. controls: 44.91 {+/-} 6.10 vs. 48.90 {+/-} 5.87 ml/100g/min, p=0.010), CMRO2 (117.69 {+/-} 17.31 vs. 136.49 {+/-} 14.48 mol/100g/min p<0.001) and DC (2.70 {+/-} 0.51 vs. 3.18 {+/-} 0.41 mol/100g/mmHg/min, p=0.002) were observed in the PwMS. No significant between-group differences were observed for OEF (PwMS vs. controls: 0.38 {+/-} 0.09 vs. 0.39 {+/-} 0.02, p=0.358). Regional analysis showed widespread reductions in CMRO2 and DC for PwMS compared to healthy volunteers. There was a significant correlation between physiological measures and T2 lesion volume, but no association with current clinical disability. Our findings demonstrate concurrent reductions in oxygen supply and consumption in the absence of an alteration in oxygen extraction that may be indicative of a reduced demand for oxygen (O2), an impaired transfer of O2 from capillaries to mitochondria, and/or a reduced ability to utilise O2 that is available at the mitochondria. With no between-group differences in GM volume, our results suggest that changes in brain physiology may precede MRI-detectable GM loss and thus may be one of the pathological drivers of neurodegeneration and disease progression.

neuroscience↗

bioRxiv2021

Alzheimer's genetic risk effects on cerebral blood flow are spatially consistent and proximal to gene expression across the lifespan

Cerebrovascular dysregulation is a hallmark feature of Alzheimers disease (AD), where alterations in cerebral blood flow (CBF) are observed decades prior to symptom onset. Genome-wide association studies (GWAS) show that AD has a polygenic aetiology, providing a tool for studying AD susceptibility across the lifespan. Here, we ascertain whether AD genetic risk effects on CBF previously observed (Chandler et al., 2019) remain consistent across the lifespan. We further provide a causal mechanism to AD genetic risk scores (AD-GRS) effects by establishing spatial convergence between AD-GRS associated regional reductions in CBF and mRNA expression of the proximal AD transcripts using independent data from the Allen Brain Atlas. We analysed grey matter (GM) CBF in a young cohort (N=75; aged 18-35) and an older cohort (N=90; aged 55-85). Critically, we observed that AD-GRS was negatively associated with whole brain GM CBF in the older cohort (standardised {beta} -0.38 [-0.68 - -0.09], P = 0.012), consistent with our prior observation in younger healthy adults (Chandler et al., 2019). We then demonstrate that the regional impact of AD-GRS on GM CBF was spatially consistent across the younger and older samples (r = 0.233, P = 0.035). Finally, we show that CBF across the cortex was related to the regional expression of the genes proximal to SNPs used to estimate AD-GRS in both younger and older cohorts (ZTWO-TAILED = -1.99, P= 0.047; ZTWO-TAILED = -2.153 P = 0.032, respectively). These observations collectively demonstrate that AD risk alleles have a negative influence on brain vascular function and likely contribute to cerebrovascular changes preceding the onset of clinical symptoms, potentially driven by regional expression of proximal AD risk genes across the brain. Our observations suggest that reduced CBF is an early antecedent of AD and a key modifiable target for therapeutic intervention in individuals with a higher cumulative genetic risk for AD. This study will further enable identification of key molecular processes that underpin AD genetic risk related reductions in CBF that could be targeted decades prior to the onset of neurodegeneration.

genetics↗

bioRxiv2020

A comparison of GABA-ergic (propofol) and non-GABA-ergic (dexmedetomidine) sedation on visual and motor cortical oscillations, using magnetoencephalography.

BackgroundUnderstanding the effects of anaesthetic drugs on cortical oscillations can help to elucidate the mechanistic link between receptor physiology and their clinical effects. Propofol produces divergent effects on visual cortical activity: increasing induced gamma-band responses (GBR) while decreasing stimulus-onset-evoked responses) 1. Dexmedetomidine, an 2-adrenergic agonist, differs from GABA-ergic sedatives both mechanistically and clinically as it allows easy arousability from deeper sedation with less cognitive side-effects. Here we use magnetoencephalography (MEG) to characterize and compare the effects of GABAergic (propofol) and non-GABA-ergic (dexmedetomidine) sedation, on visual and motor cortical oscillations. MethodsSixteen male participants received target-controlled infusions of propofol and dexmedetomidine, producing mild-sedation, in a placebo-controlled, cross-over study. MEG data was collected during a combined visual and motor task. ResultsThe key findings were that propofol significantly enhanced visual stimulus induced GBR (44% increase in amplitude) while dexmedetomidine decreased it (40%). Propofol also decreased the amplitudes of the M100 (27%) and M150 (52%) evoked responses, whilst dexmedetomidine had no effect on these. During the motor task, neither drug had any significant effect on motor GBR or movement related beta de-synchronisation (MRBD). However, dexmedetomidine increased (92%) post-movement beta synchronisation/rebound (PMBR) power while propofol reduced it (70%). ConclusionsDexmedetomidine and propofol, at equi-sedative doses, have contrasting effects on visual stimulus induced GBR, visual evoked responses and PMBR. These findings provide a mechanistic link between the known receptor physiology of these sedative drugs and their known clinical effects and may be used to explore mechanisms of other anaesthetic drugs on human consciousness.

neuroscience↗

bioRxiv2020

Most small cerebral cortical veins demonstrate significant flow pulsatility: a human phase contrast MRI study at 7T

Phase contrast MRI has been used to investigate flow pulsatility in cerebral arteries, larger cerebral veins and the cerebrospinal fluid. Such measurements of intracranial pulsatility and compliance are beginning to inform understanding of the pathophysiology of conditions including normal pressure hydrocephalus, multiple sclerosis and dementias. We demonstrate the presence of flow pulsatility in small cerebral cortical veins, for the first time using phase contrast MRI at 7 Tesla, with the aim of improving our understanding of the haemodynamics of this little-studied vascular compartment. An automated method for establishing where venous flow is pulsatile is introduced, revealing significant pulsatility in 116 out of 146 veins, across 8 healthy participants, assessed in parietal and frontal regions. Distributions of pulsatility index and pulse waveform delay were characterized, indicating a small, but statistically significant (p<0.05), delay of 59{+/-}41 ms in cortical veins with respect to the superior sagittal sinus, but no differences between veins draining different arterial supply territories. Measurements of pulsatility in smaller cortical veins, a hitherto unstudied compartment closer to the capillary bed, could lead to a better understanding of intracranial compliance and cerebrovascular (patho)physiology.

neuroscience↗

bioRxiv2019

Assessment of the effects of aerobic fitness on cerebrovascular function in young adults using multiple inversion time arterial spin labelling MRI

The cross-sectional study investigated the effects of aerobic fitness on cerebrovascular function in the healthy brain. We quantified grey matter (GM) cerebral blood flow (CBF) and cerebrovascular reactivity (CVR), in a sample of young adults within a normal fitness range. Based on existing TCD and fMRI evidence, we predicted a positive relationship between fitness and resting GM CBF, and CVR. Exploratory hypotheses that higher [Formula] peak would be associated with higher GM volume and cognitive performance were also investigated. 20 adults underwent a [Formula] peak test and a battery of cognitive tests. All subjects underwent an MRI scan where multiple inversion time (MTI) pulsed arterial spin labelling (PASL) was used to quantify resting CBF and CVR to 5% CO2. ROI analysis showed a non-significant negative correlation between whole-brain GM CBF and [Formula] peak; r=-0.4, p=0.08, corrected p (p) =0.16 and a significant positive correlation between [Formula] peak and voxelwise whole-brain GM CVR; r=0.62, p=0.003, p =0.006. Voxelwise analysis revealed a significant inverse association between [Formula] peak and resting CBF in the left and right thalamus, brainstem, right lateral occipital cortex, left intracalcarine cortex and cerebellum. The results of this study suggest that aerobic fitness is associated with lower CBF and greater CVR in young adults.

neuroscience↗

bioRxiv2019

Cerebral Metabolic Changes during Visuomotor Adaptation Assessed using Quantitative FMRI

The neural energetics underlying functional brain plasticity have not been thoroughly investigated in the healthy human brain. A better understanding of the blood flow and metabolism changes underlying plasticity will help us to address pathologies in which plasticity is compromised and, with interventions, could be enhanced for patient benefit. Calibrated fMRI was conducted in 20 healthy participants during performance of a serial reaction time task which induces rapid motor adaptation. Regions of interest (ROIs) were defined from areas showing linearly decreasing task-induced BOLD and CBF responses. BOLD, CBF and relative CMRO2 responses were calculated for each block of the task. The flow-metabolism coupling ratio, n, was also calculated for each ROI. Increases from baseline in BOLD, CBF and CMRO2 were observed in multiple brain regions including the motor and sensorimotor cortices, cerebellum and hippocampus during SRT task performance, as well as changes in the response amplitude from early to late task blocks reflecting task adaptation. CMRO2 responses on average decreased faster than BOLD or CBF responses, potentially due to rapid neural adaptation. However, the mean flow-metabolism coupling ratio was not significantly different between ROIs or across blocks. Calibrated fMRI can be used to study energetic changes during learning in the healthy brain and could be used to investigate the vascular and metabolic changes underlying reductions in plasticity in ageing and disease.

neuroscience↗

bioRxiv2017

Modeling of dynamic cerebrovascular reactivity to spontaneous and externally induced CO2 fluctuations in the brainstem respiratory control centers in the human brain using BOLD-fMRI

In this work, we investigate the regional characteristics of the dynamic interactions between arterial CO2 and BOLD (dynamic cerebrovascular reactivity - dCVR) during normal breathing and hypercapnic, externally induced step CO2 challenges. To obtain CVR curves at each voxel, we use a custom set of basis functions based on the Laguerre and gamma basis sets. This allows us to obtain robust dCVR estimates both in larger regions of interest (ROIs) as well as in individual voxels. We also implement classification schemes to identify brain regions with similar dCVR characteristics. Our results reveal considerable variability of dCVR across different brain regions, as well as during different experimental conditions (normal breathing and hypercapnia), suggesting a differential response of cerebral vasculature to spontaneous CO2 fluctuations and larger, externally induced CO2 changes. The clustering results suggest that anatomically distinct brain regions exhibit different dCVR curves that do not exhibit the standard, positive valued curves that have been previously reported using measurements of global cerebral blood flow or using larger ROIs. They also revealed a consistent set of dCVR cluster shapes for resting and forcing conditions that exhibited different distribution patterns across brain voxels.

neuroscience↗