Biology subjects

Driver, I. D.

Publications and source records attributed to Driver, I. D..

8 recordsLinked to original sources

bioRxiv2026

Neuroendocrine influences on dynamic cerebrovascular function and implications for functional MRI

To fully profile how ovarian hormones interact with cerebrovascular function, it is vital to consider, not just resting physiology, but also dynamic aspects of cerebrovasculature that support neural activity. This study uses hypercapnic cerebrovascular reactivity (CVR) and the visually-evoked haemodynamic response function (HRF) to investigate the influence of menstrual-related changes in oestradiol and progesterone on dynamic aspects of the cerebrovascular system. 20 menstruating females (age mean[SD]=23.01[4.01]years) completed a 3T MRI scanning session during the early follicular, late follicular, and mid-luteal phases of their menstrual cycle. Circulating hormones were measured via blood samples. Simultaneous blood oxygen level dependant (BOLD)-CVR and cerebral blood flow (CBF)-CVR data were collected using a pseudocontinuous arterial spin labelling (pCASL) acquisition using a dual-excitation (DEXI) readout during periods of hypercapnia (5% CO2). The HRF was estimated using a whole brain EPI scan during high-contrast radial checkerboard presentation. Both oestradiol and additional progesterone variance were associated with increased CVR (both BOLD-CVR and CBF-CVR; p<0.001) and altered HRF shape (p<0.005). No statistically significant regional effects were found. A secondary experiment investigated the impact of using either canonical or individually mapped HRF in a standard fMRI processing pipeline; namely, population receptive field (pRF) mapping. Results across phases suggest that neither hormone was associated with pRF size when modelled using a canonical HRF (both p>0.05). However, a significant neuroendocrine influence on pRF sizes was discovered when using individually measured HRFs (p<0.001). This study found evidence that dynamic cerebrovascular functions are sensitive to menstrual-related ovarian hormones, which may be a potential mechanism underlying menstrual symptomatology and has implications for fMRI studies that assume intact neurovascular coupling processes in women, regardless of menstrual staging, to make inferences about neural activity.

neuroscience↗

bioRxiv2024

Endocrine modulation of cortical and retinal blood flow across the menstrual cycle

The ovarian hormones, oestrogen and progesterone, have vaso- and neuroprotective effects, likely due to interactions with the cerebrovascular system. This study investigates their neuroendocrine influence on a range of cerebral and retinal vascular functions across a healthy menstrual cycle. Twenty-six healthy, menstruating females completed imaging sessions and assessment of circulating hormone levels during their early follicular, late follicular, and mid-luteal phase (1-4, 10-12 and 20-22 days after menses onset). Cerebral blood flow (CBF), arterial arrival time (AAT), global oxygen extraction fraction (OEF), cerebrovascular metabolic rate of oxygen (CMRO2), carotid artery radius and carotid pulsatility index (PI) were measured using 3T MRI. Retinal vessel density and blood flow resistance were assessed with optical coherence tomography angiography (OCT-A). Assessed with linear models, increased oestradiol was related to increased global CBF ({chi}2(1)=41.682; p=1.074x10-10). An independent progesterone increase was also associated with increased global CBF ({chi}2(1)=14.979; p=0.0001). In the retina, a relationship was found between oestradiol and decreased retinal blood flow resistance ({chi}2(1)=5.28; p=0.0215), which was primarily driven by centrally localised vessels. This study finds that circulating oestrogen increases blood flow in the eye and brain, while progesterone significantly impacts the brain alone. These effects suggest a potential pathway for neuroprotective mechanisms.

neuroscience↗

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↗

bioRxiv2021

Multi-centre, multi-vendor 7 Tesla fMRI reproducibility of hand digit representation in the human somatosensory cortex

Whilst considerable progress has been made in using ultra-high field fMRI to study brain function at fine spatial resolution, methods are generally optimized at a single site and do not translate to studies where multiple sites are required for sufficient subject recruitment. With a recent increase in installations of human 7 T systems, there is now the opportunity to establish a framework for multi-site 7 T fMRI studies. However, an understanding of the inter-site variability of fMRI measurements is required for datasets to be combined across sites. To address this, we employ a hand digit localization task and compare across-site and within-site reproducibility of 7 T fMRI to a hand digit localization task which requires fine spatial resolution to resolve individual digit representations. As part of the UK7T Network "Travelling Heads" study, 10 participants repeated the same hand digit localization task at five sites with whole-body 7T MRI systems to provide a measure of inter-site variability. A subset of the participants (2 per site) performed repeated sessions at each site for measurement of intra-site reproducibility. Dices overlap coefficient was used to assess reproducibility, with hand region inter-site Dice = 0.70{+/-}0.04 significantly lower than intrasite Dice = 0.76{+/-}0.06, with similar trends for the individual digit maps. Although slightly lower than intra-site reproducibility, the inter-site reproducibility results are consistent with previous single site reproducibility measurements, providing evidence that multi-site 7 T fMRI studies are feasible. These results can be used to inform sample size calculations for future multi-site somatomotor mapping studies.

neuroscience↗

bioRxiv2020

Multi-centre, multi-vendor reproducibility of 7T QSM and R2* in the human brain: results from the UK7T study

We present the reliability of ultra-high field T2* MRI at 7T, as part of the UK7T Networks "Travelling Heads" study. T2*-weighted MRI images can be processed to produce quantitative susceptibility maps (QSM) and R2* maps. These reflect iron and myelin concentrations, which are altered in many pathophysiological processes. The relaxation parameters of human brain tissue are such that R2* mapping and QSM show particularly strong gains in contrast-to-noise ratio at ultra-high field (7T) vs clinical field strengths (1.5 - 3T). We aimed to determine the inter-subject and inter-site reproducibility of QSM and R2* mapping at 7T, in readiness for future multi-site clinical studies. MethodsTen healthy volunteers were scanned with harmonised single- and multi-echo T2*-weighted gradient echo pulse sequences. Participants were scanned five times at each "home" site and once at each of four other sites. The five sites had 1x Philips, 2x Siemens Magnetom, and 2x Siemens Terra scanners. QSM and R2* maps were computed with the Multi-Scale Dipole Inversion (MSDI) algorithm (https://github.com/fil-physics/Publication-Code). Results were assessed in relevant subcortical and cortical regions of interest (ROIs) defined manually or by the MNI152 standard space. Results and DiscussionMean susceptibility ({chi}) and R2* values agreed broadly with literature values in all ROIs. The inter-site within-subject standard deviation was 0.001 - 0.005 ppm ({chi}) and 0.0005 - 0.001 ms-1 (R2*). For {chi} this is 2.1-4.8 fold better than 3T reports, and 1.1-3.4 fold better for R2*. The median ICC from within- and cross-site R2* data was 0.98 and 0.91, respectively. Multi-echo QSM had greater variability vs single-echo QSM especially in areas with large B0 inhomogeneity such as the inferior frontal cortex. Across sites, R2* values were more consistent than QSM in subcortical structures due to differences in B0-shimming. On a between-subject level, our measured {chi} and R2* cross-site variance is comparable to within-site variance in the literature, suggesting that it is reasonable to pool data across sites using our harmonised protocol. ConclusionThe harmonized UK7T protocol and pipeline delivers on average a 3-fold improvement in the coefficient of reproducibility for QSM and R2* at 7T compared to previous reports of multi-site reproducibility at 3T. These protocols are ready for use in multi-site clinical studies at 7T.

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↗

bioRxiv2018

Vascular physiology drives functional brain networks

We present the first evidence for vascular regulation driving fMRI signals in specific functional brain networks. Using concurrent neuronal and vascular stimuli, we collected 30 BOLD fMRI datasets in 10 healthy individuals: a working memory task, flashing checkerboard stimulus, and CO2 inhalation challenge were delivered in concurrent but orthogonal paradigms. The resulting imaging data were averaged together and decomposed using independent component analysis, and three \"neuronal networks\" were identified as demonstrating maximum temporal correlation with the neuronal stimulus paradigms: Default Mode Network, Task Positive Network, and Visual Network. For each of these, we observed a second network component with high spatial overlap. Using dual regression in the original 30 datasets, we extracted the time-series associated with these network pairs and calculated the percent of variance explained by the neuronal or vascular stimuli using a normalized R2 parameter. In each pairing, one network was dominated by the appropriate neuronal stimulus, and the other was dominated by the vascular stimulus as represented by the end-tidal CO2 time-series recorded in each scan. We acquired a second dataset in 8 of the original participants, where no CO2 challenge was delivered and CO2 levels fluctuated naturally with breathing variations. Although splitting of functional networks was not robust in these data, performing dual regression with the network maps from the original analysis in this new dataset successfully replicated our observations. Thus, in addition to responding to localized metabolic changes, the brains vasculature may be regulated in a coordinated manner that mimics (and potentially supports) specific functional brain networks. Multi-modal imaging and advances in fMRI acquisition and analysis could facilitate further study of the dual nature of functional brain networks. It will be critical to understand network-specific vascular function, and the behavior of a coupled vascular-neural network, in future studies of brain pathology.

neuroscience↗

bioRxiv2018

Coupling between cerebral blood flow and cerebral blood volume: Contributions of different vascular compartments

A better understanding of the coupling between changes in cerebral blood flow (CBF) and cerebral blood volume (CBV) is vital for furthering our understanding of the BOLD response. The aim of this study was to measure CBF-CBV coupling in different vascular compartments during neural activation. Three haemodynamic parameters were measured during a visual stimulus. Look-Locker Flow-sensitive Alternating Inversion Recovery (LL-FAIR) was used to measure changes in CBF and arterial CBV (CBVa) using sequence parameters optimised for each contrast. Changes in total CBV (CBVtot) were measured using a Gadolinium based contrast agent technique. Haemodynamic changes were extracted from a region of interest based on voxels that were activated in the CBF experiments. The CBF-CBVtot coupling constant tot was measured as 0.16{+/-}0.14 and the CBF-CBVa coupling constant a was measured as 0.65{+/-}0.24. Using a two compartment model of the vasculature (arterial and venous), the change in venous CBV (CBVv) was predicted for an assumed value of baseline arterial and venous blood volume. These results will enhance the accuracy and reliability of applications that rely on models of the BOLD response, such as calibrated BOLD.

neuroscience↗