Changes in arterial cerebral blood volume during lower body negative pressure measured with MRI

Cerebral Autoregulation (CA), defined as the ability of the cerebral vasculature to maintain stable levels of blood flow despite changes in systemic blood pressure, is a critical factor in neurophysiological health. Magnetic resonance imaging (MRI) is a powerful technique for investigating cerebrovascular function, offering high spatial resolution and wide fields of view (FOV), yet it is relatively underutilized as a tool for assessment of CA. The aim of this study was to demonstrate the potential of using MRI to measure changes in cerebrovascular resistance in response to lower body negative pressure (LBNP). A Pulsed Arterial Spin Labeling (PASL) approach with short inversion times (TI) was used to estimate cerebral arterial blood volume (CBVa) in eight healthy subjects at baseline and -40mmHg LBNP. We estimated group mean CBVa values of 3.13±1.00 and 2.70±0.38 for baseline and lbnp respectively, which were the result of a differential change in CBVa during -40 mmHg LBNP that was dependent on baseline CBVa. These data suggest that the PASL CBVa estimates are sensitive to the complex cerebrovascular response that occurs during the moderate orthostatic challenge delivered by LBNP, which we speculatively propose may involve differential changes in vascular tone within different segments of the arterial vasculature. These novel data provide invaluable insight into the mechanisms that regulate perfusion of the brain, and establishes the use of MRI as a tool for studying CA in more detail

Arterial CO2 fluctuations modulate neuronal rhythmicity: Implications for MEG and fMRI studies of resting-state networks

A fast emerging technique for studying human resting state networks (RSNs) is based on spontaneous temporal fluctuations in neuronal oscillatory power, as measured by magnetoencephalography. However, it has been demonstrated recently that this power is sensitive to modulations in arterial CO2 concentration. Arterial CO2 can be modulated by natural fluctuations in breathing pattern, as might typically occur during the acquisition of an RSN experiment. Here, we demonstrate for the first time the fine-scale dependence of neuronal oscillatory power on arterial CO2 concentration, showing that reductions in alpha, beta, and gamma power are observed with even very mild levels of hypercapnia (increased arterial CO2). We use a graded hypercapnia paradigm and participant feedback to rule out a sensory cause, suggesting a predominantly physiological origin. Furthermore, we demonstrate that natural fluctuations in arterial CO2, without administration of inspired CO2, are of a sufficient level to influence neuronal oscillatory power significantly in the delta-, alpha-, beta-, and gamma-frequency bands. A more thorough understanding of the relationship between physiological factors and cortical rhythmicity is required. In light of these findings, existing results, paradigms, and analysis techniques for the study of resting-state brain data should be revisited

Field strength dependence of grey matter R2* on venous oxygenation

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

The vascular properties of the BOLD signal

The work presented in this thesis is intended to contribute towards the understanding of the cerebral vascular behaviour in response to changes in neuronal activation. The blood oxygenation-level dependent (BOLD) functional magnetic resonance imaging (fMRI) signal provides an indirect measure of neuronal activation, arising from a combination of metabolic and vascular (blood flow and blood volume) changes local to the activation. Therefore the BOLD signal is dependent on local vascular properties as well as on the neuronal activation, leading to a variability of the BOLD signal, based on the underlying vascular structure. It has become an important goal to improve understanding of the mechanisms underlying the BOLD signal in order to separate out this vascular variability from the underlying correspondence with the neuronal activation. The effect of field strength on the temporal characteristics of the BOLD haemodynamic response function is investigated. An earlier BOLD response onset has been measured with increasing static magnetic field strength, consistent with an earlier microvascular (compared with macrovascular) signal response. This result can be used to improve haemodynamic models of the BOLD signal. Hypercapnia, a vasodilator, has been used both to assess the relationship between transverse relaxation and blood oxygenation at 3 and 7 Tesla and to identify vascular heterogeneity between two equivalent brain regions. A tight, linear relationship was found between the level of hypercapnia and transverse relaxation at both 3 and 7 Tesla, whilst the change in transverse relaxation due to hypercapnia increased 2.1 ± 0.5 fold from 3 to 7 Tesla, indicating an approximately linear relationship across field strength. In a separate experiment, a vascular asymmetry was found between the left and right precentral gyri using hypercapnia. This result highlights the need to account for the vascular contribution to the BOLD signal before using this BOLD signal to make comparisons of neuronal activity across brain regions. Finally, an improved model for calibrated BOLD has been proposed and implemented, which requires fewer assumptions than existing approaches. This uses the BOLD response to some task, repeated both at normoxia and hyperoxia. To assess the validity of this model, the effects of paramagnetic oxygen molecules are considered, both dissolved in blood plasma and in airspaces adjacent to the brain. These effects were found to be small, except for in the frontal cortex

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. A 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

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 brain’s 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

The venous contribution to sodium MRI in the human brain

Purpose: Sodium MRI shows great promise as a marker for cerebral metabolic dysfunction in stroke, brain tumor, and neurodegenerative pathologies. However, cerebral blood vessels, whose volume and function are perturbed in these pathologies, have elevated sodium concentrations relative to surrounding tissue. This study aims to assess whether this fluid compartment could bias measurements of tissue sodium using MRI. Methods: Density‐weighted and B1 corrected sodium MRI of the brain was acquired in 9 healthy participants at 4.7T. Veins were identified using co‐registered 1H T*2‐weighted images and venous partial volume estimates were calculated by down‐sampling the finer spatial resolution venous maps from the T*2‐weighted images to the coarser spatial resolution of the sodium data. Linear regressions of venous partial volume estimates and sodium signal were performed for regions of interest including just gray matter, just white matter, and all brain tissue. Results: Linear regression demonstrated a significant venous sodium contribution above the underlying tissue signal. The apparent venous sodium concentrations derived from regression were 65.8 ± 4.5 mM (all brain tissue), 71.0 ± 7.4 mM (gray matter), and 55.0 ± 4.7 mM (white matter). Conclusion: Although the partial vein linear regression did not yield the expected sodium concentration in blood (~87 mM), likely the result of point spread function smearing, this regression highlights that blood compartments may bias brain tissue sodium signals across neurological conditions where blood volumes may differ

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

Introduction We present the reliability of ultra-high field T2* MRI at 7T, as part of the UK7T Network's “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. Methods Ten 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 1× Philips, 2× Siemens Magnetom, and 2× 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 Discussion Mean susceptibility (χ) and R2* values agreed broadly with literature values in all ROIs. The inter-site within-subject standard deviation was 0.001–0.005 ppm (χ) and 0.0005–0.001 ms−1 (R2*). For χ 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 χ 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. Conclusion The 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

The 2dF Galaxy Redshift Survey: the clustering of galaxy groups

We measure the clustering of galaxy groups in the 2dFGRS Percolation-Inferred Galaxy Group (2PIGG) catalogue. The 2PIGG sample has 28 877 groups with at least two members. The clustering amplitude of the full 2PIGG catalogue is weaker than that of 2dFGRS galaxies, in agreement with theoretical predictions. We have subdivided the 2PIGG catalogue into samples that span a factor of ≈ 25 in median total luminosity. Our correlation function measurements span an unprecedented range of clustering strengths, connecting the regimes probed by groups fainter than L* galaxies and rich clusters. There is a steady increase in clustering strength with group luminosity; the most luminous groups are 10 times more strongly clustered than the full 2PIGG catalogue. We demonstrate that the 2PIGG results are in very good agreement with the clustering of groups expected in the ΛCDM mode

Multi-Site Harmonization of 7 Tesla MRI Neuroimaging Protocols

Increasing numbers of 7 tesla (7T) magnetic resonance imaging (MRI) scanners are in research and clinical use. 7T MRI can increase the scanning speed, spatial resolution and contrast-to-noise-ratio of many neuroimaging protocols, but technical challenges in implementation have been addressed in a variety of ways across sites. In order to facilitate multi-centre studies and ensure consistency of findings across sites, it is desirable that 7T MRI sites implement common high-quality neuroimaging protocols that can accommodate different scanner models and software versions. With the installation of several new 7T MRI scanners in the United Kingdom, the UK7T Network was established with an aim to create a set of harmonized structural and functional neuroimaging sequences and protocols. The Network currently includes five sites, which use three different scanner platforms, provided by two different vendors. Here we describe the harmonization of functional and anatomical imaging protocols across the three different scanner models, detailing the necessary changes to pulse sequences and reconstruction methods. The harmonized sequences are fully described, along with implementation details. Example datasets acquired from the same subject on all Network scanners are made available. Based on these data, an evaluation of the harmonization is provided. In addition, the implementation and validation of a common system calibration process is described. Keywords 7 tesla; MRI; Harmonization; anatomical; functional; Scanner calibration;The UK7T Network and this work was funded by the UK's Medical Research Council (MRC). [MR/N008537/1]. Centre funding The Wellcome Centre for Integrative Neuroimaging is supported by core funding from the Wellcome Trust (203139/Z/16/Z). Cardiff University Brain Research Imaging Centre is supported by the UK Medical Research Council (MR/M008932/1) and the Wellcome Trust (WT104943). This research was co-funded by the NIHR Cambridge Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. Individual funding CTR is funded by a Sir Henry Dale Fellowship from the Wellcome Trust and the Royal Society [098436/Z/12/B]