Ashley D. Harris

Gannet: A batch‐processing tool for the quantitative analysis of gamma‐aminobutyric acid–edited MR spectroscopy spectra

The purpose of this study is to describe the Gannet toolkit for the quantitative batch analysis of gamma‐aminobutyric acid (GABA) ‐edited MRS data.

Measurement of OEF and absolute CMRO2: MRI-based methods using interleaved and combined hypercapnia and hyperoxia.

Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) is most commonly used in a semi-quantitative manner to infer changes in brain activity. Despite the basis of the image contrast lying in the cerebral venous blood oxygenation level, quantification of absolute cerebral metabolic rate of oxygen consumption (CMRO2) has only recently been demonstrated. Here we examine two approaches to the calibration of fMRI signal to measure absolute CMRO2 using hypercapnic and hyperoxic respiratory challenges. The first approach is to apply hypercapnia and hyperoxia separately but interleaved in time and the second is a combined approach in which we apply hyperoxic challenges simultaneously with different levels of hypercapnia. Eleven healthy volunteers were studied at 3T using a dual gradient-echo spiral readout pulsed arterial spin labelling (ASL) imaging sequence. Respiratory challenges were conducted using an automated system of dynamic end-tidal forcing. A generalised BOLD signal model was applied, within a Bayesian estimation framework, that aims to explain the effects of modulation of CBF and arterial oxygen content to estimate venous deoxyhaemoglobin concentration ([dHb]0). Using CBF measurements combined with the estimated oxygen extraction fraction (OEF), absolute CMRO2 was calculated. The interleaved approach to hypercapnia and hyperoxia, as well as yielding estimates of CMRO2 and OEF demonstrated a significant increase in regional CBF, venous oxygen saturation (SvO2) (a decrease in OEF) and absolute CMRO2 in visual cortex in response to a continuous (20 min) visual task, demonstrating the potential for the method in measuring long term changes in CMRO2. The combined approach to oxygen and carbon dioxide modulation, as well as taking less time to acquire data, yielded whole brain grey matter estimates of CMRO2 and OEF of 184±45 μmol/100 g/min and 0.42±0.12 respectively, along with additional estimates of the vascular parameters α=0.33±0.06, the exponent relating relative increases in CBF to CBV, and β=1.35±0.13, the exponent relating deoxyhaemoglobin concentration to the relaxation rate R2*. Maps of cerebrovascular and cerebral metabolic parameters were also calculated. We show that combined modulation of oxygen and carbon dioxide can offer an experimentally more efficient approach to estimating OEF and absolute CMRO2 along with the additional vascular parameters that form an important part of the commonly used calibrated fMRI signal model.

Frequency and phase drift correction of magnetic resonance spectroscopy data by spectral registration in the time domain.

Frequency and phase drifts are a common problem in the acquisition of in vivo magnetic resonance spectroscopy (MRS) data. If not accounted for, frequency and phase drifts will result in artifactual broadening of spectral peaks, distortion of spectral lineshapes, and a reduction in signal‐to‐noise ratio (SNR). We present herein a new method for estimating and correcting frequency and phase drifts in in vivo MRS data.

Robustly measuring vascular reactivity differences with breath-hold: Normalising stimulus-evoked and resting state BOLD fMRI data

Inter-subject differences in local cerebral blood flow (CBF) and cerebral blood volume (CBV) contribute to differences in BOLD signal reactivity and, therefore, unmodelled variance in group level fMRI analyses. A simple way of elevating blood CO(2) concentrations to characterise subject differences in vascular reactivity is through breath-holds but two aspects of this measure are often neglected: (1) breath-holds are usually modelled as blocks even though CO(2) accumulates over time and (2) increases in CO(2) differ between subjects. This study demonstrates that the BOLD breath-hold response is best modelled by convolving the end-tidal CO(2) trace with a standard haemodynamic response function and including its temporal derivative. Inclusion of the BOLD breath-hold response as a voxel-dependent covariate in a group level analysis increases the spatial extent of activation in stimulus evoked and resting state datasets. By expressing the BOLD breath-hold response as a percentage signal increase with respect to an absolute change in the partial pressure of CO(2) (expressed in mmHg), the spatial extent of stimulus-evoked activation is further improved. This demonstrates that individual end-tidal CO(2) increases to breath-hold should be accounted for to provide an accurate measure of vascular reactivity resulting in more statistically active voxels in group level analyses.

Impact of frequency drift on gamma-aminobutyric acid-edited MR spectroscopy

To investigate the quantitative impact of frequency drift on Gamma‐Aminobutyric acid (GABA+)‐edited MRS of the human brain at 3 Tesla (T).

Tissue correction for GABA-edited MRS: Considerations of voxel composition, tissue segmentation, and tissue relaxations

To develop a tissue correction for GABA‐edited magnetic resonance spectroscopy (MRS) that appropriately addresses differences in voxel gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) fractions.

Spectral-Editing Measurements of GABA in the Human Brain with and without Macromolecule Suppression

The conventional spectral‐editing experiment used to measure GABA in the human brain also contains a contribution from macromolecules (MM), and the combined GABA plus MM signal is often referred to as “GABA+”. More recently, methods have been developed to estimate GABA free from MM contamination. In this study, the relationship between GABA acquired with MM suppression and conventional GABA+ measurements was examined.

A comparison of images generated from diffusion-weighted and diffusion-tensor imaging data in hyper-acute stroke

To compare isotropic (combined diffusion‐weighted image [CMB], apparent diffusion coefficient [ADC], TRACE, exponential ADC [eADC], and isotropically‐weighted diffusion image [isoDWI]) and anisotropic (relative anisotropy [RA], fractional anisotropy [FA], and volume ratio [VR]) diffusion images collected with fast magnetic resonance (MR) diffusion‐weighted (DWI) and diffusion‐tensor (DTI) acquisition strategies (each less than one minute) in hyper‐acute stroke.

Edited 1H magnetic resonance spectroscopy in vivo: Methods and metabolites

The Proton magnetic resonance (1H‐MRS) spectrum contains information about the concentration of tissue metabolites within a predefined region of interest (a voxel). The conventional spectrum in some cases obscures information about less abundant metabolites due to limited separation and complex splitting of the metabolite peaks. One method to detect these metabolites is to reduce the complexity of the spectrum using editing. This review provides an overview of the one‐dimensional editing methods available to interrogate these obscured metabolite peaks. These methods include sequence optimizations, echo‐time averaging, J‐difference editing methods (single BASING, dual BASING, and MEGA‐PRESS), constant‐time PRESS, and multiple quantum filtering. It then provides an overview of the brain metabolites whose detection can benefit from one or more of these editing approaches, including ascorbic acid, γ‐aminobutyric acid, lactate, aspartate, N‐acetyl aspartyl glutamate, 2‐hydroxyglutarate, glutathione, glutamate, glycine, and serine. Magn Reson Med 77:1377–1389, 2017.

Reduced GABA and altered somatosensory function in children with autism spectrum disorder

Background: Abnormal responses to tactile stimuli are a common feature of autism spectrum disorder (ASD). Several lines of evidence suggest that GABAergic function, which has a crucial role in tactile processing, is altered in ASD. In this study, we determine whether in vivo GABA levels are altered in children with ASD, and whether alterations in GABA levels are associated with abnormal tactile function in these children.