Daniel Gallichan

A calibration method for quantitative BOLD fMRI based on hyperoxia

The estimation of changes in CMR(O2) using functional MRI involves an essential calibration step using a vasoactive agent to induce an isometabolic change in CBF. This calibration procedure is performed most commonly using hypercapnia as the isometabolic stimulus. However, hypercapnia possesses a number of detrimental side effects. Here, a new method is presented using hyperoxia to perform the same calibration step. This procedure requires independent measurement of Pa(O2), the BOLD signal, and CBF. We demonstrate that this method yields results that are comparable to those derived using other methods. Further, the hyperoxia technique is able to provide an estimate of the calibration constant that has lower overall intersubject and intersession variability compared to the hypercapnia approach.

Flow-metabolism coupling in human visual, motor, and supplementary motor areas assessed by magnetic resonance imaging.

Combined blood oxygenation level‐dependent (BOLD) and arterial spin labeling (ASL) functional MRI (fMRI) was performed for simultaneous investigation of neurovascular coupling in the primary visual cortex (PVC), primary motor cortex (PMC), and supplementary motor area (SMA). The hypercapnia‐calibrated method was employed to estimate the fractional change in cerebral metabolic rate of oxygen consumption (CMRO2) using both a group‐average and a per‐subject calibration. The group‐averaged calibration showed significantly different CMRO2−CBF coupling ratios in the three regions (PVC: 0.34 ± 0.03; PMC: 0.24 ± 0.03; and SMA: 0.40 ± 0.02). Part of this difference emerges from the calculated values of the hypercapnic calibration constant M in each region (MPVC = 6.6 ± 3.4, MPMC = 4.3 ± 3.5, and MSMA = 7.2 ± 4.1), while a relatively minor part comes from the spread and shape of the sensorimotor BOLD–CBF responses. The averages of the per‐subject calibrated CMRO2−CBF slopes were 0.40 ± 0.04 (PVC), 0.31 ± 0.03 (PMC), and 0.44 ± 0.03 (SMA). These results are 10–30% higher than group‐calibrated values, and are potentially more useful for quantifying individual differences in focal functional responses. The group‐average calibrated motor coupling value is increased to 0.28 ± 0.03 when stimulus‐correlated increases in end‐tidal CO2 are included. Our results support the existence of regional differences in neurovascular coupling, and argue for the importance of achieving optimal accuracy in hypercapnia calibrations to resolve method‐dependent variations in published results. Magn Reson Med 57:538–547, 2007.

Measuring the effects of remifentanil on cerebral blood flow and arterial arrival time using 3D GRASE MRI with pulsed arterial spin labelling

Arterial spin labelling (ASL) has proved to be a promising magnetic resonance imaging (MRI) technique to measure brain perfusion. In this study, volumetric three-dimensional (3D) gradient and spin echo (GRASE) ASL was used to produce cerebral blood flow (CBF) and arterial arrival time (AAT) maps during rest and during an infusion of remifentanil. Gradient and spin echo ASL perfusion-weighted images were collected at multiple inflow times (500 to 2,500 ms in increments of 250 ms) to accurately fit an ASL perfusion model. Fit estimates were assessed using z-statistics, allowing voxels with a poor fit to be excluded from subsequent analyses. Nonparametric permutation testing showed voxels with a significant difference in CBF and AAT between conditions across a group of healthy participants (N = 10). Administration of remifentanil produced an increase in end-tidal CO2, an increase in CBF from 57 ± 12.0 to 77 ± 18.4 mL/100 g tissue per min and a reduction in AAT from 0.73 ± 0.073 to 0.64 ± 0.076 secs. Within grey matter, remifentanil produced a cerebrovascular response of 5.7 ± 1.60 %CBF per mm Hg. Significant differences between physiologic conditions were observed in both CBF and AAT maps, indicating that 3D GRASE-ASL has the sensitivity to study changes in physiology at a voxel level.

Addressing a systematic vibration artifact in diffusion-weighted MRI

We have identified and studied a pronounced artifact in diffusion‐weighted MRI on a clinical system. The artifact results from vibrations of the patient table due to low‐frequency mechanical resonances of the system which are stimulated by the low‐frequency gradient switching associated with the diffusion‐weighting. The artifact manifests as localized signal‐loss in images acquired with partial Fourier coverage when there is a strong component of the diffusion‐gradient vector in the left–right direction. This signal loss is caused by local phase ramps in the image domain which shift the apparent k‐space center for a particular voxel outside the covered region. The local signal loss masquerades as signal attenuation due to diffusion, severely disrupting the quantitative measures associated with diffusion‐tensor imaging (DTI). We suggest a way to improve the interpretation of affected DTI data by including a co‐regressor which accounts for the empirical response of regions affected by the artifact. We also demonstrate that the artifact may be avoided by acquiring full k‐space data, and that subsequent increases in TE can be avoided by employing parallel acceleration. Hum Brain Mapp, 2010.

Neuroprotection by Dimethyloxalylglycine following Permanent and Transient Focal Cerebral Ischemia in Rats

Dimethyloxalylglycine (DMOG) is an inhibitor of prolyl-4-hydroxylase domain (PHD) enzymes that regulate the stability of hypoxia-inducible factor (HIF). We investigated the effect of DMOG on the outcome after permanent and transient middle cerebral artery occlusion (p/tMCAO) in the rat. Before and after pMCAO, rats were treated with 40 mg/kg, 200 mg/kg DMOG, or vehicle, and with 40 mg/kg or vehicle after tMCAO. Serial magnetic resonance imaging (MRI) was performed to assess infarct evolution and regional cerebral blood flow (rCBF). Both doses significantly reduced infarct volumes, but only 40 mg/kg improved the behavior after 24 hours of pMCAO. Animals receiving 40 mg/kg were more likely to maintain rCBF values above 30% from the contralateral hemisphere within 24 hours of pMCAO. DMOG after tMCAO significantly reduced the infarct volumes and improved behavior at 24 hours and 8 days and also improved the rCBF after 24 hours. A consistent and significant upregulation of both mRNA and protein levels of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) was associated with the observed neuroprotection, although this was not consistently related to HIF-1α levels at 24 hours and 8 days. Thus, DMOG afforded neuroprotection both at 24 hours after pMCAO and at 24 hours and 8 days after tMCAO. This effect was associated with an increase of VEGF and eNOS and was mediated by improved rCBF after DMOG treatment.

Simultaneously driven linear and nonlinear spatial encoding fields in MRI

Spatial encoding in MRI is conventionally achieved by the application of switchable linear encoding fields. The general concept of the recently introduced PatLoc (Parallel Imaging Technique using Localized Gradients) encoding is to use nonlinear fields to achieve spatial encoding. Relaxing the requirement that the encoding fields must be linear may lead to improved gradient performance or reduced peripheral nerve stimulation. In this work, a custom‐built insert coil capable of generating two independent quadratic encoding fields was driven with high‐performance amplifiers within a clinical MR system. In combination with the three linear encoding fields, the combined hardware is capable of independently manipulating five spatial encoding fields. With the linear z‐gradient used for slice‐selection, there remain four separate channels to encode a 2D‐image. To compare trajectories of such multidimensional encoding, the concept of a local k‐space is developed. Through simulations, reconstructions using six gradient‐encoding strategies were compared, including Cartesian encoding separately or simultaneously on both PatLoc and linear gradients as well as two versions of a radial‐based in/out trajectory. Corresponding experiments confirmed that such multidimensional encoding is practically achievable and demonstrated that the new radial‐based trajectory offers the PatLoc property of variable spatial resolution while maintaining finite resolution across the entire field‐of‐view. Magn Reson Med, 2011.

Optimal design of pulsed arterial spin labeling MRI experiments.

Quantitative measurement of cerebral blood flow (CBF) using arterial spin labeling (ASL) MRI requires the acquisition of multiple inversion times (TIs) and the application of an appropriate kinetic model. The choice of these sampling times will have an impact on the precision of the estimated parameters. Here, optimal sampling schedule (OSS) design techniques, based on the Fisher Information approach, are applied in order to derive an optimal sampling scheme for pulsed arterial spin labeling (PASL) experiments. Such an approach should improve the precision of parameter estimation from experimental data, and provide a formal framework for optimally selecting a limited number of samples. In this study, we aimed to optimize the estimation precision of CBF and bolus arrival time from the PASL data. The performance of OSS was compared to a more standard evenly distributed sampling schedule (EDS) using both simulated and measured experimental data sets. It was found that OSS was able to significantly improve the precision of parameter estimation in PASL studies that sought to estimate either both CBF and bolus arrival time, or CBF alone. Magn Reson Med, 2008.

Bayesian inference of hemodynamic changes in functional arterial spin labeling data.

The study of brain function using MRI relies on acquisition techniques that are sensitive to different aspects of the hemodynamic response contiguous to areas of neuronal activity. For this purpose different contrasts such as arterial spin labeling (ASL) and blood oxygenation level dependent (BOLD) functional MRI techniques have been developed to investigate cerebral blood flow (CBF) and blood oxygenation, respectively. Analysis of such data typically proceeds by separate, linear modeling of the appropriate CBF or BOLD time courses. In this work an approach is developed that provides simultaneous inference on hemodynamic changes via a nonlinear physiological model of ASL data acquired at multiple echo times. Importantly, this includes a significant contribution by changes in the static magnetization, M, to the ASL signal. Inference is carried out in a Bayesian framework. This is able to extract, from dual‐echo ASL data, probabilistic estimates of percentage changes of CBF, R  2* , and the static magnetization, M. This approach provides increased sensitivity in inferring CBF changes and reduced contamination in inferring BOLD changes when compared with general linear model approaches on single‐echo ASL data. We also consider how the static magnetization, M, might be related to changes in CBV by assuming the same mechanism for water exchange as in vascular space occupancy. Magn Reson Med, 2006.

Modeling the effects of dispersion and pulsatility of blood flow in pulsed arterial spin labeling

Arterial spin labeling (ASL) is a method of using MRI to image cerebral perfusion. For the measurement to be calibrated, a model is required describing the kinetics of the flow of the inverted blood from the labeling region to the imaging region. It is common to assume plug‐flow, but alternatives such as a Gaussian distribution of arrival times have also been suggested. In this study a physiologically based model for dispersion is developed and compared to existing models when fit to experimental data. The model is based on the assumption of parabolic flow in the major arteries, and also allows inclusion of cardiac pulsatility. It was found that fitting using the proposed model leads to higher perfusion estimates, with the difference becoming more pronounced in regions where the dispersion is greater. This suggests that current models may underestimate perfusion in these areas. However, fitting using the proposed model also leads to high uncertainties in parameter estimates due to non‐orthogonality of the parameters. Effects due to pulsatility are expected to be observable, but when no cardiac‐gating is used the mean curve over several cardiac cycles is predicted to closely match the curve which assumes constant flow. Magn Reson Med 60:53–63, 2008.

Reducing distortions in diffusion‐weighted echo planar imaging with a dual‐echo blip‐reversed sequence

The inherent distortions in echo‐planar imaging that arise due to inhomogeneities in the static magnetic field can lead to difficulties when attempting to obtain structurally accurate diffusion‐tensor imaging data. Parallel acceleration techniques can reduce the magnitude of these distortions but do not remove them entirely. Images can be corrected using a measured field map, but this is prone to error. One approach to correcting for these distortions, referred to here as “blip‐reversed” echo‐planar imaging, involves collecting a second set of images with the phase encoding reversed. Here, a novel approach to collecting blip‐reversed echo‐planar imaging data for diffusion‐tensor imaging is presented: a dual‐echo sequence is used in which the phase‐encoding direction of the second echo is swapped compared to the first echo. This allows benefits of the blip‐reversed approach to be exploited, with only a modest increase in scan time and, due to the extra data acquired, no significant loss of signal‐to‐noise efficiency. A novel approach to recombining blip‐reversed data is also presented, which involves refining the measured field map, using an algorithm to minimize the difference between the corrected images. The field map refinement is also applicable to conventionally acquired blip‐reversed sequences. Magn Reson Med, 2010.