Neurovascular coupling is brain region-dependent.

Despite recent advances in alternative brain imaging technologies, functional magnetic resonance imaging (fMRI) remains the workhorse for both medical diagnosis and primary research. Indeed, the number of research articles that utilise fMRI have continued to rise unabated since its conception in 1991, despite the limitation that recorded signals originate from the cerebral vasculature rather than neural tissue. Consequently, understanding the relationship between brain activity and the resultant changes in metabolism and blood flow (neurovascular coupling) remains a vital area of research. In the past, technical constraints have restricted investigations of neurovascular coupling to cortical sites and have led to the assumption that coupling in non-cortical structures is the same as in the cortex, despite the lack of any evidence. The current study investigated neurovascular coupling in the rat using whole-brain blood oxygenation level-dependent (BOLD) fMRI and multi-channel electrophysiological recordings and measured the response to a sensory stimulus as it proceeded through brainstem, thalamic and cortical processing sites - the so-called whisker-to-barrel pathway. We found marked regional differences in the amplitude of BOLD activation in the pathway and non-linear neurovascular coupling relationships in non-cortical sites. The findings have important implications for studies that use functional brain imaging to investigate sub-cortical function and caution against the use of simple, linear mapping of imaging signals onto neural activity.

Simultaneous laser Doppler flowmetry and arterial spin labeling MRI for measurement of functional perfusion changes in the cortex.

This study compares laser Doppler flowmetry (LDF) and arterial spin labeling (ASL) for the measurement of functional changes in cerebral blood flow (CBF). The two methods were applied concurrently in a paradigm of electrical whisker stimulation in the anaesthetised rat. Multi-channel LDF was used, with each channel corresponding to different fiber separation (and thus measurement depth). Continuous ASL was applied using separate imaging and labeling coils at 3 T. Careful experimental set up ensured that both techniques recorded from spatially concordant regions of the barrel cortex, where functional responses were maximal. Strong correlations were demonstrated between CBF changes measured by each LDF channel and ASL in terms of maximum response magnitude and response time-course within a 6-s-long temporal resolution imposed by ASL. Quantitatively, the measurements of the most superficial LDF channels agreed strongly with those of ASL, whereas the deeper LDF channels underestimated consistently the ASL measurement. It was thus confirmed that LDF quantifies CBF changes consistently at a superficial level, and for this case the two methods provided concordant measures of functional CBF changes, despite their essentially different physical principles and spatiotemporal characteristics.

k-space correction of eddy-current-induced distortions in diffusion-weighted echo-planar imaging.

This paper describes a method for correcting eddy-current (EC)-induced distortions in diffusion-weighted echo-planar imaging (DW-EPI). First, reference measurements of EC fields within the EPI acquisition window are performed for DW gradient pulses applied separately along each physical axis of the gradient set and for a range of gradient amplitudes. EC fields caused by the DW gradients of the DW-MRI protocol are then calculated using the reference EC measurements. Finally, these calculated fields are used to correct the respective DW-EPI raw (k-space) data during image reconstruction. The technique was implemented in a small-bore MRI scanner with no digital preemphasis. It corrected EC-induced image distortions in both phantom and in vivo brain diffusion tensor imaging (DTI) data more effectively than commonly used image-based techniques. The method did not increase imaging time, since the same reference EC measurements were used to correct data acquired from different phantoms, subjects, and DTI protocols. Because of the simplicity of the reference EC measurements, the method can easily be implemented in clinical scanners.

Approaching an ecologically valid functional anatomy of spontaneous "willed" action.

We used functional magnetic resonance imaging of healthy subjects to investigate the neural basis for spontaneous "willed" action. We hypothesised that such action involves prefrontal cortex (PFC) and supplementary motor area (SMA), in addition to primary motor cortex. Furthermore, we predicted that PFC and SMA would demonstrate similar temporal response dynamics, distinct from primary motor cortex. Specifically, we predicted earlier activation in PFC and SMA, manifest as shorter response latencies compared with primary motor cortex. Six right-handed males participated in an event-related design and were required to generate spontaneous motor acts inside the scanner. By deciding "which" of two buttons to press, and "when" to press them, subjects generated sequences of action that were of high information content ("novelty" or "randomness"). Utilising a short repetition time (1 s), we acquired functional images that covered most of the frontal and parietal cortices. The onset of action was associated with significant activation in bilateral PFC, left primary motor cortex, and, close to the midline, SMA. Following action, mean time to half-maximum blood oxygenation level-dependent response was significantly earlier in left PFC and SMA than primary motor cortex. Our findings suggest that neural correlates of spontaneous willed action are distributed in executive and motor centres, and that temporal response dynamics differentiate "higher" regions from subordinate motor areas.

A measure of curve fitting error for noise filtering diffusion tensor MRI data.

A parameter, chi2p, based on the fitting error was introduced as a measure of reliability of DT-MRI data, and its properties were investigated in simulations and human brain data. Its comparison with the classic chi2 revealed its sensitivity to both the goodness of fit and the pixel signal-to-noise-ratio (SNR), unlike the classic chi2, which is sensitive only to the goodness of fit. The new parameter was thus able to separate effectively pixels with coherent signals (having small fitting error and/or high SNR) from those with random signals (having inconsistent fitting and/or low SNR). A practical advantage of chi2p over the classic chi2 was that chi2p is quantified directly from the data of each pixel, without requiring accurate estimation of data-dependent parameters (such as noise variance), which often makes application of the classic chi2 problematic. Analytical approximations of chi2p enabled an objective (data-independent) and automated calculation of a threshold value, used for internal scaling of the chi2p map. Apart from assessing data reliability on a pixel-by-pixel basis, chi2p was used to develop an objective and generic methodology for the exclusion of pixels with unreliable DT information by discarding pixels with chi2p values exceeding the threshold. Pixels corresponding to very low SNR, and poorly fitted cerebrospinal fluid and surrounding brain tissue, had increased chi2p values and were successfully excluded, providing DT anisotropy maps free from artifactual anisotropic appearance.

Study of the effect of CSF suppression on white matter diffusion anisotropy mapping of healthy human brain.

Healthy human brain diffusion anisotropy maps derived from standard spin echo diffusion tensor imaging (DTI) were compared with those using fluid-attenuated inversion recovery (FLAIR) preparation prior to DTI to null the signal from cerebrospinal fluid (CSF). Consistent comparisons entailed development of DTI postprocessing methods, image masking based on fitting quality, and an objective region-of-interest-based method for assessment of white matter extent. FLAIR DTI achieved an extended delineation of major white-matter tracts (genu, splenium, and body of the corpus callosum) close to large CSF-filled spaces (lateral ventricles), but did not affect representation of tracts remote from CSF (internal and external capsules and coronal radiation). This result, which was detectable qualitatively (visual inspection), was verified quantitatively by analyses of the relative anisotropy (RA) distribution over white matter structures for 11 subjects. FLAIR DTI thus suppresses the CSF signal that otherwise masks underlying anisotropic parenchymal tissue through partial volume averaging.