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Data acquired with functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) are often interpreted in terms of the underlying neuronal activity, despite mounting evidence that these signals do not always correlate with electrophysiological recordings. Therefore, considering the increasing popularity of functional neuroimaging, it is clear that a more comprehensive theory is needed to reconcile these apparent disparities and more accurately explain the mechanisms through which various PET and fMRI signals arise. In the present article, we have turned our attention to astrocytes, which vastly outnumber neurons and are known to serve a number of functions throughout the central nervous system (CNS). For example, astrocytes are known to be critically involved in neurotransmitter uptake and recycling, and empirical data suggests that brain activation increases both oxidative and glycolytic astrocyte metabolism. Furthermore, a number of recent studies imply that astrocytes are likely to play a key role in regulating cerebral blood delivery. Therefore, we propose that, by mediating neurometabolic and neurovascular processes throughout the CNS, astrocytes could provide a common physiological basis for fMRI and PET signals. Such a theory has significant implications for the interpretation of functional neuroimaging signals, because astrocytic changes reflect subthreshold neuronal activity, simultaneous excitatory/inhibitory synaptic inputs, and other transient metabolic demands that may not elicit electrophysiological changes. It also suggests that fMRI and PET signals may have inherently less sensitivity to decreases in synaptic input (i.e. 'negative activity') and/or inhibitory (GABAergic) neurotransmission.

Given the growing popularity of T1 -weighted/T2 -weighted (T1 w/T2 w) ratio measurements, the objective of the current study was to evaluate the concordance between T1 w/T2 w ratios obtained using conventional fast spin echo (FSE) versus combined gradient and spin echo (GRASE) sequences for T2 w image acquisition, and to compare the resulting T1 w/T2 w ratios with histologically validated myelin water fraction (MWF) measurements in several subcortical brain structures. In order to compare these measurements across a relatively wide range of myelin concentrations, whole-brain T1 w magnetization prepared rapid acquisition gradient echo (MPRAGE), T2 w FSE and three-dimensional multi-echo GRASE data were acquired from 10 participants with multiple sclerosis at 3 T. Then, after high-dimensional, non-linear warping, region of interest (ROI) analyses were performed to compare T1 w/T2 w ratios and MWF estimates (across participants and brain regions) in 11 bilateral white matter (WM) and four bilateral subcortical grey matter (SGM) structures extracted from the JHU_MNI_SS 'Eve' atlas. Although the GRASE sequence systematically underestimated T1 w/T2 w values compared to the FSE sequence (revealed by Bland-Altman and mountain plots), linear regressions across participants and ROIs revealed consistently high correlations between the two methods (r2 = 0.62 for all ROIs, r2 = 0.62 for WM structures and r2 = 0.73 for SGM structures). However, correlations between either FSE-based or GRASE-based T1 w/T2 w ratios and MWFs were extremely low in WM structures (FSE-based, r2 = 0.000020; GRASE-based, r2 = 0.0014), low across all ROIs (FSE-based, r2 = 0.053; GRASE-based, r2 = 0.029) and moderate in SGM structures (FSE-based, r2 = 0.20; GRASE-based, r2 = 0.17). Overall, our findings indicated a high degree of correlation (but not equivalence) between FSE-based and GRASE-based T1 w/T2 w ratios, and low correlations between T1 w/T2 w ratios and MWFs. This suggests that the two T1 w/T2 w ratio approaches measure similar facets of subcortical tissue microstructure, whereas T1 w/T2 w ratios and MWFs appear to be sensitized to different microstructural properties. On this basis, we conclude that multi-echo GRASE sequences can be used in future studies to efficiently elucidate both general (T1 w/T2 w ratio) and myelin-specific (MWF) tissue characteristics.

Spinal cord (SC) motion is thought to be the dominant source of error in current diffusion and spinal functional MRI (fMRI) methods. However, until now, such motion has not been well characterized in three dimensions. While previous studies have predominantly examined motion in the superior/inferior (S/I) direction, the foci of the present study were the anterior/posterior (A/P) and right/left (R/L) components of human cervical and upper thoracic SC motion. Cardiac-gated, turbofast low-angle shot (turbo-FLASH) cinematic MRI was employed at 3T to acquire images of the cord at 24 phases throughout the cardiac cycle. Time-dependent signal fluctuations within voxels adjacent to the cord/cerebrospinal fluid (CSF) interface were then used to measure SC motion, which was found to occur predictably as a function of cardiac activity. Cord movement was largest in the A/P direction, for which principal components of motion were calculated, thereby indicating consistent patterns of SC oscillation that can potentially be used to improve SC imaging. Magn Reson Med 58:185–189, 2007. © 2007 Wiley-Liss, Inc.