Transient signal changes in diffusion‐weighted stimulated echoes during neuronal stimulation at 3T

Abstract

Purpose: To develop a sensitive method for detecting minute transient signal changes that can arise due to variations in the extravascular apparent self-diffusion coefficient, D, during neuronal activation. Materials and Methods:A three-pulse sequence that reads out a moderately diffusion-weighted (DW) primary echo (PRE) and a heavily DW stimulated echo (STE) was employed to investigate whether small transient signal changes in extravascular D occur in response to a visual stimulus. Contributions to signal changes caused by subtle differences in the transient variations of the apparent transverse relaxation constant, T 2 , between the PRE and STE were also quantified. Results:On z-maps obtained from the STE, more voxels showed significant stimulus-related signal changes compared to maps of the PRE. The average maximum signal change of the STE was larger than that of the PRE. The observed increase in the relative signal change was independent of the strength of the diffusion weighting. Conclusion:The STE is more sensitive to neuronal activity than the PRE. The discrepancy between the two echoes does not arise from transient changes in D, but from subtle differences in stimulus-related variations of T 2 between the two echoes. THE BLOOD OXYGEN LEVEL-DEPENDENT (BOLD) effect detects activation only indirectly by the vascular response; therefore, the search for alternative functional magnetic resonance imaging (fMRI) methods to probe neuronal activity more directly is an area of ongoing research. It was recently hypothesized that the apparent water self-diffusion coefficient, D, decreases in the primary visual cortex during visual stimulation (1). It is assumed that cellular microstructure and morphology change as a result of neuronal activity, which can potentially be probed using diffusion-weighted (DW) fMRI. Swelling of neurons or astrocytes and associated morphological changes of the macromolecular matrix in brain tissue and the spinal cord have been intensively investigated with the use of intrinsic optical signals (2-7). Microstructural changes have been observed under various pathological conditions, including stroke, ischemia, and osmotic challenge. Furthermore, it has been demonstrated that electrically induced neuronal activity causes cellular swelling accompanied by structural changes in the macromolecular matrix.Water motion in biological tissue is affected by interaction with cell membranes and macromolecules. The non-monoexponential signal decay in DW MRI (DWI) strongly suggests that water self-diffusion is a sensitive probe for assessing structure and morphology on the cellular level. Initially, non-exponential behavior was assumed to reflect diffusion in the intra-and extracellular compartments. However, it has been shown that the two-compartment model oversimplifies the more complex interaction between water and the microanatomical environment in biological tissue (8 -10). It was also demonstrated that structural and morphological changes induced by pathological conditions known to cause cellular swe...

Functional diffusion tensor imaging at 3 Tesla

“…In addition, for the B0 signal the corresponding mean percent signal change was 0.10% for the tactile task and 0.14% for the visual task. This pattern of a relatively large mean percent signal change for FA compared with the mean percent signal change in MD and B0 is more in line with the hypothesized activity-related morphological glial cell changes and suggests that the observed signal changes cannot be explained by hemodynamics alone (Song et al, 1996; Does et al, 1999; Goerke and Moller, 2007; Miller et al, 2007; Lu et al, 2009). Thus, a possible hemodynamic contribution (and if present by itself a valid and interesting contrast mechanism for measuring activation in white matter) may not fully explain the measured fDTI signal.…”

“…However, it was shown that gradient coupling between changes in extravascular susceptibility gradients (i.e., BOLD effect) and the diffusion gradients can result in substantial changes in ADC (Zhong et al, 1991; Hong and Dixon, 1992). These results implicate that DfMRI is not immune to possible hemodynamic effects and posed the question whether or not the reported DfMRI activity-related ADC changes can be fully explained by this gradient coupling effect (Song et al, 1996; Does et al, 1999; Goerke and Moller, 2007; Miller et al, 2007; Lu et al, 2009; Ding et al, 2012; Rudrapatna et al, 2012). Although the results presented in (Stroman et al, 2008; Flint et al, 2009; Tirosh and Nevo, 2013) do provide important evidence that neuronal activation significantly reduces water displacement that can be measured using DfMRI it does not provide information on the relative contributions of the different contrast mechanisms to the measured ADC changes in gray matter.…”

Enhanced relative BOLD signal changes in T2‐weighted stimulated echoes

“…Figure 3c shows that the maximal relative signal change of the STE increases as a function of mixing time. This finding is consistent with previous observation, in which a larger relative signal change of the STE compared to the PRE was reported (24). Furthermore, the rise time and the signal undershoot after the stimulation period observed in the STE trial averages are very similar to the ones of the PRE, which shows the typical temporal characteristics of the BOLD response.…”

Functional localization of the human color center by decreased water displacement using diffusion‐weighted fMRI

“…Prior literature finding temporal equivalence between BOLD and DfMRI have cited this as evidence for dominance of the BOLD component in the diffusion signal (Goerke and Moller 2007; Yacoub et al. 2008; Rudrapatna et al.…”