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...