Compartment-Specific Investigation of Neural Tissue Microstructure with Diffusion Weighted MR Spectroscopy
Diffusion of water molecules in tissue has been long used in MRI to reflect microscopic characteristics of tissue in health and disease. In particular, diffusion tensor imaging (DTI) has been primarily used to characterize brain tissue structure and connectivity. The lack of compartmental specificity of the DTI signal leaves large gaps in the interpretation of the various quantities associated with the DTI measurement, e.g. fractional anisotropy and mean diffusivity. Here we suggest a complementary method, based on the acquisition and analysis of diffusion properties of brain metabolites that reside in specific tissue compartments. The compartmental specificity of metabolites such as N-acetyl aspartate (NAA) and others allows increase the sensitivity of diffusion measurements of these metabolites to the microstructure of the compartments in which they reside. It is shown, that, e.g., the sensitivity of FA(NAA) to axonal diameter in the human corpus callosum is higher than that of water, despite the generally lower SNR of the measurement. It is hoped that the combination of the high-resolution/high-specificity of standard DTI measurements and high compartmental specificity of diffusion spectroscopic measurements may provide a method that is able to detect early, pre-symptomatic changes in tissue characteristics in pathologies such as multiple sclerosis, where DTI alone shows measurable changes in the post-symptomatic phase.