Brain White-Matter Degeneration Due to Aging and Parkinson Disease as Revealed by Double Diffusion Encoding

Microstructure imaging by means of multidimensional diffusion encoding is increasingly applied in clinical research, with expectations that it yields a parameter that better correlates with clinical disability than current methods based on single diffusion encoding. Under the assumption that diffusion within a voxel can be well described by a collection of diffusion tensors, several parameters of this diffusion tensor distribution can be derived, including mean size, variance of sizes, orientational dispersion, and microscopic anisotropy. The information provided by multidimensional diffusion encoding also enables us to decompose the sources of the conventional fractional anisotropy and mean kurtosis. In this study, we explored the utility of the diffusion tensor distribution approach for characterizing white-matter degeneration in aging and in Parkinson disease by using double diffusion encoding. Data from 23 healthy older subjects and 27 patients with Parkinson disease were analyzed. Advanced age was associated with greater mean size and size variances, as well as smaller microscopic anisotropy. By analyzing the parameters underlying diffusion kurtosis, we found that the reductions of kurtosis in aging and Parkinson disease reported in the literature are likely driven by the reduction in microscopic anisotropy. Furthermore, microscopic anisotropy correlated with the severity of motor impairment in the patients with Parkinson disease. The present results support the use of multidimensional diffusion encoding in clinical studies and are encouraging for its future clinical implementation.