Pixel-based comparison of spinal cord MR diffusion anisotropy with axon packing parameters

Water diffusion in nerve fibers is strongly influenced by axon architecture. In this study, fractional diffusion anisotropy and transverse and longitudinal diffusion coefficients were measured in excised human cervical spinal cord with MR line-scan diffusion imaging, at 625 microm in-plane resolution and 3 mm slice thickness. A pixel-based comparison of fractional diffusion anisotropy, transverse diffusion coefficient, and longitudinal diffusion coefficient data with axon packing parameters derived from corresponding stained histological sections was performed for four slices. The axon packing parameters, axon density, axon area-fraction, and average axon size for entire specimen cross-sections were calculated by computerized segmentation of optical microscopy data obtained at 0.53 microm resolution. Salient features could be recognized on fractional diffusion anisotropy, transverse diffusion coefficient, axon density, axon area fraction, and average axon size maps. For white matter regions only, the average correlation coefficients for fractional diffusion anisotropy compared to histology-based parameters axon density and axon area fraction were 0.37 and 0.21, respectively. For transverse diffusion coefficient compared to axon density and axon area fraction, they were -0.40 and -0.36, and for longitudinal diffusion coefficient compared to axon density and axon area fraction, -0.14 and -0.30. All average correlation coefficients for average axon size were low. Correlation coefficients for collectively analyzed white and gray matter regions were significantly higher than correlation coefficients derived from analysis of white matter regions only.