In vivo mapping of human spinal cord microstructure at 300 mT/m

The ability to characterize white matter microstructure non-invasively has important applications for the diagnosis and follow-up of several neurological diseases. There exists a family of diffusion MRI techniques, such as AxCaliber, that provide indices of axon microstructure, such as axon diameter and density. However, to obtain accurate measurements of axons with small diameters (<5 μm), these techniques require strong gradients, i.e. an order of magnitude higher than the 40–80 mT/m currently available in clinical systems. In this study we acquired AxCaliber diffusion data at a variety of different q-values and diffusion times in the spinal cord of five healthy subjects using a 300 mT/m whole body gradient system. Acquisition and processing were optimized using state-of-the-art methods (e.g., 64-channel coil, template-based analysis). Results consistently show an average axon diameter of 4.5 +/− 1.1 μm in the spinal cord white matter. Diameters ranged from 3.0 μm (gracilis) to 5.9 μm (spinocerebellar tracts). Values were similar across laterality (left-right), but statistically different across spinal cord pathways (p<10(−5)). The observed trends are similar to those observed in animal histology. This study shows, for the first time, in vivo mapping of axon diameter in the spinal cord at 300 mT/m, thus creating opportunities for applications in spinal cord diseases