Cytosolic diffusivity and microscopic anisotropy of N‐acetyl aspartate in human white matter with diffusion‐weighted MRS at 7 T

Metabolite diffusion measurable in humans in vivo with diffusion‐weighted spectroscopy (DW‐MRS) provides a window into the intracellular morphology and state of specific cell types. Anisotropic diffusion in white matter is governed by the microscopic properties of the individual cell types and their structural units (axons, soma, dendrites). However, anisotropy is also markedly affected by the macroscopic orientational distribution over the imaging voxel, particularly in DW‐MRS, where the dimensions of the volume of interest (VOI) are much larger than those typically used in diffusion‐weighted imaging. One way to address the confound of macroscopic structural features is to average the measurements acquired with uniformly distributed gradient directions to mimic a situation where fibers present in the VOI are orientationally uniformly distributed. This situation allows the extraction of relevant microstructural features such as transverse and longitudinal diffusivities within axons and the related microscopic fractional anisotropy. We present human DW‐MRS data acquired at 7 T in two different white matter regions, processed and analyzed as described above, and find that intra‐axonal diffusion of the neuronal metabolite N‐acetyl aspartate is in good correspondence to simple model interpretations, such as multi‐Gaussian diffusion from disperse fibers where the transverse diffusivity can be neglected. We also discuss the implications of our approach for current and future applications of DW‐MRS for cell‐specific measurements.