Multi-parametric quantitative MRI reveals three different white matter subtypes

INTRODUCTION: Magnetic resonance imaging (MRI) shows slight spatial variations in brain white matter (WM). We used quantitative multi-parametric MRI to evaluate in what respect these inhomogeneities could correspond to WM subtypes with specific characteristics and spatial distribution. MATERIALS AND METHODS: Twenty-six controls (12 women, 38 ±9 Y) took part in a 60-min session on a 3T scanner measuring 7 parameters: R(1) and R(2), diffusion tensor imaging which allowed to measure Axial and Radial Diffusivity (AD, RD), magnetization transfer imaging which enabled to compute the Macromolecular Proton Fraction (MPF), and a susceptibility-weighted sequence which permitted to quantify R(2)* and magnetic susceptibility (χ(m)). Spatial independent component analysis was used to identify WM subtypes with specific combination of quantitative parameters values. RESULTS: Three subtypes could be identified. t-WM (track) mostly mapped on well-formed projection and commissural tracts and came with high AD values (all p < 10(−18)). The two other subtypes were located in subcortical WM and overlapped with association fibers: f-WM (frontal) was mostly anterior in the frontal lobe whereas c-WM (central) was underneath the central cortex. f-WM and c-WM had higher MPF values, indicating a higher myelin content (all p < 1.7 10(−6)). This was compatible with their larger χ(m) and R(2), as iron is essentially stored in oligodendrocytes (all p < 0.01). Although R(1) essentially showed the same, its higher value in t-WM relative to c-WM might be related to its higher cholesterol concentration. CONCLUSIONS: Thus, f- and c-WMs were less structured, but more myelinated and probably more metabolically active regarding to their iron content than WM related to fasciculi (t-WM). As known WM bundles passed though different WM subtypes, myelination might not be uniform along the axons but rather follow a spatially consistent regional variability. Future studies might examine the reproducibility of this decomposition and how development and pathology differently affect each subtype.