The goal of this paper is to develop a method for assessment of microstructural properties of the fornix in conventional (low resolution, single non-zero b-value) diffusion-weighted magnetic resonance imaging (DW-MRI) data. For this purpose, a bi-tensor model, comprising of an isotropic and an anisotropic diffusion compartment, was fitted to the diffusion-weighted images. Two subject-specific constraints were studied to solve the ill-posedness of the parameter estimation at a single (non-zero) b-value, namely by fixating the mean diffusivity (MD) or the axial diffusivity (AxD) of the anisotropic compartment. The bi-tensor statistics were compared to conventional diffusion statistics using simulated fiber bundles with different diameters and using fornix segmentations of 577 elderly subjects. Based on simulated fiber bundles, the anisotropy (FA) estimated by the bi-tensor model did not become biased with decreasing fiber bundle diameter, unlike conventional diffusion statistics such as FA and MD estimated by the single tensor model. In the population-based study, the bi-tensor tissue fraction decreased significantly with age, suggesting an increase of free water. The FA estimated by the bi-tensor model decreased with age, but this relation was not significant when the subject-specific values to which MD or AxD were constrained were added as covariates in the regression analysis. The distinction of an isotropic and an anisotropic diffusion compartment may allow a more sophisticated analysis of the fornix based on conventional DW-MRI data.@en

White matter microstructural integrity has been related to cognition. Yet, the potential role of specificwhite matter tracts on top of a global white matter effect remains unclear, especially when consideringspecific cognitive domains. Therefore, we determined the tract-specific effect of white matter micro-structure on global cognition and specific cognitive domains. In 4400 nondemented and stroke-freeparticipants (mean age 63.7 years, 55.5% women), we obtained diffusion magnetic resonance imagingparameters (fractional anisotropy and mean diffusivity) in 14 white matter tracts using probabilistictractography and assessed cognitive performance with a cognitive test battery. Tract-specific whitematter microstructure in all supratentorial tracts was associated with poorer global cognition. Lowerfractional anisotropy in association tracts, primarily the inferior fronto-occipital fasciculus, and highermean diffusivity in projection tracts, in particular the posterior thalamic radiation, most strongly relatedto poorer cognition. Altered white matter microstructure related to poorer information processing speed,executive functioning, and motor speed, but not to memory. Tract-specific microstructural changes mayaid in better understanding the mechanism of cognitive impairment and neurodegenerative diseases.@en