Age-related microstructural and physiological changes in normal brain measured by MRI γ-metrics derived from anomalous diffusion signal representation.

Nowadays, increasing longevity associated with declining cerebral nervous system functions, suggests the need for continued development of new imaging contrast mechanisms to support the differential diagnosis of age-related decline. In our previous papers, we developed a new imaging contrast metrics derived from anomalous diffusion signal representation and obtained from diffusion-weighted (DW) data collected by varying diffusion gradient strengths. Recently, we highlighted that the new metrics, named γ-metrics, depended on the local inhomogeneity due to differences in magnetic susceptibility between tissues and diffusion compartments in young healthy subjects, thus providing information about myelin orientation and iron content within cerebral regions. The major structural modifications occurring in brain aging are myelinated fibers damage in nerve fibers and iron accumulation in gray matter nuclei. Therefore, we investigated the potential of γ-metrics in relation to other conventional diffusion metrics such as DTI, DKI and NODDI in detecting age-related structural changes in white matter (WM) and subcortical gray matter (scGM). DW-images were acquired in 32 healthy subjects, adults and elderly (age range 20-77 years) using 3.0T and 12 b-values up to 5000 s/mm2. Association between diffusion metrics and subjects' age was assessed using linear regression. A decline in mean γ (Mγ) in the scGM and a complementary increase in radial γ (γ⊥) in frontal WM, genu of corpus callosum and anterior corona radiata with advancing age were found. We suggested that the increase in γ⊥ might reflect declined myelin density, and Mγ decrease might mirror iron accumulation. An increase in D// and a decrease in the orientation dispersion index (ODI) were associated with axonal loss in the pyramidal tracts, while their inverted trends within the thalamus were thought to be linked to reduced architectural complexity of nerve fibers. γ-metrics together with conventional diffusion-metrics can more comprehensively characterize the complex mechanisms underlining age-related changes than conventional diffusion techniques alone.