For Fractional Anisotropy Values Research Articles

Genetics of microstructure of cerebral white matter using diffusion tensor imaging

We analyzed the degree of genetic control over intersubject variability in the microstructure of cerebral white matter (WM) using diffusion tensor imaging (DTI). We performed heritability, genetic correlation and quantitative trait loci (QTL) analyses for the whole-brain and 10 major cerebral WM tracts. Average measurements for fractional anisotropy (FA), radial (L⊥) and axial (L║) diffusivities served as quantitative traits. These analyses were done in 467 healthy individuals (182 males/285 females; average age 47.9±13.5 years; age range: 19–85 years), recruited from randomly-ascertained pedigrees of extended families. Significant heritability was observed for FA (h2=0.52±0.11; p=10−7) and L⊥ (h2=0.37±0.14; p=0.001), while L║ measurements were not significantly heritable (h2=0.09±0.12; p=0.20). Genetic correlation analysis indicated that the FA and L⊥ shared 46% of the genetic variance. Tract-wise analysis revealed a regionally diverse pattern of genetic control, which was unrelated to ontogenic factors, such as tract-wise age-of-peak FA values and rates of age-related change in FA. QTL analysis indicated linkages for whole-brain average FA (LOD=2.36) at the marker D15S816 on chromosome 15q25, and for L⊥ (LOD=2.24) near the marker D3S1754 on the chromosome 3q27. These sites have been reported to have significant co-inheritance with two psychiatric disorders (major depression and obsessive-compulsive disorder) in which patients show characteristic alterations in cerebral WM. Our findings suggest that the microstructure of cerebral white matter is under a strong genetic control and further studies in healthy as well as patients with brain-related illnesses are imperative to identify the genes that may influence cerebral white matter.

Development and aging of the healthy human brain uncinate fasciculus across the lifespan using diffusion tensor tractography

The human brain uncinate fasciculus (UF) is an important cortico-cortical white matter pathway that directly connects the frontal and temporal lobes, although there is a lack of conclusive support for its exact functional role. Using diffusion tensor tractography, we extracted the UF, calculated its volume and normalized it with respect to each subject's intracranial volume (ICV) and analyzed its corresponding DTI metrics bilaterally on a cohort of 108 right-handed children and adults aged 7–68 years. Results showed inverted U-shaped curves for fractional anisotropy (FA) with advancing age and U-shaped curves for radial and axial diffusivities reflecting white matter progressive and regressive myelination and coherence dynamics that continue into young adulthood. The mean FA values of the UF were significantly larger on the left side in children ( p = 0.05), adults ( p = 0.0012) and the entire sample ( p = 0.0002). The FA leftward asymmetry (Left > Right) is shown to be due to increased leftward asymmetry in the axial diffusivity ( p < 0.0001) and a lack of asymmetry ( p > 0.23) for the radial diffusivity. This is the first study to provide baseline normative macro and microstructural age trajectories of the human UF across the lifespan. Results of this study may lend themselves to better understanding of UF role in future behavioral and clinical studies.