Iron deposition influences the measurement of water diffusion tensor in the human brain: a combined analysis of diffusion and iron-induced phase changes

This study aims to evaluate the impact of iron deposition during aging on the measurement of water diffusion in the brain. Diffusion tensor images (DTI) and phase images collected from a group of healthy adults from 23 to 72 years old were retrospectively analyzed. The axial diffusivity, radial diffusivity, mean diffusivity (MD), and fractional anisotropy (FA) in the frontal white matter and deep gray matter nuclei were calculated. The phase changes in these regions were used to estimate local iron concentration. Pearson correlation analysis was used to evaluate the age dependence of DTI metrics and iron concentration. Multiple linear regression models were then built to examine the independent effect of age and iron deposition on DTI metrics. Age-related iron deposition occurred in the putamen (r = 0.680, P < 0.001) and frontal white matter (r = 0.333, P = 0.007). In the putamen, FA increased with elevated iron concentration (P = 0.042) excluding the effect of age, and MD decreased with iron deposition with marginal statistical significance (P = 0.067). In the frontal white matter, increase in iron level was also associated with a decrease in MD and an increase in FA. Moreover, radial diffusivity was more reduced than axial diffusivity as local iron concentration increased. Iron deposition in the brain during aging decreases water diffusion and increases the degree of anisotropy. Caution is needed when using DTI metrics for diagnosis of various neurological diseases involving abnormal iron deposition.