White Matter Changes of Neurite Density and Fiber Orientation Dispersion during Human Brain Maturation

Abstract

Diffusion tensor imaging (DTI) studies of human brain development have consistently shown widespread, but nonlinear increases in white matter anisotropy through childhood, adolescence, and into adulthood. However, despite its sensitivity to changes in tissue microstructure, DTI lacks the specificity to disentangle distinct microstructural features of white and gray matter. Neurite orientation dispersion and density imaging (NODDI) is a recently proposed multi-compartment biophysical model of brain microstructure that can estimate non-collinear properties of white matter, such as neurite orientation dispersion index (ODI) and neurite density index (NDI). In this study, we apply NODDI to 66 healthy controls aged 7–63 years to investigate changes of ODI and NDI with brain maturation, with comparison to standard DTI metrics. Using both region-of-interest and voxel-wise analyses, we find that NDI exhibits striking increases over the studied age range following a logarithmic growth pattern, while ODI rises following an exponential growth pattern. This novel finding is consistent with well-established age-related changes of FA over the lifespan that show growth during childhood and adolescence, plateau during early adulthood, and accelerating decay after the fourth decade of life. Our results suggest that the rise of FA during the first two decades of life is dominated by increasing NDI, while the fall in FA after the fourth decade is driven by the exponential rise of ODI that overcomes the slower increases of NDI. Using partial least squares regression, we further demonstrate that NODDI better predicts chronological age than DTI. Finally, we show excellent test—retest reliability of NODDI metrics, with coefficients of variation below 5% in all measured regions of interest. Our results support the conclusion that NODDI reveals biologically specific characteristics of brain development that are more closely linked to the microstructural features of white matter than are the empirical metrics provided by DTI.

Neurite density is reduced in the presymptomatic phase ofC9orf72disease

“…However, the reliability of NODDI has been assessed in previous studies 38 39. NODDI metrics were shown to have excellent reproducibility with coefficients of variation below 5% in all measured ROIs and even below 3% in the vast majority of regions 39. Furthermore, the reproducibility of NODDI metrics was shown to be comparable with that of conventional DTI 38.…”

Age effects and sex differences in human brain white matter of young to middle-aged adults: A DTI, NODDI, and q-space study

“…The age-related changes of ICVF have mixed results in previous studies. Increases of ICVF with age in white matter were found using a linear regression model in (Billiet et al 2015) and using a logarithmic growth model in (Chang et al 2015). Mixed increases and decreases of ICVF with age were found using a quadratic model in (Billiet et al 2015).…”

“…Thus, NODDI indices are potentially less ambiguous than DTI in the interpretation of diffusion-weighted microstructural characterization with increased specificity in clinical studies of the human brain. The NODDI model has been applied in studies of white matter changes in aging relative studies (Kunz et al 2014, Billiet et al 2015, Chang et al 2015, Nazeri et al 2015), and other neurologic disorders (Adluru et al 2014, Billiet et al 2014, Winston et al 2014, Timmers et al 2015). …”

Local volume fraction distributions of axons, astrocytes, and myelin in deep subcortical white matter

“…The robustness of the full orientation dispersion assumption was also tested. We simulated cylinders which were not fully dispersed but with dispersion values typical of DWM (Chang et al, 2015). Results show that errors were low even in that scenario.…”