Age-related topographic map of magnetic resonance diffusion metrics in neonatal brains

Abstract

Accelerated maturation of brain parenchyma close to term-equivalent age leads to rapid changes in diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) metrics of neonatal brains, which can complicate the evaluation and interpretation of these scans. In this study, we characterized the topography of age-related evolution of diffusion metrics in neonatal brains. We included 565 neonates who had MRI between 0 and 3 months of age, with no structural or signal abnormality-including 162 who had DTI scans. We analyzed the age-related changes of apparent diffusion coefficient (ADC) values throughout brain and DTI metrics (fractional anisotropy [FA] and mean diffusivity [MD]) along white matter (WM) tracts. Rate of change in ADC, FA, and MD values across 5 mm cubic voxels was calculated. There was significant reduction of ADC and MD values and increase of FA with increasing gestational age (GA) throughout neonates' brain, with the highest temporal rates in subcortical WM, corticospinal tract, cerebellar WM, and vermis. GA at birth had significant effect on ADC values in convexity cortex and corpus callosum as well as FA/MD values in corpus callosum, after correcting for GA at scan. We developed online interactive atlases depicting age-specific normative values of ADC (ages 34-46 weeks), and FA/MD (35-41 weeks). Our results show a rapid decrease in diffusivity metrics of cerebral/cerebellar WM and vermis in the first few weeks of neonatal age, likely attributable to myelination. In addition, prematurity and low GA at birth may result in lasting delay in corpus callosum myelination and cerebral cortex cellularity.

Keywords: diffusion tensor imaging; diffusion-weighted imaging; magnetic resonance imaging; neonates.

FIGURE 1

Neonate inclusion flowchart for (a) apparent diffusion coefficient (ADC) and (b) diffusion tensor imaging (DTI) metrics analysis

FIGURE 2

Histogram displaying gestational age at scan distribution for (a) diffusion‐weighted imaging (DWI) cohort and (b) diffusion tensor imaging (DTI) cohort

FIGURE 3

Tract‐based spatial statistics (TBSS) and general linear model (GLM) analysis of (a) significant increase in fractional anisotropy (FA) and (b) decline in mean diffusivity (MD) in white matter tracts, when assessing the influence of increasing gestational age (GA) at the time of scan. Green areas display the estimated white matter tract FA skeleton; red areas depict sites where high GA at scan had a significant impact on FA or MD values (p < .05).

FIGURE 4

Topology of age‐related decline in apparent diffusion coefficient (ADC) and mean diffusivity (MD) values and increase in fractional anisotropy (FA). Color bars display the slope values derived from linear regression analysis between gestational age (GA) at the scan time and diffusion metrics at each 5 mm isotropic voxel. (a) The rate of decline in ADC values with increasing GA at scan. Values are negated, with higher intensities representing faster rates of decline. Color bar values are expressed in ×10⁻⁶ mm²/s; (b) the rate of increase in FA values with increasing gestational age at the time of scan. Higher intensities represent faster rates of increase; (c) the rate of decline in MD values with increasing gestational age at the time of scan. Values are negated, with higher intensities representing faster rates of decline. Color bar values are expressed in mm²/s.

FIGURE 5

Tract‐based spatial statistics (TBSS) and general linear model (GLM) analysis showing areas of (a) higher fractional anisotropy (FA) and (b) lower mean diffusivity (MD) values with increasing gestational age (GA) at birth independent of gestational age at the time of scan. Green areas display the estimated white matter tract FA skeleton; red areas depict sites where increasing GA at birth had a significant impact on FA or MD values (p < .05).

FIGURE 6

An online normative atlas of age‐specific diffusion metrics in neonatal brains (https://www.brain‐diffusion‐atlas.com). The users can scroll through a representative apparent diffusion coefficient (ADC) scan and click on any location (5 mm isotropic voxel) to generate a plot displaying the mean ± standard deviation of ADC (currently selected), fractional anisotropy (FA) or mean diffusivity (MD) values for different gestational age at the time of scan, in the selected voxel (red square). Hovering over a plot point will depict additional information about the sample size of neonates that contributed to the measurement at that particular week of gestational age.