Spatiotemporal changes in diffusivity and anisotropy in fetal brain tractography

Abstract

Population averaged diffusion atlases can be utilized to characterize complex microstructural changes with less bias than data from individual subjects. In this study, a fetal diffusion tensor imaging (DTI) atlas was used to investigate tract-based changes in anisotropy and diffusivity in vivo from 23 to 38 weeks of gestational age (GA). Healthy pregnant volunteers with typically developing fetuses were imaged at 3 T. Acquisition included structural images processed with a super-resolution algorithm and DTI images processed with a motion-tracked slice-to-volume registration algorithm. The DTI from individual subjects were used to generate 16 templates, each specific to a week of GA; this was accomplished by means of a tensor-to-tensor diffeomorphic deformable registration method integrated with kernel regression in age. Deterministic tractography was performed to outline the forceps major, forceps minor, bilateral corticospinal tracts (CST), bilateral inferior fronto-occipital fasciculus (IFOF), bilateral inferior longitudinal fasciculus (ILF), and bilateral uncinate fasciculus (UF). The mean fractional anisotropy (FA) and mean diffusivity (MD) was recorded for all tracts. For a subset of tracts (forceps major, CST, and IFOF) we manually divided the tractograms into anatomy conforming segments to evaluate within-tract changes. We found tract-specific, nonlinear, age related changes in FA and MD. Early in gestation, these trends appear to be dominated by cytoarchitectonic changes in the transient white matter fetal zones while later in gestation, trends conforming to the progression of myelination were observed. We also observed significant (local) heterogeneity in within-tract developmental trajectories for the CST, IFOF, and forceps major.

Keywords: anisotropy; atlas; diffusion; fetal; myelination; tractography.

FIGURE 1

Longitudinal tractography of the fetal DTI templates. Deterministic tractography on selected GA templates; tracts are superimposed on the corresponding FA map. The outlined tracts include forceps major (F major), forceps minor (F minor), corticospinal tract (CST), inferior fronto‐occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), and uncinate fasciculus (UF). GW, gestational weeks

FIGURE 2

Whole‐tract analysis of commissural tracts. GA‐related changes in FA and MD in the forceps major (a,c) and forceps minor (b,d). Regression model using linear terms (a) and quadratic terms (b–d) are shown. Rate of change and statistical significance are shown in Table 2

FIGURE 3

Whole‐tract analysis of projection tracts. GA‐related changes in FA and MD in the CST. Regression models are shown, rate of change and significance is shown in Table 2. Laterality was included in the regression model, but was not statistically significant (p >.05)

FIGURE 4

Whole‐tract analysis of association tracts. GA‐related changes in FA and MD in the inferior fronto‐occipital fasciculus (IFOF) (a,d), inferior longitudinal fasciculus (ILF) (b,e), and uncinate fasciculus (UF) (c,f). Regression models are shown, rate of change and significance are shown in Table 2. Laterality was included in the regression model but was not statistically significant (p >.05) for any tract

FIGURE 5

Within‐tract analysis of forceps major. Microstructural changes in the central (green) and peripheral (red) segments of the forceps major. The central segment shows gestational age (GA)‐related increase in FA whereas the peripheral segment shows a decrease in FA. The MD of both segments shows a similar pattern, with a peak around 30 weeks of gestational age (GA). Rate of change and significance are shown in Table 3

FIGURE 6

Within‐tract analysis of CST. Heterogeneity in development of the CST. (a) Microstructural changes in the superior (blue), mid (green), and inferior (red) segments of the CST. The superior segment shows nadir in FA at approximately 30 weeks of gestational age (GA). The mid segment shows linear GA‐related increase in FA and decrease in MD. The inferior segment shows an increase in FA early in the second trimester with lower rate of change later in gestation. Rates of change and significance are shown in Table 3. (b) Heat maps of FA and MD at 31 and 38 weeks of GA show within tract heterogeneity in progression of microstructural changes

FIGURE 7

Within‐tract analysis of IFOF. Microstructural changes in the rostral (blue), mid (green), and caudal (red) segments of the IFOF. The rostral and caudal segments show a decrease in FA at ≤30 weeks of GA probably as a result of expansion of the subplate. After >30 weeks of GA, the caudal segment shows GA‐related increase in FA that exceeds that of the rostral segment, representing the expected progression of myelination. The mid segment shows a continuous GA‐related increase in FA as it is not influenced by changes in transient telencephalic zones. For all segments, the MD shows central peak, although the trajectories are slightly different. Rates of change and significance are shown in Table 3