Cerebral White Matter Maturation Patterns in Preterm Infants: An MRI T2 Relaxation Anisotropy and Diffusion Tensor Imaging Study

Abstract

Background and purpose: Preterm birth is associated with worse neurodevelopmental outcome, but brain maturation in preterm infants is poorly characterized with standard methods. We evaluated white matter (WM) of infant brains at term-equivalent age, as a function of gestational age at birth, using multimodal magnetic resonance imaging (MRI).

Methods: Infants born very preterm (<32 weeks gestation) and late preterm (33-36 weeks gestation) were scanned at 3 T at term-equivalent age using diffusion tensor imaging (DTI) and T2 relaxometry. MRI data were analyzed using tract-based spatial statistics, and anisotropy of T2 relaxation was also determined. Principal component analysis and linear discriminant analysis were applied to seek the variables best distinguishing very preterm and late preterm groups.

Results: Across widespread regions of WM, T2 is longer in very preterm infants than in late preterm ones. These effects are more prevalent in regions of WM that myelinate earlier and faster. Similar effects are obtained from DTI, showing that fractional anisotropy (FA) is lower and radial diffusivity higher in the very preterm group, with a bias toward earlier myelinating regions. Discriminant analysis shows high sensitivity and specificity of combined T2 relaxometry and DTI for the detection of a distinct WM development pathway in very preterm infants. T2 relaxation is anisotropic, depending on the angle between WM fiber and magnetic field, and this effect is modulated by FA.

Conclusions: Combined T2 relaxometry and DTI characterizes specific patterns of retarded WM maturation, at term equivalent age, in infants born very preterm relative to late preterm.

Keywords: MRI; T2 relaxometry; diffusion tensor imaging; preterm birth; white matter.

Figure 1

Boxplots of TBSS-derived medians for DTI scalars and T2 across the whole cohort. The graphs are sorted by descending FA within each myelogenesis group (indicated by color) are as follows: A = myelination detectable at term age; B1 = no myelination detectable at term age, fast rate of myelination after birth; B2 = no myelination detectable at term age, intermediate rate of myelination after birth; B3/other = no myelination detectable at term age, slow rate of myelination after birth. Abbreviations used: FA = fractional anisotropy; MD = mead diffusivity. See Table 2 for white matter tract abbreviations.

Figure 2

Clusters in which VP infants differ from LP MCDA twins. Row a: FA(VP) < FA(LP), Row b: T2(VP) > FA(LP), Row c: MD(VP) > MD(LP), Panel 3: RD(VP) > RD(LP). VP = very pre-term, LP = late pre-term MCDA twins. Colored voxels belong to clusters identified using threshold-free cluster enhancement at the p < 0.05 level using 500 permutations. Green marks the TBSS-demarcated WM skeleton. Results are shown on the JHU-Neonate FA template. Abbreviations used: MCDA = monochorionic diamniotic twin; MD = mean diffusivity; RD = radial diffusivity; WM = white matter; FA = fractional anisotropy.

Figure 3

Number of voxels in each WM tract separating the VP from LP groups at term-equivalent age. Abbreviations used: VP = very preterm; LP = late preterm; WM = white matter; RD = radial diffusivity; FA = fractional anisotropy. See Table 2 for WM tract abbreviations

Figure 4

PCA and LDA of tract-wise median DTI scalars and T2 in the TBSS-positive ROI. Panel a shows PCA, reduced to 2 dimensions, with the original variables labelled as projections. The projections are labelled (and in solid color) if their projection normal to the LDA hyperplane is > 0.15, which implies that more than 15% of the variance in that variable is accounted for by group. Text labels are colored by myelogenesis group. Panel b shows the PCA with data points labelled by group, as well as the LDA hyperplane as a solid line. Abbreviations used: PCA = principal component analysis; LDA = linear discriminant analysis; VP = very preterm; LP = late preterm. See Table 2 for WM tract abbreviations.

Figure 5

T2 anisotropy in the term-equivalent infant brain. Panels a and b show surfaces of T2 against FA and the fibre-to-field angle obtained from DTI, with each plotted value of the opaque surface being the average value in the corresponding 2D bin range. Magenta points are the fit of Eq. 1. The VP and LP groups are plotted in a and b respectively. Panels c-f show, respectively, the fitted values at each FA bin range of the amplitude of anisotropy A, T2^Δ, T2^|| and T2^per. Abbreviations used: VP = very preterm; LP = late preterm; FA = fractional anisotropy.