Microstructural Development of Human Newborn Cerebral White Matter Assessed in Vivo by Diffusion Tensor Magnetic Resonance Imaging

Abstract

Alterations of the architecture of cerebral white matter in the developing human brain can affect cortical development and result in functional disabilities. A line scan diffusion-weighted magnetic resonance imaging (MRI) sequence with diffusion tensor analysis was applied to measure the apparent diffusion coefficient, to calculate relative anisotropy, and to delineate three-dimensional fiber architecture in cerebral white matter in preterm (n = 17) and full-term infants (n = 7). To assess effects of prematurity on cerebral white matter development, early gestation preterm infants (n = 10) were studied a second time at term. In the central white matter the mean apparent diffusion coefficient at 28 wk was high, 1.8 microm2/ms, and decreased toward term to 1.2 microm2/ms. In the posterior limb of the internal capsule, the mean apparent diffusion coefficients at both times were similar (1.2 versus 1.1 microm2/ms). Relative anisotropy was higher the closer birth was to term with greater absolute values in the internal capsule than in the central white matter. Preterm infants at term showed higher mean diffusion coefficients in the central white matter (1.4 +/- 0.24 versus 1.15 +/- 0.09 microm2/ms, p = 0.016) and lower relative anisotropy in both areas compared with full-term infants (white matter, 10.9 +/- 0.6 versus 22.9 +/- 3.0%, p = 0.001; internal capsule, 24.0 +/- 4.44 versus 33.1 +/- 0.6% p = 0.006). Nonmyelinated fibers in the corpus callosum were visible by diffusion tensor MRI as early as 28 wk; full-term and preterm infants at term showed marked differences in white matter fiber organization. The data indicate that quantitative assessment of water diffusion by diffusion tensor MRI provides insight into microstructural development in cerebral white matter in living infants.

Diffusion MR imaging characteristics of the developing primate brain

“…Two or more brains have been investigated at all gestational ages, and in all cases the inter-animal variability is less than inter-age-group variability (data not shown). The diminishing gray-white contrast of D av maps with increasing gestational age is identical to the observations for the human infant (Huppi et al, 1998;Neil et al, 1998). Furthermore, the principal axis of diffusion in cerebral cortex is oriented radially, as has been shown for developing human cortex (McKinstry et al, 2002).…”

“…Diffusion MRI, in particular, is being applied to assess brain development (Huppi et al, 1998;Neil et al, 2002;Partridge et al, 2004;Rutherford et al, 2004). Diffusion MRI provides information about the directional dependence of water displacements due to diffusion.…”

“…Thus, water diffusion in myelinated white matter is anisotropic. The regional changes in diffusion anisotropy within the developing white matter of the newborn brain have been well appreciated for some time (Huppi et al, 1998;Neil et al, 1998).…”

“…Thus, water diffusion in myelinated white matter is anisotropic. The regional changes in diffusion anisotropy within the developing white matter of the newborn brain have been well appreciated for some time (Huppi et al, 1998;Neil et al, 1998).Diffusion anisotropy has also been described within cerebral cortical gray matter in the developing human brain. Anisotropy is high early in development, with the preferred displacement direction oriented radially with respect to the cortical surface (Maas et al, 2004;Mori et al, 2001;Neil et al, 1998).…”

Multimodal image analysis of clinical influences on preterm brain development

“…In previous studies of similar cohorts, we and others have observed decreased frontotemporal volume, increased thalamic diffusivity, and decreased FA in the central white matter with increasing prematurity 7, 10, 12, 35. Here, we show these changes are coupled, independent of age at scan and total intracranial volume, and exacerbated by comorbid markers of neonatal sickness.…”