Diffusion-tensor MR imaging of gray and white matter development during normal human brain maturation

Abstract

Background and purpose: Conventional MR imaging findings of human brain development are thought to result from decreasing water content, increasing macromolecular concentration, and myelination. We use diffusion-tensor MR imaging to test theoretical models that incorporate hypotheses regarding how these maturational processes influence water diffusion in developing gray and white matter.

Methods: Experimental data were derived from diffusion-tensor imaging of 167 participants, ages 31 gestational weeks to 11 postnatal years. An isotropic diffusion model was applied to the gray matter of the basal ganglia and thalamus. A model that assumes changes in the magnitude of diffusion while maintaining cylindrically symmetric anisotropy was applied to the white matter of the corpus callosum and internal capsule. Deviations of the diffusion tensor from the ideal model predictions, due to measurement noise, were estimated by using Monte Carlo simulations.

Results: Developing gray matter of the basal ganglia and developing white matter of the internal capsule and corpus callosum largely conformed to theory, with only small departures from model predictions in older children. However, data from the thalamus substantially diverged from predicted values, with progressively larger deviations from the model with increasing participant age.

Conclusion: Changes in water diffusion during maturation of central gray and white matter structures can largely be explained by theoretical models incorporating simple assumptions regarding the influence of brain water content and myelination, although deviations from theory increase as the brain matures. Diffusion-tensor MR imaging is a powerful method for studying the process of brain development, with both scientific and clinical applications.

Fig 1.

Region of interest placement is illustrated on a transverse diffusion anisotropy (Aσ) image obtained through the level of the basal ganglia in a 1-year-old child. Diffusion anisotropy is computed from a single shot echo-planar diffusion-tensor sequence: 3000/97.4/1 (TR/TE/number of excitations), using four tetrahedrally oriented diffusion gradients (b = 1012.4 s/mm²) and three orthogonally oriented diffusion gradients (b = 337.5 s/mm²). Regions of interest in gray matter are marked as white ellipses, and regions of interest in white matter are marked as black ellipses. Values from the left and right regions of interest were averaged. 1, head of the caudate nucleus; 2, lentiform nucleus; 3, posterior limb of the internal capsule; 4, thalamus; 5, splenium of the corpus callosum.

Fig 2.

Decrease in the eigenvalues of the diffusion tensor during normal brain maturation is illustrated in five participants ranging in age from 31 gestational weeks (preterm) to 6 postnatal years. Diffusion-tensor imaging parameters are as in Figure 1, except for the preterm neonate, for whom the parameters were 3000/106/1 with four tetrahedrally oriented diffusion gradients (b = 800 s/mm²) and three orthogonally oriented diffusion gradients (b = 340 s/mm²). All images are transverse sections obtained at the level of the basal ganglia. All images are displayed with identical window and level settings to allow direct comparison of signal intensity across participants. The eigenvalues are rotationally invariant measures of the rate of water diffusion along each of the three principal axes of the diffusion tensor at each MR imaging voxel. λ_min (top row) is the eigenvalue with the smallest magnitude, λ_int (middle row) has intermediate values, and λ_max (bottom row) has the greatest magnitude.

Fig 3.

The signal-to-noise ratio of diffusion-tensor imaging decreases with brain maturation. A, Noise in the diffusion-weighted images is age-independent. In 20 participants, the noise is calculated as the SD of pixel values in an air-filled region of interest outside the brain in the b = 337.5 s/mm² diffusion-weighted images (see Methods). The postconceptional age of each participant is the estimated gestational age added to the postnatal age. The data are fit with linear regression. The Pearson correlation coefficient of the noise with postconceptional age is 0.23, which is not statistically significant (P > .3). B, SNR in diffusion-weighted imaging declines steeply during the first 2 years of postnatal life in the white matter of the posterior limb of the internal capsule. SNR is the quotient of signal intensity divided by noise. The signal intensity is obtained from regions of interest within the brain on b = 337.5 s/mm² diffusion-weighted images. The data are fit with a function (equation 8 in Methods) that defines the theoretical relationship between SNR and participant age. Vertical dashed line indicates the age of normal term birth: 40 gestational weeks. C, SNR in diffusion-weighted imaging declines steeply during the first 2 years of postnatal life in the gray matter of the lentiform nucleus. Vertical dashed line indicates the age of normal term birth: 40 gestational weeks.

Fig 4.

Maturational decreases of the three diffusion tensor eigenvalues (λ_max, λ_int, λ_min) in the gray matter of the lentiform nucleus and the gray matter of the head of the caudate nucleus for 161 participants of postconceptional ages 7 months to 12 years. Vertical dashed line indicates age of normal term birth: 40 gestational weeks. Solid lines through data are theoretical predictions for the age-varying values of λ_max (top line), λ_int (middle line), and λ_min (bottom line) from Monte Carlo simulation of a spherical diffusion model, to which the age-dependent parameters D̄ and SNR are given as input (see Methods for details of the theoretical model). A, Gray matter of the lentiform nucleus. Values of λ_max (open inverted triangles), λ_int (closed circles), and λ_min (open squares) are in 10⁻³ mm²/s. B, Gray matter of the lentiform nucleus. Each eigenvalue is expressed in terms of its fraction of the trace of the diffusion tensor Trace(D), where Trace(D) is the sum of the three eigenvalues. C, Gray matter of the head of the caudate nucleus. Values of λ_max (open inverted triangles), λ_int (closed circles), and λ_min (open squares) are in 10⁻³ mm²/s. D, Gray matter of the head of the caudate nucleus. Each eigenvalue is expressed in terms of its fraction of the trace of the diffusion tensor Trace(D), where Trace(D) is the sum of the three eigenvalues.

Fig 5.

Maturational decreases of the three diffusion tensor eigenvalues (λ_max, λ_int, λ_min) in the white matter of the splenium of the corpus callosum and the white matter of the posterior limb of the internal capsule for 161 participants of postconceptional ages 7 months to 12 years. Vertical dashed line indicates age of normal term birth: 40 gestational weeks. Dashed line through the λ_max data represents an empirical fit to a biexponential function. Solid lines through λ_int data (top solid line) and λ_min data (bottom solid line) are theoretical predictions for their age-varying values from Monte Carlo simulation of a cylindrical diffusion model, in which the age-dependent parameters D̄, λ_max, and SNR are given as input (see Methods for details of the theoretical model). A, White matter of the splenium of the corpus callosum. Values of λ_max (open inverted triangles), λ_int (closed circles), and λ_min (open squares) are in 10⁻³ mm²/s. B, White matter of the splenium of the corpus callosum. Each eigenvalue is expressed in terms of its fraction of the trace of the diffusion tensor Trace(D), where Trace(D) is the sum of the three eigenvalues. C, White matter of the posterior limb of the internal capsule. Values of λ_max (open inverted triangles), λ_int (closed circles), and λ_min (open squares) are in 10⁻³ mm²/s. D, White matter of the posterior limb of the internal capsule. Each eigenvalue is expressed in terms of its fraction of the trace of the diffusion tensor Trace(D), where Trace(D) is the sum of the three eigenvalues.

Fig 6.

Maturational decreases of the three diffusion tensor eigenvalues (λ_max, λ_int, λ_min) in the thalamus for 161 participants of postconceptional ages 7 months to 12 years. Vertical dashed line indicates age of normal term birth: 40 gestational weeks. Solid lines through data are theoretical predictions for the age-varying values of λ_max (top line), λ_int (middle line), and λ_min (bottom line) from Monte Carlo simulation of a spherical diffusion model, to which the age-dependent parameters D̄ and SNR are given as input (see Methods for details of the theoretical model). A, Values of λ_max (open inverted triangles), λ_int (closed circles), and λ_min (open squares) are in 10⁻³ mm²/s. B, Each eigenvalue is expressed in terms of its fraction of the trace of the diffusion tensor Trace(D), where Trace(D) is the sum of the three eigenvalues.