Quantitative cortical mapping of fractional anisotropy in developing rat brains

Abstract

Cortical development is associated with a series of events that involve axon and dendrite growth and synaptic formation. Although these developmental processes have been investigated in detail with histology, three-dimensional and quantitative imaging methods for rodent brains may be useful for genetic and pharmacological studies in which cortical developmental abnormalities are suspected. It has been shown that diffusion tensor imaging (DTI) can delineate the columnar organization of the fetal and early neonatal cortex based on a high degree of diffusion anisotropy along the columnar structures. This anisotropy is known to decrease during brain development. In this study, we applied DTI to developing rat brains at five developmental stages, postnatal days 0, 3, 7, 11 and 19, and used diffusion anisotropy as an index to characterize the structural change. Statistical analysis reveals four distinctive cortical areas that demonstrate a characteristic time course of anisotropy loss. This method may provide a means to delineate specific cortical areas and a quantitative method to detect abnormalities in cortical development in rodent pathological models.

Figure 1.

A three-dimensional view of a P19 rat brain and locations of coronal slices for cortical FA measurements.

Figure 2.

FA maps and color-coded orientation maps of developing rat brains at 1/5L (a), 2/5L (b), 3/5L (c), and 3/4L (d) slices defined in Figure 1. FA and color-coded maps are shown for the right and left hemispheres of the P0, P3, P7, P11, and P19 rat brains. The FA map of a P19 brain is enlarged, and the anatomical definition from the Paxinos atlas is superimposed. Yellow dots indicate the locations of sampling points for cortical FA measurements. The inset in a illustrates the three segments defined in this study for FA measurements. For the color-coded maps, red, green, and blue colors indicate structures aligning along left–right, anterior–posterior, and superior–inferior orientations, respectively.

Figure 3.

FA mapping of the cortical surfaces of rat brains from P0 to P19. The color represents FA values as shown in the color bar. The sampling points used in Figure 4 are also labeled on the surfaces.

Figure 4.

FA measurement results from various cortical regions during the P0–P19 period. The FA values averaged over all sixteen measurement points are shown as reference curves, with error bars indicating SDs. a, The cingulate (C1, C2) and the prelimbic (C3) cortices; b, the insula cortex (I1, I2); c, the somatosensory cortex (S1–S4); d, the motor cortex (M1, M2); e, the visual cortex (V1–V3); and f, the auditory cortex (A1, A2).

Figure 5.

Time-dependent changes of the radial (λ₁) and tangential [(λ₂ + λ₃)/2] diffusivity of the prelimbic (C3) and somatosensory (S2) cortices.