Characterization of brain development in the ferret via MRI

Abstract

Animal models with complex cortical development are useful for improving our understanding of the wide spectrum of neurodevelopmental challenges facing human preterm infants. MRI techniques can define both cerebral injury and alterations in cerebral development with translation between animal models and the human infant. We hypothesized that the immature ferret would display a similar sequence of brain development [both gray (GM) and white matter (WM)] to that of the preterm human infant. We describe postnatal ferret neurodevelopment with conventional and diffusion MRI. The ferret is born lissencephalic with a thin cortical plate and relatively large ventricles. Cortical folding and WM maturation take place during the first month of life. From the mid-second through the third week of postnatal life, the ferret brain undergoes a similar, though less complex, pattern of maturational changes to those observed in the human brain during the second half of gestation. GM anisotropy decreases rapidly in the first 3 wks of life, followed by an upward surge of surface folding and WM anisotropy over the next 2 wks.

Figure 1

(A) In vivo imaging apparatus with postnatal day 28 (P28) male ferret. (B) T2-weighted horizontal MR slices at the level of the centrum semi-ovale in a male ferret imaged weekly from P7 through P42.

Figure 2

(A) Photographs of fixed ferret brains from postnatal day 4 (P4) through adulthood. (B) Plot of brain weights from P4-83.

Figure 3

T2-weighted horizontal mid-caudate level MR slices of fixed ferrets from postnatal day 4 (P4) through adulthood. Note the increase in cortical folding occurring prior to myelination. The reversal in image intensity occurs at P37.

Figure 4

Diffusion anisotropy in cortical grey (+) and white (○) matter, along with the surface-folding index (■) in ferrets from postnatal day 4 through 37. Note the earliest change is a decrease in grey matter occurring prior to the increase in WM anisotropy. Surface folding parallels the change in WM anisotropy. The locations of regions of interest used for anisotropy are shown in a horizontal slice from a P8 brain.

Figure 5

(A) Curvatures are mapped on 3D cortical surfaces at postnatal day 4, 10, 17, and 24. (B) Area ratios quantify the degree of cortical packing in 10 fixed (◆) and 4 in vivo (□) ferret brains from postnatal day 4 through adulthood and postnatal day 7 through 28, respectively.

Figure 6

3D reconstructions of (A) postnatal day 4, 10, 17, and adult ferret brains and (B) human brains at 25, 30, 33, and 39 weeks gestation and adult maturation.