[S26]: Postnatal brain development in rats: In vivo diffusion tensor imaging

Recent studies on rodents suggest that neonatal hypoxia interferes with normal neurodevelopment. In general the assessment of neurodevelopment is based on histology, which provides only a snap shot information at a single time point. Based on the human studies and ex vivo animal studies, diffusion tensor imaging (DTI) allows to noninvasively following neurodevelopment in the same group of animals. Majority of DTI studies on neurodevelopment in rodents, mainly in mice, have so far been performed on excised brains. Before DTI can be utilized to study the effect of neonatal hypoxia on neurodevelopment, it is essential to investigate the potential role of DTI in normal animals in vivo. Methods: Wistar rat pups were scanned on days 0, 2, 4, 6, 8, 14, 21, and 28. All the MRI studies were performed at 7 T on Bruker MR scanner with the animals under anaesthesia. Animals were anesthetized by ventilating with isoflurane. During the scan, the animal’s body temperature was maintained by blowing temperature controlled warm air. Animal’s respiration, EKG, and body temperature were continuously monitored. High resolution dual echo fast spin echo images covering thewhole brain were acquired with a slice thickness of o.5 mm. Diffusion weighted images were acquired with diffusion encoding directions applied along 21 directions. The mean diffusivity (Dav) and fractional anisotropy (FA) were calculated from the diffusion weighted images. Results and discussion: Fig. 1 shows the MR images at the bregma level at different time points. The development of various brain structures and improved image contrast, associated with myelination can be easily appreciated on this figure. Fig. 2 shows color-coded FA maps at different time points. In this figure the intensity indicates the degree of anisotropy and the color indicates the orientation (blue: rostral-caudal; green: dorsalventral; red: left-right). As can be seen from this figure, the anisotropy in the cortex decreases with post-natal age and practically disappears by day 8. This is also true with germinal matrix. Since neurons in the developing brain migrate from germinal matrix towards the cortical plate, these results suggest ongoing neuronal migration to cortex. These are the first in vivo DTI studies of rats, starting as early as day 0 postnatal, for following the neurodevelopment. While the conventional MRI clearly shows the brain development, the FA maps, based on DTI, provide tract specific developments and ongoing neuronal migration. This information could be of considerable value in studying neurodevelopmental delays caused by various insults such as neonatal hypoxia.