Using Volumetric MRI and AMIRA to Monitor Brain Development in a Murine Model of Rett Syndrome
S.Agarwal; K.Swann; K.Wang; N.Nag; J.E.Berger-Sweeney; N.H.Kolodny.
Abstract
Rett Syndrome (RTT) is the result of a mutation in the MECP2 gene located on the X-chromosome that alters the synthesis of the MECP2 transcriptional repressor. In human RTT, MRI and pathological analysis of the brain have revealed a reduction in total brain volume, and also in regions associated with the observed behavioral deficits, such as the striatum and hippocampus. MECP2 mice, a model of RTT, exhibit RTT-like behavioral and anatomical abnormalities in the first weeks of life. We hypothesized that the Mecp2 null RTT mice would have slower rates of growth in both the whole brain and hippocampus in development, and decreased volumes in the whole brain and striatum in adulthood, compared to wildtype mice. Volumetric magnetic resonance imaging (MRI) at 9.4T using a Bruker Avance NMR spectrometer equipped with a micro-imaging accessory, was used to monitor brain development longitudinally from postnatal day 16-41. Volume measurements were taken from T2-weighted MR images by 2 independent observers in 2 trials per mouse. For single time point studies (42 days), brain and striatal volumes were estimated on Nissl-stained coronal sections, using the computer tracing program AMIRA. Results from MRI showed a decreased rate of brain growth, in addition to a reduction in whole brain volumes in the mutant mice as compared to wildtypes. In contrast, the rate of hippocampal growth was similar in the wildtype and mutant mice. Volumetric measurements of the striatum were inconclusive. However, a larger range of striatal volumes were noted in the mutant mice as compared to wildtypes. Our data suggest that volumetric measurements from MR images and Nissl-stained sections provide valuable and complementary data on whole brain and regional changes in the brains of the RTT mutant mice.
Lay Summary
It is known in classic RTT that within a few weeks of birth the child's head size may fail to increase at the normal rate, indicating failure of the brain to grow normally. In this abstract, the authors describe the use of MRI, a mouse model of RTT, and computer image reconstruction to examine rates of growth in both the whole brain, as well as individual brain regions, during development. Their results describe regional-specific alterations in rate of brain growth, as compared to non-affected mice.