Joint analysis of three-dimensional anatomical and functional data considering the cerebral post mortem imaging in rodents

The recent development of dedicated small animal anatomical (MRI) and functional (micro-PET) scanners has opened up the possibility of performing repeated functional in vivo studies in the same animal as the longitudinal follow-up of cerebral glucose metabolism. However, these systems still suffer technical limitations including a limited sensitivity and a reduced spatial resolution. Hence, autoradiography and histological studies remain the reference and widely used techniques for biological studies in small animals. The major disadvantage of these post mortem imaging techniques is that they require brain tissue sectioning, entailing the production of large numbers (up to several hundreds) of serial sections and the inherent loss of three-dimensional (3D) spatial consistency. The first step towards improving the analysis of this post mortem information was the development of reliable, automated procedures for the 3D reconstruction of the whole brain sections. We first developed an optimized data acquisition from large numbers of post mortem data (2D sections and block-face photographs). Then, we proposed different strategies of 3D reconstruction of the corresponding volumes. We also addressed the histological to autoradiographic sections and to block-face photographs co-registration problem (the photographic volume is intrinsically spatially consistent). These developments were essential for the 3D reconstruction but also enabled the evaluation of different methods of functional data analysis, from the most straightforward (manual delineation of regions of interest) to the most automated (Statistical Parametric Mapping-like approaches for group analysis). Two biological applications were carried out: visual stimulation in rats and cerebral metabolism in a transgenic mouse model of Alzheimer's disease. One perspective of this work is to match reconstructed post mortem data with in vivo images of the same animal. (author)