At the beginning, these methods have been developed to analyse autoradiographic data in 3D using complementary histological information. The 3D reconstruction of biological volumes arising from several histological and/or autoradiographic sections enables to take advantage of the high resolution of ex vivo autoradiography as well as of the diversity of available histological stainings.
The analysis of autoradiographic data, 3D reconstructed or not, remains traditionally limited to conventional region of interest (ROI)-based analysis. Although the users have the corresponding histological stained sections available to consider anatomical information, the delineation of ROI(s) to be analyzed is usually directly performed on the autoradiographic sections, which may be inaccurate and subject to observer bias. To overcome this limitation, BrainRAT enables to perform multimodal co-registration between slices or 3D reconstructed volumes.
Recent studies have highlighted the ability of voxel-wise statistical analysis to deal with 3D reconstructed autoradiographic volumes for group comparisons. This automated, exploratory, whole-brain approach can be used to analyze local functional differences between population groups without the need for prior assumptions. BrainRAT provides useful tools to carry out such studies in optimal conditions (optimized digitization, 3D reconstruction algorithms, activity conversion and intensity normalization procedures).
These methods have been applied to Nissl stained (cresyl violet) sections and [14C]-2DG autoradiography, and intensively validated both in rat and mouse brain. They have been also successfully tested on other post mortem imaging modalities such as immunohistochemistry, fluorescence, etc. They could now be extended to various biological applications (activation models, morphology, lesion extension, development, etc.) and to domains of application including pathological and therapeutic studies involving animal models of various brain diseases (neurodegenerative diseases, ischemia, and cancer).