Population based MRI and DTI templates of the adult ferret brain and tools for voxelwise analysis

- The ferret is a human-relevant species for studying the brain with a folded cortical surface and high white matter volume as well as body dimensions that enable neuroimaging studies using pre-clinical MRI scanners.
- In-vivo and ex-vivo MRI and DTI templates were built for the ferret brain using optimized template building tools including diffeomorphic and diffusion tensor based registration.
- The brain volume was parcellated into regions of interest using a combination of automatic and manual segmentation with reference to known ferret neuroanatomy.
- Several demonstrations are presented to illustrate voxelwise and template based analysis approaches that may be advantageous for use in neuroimaging studies.
- The templates and masks are available as downloadable files and were also used to generate a web-based viewer for browsing the ferret brain images and maps as well as for open annotation of information about brain regions or contribution of images.

Non-invasive imaging has the potential to play a crucial role in the characterization and translation of experimental animal models to investigate human brain development and disorders, especially when employed to study animal models that more accurately represent features of human neuroanatomy. The purpose of this study was to build and make available MRI and DTI templates and analysis tools for the ferret brain as the ferret is a well-suited species for pre-clinical MRI studies with folded cortical surface, relatively high white matter volume and body dimensions that allow imaging with pre-clinical MRI scanners. Four ferret brain templates were built in this study - in-vivo MRI and DTI and ex-vivo MRI and DTI - using brain images across many ferrets and region of interest (ROI) masks corresponding to established ferret neuroanatomy were generated by semi-automatic and manual segmentation. The templates and ROI masks were used to create a web-based ferret brain viewing software for browsing the MRI and DTI volumes with annotations based on the ROI masks. A second objective of this study was to provide a careful description of the imaging methods used for acquisition, processing, registration and template building and to demonstrate several voxelwise analysis methods including Jacobian analysis of morphometry differences between the female and male brain and bias-free identification of DTI abnormalities in an injured ferret brain. The templates, tools and methodological optimization presented in this study are intended to advance non-invasive imaging approaches for human-similar animal species that will enable the use of pre-clinical MRI studies for understanding and treating brain disorders.