Semi-automated registration-based anatomical labelling, voxel based morphometry and cortical thickness mapping of the mouse brain

Background: Morphoanatomical MRI methods have recently begun to be applied in the mouse. However, substantial differences in the anatomical organisation of human and rodent brain prevent a straightforward extension of clinical neuroimaging tools to mouse brain imaging. As a result, the vast majority of the published approaches rely on tailored routines that address single morphoanatomical readouts and typically lack a sufficiently-detailed description of the complex workflow required to process images and quantify structural alterations. New method: Here we provide a detailed description of semi-automated registration-based procedures for voxel based morphometry, cortical thickness estimation and automated anatomical labelling of the mouse brain. The approach relies on the sequential use of advanced image processing tools offered by ANTs, a flexible open source toolkit freely available to the scientific community. Results: To illustrate our procedures, we described their application to quantify morphological alterations in socially-impaired BTBR mice with respect to normosocial C57BL/6J controls, a comparison recently described by us and other research groups. We show that the approach can reliably detect both focal and large-scale grey matter alterations using complementary readouts. Comparison with existing methods: No detailed operational workflows for mouse imaging are available for direct comparison with our methods. However, empirical assessment of the mapped inter-strain differences is in good agreement with the findings of other groups using analogous approaches. Conclusion: The detailed operational workflows described here are expected to help the implementation of rodent morphoanatomical methods by non-expert users, and ultimately promote the use of these tools across the preclinical neuroimaging community.