A MULTIMODAL MRI FRAMEWORK FOR CROSS-SPECIES COMPARISON OF C57BL6 MOUSE AND SPRAGUE DAWLEY RAT BRAIN ORGANIZATION

Mice and rats are the most used species in preclinical neuroscience models. However, the choice between them is often based on tradition in a (sub)field, rather than systematic consideration of brain organization. Informed species selection requires direct comparison of brain architectures. This comparison remains scarce despite the increasing availability of comparable neuroimaging data from both species. To address this, we developed standardised multimodal brain MRI templates of the C57BL6 mouse and Sprague Dawley rat and constructed a mouse-rat template to serve as a common denominator for “like-for-like” comparison. We applied a Multimodal Registration Framework (MMORF), a newly developed tool that performs simultaneous iterative registration of scalar (T2) and diffusion (tensor) MRI data. Integrating both modalities maximizes complementary anatomical and microstructural information from both modalities to improve registration accuracy. The templates show sharp structural boundaries in T2, clear orientation preferences in DTI, and brain shapes in the mid-spaces of the animals, making them excellent targets for multimodal analysis across species. By registering both species to the same template, we perform cross species comparison using the Jacobian determinants, which quantify local deformations after accounting for global size differences. Preliminary results reveal regional differences across brains of mice and rats, with particularly notable divergence in hippocampal region CA3. This work establishes a multimodal MRI framework for cross-species brain comparison and demonstrates the utility of MMORF for high resolution template construction. Together, this approach provides a quantitative basis for interpreting species-specific brain organization and supports informed choices between rodent models to enhance translational relevance.