Multimodal Cross-registration and Quantification of Metric Distortions in Whole Brain Histology of Marmoset using Diffeomorphic Mappings

Whole brain neuroanatomy using tera-voxel light-microscopic data sets is of much current interest. A fundamental problem in this field is the mapping of individual brain data sets to a reference space. Previous work has not rigorously quantified the distortions in brain geometry from in-vivo to ex-vivo brains due to the tissue processing, which will be important when computing properties such as local cell and process densities at the voxel level in creating reference brain maps. Further, existing approaches focus on registering uni-modal volumetric data; however, given the increasing interest in the marmoset model for neuroscience research, it is necessary to cross-register multi-modal data sets including MRIs and multiple histological series that can help address individual variations in brain architecture. Here we present a computational approach for same-subject multimodal MRI guided reconstruction of a histological series, jointly with diffeomorphic mapping to a reference atlas. We quantify the scale change during the different stages of histological processing of the brains using the Jacobian determinant of the diffeomorphic transformations involved. There are two major steps in the histology process with associated scale distortions (a) brain perfusion (b) histological sectioning and reassembly. By mapping the final image stacks to the ex-vivo post fixation MRI, we show that tape-transfer histology can be reassembled accurately into 3D volumes with a local scale change of 2.0 $\pm$ 0.4% per axis dimension. In contrast, the perfusion step, as assessed by mapping the in-vivo MRIs to the ex-vivo post fixation MRIs, shows a larger local scale change of 6.9 $\pm$ 2.1% per axis dimension. This is the first systematic quantification of the local metric distortions associated with whole-brain histological processing, and we expect that the results will generalize to other species.