Multimodal cross‐registration and quantification of metric distortions in marmoset whole brain histology using diffeomorphic mappings

• Published in: Journal of comparative neurology (1911) 2021-02, Vol.529 (2), p.281-295
• Main Authors: Lee, Brian C., Lin, Meng K., Fu, Yan, Hata, Junichi, Miller, Michael I., Mitra, Partha P.
• Format: Article
• Language: English
• Subjects: Anatomy; Animals; Brain - anatomy & histology; Brain - diagnostic imaging; Brain architecture; brain architecture project (RRID:SCR_004283); Brain mapping; Brain Mapping - methods; Callithrix - anatomy & histology; Callithrix jacchus (RRID:NCBITaxon_9483); Computational neuroscience; Databases, Factual; Datasets; diffeomorphic mapping; digital brain atlas of the common marmoset (RRID:SCR_005069); Imaging, Three-Dimensional - methods; Imaging, Three-Dimensional - standards; large deformation diffeomorphic metric mapping (RRID:SCR_009590); Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Magnetic Resonance Imaging - standards; multimodal histology reconstruction; Nervous system; Perfusion; tissue distortion quantification
• ISSN: 0021-9967; 1096-9861
• DOI: 10.1002/cne.24946

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 in‐vivo to ex‐vivo distortions in brain geometry from tissue processing. Further, existing approaches focus on registering unimodal volumetric data; however, given the increasing interest in the marmoset model for neuroscience research and the importance of addressing individual brain architecture variations, new algorithms are necessary to cross‐register multimodal data sets including MRIs and multiple histological series. Here we present a computational approach for same‐subject multimodal MRI‐guided reconstruction of a series of consecutive histological sections, jointly with diffeomorphic mapping to a reference atlas. We quantify the scale change during different stages of brain histological processing using the Jacobian determinant of the diffeomorphic transformations involved. By mapping the final image stacks to the ex‐vivo post‐fixation MRI, we show that (a) tape‐transfer assisted histological sections can be reassembled accurately into 3D volumes with a local scale change of 2.0 ± 0.4% per axis dimension; in contrast, (b) tissue perfusion/fixation as assessed by mapping the in‐vivo MRIs to the ex‐vivo post fixation MRIs shows a larger median absolute scale change of 6.9 ± 2.1% per axis dimension. This is the first systematic quantification of local metric distortions associated with whole‐brain histological processing, and we expect that the results will generalize to other species. These local scale changes will be important for computing local properties to create reference brain maps. In this article, we present methods for guided volume reconstruction of serial section animal brain histology with an evaluation of registration accuracy. Using methods derived from diffeomorphometry, we quantify the 3D distortion caused by two steps in the histology tissue processing pipeline: (a) reassembly of tape‐transfer assisted histology sections and (b) tissue perfusion and fixation.