In vivo microscopic voxel-based morphometry with a brain template to characterize strain-specific structures in the mouse brain

Keigo Hikishima,Yasuyuki Ohnishi,Yuji Komaki,Hideyuki Okano,Fumiko Seki,Hirotaka J. Okano

doi:10.1038/s41598-017-00148-1

Abstract

Hundreds of inbred mouse strains are established for use in a broad spectrum of basic research fields, including genetics, neuroscience, immunology, and cancer. Inbred mice exhibit identical intra-strain genetics and divergent inter-strain phenotypes. The cognitive and behavioral divergences must be controlled by the variances of structure and function of their brains; however, the underlying morphological features of strain-to-strain difference remain obscure. Here, in vivo microscopic magnetic resonance imaging was optimized to image the mouse brains by using an isotropic resolution of 80 μm. Next, in vivo templates were created from the data from four major inbred mouse strains (C57Bl/6, BALB/cBy, C3H/He, and DBA/2). A strain-mixed brain template was also created, and the template was then employed to establish automatic voxel-based morphometry (VBM) for the mouse brain. The VBM assessment revealed strain-specific brain morphologies concerning the gray matter volume of the four strains, with a smaller volume in the primary visual cortex for the C3H/He strain, and a smaller volume in the primary auditory cortex and field CA1 of the hippocampus for the DBA/2 strain. These findings would contribute to the basis of for understanding morphological phenotype of the inbred mouse strain and may indicate a relationship between brain morphology and strain-specific cognition and behavior.

Highlights

In vivo MRI was performed by using a seven-tesla (7-T) Biospec 70/16 MRI system equipped with actively shielded gradients at a maximum strength of 700 mT/m (Bruker Biospec GmbH, Ettlingen, Germany) and a cryogenic quadrature RF surface probe (CryoProbe; Bruker BioSpin AG, Fällanden, Switzerland)
The obtained images were de-noised with a 3D non-local means (NLM) filter implemented within Amira version 5.4 (FEI Visualization Sciences Group, Burlington, MA) for VBM analysis, which helps the segmentation process by removing noise while preserving edges[15]
We created a brain template for the mouse to support the use of automatized VBM in mouse models

Summary

Introduction

Cryogenic coils are available for mice, and in vivo measurements of the mouse brain can be realized at extremely high spatial resolution[12]. In vivo VBM of the mouse brain has been used to detect increased hippocampal volume during physical exercise[13]. We obtained in vivo T1-weighted MR images with an isotropic spatial resolution of 80 μm from four major inbred mouse strains: C57Bl/6, BALB/cBy, C3H/He, and DBA/2. We created brain templates from these strains to automatically analyze the morphology of the mouse brain. We created a strain-mixed template and used the brain template to conduct a VBM analysis of all four strains, with the goal of discriminating differences in brain morphology among them

Methods

Results

Conclusion