title: Semi-automated registration-based anatomical labelling, voxel based morphometry and cortical thickness mapping of the mouse brain.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Functional Neuroimaging Laboratory, Center for Neuroscience and Cognitive Systems, Istituto Italiano di Tecnologia, Rovereto (TN), Italy; Centro Interdipartimentale Mente/Cervello (CIMeC)-University of Trento, Rovereto (TN), Italy. Electronic address: marco.pagani@iit.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Pagani
authors.affiliation: Functional Neuroimaging Laboratory, Center for Neuroscience and Cognitive Systems, Istituto Italiano di Tecnologia, Rovereto (TN), Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Damiano
authors.affiliation: Functional Neuroimaging Laboratory, Center for Neuroscience and Cognitive Systems, Istituto Italiano di Tecnologia, Rovereto (TN), Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Galbusera
authors.affiliation: Institute for Digital Communications, School of Engineering, University of Edinburgh, Thomas Bayes Road, EH9 3FG, Edinburgh, UK; IMT Institute for Advanced Studies, Lucca (LU), Italy.
authors.forename: Sotirios A
authors.initials: SA
authors.lastname: Tsaftaris
authors.affiliation: Functional Neuroimaging Laboratory, Center for Neuroscience and Cognitive Systems, Istituto Italiano di Tecnologia, Rovereto (TN), Italy. Electronic address: alessandro.gozzi@iit.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gozzi
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging*; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009929:Organ Size; D010363:Pattern Recognition, Automated / Q000379:methods*
keywords: Anatomical labelling; Cortical thickness; MRI; Mouse brain; Voxel based morphometry