Frontiers in Neuroanatomy (May 2016)
3D Reconstructed Cyto-, Muscarinic M2 Receptor, and Fiber Architecture of the Rat Brain Registered to the Waxholm Space Atlas
Abstract
High-resolution multiscale and multimodal 3D models of the brain are essential tools tounderstand its complex structural and functional organization. Neuroimaging techniquesaddressing different aspects of brain organization should be integrated in a reference spaceto enable topographically correct alignment and subsequent analysis of the various datasetsand their modalities. The Waxholm Space (http://software.incf.org/software/waxholm-space) is apublicly available 3D coordinate-based standard reference space for the mapping and registrationof neuroanatomical data in rodent brains. This paper provides a newly developed pipelinecombining imaging and reconstruction steps with a novel registration strategy to integrate newneuroimaging modalities into the Waxholm Space atlas. As a proof of principle, we incorporatedlarge scale high-resolution cyto-, muscarinic M2 receptor, and fiber architectonic images of ratbrains into the 3D digital MRI based atlas of the Sprague Dawley rat in Waxholm Space. Wedescribe the whole workflow, from image acquisition to reconstruction and registration of thesethree modalities into the Waxholm Space rat atlas. The registration of the brain sections intothe atlas is performed by using both linear and non-linear transformations. The validity of theprocedure is qualitatively demonstrated by visual inspection, and a quantitative evaluation isperformed by measurement of the concordance between representative atlas-delineated regionsand the same regions based on receptor or fiber architectonic data. This novel approach enablesfor the first time the generation of 3D reconstructed volumes of nerve fibers and fiber tracts, orof muscarinic M2 receptor density distributions, in an entire rat brain. Additionally, our pipelinefacilitates the inclusion of further neuroimaging datasets, e.g. 3D reconstructed volumes ofhistochemical stainings or of the regional distributions of multiple other receptor types, intothe Waxholm Space. Thereby, a multiscale and multimodal rat brain model was created in theWaxholm Space atlas of the rat brain. Since the registration of these multi-modal high-resolutiondatasets into the same coordinate system is an indispensable requisite for multi-parameteranalyses, this approach enables combined studies on receptor and cell distributions as well asfiber densities in the same anatomical structures at microscopic scales for the first time.
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