Relating function to structure: fMRI in (transgenic) mice and the Waxholm Space Reference System

Andreas Hess (I.f. Pharmacology, FAU Erlangen Nuremberg, Germany), Silke Kreitz (I.f. Pharmacology, FAU Erlangen Nuremberg, Germany), Marina Sergejeva (I.f. Pharmacology, FAU Erlangen Nuremberg, Germany), Alexandra Badea (Center for In Vivo Microscopy, Duke University, USA), G. Allan Johnson (Center for In Vivo Microscopy, Duke University, USA), Laura Konnerth (I.f. Pharmacology, FAU Erlangen Nuremberg, Germany)

The interpretation of functional brain activation requires a spatial reference, fully 3D and as exact as possible. In an optimal workflow, this spatial reference does not only provide high resolution anatomical information but also labels, atlas information, i.e. the identification of an activated brain region. In a next step this identification would allow gathering additional meta-information about the activated brain region. Such information can be e.g. different anatomical naming, hierarchical information, functional connectivity, neurotransmitter and electrophysiological data, and last but not least gene expression patterns. Partially, such databases already exist for mice. However, they are not yet integrated in a workflow for analyzing brain function in mice.

The International Neuroinformatics Coordinating Facility (INCF, has launched a Digital Atlasing Program (, which came up with the Waxholm space (WHS, Boline et al, 2007, Nature Preceedings, doi:10.1038/npre.2007.1046.1) as a new fully 3D multimodal reference system for mouse brain anatomy (vision of the project see: Hawrylycz et al, 2009, Nature Precedings doi:10.1038/npre.2009.4000.1).

Recent developments in MRI have led to a dramatic increase of spatial resolution (21.5 µm isotropic resolution Johnson et al., Neuroimage, 2007). The new mouse brain atlas, WHS, is based on different datasets: besides histology (Nissl) it incorporates such highly resolved MR images of three modalities (T1, T2, T2*) together with label information of 37 brain structures (Johnson et al., Neuroimage 2010 doi:10.1016/j.neuroimage.2010.06.067) and high resolution DTI data (Jiang and Johnson, Neuroimage, 2011 doi:10.1016/j.neuroimage.2011.03.031). Most importantly, the WHS provides the flexibility to work with group average data. Consequently, WHS serves as a 3D high resolution multimodal anatomical atlas system. Moreover, the INCF has established atlas hub infrastructures and the WaxML language for accessing this atlas information.  Of particular interest here is the coordinate transformation between different atlases like Paxinos, WHS, ABA, AGEA and EMAP. Using this infrastructure we were able to transform the coordinates from a functional active region (our fMRI space) to Paxinos and/or WHS space and form that to the Allen Brain atlas (ABA). Thereby, we are now able to obtain a gene expression pattern (ABA) of an active brain region and to overlay this on a high resolution atlas and label information (WHS). Since MR allows acquiring both, functional as well as (high resolution) anatomical information for each single subject, we have implemented these functionalities in our fMRI analysis program MagnAn. This framework allows us to perform all different aspects of fMRI data analysis and to fuse this with newest digital atlas information. This approach is exemplified in studies of the pain system of (transgenic) mice (Heindl-Erdmann et al., 2010, Neely et al., Cell 2010, Hess PNAS 2011) by fMRI. Here, combining the cutting-edge technologies – fMRI and creation of transgenic mice - we were able to show, that transmission in the pain system is modulated not only by pharmacological interventions but also by genetic background.

Because state-of-the-art fast functional MRI sequences (echo planar imaging) are prone to geometric distortions caused by susceptibility differences of the varying tissues, the transformation of geometric information is critical. With respect to this fully integrated functional-structural relationship, future research has to address questions of the precision of coordinate transformation across the different atlas systems as well as spatial variations across different mouse strains and different transgenic mice.

Preferred presentation format: Poster
Topic: Neuroimaging

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