Elsevier

Neuroscience

Volume 144, Issue 2, 19 January 2007, Pages 604-615
Neuroscience

Neuroanatomy
Development of a high resolution three-dimensional surgical atlas of the murine head for strains 129S1/SvImJ and C57Bl/6J using magnetic resonance imaging and micro-computed tomography

https://doi.org/10.1016/j.neuroscience.2006.08.080Get rights and content

Abstract

The mouse has emerged as a major experimental model system for examining the functional properties of the mammalian CNS; both during development and following CNS injury. Histologic procedures currently used to determine the relative position of structures within the CNS are presently limited in their ability to take full advantage of this system for surgical and morphometric procedures. We present here the first three-dimensional interactive digital atlas of the murine brain and skull for two genetically important strains of mice; 129S1/SvImJ and C57Bl/6J. The final resolution of these digital atlases is 54 μm3. These representations of the murine brain and skull, in conjunction with our development of a new, more dynamic master coordinate system, provide improved accuracy with respect to targeting CNS structures during surgery compared with previous systems. The interactive three-dimensional nature of these atlases also provide users with stereotactic information necessary to perform accurate “off-axis” surgical procedures, as is commonly required for experiments such as in vivo micro-electroporation. In addition, three-dimensional analysis of the brain and skull shape in C57Bl, 129Sv, CD1, and additional murine strains, suggests that a stereotactic coordinate system based upon the lambda and rostral confluence of the sinuses at the sagittal midline, provides improved accuracy compared with the traditional lambda–bregma landmark system. These findings demonstrate the utility of developing highly accurate and robust three-dimensional representations of the murine brain and skull, in which experimental outputs can be directly compared using a unified coordinate system. The aim of these studies is to enhance comparative morphometric analyses and stereotactic surgical procedures in mice.

Section snippets

Animals and tissue preparation

Eight-week old inbred 129S1/SvImJ (Jackson Laboratories [JL], Bar Harbor, ME, USA), C57Bl/6J (Charles River Laboratories, Inc. [CR], Wilmington, MA, USA) and outbred CD1 (CR) or ICR (JL) male mice were obtained from either JL or CR and housed in our gnotobiotic animal colony for 72 h following arrival. Individuals for additional strain comparisons (BALB/cJ, C57BL/6J, DBA/2J, A/J, FVB/NJ, C3H/HeJ) were also obtained from JL or from our own colony at the Samuel Lunenfeld Research Institute, Mount

Low resolution MRI of the murine head

As a first step toward generating 3D atlases of the murine head, whole heads of eight week old 129S1/SvImJ or C57Bl/6J male mice were imaged with MR at a resolution of 121 μm immediately following tissue preparation (see Experimental Procedures) and removal of external skin. To prevent movement of the sample within the imaging coil, heads were placed in 3% solidified PFA-agarose. For these experiments, MR contrast of the spin echo pulse sequence was adjusted to maximize visualization of both

Discussion

Recent enhancements in the resolving capability of non-destructive imaging methods such as magnetic resonance and micro-CT, have allowed us to develop high-resolution (voxel size 54 μm) digital atlases of the murine head. The combined use of MR and CT imaging techniques has allowed us to interactively visualize the brain and skull as a unified whole, improving the accuracy of stereotactic manipulations by directly linking visible landmarks on the dorsal skull to CNS structures. These data

Acknowledgments

We are indebted to N. Lifshitz, and J. Bishop and L. Yu for technical assistance. This work was supported by grants from Canadian Institute for Health Research to J.T.H and M.H., from the Ontario Research Development Challenge Fund to R.M.H; and a NARSAD Young Investigator award to J.T.H.

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    Authors contributed equally to this work.

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