Abstract
Optical molecular imaging in small animals harnesses the power of highly specific and biocompatible contrast agents for drug development and disease research1,2,3,4,5,6,7. However, the widespread adoption of in vivo optical imaging has been inhibited by its inability to clearly resolve and identify targeted internal organs. Optical tomography8,9,10,11 and combined X-ray and micro-computed tomography (micro-CT)12 approaches developed to address this problem are generally expensive, complex or incapable of true anatomical co-registration. Here, we present a remarkably simple all-optical method that can generate co-registered anatomical maps of a mouse's internal organs, while also acquiring in vivo molecular imaging data. The technique uses a time series of images acquired after injection of an inert dye. Differences in the dye's in vivo biodistribution dynamics allow precise delineation and identification of major organs. Such co-registered anatomical maps permit longitudinal organ identification irrespective of repositioning or weight gain, thereby promising greatly improved accuracy and versatility for studies of orthotopic disease, diagnostics and therapies.
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Acknowledgements
This work was funded by National Institutes of Health grants: 1R01DK072137, 5R01DK064850, R21DK071225 and 1U54CA126513. The authors wish to sincerely thank R. M. Levenson and X. E. Guo for helpful discussions and guidance. We also acknowledge the contributions of S. B. Raymond, B. J. Bacskai, M. Bouchard and D. A. Boas at Massachusetts General Hospital.
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E.M.C.H. conceived the technique, designed and performed the experiments, analysed the data and wrote the manuscript. A.M. prompted and guided development of the concept and aided in data acquisition, data interpretation and manuscript preparation.
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A patent application was filed on 1 June 2007 by Massachusetts General Hospital on the method described in this paper with Elizabeth M. C. Hillman as the sole inventor.
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Hillman, E., Moore, A. All-optical anatomical co-registration for molecular imaging of small animals using dynamic contrast. Nature Photon 1, 526–530 (2007). https://doi.org/10.1038/nphoton.2007.146
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DOI: https://doi.org/10.1038/nphoton.2007.146
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