Abstract
Manganese-enhanced MRI (MRI) is a technique that allows for a noninvasive in vivo estimation of neuronal transport. It relies on the physicochemical properties of manganese, which is both a calcium analogue being transported along neurons by active transport, and a paramagnetic compound that can be detected on conventional T1-weighted images. Here, we report a multi-session MEMRI protocol that helps establish time-dependent curves relating to neuronal transport along the olfactory tract over several days. The characterization of these curves via unbiased fitting enables us to infer objectively a set of three parameters (the rate of manganese transport from the maximum slope, the peak intensity, and the time to peak intensity). These parameters, measured previously in wild type mice during normal aging, have served as a baseline to demonstrate their significant sensitivity to pathogenic processes associated with Tau pathology. Importantly, the evaluation of these three parameters and their use as indicators can be extended to monitor any normal and pathogenic processes where neuronal transport is altered. This approach can be applied to characterize and quantify the effect of any neurological disease conditions on neuronal transport in animal models, together with the efficacy of potential therapies.
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Acknowledgments
This work was supported by the following grants: AG032611 and AG020197, and a Zenith grant from the Alzheimer Association to EMS; Alzheimer Association IIRG-08-91618 and American Health Assistance Foundation Alzheimer Disease Research Grant A2008-155 to YZW. This work was also performed at the Preclinical Imaging Laboratory, a shared resource partially supported by NIH/SIG 1S10OD018337, the Laura and Isaac Perlmutter Cancer Center Support Grant NIH/NCI 5P30CA016087 and NIBIB Biomedical Technology Resource Center Grant NIH P41 EB017183.
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Bertrand, A. et al. (2018). In Vivo Evaluation of Neuronal Transport in Murine Models of Neurodegeneration Using Manganese-Enhanced MRI. In: Sigurdsson, E., Calero, M., Gasset, M. (eds) Amyloid Proteins. Methods in Molecular Biology, vol 1779. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7816-8_33
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DOI: https://doi.org/10.1007/978-1-4939-7816-8_33
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