King's College London

Research portal

In vivo multi-parametric manganese-enhanced MRI for detecting amyloid plaques in rodent models of Alzheimer's disease

Research output: Contribution to journalArticlepeer-review

Eugene Kim, Davide Di Censo, Mattia Baraldo, Camilla Simmons, Ilaria Rosa, Karen Randall, Clive Ballard, Ben R Dickie, Steven C R Williams, Richard Killick, Diana Cash

Original languageEnglish
Article number12419
Pages (from-to)12419
JournalScientific Reports
Volume11
Issue number1
DOIs
PublishedDec 2021

Bibliographical note

Funding Information: The authors thank the Wohl Cellular Imaging Centre (http://www.kclwcic.co.uk) for the use of their slide scanner. SCRW would also like to thank the Wellcome Trust and Medical Research Council for their ongoing support of our neuroimaging research. Funding Information: This work was supported by the Alzheimer’s Society [AS-PhD-18B-015] and internal funding as “pump-priming” for developing novel imaging methodologies. Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors

Abstract

Amyloid plaques are a hallmark of Alzheimer's disease (AD) that develop in its earliest stages. Thus, non-invasive detection of these plaques would be invaluable for diagnosis and the development and monitoring of treatments, but this remains a challenge due to their small size. Here, we investigated the utility of manganese-enhanced MRI (MEMRI) for visualizing plaques in transgenic rodent models of AD across two species: 5xFAD mice and TgF344-AD rats. Animals were given subcutaneous injections of MnCl2 and imaged in vivo using a 9.4 T Bruker scanner. MnCl2 improved signal-to-noise ratio but was not necessary to detect plaques in high-resolution images. Plaques were visible in all transgenic animals and no wild-types, and quantitative susceptibility mapping showed that they were more paramagnetic than the surrounding tissue. This, combined with beta-amyloid and iron staining, indicate that plaque MR visibility in both animal models was driven by plaque size and iron load. Longitudinal relaxation rate mapping revealed increased manganese uptake in brain regions of high plaque burden in transgenic animals compared to their wild-type littermates. This was limited to the rhinencephalon in the TgF344-AD rats, while it was most significantly increased in the cortex of the 5xFAD mice. Alizarin Red staining suggests that manganese bound to plaques in 5xFAD mice but not in TgF344-AD rats. Multi-parametric MEMRI is a simple, viable method for detecting amyloid plaques in rodent models of AD. Manganese-induced signal enhancement can enable higher-resolution imaging, which is key to visualizing these small amyloid deposits. We also present the first in vivo evidence of manganese as a potential targeted contrast agent for imaging plaques in the 5xFAD model of AD.

View graph of relations

© 2020 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454