Imaging of activated complement using ultrasmall superparamagnetic iron oxide particles (USPIO) - conjugated vectors: an in vivo in utero non-invasive method to predict placental insufficiency and abnormal fetal brain development

Girardi, G; Fraser, J; Lennen, R; Vontell, R; Jansen, M; Hutchison, G

Abstract

In the current study, we have developed a magnetic resonance imaging-based method for non-invasive detection of
complement activation in placenta and foetal brain in vivo in utero. Using this method, we found that anti-complement
C3-targeted ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles bind within the inflamed placenta and foetal brain
cortical tissue, causing a shortening of the T2* relaxation time. We used two mouse models of pregnancy complications: a mouse
model of obstetrics antiphospholipid syndrome (APS) and a mouse model of preterm birth (PTB). We found that detection of C3
deposition in the placenta in the APS model was associated with placental insufficiency characterised by increased oxidative stress,
decreased vascular endothelial growth factor and placental growth factor levels and intrauterine growth restriction. We also
found that foetal brain C3 deposition was associated with cortical axonal cytoarchitecture disruption and increased
neurodegeneration in the mouse model of APS and in the PTB model. In the APS model, foetuses that showed increased C3
in their brains additionally expressed anxiety-related behaviour after birth. Importantly, USPIO did not affect pregnancy
outcomes and liver function in the mother and the offspring, suggesting that this method may be useful for detecting complement
activation in vivo in utero and predicting placental insufficiency and abnormal foetal neurodevelopment that leads to
neuropsychiatric disorders.

Citation

Girardi, G., Fraser, J., Lennen, R., Vontell, R., Jansen, M., & Hutchison, G. (2015). Imaging of activated complement using ultrasmall superparamagnetic iron oxide particles (USPIO) - conjugated vectors: an in vivo in utero non-invasive method to predict placental insufficiency and abnormal fetal brain development. Molecular Psychiatry, 20(8), 1017-1026. https://doi.org/10.1038/mp.2014.110

• Journal Article Type: Article
• Acceptance Date: Jul 21, 2014
• Online Publication Date: Sep 23, 2014
• Publication Date: 2015-08
• Deposit Date: May 20, 2016
• Publicly Available Date: May 20, 2016
• Print ISSN: 1359-4184
• Electronic ISSN: 1476-5578
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 20
• Issue: 8
• Pages: 1017-1026
• DOI: https://doi.org/10.1038/mp.2014.110
• Keywords: Magnetic resonance imaging, non-invasive detection, foetal brain, in vivo in utero,
• Public URL: http://researchrepository.napier.ac.uk/id/eprint/10270
• Contract Date: May 20, 2016