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MicroCT imaging reveals differential 3D micro-scale remodelling of the murine aorta in ageing and marfan syndrome

López-Guimet, J; Peña-Pérez, L; Bradley, RS; García-Canadilla, P; Disney, C; Geng, H; Bodey, AJ; ... Egea, G; + view all (2018) MicroCT imaging reveals differential 3D micro-scale remodelling of the murine aorta in ageing and marfan syndrome. Theranostics , 8 (21) pp. 6038-6052. 10.7150/thno.26598. Green open access

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Abstract

Aortic wall remodelling is a key feature of both ageing and genetic connective tissue diseases, which are associated with vasculopathies such as Marfan syndrome (MFS). Although the aorta is a 3D structure, little attention has been paid to volumetric assessment, primarily due to the limitations of conventional imaging techniques. Phase-contrast microCT is an emerging imaging technique, which is able to resolve the 3D micro-scale structure of large samples without the need for staining or sectioning. Methods: Here, we have used synchrotron-based phase-contrast microCT to image aortae of wild type (WT) and MFS Fbn1C1039G/+ mice aged 3, 6 and 9 months old (n=5). We have also developed a new computational approach to automatically measure key histological parameters. Results: This analysis revealed that WT mice undergo age-dependent aortic remodelling characterised by increases in ascending aorta diameter, tunica media thickness and cross-sectional area. The MFS aortic wall was subject to comparable remodelling, but the magnitudes of the changes were significantly exacerbated, particularly in 9 month-old MFS mice with ascending aorta wall dilations. Moreover, this morphological remodelling in MFS aorta included internal elastic lamina surface breaks that extended throughout the MFS ascending aorta and were already evident in animals who had not yet developed aneurysms. Conclusions: Our 3D microCT study of the sub-micron wall structure of whole, intact aorta reveals that histological remodelling of the tunica media in MFS could be viewed as an accelerated ageing process, and that phase-contrast microCT combined with computational image analysis allows the visualisation and quantification of 3D morphological remodelling in large volumes of unstained vascular tissues.

Type: Article
Title: MicroCT imaging reveals differential 3D micro-scale remodelling of the murine aorta in ageing and marfan syndrome
Open access status: An open access version is available from UCL Discovery
DOI: 10.7150/thno.26598
Publisher version: https://doi.org/10.7150/thno.26598
Language: English
Additional information: © The authors. This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/ licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Keywords: Marfan syndrome, microCT, aorta, ageing, elastic lamella
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Mechanical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/10064468
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