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Theranostics 2018; 8(21):6038-6052. doi:10.7150/thno.26598 This issue Cite

Research Paper

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

Júlia López-Guimet¹, Lucía Peña-Pérez^2,3, Robert S. Bradley^4,5, Patricia García-Canadilla², Catherine Disney⁶, Hua Geng⁶, Andrew J. Bodey⁷, Philip J. Withers⁴, Bart Bijnens^2,8, Michael J. Sherratt^6*, Gustavo Egea^1,9,10✉*

1. Departament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain.
2. PhySense group, Deptartament de Tecnologies de la Informació i les Comunicacions, Universitat Pompeu Fabra, Barcelona, Spain.
3. Center for Hematology and Regenerative Medicine, Karolinska Institute, Stockholm, Sweden (current address).
4. Henry Moseley X-ray Imaging Facility, School of Materials, University of Manchester, Manchester, United Kingdom.
5. Geotek Ltd, Daventry, United Kingdom (current address).
6. Division of Cell Matrix Biology & Regenerative Medicine, School of Biological Sciences, University of Manchester, Manchester, United Kingdom.
7. Diamond Light Source, Oxfordshire, OX11 0DE, Oxford, United Kingdom.
8. ICREA, Barcelona, Spain.
9. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
10. Institut de Nanociència i Nanotecnologia (IN2UB), Universitat de Barcelona, Barcelona, Spain.
* co-senior authors

✉ Corresponding author: Departament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, C/Casanova 143, 08036 Barcelona, Spain. Phone: (+34)934021909. E-mail: gegeaedu

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 Fbn1^C1039G/+ 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.

Keywords: Marfan syndrome, microCT, aorta, ageing, elastic lamella

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