Microscopic multifrequency magnetic resonance elastography of ex vivo abdominal aortic aneurysms for extracellular matrix imaging in a mouse model

Dilyana B Mangarova; Gergely Bertalan; Jakob Jordan; Julia Brangsch; Avan Kader; Jana Möckel; Lisa C Adams; Ingolf Sack; Matthias Taupitz; Bernd Hamm; Jürgen Braun; Marcus R Makowski

doi:10.1016/j.actbio.2021.11.026

Microscopic multifrequency magnetic resonance elastography of ex vivo abdominal aortic aneurysms for extracellular matrix imaging in a mouse model

Acta Biomater. 2022 Mar 1:140:389-397. doi: 10.1016/j.actbio.2021.11.026. Epub 2021 Nov 21.

Authors

Affiliations

¹ Department of Radiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, Berlin 10117, Germany; Department of Veterinary Medicine, Institute of Veterinary Pathology, Freie Universität Berlin, Robert-von-Ostertag-Str. 15, Building 12, Berlin 4163, Germany. Electronic address: dilyana.mangarova@charite.de.
² Department of Radiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, Berlin 10117, Germany. Electronic address: gergely.bertalan@charite.de.
³ Department of Radiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, Berlin 10117, Germany. Electronic address: jakob.jordan@charite.de.
⁴ Department of Radiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, Berlin 10117, Germany. Electronic address: julia.brangsch@charite.de.
⁵ Department of Radiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, Berlin 10117, Germany; Department of Biology, Chemistry and Pharmacy, Institute of Biology, Freie Universität Berlin, Königin-Luise-Str. 1-3, Berlin 14195, Germany. Electronic address: avan.kader@charite.de.
⁶ Department of Radiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, Berlin 10117, Germany. Electronic address: jana.moeckel@charite.de.
⁷ Department of Radiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, Berlin 10117, Germany. Electronic address: lisa.adams@charite.de.
⁸ Department of Radiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, Berlin 10117, Germany. Electronic address: ingolf.sack@charite.de.
⁹ Department of Radiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, Berlin 10117, Germany. Electronic address: matthias.taupitz@charite.de.
¹⁰ Department of Radiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, Berlin 10117, Germany. Electronic address: bernd.hamm@charite.de.
¹¹ Department of Radiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, Berlin 10117, Germany; Institute for Medical Informatics, Charité - Universitätsmedizin Berlin, Berlin, Germany, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Hindenburgdamm 30, Berlin 12200, Germany. Electronic address: juergen.braun@charite.de.
¹² Department of Radiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, Berlin 10117, Germany; Department of Diagnostic and Interventional Radiology, Technical University of Munich, Ismaninger Str. 22, Munich 81675, Germany. Electronic address: marcus.makowski@charite.de.

PMID: 34818577
DOI: 10.1016/j.actbio.2021.11.026

Abstract

An abdominal aortic aneurysm (AAA) is a permanent dilatation of the abdominal aorta, usually accompanied by thrombus formation. The current clinical imaging modalities cannot reliably visualize the thrombus composition. Remodeling of the extracellular matrix (ECM) during AAA development leads to stiffness changes, providing a potential imaging marker. 14 apolipoprotein E-deficient mice underwent surgery for angiotensin II-loaded osmotic minipump implantation. 4 weeks post-op, 5 animals developed an AAA. The aneurysm was imaged ex vivo by microscopic multifrequency magnetic resonance elastography (µMMRE) with an in-plane resolution of 40 microns. Experiments were performed on a 7-Tesla preclinical magnetic resonance imaging scanner with drive frequencies between 1000 Hz and 1400 Hz. Shear wave speed (SWS) maps indicating stiffness were computed based on tomoelastography multifrequency inversion. As control, the aortas of 5 C57BL/6J mice were examined with the same imaging protocol. The regional variation of SWS in the thrombus ranging from 0.44 ± 0.07 to 1.20 ± 0.31 m/s was correlated fairly strong with regional histology-quantified ECM accumulation (R² = 0.79). Our results suggest that stiffness changes in aneurysmal thrombus reflect ECM remodeling, which is critical for AAA risk assessment. In the future, µMMRE could be used for a mechanics-based clinical characterization of AAAs in patients. STATEMENT OF SIGNIFICANCE: To our knowledge, this is the first study mapping the stiffness of abdominal aortic aneurysms with microscopic resolution of 40 µm. Our work revealed that stiffness critically changes due to extracellular matrix (ECM) remodeling in the aneurysmal thrombus. We were able to image various levels of ECM remodeling in the aneurysm reflected in distinct shear wave speed patterns with a strong correlation to regional histology-quantified ECM accumulation. The generated results are significant for the application of microscopic multifrequency magnetic resonance elastography for quantification of pathological remodeling of the ECM and may be of great interest for detailed characterization of AAAs in patients.

Keywords: AAA; Magnetic resonance elastography; Proof-of-concept; Stiffness.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Aorta, Abdominal / diagnostic imaging
Aorta, Abdominal / pathology
Aortic Aneurysm, Abdominal* / diagnostic imaging
Aortic Aneurysm, Abdominal* / pathology
Disease Models, Animal
Elasticity Imaging Techniques*
Extracellular Matrix / pathology
Humans
Magnetic Resonance Imaging
Mice
Mice, Inbred C57BL