Publication Database

Entwicklung und Evaluierung von neuartigen Bildgebungsmodalitäten für die Charakterisierung von abdominalen Aortenaneurysmen im Mausmodell (2022)

Art

Hochschulschrift

Autor

Mangarova, Dilyana Branimirova (WE 12)

Quelle

Berlin: Mensch & Buch Verlag, 2022 — VI, 106 Seiten

Verweise

URL (Volltext): https://refubium.fu-berlin.de/handle/fub188/35946

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

An abdominal aortic aneurysm (AAA) is defined as a permanent local dilatation of the abdominal aorta, usually accompanied by thrombus formation. Once ruptured, an AAA is associated with an overall mortality rate of over 90%. Even though AAAs represent one of the leading causes of sudden death in developed countries, the exact etiology and pathophysiology have not yet been fully elucidated. Nowadays, AAAs are clinically diagnosed by either computed tomography, ultrasound or magnetic resonance imaging (MRI), yet those modalities only deliver information on the aneurysm anatomy, size and form. It is generally accepted that AAA size correlates with the probability for rupture and related clinical events. However, a growing body of literature argues that the pathophysiology of AAA expansion is more multifaceted, with inflammation and degradation of the extracellular matrix (ECM) playing a pivotal role. Visualizing the complex nature of aneurysms requires the development of novel imaging modalities that facilitate more detailed depiction of AAAs. Magnetic resonance elastography (MRE) is an imaging technology that combines lowfrequency vibrations and MRI to create stiffness maps of body tissues. Remodeling of the ECM during AAA progression leads to stiffness changes, providing a potential imaging marker. Therefore, we assessed murine aneurysms by ex vivo microscopic multifrequency magnetic resonance elastography (μMMRE). By examining the aneurysmal thrombus, we discovered that regional variations in stiffness were strongly correlated to local histology-quantified ECM accumulation. With this proof-of-concept study, we demonstrated that MRE represents a suitable method for detecting shear wave speed changes reflected in varying stiffness values in the aneurysmal thrombus that in turn are representative of ECM remodeling. With successful clinical translation, this imaging modality could help detect potential fatal changes in the biomechanical structure of the AAA mimicked by ECM changes. Magnetic particle imaging (MPI) is an innovative imaging modality, enabling a highly sensitive detection of magnetic nanoparticles (MNPs). Since MNPs are a suitable surrogate marker for molecular targeting of macrophages and the aneurysmal development involves inflammation as a fundamental process, we tested the feasibility of imaging AAA inflammation with MPI. We demonstrated that the MNP accumulation in ex vivo murine aneurysms can be visualized and quantified with MPI. In addition, the colocalization of macrophages and MNPs was visible in histology. The ability to detect the spatial distribution and local concentration of MNPs establishes MPI as a promising tool for monitoring inflammatory progression in AAAs.