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Simultaneous molecular MRI of extracellular matrix collagen and inflammatory activity to predict abdominal aortic aneurysm rupture

  • Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease with an up to 80% mortality in case of rupture. Current biomarkers fail to account for size-independent risk of rupture. By combining the information of different molecular probes, multi-target molecular MRI holds the potential to enable individual characterization of AAA. In this experimental study, we aimed to examine the feasibility of simultaneous imaging of extracellular collagen and inflammation for size-independent prediction of risk of rupture in murine AAA. The study design consisted of: (1) A outcome-based longitudinal study with imaging performed once after one week with follow-up and death as the end-point for assessment of rupture risk. (2) A week-by-week study for the characterization of AAA development with imaging after 1, 2, 3 and 4 weeks. For both studies, the animals were administered a type 1 collagen-targeted gadolinium-based probe (surrogate marker for extracellular matrix (ECM) remodeling) andAbdominal aortic aneurysm (AAA) is a life-threatening vascular disease with an up to 80% mortality in case of rupture. Current biomarkers fail to account for size-independent risk of rupture. By combining the information of different molecular probes, multi-target molecular MRI holds the potential to enable individual characterization of AAA. In this experimental study, we aimed to examine the feasibility of simultaneous imaging of extracellular collagen and inflammation for size-independent prediction of risk of rupture in murine AAA. The study design consisted of: (1) A outcome-based longitudinal study with imaging performed once after one week with follow-up and death as the end-point for assessment of rupture risk. (2) A week-by-week study for the characterization of AAA development with imaging after 1, 2, 3 and 4 weeks. For both studies, the animals were administered a type 1 collagen-targeted gadolinium-based probe (surrogate marker for extracellular matrix (ECM) remodeling) and an iron oxide-based probe (surrogate marker for inflammatory activity), in one imaging session. In vivo measurements of collagen and iron oxide probes showed a significant correlation with ex vivo histology (p < 0.001) and also corresponded well to inductively-coupled plasma-mass spectrometry and laser-ablation inductively-coupled plasma mass spectrometry. Combined evaluation of collagen-related ECM remodeling and inflammatory activity was the most accurate predictor for AAA rupture (sensitivity 80%, specificity 100%, area under the curve 0.85), being superior to information from the individual probes alone. Our study supports the feasibility of a simultaneous assessment of collagen-related extracellular matrix remodeling and inflammatory activity in a murine model of AAA.zeige mehrzeige weniger

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Metadaten
Autor*innen:L. C. Adams, J. Brangsch, C. Reimann, Jan Ole Kaufmann, R. Buchholz, U. Karst, R. M. Botnar, B. Hamm, M. R. Makowski
Dokumenttyp:Zeitschriftenartikel
Veröffentlichungsform:Verlagsliteratur
Sprache:Englisch
Titel des übergeordneten Werkes (Englisch):Scientific Reports
Jahr der Erstveröffentlichung:2020
Organisationseinheit der BAM:1 Analytische Chemie; Referenzmaterialien
1 Analytische Chemie; Referenzmaterialien / 1.5 Proteinanalytik
Veröffentlichende Institution:Bundesanstalt für Materialforschung und -prüfung (BAM)
Verlag:Springer Nature Limited
Verlagsort:London, New York, Berlin, Shanghai and Tokyo
Jahrgang/Band:10
Ausgabe/Heft:1
Erste Seite:15206
DDC-Klassifikation:Naturwissenschaften und Mathematik / Chemie / Analytische Chemie
Freie Schlagwörter:Atherosclerosis; Ferumoxytol; Gadolinium; ICP-MS; Inductively‑coupled mass spectrometry; Iron oxide; LA-ICP-MS; Laser ablation; Magnetic resonance imaging; Specific probe
Themenfelder/Aktivitätsfelder der BAM:Chemie und Prozesstechnik
DOI:10.1038/s41598-020-71817-x
URN:urn:nbn:de:kobv:b43-525864
URL:https://www.nature.com/articles/s41598-020-71817-x
Verfügbarkeit des Dokuments:Datei für die Öffentlichkeit verfügbar ("Open Access")
Lizenz (Deutsch):License LogoCreative Commons - CC BY - Namensnennung 4.0 International
Datum der Freischaltung:05.05.2021
Referierte Publikation:Ja
Datum der Eintragung als referierte Publikation:05.05.2021
Schriftenreihen ohne Nummerierung:Wissenschaftliche Artikel der BAM
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