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Assessment of albumin ecm accumulation and inflammation as novel in vivo diagnostic targets for multi-target mr imaging

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Jana Möckel, Julia Brangsch, Carolin Reimann, Jan O. Kaufmann, Ingolf Sack, Dilyana B. Mangarova, Avan Kader, Matthias Taupitz, Lisa C. Adams, Sarah Keller, Antje Ludwig, Bernd Hamm, Rene M. Botnar, Marcus R. Makowski

Original languageEnglish
Article number964
Issue number10
Early online date27 Sep 2021
E-pub ahead of print27 Sep 2021
PublishedOct 2021

Bibliographical note

Funding Information: Funding: This project was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—project number 372486779-SFB 1340/1 2018, B01, the Deutsche Forschungsgemein-schaft (MA 5943/3-1/4-1/9-1), and the BHF (RG/12/1/29262). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors


Atherosclerosis is a progressive inflammatory vascular disease characterized by endothelial dysfunction and plaque burden. Extracellular matrix (ECM)-associated plasma proteins play an important role in disease development. Our magnetic resonance imaging (MRI) study investigates the feasibility of using two different molecular MRI probes for the simultaneous assessment of ECM-associated intraplaque albumin deposits caused by endothelial damage and progressive inflammation in atherosclerosis. Male apolipoprotein E-deficient (ApoE-/- )-mice were fed a high-fat diet (HFD) for 2 or 4 months. Another ApoE-/--group was treated with pravastatin and received a HFD for 4 months. T1-and T2*-weighted MRI was performed before and after albumin-specific MRI probe (gadofosveset) administration and a macrophage-specific contrast agent (ferumoxytol). Thereafter, laser ablation inductively coupled plasma mass spectrometry and histology were performed. With advancing atherosclerosis, albumin-based MRI signal enhancement and ferumoxytol-induced signal loss areas in T2*-weighted MRI increased. Significant correlations between contrast-to-noise-ratio (CNR) post-gadofosveset and albumin stain (R2 = 0.78, p < 0.05), and signal loss areas in T2*-weighted MRI with Perls’ Prussian blue stain (R2 = 0.83, p < 0.05) were observed. No interference of ferumoxytol with gadofosveset enhancement was detectable. Pravastatin led to decreased inflammation and intraplaque albumin. Multi-target MRI combining ferumoxytol and gadofosveset is a promising method to improve diagnosis and treatment monitoring in atherosclerosis.

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