Assessment of Albumin ECM Accumulation and Inflammation as Novel In Vivo Diagnostic Targets for Multi-Target MR Imaging
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
Affiliations
Jana Möckel
Department of Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
Julia Brangsch
Department of Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
Carolin Reimann
Department of Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
Jan O. Kaufmann
Division 1.5 Protein Analysis, Federal Institute for Materials Research and Testing, Richard-Willstätter-Str. 11, 12489 Berlin, Germany
Ingolf Sack
Department of Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
Dilyana B. Mangarova
Department of Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
Avan Kader
Department of Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
Matthias Taupitz
Department of Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
Lisa C. Adams
Department of Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
Sarah Keller
Department of Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
Antje Ludwig
Department of Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
Bernd Hamm
Department of Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
Rene M. Botnar
Wellcome Trust/EPSRC Centre for Medical Engineering, King’s College London, London WC2R 2LS, UK
Marcus R. Makowski
Department of Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
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 2 = 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.
