Assessment of Albumin ECM Accumulation and Inflammation as Novel In Vivo Diagnostic Targets for Multi-Target MR Imaging
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 u...
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| Format: | Article |
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MDPI AG
2021-09-01
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| Series: | Biology |
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| Online Access: | https://www.mdpi.com/2079-7737/10/10/964 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Jana Möckel |
| collection | DOAJ |
| description | 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 (<i>ApoE<sup>-/-</sup></i>)-mice were fed a high-fat diet (HFD) for 2 or 4 months. Another <i>ApoE<sup>-/-</sup></i>-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 (R<sup>2</sup> = 0.78, <i>p</i> < 0.05), and signal loss areas in T2*-weighted MRI with Perls’ Prussian blue stain (R<sup>2</sup> = 0.83, <i>p</i> < 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. |
| first_indexed | 2024-03-10T06:43:05Z |
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| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-10T06:43:05Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj.art-1459b56f3180452e8e417056a67258b82023-11-22T17:27:38ZengMDPI AGBiology2079-77372021-09-01101096410.3390/biology10100964Assessment of Albumin ECM Accumulation and Inflammation as Novel In Vivo Diagnostic Targets for Multi-Target MR ImagingJana Möckel0Julia Brangsch1Carolin Reimann2Jan O. Kaufmann3Ingolf Sack4Dilyana B. Mangarova5Avan Kader6Matthias Taupitz7Lisa C. Adams8Sarah Keller9Antje Ludwig10Bernd Hamm11Rene M. Botnar12Marcus R. Makowski13Department of Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, GermanyDepartment of Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, GermanyDepartment of Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, GermanyDivision 1.5 Protein Analysis, Federal Institute for Materials Research and Testing, Richard-Willstätter-Str. 11, 12489 Berlin, GermanyDepartment of Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, GermanyDepartment of Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, GermanyDepartment of Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, GermanyDepartment of Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, GermanyDepartment of Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, GermanyDepartment of Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, GermanyDepartment of Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, GermanyDepartment of Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, GermanyWellcome Trust/EPSRC Centre for Medical Engineering, King’s College London, London WC2R 2LS, UKDepartment of Radiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, GermanyAtherosclerosis 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 (<i>ApoE<sup>-/-</sup></i>)-mice were fed a high-fat diet (HFD) for 2 or 4 months. Another <i>ApoE<sup>-/-</sup></i>-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 (R<sup>2</sup> = 0.78, <i>p</i> < 0.05), and signal loss areas in T2*-weighted MRI with Perls’ Prussian blue stain (R<sup>2</sup> = 0.83, <i>p</i> < 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.https://www.mdpi.com/2079-7737/10/10/964serum albuminextracellular matrixmacrophagesatherosclerosismagnetic resonance imaging |
| spellingShingle | 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 Assessment of Albumin ECM Accumulation and Inflammation as Novel In Vivo Diagnostic Targets for Multi-Target MR Imaging Biology serum albumin extracellular matrix macrophages atherosclerosis magnetic resonance imaging |
| title | Assessment of Albumin ECM Accumulation and Inflammation as Novel In Vivo Diagnostic Targets for Multi-Target MR Imaging |
| title_full | Assessment of Albumin ECM Accumulation and Inflammation as Novel In Vivo Diagnostic Targets for Multi-Target MR Imaging |
| title_fullStr | Assessment of Albumin ECM Accumulation and Inflammation as Novel In Vivo Diagnostic Targets for Multi-Target MR Imaging |
| title_full_unstemmed | Assessment of Albumin ECM Accumulation and Inflammation as Novel In Vivo Diagnostic Targets for Multi-Target MR Imaging |
| title_short | Assessment of Albumin ECM Accumulation and Inflammation as Novel In Vivo Diagnostic Targets for Multi-Target MR Imaging |
| title_sort | assessment of albumin ecm accumulation and inflammation as novel in vivo diagnostic targets for multi target mr imaging |
| topic | serum albumin extracellular matrix macrophages atherosclerosis magnetic resonance imaging |
| url | https://www.mdpi.com/2079-7737/10/10/964 |
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