René M Botnar1, Andrea J Wiethoff1, Ullrich Ebersberger1, Sara Lacerda1, Ulrike Blume1, Alice Warley1, Christian H P Jansen1, David C Onthank1, Richard R Cesati1, Reza Razavi1, Michael S Marber1, Bernd Hamm1, Tobias Schaeffter1, Simon P Robinson1, Marcus R Makowski2. 1. From the Division of Imaging Sciences (R.M.B., A.J.W., S.L., U.B., C.H.P.J., R.R., T.S., M.R.M.), BHF Centre of Excellence (R.M.B., S.L., R.R., M.S.M., T.S., M.R.M.), Cardiovascular Division (M.S.M.), Centre for Ultrastructural Imaging (A.W.), Wellcome Trust and EPSRC Medical Engineering Center (R.M.B., S.L., R.R., T.S.), and NIHR Biomedical Research Centre (R.M.B., S.L., R.R., M.S.M., T.S.), King's College London, London, United Kingdom; Philips Healthcare, Guildford, United Kingdom (A.J.W.); Lantheus Medical Imaging, North Billerica, MA (D.C.O., R.R.C., S.P.R.); Department of Cardiology and Intensive Care Medicine, Heart Center Munich-Bogenhausen, Munich, Germany (U.E.); and Department of Radiology, Charite, Berlin, Germany (B.H., M.R.M.). 2. From the Division of Imaging Sciences (R.M.B., A.J.W., S.L., U.B., C.H.P.J., R.R., T.S., M.R.M.), BHF Centre of Excellence (R.M.B., S.L., R.R., M.S.M., T.S., M.R.M.), Cardiovascular Division (M.S.M.), Centre for Ultrastructural Imaging (A.W.), Wellcome Trust and EPSRC Medical Engineering Center (R.M.B., S.L., R.R., T.S.), and NIHR Biomedical Research Centre (R.M.B., S.L., R.R., M.S.M., T.S.), King's College London, London, United Kingdom; Philips Healthcare, Guildford, United Kingdom (A.J.W.); Lantheus Medical Imaging, North Billerica, MA (D.C.O., R.R.C., S.P.R.); Department of Cardiology and Intensive Care Medicine, Heart Center Munich-Bogenhausen, Munich, Germany (U.E.); and Department of Radiology, Charite, Berlin, Germany (B.H., M.R.M.). marcus.makowski@kcl.ac.uk.
Abstract
BACKGROUND: The incidence of abdominal aortic aneurysms (AAAs) has increased during the last decades. However, there is still controversy about the management of medium-sized AAAs. Therefore, novel biomarkers, besides aneurysmal diameter, are needed to assess aortic wall integrity and risk of rupture. Elastin is the key protein for maintaining aortic wall tensile strength and stability. The progressive breakdown of structural proteins, in particular, medial elastin, is responsible for the inability of the aortic wall to withstand intraluminal hemodynamic forces. Here, we evaluate the usefulness of elastin-specific molecular MRI for the in vivo characterization of AAAs. METHODS AND RESULTS: To induce AAAs, ApoE(-/-) mice were infused with angiotensin-II. An elastin-specific magnetic resonance molecular imaging agent (ESMA) was administered after 1, 2, 3, and 4 weeks of angiotensin-II infusion to assess elastin composition of the aorta (n=8 per group). The high signal provided by ESMA allowed for imaging with high spatial resolution, resulting in an accurate assessment of ruptured elastic laminae and the compensatory expression of elastic fibers. In vivo contrast-to-noise ratios and R1-relaxation rates after ESMA administration were in good agreement with ex vivo histomorphometry (Elastica van Gieson stain) and gadolinium concentrations determined by inductively coupled plasma mass spectroscopy. Electron microscopy confirmed colocalization of ESMA with elastic fibers. CONCLUSIONS: Changes in elastin content could be readily delineated and quantified at different stages of AAAs by elastin-specific molecular magnetic resonance imaging. ESMA-MRI offers potential for the noninvasive detection of the aortic rupture site prior to dilation of the aorta and the subsequent in vivo monitoring of compensatory repair processes during the progression of AAAs.
BACKGROUND: The incidence of abdominal aortic aneurysms (AAAs) has increased during the last decades. However, there is still controversy about the management of medium-sized AAAs. Therefore, novel biomarkers, besides aneurysmal diameter, are needed to assess aortic wall integrity and risk of rupture. Elastin is the key protein for maintaining aortic wall tensile strength and stability. The progressive breakdown of structural proteins, in particular, medial elastin, is responsible for the inability of the aortic wall to withstand intraluminal hemodynamic forces. Here, we evaluate the usefulness of elastin-specific molecular MRI for the in vivo characterization of AAAs. METHODS AND RESULTS: To induce AAAs, ApoE(-/-) mice were infused with angiotensin-II. An elastin-specific magnetic resonance molecular imaging agent (ESMA) was administered after 1, 2, 3, and 4 weeks of angiotensin-II infusion to assess elastin composition of the aorta (n=8 per group). The high signal provided by ESMA allowed for imaging with high spatial resolution, resulting in an accurate assessment of ruptured elastic laminae and the compensatory expression of elastic fibers. In vivo contrast-to-noise ratios and R1-relaxation rates after ESMA administration were in good agreement with ex vivo histomorphometry (Elastica van Gieson stain) and gadolinium concentrations determined by inductively coupled plasma mass spectroscopy. Electron microscopy confirmed colocalization of ESMA with elastic fibers. CONCLUSIONS: Changes in elastin content could be readily delineated and quantified at different stages of AAAs by elastin-specific molecular magnetic resonance imaging. ESMA-MRI offers potential for the noninvasive detection of the aortic rupture site prior to dilation of the aorta and the subsequent in vivo monitoring of compensatory repair processes during the progression of AAAs.
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