title: In vivo assessment of aortic aneurysm wall integrity using elastin-specific molecular magnetic resonance imaging.
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.
  
  
  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.
authors.affiliation: 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.).
authors.forename: René M
authors.initials: RM
authors.lastname: Botnar
authors.affiliation: 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.).
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Wiethoff
authors.affiliation: 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.).
authors.forename: Ullrich
authors.initials: U
authors.lastname: Ebersberger
authors.affiliation: 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.).
authors.forename: Sara
authors.initials: S
authors.lastname: Lacerda
authors.affiliation: 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.).
authors.forename: Ulrike
authors.initials: U
authors.lastname: Blume
authors.affiliation: 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.).
authors.forename: Alice
authors.initials: A
authors.lastname: Warley
authors.affiliation: 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.).
authors.forename: Christian H P
authors.initials: CH
authors.lastname: Jansen
authors.affiliation: 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.).
authors.forename: David C
authors.initials: DC
authors.lastname: Onthank
authors.affiliation: 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.).
authors.forename: Richard R
authors.initials: RR
authors.lastname: Cesati
authors.affiliation: 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.).
authors.forename: Reza
authors.initials: R
authors.lastname: Razavi
authors.affiliation: 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.).
authors.forename: Michael S
authors.initials: MS
authors.lastname: Marber
authors.affiliation: 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.).
authors.forename: Bernd
authors.initials: B
authors.lastname: Hamm
authors.affiliation: 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.).
authors.forename: Tobias
authors.initials: T
authors.lastname: Schaeffter
authors.affiliation: 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.).
authors.forename: Simon P
authors.initials: SP
authors.lastname: Robinson
authors.affiliation: 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.
authors.forename: Marcus R
authors.initials: MR
authors.lastname: Makowski
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000737:chemistry* / Q000503:physiopathology / Q000648:ultrastructure; D017544:Aortic Aneurysm, Abdominal / Q000175:diagnosis* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004548:Elasticity; D004549:Elastin / Q000032:analysis*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D057054:Molecular Imaging / Q000379:methods*
chemical_list: D004549:Elastin
keywords: aortic aneurysm, abdominal; elastin; magnetic resonance imaging