title: Assessment of elastin deficit in a Marfan mouse aneurysm model using an elastin-specific magnetic resonance imaging contrast agent.
abstract: BACKGROUND
  Ascending aortic dissection and rupture remain a life-threatening complication in patients with Marfan syndrome. The extracellular matrix provides strength and elastic recoil to the aortic wall, thereby preventing radial expansion. We have previously shown that ascending aortic aneurysm formation in Marfan mice (Fbn1(C1039G/+)) is associated with decreased aortic wall elastogenesis and increased elastin breakdown. In this study, we test the feasibility of quantifying aortic wall elastin content using MRI with a gadolinium-based elastin-specific magnetic resonance contrast agent in Fbn1(C1039G/+) mice.
  
  
  RESULTS
  Ascending aorta elastin content was measured in 32-week-old Fbn1(C1039G/+) mice and wild-type (n=9 and n=10, respectively) using 7-T MRI with a T1 mapping sequence. Significantly lower enhancement (ie, lower R1 values, where R1=1/T1) was detected post-elastin-specific magnetic resonance contrast agent in Fbn1(C1039G/+) compared with wild-type ascending aortas (1.15±0.07 versus 1.36±0.05; P<0.05). Post-elastin-specific magnetic resonance contrast agent R1 values correlated with ascending aortic wall gadolinium content directly measured by inductively coupled mass spectroscopy (P=0.006).
  
  
  CONCLUSIONS
  Herein, we demonstrate that MRI with elastin-specific magnetic resonance contrast agent accurately measures elastin bound gadolinium within the aortic wall and detects a decrease in aortic wall elastin in Marfan mice compared with wild-type controls. This approach has translational potential for noninvasively assessing aneurysm tissue changes and risk, as well as monitoring elastin content in response to therapeutic interventions.
authors.affiliation: From the Departments of Cardiothoracic Surgery (H.O., A.R.D., F.E., B.A.D., M.A., M.P.F.), Radiology (L.J.P.), and Pathology (A.J.C.), Stanford University, CA; Department of Cardiovascular Surgery, Jichi Medical University, Saitama Medical Center, Saitama, Japan (H.O., M.A., H.A.); Lantheus Medical Imaging, North Billerica, MA (D.C.O., R.R.C., S.P.R.); Agilent Technologies, Yarnton, Oxford, United Kingdom (M.M.); Departments of Radiology (G.K.) and Medical Informatics and Radiology (H.S.), Erasmus MC, Rotterdam, The Netherlands; and Division of Cardiovascular Medicine, Stanford University, CA (M.V.M.).
authors.forename: Homare
authors.initials: H
authors.lastname: Okamura
authors.affiliation: From the Departments of Cardiothoracic Surgery (H.O., A.R.D., F.E., B.A.D., M.A., M.P.F.), Radiology (L.J.P.), and Pathology (A.J.C.), Stanford University, CA; Department of Cardiovascular Surgery, Jichi Medical University, Saitama Medical Center, Saitama, Japan (H.O., M.A., H.A.); Lantheus Medical Imaging, North Billerica, MA (D.C.O., R.R.C., S.P.R.); Agilent Technologies, Yarnton, Oxford, United Kingdom (M.M.); Departments of Radiology (G.K.) and Medical Informatics and Radiology (H.S.), Erasmus MC, Rotterdam, The Netherlands; and Division of Cardiovascular Medicine, Stanford University, CA (M.V.M.).
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Pisani
authors.affiliation: From the Departments of Cardiothoracic Surgery (H.O., A.R.D., F.E., B.A.D., M.A., M.P.F.), Radiology (L.J.P.), and Pathology (A.J.C.), Stanford University, CA; Department of Cardiovascular Surgery, Jichi Medical University, Saitama Medical Center, Saitama, Japan (H.O., M.A., H.A.); Lantheus Medical Imaging, North Billerica, MA (D.C.O., R.R.C., S.P.R.); Agilent Technologies, Yarnton, Oxford, United Kingdom (M.M.); Departments of Radiology (G.K.) and Medical Informatics and Radiology (H.S.), Erasmus MC, Rotterdam, The Netherlands; and Division of Cardiovascular Medicine, Stanford University, CA (M.V.M.).
authors.forename: Alex R
authors.initials: AR
authors.lastname: Dalal
authors.affiliation: From the Departments of Cardiothoracic Surgery (H.O., A.R.D., F.E., B.A.D., M.A., M.P.F.), Radiology (L.J.P.), and Pathology (A.J.C.), Stanford University, CA; Department of Cardiovascular Surgery, Jichi Medical University, Saitama Medical Center, Saitama, Japan (H.O., M.A., H.A.); Lantheus Medical Imaging, North Billerica, MA (D.C.O., R.R.C., S.P.R.); Agilent Technologies, Yarnton, Oxford, United Kingdom (M.M.); Departments of Radiology (G.K.) and Medical Informatics and Radiology (H.S.), Erasmus MC, Rotterdam, The Netherlands; and Division of Cardiovascular Medicine, Stanford University, CA (M.V.M.).
authors.forename: Fabian
authors.initials: F
authors.lastname: Emrich
authors.affiliation: From the Departments of Cardiothoracic Surgery (H.O., A.R.D., F.E., B.A.D., M.A., M.P.F.), Radiology (L.J.P.), and Pathology (A.J.C.), Stanford University, CA; Department of Cardiovascular Surgery, Jichi Medical University, Saitama Medical Center, Saitama, Japan (H.O., M.A., H.A.); Lantheus Medical Imaging, North Billerica, MA (D.C.O., R.R.C., S.P.R.); Agilent Technologies, Yarnton, Oxford, United Kingdom (M.M.); Departments of Radiology (G.K.) and Medical Informatics and Radiology (H.S.), Erasmus MC, Rotterdam, The Netherlands; and Division of Cardiovascular Medicine, Stanford University, CA (M.V.M.).
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Dake
authors.affiliation: From the Departments of Cardiothoracic Surgery (H.O., A.R.D., F.E., B.A.D., M.A., M.P.F.), Radiology (L.J.P.), and Pathology (A.J.C.), Stanford University, CA; Department of Cardiovascular Surgery, Jichi Medical University, Saitama Medical Center, Saitama, Japan (H.O., M.A., H.A.); Lantheus Medical Imaging, North Billerica, MA (D.C.O., R.R.C., S.P.R.); Agilent Technologies, Yarnton, Oxford, United Kingdom (M.M.); Departments of Radiology (G.K.) and Medical Informatics and Radiology (H.S.), Erasmus MC, Rotterdam, The Netherlands; and Division of Cardiovascular Medicine, Stanford University, CA (M.V.M.).
authors.forename: Mamoru
authors.initials: M
authors.lastname: Arakawa
authors.affiliation: From the Departments of Cardiothoracic Surgery (H.O., A.R.D., F.E., B.A.D., M.A., M.P.F.), Radiology (L.J.P.), and Pathology (A.J.C.), Stanford University, CA; Department of Cardiovascular Surgery, Jichi Medical University, Saitama Medical Center, Saitama, Japan (H.O., M.A., H.A.); Lantheus Medical Imaging, North Billerica, MA (D.C.O., R.R.C., S.P.R.); Agilent Technologies, Yarnton, Oxford, United Kingdom (M.M.); Departments of Radiology (G.K.) and Medical Informatics and Radiology (H.S.), Erasmus MC, Rotterdam, The Netherlands; and Division of Cardiovascular Medicine, Stanford University, CA (M.V.M.).
authors.forename: David C
authors.initials: DC
authors.lastname: Onthank
authors.affiliation: From the Departments of Cardiothoracic Surgery (H.O., A.R.D., F.E., B.A.D., M.A., M.P.F.), Radiology (L.J.P.), and Pathology (A.J.C.), Stanford University, CA; Department of Cardiovascular Surgery, Jichi Medical University, Saitama Medical Center, Saitama, Japan (H.O., M.A., H.A.); Lantheus Medical Imaging, North Billerica, MA (D.C.O., R.R.C., S.P.R.); Agilent Technologies, Yarnton, Oxford, United Kingdom (M.M.); Departments of Radiology (G.K.) and Medical Informatics and Radiology (H.S.), Erasmus MC, Rotterdam, The Netherlands; and Division of Cardiovascular Medicine, Stanford University, CA (M.V.M.).
authors.forename: Richard R
authors.initials: RR
authors.lastname: Cesati
authors.affiliation: From the Departments of Cardiothoracic Surgery (H.O., A.R.D., F.E., B.A.D., M.A., M.P.F.), Radiology (L.J.P.), and Pathology (A.J.C.), Stanford University, CA; Department of Cardiovascular Surgery, Jichi Medical University, Saitama Medical Center, Saitama, Japan (H.O., M.A., H.A.); Lantheus Medical Imaging, North Billerica, MA (D.C.O., R.R.C., S.P.R.); Agilent Technologies, Yarnton, Oxford, United Kingdom (M.M.); Departments of Radiology (G.K.) and Medical Informatics and Radiology (H.S.), Erasmus MC, Rotterdam, The Netherlands; and Division of Cardiovascular Medicine, Stanford University, CA (M.V.M.).
authors.forename: Simon P
authors.initials: SP
authors.lastname: Robinson
authors.affiliation: From the Departments of Cardiothoracic Surgery (H.O., A.R.D., F.E., B.A.D., M.A., M.P.F.), Radiology (L.J.P.), and Pathology (A.J.C.), Stanford University, CA; Department of Cardiovascular Surgery, Jichi Medical University, Saitama Medical Center, Saitama, Japan (H.O., M.A., H.A.); Lantheus Medical Imaging, North Billerica, MA (D.C.O., R.R.C., S.P.R.); Agilent Technologies, Yarnton, Oxford, United Kingdom (M.M.); Departments of Radiology (G.K.) and Medical Informatics and Radiology (H.S.), Erasmus MC, Rotterdam, The Netherlands; and Division of Cardiovascular Medicine, Stanford University, CA (M.V.M.).
authors.forename: Matteo
authors.initials: M
authors.lastname: Milanesi
authors.affiliation: From the Departments of Cardiothoracic Surgery (H.O., A.R.D., F.E., B.A.D., M.A., M.P.F.), Radiology (L.J.P.), and Pathology (A.J.C.), Stanford University, CA; Department of Cardiovascular Surgery, Jichi Medical University, Saitama Medical Center, Saitama, Japan (H.O., M.A., H.A.); Lantheus Medical Imaging, North Billerica, MA (D.C.O., R.R.C., S.P.R.); Agilent Technologies, Yarnton, Oxford, United Kingdom (M.M.); Departments of Radiology (G.K.) and Medical Informatics and Radiology (H.S.), Erasmus MC, Rotterdam, The Netherlands; and Division of Cardiovascular Medicine, Stanford University, CA (M.V.M.).
authors.forename: Gyula
authors.initials: G
authors.lastname: Kotek
authors.affiliation: From the Departments of Cardiothoracic Surgery (H.O., A.R.D., F.E., B.A.D., M.A., M.P.F.), Radiology (L.J.P.), and Pathology (A.J.C.), Stanford University, CA; Department of Cardiovascular Surgery, Jichi Medical University, Saitama Medical Center, Saitama, Japan (H.O., M.A., H.A.); Lantheus Medical Imaging, North Billerica, MA (D.C.O., R.R.C., S.P.R.); Agilent Technologies, Yarnton, Oxford, United Kingdom (M.M.); Departments of Radiology (G.K.) and Medical Informatics and Radiology (H.S.), Erasmus MC, Rotterdam, The Netherlands; and Division of Cardiovascular Medicine, Stanford University, CA (M.V.M.).
authors.forename: Henk
authors.initials: H
authors.lastname: Smit
authors.affiliation: From the Departments of Cardiothoracic Surgery (H.O., A.R.D., F.E., B.A.D., M.A., M.P.F.), Radiology (L.J.P.), and Pathology (A.J.C.), Stanford University, CA; Department of Cardiovascular Surgery, Jichi Medical University, Saitama Medical Center, Saitama, Japan (H.O., M.A., H.A.); Lantheus Medical Imaging, North Billerica, MA (D.C.O., R.R.C., S.P.R.); Agilent Technologies, Yarnton, Oxford, United Kingdom (M.M.); Departments of Radiology (G.K.) and Medical Informatics and Radiology (H.S.), Erasmus MC, Rotterdam, The Netherlands; and Division of Cardiovascular Medicine, Stanford University, CA (M.V.M.).
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Connolly
authors.affiliation: From the Departments of Cardiothoracic Surgery (H.O., A.R.D., F.E., B.A.D., M.A., M.P.F.), Radiology (L.J.P.), and Pathology (A.J.C.), Stanford University, CA; Department of Cardiovascular Surgery, Jichi Medical University, Saitama Medical Center, Saitama, Japan (H.O., M.A., H.A.); Lantheus Medical Imaging, North Billerica, MA (D.C.O., R.R.C., S.P.R.); Agilent Technologies, Yarnton, Oxford, United Kingdom (M.M.); Departments of Radiology (G.K.) and Medical Informatics and Radiology (H.S.), Erasmus MC, Rotterdam, The Netherlands; and Division of Cardiovascular Medicine, Stanford University, CA (M.V.M.).
authors.forename: Hideo
authors.initials: H
authors.lastname: Adachi
authors.affiliation: From the Departments of Cardiothoracic Surgery (H.O., A.R.D., F.E., B.A.D., M.A., M.P.F.), Radiology (L.J.P.), and Pathology (A.J.C.), Stanford University, CA; Department of Cardiovascular Surgery, Jichi Medical University, Saitama Medical Center, Saitama, Japan (H.O., M.A., H.A.); Lantheus Medical Imaging, North Billerica, MA (D.C.O., R.R.C., S.P.R.); Agilent Technologies, Yarnton, Oxford, United Kingdom (M.M.); Departments of Radiology (G.K.) and Medical Informatics and Radiology (H.S.), Erasmus MC, Rotterdam, The Netherlands; and Division of Cardiovascular Medicine, Stanford University, CA (M.V.M.).
authors.forename: Michael V
authors.initials: MV
authors.lastname: McConnell
authors.affiliation: From the Departments of Cardiothoracic Surgery (H.O., A.R.D., F.E., B.A.D., M.A., M.P.F.), Radiology (L.J.P.), and Pathology (A.J.C.), Stanford University, CA; Department of Cardiovascular Surgery, Jichi Medical University, Saitama Medical Center, Saitama, Japan (H.O., M.A., H.A.); Lantheus Medical Imaging, North Billerica, MA (D.C.O., R.R.C., S.P.R.); Agilent Technologies, Yarnton, Oxford, United Kingdom (M.M.); Departments of Radiology (G.K.) and Medical Informatics and Radiology (H.S.), Erasmus MC, Rotterdam, The Netherlands; and Division of Cardiovascular Medicine, Stanford University, CA (M.V.M.). mfischbe@stanford.edu.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Fischbein
mesh_terms: D000784:Aortic Dissection / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000737:chemistry* / Q000473:pathology; D017545:Aortic Aneurysm, Thoracic / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D002614:Chelating Agents; D003287:Contrast Media; D004195:Disease Models, Animal; D004549:Elastin / Q000032:analysis / Q000172:deficiency*; D005240:Feasibility Studies; D006573:Heterocyclic Compounds, 1-Ring; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008382:Marfan Syndrome / Q000150:complications* / Q000175:diagnosis / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D015203:Reproducibility of Results
chemical_list: D002614:Chelating Agents; D003287:Contrast Media; D006573:Heterocyclic Compounds, 1-Ring; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D004549:Elastin
keywords: Marfan syndrome; aortic aneurysm, thoracic; magnetic resonance imaging