Homare Okamura1, Laura J Pisani1, Alex R Dalal1, Fabian Emrich1, Benjamin A Dake1, Mamoru Arakawa1, David C Onthank1, Richard R Cesati1, Simon P Robinson1, Matteo Milanesi1, Gyula Kotek1, Henk Smit1, Andrew J Connolly1, Hideo Adachi1, Michael V McConnell1, Michael P Fischbein2. 1. 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.). 2. 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.
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. METHODS AND 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.
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. METHODS AND 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.
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