Assessment of elastin defcit in a Marfan mouse aneurysm model using an elastin-specifc magnetic resonance imaging contrast agent
Circulation. Cardiovascular Imaging , Volume 7 - Issue 4 p. 690- 696
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 (Fbn1C1039G/+) 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-specifc magnetic resonance contrast agent in Fbn1C1039G/+ mice. Methods and Results-Ascending aorta elastin content was measured in 32-week-old Fbn1C1039G/+ mice and wild-type (n=9 and n=10, respectively) using 7-T MRI with a T1 mapping sequence. Signifcantly lower enhancement (ie, lower R1 values, where R1=1/T1) was detected post-elastin-specifc 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-specifc 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-specifc 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.
|, , ,|
|Circulation. Cardiovascular Imaging|
|Organisation||Department of Radiology|
Okamura, H, Pisani, G, Dalal, K, Emrich, F, Dake, B.A, Arakawa, M, … Fischbein, M.P. (2014). Assessment of elastin defcit in a Marfan mouse aneurysm model using an elastin-specifc magnetic resonance imaging contrast agent. Circulation. Cardiovascular Imaging, 7(4), 690–696. doi:10.1161/CIRCIMAGING.114.001658