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) 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. (Circ Cardiovasc Imaging. 2014;7:690-696.)

Enhanced Caspase Activity Contributes to Aortic Wall Remodeling and Early Aneurysm Development in a Murine Model of Marfan Syndrome

“…Importantly, Q-VD-OPh treatment also significantly reduced aortic diameter at 3, 4, 5 and, 6 weeks in the Fbn1 C1039G/+ mice although the diameters remain greater than WT control ( Figure 2C), confirming that apoptosis participates in the pathogenesis of early aneurysm development. Although we have reported increased aortic wall thickness in Fbn1 C1039G/+ versus WT mice at 32 weeks, 8 no significant difference was detected at 2 to 6 weeks. Moreover, no difference in wall thickness was distinguished when comparing Q-VD-OPh versus vector control-treated Fbn1 C1039G/+ mice (data not shown).…”

Aortic and Cardiac Structure and Function Using High-Resolution Echocardiography and Optical Coherence Tomography in a Mouse Model of Marfan Syndrome

“…A more detailed examination of this approach can be seen in our previous study [11] the basic results of which are corroborated in the present study. Recently an MRI-based study was performed with LMI1174—a gadolinium-based elastin-specific magnetic resonance contrast agent (ESMA) which accurately measures elastin bound gadolinium within the aortic wall [48]. In this study they found that in the 8 month Fbn1 C1039G/+ MFS mouse, there was a significant decrease in aortic wall elastin compared to WT.…”

Identification of type IV collagen exposure as a molecular imaging target for early detection of thoracic aortic dissection

“…The authors used an elastin-specific magnetic resonance imaging contrast agent to monitor the AAAs by assessing the elastin content within the ascending aortic aneurysm wall. MRI based on targeted probes was able to detect advanced, but not early, aneurysms 34 . An imbalance in collagen deposition/degradation, especially Col-I, is a key factor in the prognosis of AAAs 35 .…”