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Molecular assessment of aortic aneurysm wall integrity using an elastin-specific MR imaging probe
Journal of Cardiovascular Magnetic Resonance volume 15, Article number: O4 (2013)
The incidence of abdominal aortic aneurysms (AAAs) has increased in western societies and complications often lead to life threatening events. There is still controversy regarding 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 stability of the aortic and aneurysmal wall. Elastin degradation due to inflammation and metalloproteinases (MMPs) expression as well as de novo synthesis of immature elastin are considered key events in the development of AAAs.
The aim of this study was to test a novel small-molecular-weight elastin-specific MR probe for the in vivo assessment of arterial wall integrity in AAAs.
ApoE-/- mice were infused with angiotensin II for up to 4 weeks (1000ng/kg/min). An elastin-specific MR probe (Lantheus Medical Imaging, USA) was administered 1-4 weeks following Ang-II infusion. Mice were scanned at each time point pre, post control agent (Gd-DTPA) and after administration of the elastin-specific probe. Imaging was performed using a 3T Philips Achieva MR scanner with mice positioned on top of a microscopy coil. For the assessment of contrast agent distribution, delayed enhancement (DE) MRI scans were preceded by a 2D-Look-Locker to determine the optimal inversion time for blood signal nulling. Imaging parameters of the IR-3D GE DE-MRI were: FOV=30mm, matrix=300, spatial resolution=0.1, 0.5mm slice thickness, TR/TE=28/8.2ms, TR between IR pulses=1000ms and flip angle=30°. Immediately after the DE-MRI scan, a 3D-T1 mapping sequence was performed, consisting of 2 inversion-recovery prepared modified Look-Locker trains. Aneurysmal aortic wall samples were analysed ex vivo by inductively coupled plasma mass spectroscopy and histological staining.
The high signal provided by the elastin-specific MR probe allowed for imaging with high spatial resolution (100μm). In vivo AAA area measurements were in good agreement (R2=0.95, p<0.05, Fig. 1) with ex vivo measurement on histology (ElasticavanGiesson stain, Fig. 1). Contrast-to-noise-ratios (CNR) and R1 relaxation rates were in good agreement with ex vivo histomorphometry (Elastica stain, R2=0.77, p<0.05) and Gd concentrations determined by inductively coupled plasma mass spectroscopy (R2=0.74, p<0.05). Changes in elastin content could be readily delineated and quantified at different stages of AAAs. The most significant increase in elastin accumulation was observed in late stage aortic aneurysms (Fig. 2) and is likely related to compensatory remodeling and de novo synthesis of elastin fibers.
MRI in combination with an elastin-specific MR probe offers potential for the non-invasive characterisation of the aneurysmal aortic wall during development of AAAs and may help guiding treatment decisions.
The MRI scanner is partly supported by Philips Healthcare. A Wiethoff is an employee of Philips Healthcare. D Onthank, R Cesati and S Robinson are employees of Lantheus Medical Imaging. The study was funded by the British Heart Foundation (PG/09/061) and the contrast agent was provided by Lantheus Medical Imaging. Otherwise, there are no financial or other relations that could lead to a conflict of interest.
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Makowski, M.R., Wiethoff, A., Ebersberger, U. et al. Molecular assessment of aortic aneurysm wall integrity using an elastin-specific MR imaging probe. J Cardiovasc Magn Reson 15, O4 (2013). https://doi.org/10.1186/1532-429X-15-S1-O4
- Aortic Aneurysm
- Abdominal Aortic Aneurysm
- Delay Enhancement
- Elastin Degradation
- Microscopy Coil