Abstract
Background—The incidence of abdominal aortic aneurysms (AAAs) has increased during the last decades. However, 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 aortic wall tensile strength and stability. The progressive breakdown of structural proteins, in particular medial elastin, is responsible for the inability of the aortic wall to withstand intraluminal hemodynamic forces. Here we evaluate the usefulness of elastin-specific molecular MR-imaging for the in vivo characterization of AAAs.
Methods and Results—To induce AAAs, Apoe-/--mice were infused with angiotensin-II (Ang-II). An elastin-specific magnetic-resonance molecular imaging agent (ESMA) was administered after one, two, three and four weeks of Ang-II infusion to assess elastin composition of the aorta (n=8 per group). The high signal provided by ESMA allowed for imaging with high spatial-resolution, resulting in an accurate assessment of ruptured elastic laminae and the compensatory expression of elastic fibers. In vivo contrast-to-noise-ratios (CNR) and R1-relaxation-rates after ESMA administration were in good agreement with ex vivo histomorphometry (ElasticaVanGiesson-stain) and gadolinium concentrations determined by inductively-coupled-plasma-mass-spectroscopy. Electron-microscopy confirmed colocalization of ESMA with elastic fibers.
Conclusions—Changes in elastin content could be readily delineated and quantified at different stages of AAAs by elastin-specific molecular MR-imaging. ESMA-MRI offers potential for the noninvasive detection of the aortic rupture site prior to dilation of the aorta and the subsequent in vivo monitoring of compensatory repair processes during the progression of AAAs.
Methods and Results—To induce AAAs, Apoe-/--mice were infused with angiotensin-II (Ang-II). An elastin-specific magnetic-resonance molecular imaging agent (ESMA) was administered after one, two, three and four weeks of Ang-II infusion to assess elastin composition of the aorta (n=8 per group). The high signal provided by ESMA allowed for imaging with high spatial-resolution, resulting in an accurate assessment of ruptured elastic laminae and the compensatory expression of elastic fibers. In vivo contrast-to-noise-ratios (CNR) and R1-relaxation-rates after ESMA administration were in good agreement with ex vivo histomorphometry (ElasticaVanGiesson-stain) and gadolinium concentrations determined by inductively-coupled-plasma-mass-spectroscopy. Electron-microscopy confirmed colocalization of ESMA with elastic fibers.
Conclusions—Changes in elastin content could be readily delineated and quantified at different stages of AAAs by elastin-specific molecular MR-imaging. ESMA-MRI offers potential for the noninvasive detection of the aortic rupture site prior to dilation of the aorta and the subsequent in vivo monitoring of compensatory repair processes during the progression of AAAs.
| Original language | English |
|---|---|
| Number of pages | 42 |
| Journal | Circulation-Cardiovascular imaging |
| DOIs | |
| Publication status | E-pub ahead of print - 2014 |