## 3 Cardiovascular Disease
### Abdominal Aortic Aneuryss
#### 3.5.3 Imaging AAA  
Elastin  
Elastin underpins the structural integrity of the aortic wall and constitutes up to a third of its weight [155]. In a mouse model of aortic aneurysm, [PERSON] et al. demonstrated the feasibility of an elastin-specific MR agent (ESMA) to monitor the in vivo stages of aortic wall remodelling prior to and during aortic dilatation, with subsequent histopathological validation (Figure 24) [156]. Figure 24: In vivo assessment of the aortic rupture site prior to the dilation of the aorta. In an ApoE/mouse 1 week after continuous infusion of angiotensin II, the angiogram demonstrates an aortic lumen without dilatation or luminal irregularities (**A1**). The red line indicates the location of the corresponding transverse images. On elastin-specific magnetic resonance molecular imaging agent (ESMA)-MRI, the rupture of elastic laminae could be clearly visualized in vivo (**A4**,**A5**). Corresponding ex vivo histological sections (**A6**,**A7**) confirmed the rupture of elastic laminae in this area (magnification of A6, orange arrows). On pre-contrast (**A2**) and gadolinium diethylenetriamine penta-acetic acid enhanced images (**A3**), only minor enhancement of the arterial wall was observed. aA—abdominal aorta; EvG—Elastica van Gieson; HE—hematoxylin and eosin; rRA—right renal artery; and TOF—time of flight. Reproduced with permission from [PERSON] et al., 2014 [156]. Similarly, in a Marfan mouse model [PERSON] et al. demonstrated the potential of ESMA to detect decreased aortic wall levels of elastin compared with wild-type controls [157]. Recently, [PERSON] et al. advanced our understanding of dysfunctional elastogenesis in AAA disease by employing a newly developed gadolinium labelled tropoelastin-binding MRI agent (TESMA). This study assessed whether quantifying regional tropoelastin turnover correlates with aortic expansion in an Angio-II-infused murine model (Figure 25) [158]. The authors demonstrated that tropoelastin overexpression and the uptake of the contrast agent were confined within aneurysmal walls. Significantly, a parallel longitudinal imaging study demonstrated a greater proportion of tropoelastin:elastin in dilating compared to non-dilating aortas, which correlated with the rate of aortic expansion. Interestingly, treatment with aspirin and statins did not affect tropoelastin turnover or aortic dilatation in a small cohort of mice. Finally, TESMA was able to identify accumulation of tropoelastin in a small number of excised human aortic aneurysmal tissue as confirmed by histology. Collagen  
Despite an initial compensatory increase in collagen synthesis in the early stages of AAA onset, enzymatic (e.g., MMPs and cathepsin) collagen degradation dominates the subsequent progressive stages of AAA development, paving the way for aortic dilatation [159; 160]. In a mouse model of aortic aneurysm and rupture, [PERSON] et al. assessed the feasibility of in vivo molecular MRI of collagen using paramagnetic/fluorescent micellar nanoparticles functionalized with the collagen-binding protein  
Figure 25: MRI of tropoelastin shows enhancement at sites of aortic aneurysm or dissection. **(A)** A reformatted MRA of an Ang II-infused ApoE\({}^{-/-}\) mouse shows two regions of aortic dilation. **(B–G)** MRA, LGE-MRI, and histology of a non-dilated segment show a normal aortic size, low enhancement after administration of Gd-TESMA, and lack of tropoelastin, respectively. **(H–M)** At the level of the first aortic dilation, there is vascular enhancement of the aneurysm after administration of Gd-TESMA that co-localized with the accumulation of tropoelastin as verified histologically. **(N–P,T–V)** At the level of the second aortic dilation, MRI images show the formation of a false lumen indicative of an aortic dissection, with aortic enhancement after administration of Gd-TESMA and retrograde blood flow. **(Q–S)** Histology verified the formation of two lumens and the accumulation of tropoelastin in areas where vascular enhancement was observed in vivo using the tropoelastin agent.