## 3 Cardiovascular Disease
### Abdominal Aortic Aneuryss
#### 3.5.3 Imaging AAA
Ao, aorta; FL, false lumen. Reproduced with permission from [PERSON] et al., 2019 [158]. CNA-35 [161]. Injection of CNA-35 micelles resulted in a significantly higher MRI signal enhancement in aneurysmal walls compared with nonspecific micelles. Histological analysis demonstrated that CNA-35 colocalized with type I collagen, although it is known to bind to all fibrillar collagens and collagen type IV [161]. Furthermore, the investigators also showed that stable aneurysms were associated with increased expression of collagen in the aortic wall and high CNA-35 uptake, whilst ruptured aneurysms displayed significant collagen degradation and low CNA-35 uptake demonstrating the potential of collagen imaging in the diagnosis and risk stratification of AAA. Given the most abundant collagens in the aortic wall are type I and III collagen, [PERSON] el al investigated whether changes of the propeptide of type III collagen (PIIINP) in serum could be associated with characteristics of AAA. PINNP measures the turnover of type III collagen [162]. [PERSON] et al. quantified the levels of animoterminal PIIINP and carboxyterminal propeptide of type I collagen by radioimmunoassays in patient samples of AAA and reported an increase in type III collagen in the serum of patients with AAA compared with controls. These result could be attributed to increased synthesis of type III collagen, increased degradation or both in these patients [162]. Fibrin  
Fibrin is a key protein in the formation of focal hematoma associated with aortic dissection and the development of larger thrombi during the progression of AAAs [154]. [PERSON] et al. used the fibrin-specific molecular MRI probe (EP2104R) in an angiotensin-II-infused ApoE-/- mouse model of AAA [149]. EP2104R enabled visualization of the small fibrin-rich hematoma located at the site of aortic dissection prior to aortic dilation and during the progression of AAA (Figure 26). In early thrombi, a strong in vivo signal and increased fibrin deposition was measured, which was confirmed by ex vivo analysis. In advanced thrombi, an increased remodelling of the matrix of the thrombus was observed and a relative decrease in fibrin expression was measured in vivo. This could potentially enable differentiation between early fibrin-rich and advanced remodelled aortic aneurysm thrombi. Figure 26: Assessment of a focal fibrin-rich intramural hematoma before the dilation of the aorta by fibrin MRI. A, On the TOF angiogram (**A1**), a nondilated aortic lumen without luminal irregularities can be appreciated in an ApoE-/- mouse 1 week after continuous infusion of angiotensin II. The red line indicates the alignment of in vivo MRI sequences and ex vivo histology. No significant enhancement of the aorta was measured on pre-contrast scans (**A2**) and following the administration of the nonspecific control agent (Gd-DTPA, **A3**). Following the administration of the fibrin-specific molecular probe, a strong focal enhancement was measured at the dissection side (**A4**–**A6**). On the EvG stain, the dissection of elastic laminae can be clearly visualised on magnified images (**B2**). In between the dissection, a fibrin-rich mural hematoma can be visualised (**B2**–**B4**). It is a strong signal from the fibrin that antibody was measured at the location of the intramural hematoma (**B4**). No relevant formation of elastin or collagen fibres was measured in the hematoma on histologic sections (**B1**–**B3**), indicating that no remodelling of the hematoma has occurred. aA—abdominal aorta; Gd-DTPA—gadopentetate dimeglumine; MRI—magnetic resonance imaging; rRA—right renal artery; TOF—time of flight. Reproduced with permission from [PERSON] et al., 2018 [149]. Matrix Metalloproteinases  
Similar to atherosclerotic arterial disease, MMPs play a significant role in aortic remodelling during the evolution of AAA (e.g., the degradation of elastin and collagen) [153; 154]. [PERSON] et al. used the MMP targeting MRI probe (P947) in an elastase-infused rat model of AAA [163].