## 3 Cardiovascular Disease
### Atherosclerotic Arterial Disease
#### 3.2.3 Imaging Atherosclerosis
Figure 9: **(A)** Typical MR images, (B) normalised enhancement ratio of the aortic wall to muscle (NER\({}_{\text{w}}\)) and (C) the difference between the contrast-to-noise ratio from the aortic wall to muscle pre- and post-contrast injection of abdominal atherosclerotic plaques for pre- and 24 h post-injection (\(\Delta\)CNR\({}_{\text{w}}\)) of HDL, EP3533-HDL, and EP3612-HDL at day 0 (yellow bars) and day 28 (green bars) of Reversa mice in the regression group. The red arrows point to the aortas. Error bars are representing mean \(\pm\) SD. Statistical significance at \(p<0.05\) (n = 25) is indicated by the asterisks (*). HDL—high density lipoprotein. Reproduced with permission from [PERSON] et al., 2013 [65]. Fibrin  
Fibrin plays a crucial role during plaque progression, development of intraplaque haemorrhage and formation of thrombus following plaque rupture [71; 72]. It is therefore an important target for molecular imaging of atherosclerotic plaque. [PERSON] et al. demonstrated the feasibility of molecular MRI of fibrin clots ex vivo using a novel fibrin-targeted contrast agent with a lipid-encapsulated perfluorocarbon nanoparticle incorporating numerous Gd-DTPA complexes into its outer surface [73]. The ability to visualise human clots of variable sizes (0.5-7.0 mm) ex vivo was significantly improved after administration of this contrast agent compared to non-contrast T1 weighted imaging. In another study, the use of fibrin-specific paramagnetic nanoparticles enabled efficient targeting and signal enhancement of thrombi in the external jugular vein of a canine model in vivo [74]. Instead of nanoparticles, [PERSON] et al. used a gadolinium-based, small molecular weight, fibrin-binding MRI agent (EP-1242; EPIX Pharmaceutical) to image acute carotid plaque thrombus in guinea pigs [75]. Later on, [PERSON] et al. demonstrated the feasibility of in vivo molecular MRI of acute and subacute plaque thrombosis following plaque rupture using the gadolinium-based fibrin-binding MRI contrast agent (EP-1873) in a rabbit model of plaque rupture and thrombosis [76] (Figure 10). The same group also demonstrated the feasibility of acute coronary thrombus detection using a similar gadolinium based fibrin-binding contrast agent, EP-2104R, in a swine model [77] (Figure 11). EP-2104R was subsequently successfully translated into humans, demonstrating the in vivo potential of this fibrin-specific MRI contrast agent for the detection of acute venous and arterial thrombus in patients for the first time [78; 79] (Figure 12). Figure 10: **(A)**, Reformatted view of a coronal 3D data set shows sub-renal aorta \(\approx\)20 h after EP-1873 administration. Three well-delineated mural thrombi (arrows) can be observed, with good contrast between thrombus (numbered), arterial blood (dotted arrow), and vessel wall (dashed arrow). The in-plane view of the aorta allows simultaneous display of all thrombi, showing head, tail, length, and relative location. **(B–D)**, Corresponding cross-sectional views show good agreement with histopathology **(E–G)**. Reproduced with permission from [PERSON] et al., 2004 [76].