## 3 Cardiovascular Disease
### Myocardial Infarction
#### 3.3.3 Imaging Myocardial Infarction
Despite the final measured area of infarction being similar to that measured with a conventional Gd-based contrast agent, the authors observed progressively increased ESMA uptake within the infarcted area, peaking at day 21 post-MI, which correlated with increased synthesis of tropoelastin and improvement in ejection fraction, suggesting some compensatory properties of elastin post myocardial injury in a mouse of permanent occlusion (Figure 16) [108; 109]. Figure 15: **(a,b,d,e)** Gradient-echo IR MR images and (**c,f**) corresponding picrosirius red–stained histologic sections of the LV. Arrows point to area of scarring. (**a,d**) Standard anatomic MR images acquired by using a double IR gradient-echo sequence (8.0/3.7/R-R interval). (**b,e**) Regions of contrast enhancement on midventricular short-axis MR images (7.1/3.0/430) of the LV at two section locations obtained 40 min after EP-3533 injection correlate closely with (**c,f**) photomicrographs of picrosirius red–stained tissue sections shown at nine times their original size. LV—left ventricle. Reproduced with permission from [PERSON] et al., 2008 [107]. In an alternative approach, perfluorocarbons were combined with elastin MRI to enable simultaneous assessment of inflammation and elastin remodelling in a murine model of myocardial infarction using a single loop multinuclear \({}^{1}\)H/\({}^{19}\)F send receive coil [110]. This confirmed an early inflammatory response (peaking at day 7 post infarction) followed by elevated elastin remodelling (peaking at day 21 post MI) (Figure 17) [110]. Figure 16: Gadolinium-based elastin-specific MR contrast agent (Gd-ESMA) for imaging of myocardial scar. (**A**), Chemical structure of Gd-ESMA. (**B**), Cross-sectional cardiac MR images of C57 BL/6] mouse on postoperative day 7 after myocardial infarction. Two-chamber view and short-axis view obtained at the level of the blue lines in first 4-chamber (image) show accumulation of Gd-ESMA (second and third image) in the myocardial scar, corresponding to the infarct area on triphenyltetrazolchloride (TTC) staining (last image). Reproduced with permission from [PERSON] et al., 2014 [108]. Figure 17: (**A**): Assessment of inflammatory response after myocardial infarction in mice at 3T magnetic resonance imaging (MRI) using 19F perfluorocarbons. Representative short-axis views of co-registered 1H + 19F images (left column; N = 8 MI animals/time-point; N = 6 SHAM-operated animals/time-point) and macrophage immunohistochemistry (IHC; macrophages identified as MAC-3 positive, brown; N = 4 MI animals/time-point; N = 3 SHAM-operated animals/time-point) from the heart at 3, 7, 14, and 21 days after MI. (**B**): In vivo imaging of extracellular matrix remodelling after myocardial infarction with a gadolinium-based elastin/tropoelastin-specific contrast agent Representative short-axis images of relaxation rate (RI, left columns) maps and tropoelastin immunohistochemistry (IHC; right columns) of the hearts sections at 7, 14, and 21 days post-myocardial infarction (MI) at 3T magnetic resonance imaging (MRI). Tropoelastin fibres were identified as black fine fibre network. Reproduced with permission from [PERSON] et al., 2018 [110]. Matrix Metalloproteinases  
Targeting the extensive role of MMPs in post-MI remodelling, [PERSON] et al. proposed a novel and highly sensitive MMP-targeted imaging approach in a murine model [111]. This study used an MMP-targeted \({}^{99\text{m}}\)Tc-labelled compound (\({}^{99\text{m}}\)Tc-RP805), which acted on the activated catalytic domain and therefore exhibit enzyme inhibitory effects. Using SPECT imaging, \({}^{99\text{m}}\)Tc-RP805 uptake was increased threefold and twofold within the infarcted and remote myocardium regions, respectively, compared with control mice; confirming the significant role of MMPs within both the infarcted and remote myocardium following an ischaemic insult. In a review article by [PERSON] et al., further applications of the RP805 probe for imaging the ECM in CVD are discussed [12].