## 5 Clinical Applications in Myocardial Imaging  
Multiple studies have assessed the role of USPIO-enhanced CMR in ischaemic cardiomyopathy (Figure 2). In a study that included 16 patients with acute ST-segmentelevation myocardial infarction, [PERSON] et al. demonstrated that USPIO were taken up by the infarcted myocardial tissue and, to a lesser degree, by the peri-infarct and the remote myocardium, as evidenced by increased R2* values [34]. This was in keeping with the results of an NIMINI-2 (Non-invasive Myocardial Inflammation Imaging Based on New Molecular Magnetic Resonance Imaging) study, which showed that the absolute T2* values were decreased in the infarcted myocardial zone and, again to a lesser degree, in the peri-infarct zone [30]. In the same study, ex vivo analysis revealed that USPIO uptake was detected specifically in cultured macrophages and not in the peripheral blood monocytes, supporting the theory that USPIO absorption is mainly due to their accumulation in infiltrating myocardial macrophages or their passive accumulation in areas of loss of endothelial integrity rather than their phagocytosis by peripheral macrophages that then relocate to the heart [30]. These two proof-of-concept studies laid the foundation for further trials that followed and demonstrated that USPIO accumulation following acute myocardial infarction reflects active cellular inflammation in the myocardium [31, 41]. As mentioned above, these studies showed that USPIO accumulated, albeit to a lesser degree, not only in the infarcted and peri-infarct but also in the remote myocardium, generating the hypothesis that inflammation and macrophage infiltration in the remote myocardium may lead to adverse myocardial remodelling. More recently, in a study that included patients with acute MI and with chronic ischaemic cardiomyopathy, [PERSON] et al. demonstrated that a USPIO-enhanced multi-parametric multi-time-point CMR methodology specifically differentiates active myocardial macrophage infiltration from the passive distribution of dissolved USPIO in the tissue interstitium [1]. Importantly, it was shown for the first time that there is persistent active inflammation, as evidenced by macrophage infiltration, both in the infarcted and the remote myocardium in the chronic phase following an MI [1]. Larger studies using USPIO-enhanced CMR are now needed to examine the potential role of active macrophage  
Figure 2: Examples of myocardial oedema and ferumoxytol enhancement in the infarct area after myocardial infarction (MI). Three examples of MI (1, anteroseptal, 2, lateral and 3, inferior) showing LGE on T1-weighted imaging (**1A**–**3A**), ferumoxytol enhancement (**R2* maps) (**1B**–**3B**,**1C**–**3C**), and oedema (T2 maps) (**1D**–**3D**,**1E**–**3E**) at early (up to 10 days in (**1B**–**3B**,**1D**–**3D**)) and late (3 months in (**1C**–**3C**,**1E**–**3E**)) post-MI. Early inflammation and oedema seen on R2* maps (dark region) and T2 maps (light region), respectively, have improved or resolved by three months [31]. Reproduced with permission from [PERSON] et al. [31] under a Creative Commons Attribution 4.0 International License. infiltration in the pathogenesis of adverse myocardial remodelling in ischaemic cardiomyopathy. The limited available data on USPIO uptake following coronary artery bypass graft (CABG) have demonstrated that myocardial injury following CABG may be less dependent on macrophage infiltration and inflammation, as there was no correlation between USPIO uptake and high-sensitivity cardiac troponin or the cardiopulmonary bypass time [42]. USPIO-enhanced CMR has provided essential insights into the pathophysiology of Takotsubo cardiomyopathy. While it has been known that oedema and inflammation play a central role in this disease, [PERSON] et al. demonstrated for the first time that active macrophage infiltration drives the pathological ventricular response and cellular inflammation [43; 44].