Normal myocardium has low to intermediate signal on T2W images, but increased regional water content, such as infarct related edema, causes an increase in the T2-relaxation time and T2W signal intensity [15]. Hemorrhage and the breakdown of oxygenated hemoglobin also influence magnetic properties of the surrounding tissue. The effects of hemoglobin degradation have been extensively studied in patients with cerebral hemorrhage; they are complex and strongly dependent on the age of the hematoma and the integrity of the erythrocyte membrane [8]. T2W signal is high in the very early, hyperacute phase, but then falls because of the paramagnetic effects of deoxyhemoglobin and intracellular methemoglobin [8]. Especially in the core of the hematoma, where there is marked hypoxia, signal may remain very low for a prolonged period of time [16]. Lotan et al. studied IMH in a canine myocardial infarction model using ex-vivo T2W [9]. They found areas of low signal within the zone of increased signal that accurately matched the location of macroscopic hemorrhage in all animals but one (with a very small hemorrhage), and no hypointense T2W regions in the animals without hemorrhage. Hemorrhage size according to CMR correlated closely to size determined from tissue slices and according to labeled red blood cells. Basso et al. recently compared in vivo and ex-vivo CMR to histopathological findings in two patients that had died 12 and 24 days after percutaneous revascularization, respectively [17]. Both patients had hemorrhagic infarcts, with massive bleeding at the core of the infarct. Both in vivo and ex-vivo T2W showed areas of low signal intensity within areas of high signal intensity that corresponded to hemorrhage and edema, respectively. Thus, although we have no direct proof of the presence of hemorrhage in our patients, we believe that these studies sufficiently show that hemorrhage and hemoglobin breakdown leads to T2W signal attenuation as documented in our study. Our results are roughly in line with the results from previous studies that used T2*(‘star’)-weighted gradient-echo techniques to visualize IMH [10, 11]. Asanuma et al. found IMH in 9 of 24 (38%) patients with reperfused anterior MI [10]. Patients with IMH had larger enzymatic infarct size, more Q-wave infarctions and less improvement in echocardiographic wall motion score. Ochiai et al. showed IMH in 13 of 39 (33%) patients with reperfused infarction, and also found an association between IMH, infarct severity and less improvement of ventriculographic ejection fraction [11]. There are no studies comparing T2W spinecho imaging to T2*-weighted gradient-echo imaging for the assessment of IMH, and, at this point, it is not clear which is the optimal technique for its visualisation. Cardiac application of both techniques has been validated in a limited number of experimental and pathological studies [9, 11, 18]. Although T2*-weighted gradient-echo imaging is very sensitive to the paramagnetic effects of the deoxyhemoglobin and methemoglobin, it requires relatively long echo times that may degrade image quality during cardiac imaging [8]. T2W spinecho imaging has the advantage that it also depicts infarct related edema, which has been shown to correspond to the area at risk [19, 20]. In line with a recent report by Friedrich et al., we found that mean (single slice) T2W infarct area was (approximately 70%) larger than DE infarct area [20].

Hemorrhagic myocardial infarction was rarely seen in autopsy studies in the pre-reperfusion era, but its reported incidence markedly increased after the introduction of thrombolytic therapy [6, 21]. Later studies showed that it also occurred after primary PCI [10, 11]. The appearance of hemorrhage therefore depends on the coexistence of myocardial reperfusion and microvascular damage in the setting of severe myocardial ischemia [7, 17]. The large majority (81%) of our patients with MVO also had IMH, and MVO size in the 5 patients without IMH was very small (< 1% of total infarct size). Further more, our results suggest that hemorrhage severity, as reflected by the degree of T2W signal attenuation as contrast-to-noise ratio, is related to infarct and MVO extent, but does not have prognostic value beyond MVO. In early studies in the mid-seventies, Kloner et al. already demonstrated that extravasation of erythrocytes is one of the morphological features found in areas of no-reflow [22]. This close relation between MVO and IMH might explain the lack of additional prognostic significance as seen in our study. Figure 2 illustrates the co-existence of edema, IMH and MVO in a patient who died 3 days after inferoposterior myocardial infarction (patient was not included in the study group).

The non-invasive assessment of IMH by CMR might be used to indicate infarct severity and underlying microvascular injury, e.g. in patients with (moderate to severe) renal insufficiency, who have a relative contra-indication against the use of gadolinium compounds [23]. However, further study is needed to define the optimum CMR technique to assess IMH, and to determine the exact role of IMH in the myocardial healing process.

Spatial coverage of the T2W images was limited as we focused on the identification of hemorrhage in the core of the infarct. As a result, we may have missed regions of signal attenuation in adjacent slices in the five patients with MVO but without IMH.

Signal-to-noise ratios are related to scan parameters such as voxel size, and therefore our results may not be directly applicable when other scanners are used.

The current breath-hold T2W spin-echo imaging technique is limited by its sensitivity to artifacts caused by cardiac or respiratory motion, as illustrated by the considerable number of non-diagnostic images in our study group (10% of long axis images, 20% of short axis images). A recently proposed adaptation of the technique to optimize performance has not yet been evaluated in a clinical setting [24].