After reperfusion of acutely ischaemic myocardium, previous studies showed that average T1 and T2* values change in the affected area as the result of infarction-related oedema [
1,
4,
8,
23].Our study confirmed these findings and shows that patients with microvascular injury have decreased T1 and T2* values in the MI core. This has implications for the interpretation of native T1 mapping values shortly after AMI as, without the proper use of T2* mapping, myocardium with MVI may be incorrectly classified as normal, unaffected myocardium.
LGE studies have shown that microvascular injury may affect up to 30 to 50% of patients with AMI [
24‐
26]. MVI is associated with increased infarct size, and is a well-established predictor of impaired functional recovery, remodelling and increased incidence of major adverse cardiac events [
25‐
27]. Histological studies of MVI show that intramyocardial haemorrhage is a major component of the injury, due to disruption of the microvasculature and extravasation of blood cells upon reperfusion [
7,
28‐
30]. A number of erythrocyte haemoglobin breakdown products, most notably deoxyhaemoglobin and methaemoglobin, induce paramagnetic effects, effectively altering the tissue relaxation times in the area of MVI [
31,
32]. From brain ischaemia studies, it is known that local T1 and T2 relaxation time values shorten due to fibrin clot formation and retraction, erythrocyte dehydration, and changes in the water hydration layer due to resorption of water from the protein solutions in the haemorrhagic area [
31,
33]. Previous studies already suggested that T1 values might be suggestive of the severity of injury in the reperfused MI core [
3,
4]. Dall’armellina et al. showed how T1 values rise in more severe forms of myocardial infarction, but did not incorporate the presence or absence of MVI [
3]. Carrick et al. demonstrated in a large cohort that decrease in T1 values in the MI core is associated with worse outcome and postulated that it is most likely caused by haemorrhage [
4]. However, no cine images or STIR-targeted T1 maps of the MI core were made. Our study confirms the aforementioned findings and demonstrates that T2* mapping corroborates that the changes in T1 values are likely caused by the effects of haemorrhage [
7]. T2* is considered even more sensitive to the effects of the haemoglobin breakdown and haemorrhage than T2-weighted imaging [
34]. During spin echo signal creation in T2 weighted imaging, magnetic spins are refocused and rephased using 180 degree RF pulses prior to signal detection, thus correcting the loss of signal due to static susceptibility influences. T2* imaging on the other hand, is sensitive to static susceptibility effects and strongly decreases due to iron in haemoglobin breakdown products. T2* mapping is a well-established technique to detect myocardial iron deposition in transfusion dependent patients, [
35‐
37] with values below 20 ms considered to be abnormal. It has been shown that lower T2* values are associated with lower LVEF and adverse remodelling [
8]. We confirmed that T2* values in the MI core of patients with MVI are around this lower limit of normal, and clearly lower than in patients without MVI, or in remote areas. Comparable to T2 relaxation, T2* increases in the presence of myocardial oedema, which explains the higher values in the MI border zones of the infarction.
The magnetic susceptibility effects related to the presence of haemorrhage in the MI core are a potential pitfall in the interpretation of T1 measurements in patients with a recently reperfused AMI. MI border zone T1 was higher in patients with MVI, reflecting more severe myocardial injury and inflammation. Interestingly, previous studies have found that increased T1 values were associated with more severe myocardial injury and less functional improvement [
3,
38]. In these studies, the T1 relaxation times were averaged for the entire myocardium, and the high T1 found in the MI border zone of the infarct may have more than offset the lower values in the MI cores of the patients with MVI. Our results support earlier findings that local differences in T1 relaxation due to the presence of MVI and haemorrhage need to be considered [
4]. A wide range of T1 values was found for remote myocardium, which may be explained by differences in myocardial perfusion [
39]. However, further studies are needed to investigate this phenomenon and its cause. An inherent limitation of MOLLI acquisitions are its relatively long breath-holds (17 heart beats) which make it sensitive to motion artefacts. This led to an exclusion of nine of our 52 participating patients, making it the most common reason for study exclusion. This could, theoretically, be tackled by using a shorter acquisition technique, such as ShMolli [
40,
41]. However, as remote T1 values were similar in both patient groups, a significant measurement error seems unlikely. Although our study group was relatively small, T2* values showed a correlation with volumes and ejection fraction where T1 values did not. This supports earlier findings that T2* values may confer additional prognostic value [
8]. Further studies in larger study populations are necessary to define the prognostic significance of T1 and T2* values.
Limitations
As our study group was relatively small, subgroup analyses on differences in T1 and T2* values for infarcts in different coronary territories was not possible. Earlier findings suggest that T2* values may confer prognostic value on cardiac function [
8]. However, the numbers in our study are too small for creating a reliable model with proper correction for confounding factors. Further studies with a larger number of patients are necessary to assess the prognostic significance of T1 and T2* values.
MOLLI T1 mapping causes a systematic underestimation of T1 relaxation in tissues with short T2 values [
42]. As the T2 and T2* relaxation are interdependent, it is expected that MOLLI underestimates T1 relaxation in tissues with short T2* values. Whether the shortened T1 values in the areas with MVI are based on a MOLLI-specific artefact or ‘genuinely’ shortened T1 values remains to be investigated using a technique like SACHA, [
40,
43] but for clinical purposes the presence of MVI should be considered when using MOLLI-measured T1 maps, as the MOLLI technique is one of the most widely applied techniques for myocardial T1 assessment today [
44]. Additionally, it should be noted that the MOLLI sequence parameters have been improved in the last years [
40,
41]. However, our study was performed with the MOLLI sequence parameters that were used at the start of the study, in 2011 [
40].
Finally, we did not assess myocardial T2 relaxation in our study, which poses a limitation to our data as T2 mapping would have given us additional insight in the tissue characteristics. However, a robust version of this sequence was not available at the time of initiation.