The main findings of our study are: 1) quantitative T1-mapping is a more robust technique compared to T2W, as T1 measurements show a significantly lower variability than T2W, their acquisition is faster with a better spatial resolution (reconstructed pixel size of 0.9 × 0.9 mm/experimental pixel size 1.8 × 1.8 mm versus 2.1 × 1.6 mm) 2) non contrast T1-mapping accurately detect acutely injured myocardium in MI patients when compared to T2W and LGE as markers of acute injury; 3) the diagnostic performance of T1-mapping is at least as good as that of T2W-CMR for detecting acute myocardial injury, 4) non-contrast T1-mapping allows assessment of the extent of acute myocardial damage on a segmental level 5) myocardial salvage index can be calculated based on T1-mapping with similar results compared to T2W 6) T1 values are strongly related to the likelihood of functional improvement at 6 months.
We believe that the results of this study are of direct clinical relevance. For the first time we report on the potential use of quantitative pre-contrast T1-mapping techniques to further improve our ability to characterize the presence and extent of acute myocardial injury and to determine reversible myocardial injury and salvaged myocardium by CMR. The current CMR imaging techniques used to assess acute ischemic injury, T2W and LGE imaging, have important limitations in relation to: a) their clinical applicability in acutely ill patients not always capable to hold their breath; b) the accurate assessment of the injury due to inherent issues such as variability of the measurements because of image gradients, partial volume effects and threshold dependent postprocessing. T1-mapping allows for faster acquisition compared to standard T2W and LGE techniques, and it is a more robust technique with less variability in T1 measurements at improved spatial resolution. Furthemore, both LGE and T2W are semi-quantitative methods which rely on the use of an arbitrary threshold, usually set at 2 SD above remote 'normal' myocardium, to delineate areas of myocardial oedema and/or scarring . However, the use of a reference ROI in the remote myocardium may lead to false negative findings when systemic processes globally affect the heart. Secondly, it is unclear whether this arbitrary threshold of 2 SD (rather than 3 SD or 5 SD) accurately reflects myocardial tissue changes occurring early after myocardial infarction . Thirdly, post processing is time-consuming and not always suitable to applications in acute setting. We recently showed that, due to the dynamic pathophysiological tissue changes occurring very early after an acute ischemic event, there is a significant variability in acute CMR imaging findings, and consequently in derived clinical prognostic indices such as salvageable myocardium . These issues often make the interpretation of CMR findings in acute MI difficult. A novel CMR technique, which would allow for a more detailed and quantitative characterization of acutely injured myocardium, would thus be highly desirable. Our findings suggest that quantitative T1-mapping techniques are a suitable tool for this. A recently validated improved technique (ShMOLLI) allows for fast acquisition of high resolution pre-contrast T1-mapseven at patients with high heart rates and therefore it is well suited for imaging ACS patients .
This is the first study in patients with ACS that has used T1-mapping at 3 Tesla to assess the presence and the extent of acute ischemic injury compared to accepted gold standard measurements of salvageable myocardium such as T2W and LGE-CMR. To the best of our knowledge, no other T1-mapping studies have been conducted at 3T; however previous work conducted at 1.5T CMR by Messroghli et al. demonstrated that pre-contrast T1-mapping can detect acute myocardial infarction with high sensitivity and specificity (96% and 91%, respectively), against LGE as the gold standard. Goldfarb et al. also showed increased T1 values in LGE positive myocardial infarcts up to 1 month after the acute event. However, in both these studies, oedema imaging by T2W-CMR was not performed [20, 21]. As shown in previous animal studies, the mechanism underlying the increase in T1 values in acutely ischemic myocardium is likely related to the increase in tissue water content, which has been shown to exceed the area of infarction by histological assessment [19, 31]. We confirm these experimental findings in the clinical setting, as we demonstrated higher T1 values in areas of oedematous myocardium within 24 hours after an acute ischemic event. Our results also indicate that quantitative T1-mapping measurements correlate well withT2W measurements, but show significantly lower variability than T2W-CMR. Therefore, T1-mapping may be superior to T2W-CMR for assessment of acute myocardial injury in MI. Indeed, this is further supported by the better diagnostic performance of T1-mapping compared to T2W-CMR in detecting small areas of acute myocardial injury in patients with NSTEMI.
Our results also indicate that T1-mapping allows for the assessment of the extent of segmental injury in the acute setting. This is further supported by the relationship between T1 values and contractile function. The impairment of contractile function in regions with high T1 values is due to severe myocardial damage. The assessment of irreversible injury in the early days following an acute ischemic event is challenging due to several issues. Recently published data,[6–9] showed a rapid reduction in LGE volumes occurring in the days following the acute event and have therefore challenged the view that acute LGE equals to stable irreversible injury but may rather reflect a dynamic process resulting from. Therefore, acute LGE (within 7 days of acute MI) might not be a reliable predictor of functional recovery in this setting. Furthermore, Matsumoto et al. recently validated early gadolinium enhancement imaging to assess area at risk, indicating that the imaging time to assess irreversible injury acutely is critical and poorly defined. Others have suggested that, to obtain an accurate assessment of the irreversible injury, late gadolinium should be acquired 20 minutes post injection  with consequent prolongation of the acquisition protocol and limited applicability in unstable acutely infarcted patients. Based on our findings, high T1 values in acutely ischemic myocardium reflect both, areas positive for T2W and for LGE. Previous reports in experimental models have shown that, following prolonged ischemia, T1 values may increase above and beyond the corresponding increase in water content; this may be related to a more severe degree of cellular injury with consequent release of intracellular ions into the extracellular space . In keeping with these experimental findings, our results indicate that the likelihood of improvement in function at 6 months decreases with incremental increases of T1 values. Based on these results, T1-mapping may be considered a better predictor of recovery of function compared to acute LGE although the predictive value of T1-mapping does not reach the predictive value of chronic LGE . Clearly, acute T1-mapping reflects the sum of reversible and irreversible injury while chronic LGE represents irreversible injury only, therefore a better relationship with 6 months functional improvement is expected for the latter [29, 33]. However, information on chronic LGE findings is not available when assessing patients acutely. Further studies will be needed to assess the potential of T1-mapping to depict the changes occurring in the myocardium in the early days post MI and their predictive value.
Finally, we demonstrated that T1 values are significantly lower in areas of MO compared to T1 values in infarcted areas without MO. This is likely to a combination of blood degradation products (hemorrhage) and reduced water content, which both result in lower T1 values compared to infarcts without MO. The prognostic value of MO/hemorrhage as a predictor of adverse LV remodeling [34, 35] is well recognized. Further work is needed to better characterize areas of MO with non-contrast T1-mapping and to determine whether additional prognostic information can be derived by ShMOLLI T1-mapping in this setting.
Even though T1-mapping is an inherently quantitative method providing pixel-wise absolute T1 values, the lack of invasive tissue sampling only permits comparisons between arbitrary chosen thresholds. We chose 1271 msec as the closest value to replicate the common 2 SD threshold used in T2W oedema imaging. The use of an arbitrary choice is unavoidable in signal-intensity based imaging methods and it makes the method robust to different field strength and acquisition sequences . However, a 10% threshold might still change, and further investigation (possibly with histologic comparison) will be needed to fully address this issue.
Also, at 3T we encountered frequent SSFP off-resonance artifacts despite shim correction, and 10% of ShMOLLI segments had to be excluded from analysis. This limitation is strictly related to high-field imaging: in fact the incidence of these artifacts is expected to be lower at 1.5Tallowing for application in clinical routine practice. Secondly, T2 mapping is a promising new CMR technique for assessing acute myocardial injury , which was not included in this study. We did, however, compare our T1-mapping approach with a novel, state-of-the-art T2prep-SSFP sequence shown to be superior to traditional T2W STIR imaging and widely considered a gold standard for oedema imaging in the acute setting. Thirdly, the 6 months follow up was not performed in 17% of our acute population. Although a complete follow up would have been desirable, the final sample size used to assess the relationship between T1 values in acute and long term functional improvement was adequate based on 80% power calculation with an accuracy of 0.05. Finally, we do not provide histopathological confirmation of our findings and the precise mechanisms leading to increase T1 values in acute myocardial injury warrant further investigation.