Determining the Severity of Tissue Injury in Acute MI with a 20-minute, Free-Running, Whole-heart Cardiac MRI

Background: Staging irreversible tissue injury in MI is essential for assessing risk of post-MI cardiovascular events. The Canadian Cardiovascular Society (CCS) classification¹ highlights progressive injury stages, from necrosis to microvascular obstruction (MVO) and intramyocardial hemorrhage (IMH), the latter carrying the highest risk (Fig. 1). While cardiac MRI is the preferred tool for staging severity of tissue injury in MI, it currently requires nearly an hour of multiple breath-held, ECG-gated acquisitions, limiting its utility. We sought to develop a 3D, free-breathing, non-ECG gated MRI approach for CCS staging of irreversible MI, including comprehensive assessment of microvascular injury patterns, that can be completed in < 20 minutes.

Methods: Image Model: A free-running 3D MRI method with low-rank tensor (LRT) reconstruction2,3 was developed to simultaneously capture cardiac and respiratory motion plus T1 and T2* dynamics after contrast injection for 14 min. Image Reconstruction: Time-resolved data were assigned to 15 bins (~57 sec/bin) and and temporal coefficients were estimated from training data using Bloch-constrained LRT completion. Data acquisition: Canine models with reperfused myocardial infarction (MI) were imaged at weeks 1 (n=12) and 8 (n=9) post-MI in a 3T clinical system with the proposed LRT acquisition and compared to clinical 2D breath-hold sequences. Data Analysis: Left-ventricular ejection fraction (LVEF), MI size and transmurality, microvascular obstruction (MVO) on early/late enhancement (2 and 15 min post-Gd), and intramyocardial hemorrhage (IMH) volume (T2*w, TE=11.42 ms) were measured using proposed and conventional methods. Histological Validation: Trichrome and Prussian Blue staining were used to validate MI and IMH.

Results: The proposed method reduced acquisition time by >50%. There was no difference in LVEF: 31.28±5.42% vs. 34.34±3.89%, P = 0.54. MI volume were comparable (%LV): MI volume - 16.30±8.93 vs. 16.17±8.23, P=0.57; and MI transmurality - 58.41±10.07 vs. 56.97±9.76, P=0.13. Detection of acute MI achieved AUC=0.94 and chronic MI AUC=0.93 (Fig. 2). MVO (%LV) and IMH volume (%LV) were also not different: MVO - 6.94±5.42 vs. 6.11±4.93, P = 0.17; IMH - 4.57±3.30 vs. 4.57±3.31, P = 0.98. Early and persistent MVO yielded AUC=0.93 and AUC=0.92, respectively (Fig. 3A-C). IMH volume showed equivalent quantification (4.6±3.3% vs. 4.6±3.3%, P=0.98; R²=0.95), with reduced off-resonance artifacts. AUC for IMH detection were 0.93 in the acute phase and AUC=0.92 in the chronic phase (Fig. 3D-F). Histopathology confirmed cardiac MRI evidence of tissue injury (Fig. 3G).

Conclusion: Proposed cardiac MRI approach permits determination of tissue injury within 20 min in scan time without breath-holding or ECG gating, enabling CCS staging (Stages II–IV) with strong agreement to conventional protocols. While the method remains to be tested in patients, it has the capacity to facilitate efficient use of cardiac MRI for staging severity of tissue injury in MI.

Figure 1. Schematic diagram of Canadian Cardiovascular Society (CCS) staging of irreversible myocardial infarction (Stage II – Stage IV) and proposed free-running CMR protocol within 20 min to determining cardiac function, severity of tissue necrosis and microvascular damage in reperfused MI with whole-heart coverage.
Figure 2. MI Size and Transmurality with Proposed and Conventional Approaches. A) Representative images from canine acquired using conventional and the proposed approaches. D) ROC analysis for MI detection for subjects with acute and chronic timepoints, along with corresponding AUC, are shown. C) – D) Linear regression analysis and bland-altman analysis of MI size and MI transmurality determined using the Conventional and the proposed approaches, across all animals (along with line and equation of best fit, R2 and P values) and corresponding Bland-Altman analysis (along with RPC) are shown.
Figure 3. Validation between conventional 2D (Conv.) and proposed (Prop.) measures of microvascular obstruction (MVO) and intramyocardial hemorrhage (IMH): A) and D) are representative subjects of MVO characterization and IMH characterization between the two methods, respectively. B) and E) are linear regression between the two methods in MVO and IMH characterization. C) and F) ROC analysis between the two approaches, the area-under-the-curve (AUC) of ROC analysis is shown. G) Histological validation of MI and IMH using Trichrome and Prussian Blue staining.