Noninvasive Imaging of Hemorrhagic Myocardial infarction with Confounder-Corrected T2* Cardiac MRI

The current gold-standard approach for detection and quantification of intramyocardial hemorrhage (IMH) is T2* cardiovascular magnetic resonance imaging (CMR). T2*-based imaging techniques have been demonstrated to have high sensitivity for detecting hemorrhage and residual iron. The conventional T2*-based imaging employed for IMH imaging is based on a 2D breath-held, ECG-triggered, segmented, multi-gradient-echo sequence. More recently, a dark-blood cardiac T2* MRI technique has emerged for imaging of global iron overload such as thalassemia. It has been interchangeably used with bright-blood T2* MRI for imaging of local iron overload such as intramyocardial hemorrhage. To date however, dark-blood T2* techniques for intramyocardial hemorrhage characterization has not been validated. In Chapters 2 and 3, we investigated the diagnostic capacity of dark-blood T2* MRI against bright-blood T2* MRI for intramyocardial hemorrhage characterization in both clinical and preclinical settings. We found that double-inversion-recovery prepared dark-blood T2* images provide lower signal-to-noise ratio and lower contrast-to-noise ratio between hemorrhage and remote myocardium, consequently underestimating the hemorrhage extent. Dark-blood T2* MRI also demonstrated weaker sensitivity, specificity, accuracy, and inter-observer variability compared to bright-blood T2*-weighted MRI. Our studies also showed that the loss in SNR and CNR in dark-blood T2* imaging emerges from the signal loss following double-inversion-recovery preparation and insufficient recovery time between double-inversion-recovery preparation and readout. Hence, we conclude that dark-blood T2* MRI does not have the same diagnostic capacity for assessment of intramyocardial hemorrhage and bright-blood T2* MRI should be the preferred choice for clinical use. Studies have shown that fat infiltration is a common phenomenon in chronic myocardial infarction. However, signal from fat protons can confound the T2* assessment of intramyocardial hemorrhage. To address this issue, in Chapter 4, we studied the influence of fat infiltration on iron quantification in T2* mapping using a widely accepted water-fat separation algorithm. Specifically, we evaluated the temporal dependence of fat infiltration in hemorrhagic myocardial infarctions. We found that fat infiltration was observed in early and late chronic phases of myocardial infarctions, which if not corrected for, can underestimate the extent of iron content within the infarct zone. Notably, we also found that the amount of fat infiltration in chronic phase of MI was closely correlated with the amount of iron. Another major confounder in conventional 2D breath-held ECG-gated T2* imaging is motion artifacts. In clinical settings, patients with acute myocardial infarctions often find it difficult to hold their breath during cardiac MRI exams. Some patients may even suffer from arrhythmia (irregular heartbeat). Both situations can lead to unsuccessful gating during data acquisition leading to motion artifacts on T2* images especially with long echo times. To address this issue, in Chapter 5, we developed a motion-resolved fully ungated free-breathing 3D cardiac T2* imaging technique using a low-rank tensor framework to accommodate clinical needs and to mitigate motion artifacts due to unsuccessful breath-holds or ECG gating. We tested our 3D LRT technique in healthy volunteers and animal models for image quality, SNR and T2*. We found that the proposed 3D LRT technique can provide superior image quality compared to conventional T2* techniques at the same level of signal-to-noise ratio. T2* measured from proposed 3D LRT data showed excellent agreement with T2* from conventional 2D approach. We also found that a key benefit of 3D acquisition is that it permits the reconstruction of high-resolution T2* images using the proposed 3D LRT T2* approach. High-resolution T2* images from proposed 3D LRT approach showed superior image quality and diagnostic capacity for assessment of intramyocardial hemorrhage. In Chapter 6, the proposed 3D LRT T2* imaging approach was validated on an animal model for feasibility and capability for characterization of intramyocardial hemorrhage. We found that our 3D LRT approach had excellent image quality and diagnostic accuracy in the assessment of intramyocardial hemorrhage compared to the 2D breath-held and gated acquisitions. Broadly, this dissertation identified and corrected a number of critical confounders affecting the accuracy of T2* MRI in assessment of intramyocardial hemorrhage. By identifying and solving these confounders in T2* imaging, we aim to improve the diagnostic capability of MRI for prognosis and therapeutic care of patients with hemorrhagic myocardial infarctions. In future work, feasibility of the newly developed fully ungated free-breathing 3D LRT T2* imaging technique will be investigated on patients for imaging of intramyocardial hemorrhage. And the potential of high-resolution T2* imaging which greatly improved intravoxel dephasing due to off-resonance will be explored