MRI Relaxometry and Calibration in Iron-Overloaded Tissues
In 2005, we probed the mechanisms of tissue-iron interaction using MRI relaxation - R1 (1/T1), R2 (1/T2) and multi-echo R2 in fresh human liver biopsy specimens taken from patients with transfusion-dependent anemia. Our study demonstrated that to standardize in vivo calibration (inter-site and -sequence variability), it is important to understand the complex interaction of stored iron particles and water protons within the tissue of interest. In 2011, we were the first to develop a ‘human-derived’ Monte-Carlo framework for probing the underlying biophysics in hepatic iron overload; this demonstrated that knowledge of iron susceptibility/distribution and proton mobility are sufficient to characterize MRI relaxation. In 2015, we demonstrated the use of this model to predict R2- and R2*-iron relationship at higher field strengths in patients. The important application of such tissue-specific models is in the iron calibration of inaccessible organs like heart, where tissue biopsy is not an option. Establishing these models will avoid recalibration in patients for MRI sequence, field strength, iron-chelation therapy and organ.
Quantitative MRI in Myocardial Infarction (MI)
In 2011, we demonstrated that multi-parametric MRI exploiting T2 and T2* relaxation and the BOLD response can assess the state of myocardial tissue (edema, hemorrhage, microvascular reactivity) in vivo in a preclinical model of MI. In 2013, we demonstrated that such characterization can further distinguish the intrinsic remodeling mechanisms based on severity of injury. A figure from this publication was featured on the cover of the journal Magnetic Resonance in Medicine. Thus, quantitative MRI techniques allow regional, longitudinal, and cross-subject comparisons, and hence are powerful tools for evaluating treatment strategies, potentially improving clinical outcomes.
Impact of Hemorrhage in MI
In 2017, we were the first to mechanistically demonstrate that reperfusion hemorrhage is an active contributor to inflammation and myocardial and microvascular damage post-MI, beyond the initial ischemic insult. We have recently further demonstrated that hemorrhagic iron deposition can result in chronic adverse remodeling post-MI as well along with vasodilator dysfunction and matrix alterations in the remote myocardial regions.
Complementing the preclinical framework, our validated MRI protocol has also been successfully translated into our clinical research program. The human studies clearly demonstrate the role of MRI relaxation parameters in monitoring heart disease progression in a quantitative manner. Since 2012, we have had several publications demonstrating the utility of MRI mapping techniques to evaluate risk factors associated with diabetes including inflammation and microvascular disease. The striking correspondence between clinical and experimental findings has been very encouraging justifying the use of these quantitative MRI protocols for clinical translation.
Imaging for Cardiac Regenerative Medicine
My group has been collaborating with stem cell biologists to determine efficacy of stem cell derived cardiomyocytes in remuscularizing scar tissue to improve outcomes. Using MRI biomarkers for cardiac function and viability, we have shown that these cells can demonstrate successful engraftment in the scar region in an experimental model of MI (published in Stem Cell Reports). To aid accurate cell delivery and improve engraftment, my group is the first to explore an integrative image guidance system utilizing 3D MRI roadmaps and augmented reality (AR) for improving the intraoperative workflow for cell delivery.