MRI Relaxometry 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. Later in 2006, we were the first to demonstrate inequivocally that cardiac R2 and R2* are predominantly determined by cardiac iron concentration in humans. Since tissue biopsy is not a feasible option for the heart in the clinic, this data further supported the clinical use of cardiac MRI in iron-overload syndromes.
MRI-Iron Calibration by Monte-Carlo Modeling: 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. The iron size and structure was incorporated into a virtual liver model to interrogate R2 and R2* under various iron morphologies and concentrations. 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 following Acute Myocardial Infarction (AMI): In 2011, we demonstrated that multi-parametric MRI exploiting T2 and T2* relaxation properties can assess the state of myocardial tissue (edema, hemorrhage, microvascular reactivity) in vivo in a preclinical model of AMI. We have also demonstrated the value of T2 relaxation for vasodilatory function using the BOLD effect. In 2013, we demonstrated that such characterization can also distinguish the intrinsic remodeling mechanisms based on severity of injury. In 2017, we were the first to mechanistically demonstrate that hemorrhage is an active contributor to inflammation and myocardial and microvascular damage post-AMI, beyond the initial ischemic insult. Thus, quantitative MRI techniques allow regional, longitudinal, and cross-subject comparisons, and hence are powerful tools for evaluating treatment strategies, potentially improving clinical outcomes.
Clinical Studies: In 2012, we demonstrated the utility of quantitative MRI techniques in evaluating disease progression post-PCI in patients presenting with STEMI. One study demonstrated that quantitative T2 and T2* mapping can visualize edema and hemorrhage, respectively in human AMI and that remote zone remodeling in the hemorrhagic group may be indicative of more adverse remodeling. In another study we showed that thrombus aspiration during PCI was associated with reduced myocardial edema, hemorrhage and microvascular obstruction. This study was recognized as a ‘highly accessed article relative to age’ in JCMR with more than 1000 reads within the first month of publication. Since 2012, we have several publications demonstrating the utility of MRI mapping techniques to evaluate risk factors associated with diabetes including inflammation and microvascular disease.