Date(s) - 01/20/2016
Engineering Magnetic Resonance Imaging Methods for Non-Invasive Investigation of Heart Function, Failure, and Regeneration from the Cellular to Whole Organ Levels
Magnetic resonance imaging (MRI) is widely used to non-invasively obtain high quality anatomical and functional images of the heart. Clinical diagnosis from such images relies upon the observation of changes in structure or function at the whole organ level that may only be present at late disease stages, and ignores the myriad alterations at the molecular, cellular, and tissue levels that precede outright heart failure. Such changes represent both potential early biomarkers of disease and possible therapeutic avenues by which to attenuate disease progression. We utilize a biomedical engineering approach towards MRI sequence development that exploits the interplay between physiological changes in diseased tissue and corresponding changes in tissue magnetic properties as a framework for the design of unique MRI pulse sequences for molecular imaging of the heart in both pre-clinical and clinical settings. In pre-clinical models we have developed novel methods for multi-color tracking of cell fate decisions (survival/proliferation vs. rejection) in cardio-regenerative medicine, non-invasive monitoring of cardiac metabolic markers, and imaging of gene therapy. These techniques can both enable more robust in vivo studies in pre-clinical models of regenerative medicine, and can follow successful strategies to clinical implementation. In clinical settings we have developed a method to quantify cardiac fibrosis without the use of gadolinium based contrast agents, and applied this method to examine the roles of various potential biomarkers in promoting tissue fibrosis and sudden death in individuals with end stage renal failure. Such imaging can further be used to assess the efficacy of emerging therapies and to longitudinally and non-invasively monitor patient status without the need for painful repeated biopsies. Ultimately, we seek to expand the application of our imaging methods for screening of individuals likely to benefit from implantable cardiac defibrillators, for surgical planning of site specific ablation in arrhythmia treatment, and for non-invasive monitoring of transplant rejection.