Engineering of molecular MRI to elucidate biological mechanisms of disease and regeneration in the murine and human hearts
Assistant Professor, Bioengineering
University of California Berkeley
April 12, 2018
Foege N130A, Wallace H. Coulter Seminar Room
Emerging treatments for heart failure including gene therapy and reparative cell therapy seek to improve cardiac function or replace lost myocardium via targeting of genetic, cellular, and tissue scale mechanisms. Within clinical settings, imaging modalities including cardiac magnetic resonance imaging (MRI) are used to assess the subsequent impact on global ventricular structure and function, and changes in dense scar tissue. Although such measurements can be performed non-invasively and serially, the macro-level imaging measurements derived from such scans do not truly reflect underlying changes at the molecular, cellular and tissue levels. Subsequently, when promising therapies fail to demonstrate efficacy, the source of failure often remains unknown. The absence of suitable imaging methodologies represents a fundamental barrier to further development of such treatments. In our lab we utilize a first principles approach to unify changes in myocardial MRI physics properties with advanced pulse sequence design and analysis in order to transform cardiac MRI into a multi-scale molecular imaging tool for unmet needs in cardiology. Using a process of chemical exchange saturation transfer (CEST) we have designed pre-clinical methods to quantify gene transfer following adenoviral driven gene therapy, and to longitudinally quantify cell survival/proliferation following intra-myocardial implantation in mouse models of regenerative cell therapy. In addition, cardiac CEST approaches for imaging of myocardial creatine levels and endogenous contrast fibrosis imaging have been translated to clinical application in obese adults and renal failure patients on routine hemodialysis. When integrated, these approaches can enable serially non-invasive and multi-scale analysis from the level of gene expression up to whole organ function in the failing or healing heart.
I received my bachelors degree in Bioengineering at the University of California, San Diego before moving to the University of Virginia to pursue graduate research under Dr. Frederick Epstein in the development of pre-clinical cardiac MRI pulse sequences for imaging of calcium cycling and myocardial perfusion. After completing my graduate students I pursued postdoctoral research at the Weizmann Institute of Science funded by a Whitaker Foundation fellowship. My work at the Weizmann Institute focused on the development of cellular/molecular imaging approaches using chemical exchange saturation transfer MRI. In 2013 I launched my lab at the University of Kentucky focusing initially on further development of cardiac cell/gene therapy imaging techniques and the translation of CEST-MRI for human myocardial fibrosis imaging. In 2016 I moved to the U.C. Berkeley Department of Bioengineering. At Berkeley my lab has expanded outwards towards imaging directed studies of molecular mechanisms of myocardial fibrosis in end stage renal disease, accelerated cardiac CEST-MRI approaches for cardiac gene therapy, and metabolic imaging in the setting of obesity.