Multiplexed imaging of endogenous molecular beacons with MRI
Date:
Lecture / Seminar
Time: 09:30-10:30
Location: Gerhard M.J. Schmidt Lecture Hall
Lecturer: Prof. Moriel Vandsburger
Organizer: Clore Institute for High-Field Magnetic Resonance Imaging and Spectroscopy
Details: Department of Bioengineering, U.C. Berkeley
Abstract: Novel treatments that are under development for heart failure, metabolic disorde ... Read more Novel treatments that are under development for heart failure, metabolic disorders, kidney disease, and other debilitating illnesses generally target specific molecular and cellular mechanisms of action. However, assessment of such treatments is often complicated by the lack of easily measurable blood biomarkers, and a reliance upon repeated tissue biopsy. Subsequently, many exploratory studies utilize non-invasive imaging methods to characterize changes in whole organ structure and function as surrogate markers for underlying cellular and molecular changes. Although such measurements can be performed serially, such macro-level imaging measurements are often insensitive to physiologically meaningful treatment responses. In addition, the lack of target specificity represents a fundamental barrier both in pre-clinical development and clinical trials where the information potentially gleaned from a more physiologically rich data set would be of high value to further therapeutic development. My primary research interest is in using magnetic resonance imaging (MRI) as a platform technology for non-invasive and multiplexed molecular imaging in heart and kidney failure. Using a first principles approach, my group seeks to unify changes in myocardial and kidney MRI physics properties with advanced pulse sequence design and analysis in order to enable integrative physiological imaging that both identifies mechanisms of failure earlier than existing diagnostics, and directly measures the impacts of new therapies on their intended therapeutic targets. Using a process of chemical exchange saturation transfer (CEST) we have designed pre-clinical methods to quantify viral carriers of somatic cell gene editing machinery, gene transfer following adeno associated viral 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 and fibrosis using endogenous contrast mechanisms have been translated from mouse models to clinical application in obese adults and renal failure patients on routine hemodialysis. Most recently we have developed methods to probe renal physiology and failure based on endogenous CEST contrast generated by urea. 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 disease settings that currently have limited non-invasive molecular tools. Close abstract
