Imaging Reactive Oxygen Species to Detect Oxidative Stress
Objective
Elevated Hydrogen Peroxide (H2O2) levels (>30µM) in tissues are the hallmark of oxidative stress that is implicated in many diseases, including cancer. There is no current method to detect H2O2 in vivo except for optical imaging, which is severely limited by poor penetration. To that end, the goal of this project is to develop an ultrasound-based strategy for in vivo H2O2 detection.
Method
We formulated silica nanoshell particles (NSP) containing catalase, an enzyme that converts H2O2 into O2 and water and aimed to detect O2 microbubbles with ultrasound. In vitro imaging was performed with a Siemens Sequoia 512 (15L8 transducer).
Phase-Shift Very Low Boiling Point Nanodroplets
Objective
Acoustic droplet vaporization (ADV) of superheated perfluorocarbon nanodroplets (NDs) demonstrates potential as an extravascular ultrasound contrast agent that may facilitate ultrasound-based therapeutic applications, yet these agents are metastable and difficult to manufacture in high yield. We hypothesized that emulsification optimization and a surfactant/co-surfactant strategy would improve the yield, stability, and shelf-life of these agents.
Method
Emulsions of perfluorobutane obtained through direct emulsion combined with surfactants and/or co-surfactants were characterized using particle counters and sizers and their acoustic response was investigated with an Acuson Sequoia S512 ultrasound system with a 15L8 transducer.
Detection of Acute Thrombosis with New Activatable Contrast Agents
Objective
Acute deep vein thrombosis (DVT) is the formation of a blood clot in the deep veins of the body that can lead to fatal pulmonary embolism. Acute DVT is difficult to distinguish from chronic DVT and is therefore treated aggressively with anticoagulants, which can lead to internal bleeding. We aim to develop a contrast agent that detects acute thrombosis with ultrasound imaging.
Method
Acute clotting occurs when thrombin is activated. We are using activatable cell-penetrating peptides (ACPP) composed of a fluorescently-labeled (FITC) polycationic chain and a polyanionic chain that neutralizes the charge. Upon cleavage of the peptide by thrombin, the polyanionic peptide is dissociated, yielding the polycationic-labeled reporter that adheres to cell membranes.