Steven Yarmoska

PhD Proposal Presentation

Date:               Thursday, September 20, 2018

Time:              10:00am

Location:        Molecular Science and Engineering Building (MoSE) 3201A

Committee Members:

Stanislav Emelianov, Ph.D.    (GT, ECE/BME)(Advisor)

J. Brandon Dixon, Ph.D.         (GT, ME/BME)

Paul Garcia, M.D., Ph.D.        (Columbia University Medical Center, Anesthesiology)

Melissa Gilbert-Ross, Ph.D.   (Emory University, Hematology and Medical Oncology)

Brooks Lindsey, Ph.D.            (GT, BME)

Title: Perfluorocarbon Nanodroplets for Extravascular Imaging Applications

Abstract: Gas microbubbles are the most ubiquitously used agent for contrast enhancement in ultrasound imaging. However, microbubbles are only stable at sizes between 1-10 micrometers, and so they are effectively restricted to vascular imaging applications. In response to this limitation, perfluorocarbon nanodroplets (PFCnDs) were developed as a new class of biocompatible phase-change ultrasound and photoacoustic contrast agents. PFCnDs have a liquid perfluorocarbon core, which allows the construct to be stable at sub-micrometer sizes prior to on-demand contrast generation via an acoustic or laser energy pulse to trigger core vaporization. Still, despite being heralded as the harbinger of extravascular contrast-enhanced ultrasound imaging, PFCnDs have been largely relegated to the realm of in vitro technological demonstrations and vascular use. These proposed studies will seek to fulfill a promise reneged on by the field for nearly two decades, using realistic murine models of metastatic breast cancer as a platform for extravascular imaging with PFCnDs. In Aim 1, we will utilize PFCnDs in a sentinel-lymph-node-biopsy-like paradigm a) to detect tumor draining lymph nodes, b) to assess them for metastases by functionalizing our particles to afford molecular specificity, and c) to treat metastases via the image-guided controlled delivery and release of therapeutic to metastatic nodes. In Aim 2, we will deliver PFCnDs systemically to primary tumors and generate a robust body of evidence to conclusively demonstrate that PFCnDs extravasate through neovascular fenestrations and into the tumor stroma, paving the way for a host of diagnostic and therapeutic applications of PFCnDs in primary tumors. The successful completion of these studies will serve as the vanguard for a new era of PFCnD-based extravascular contrast-enhanced ultrasound imaging.

**Light breakfast will be served.**