Steve Yarmoska

BME PhD Defense Presentation

Date: Friday, March 13, 2020

Time: 2:00pm

Location: Engineered Biosystems Building (EBB), CHOA Seminar Room (1005)

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/ECE)

Title: Perfluorocarbon Nanodroplets for Extravascular Imaging Applications

Abstract: Gas microbubbles are the most ubiquitously used contrast agent in ultrasound imaging. However, microbubbles are only stable at sizes between 1-10 micrometers, and so they are effectively restricted to intravascular imaging applications. In response to this limitation, perfluorocarbon nanodroplets (PFCnDs) were developed as a new class of phase-change ultrasound and photoacoustic (US/PA) contrast agents. PFCnDs have a liquid fluoroalkane core, which allows the construct to be stable at submicrometer sizes prior to on-demand contrast generation via an acoustic or laser energy pulse to trigger core vaporization. Here, we utilize a class of optically triggered PFCnDs with a perfluorohexane core (PFHnDs), which allows the agent to repeatably vaporize and recondense in response to multiple laser pulses. This potentiates the use of PFHnDs for longitudinal imaging. Optically triggered PFHnDs leverage the transport characteristics of a small particle while retaining the imaging capabilities of a large particle for contrast-enhanced US/PA in extravascular locations.

The goals of these dissertation studies were to develop and to demonstrate optically triggered PFHnDs for extravascular imaging applications. In Aim 1, we developed synthesis and imaging strategies for creating small, monodisperse PFHnDs and for improving the detection of these agents in extravascular tissue. In Aim 2, we imaged optically triggered PFHnDs longitudinally in draining lymphatics in naïve and tumor-bearing mice. Then, we developed a new class of adjuvant-loaded PFHnDs for image-guided US/PA immunotherapy. In Aim 3, we developed targeted and on-particle FRET PFHnDs for imaging extravasation in primary tumors and investigated PFHnD extravasation in small animal models of breast cancer. Altogether, these studies push the paradigm for the expanded use of PFCnDs in applications-based research.

**Heavy hors d'oeuvres will be served**