Ph.D. Thesis Defense: Kristian Sexton

Thursday, May 8, 2014, 2:00-4:00pm

Jackson Conference Room

“System and Methodology for Receptor-Level Fluorescence Imaging During Surgery”

Thesis Committee:
Brian W. Pogue, Ph.D. (Chair)
Kimberley S. Samkoe, Ph.D.
Keith D. Paulsen, Ph.D.
Sylvain Gioux, Ph.D.

Abstract: Fluorescence molecular imaging will have an important clinical impact in the area of guided oncology surgery, where emerging technologies are poised to provide the surgeon with realtime molecular information to guide resection, using targeted molecular probes. The development of advanced surgical systems has gone hand in hand with probe development, and both aspects are analyzed in this work. A pulsed-light fluorescence guided surgical (FGS) system has been introduced to enable video rate visible light molecular imaging under normal room light conditions. The concepts behind this system design are presented and performance is compared with a commercial system in both phantom and in vivo animal studies using PpIX fluorescence.

The second critical advance in the emergence of these technologies has been the development of targeted near infrared (NIR) probes. A small, engineered three-helix protein was analyzed for imaging of glioma tumors. The blood brain barrier affects delivery of probes and the superior delivery of a smaller targeted protein (anti-EGFR Affibody) as compared to a full sized antibody is shown using a murine model and ex vivo tissue slices and a commercial imaging system. This small targeted probe is examined further for its possible application in FGS using the pulsed light imaging system. A concentration sensitivity analysis to determine the lower bounds on concentration needed for effective imaging is performed with this culminating analysis carried out in a murine orthotopic glioma tumor model.

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