Defense of Thesis Proposal: Kristian Sexton

Friday, November 15, 2013, 9:00-11:00am

MacLean 201

“Development and Testing of a New System and Methodology for Receptor-Level Fluorescence Imaging During Surgery”

Thesis Committee:
Brian Pogue, Ph.D. (Chair)
Kim Samkoe, Ph.D.
Keith 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 real time 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. The framework describing the concepts behind this system is 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. Molecular probe localization depends on a number of factors and so accurate quantitative molecular imaging is more complicated than simple imaging of fluorescence signal intensity. A dual probe technique that enables quantitative molecular imaging has been developed and its application to FGS is examined. The primary clinical goal for FGS at Dartmouth is the enhanced resection of gliomas and so this has been the focus of much of this work.

The proposed plans to complete this thesis consist of a number of studies utilizing the pulsed FGS system. The potential of anti-EGFR targeted Affibodies for glioma imaging will be examined further in detailed in vivo studies using a murine glioma model to assess the lower limits on detection and accuracy with both the pulsed system and the Zeiss Pentero. Crucial to the success of dual tracer studies is an understanding and assessment of cross talk within the system. Phantom studies examining and characterizing the level of cross talk will be performed. The system also enables kinetic imaging and this capability will demonstrated with in vivo plasma excretion studies. The limits of optical property correction using reflectance data will be examined and characterized through calibrated phantom studies. Contingent on time and IRB approval, the limits on detection of PpIX in human skin lesions will also be examined.

For more information, contact Daryl Laware at daryl.a.laware@dartmouth.edu.