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Abstract

Fluorescence guided surgery (FGS) is a specific and sensitive surgical technique that provides clinicians real-time visualization of tissue structure and function to assist in surgical decision making. This approach is particularly useful when the identification of tumor tissue is critical in achieving more accurate and complete resections while simultaneously minimizing damage to surrounding healthy tissue. The cornerstone of tumor visualization for FGS is the administration of fluorescent contrast agents to provide tumor contrast from background tissue and many novel agents are being investigated. Although these agents can provide elevated contrast, many require long incubation times and may be sensitive to tumor heterogeneity.
 
We aim to improve FGS techniques for tumor resection by advancing new fluorescent contrast agents with more favorable properties that include a shorter administration to imaging time with elevated and diagnostically accurate contrast that persists well into surgical procedures. To do so, we use hyperspectral whole-body fluorescence cryo-imaging to comprehensively evaluate candidate fluorescent contrast agents. Specifically, we focus on applications in neurosurgical fluorescence guidance by visualizing 3-D fluorescent contrast agent biodistributions and assessing volumetric tumor contrast metrics in several animal models to advance contrast agents with these favorable properties. Co-registered gadolinium enhanced MRI and histopathology are also acquired for comparison. The whole-body fluorescence cryo-imaging system is further leveraged in this proposal to investigate the delivery of genetic medicines and the metastatic spread of tumor models in-vivo.

Thesis Committee

Scott Davis (chair); Kimberley Samkoe; Keith Paulsen; David Roberts, MD; John Lee, MD, MSCE (University of Pennsylvania)