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"Advancing fluorescent contrast agent recovery methods for surgical guidance applications"

Abstract

As a non-ionizing, molecular imaging modality, fluorescence imaging has played an integral part in drug discovery and surgical guidance. The scope of this thesis focuses on novel fluorescence imaging devices, techniques, and contrast agents that could improve specific surgical challenges such as breast cancer margin assessment, brain angiography, and glioma resection guidance.

Building on the expertise in paired-agent imaging at Dartmouth, a clinical pilot study was carried out using paired-agent imaging on mastectomy specimens to assess translational benefit for breast cancer margin assessment. While conventional widefield fluorescence imaging is typically limited to the top few millimeters of tissue, we’ve also investigated ways to recover deeper fluorescence signals, including second window infrared (SWIR/NIR-II) imaging and 3D whole-animal cryo-imaging.

The crux of this work lays on the development of a multichannel, hyperspectral cryo-imaging system and image-processing techniques to accurately recapitulate 3D biodistributions in whole-animal experiments. Specifically, the goal is to correct each cryo-imaging dataset such that it becomes a useful reporter for full-body uptake distributions in relevant disease models. With such data-rich, 3D information and the capability to co-register cryo-, MRI, and histopathology data, we are able to better illuminate the biodistribution of multiple fluorescent contrast agents. A specific focus is placed on evaluating untargeted contrast agents for glioma resection guidance by comparing cryo-fluorescence volumes with gold-standard Gd-MRI datasets on a direct, voxel-to-voxel basis. Moving forward, the multi-modal, hyperspectral cryo-imaging platform developed within this thesis represents a major step towards rigorously understanding contrast agent behavior and drug biodistributions in whole-body disease models.

Thesis Committee

• Scott Davis (Chair)
• Brian Pogue
• Kimberley Samkoe
• Xiaoyao Fan
• Mark Niedre (external)

Contact

For more information, contact Theresa Fuller at theresa.d.fuller@dartmouth.edu.