Miniaturized 4-Channel Fluorescence Imaging Probe for Gastrointestinal Cancer Surveillance in Murine Models

Abstract

Fluorescence imaging, a method by which fluorescent species are spatially detected to visualize biological structures and processes, has proven invaluable for deciphering the nuanced development of gastrointestinal cancer in animal research models. In such studies, it is necessary to assess the evolution of tumor sites at different timepoints to investigate growth kinetics and functional mechanisms imperative for improving cancer detection and treatment. Unfortunately, these measurements typically require sacrificing animals at each timepoint, significantly increasing cost and animal use burden as well as prohibiting true longitudinal observation of tumors in individual subjects. A tool enabling in vivo tumor monitoring for mouse models of gastrointestinal cancer could improve the verity of these models and enable the extraction of more robust growth characteristics by providing accurate longitudinal measurements. Through tracking relevant biological features with highly specific fluorescent probes, tumor assessment may be performed optically, thus, enabling detection and measurement with minimally invasive fluorescence imaging. However, utilizing fluorescence imaging in vivo in mice poses challenges owing to the tortuous anatomy and minute gastrointestinal lumen caliber of this model. This thesis reports a miniature fluorescence imaging probe equipped for fluorescence imaging of multiplexed fluorescently labelled cancerous tissue in four distinct wavelength bands, as well as white light imaging and tissue biopsy. We present the design, characterization, and early demonstration of this device in addition to the concurrent development and assessment of a xenografted mouse model of gastrinoma. Along with enabling longitudinal cancer studies in research mice, this work illuminates the promise of fluorescence imaging devices in fluorescence-guided surgery and supports the development efforts of fluorescent probes as cancer contrast agents for clinical settings.