First Advisor

Summer Gibbs

Date of Award

Spring 6-2026

Document Type

Thesis

Degree Name

Bachelor of Science (B.S.) in Biology and University Honors

Department

Biology

Language

English

Subjects

fluorescence, microscopy, sectioning, imaging, tissue processing, fluorescence guided surgery

Abstract

Brain and spinal cord cancers make up about 1% of new cancers in the US each year.1 For these patients, survival and quality of life correlates strongly with the success of the resection of the tumor. Achieving maximal tumor removal while preserving critical tissue in the brain (such as the white matter tracts (WMTs)) remains a central challenge in neurosurgery, as current standard visualization with white light provides insufficient contrast to delineate between malignant tumor and the WMTs. The morbidity risk of WMT injury can outweigh the benefit of complete tumor resection, forcing surgeons to leave residual tumor to avoid damaging healthy tissue, when tumor margins border critical WMTs. To increase real-time intraoperative contrast between malignant tumor and healthy tissue, fluorescent probes are increasingly utilized to aid surgeons in fluorescence guided surgery (FGS). The Gibbs laboratory has extensive expertise in developing tissue specific small molecule fluorophores, notably for nervous tissue both in the peripheral and central nervous systems. Although FGS systems are widely available, there are currently no Food and Drug Administration (FDA) approved contrast agents that selectively label the WMTs of the brain to support real time intraoperative decision-making and increase confidence in tumor resection margins. The successful development and validation of clinically useful and compatible fluorophores is complex and costly, requiring comprehensive evaluation of a probe’s performance in non-human models prior to clinical translation. Extensive lead selection in mice from a library of over 500 fluorophores has identified LGW14-63 as a strong candidate for fluorescence guided neurosurgery, but its ability to robustly highlight all WMTs within the brain, as well as its molecular level binding remain undetermined. High resolution fluorescence imaging can allow the binding of LGW14-63 to be observed and conclusions to be drawn regarding binding patterns, and potential binding sites. These spatial localization data can then be compared with known distributions of proteins within WMTs to form hypotheses regarding likely molecular targets. To assist further research regarding these targets, this work describes efforts to optimize high-resolution fluorescence microscopy to construct a pseudo “brain atlas” that qualitatively demonstrates central nervous system highlighting of WMTs by LGW14-63, and determine likely binding partners and sites for LGW14-63.

Available for download on Thursday, July 29, 2027

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