In Vivo Imaging of the Olfactory Epithelium Using Confocal Laser Endomicroscopy

This research is being done to better characterize the part of the nose that helps us smell. Currently, the only ways to study smell loss mostly rely on how people report it, rather than being able to see the underlying structures directly. In this study, we will use a special microscope (Confocal Laser Endomicroscopy (CLE)), originally developed for brain tissue, to look at the part of the nose that helps to detects smell. We hope to identify the tiny structures in that area and see how they might be different in people who have smell loss compared to those who do not.

Aim 1: Evaluate the feasibility of in vivo CLE imaging of the olfactory cleft and nasal turbinate and determine whether CLE features correlate with validated psychophysical olfactory testing and patient-reported quality-of-life measures. We will obtain preoperative Sniffin' Sticks threshold-discrimination-identification (TDI) scores and questionnaires in 36 surgical patients recruited from NH and VT, followed by intraoperative CLE imaging after intravenous fluorescein. CLE images will be assessed for epithelial features such as neuronal loss, epithelial thinning, basement membrane irregularity, and inflammatory changes. Aim 2: Compare in vivo CLE imaging features with histopathologic findings from superior turbinate tissue, when available, to identify candidate in vivo imaging biomarkers. When routine surgery includes removal of superior turbinate tissue, CLE images will be paired with histopathology to assess concordance in features such as neuronal density, sustentacular cell integrity, and inflammation.

Inclusion Criteria: * Adults aged ≥18 years * Undergoing endoscopic sinus or endonasal skull base surgery while under - general anesthesia where the nasal turbinate is accessible * Able to complete study questionnaires and psychophysical smell testing * Able to provide informed consent. Exclusion Criteria: * Known allergy or hypersensitivity to fluorescein * Pregnancy * Medical instability precluding participation * Severe anatomic obstruction preventing safe access to the olfactory cleft and nasal turbinate * Any other safety concern identified by the investigator