In Vivo Imaging of the Olfactory Epithelium Using Confocal Laser Endomicroscopy

Early Phase 1Active Not RecruitingNCT07546617

Dartmouth-Hitchcock Medical Center36 enrolled

Overview

This research is being done to better characterize the part of the nose that helps people 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, the team 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. The study team hopes 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. Participation in the study includes completing a smell test (Sniffin' Sticks Extended test), a cognitive screening test, and two questionnaires.

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. The study team 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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

DIAGNOSTIC

Masking

NONE

Enrollment

Interventions

CONVIVO systemDEVICE

Approximately 2-5 minutes following administration of FNa in situ imaging will be performed by the participating surgeon ensuring proper technique. Prior to entering the surgical field, the probe will be covered in a disposable sterile sheath that is manufactured with quality assurance for this purpose. The probe will gently be held against the tissue interface while imaging occurs. Following image acquisition, a pathologist present in the operating room, will review and capture each image.

Fluorescein injection, USP 10%DRUG

Sodium fluorescein will be administered intravenously or topically (applied directly to nasal mucosa) at doses of 5-10 mg/kg (not exceeding 20 mg/kg cumulative). Administration will be performed by the anesthesia team in the operating room.

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

(1) High feasibility (≥85% interpretable images); (2) identifiable CLE signatures associated with OD severity; (3) significant correlations between CLE features, TDI scores, and symptom burden.

Time frame: On day of Surgery, Day 0

Secondary Outcomes

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. Expected Outcomes: Identification of CLE features corresponding to gold-standard histopathology, generating preliminary in vivo imaging biomarkers.