In Vivo Imaging of the Olfactory Epithelium Using Confocal Laser Endomicroscopy

In Vivo Imaging of Olfactory Epithelium in Humans With Olfactory Impairment 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.

Study Overview

• Status: Not yet recruiting
• Conditions: Endoscopic Sinus Surgery; Olfactory Dysfunction; Endonasal Surgery
• Intervention / Treatment: Device: CONVIVO system; Other: Conventional histologic evaluation; Drug: Fluorescein injection, USP 10%

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 36

Contacts and Locations

• Study Contact: Name: Michaela M Geffert, MS; Phone Number: 603-650-2054; Email: Michaela.M.Geffert@Hitchcock.org
• Study Contact Backup: Name: Ryan E Little, MD; Phone Number: 603-650-8123; Email: Ryan.E.Little@Hitchcock.org

Study Locations

• United States
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03755
      • Dartmouth-Hitchcock Medical Center
      • Contact: Ryan E Little, MD; Phone Number: 603-650-8123; Email: Ryan.E.Little@Hitchcock.org
      • Principal Investigator: Ryan E Little, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Adults undergoing endoscopic sinus or endonasal skull base surgery while under general anesthesia where the nasal turbinate is accessible at Dartmouth Hitchcock Medical Center.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Target Group (Patients with Olfactory Complaints); Patients who have olfactory complaints and are undergoing endoscopic sinus or endonasal skull base surgery while under general anesthesia where the nasal turbinate is accessible, per their standard of care.	Device: CONVIVO system; 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.; Other: Conventional histologic evaluation; Following image acquisition, if clinically indicated, the tissue region imaged with the CONVIVO system will then be biopsied. This will be passed immediately off the surgical field as a research specimen and provided to a member of the research team to be prepared for conventional histologic evaluation. The specimen will be labeled with the deidentified subject and sample number. This sequence will then be repeated for each successive sample.; Drug: Fluorescein injection, USP 10%; 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.; Other Names: AK-FLUOR; FNa
Control Group; Controls will consist of surgical patients without subjective olfactory complaints and with expected normal psychophysical testing. Patients who are already undergoing endoscopic sinus or endonasal skull base surgery while under general anesthesia where the nasal turbinate is accessible, per their standard of care.	Device: CONVIVO system; 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.; Other: Conventional histologic evaluation; Following image acquisition, if clinically indicated, the tissue region imaged with the CONVIVO system will then be biopsied. This will be passed immediately off the surgical field as a research specimen and provided to a member of the research team to be prepared for conventional histologic evaluation. The specimen will be labeled with the deidentified subject and sample number. This sequence will then be repeated for each successive sample.; Drug: Fluorescein injection, USP 10%; 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.; Other Names: AK-FLUOR; FNa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	On day of Surgery, Day 0

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	On day of Surgery, Day 0

Collaborators and Investigators

• Sponsor: Dartmouth-Hitchcock Medical Center
• Collaborators: National Center for Advancing Translational Sciences (NCATS)

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): July 31, 2027

Study Registration Dates

• First Submitted: April 16, 2026
• First Submitted That Met QC Criteria: April 16, 2026
• First Posted (Actual): April 23, 2026

Study Record Updates

• Last Update Posted (Actual): April 23, 2026
• Last Update Submitted That Met QC Criteria: April 16, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Endoscopic Sinus Surgery; Confocal Laser Endomicroscopy; Smell Loss; Olfactory Dysfunction; Endonasal Skull Base Surgery
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Sensation Disorders; Olfaction Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Anosmia; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Hydrocarbons, Cyclic; Polycyclic Compounds; Heterocyclic Compounds, 3-Ring; Spiro Compounds; Xanthenes; Fluorescein; Fluoresceins
• Other Study ID Numbers: STUDY02003356; UM1TR004772 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No