Endoscopic ΜOCT/DΜOCT for identification and characterization of human olfactory epithelium in vivo - loss of sense of smell is an under-recognized condition that affects approximately 10% of the…

The National Institute on Deafness and Other Communication Disorders awarded The General Hospital Corporation (doing business as Massachusetts General Hospital) $676,345 on August 3, 2026, under the Research Related to Deafness and Communication Disorders program (CFDA 93.173) to develop endoscopic micro-optical coherence tomography (MOCT) and dynamic MOCT (DMOCT) imaging techniques for identifying and characterizing human olfactory epithelium in vivo.

The research addresses olfactory loss, which affects approximately 10 percent of the population and significantly impacts quality of life, nutrition, and safety. Olfactory epithelium shows characteristic changes in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease prior to symptom onset, making it a candidate for early detection. Current clinical and research capabilities cannot distinguish olfactory epithelium from surrounding respiratory epithelium or identify regions of neuronal loss due to injury or age, limiting diagnostic and prognostic information for patients with smell loss and preventing accurate biopsy sampling.

The project will advance previously developed intranasal MOCT probes demonstrated in awake, unsedated human subjects and recently developed DMOCT technology that acquires repeated images to reconstruct frequency signatures of intracellular motion as a proxy for metabolic activity. Early ex vivo results in mouse and human olfactory clefts show the ability to visualize olfactory epithelium morphology, including ducts and motile versus non-motile cilia.

Performance occurs in Boston, Massachusetts from August 3, 2026, through July 31, 2031.

Endoscopic ΜOCT/DΜOCT for identification and characterization of human olfactory epithelium in vivo - loss of sense of smell is an under-recognized condition that affects approximately 10% of the population. Beyond the inability to sense odors, there is a considerable negative impact on quality of life, nutrition, and safety due to a suppressed ability to detect hazards such as smoke, natural gas, and spoiled food. Olfactory loss is also a feature of neurodegenerative diseases such as alzheimer's disease (ad) and parkinson's disease (PD), which show characteristic changes in the olfactory epithelium (OE) prior to symptom onset, making the OE a prime candidate for early detection when treatments are most likely to be effective. Unfortunately, human olfactory mucosa remains a "black box" clinically and from a research standpoint. The OE, which contains the crucial olfactory sensory neurons (OSNS), is indistinguishable from surrounding respiratory epithelium (RE) and from regions of neuronal loss due to injury or age. This inability to identify the OE limits diagnostic and prognostic information for patients presenting with smell loss, prevents accurate biopsy sampling, and confounds both research and patient care. Micro-optical coherence tomography (ΜOCT) provides high-resolution cross-sectional imaging of nasal RE and its surface ciliary activity, offering a way to differentiate RE from the non-motile cilia of the OE. Previously, we developed an intranasal ΜOCT probe and demonstrated visualization of ciliated RE in awake, unsedated human subjects, showing differences between cystic fibrosis patients and controls. More recently, we developed dynamic ΜOCT (DΜOCT), which acquires repeated images at the same site to reconstruct frequency signatures of intracellular motion, a proxy for metabolic activity. Early results with 2D and 3D DΜOCT in mouse and human olfactory clefts EX vivo show the ability to visualize OE morphology, including ducts, motile versus non-motile cilia, OSNS and their dendrites, and neuronal OE VS. Aneuronal OE from functional dynamic contrast. Preliminary data suggest that DΜOCT may also be sensitive to neuronal activation, raising the possibility of real-time functional readouts of OSN activity. Here, we propose to advance ΜOCT/DΜOCT by: (1) determining its capacity to distinguish OE from RE with manual and AI algorithms; (2) demonstrating DΜOCT visualization of OSN activation; (3) developing a robotically stabilized probe that snaps onto a hopkins endoscope for image-guided biopsy or detaches for olfactory cleft scanning; and (4) validating this technology for OE discrimination and OSN surface area quantification in patients with smell disorders. "seeing is believing." this research will, for the first time, allow clinicians and scientists to view both the structure and function of human OE in real time with a label-free, minimally invasive technique in vivo, propelling the field forward with major implications for understanding olfactory disease, managing smell loss, and enabling early diagnosis of neurodegenerative disease.