Development of a high resolution endoscope for non-invasive imaging of the human olfactory epithelium

About This Grant

F.220: 7. PROJECT SUMMARY / ABSTRACT The olfactory epithelium (OE) is a pseudostratified tissue deep within the nasal cavity, near the cribriform palate. It primarily contains olfactory sensory neurons (OSNs) that are responsible for transmitting odor- detecting signals to the olfactory neural pathway, as well as basal progenitor cells and supporting cells1,2. Anosmia (the loss of the sense of smell) arises from conditions where OSN regeneration is diminished, leaving behind depleted regions without OSNs3,4. This can happen due to normal aging, neurodegenerative diseases, viral infections, congenital disorders, and exposure to external toxins3,5,6. More than half of people aged 65 or older will experience some degree of anosmia5. When a patient presents with anosmia, clinical evaluation involves a combination of the patient's medical history and functional tests. These tests have been shown to be subjective due to cultural and environmental factors5, and they do not discern whether the problem lies with OSNs and their transmission or elsewhere in the olfactory neural pathway. Biopsies are reserved for extreme cases since they carry a risk of damaging the already scarce OE tissues, offer extremely limited sampling, and require significant time and expertise5,7. There is currently no endoscopic tool that can reliably identify and image the olfactory epithelium in humans in real time with high spatial and temporal resolution. This type of imaging has been difficult to achieve due to anatomical complexity, inability to differentiate between cell types, and optical limitations. The OE is located deep within the nasal cavity, behind bony structures and cartilage, requiring careful and precise navigation to access1. Even when reached, the OE exists as scattered patches that constitute only ~10% of the nasal epithelia1. These patches have no clear macroscopic boundaries and are nearly indistinguishable from their surrounding RE without the aid of external markers1,8. Furthermore, these patches shrink with age and disease progression3,5,9,10, making identification even more difficult. In this proposal, I aim to develop a nasal endoscope tool that can reliably distinguish between OE and RE while also providing real-time imaging of the OE at high spatial and temporal resolution. This device would be designed for use by clinicians in outpatient settings to enable direct assessment of the OE in patients. The proposed tool would significantly advance both biomedical research and clinical practice. By enabling direct visualization of the spatial distribution of OSNs, this technology would allow researchers and clinicians to visually assess the size, uniformity, and patchiness of the OE. Because these features change with aging and disease, they can offer valuable insights into the underlying biology of olfactory dysfunction. This tool will enable longitudinal studies of OE regeneration and response to therapies, informing the development of targeted treatments. Clinically, this tool would provide a more objective assessment of anosmia than current smell tests, allow for the monitoring of OE changes over time, and significantly improve diagnostic accuracy.