Translational optical coherence tomography for quantitative assessments of eardrum biomechanics, effusions, and biofilm response during otitis media

Abstract

A middle ear infection, also known as otitis media (OM), is a prevalent pediatric disease caused by bacteria or viral pathogens in the middle ear. OM is clinically characterized by a presence of a middle ear effusion (MEE), accumulated fluid in a normally air-filled middle ear cavity. The persistent MEEs can lead to temporary hearing loss. Unfortunately, one out of three acute OM cases come back and repeated in young children. Previous studies showed that a bacterial biofilm, aggregated bacteria embedded within a slimy matrix in the middle ear, may be responsible for recurrent and chronic OM. However, current diagnostic technologies in non-invasively examining the middle ear cavity are limited. The standard tool, an otoscope, illuminates and magnifies the surface view of an eardrum, but assessing the MEEs and biofilms behind the semi-opaque eardrum during OM is challenging. Recent studies have integrated an advanced optical imaging technique, called optical coherence tomography (OCT), into a handheld probe to non-invasively provide cross-sectional visualization of the middle ear cavity, and showed that OCT can identify and quantify the eardrum thickness, the presence of the MEEs and biofilms, which were correlated with clinical diagnosis.

This dissertation takes the next step and establishes: 1) dynamic measurements of the eardrum mobility, 2) optical characterization and biological correlation of the MEEs in humans and in an OM-induced animal model, 3) in vivo monitoring of middle ear biofilms to antibiotic therapy, 4) development of a compact OCT device integrated with an automated classifier, and 5) investigation of a new therapeutic method for OM using cold plasma. Collectively, these results demonstrate new technologies that non-invasively provide quantitative and clinically relevant information inside the middle ear during OM, and form a bridge that links engineering and biomedicine in OM research for further translation.