Cochlear fluid mixing: A computational study
Mohammad Shokrian, PhD Qualifying Exam, Advised by Professor Jong-Hoon Nam
Tuesday, April 12, 2022
Limited accessibility to the cochlea has remained a challenge for the inner ear drug delivery. Systemic delivery has low precision whereas the invasive approach potentially causes a lasting or temporary hearing loss. One of the less invasive procedures is by applying the drug at the round window. The cochlea is filled with two lymphatic fluids. The sensory epithelium called the organ of Corti separates the two fluid spaces. It has been shown that the drug travels along the length of the cochlear fluids via diffusion. The rate at which the drug travels toward the apical end progressively decreases so much so that the apical regions are considered inaccessible. The sound entering the cochlea duct induces a pressure difference across the organ of Corti micro-structure. The pressure difference results in the vibration of this structure. The electro-motile outer hair cells, a type of sensory cells in the organ of Corti modify this vibration. The vibration moves apically along a traveling wave as a result of the organ of Corti stiffness gradient. Recent studies reported that the outer hair cells amplify the organ of Corti top surface motion along the length of the traveling wave.
The Corti fluid space as a drug pathway was never studied. The micro-scale width of the Corti fluid along with the infinitesimal vibration at the boundaries have led others to assume a stagnant flow in this space. The vulnerability of the organ of Corti local potassium homeostasis along with the recent measurements of organ of Corti vibrations have motivated us to study the Corti fluid mixing. Our aims are three-fold. 1) first, we will investigate the conditions required for fluid mixing in the Corti fluid. We hypothesized that the peristaltic motion caused by the organ of Corti vibration induces a circulatory flow that improves mixing. 2) Second, we will quantify the peristaltic motion caused by the organ of Corti vibration. We hypothesized that the outer hair cells induce peristaltic pumping in the confined space of the Corti fluid under physiological conditions. Another hypothesis is that the outer hair cell generated peristalsis is larger at the tail of the traveling wave. 3) Finally, we will verify the Corti fluid as the main drug pathway for sound-driven drug delivery. We hypothesized that the Corti fluid has a larger longitudinal flow compared to the scalae fluids. Also, the active motility of the outer hair cells contributes to the faster mixing inside the Corti fluid.
We will accomplish these aims by modeling the fluid-structure interaction of the organ of Corti with the cochlear fluids including the Corti fluid. The computational model will be used to study the cross-sectional area changes of the organ of Corti. The computational findings will be cross validated with the experimental in vitro measurements of the organ of Corti vibration. We will expand our experimental observations to the physiological conditions of the intact cochlea by means of the computational model. We will investigate the sound-driven drug delivery conditions using a mass transfer model of the drug pathways, namely the scala tympani and the Corti fluid.