Noninvasive technique for monitoring drug transport through the murine cochlea using micro-computed tomography.

Abstract

Local delivery of drugs to the inner ear has the potential to treat inner ear disorders including permanent hearing loss or deafness. Current mathematical models describing the pharmacokinetics of drug delivery to the inner ear have been based on large rodent studies with invasive measurements of concentration at few locations within the cochlea. Hence, estimates of clearance and diffusion parameters are based on fitting measured data with limited spatial resolution to a model. To overcome these limitations, we developed a noninvasive imaging technique to monitor and characterize drug delivery inside the mouse cochlea using micro-computed tomography (μCT). To increase the measurement accuracy, we performed a subject-atlas image registration to exploit the information readily available in the atlas image of the mouse cochlea and pass segmentation or labeling information from the atlas to our μCT scans. The approach presented here has the potential to quantify concentrations at any point along fluid-filled scalae of the inner ear. This may permit determination of spatially dependent diffusion and clearance parameters for enhanced models.