Noninvasive Targeted Temperature Management of the Inner Ear: Numerical Simulations and Experimental Measurements in a Human Cadaver Model.

Hypothesis: Mild therapeutic hypothermia (MTH) could be delivered to the human inner ear using a localized, noninvasive approach to achieve protective temperature reductions without systemic side effects.

Background: MTH has demonstrated protective effects in the cochlea following injuries such as device implantation, ototoxicity, and noise overexposure. It targets key cellular mechanisms, including proinflammatory pathways, oxidative stress, pyroptosis, and apoptosis. However, systemic and invasive methods for MTH carry risks and are less practical for broader clinical applications. Developing a localized, noninvasive approach could offer a safer, more accessible solution for hearing preservation after cochlear injury.

Methods: Cadaveric middle and inner ear structures, maintained near physiological conditions, were used to test a custom-designed cooling gel pack (ReBound) placed externally on the temporal bone. Temperature changes were recorded over 60 or 30 minutes. To complement experimental findings, three-dimensional geometrical models were created from imaging data, and finite element heat transfer analysis simulated temperature changes across inner ear structures.

Results: With external gel pack application, inner ear temperatures dropped by 2.9°C within 30 minutes and 4.6°C within 60 minutes. Cooling persisted for 10 minutes post-device removal. Numerical modeling corroborated these findings, indicating average temperature reductions of 2°C to 4°C. Biological sex differences were observed in cooling efficiency and overall temperature drop.

Conclusion: This study demonstrates that localized, noninvasive MTH can effectively reduce inner ear temperatures to therapeutically relevant levels. These findings support a promising, clinically translatable approach for protecting cochlear structure and function after injury, with minimal systemic risks.