Medical Applications of Thermoelectric Temperature Control

Abstract

The human body is a complex machine that operates within a narrow thermal range. Alongside internal thermogenicity, local heat fluxes regulate various functions in the body that are critical for healthy living. For example, digestion, immune response, fitness, and hair/skin quality are all affected by bodily temperature. As significant as heat management is for good health, the body constantly monitors internal and environmental temperatures for homeostasis.

Humans have historically understood the importance of temperature, and leveraged heat to enhance or restore health. In 370 BC, Hippocrates was the first to identify cold (i.e., ice) as a therapeutic for swelling on soldiers. In the modern day, hypothermia is widely used to alleviate the detrimental effects of inflammation, cardiac arrest and fever. However, questions remain on how to best deliver cooling to deep tissues and quantify its responses to the external temperature. Current medical cooling technologies are uncontrollable in cooling rate, cooling region, and/or target temperature. Ethical and surgical barriers also discourage direct experimentation on humans. Overall, the lack of a sophisticated cooling and measuring method for deep tissue heat transfer inhibits the engineering and implementation of optimal cooling in clinics. Through a combination of animal models and computational simulations, this thesis aims to propose improved techniques for cooling therapy with concentrated thermoelectric cooling elements (TEC) and understand the mechanisms of cold therapy on the body. TECs are an advantageous tool for this purpose as they are feedback-controllable, precise, rapid, and can also quantify the heat that is removed.

Using TECs and rodent models, we developed a novel tool and surgical protocol for extravascular carotid blood cooling in vivo, for which we achieved a temperature change of -4.74 ± 2.9 ˚C/hr when a single artery is cooled at 0 ˚C. Following success with blood cooling, we demonstrated that cold blood in the carotid artery convectively cools rodent brain tissue independently of the core (carotid: -4.19 ± 3.15 ˚C/hr at core: -0.84 ± 2.59 ˚C/hr). This selective brain cooling technique is unique in the field as an extravascular (not intravascularly accessed), conduction-convection heat transfer medical device that can cool an organ by targeting its major artery. Computational models of human carotid arteries were used to identify the scope of cooling that is possible with the extravascular cooling technique (approximately 1 ˚C decrease in outlet blood temperature of the human carotid), subject to further technical improvements.

Concurrently, we quantitatively studied how cold information is delivered to and perceived in the brain. For this purpose, a skin cooling device that can accurately apply temperatures and simultaneously deliver nonpainful pokes to the same area was devised. Data from the sensory cortex of non-human primate models were used to train decoding algorithms linking neural firing rates to applied skin temperature. Preliminarily the algorithms reached a maximum of 76% accuracy when discriminating between cold and warm temperatures. Future improvements in the algorithm will allow for the prediction of cold sensation and cold-induced anesthesia.

This research will inform researchers and clinicians in quantifying and predicting the body’s response to cold, how to manipulate the temperature of select regions in the body, and move towards an advanced cooling medical device and optimized clinical workflow. Ultimately, we seek to ensure medical application of cold as a precise and controlled therapy through which we heal and enhance the body.