University of Minnesota Ph.D. dissertation. March 2019. Major: Mechanical Engineering. Advisor: John Bischof. 1 computer file (PDF); xvi, 153 pages.Atrial Fibrillation (AF) is a major heart disease affecting millions of people every year. If left untreated, AF can cause cardiovascular disease, stroke and even death. Cryoablation for PV (Pulmonary Vein) isolation has been used for more than 10 years in AF treatment, which involves freezing (< -60 0C) and subsequent scarring of PV using a cold balloon/ catheter surface. Despite widespread and growing clinical use, the precise dosing and treatment times for cryoablation can vary depending on cooling surface contact, tissue thickness, and freeze completion through the wall. Without this knowledge, the treatment can be expected to have diminishing efficacy and may contribute to collateral injury. For instance, under-freezing may lead to inadequate treatment, while over-freezing can damage adjacent tissues (esophagus, lung and nerves), thereby creating complications. Clearly, there is a need to monitor this process to ensure complete treatment while avoiding complications. Unfortunately, the approaches for monitoring cryotherapy in the treatment of other diseases using clinical imaging cannot work for PV due to poor spatial resolution (mm). Thus, there is a pressing need to improve monitoring of cryoablation of the PV to reproducibly supply information on freezing within tissues at the millimeter to sub-millimeter level. Here then we present a response to this need through development of a micro- thermal sensor based on the “3ω” technique. We propose that a disposable thermal sensor based on 3ω technology can be deployed on a balloon to measure tissue contact, thickness and the initiation and completion of freezing in the PV all with an accuracy better than 1 mm. The 3ω technique, on which the sensor is based, was originally developed for thin inorganic materials. The technique was first modified for measurement of thermal conductivity of soft, hydrated biological tissues. Using the new sensor, for the first time, we have measured the thermal conductivity of thin porcine cardiac tissues in vitro addressing a major knowledge gap to inform focal therapy modeling for atrial fibrillation. This information is critical for successful treatment planning/prediction of therapy impact in the PV and surrounding tissues. Next, we show a dynamic use of the sensor for monitoring an idealized therapy in in vitro thin tissues (≤ 2 mm). For this, we demonstrated the ability of the sensor (on a flat substrate) to sense contact, flow, tissue thickness and freeze front in idealized systems. Specifically, the sensor was used to sense contact with tissue vs. water, ice (frozen agargel) thickness, and freeze initiation and completion. The success of this study suggests that integration of “3ω” sensors onto cardiology probe surfaces (i.e. balloons or catheters) can monitor cryoablation and by extension other PV focal therapies. As a next step, we integrated these sensors onto cryoballoons using transfer printing techniques. The 3ω sensor technology has traditionally been used for flat and rigid substrates. Therefore, we modified the shape of the sensor from a linear to a serpentine shape for integration onto balloon substrates. Next, using numerical analyses, we investigated the ability of the modified sensor on a flat substrate to differentiate measurements in limiting cases of ice, water and fat. These numerical results were then complemented by experimentation by micro-patterning the serpentine sensor onto a flat substrate and onto a flexible balloon. In both formats (flat and balloon) the serpentine sensor was experimentally shown to: (1) identify tissue contact vs. fluid, (2) distinguish tissue thickness in the 0.5 to 2 mm range, and (3) measure the initiation and completion of freezing as previously reported for a linear sensor. This study demonstrates proof of principle that a serpentine 3ω sensor on a balloon can monitor tissue contact, thickness and phase change which is relevant for cryo and other focal thermal treatments of PV to treat atrial fibrillation
