Prediction and Visualization of Temperature Histories in Optically-Irradiated Cryogenic Tissues

Cryosurgery is a useful technique in the selective destruction of undesirable tissues, such as tumors, within the human body. Cryosurgery's primary benefit is that as a percutaneous method, it reduces the invasiveness and cost associated with traditional surgery. The objective of cryosurgery is to ensure complete destruction of the target tissue while simultaneously minimizing collateral damage to surrounding tissues. In addition to the problem of collateral damage, the nature of cryosurgery can make it difficult to ascertain the extent of cryoinjury during the surgical procedure. The scope of this work is to provide tools to minimize collateral damage, visualize cryoinjury following cryoinsult, and to better simulate cryosurgical outcomes.A method to counteract the collateral damage of cryosurgery was developed, which employs laser heating to thermally protect tissues surrounding a target tissue (e.g. tumor). A mouse hepatic tissue sample was cryogenically frozen with a cryoprobe on one side of the tissue, while freezing of the other side was prevented using selective laser heating. Tissue biopsies confirmed that this method can successfully protect regions of tissue from cryogenic damage through gentle laser heating.To visually characterize the regions of tissue damage following cryoinjury, Green Fluorescent Protein (GFP) transfected tissues were cryoinjured using a cryoprobe circulating liquid nitrogen. The long-term fluorescent yield of transfected tissues was observed in a controlled environment to determine the tissue's fluorescent response to cryoinjury. Other phenomena that impact fluorescent intensity were controlled and/or observed to eliminate these effects as the source of changing fluorescent intensity. It was observed that following cryoinjury, GFP fluorescence within tissues decays with a trend that follows Fick's second law of diffusion, suggesting that cryoinjury does not directly affect fluorescence, but allows the onset of GFP diffusion through and out of cryoinjured regions. Additional studies designed to account for the movement of all GFP within a closed system support this conclusion. It was determined that GFP-transfected tissues can effectively indicate cryoinjury, provided that conditions are favorable to diffusion.Emerging techniques that combine cryosurgery with laser heating need accurate methods to simulate the thermal response of a cryogenic tissue to optical irradiation. Light transport in tissue has been studied in great depth, and various computer programs and models currently exist that simulate light transport in simple systems. Light transport in tissues that undergo large changes in temperature, such as those encountered with laser-irradiated cryogenic tissues, cannot be accurately modeled with traditional methods, as those methods rely on simple geometries and optical properties which are constant with respect to temperature. A computer program and the supporting algorithms was developed which allows for the simulation of light transport in arbitrarily-shaped tissues which have temperature-dependent thermal and optical properties. The program first determines the optical distribution/deposition within the tissue, using a Monte Carlo photon heating simulation. The volumetric heating data is then used in determining heat transfer within the system. Optical properties based on the new thermal profile are interpolated and the optical distribution is repeated using these updated optical properties. This process repeats itself as necessary for the duration of the simulation. The simulation results compare favorably to established laser-tissue simulations, and to fundamental laws, validating the accuracy of the simulation outputs. The simulation can accurately predict the thermal response of a geometrically-complicated system to optical irradiation, including systems that undergo large changes in temperature and thus large changes in optical and thermal properties.