Temperature evolution, injury enhancement and treatment planning in cryosurgery

Cryosurgery is the in situ ablation of target tissues by exposing them to low subzero temperatures. The last ten years have seen a resurgence of the interest in low temperature medicine and an advancement in the technologies used to inflict a freezing injury. Based on a comparative study, a new Joule-Thompson based cryomachine was found to have superior control than the standard liquid nitrogen cryomachine tested. The ability of the new generation of machines to quickly change temperatures led to the hypothesis that Dynamic Cryosurgery, the generation of thermal waves by oscillating cryoprobe tip temperatures, may increase the direct injury to cells within a cryosurgical iceball. An alternative means of accomplishing the same goal is to hold the iceball at a constant size once the critical temperature has been reached by the target tissue thereby increasing the hold time of cells at subzero temperatures. This alternative was tested in-vivo with an AT-1 Dunning rat prostate model and was found to increase the lethality of the iceball. To further the understanding of the cell damage mechanisms occurring during cryosurgery freezing and thawing rates that would be experienced clinically were mimicked on a cryostage and an in-vitro map of cellular damage was created, again using the Dunning cell line. Single and double freeze-thaw cycle experiments were performed. No intracellular ice was observed during the first freeze thaw cycle and viable cells were found in all regions of the iceball. This finding supports the role of ischemia resulting from post-treatment vascular stasis as a major contributor to cell killing. Cryosurgery is currently preformed with the goal of enclosing the target tissue within a critical isotherm assumed to insure necrosis. A three dimensional model of temperatures about multiple cryoprobes was developed to predict temperatures during cryosurgery and compared to experimental data. Predictions of this model were found to be accurate within experimental error. The ablative ratio, a measure of iceball potency, was calculated for one, three and five cryoprobe configurations. Multiple cryoprobe arrays produce an iceball with an ablative ratio that increases with time then plateaus. This contrasts with the ablative ratio for a single cryoprobe which is a continually decreasing as a function of time. In an attempt to simulate the thermal environment which occurs during prostate cryosurgery a thermal model was created taking into account the heating effects of the bladder and urethra. Computer generated three-dimensional visualization of isotherms overlaid on the relevant anatomy with temperature-volume-histograms and regions of concern maps allowed quantitative assessment of the planned treatment.