Quantification of macromolecular, cell, and tissue injury in thermal therapy of urologic systems

Thermal therapy, or tissue destruction by controlled heating, has been investigated as a possible alternative to surgical intervention in the treatment of many diseases. However, one main hurdle to the technique gaining widespread acceptance is the lack of understanding of the thermal and injury behavior resulting from thermal therapy within the body. This research is designed to investigate the thermal and injury process in thermal therapy of urologic systems at three different levels: macromolecular, cell, and tissue (i.e., cell and vascular). The injury kinetics and/or thermal histories at all the three levels were quantified and kinetic injury parameters were determined. At the macromolecular level, the overall thermal protein denaturation in suspended Dunning AT-1 prostate tumor cells studied using both Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC), was found to correlate very well with both acute (3 hour post treatment, membrane integrity dye assay) and chronic (7--10 days, clonogenic assay) cell injury. This result suggests that overall in situ thermal protein denaturation is an important mechanism of direct hyperthermic cell injury in AT1 cells. To further understand the cellular injury, the thermal injury behavior of both suspended and attached human renal cell carcinoma (RCC) SN12 cells under conditions of thermal therapy was investigated. It was found that suspended SN12 cells are more heat susceptible than attached ones, which suggests that cells in tissue may have different thermal sensitivity from isolated single cells. Therefore, a tissue level study was conducted to assess the thermal history and corresponding tissue injury patterns resulting from microwave treatment of the porcine renal cortex in three groups of kidneys: in vitro, in vivo 2-hour post-treatment (acute), and in vivo 7-day post-treatment (chronic). Both microvascular and tissue injury were quantified using histology and correlated to measured thermal histories. The threshold thermal history for chronic necrosis was found to be lower than that for acute necrosis implicating enhancement of tissue injury due to microvascular injury. This result suggests that vascular injury determines the extent of tissue damage in microwave thermal therapy of in vivo chronic porcine kidneys.