The long-term goal of this work is the investigation of tissue electrical impedance changes as a method for detecting and monitoring, in real-time, the tissue changes occurring during therapeutic hyperthermia administered in the clinic. In therapeutic hyperthermia, thermal dose, defined as some function of heating temperature and duration, while being related to, has not invariably proven predictive of a tissue's response to heating. Therefore, to determine whether a treatment goal has been reached during a particular treatment, numerous techniques are being investigated for directly obtaining information on hyperthermia-induced tissue changes.The monitoring of tissue electrical impedance changes is being proposed as an additional method which can provide unique information of tissue response at the cellular level. Extensive data using fresh excised tissue, and preliminary in vivo results, show that tissue impedance changes can be linked with major hyperthermia-induced histological changes occurring at the cell and tissue structure levels. The proposed work takes the next essential step by fully investigating the relationship between in vivo tissue electrical impedance changes and concurrent, hyperthermia-induced histological changes in three experimental tumors. The work is divided into two phases. First, the tumors will be heated in vivo in a water bath, and at selected times, cooled, excised, and measured under controlled conditions in an impedance measurement cell. To relate the tissue electrical impedance changes to the in vivo hyperthermia-induced histological changes existing after different heating times, identically treated tumors will be histologically and morphometrically characterized. Second, utilizing the results from phase I, selected in vivo impedance measurement techniques for providing real-time tissue impedance information simultaneously with the application of hyperthermia to the tumors will be evaluated. The optimum method will then be employed to obtain continuous, in vivo, real-time impedance data on the histological changes occurring in the three tumors during hyperthermia. This leads to subsequent work correlating these impedance changes with tumor growth- delay endpoints.
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