Feasibility of ultrasound hyperthermia in the treatment of malignant brain tumors.

In order to test the biological feasibility of using ultrasound-generated hyperthermia for the treatment of brain tumors, damage threshold studied and thermal dosimetry studies as a function of temperature were performed in 44 acute experiments in cats. Bilateral craniotomies were performed to expose the dural surface. Ultrasonic radiation was applied for 50 minutes at different intensities to generate temperatures up to 48 degrees C. Thermal fields were mapped using an electrode array of three triple-junction thermocouple probes. Each probe left a track easily identified histologically. Serial sections of each brain were cut and stained, allowing for precise correlation of histology and thermocouple location and temperature. At temperatures of less than 42 degrees C for 50 minutes, no evidence of damage could be detected in either gray or white matter. At 43 degrees C partial loss of neurons was seen in the brain adjacent to the probe, but at the same temperature in white matter, only edema was seen. At temperatures of 44-45 degrees C there was definite loss of both neurons in the gray matter and myelin tracts in the white matter. The lesions created by using ultrasound-generated hyperthermia were sharply marginated. This sharp demarcation histologically correlated well with the abrupt fall off in temperature as a function of distance from the lesion edge. The results of this study are important in two respects. First, it demonstrates that ultrasound can effectively heat the brain in an extremely controlled and precise manner. Second, the brain can withstand temperatures to 42 degrees C without showing histological evidence of damage, which is the temperature range at which neoplastic cells begin to show cytotoxic effects.