Non-invasive,in-vivoelectrical impedance of EMT-6 tumours during hyperthermia: Correlation with morphology and tumour-growth-delay

Abstract

The electrical impedance at frequencies from 100 Hz to 40 MHz of EMT-6 tumours was measured non-invasively, in vivo, during hyperthermia using an apparatus constructed for this purpose. Histology and morphometry were performed on tumours harvested periodically during the heating. A ratio of conductivities at two frequencies (sigma (10MHz)/sigma (10kHz)), which minimizes the tissues temperature-coefficient effects, was used to correlate impedance changes with the histopathological changes. The bulk of the cell population followed a necrotic cell death sequence during heating. Initial increase of the sigma-ratio correlated with cell swelling, and a reversal of the rate of this increase correlated with the appearance of small membrane breaks and evidence of mitochondrial damage. A continued, slowing sigma-ratio increase to a maximum correlated with continued cell swelling accompanied by increasing membrane disruption. The subsequent decrease in sigma-ratio correlated with continued general cell lysing. Between the appearance of the first membrane breaks (sigma-ratio peak) and the evidence of general lysing (sigma-ratio peak), the tumour-growth-delay increased non-linearly. Because the sigma-ratio consistently discerned these events, these measurements were able to predict the fate of this cell population when subjected to hyperthermia. Knowledge of temperature or time of heating was not required.