ABSTRACT
The temperature is one of the principal controlling parameters of oncological hyperthermia. However, local heating forms a complicated thermal distribution in space and has developed over time, too. The decisional factors are the heterogeneity of the targeted volume, the electrolyte perfusions controlled by thermal homeostasis, and the spreading of the heat energy with time. A further complication is that the energy absorption sharply changes by depth, so the spatiotemporal development of the temperature distribution requires specialized methods to control. Most of the temperature imaging facilities (thermography, radiometry, electric impedance tomography, etc.) are less precise than the medical practice needs. In contrast, precise point sensing (like thermocouples, thermistors, and fluoroptical methods) is invasive and measures only a discrete point in the robustly changing thermal map. The two most precise thermal imaging methods, computer tomography, and magnetic resonance are expensive and have numerous technical complications. Our objective is to show the complexity of the temperature distribution inside the human body, and offer a relatively simple and cheap method to visualize its spatiotemporal development. A novel emerging technology, the application of ultrasound microbubble contrast agents is a promising method for solving complicated tasks of thermal distribution deep inside the living body. Noteworthy, the temperature distribution does not determine the full hyperthermia process, nonthermal effects make considerable impact, too. Additionally to the difficulties to measure the thermal heterogeneity during hyperthermia in oncology, numerous nonthermal processes, molecular and structural changes are triggered by the incoming electromagnetic energy, which presently has no spatiotemporal visualization technique. Microbubble imaging has a suitable spatiotemporal thermal resolution, and also it is sensitive to nonthermal effects. Its application for characterization of the modulated electrohyperthermia (mEHT) may open a new theranostic facility, using the synergy of the thermal and nonthermal effects of the radiofrequency delivered energy. This complex approach gives facility to follow the mEHT processes, and the proposed microbubble ultrasound imaging has a particularly promising advantage sensing and acting also nonthermally, having potential to characterize the thermally conditioned nonthermal electromagnetic effects in oncologic hyperthermia. The mEHT combined with microbubble ultrasound images could be a robust theranostic method against cancer.