Measurement of Ultrasound Attenuation and Protein Denaturation Behavior During Hyperthermia Monitoring

Abstract

Recently, there is increasing interest in the use of local hyperthermia therapy such as RF ablation, high intensity focused ultrasound and magnetic nanoparticles for a variety of clinical applications. The desired therapeutic outcome in these therapies is achieved by raising the local temperature to surpass the tissue coagulation threshold, resulting in tissue necrosis. However, the inability to closely monitor temperature elevation from hyperthermia therapy in real time with high accuracy continues to limit its clinical applicability. During therapy, temperature monitoring is essential for controlling thermal dose and this issue has been an ongoing difficulty in hyperthermia treatment. Ultrasound is an attractive and promising imaging modality to guide and monitor hyperthermia treatment because it is non-ionizing, inexpensive, portable and capable of real time imaging. Many methods for ultrasound thermometry have been presented previously including the manipulation of pixel value, the exploitation of thermal strain and most popular, the quantification of frequency dependence attenuation, backscatter coefficient and speed of sound in tissue. However, previous studies do not quantify the changes in ultrasound properties with microstructural and chemical changes in tissue. Hence, it is very hard to gauge the sensitivity of the reported ultrasound parameter to the given thermal intensity during hyperthermia treatment. This study focused on the quantification of ultrasound attenuation changes to total protein during hyperthermia therapy. In this study, A-Mode ultrasound was used to monitor a set of normal and DMBA-induced virgin female mice breast tissue in hyperthermia treatment at a temperature of 37, 55 and 65 degrees C. The objective was to investigate the relationship between thermal exposure during hyperthermia with changes in ultrasound attenuation and protein denaturation level. The application of heat on tissue in this study induced changes in the tissue structure due to protein coagulation. The heating process altered the way ultrasound propagates through the tissue, as protein coagulation changes tissue density and compressibility. From the result, it can be seen that ultrasound attenuation was very sensitive to changes in tissue microstructure due to hyperthermia. On the other hand, protein content in pathological tissues denatured at a higher rate compared to protein in normal tissue. Further study is ongoing to assess the relationship between attenuation, protein denaturation and thermal intensity. Ultrasound attenuation is expected to have high sensitivity to protein denaturation, which will be a good indicator for tissue necrosis.