Ultrasound irradiation to a certain site of the body affects the efficacy of drug delivery through changes in the permeability of cell membrane. Temperature increase in irradiated area may be affected by frequency, intensity, period of ultrasound, and blood perfusion. The aim of present study is to use computer simulation and offer an appropriate model for thermal distribution profile in prostate tumor. Moreover, computer model was validated by in vivo experiments.
Prostate cancer is one of the most common malignant cancers in men [
Traditionally, ultrasound waves have been used either for ultrasound hyperthermia or physiotherapy to warm the tissue or to kill cancerous cells [
In order to get precise prediction of response of exposed tissue to the ultrasound wave, it is important to determine thermal distribution of absorbed ultrasound wave in the region of interest [
Effects of ultrasound on tissue heating were modeled in two phases. At first, the acoustic pressure of sound in tissue was solved using wave equations. Secondly, the diffusion of heat in the tissue was calculated using the obtained acoustic pressure as the source term. In order to calculate pressure field generated by the acoustic source in attenuation media, Helmholtz equation was used:
Here,
Thermal properties of tumor and blood used in numerical calculation [
Tissue |
|
|
|
|
---|---|---|---|---|
Prostate tumor | 1086 | 3310 | 0.45 | 1660 |
Blood | 1058 | 3850 | 0.47 | — |
The simulation was performed by COMSOL software at three different intensities of 0.3, 0.5, and 1 w/cm2 and the frequency of 3 MHz. The initial temperature of the tumor was set at 37°C for all performed simulations and run time (ultrasound exposure) was set at 300 seconds.
Human prostate cancer cells (DU145 cell line) were obtained from Pasteur Institute of Iran. Cells were grown in RPMI 1640 medium with 10% fetal calf serum, 100 units/mL penicillin, and 100
Due to the capability of deep penetration and transferring energy, ultrasound waves are being used in medicine for treatment and diagnosis purposes. In drug delivery, as a main application of therapeutic ultrasound, mechanism of drug releasing in intracellular environment and tissue’s drug uptake may be affected by ultrasound intensity and frequency. Present study which was performed in two phases revealed that ultrasound pressure distribution and thermal distribution are inhomogeneous.
Figure
Computer simulation of acoustic pressure map in tumor.
Temperature-time curve of ultrasound wave at frequency of 3 MHz, intensity of 0.3 w/cm2, and at run time 300 seconds (a) in simulation and (b) in in vivo experiment.
Temperature-time curve of ultrasound wave at frequency of 3 MHz, intensity of 0.5 w/cm2, and at run time 300 seconds (a) in simulation and (b) in in vivo experiment.
Temperature-time curve of ultrasound wave at frequency of 3 MHz, intensity of 1 w/cm2, and at run time 300 seconds (a) in simulation and (b) in in vivo experiment.
As mentioned above, ultrasound may be effective in targeted chemotherapy by increasing drug uptake level of the tumor through macroscopic mechanisms of macromolecular massage of the cell membrane [
We present computer simulations to predict the amount of temperature elevation during ultrasound exposure of prostate tumor at different intensities. Our model suggests a direct correlation between temperature elevation and intensity of ultrasound for the same period of sonication. The rate of temperature rise was directly proportional to ultrasound intensity. Modeling results agree with preliminary in vivo results in xenograft nude mice model with regard to temperature elevation. In conclusion, data obtained in both computational and experimental studies holds great promise to develop a model which is able to predict temperature distribution profile with in vivo condition.
The authors declare that there is no conflict of interests.