Temperature Monitor And Mathematical Model Simulation Of Tumor During The Process Of Selective Photothermal Therapy

ObjectivePhotothermal therapy is an important part of laser immunotherapy.Laser immunotherapy has gotten great effect in animal experiment and clinical trials.The thermal effect induced by photothermal therapy contributed a lot to the great effect.Literature demonstrated that different thermal effect and immune effect could be induced by different temperature.Therefore,the change of temperature during photothermal therapy makes a significant effect in the treatment of cancer.There are a great number of studies about the effect of photothermal therapy,but few study had been conducted to investigate the characteristics of temperature change and temperature distribution during the photothermal therapy.This study aims to investigate the characteristics of temperature change during photothermal therapy by infrared thermometer in the solution of indocyanine green and tumor-bearing mice treated by laser and indocyanine green,and to observe morphological change of tumor tissue by Haematoxylin-Eosin staining after photothermal therapy.In addition,we will investigate the temperature distribution in tumor tissue and surrounding health tissue of tumor bearing mice during photothermal therapy applying mathematical simulation model.MethodsIn this study,spectrophotometer was applied to measure the absorbance spectrum of ICG with different concentration.Infrared thermometer was applied to monitor the temperature of solution with different concentration of ICG.In animal experiment,4T1 breast cancer cells were cultured and were inoculated to mice and the tumor bearing mice models were constructed.Various parameters of power density and ICG concentration were used to treat the 4T1tumor-bearing Balb/c mice.During the photothermal therapy,the infrared thermometer was applied to monitor the surface temperature of tumor tissue.According to the process of photothermal therapy treating the tumor bearing mice,Monte Carlo method and the Pennes bio-heat equation were used to calculate the light distribution and heat energy.To solve the Pennes bio-heat equation,COMSOL Multiphysic was adopted to construct three dimensional temperature distribution model of the tumor tissue and surrounding healthy tissue.ResultsIn the experiment of solution,the temperature of ICG solution gradually elevated as the concentration of ICG increased.When the concentration of indocyanine green were 0 mg/ml and 0.0187 mg/ml,laser power density was1W/cm~2,the temperature of water elevated 3°C and 28°C respectively.In the experiment of tumor bearing mice,when the concentration of indocyanine green were 0mg/ml and 0.1mg/ml,laser power density was 1 W/cm~2,the temperature of tumor bearing mice elevated 6.9°C and 28.5°C respectively at t=600s.With the increase of laser power density(0.6W/cm~2,0.8W/cm~2,1.0 W/cm~2),the temperature increased gradually(23.3°C,26.7°C,28.5°C).Pathological section demonstrated that large number of tumor cells experienced necrosis and the envelope of tumor was destroyed.Numerous inflammation cells,especially lymphocytes infiltrated into tumor tissue after tumor tissue was treated by laser combined with indocyanine green.The data calculated by simulation model is in good agreement with the surface temperature monitored by infrared thermometer.Effected by the optical parameters and boundary conditions of tissue,the highest temperature of tissue treated by laser combined with indocyanine green was about 65°C which located in tumor tissue and the highest temperature of tissue treated by laser was about 43°C which located under the tumor tissue.The temperature difference was about 20°C.Temperature distribution in tissue was not uniform.The temperature difference in different parts of tumor tissue raised up to 15°C.The temperature of tumor tissue treated by laser combined with indocyanine green was about 20°C higher than that of the surrounding healthy tissue.The first 240s of laser irradiation,the temperature gradually increased;After laser irradiation of 240s,with the prolonged exposure time,the temperature increase was not obvious.ConclusionThis study indicated that laser combined with indocyanine green could significantly increased the temperature of water solution and tumor bearing mice.The increase of temperature is proportional to the concentration of indocyanine green and laser power density.The concentration of indocyanine green and laser power density contribute a lot to the temperature elevation,especially the concentration of indocyanine green.Reasonably good matching between the calculated temperature and the measured temperature was achieved,thus demonstrated great utility of our modeling method and approaches for deepening understand in the temperature distribution in tumor tissue and surrounding healthy tissue during the laser combined with photosensitizer.The simulation model could provide guidance and reference function for the effect of photothermal therapy.