New experimental model for single liver lobe hyperthermia in small animals using non-directional microwaves

Abstract

Purpose: Our aim was to develop a new experimental model for in vivo hyperthermia using non-directional microwaves, applicable to small experimental animals. We present an affordable approach for targeted microwave heat delivery to an isolated liver lobe in rat, which allows rapid, precise and stable tissue temperature control.

Materials and methods: A new experimental model is proposed. We used a commercial available magnetron generating 2450 MHz, with 4.4V and 14A in the filament and 4500V anodic voltage. Modifications were required in order to adjust tissue heating such as to prevent overheating and to allow for fine adjustments according to real-time target temperature. The heating is controlled using a virtual instrument application implemented in LabView® and responds to 0.1° C variations in the target. Ten healthy adult male Wistar rats, weighing 250-270 g were used in this study. The middle liver lobe was the target for controlled heating, while the rest of the living animal was protected.

Results: In vivo microwave delivery using our experimental setting is safe for the animals. Target tissue temperature rises from 30°C to 40°C with 3.375°C / second (R2 = 0.9551), while the increment is lower it the next two intervals (40-42°C and 42-44°C) with 0.291°C/ s (R2 = 0.9337) and 0.136°C/ s (R2 = 0.7894) respectively, when testing in sequences. After reaching the desired temperature, controlled microwave delivery insures a very stable temperature during the experiments.

Conclusions: We have developed an inexpensive and easy to manufacture system for targeted hyperthermia using non-directional microwave radiation. This system allows for fine and stable temperature adjustments within the target tissue and is ideal for experimental models testing below or above threshold hyperthermia.

Fig 1. Wiring diagram of the magnetron.

U1, U2 –dor close switch; A1, A2 –connectors; I1 –main breaker; Ls1, Ls2 –signaling lamps; Tr–transformer; S1, S2 –fuses; BSM–manual command button; A–ampermeter; F1 –power filter; C–capacitor; D1 –diode HVR-U62; D2 –diode HVR; VM–magnetron chiller; M–magnetron.

Fig 2. Magnetron duty cycle.

Magnetron duty cycle in an experiment aiming to liver heating at 42°C (graph in the upper panel); On-off cycle during the first 2 seconds after reaching set temperature (graph in lower panel).

Fig 3. Electromagnetic/Thermal co-simulation.

Electromagnetic/Thermal co-simulation using CST Studio Suit; vertical plane—upper panel; horizontal plane -lower panel.

Fig 4. Virtual instrument programming module.

Block diagram.

Fig 5. Aluminum foil wrapping.

Mobilized middle liver lobe remains uncovered for microwave exposure.

Fig 6. Thermal imaging after microwave exposure.

Demonstration of the lack of hot spots outside experimental tissue. Infrared image obtained seconds after microwave heating—thermal gradient on the surface of the liver are inherent to rapid cooling in the periphery of the experimental lobe.

Fig 7. Continuous recording of tissue temperature.

Temperature recorded for three successive targets (40, 42 and 44°C) (n = 10). T1—average of the temperatures values acquired from heated liver lobe. T2—average of the temperatures values acquired from control liver lobe. Dotted lines represent standard deviation.

Fig 8. Linear regression indicating the rate of temperature increase in the heated lobe (n = 10).

Thick dotted line: 30°C to 40°C at 3.375°C / second (R2 = 0.9551; p<0.0001); Thick black line: 40 to 42°C at 0.291°C/ second (R2 = 0.9337; p<0.0001); Thick gray line: 42 to 44°C at 0.136°C/ s (R2 = 0.7894; p<0.0001). Thin solid and dotted lines are average and respectively, standard deviation of recorded temperatures.