Hyperthermia has been used for many years, primarily as an adjuvant to radiation and/or chemotherapy to improve cancer outcomes. There is extensive clinical experience with microwave heating of superficial tissues extending about 3 cm from the skin surface. Typical hyperthermia treatments consist of raising the target tissue temperature from a baseline of 35–37°C to 40–45°C within about 5–10 minutes of power on (i.e. about 0.5–1°C/min heating rate) and maintained within this range for approximately 1 hour [10–13]. It should be noted that there are numerous reversible changes in biological tissue in this range of thermal dose which involves temperatures of 40–45°C for treatment times of about 60 minutes [14
]. The new device for non-invasive vesicoureteral reflux detection aims to use this same microwave heating technology at a lower thermal dose level of 40–44°C for 20 minutes, producing comfortable bladder warming. It is assumed that the bladder contents will rapidly homogenize in temperature due to natural convection within the bladder, which will minimize temperature gradients arising during external bladder warming and provide stable warm urine ready for the reflux event.
Phantom heating experiments with single DCC microwave antenna at 915 MHz demonstrated the feasibility of localized heating of 40–44°C in a 75 mL urinary bladder model with low temperatures in overlying fat and muscle (≤38 °C), as shown in . This is indicative of low patient discomfort and minimal complications. The phantom studies provided sufficient data to move on to confirmation of these results in in vivo
porcine bladder experiments. A 2×1 DCC antenna array was used for the pig bladder warming experiments due to the larger bladder volume (180 mL urine surrogate) typical for older patients (3–5 year old). A pulsed power heating protocol with 30 Watts alternately to each antenna and 75% duty cycle for the first 3–4 minutes followed by 25% duty cycle for the next 20minutes was determined based on heating cycles delivered to several protocol determination pigs. The high electrical conductivity of urine contained inside the bladder leads to preferential power absorption when irradiated using a microwave hyperthermia applicator [5
]. At our advantage, the lack of blood perfusion and the presence of a thermal barrier inside the bladder result in heat retention by the urine. Thus, the urine cools significantly slower when power is turned off for short durations than the surrounding perfused muscle and subcutaneous tissues. In contrast, temperature in the surrounding muscle and skin loses temperature quickly when microwave power is turned off primarily due to cooling from blood perfusion in these normal tissues [16
] as well as cooling from the room temperature waterbolus on the skin [17
]. Thus, the differential heating of urine was enhanced by the power modulation scheme, by allowing surface tissues to cool intermittently during periods of power off while the bladder contents continued to rise due to heating alternately from one antenna or the other which both couple the same stagnant urine reservoir.
The predetermined heating protocol was administered to three pigs destined for pathologic examination and the bladder (urine) temperature was raised to 40–44°C within the first 3–4 minutes with low skin/muscle tissues as seen in . The time delay between second and third repeated heat exposures was determined for these three pigs such that the urine and abdominal tissues cooled down to their respective base temperatures that were recorded prior to the first heat cycle. Each 20 minutes heat cycle used almost similar power levels with few Watts variation for the 6 heat exposures in 3 pigs and slight variations in temperature probe placement, and initial core temperatures. Pathology results of the three pigs demonstrated safe heating of the bladder, urine and upper pelvis for intra-bladder temperatures of 40–44°C without significant tissue damage.
We were pleased to find that the power necessary to warm even large (180 mL)bladder to 40–44°C could be delivered from the simple low profile printed circuit board type DCC antennas with a modulation (75% on/off cycle followed by 25% on/off cycle) that provided sparing of surface tissues. By minimizing the time averaged power per antenna, the skin and overlying structures were spared any thermal damage as evidenced in the pathology examination of the skin, subcutaneous fatty tissues, abdominal musculature, anterior and posterior bladder wall, peritoneum, ovaries, and vagina.