Miniature microwave applicator for murine bladder hyperthermia studies.

PURPOSE: Novel combinations of heat with chemotherapeutic agents are often studied in murine tumour models. Currently, no device exists to selectively heat small tumours at depth in mice. In this project we modelled, built and tested a miniature microwave heat applicator, the physical dimensions of which can be scaled to adjust the volume and depth of heating to focus on the tumour volume. Of particular interest is a device that can selectively heat murine bladder. MATERIALS AND METHODS: Using Avizo(®) segmentation software, we created a numerical mouse model based on micro-MRI scan data. The model was imported into HFSS™ (Ansys) simulation software and parametric studies were performed to optimise the dimensions of a water-loaded circular waveguide for selective power deposition inside a 0.15 mL bladder. A working prototype was constructed operating at 2.45 GHz. Heating performance was characterised by mapping fibre-optic temperature sensors along catheters inserted at depths of 0-1 mm (subcutaneous), 2-3 mm (vaginal), and 4-5 mm (rectal) below the abdominal wall, with the mid depth catheter adjacent to the bladder. Core temperature was monitored orally. RESULTS: Thermal measurements confirm the simulations which demonstrate that this applicator can provide local heating at depth in small animals. Measured temperatures in murine pelvis show well-localised bladder heating to 42-43°C while maintaining normothermic skin and core temperatures. CONCLUSIONS: Simulation techniques facilitate the design optimisation of microwave antennas for use in pre-clinical applications such as localised tumour heating in small animals. Laboratory measurements demonstrate the effectiveness of a new miniature water-coupled microwave applicator for localised heating of murine bladder.

Non-invasive measurement of brain temperature with microwave radiometry: demonstration in a head phantom and clinical case.

This study characterizes the sensitivity and accuracy of a non-invasive microwave radiometric thermometer intended for monitoring body core temperature directly in brain to assist rapid recovery from hypothermia such as occurs during surgical procedures. To study this approach, a human head model was constructed with separate brain and scalp regions consisting of tissue equivalent liquids circulating at independent temperatures on either side of intact skull. This test setup provided differential surface/deep tissue temperatures for quantifying sensitivity to change in brain temperature independent of scalp and surrounding environment. A single band radiometer was calibrated and tested in a multilayer model of the human head with differential scalp and brain temperature. Following calibration of a 500MHz bandwidth microwave radiometer in the head model, feasibility of clinical monitoring was assessed in a pediatric patient during a 2-hour surgery. The results of phantom testing showed that calculated radiometric equivalent brain temperature agreed within 0.4°C of measured temperature when the brain phantom was lowered 10°C and returned to original temperature (37°C), while scalp was maintained constant over a 4.6-hour experiment. The intended clinical use of this system was demonstrated by monitoring brain temperature during surgery of a pediatric patient. Over the 2-hour surgery, the radiometrically measured brain temperature tracked within 1-2°C of rectal and nasopharynx temperatures, except during rapid cooldown and heatup periods when brain temperature deviated 2-4°C from slower responding core temperature surrogates. In summary, the radiometer demonstrated long term stability, accuracy and sensitivity sufficient for clinical monitoring of deep brain temperature during surgery.

Design and optimization of an ultra wideband and compact microwave antenna for radiometric monitoring of brain temperature.

We present the modeling efforts on antenna design and frequency selection to monitor brain temperature during prolonged surgery using noninvasive microwave radiometry. A tapered log-spiral antenna design is chosen for its wideband characteristics that allow higher power collection from deep brain. Parametric analysis with the software HFSS is used to optimize antenna performance for deep brain temperature sensing. Radiometric antenna efficiency (η) is evaluated in terms of the ratio of power collected from brain to total power received by the antenna. Anatomical information extracted from several adult computed tomography scans is used to establish design parameters for constructing an accurate layered 3-D tissue phantom. This head phantom includes separate brain and scalp regions, with tissue equivalent liquids circulating at independent temperatures on either side of an intact skull. The optimized frequency band is 1.1-1.6 GHz producing an average antenna efficiency of 50.3% from a two turn log-spiral antenna. The entire sensor package is contained in a lightweight and low-profile 2.8 cm diameter by 1.5 cm high assembly that can be held in place over the skin with an electromagnetic interference shielding adhesive patch. The calculated radiometric equivalent brain temperature tracks within 0.4 °C of the measured brain phantom temperature when the brain phantom is lowered 10 °C and then returned to the original temperature (37 °C) over a 4.6-h experiment. The numerical and experimental results demonstrate that the optimized 2.5-cm log-spiral antenna is well suited for the noninvasive radiometric sensing of deep brain temperature.

Numerical 3D modeling of heat transfer in human tissues for microwave radiometry monitoring of brown fat metabolism.

BACKGROUND: Brown adipose tissue (BAT) plays an important role in whole body metabolism and could potentially mediate weight gain and insulin sensitivity. Although some imaging techniques allow BAT detection, there are currently no viable methods for continuous acquisition of BAT energy expenditure. We present a non-invasive technique for long term monitoring of BAT metabolism using microwave radiometry. METHODS: A multilayer 3D computational model was created in HFSS™ with 1.5 mm skin, 3-10 mm subcutaneous fat, 200 mm muscle and a BAT region (2-6 cm3) located between fat and muscle. Based on this model, a log-spiral antenna was designed and optimized to maximize reception of thermal emissions from the target (BAT). The power absorption patterns calculated in HFSS™ were combined with simulated thermal distributions computed in COMSOL® to predict radiometric signal measured from an ultra-low-noise microwave radiometer. The power received by the antenna was characterized as a function of different levels of BAT metabolism under cold and noradrenergic stimulation. RESULTS: The optimized frequency band was 1.5-2.2 GHz, with averaged antenna efficiency of 19%. The simulated power received by the radiometric antenna increased 2-9 mdBm (noradrenergic stimulus) and 4-15 mdBm (cold stimulus) corresponding to increased 15-fold BAT metabolism. CONCLUSIONS: Results demonstrated the ability to detect thermal radiation from small volumes (2-6 cm3) of BAT located up to 12 mm deep and to monitor small changes (0.5 °C) in BAT metabolism. As such, the developed miniature radiometric antenna sensor appears suitable for non-invasive long term monitoring of BAT metabolism.

Stable Microwave Radiometry System for Long Term Monitoring of Deep Tissue Temperature.

BACKGROUND: There are numerous clinical applications for non-invasive monitoring of deep tissue temperature. We present the design and experimental performance of a miniature radiometric thermometry system for measuring volume average temperature of tissue regions located up to 5cm deep in the body. METHODS: We constructed a miniature sensor consisting of EMI-shielded log spiral microstrip antenna with high gain on-axis and integrated high-sensitivity 1.35GHz total power radiometer with 500 MHz bandwidth. We tested performance of the radiometry system in both simulated and experimental multilayer phantom models of several intended clinical measurement sites: i) brown adipose tissue (BAT) depots within 2cm of the skin surface, ii) 3-5cm deep kidney, and iii) human brain underlying intact scalp and skull. The physical models included layers of circulating tissue-mimicking liquids controlled at different temperatures to characterize our ability to quantify small changes in target temperature at depth under normothermic surface tissues. RESULTS: We report SAR patterns that characterize the sense region of a 2.6cm diameter receive antenna, and radiometric power measurements as a function of deep tissue temperature that quantify radiometer sensitivity. The data demonstrate: i) our ability to accurately track temperature rise in realistic tissue targets such as urine refluxed from prewarmed bladder into kidney, and 10°C drop in brain temperature underlying normothermic scalp and skull, and ii) long term accuracy and stability of ∓0.4°C over 4.5 hours as needed for monitoring core body temperature over extended surgery or monitoring effects of brown fat metabolism over an extended sleep/wake cycle. CONCLUSIONS: A non-invasive sensor consisting of 2.6cm diameter receive antenna and integral 1.35GHz total power radiometer has demonstrated sufficient sensitivity to track clinically significant changes in temperature of deep tissue targets underlying normothermic surface tissues for clinical applications like the detection of vesicoureteral reflux, and long term monitoring of brown fat metabolism or brain core temperature during extended surgery.

Microwave Radiometry for Non-Invasive Detection of Vesicoureteral Reflux (VUR) Following Bladder Warming.

BACKGROUND: Vesicoureteral reflux (VUR) is a serious health problem leading to renal scarring in children. Current VUR detection involves traumatic x-ray imaging of kidneys following injection of contrast agent into bladder via invasive Foley catheter. We present an alternative non-invasive approach for detecting VUR by radiometric monitoring of kidney temperature while gently warming the bladder. METHODS: We report the design and testing of: i) 915MHz square slot antenna array for heating bladder, ii) EMI-shielded log spiral microstrip receive antenna, iii) high-sensitivity 1.375GHz total power radiometer, iv) power modulation approach to increase urine temperature relative to overlying perfused tissues, and v) invivo porcine experiments characterizing bladder heating and radiometric temperature of aaline filled 30mL balloon "kidney" implanted 3-4cm deep in thorax and varied 2-6°C from core temperature. RESULTS: SAR distributions are presented for two novel antennas designed to heat bladder and monitor deep kidney temperatures radiometrically. We demonstrate the ability to heat 180mL saline in in vivo porcine bladder to 40-44°C while maintaining overlying tissues <38°C using time-modulated square slot antennas coupled to the abdomen with room temperature water pad. Pathologic evaluations confirmed lack of acute thermal damage in pelvic tissues for up to three 20min bladder heat exposures. The radiometer clearly recorded 2-6°C changes of 30mL "kidney" targets at depth in 34°C invivo pig thorax. CONCLUSION: A 915MHz antenna array can gently warm in vivo pig bladder without toxicity while a 1.375GHz radiometer with log spiral receive antenna detects ≥2°C rise in 30mL "urine" located 3-4cm deep in thorax, demonstrating more than sufficient sensitivity to detect Grade 4-5 reflux of warmed urine for non-invasive detection of VUR.