Magnetic fluid hyperthermia for bladder cancer: a preclinical dosimetry study.

PURPOSE: This paper describes a preclinical investigation of the feasibility of thermotherapy treatment of bladder cancer with magnetic fluid hyperthermia (MFH), performed by analysing the thermal dosimetry of nanoparticle heating in a rat bladder model. MATERIALS AND METHODS: The bladders of 25 female rats were instilled with magnetite-based nanoparticles, and hyperthermia was induced using a novel small animal magnetic field applicator (Actium Biosystems, Boulder, CO). We aimed to increase the bladder lumen temperature to 42 °C in <10 min and maintain that temperature for 60 min. Temperatures were measured within the bladder lumen and throughout the rat with seven fibre-optic probes (OpSens Technologies, Quebec, Canada). An MRI analysis was used to confirm the effectiveness of the catheterisation method to deliver and maintain various nanoparticle volumes within the bladder. Thermal dosimetry measurements recorded the temperature rise of rat tissues for a variety of nanoparticle exposure conditions. RESULTS: Thermal dosimetry data demonstrated our ability to raise and control the temperature of rat bladder lumen ≥1 °C/min to a steady state of 42 °C with minimal heating of surrounding normal tissues. MRI scans confirmed the homogenous nanoparticle distribution throughout the bladder. CONCLUSION: These data demonstrate that our MFH system with magnetite-based nanoparticles provides well-localised heating of rat bladder lumen with effective control of temperature in the bladder and minimal heating of surrounding tissues.

The impact of temperature and urinary constituents on urine viscosity and its relevance to bladder hyperthermia treatment.

PURPOSE: The aim of this study was to determine the kinematic viscosity of human urine and factors associated with its variability. This value is necessary for accurate modelling of fluid mechanics and heat transfer during hyperthermia treatments of bladder cancer. MATERIALS AND METHODS: Urine samples from 64 patients undergoing routine clinical testing were subject to dipstick urinalysis and measurement of viscosity with a Cannon-Fenske viscometer. Viscosity measurements were taken at relevant temperatures for hyperthermia studies: 20 °C (room temperature), 37 °C (body temperature), and 42 °C (clinical hyperthermia temperature). Factors that might affect viscosity were assessed, including glucosuria, haematuria, urinary tract infection status, ketonuria and proteinuria status. The correlation of urine specific gravity and viscosity was measured with Spearman's rho. RESULTS: Urine kinematic viscosity at 20 °C was 1.0700 cSt (standard deviation (SD) = 0.1076), at 37 °C 0.8293 cSt (SD = 0.0851), and at 42 °C 0.6928 cSt (SD = 0.0247). Proteinuria appeared to increase urine viscosity, whereas age, gender, urinary tract infection, glucosuria, ketonuria, and haematuria did not affect it. Urine specific gravity was only modestly correlated with urine viscosity at 20 °C (rho = 0.259), 37 °C (rho = 0.266), and 42 °C (rho = 0.255). CONCLUSIONS: The kinematic viscosity of human urine is temperature dependent and higher than water. Urine specific gravity was not a good predictor of viscosity. Of factors that might affect urine viscosity, only proteinuria appeared to be clinically relevant. Estimates of urine viscosity provided in this manuscript may be useful for temperature modelling of bladder hyperthermia treatments with regard to correct prediction of the thermal conduction effects.

Heterogeneous Anthropomorphic Phantoms with Realistic Dielectric Properties for Microwave Breast Imaging Experiments.

We present a technique for fabricating realistic breast phantoms for microwave imaging experiments. Using oil-in-gelatin dispersions that mimic breast tissue dielectric properties at microwave frequencies, we constructed four heterogeneous phantoms spanning the full range of volumetric breast densities. We performed CT scans and dielectric properties measurements to characterize each phantom.

Toward carbon-nanotube-based theranostic agents for microwave detection and treatment of breast cancer: enhanced dielectric and heating response of tissue-mimicking materials.

The experimental results reported in this paper suggest that single-walled carbon nanotubes (SWCNTs) have the potential to enhance dielectric contrast between malignant and normal tissue for microwave detection of breast cancer and facilitate selective heating of malignant tissue for microwave hyperthermia treatment of breast cancer. In this study, we constructed tissue-mimicking materials with varying concentrations of SWCNTs and characterized their dielectric properties and heating response. At SWCNT concentrations of less than 0.5% by weight, we observed significant increases in the relative permittivity and effective conductivity. In microwave heating experiments, we observed significantly greater temperature increases in mixtures containing SWCNTs. These temperature increases scaled linearly with the effective conductivity of the mixtures. This work is a first step towards the development of functionalized, tumor-targeting SWCNTs as theranostic (integrated therapeutic and diagnostic) agents for microwave breast cancer detection and treatment.

Toward contrast-enhanced microwave-induced thermoacoustic imaging of breast cancer: an experimental study of the effects of microbubbles on simple thermoacoustic targets.

Microwave-induced thermoacoustic tomography (MI-TAT) is an imaging technique that exploits dielectric contrast at microwave frequencies while creating images with ultrasound resolution. We propose the use of microbubbles as a dielectric contrast agent for enhancing the sensitivity of MI-TAT for breast cancer detection. As an initial investigation of this concept, we experimentally studied the extent to which the microwave-induced thermoacoustic response of a dielectric target is modified by the presence of air-filled glass microbubbles. We created mixtures of ethylene glycol with varying weight percentages of microbubbles and characterized both their microwave properties (0.5-6 GHz) and thermoacoustic response when irradiated with microwave energy at 3 GHz. Our data show that the microbubbles considerably lowered the relative permittivity, electrical conductivity and thermoacoustic response of the ethylene glycol mixtures. We hypothesize that the interstitial infusion of microbubbles to a tumor site will similarly create a smaller thermoacoustic response compared to the pre-contrast-agent response, thereby enhancing sensitivity through the use of differential imaging techniques.