Gold Nanostars Obviate Limitations to Laser Interstitial Thermal Therapy (LITT) for the Treatment of Intracranial Tumors.

PURPOSE: Laser interstitial thermal therapy (LITT) is an effective minimally invasive treatment option for intracranial tumors. Our group produced plasmonics-active gold nanostars (GNS) designed to preferentially accumulate within intracranial tumors and amplify the ablative capacity of LITT. EXPERIMENTAL DESIGN: The impact of GNS on LITT coverage capacity was tested in ex vivo models using clinical LITT equipment and agarose gel-based phantoms of control and GNS-infused central "tumors." In vivo accumulation of GNS and amplification of ablation were tested in murine intracranial and extracranial tumor models followed by intravenous GNS injection, PET/CT, two-photon photoluminescence, inductively coupled plasma mass spectrometry (ICP-MS), histopathology, and laser ablation. RESULTS: Monte Carlo simulations demonstrated the potential of GNS to accelerate and specify thermal distributions. In ex vivo cuboid tumor phantoms, the GNS-infused phantom heated 5.5× faster than the control. In a split-cylinder tumor phantom, the GNS-infused border heated 2× faster and the surrounding area was exposed to 30% lower temperatures, with margin conformation observed in a model of irregular GNS distribution. In vivo, GNS preferentially accumulated within intracranial tumors on PET/CT, two-photon photoluminescence, and ICP-MS at 24 and 72 hours and significantly expedited and increased the maximal temperature achieved in laser ablation compared with control. CONCLUSIONS: Our results provide evidence for use of GNS to improve the efficiency and potentially safety of LITT. The in vivo data support selective accumulation within intracranial tumors and amplification of laser ablation, and the GNS-infused phantom experiments demonstrate increased rates of heating, heat contouring to tumor borders, and decreased heating of surrounding regions representing normal structures.

Plasmonic gold nanostar-mediated photothermal immunotherapy for brain tumor ablation and immunologic memory.

Brain tumors present unique therapeutic challenges and they include glioblastoma (GBM) and metastases from cancers of other organs. Current treatment options are limited and include surgical resection, radiation therapy, laser interstitial thermal therapy and chemotherapy. Although much research has been done on the development of immune-based treatment platforms, only limited success has been demonstrated. Herein, we demonstrate a novel treatment of GBM through the use of plasmonic gold nanostars (GNS) as photothermal inducers for synergistic immuno photothermal nanotherapy (SYMPHONY), which combines treatments using gold nanostar and laser-induced photothermal therapy with checkpoint blockade immunotherapy. In the treatment of a murine flank tumor model with the CT-2A glioma cell line, SYMPHONY demonstrated the capability of producing long-term survivors that rejects rechallenge with cancer cells, heralding the successful emergence of immunologic memory. This study is the first to investigate the use of this novel therapy for the treatment of GBM in a murine model.

Thermal dosimetry for bladder hyperthermia treatment. An overview.

The urinary bladder is a fluid-filled organ. This makes, on the one hand, the internal surface of the bladder wall relatively easy to heat and ensures in most cases a relatively homogeneous temperature distribution; on the other hand the variable volume, organ motion, and moving fluid cause artefacts for most non-invasive thermometry methods, and require additional efforts in planning accurate thermal treatment of bladder cancer. We give an overview of the thermometry methods currently used and investigated for hyperthermia treatments of bladder cancer, and discuss their advantages and disadvantages within the context of the specific disease (muscle-invasive or non-muscle-invasive bladder cancer) and the heating technique used. The role of treatment simulation to determine the thermal dose delivered is also discussed. Generally speaking, invasive measurement methods are more accurate than non-invasive methods, but provide more limited spatial information; therefore, a combination of both is desirable, preferably supplemented by simulations. Current efforts at research and clinical centres continue to improve non-invasive thermometry methods and the reliability of treatment planning and control software. Due to the challenges in measuring temperature across the non-stationary bladder wall and surrounding tissues, more research is needed to increase our knowledge about the penetration depth and typical heating pattern of the various hyperthermia devices, in order to further improve treatments. The ability to better determine the delivered thermal dose will enable clinicians to investigate the optimal treatment parameters, and consequentially, to give better controlled, thus even more reliable and effective, thermal treatments.

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.

Thermal dosimetry characteristics of deep regional heating of non-muscle invasive bladder cancer.

PURPOSE: The aim of this paper is to report thermal dosimetry characteristics of external deep regional pelvic hyperthermia combined with intravesical mitomycin C (MMC) for treating bladder cancer following transurethral resection of bladder tumour, and to use thermal data to evaluate reliability of delivering the prescribed hyperthermia dose to bladder tissue. MATERIALS AND METHODS: A total of 14 patients were treated with MMC and deep regional hyperthermia (BSD-2000, Sigma Ellipse or Sigma 60). The hyperthermia objective was 42° ± 2 °C to bladder tissue for ≥40 min per treatment. Temperatures were monitored with thermistor probes and recorded values were used to calculate thermal dose and evaluate treatment. Anatomical characteristics were examined for possible correlations with heating. RESULTS: Combined with BSD-2000 standard treatment planning and patient feedback, real-time temperature monitoring allowed thermal steering of heat sufficient to attain the prescribed thermal dose to bladder tissue within patient tolerance in 91.6% of treatments. Mean treatment time for bladder tissue >40 °C was 61.9 ± 11.4 min and mean thermal dose was 21.3 ± 16.5 CEM43. Average thermal doses obtained in normal tissues were 1.6 ± 1.2 CEM43 for the rectum and 0.8 ± 1.3 CEM43 in superficial normal tissues. No significant correlation was seen between patient anatomical characteristics and thermal dose achieved in bladder tissue. CONCLUSIONS: This study demonstrates that a hyperthermia prescription of 42° ± 2 °C for 40-60 min can be delivered safely to bladder tissue with external radiofrequency phased array applicators for a typical range of patient sizes. Using the available thermometry and treatment planning, the BSD-2000 hyperthermia system was shown to be an effective method of focusing heat regionally around the bladder with good patient tolerance.

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.

A pilot clinical trial of intravesical mitomycin-C and external deep pelvic hyperthermia for non-muscle-invasive bladder cancer.

PURPOSE: This paper aims to evaluate the safety and heating efficiency of external deep pelvic hyperthermia combined with intravesical mitomycin C (MMC) as a novel therapy for non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: We enrolled subjects with bacillus Calmette-Guérin (BCG) refractory NMIBC to an early phase clinical trial of external deep pelvic hyperthermia (using a BSD-2000 device) combined with MMC. Bladders were heated to 42 °C for 1 h during intravesical MMC treatment. Treatments were given weekly for 6 weeks, then monthly for 4 months. Heating parameters, treatment toxicity, and clinical outcomes were systematically measured. RESULTS: Fifteen patients were enrolled on the clinical trial. Median age was 66 years and 87% were male. Median European Organisation for Research and Treatment of Cancer (EORTC) recurrence and progression scores were 6 and 8, respectively. The full treatment course was attained in 73% of subjects. Effective bladder heating was possible in all but one patient who could not tolerate the supine position due to lung disease. Adverse events were all minor (grade 2 or less) and no systemic toxicity was observed. The most common adverse effects were Foley catheter pain (40%), abdominal discomfort (33%), chemical cystitis symptoms (27%), and abdominal skin swelling (27%). With a median follow-up of 3.18 years, 67% experienced another bladder cancer recurrence (none were muscle invasive) and 13% experienced an upper tract recurrence. CONCLUSIONS: External deep pelvic hyperthermia using the BSD-2000 device is a safe and reproducible method of heating the bladder in patients undergoing intravesical MMC. The efficacy of this treatment modality should be explored further in clinical trials.

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.

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.

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.

Preclinical Dosimetry of Magnetic Fluid Hyperthermia for Bladder Cancer.

BACKGROUND: Despite positive efficacy, thermotherapy is not widely used in clinical oncology. Difficulties associated with field penetration and controlling power deposition patterns in heterogeneous tissue have limited its use for heating deep in the body. Heat generation using iron-oxide super-paramagnetic nanoparticles excited with magnetic fields has been demonstrated to overcome some of these limitations. The objective of this preclinical study is to investigate the feasibility of treating bladder cancer with magnetic fluid hyperthermia (MFH) by analyzing the thermal dosimetry of nanoparticle heating in a rat bladder model. METHODS: The bladders of 25 female rats were injected with 0.4 ml of Actium Biosystems magnetite-based nanoparticles (Actium Biosystems, Boulder CO) via catheters inserted in the urethra. To assess the distribution of nanoparticles in the rat after injection we used the 7 T small animal MRI system (Bruker ClinScan, Bruker BioSpin MRI GmbH, Ettlingen, Germany). Heat treatments were performed with a small animal magnetic field applicator (Actium Biosystems, Boulder CO) with a goal of raising bladder temperature to 42°C in <10min and maintaining for 60min. Temperatures were measured throughout the rat with seven fiberoptic temperature probes (OpSens Technologies, Quebec Canada) to characterize our ability to localize heat within the bladder target. RESULTS: The MRI study confirms the effectiveness of the catheterization procedure to homogenously distribute nanoparticles throughout the bladder. Thermal dosimetry data demonstrate our ability to controllably raise temperature of rat bladder ≥1°C/min to a steady-state of 42°C. CONCLUSION: Our data demonstrate that a MFH system provides well-localized heating of rat bladder with effective control of temperature in the bladder and minimal heating of surrounding tissues.

Simulation techniques in hyperthermia treatment planning.

Abstract Clinical trials have shown that hyperthermia (HT), i.e. an increase of tissue temperature to 39-44 °C, significantly enhance radiotherapy and chemotherapy effectiveness [1]. Driven by the developments in computational techniques and computing power, personalised hyperthermia treatment planning (HTP) has matured and has become a powerful tool for optimising treatment quality. Electromagnetic, ultrasound, and thermal simulations using realistic clinical set-ups are now being performed to achieve patient-specific treatment optimisation. In addition, extensive studies aimed to properly implement novel HT tools and techniques, and to assess the quality of HT, are becoming more common. In this paper, we review the simulation tools and techniques developed for clinical hyperthermia, and evaluate their current status on the path from 'model' to 'clinic'. In addition, we illustrate the major techniques employed for validation and optimisation. HTP has become an essential tool for improvement, control, and assessment of HT treatment quality. As such, it plays a pivotal role in the quest to establish HT as an efficacious addition to multi-modality treatment of cancer.

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.

Preclinical assessment of comfort and secure fit of thermobrachytherapy surface applicator (TBSA) on volunteer subjects.

A thermobrachytherapy surface applicator (TBSA) was developed for simultaneous heat and brachytherapy treatment of chest wall (CW) recurrence of breast cancer. The ability to comfortably secure the applicator over the upper torso relative to the CW target throughout treatment is assessed on volunteers. Male and postmastectomy female volunteers were enrolled to evaluate applicator secure fit to CW. Female subjects with intact breast were also enrolled to assess the ability to treat challenging cases. Magnetic resonance (MR) images of volunteers wearing a TBSA over the upper torso were acquired once every 15 minutes for 90 minutes. Applicator displacement over this time period required for treatment preplanning and delivery was assessed using MR visible markers. Applicator comfort and tolerability were assessed using a questionnaire. Probability estimates of applicator displacements were used to investigate dosimetric impact for the worst-case variation in radiation source-to-skin distance for 5 and 10 mm deep targets spread 17 × 13 cm on a torso phantom. Average and median displacements along lateral and radial directions were less than 1.2 mm over 90 minutes for all volunteers. Maximum lateral and radial displacements were measured to be less than 1 and 1.5 mm, respectively, for all CW volunteers and less than 2 mm for intact breast volunteers, excluding outliers. No complaint of pain or discomfort was reported. Phantom treatment planning for the maximum displacement of 2 mm indicated < 10% increase in skin dose with < 5% loss of homogeneity index (HI) for -2 mm uniform HDR source displacement. For +2 mm uniform displacement, skin dose decreased and HI increased by 20%. The volunteer study demonstrated that such large and uniform displacements should be rare for CW subjects, and the measured variation is expected to be low for multifraction conformal brachytherapy treatment.

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.

Utility of treatment planning for thermochemotherapy treatment of nonmuscle invasive bladder carcinoma.

PURPOSE: A recently completed Phase I clinical trial combined concurrent Mitomycin-C chemotherapy with deep regional heating using BSD-2000 Sigma-Ellipse applicator (BSD Corporation, Salt Lake City, UT, U.S.A.) for the treatment of nonmuscle invasive bladder cancer. This work presents a new treatment planning approach, and demonstrates potential impact of this approach on improvement of treatment quality. METHODS: This study retrospectively analyzes a subset of five patients on the trial. For each treatment, expert operators selected "clinical-optimal" settings based on simple model calculation on the BSD-2000 control console. Computed tomography (CT) scans acquired prior to treatment were segmented to create finite element patient models for retrospective simulations with Sigma-HyperPlan (Dr. Sennewald Medizintechnik GmbH, Munchen, Germany). Since Sigma-HyperPlan does not account for the convective nature of heat transfer within a fluid filled bladder, an effective thermal conductivity for bladder was introduced. This effective thermal conductivity value was determined by comparing simulation results with clinical measurements of bladder and rectum temperatures. Regions of predicted high temperature in normal tissues were compared with patient complaints during treatment. Treatment results using "computed-optimal" settings from the planning system were compared with clinical results using clinical-optimal settings to evaluate potential of treatment improvement by reducing hot spot volume. RESULTS: For all five patients, retrospective treatment planning indicated improved matches between simulated and measured bladder temperatures with increasing effective thermal conductivity. The differences were mostly within 1.3 °C when using an effective thermal conductivity value above 10 W/K/m. Changes in effective bladder thermal conductivity affected surrounding normal tissues within a distance of ∼1.5 cm from the bladder wall. Rectal temperature differences between simulation and measurement were large due to sensitivity to the sampling locations in rectum. The predicted bladder T90 correlated well with single-point bladder temperature measurement. Hot spot locations predicted by the simulation agreed qualitatively with patient complaints during treatment. Furthermore, comparison between the temperature distributions with clinical and computed-optimal settings demonstrated that the computed-optimal settings resulted in substantially reduced hot spot volumes. CONCLUSIONS: Determination of an effective thermal conductivity value for fluid filled bladder was essential for matching simulation and treatment temperatures. Prospectively planning patients using the effective thermal conductivity determined in this work can potentially improve treatment efficacy (compared to manual operator adjustments) by potentially lower discomfort from reduced hot spots in normal tissue.

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.

Improved hyperthermia treatment control using SAR/temperature simulation and PRFS magnetic resonance thermal imaging.

PURPOSE: This article explores the feasibility of using coupled electromagnetic and thermodynamic simulations to improve planning and control of hyperthermia treatments for cancer. The study investigates the usefulness of preplanning to improve heat localisation in tumour targets in treatments monitored with PRFS-based magnetic resonance thermal imaging (MRTI). METHODS: Heating capabilities of a cylindrical radiofrequency (RF) mini-annular phased array (MAPA) applicator were investigated with electromagnetic and thermal simulations of SAR in homogeneous phantom models and two human leg sarcomas. High frequency structure simulator (HFSS) (Ansoft) was used for electromagnetic simulations and SAR patterns were coupled into EPhysics (Ansoft) for thermal modelling with temperature-dependent variable perfusion. Simulations were accelerated by integrating tumour-specific anatomy into a pre-gridded whole body tissue model. To validate this treatment planning approach, simulations were compared with MR thermal images in both homogenous phantoms and heterogeneous tumours. RESULTS: SAR simulations demonstrated excellent agreement with temperature rise distributions obtained with MR thermal imaging in homogeneous phantoms and clinical treatments of large soft-tissue sarcomas. The results demonstrate feasibility of preplanning appropriate relative phases of antennas for localising heat in tumour. CONCLUSIONS: Advances in the accuracy of computer simulation and non-invasive thermometry via MR thermal imaging have provided powerful new tools for optimisation of clinical hyperthermia treatments. Simulations agree well with MR thermal images in both homogeneous tissue models and patients with lower leg tumours. This work demonstrates that better quality hyperthermia treatments should be possible when simplified hybrid model simulations are performed routinely as part of the clinical pretreatment plan.

Modeling the detectability of vesicoureteral reflux using microwave radiometry.

We present the modeling efforts on antenna design, frequency selection and receiver sensitivity estimation to detect vesicoureteral reflux (VUR) using microwave (MW) radiometry as warm urine from the bladder maintained at fever range temperature using a MW hyperthermia device reflows into the kidneys. The radiometer center frequency (f(c)), frequency band (Deltaf) and aperture radius (r(a)) of the physical antenna for kidney temperature monitoring are determined using a simplified universal antenna model with a circular aperture. Anatomical information extracted from the computed tomography (CT) images of children aged 4-6 years is used to construct a layered 3D tissue model. Radiometric antenna efficiency is evaluated in terms of the ratio of the power collected from the target at depth to the total power received by the antenna (eta). The power ratio of the theoretical antenna is used to design a microstrip log spiral antenna with directional radiation pattern over f(c) +/- Deltaf/2. Power received by the log spiral from the deep target is enhanced using a thin low-loss dielectric matching layer. A cylindrical metal cup is proposed to shield the antenna from electromagnetic interference (EMI). Transient thermal simulations are carried out to determine the minimum detectable change in the antenna brightness temperature (deltaT(B)) for 15-25 mL urine refluxes at 40-42 degrees C located 35 mm from the skin surface. Theoretical antenna simulations indicate maximum eta over 1.1-1.6 GHz for r(a) = 30-40 mm. Simulations of the 35 mm radius tapered log spiral yielded a higher power ratio over f(c) +/- Deltaf/2 for the 35-40 mm deep targets in the presence of an optimal matching layer. Radiometric temperature calculations indicate deltaT(B) 0.1 K for the 15 mL urine at 40 degrees C and 35 mm depth. Higher eta and deltaT(B) were observed for the antenna and matching layer inside the metal cup. Reflection measurements of the log spiral in a saline phantom are in agreement with the simulation data. The numerical study suggests that a radiometer with f(c) = 1.35 GHz, Deltaf = 500 MHz and detector sensitivity better than 0.1 K would be the appropriate tool to noninvasively detect VUR using the log spiral antenna.

Design of a water coupling bolus with improved flow distribution for multi-element superficial hyperthermia applicators.

A water bolus used in superficial hyperthermia couples the electromagnetic (EM) or acoustic energy into the target tissue and cools the tissue surface to minimise thermal hotspots and patient discomfort during treatment. Parametric analyses of the fluid pressure inside the bolus computed using 3D fluid dynamics simulations are used in this study to determine a bolus design with improved flow and surface temperature distributions for large area superficial heat applicators. The simulation results are used in the design and fabrication of a 19 x 32 cm prototype bolus with dual input-dual output (DIDO) flow channels. Sequential thermal images of the bolus surface temperature recorded for a step change in the circulating water temperature are used to assess steady state flow and surface temperature distributions across the bolus. Modelling and measurement data indicate substantial improvement in bolus flow and surface temperature distributions when changing from the previous single input-single output (SISO) to DIDO configuration. Temperature variation across the bolus at steady state was measured to be less than 0.8 degrees C for the DIDO bolus compared to 1.5 degrees C for the SISO water bolus. The new DIDO bolus configuration maintains a nearly uniform flow distribution and low variation in surface temperature over a large area typically treated in superficial hyperthermia.