Dario B. Rodrigues

Focused ultrasound for treatment of bone tumours

Abstract Purpose: Focused ultrasound (FUS) is a modality with rapidly expanding applications across the field of medicine. Treatment of bone lesions with FUS including both benign and malignant tumours has been an active area of investigation. Recently, as a result of a successful phase III trial, magnetic resonance-guided FUS is now a standardised option for treatment of painful bone metastases. This report reviews the clinical applications amenable to treatment with FUS and provides background on FUS and image guidance techniques, results of clinical studies, and future directions. Methods: A comprehensive literature search and review of abstracts presented at the recently completed fourth International Focused Ultrasound Symposium was performed. Case reports and older publications revisited in more recent studies were excluded. For clinical studies that extend beyond bone tumours, only the data regarding bone tumours are presented. Results: Fifteen studies assessing the use of focused ultrasound in treatment of primary benign bone tumours, primary malignant tumours, and metastastic tumours meeting the search criteria were identified. For these clinical studies the responders group varied within 91–100%, 85–87% and 64–94%, respectively. Major complications were reported in the ranges 0%, 0–28% and 0–4% for primary benign, malignant and metastatic tumours, respectively. Conclusions: Image-guided FUS is both safe and effective in the treatment of primary and secondary tumours. Additional phase III trials are warranted to more fully define the role of FUS in treatment of both benign and malignant bone tumours.

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.

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.

Numerical 3D modeling of heat transfer in human tissues for microwave radiometry monitoring of Brown fat metabolismo

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 HFSSTM 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 HFSSTM 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.

Reaction Chemistry Generated by Nanosecond Pulsed Dielectric Barrier Discharge Treatment is Responsible for the Tumor Eradication in the B16 Melanoma Mouse Model

Melanoma is one of the most aggressive metastatic cancers with resistance to radiation and most chemotherapy agents. This study highlights an alternative treatment for melanoma based on nanosecond pulsed dielectric barrier discharge (nsP DBD). We show that a single nsP DBD treatment, directly applied to a 5 mm orthotopic mouse melanoma tumor, completely eradicates it 66% (n = 6; p ≤ 0.05) of the time. It was determined that reactive oxygen and nitrogen species produced by nsP DBD are the main cause of tumor eradication, while nsP electric field and heat generated by the discharge are not sufficient to kill the tumor. However, we do not discount that potential synergy between each plasma generated component (temperature, electric field and reactive species) can enhance the killing efficacy.

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.

Metamaterial Antenna Arrays for Improved Uniformity of Microwave Hyperthermia Treatments

2 Abstract |Current microwave hyperthermia applicators are not well suited for uniform heating of large tissue regions. The objective of this research is to identify an optimal microwave antenna array for clinical use in hyperthermia treatment of cancer. For this aim we present a novel 434 MHz applicator design based on a metamaterial zeroth order mode resonator, which is used to build larger array congurations. These applicators are designed to effectively heat large areas extending deep below the body surface and in this work they are characterized with numerical simulations in a homogenous muscle tissue model. Their performance is evaluated using three metrics: radiation pattern-based Effective Field Size (EFS), temperature distribution-bas Therapeutic Thermal Area (TTA), and Therapeutic Thermal Volume (TTV) reaching 41{45 ◦ C. For 2 � 2 and 2 � 3 array congurations, the EFS reaching > 25% of maximum SAR in the 3.5 cm deep plane is 100% and 91% of the array aperture area, respectively. The corresponding TTA for these arrays is 95% and 86%, respectively; and the TTV attaining > 41 ◦ C is over 85% of the aperture area to a depth of over 3 cm in muscle, using

Numerical investigation of novel microwave applicators based on zero-order mode resonance for hyperthermia treatment of cancer

In this paper, three novel microwave applicator prototypes based on zero-order mode resonators are proposed for use in hyperthermia treatment of cancer. The ability of all three applicators to homogenously irradiate muscle tissue-equivalent phantoms is demonstrated with results of numerical simulations, and relative performance of the applicators is compared.

ANALYTICAL SOLUTION TO THE TRANSIENT 1D BIOHEAT EQUATION IN A MULTILAYER REGION WITH SPATIAL DEPENDENT HEAT SOURCES

An analytical solution given by Bessel series to the transient and one-dimensional (1D) bioheat equation in a multilayer region with spatial dependent heat sources is derived. Multilayer regions with 1D Cartesian, cylindrical or spherical geometries and composed of different types of biological tissues characterised by temperature-invariant physiological parameters are considered. Boundary conditions of first, second and third kinds to the temperature at the inner and outer surfaces are also assumed. In this work, the bioheat transfer model is applied to obtain the temperature profiles in a tumor bed and a surrounding healthy tissue using two spatial dependent heat source terms to simulate a magnetic fluid hyperthermia technique in the cancer treatment. The influence of these two heat sources, described by polynomial and exponential functions, on temperature is investigated.

Microwave Radiometry for Noninvasive Monitoring of Brain Temperature

Microwave radiometry is a passive and noninvasive technique that is able to measure deep tissue temperature and track changes in thermal profiles in tissue up to 5 cm below the surface over several hours. These characteristics make microwave radiometry a suitable technique to monitor brain temperature during extended hypothermic surgeries, and thus avoid potential complications that result from poorly controlled low temperature levels and return to normothermia. This chapter addresses all development stages of a radiometric brain thermometer including: radiometer electronics; antenna design and fabrication; power to temperature calibration algorithm; multilayer head phantom model with variable temperature compartments; experimental validation of sensor performance; and initial clinical implementation. In particular, a radiometric antenna is described based on a log-spiral design optimized in silico to receive energy from deep brain. The prototype is tested using a realistic head phantom that consists of an anatomical human skull with separate brain and scalp compartments in which tissue-equivalent fluid phantoms circulate at independent temperatures (32 °C for scalp and 37 °C for brain). Experimental data shows that the calculated radiometric brain temperature tracks within 0.4 °C the measured brain phantom temperature over a 4.6 h experiment, when the brain phantom is lowered 10 °C and then returned to original temperature. A clinical case confirms the ability to noninvasively monitor temperature in deep brain using microwave radiometry, with radiometric measurements that closely track changes in core temperature as measured in the nasopharynx. Both simulated and experimental results demonstrate that a 1.1–1.6 GHz radiometric sensor with 2.5 cm diameter is an appropriate tool for noninvasive monitoring of deep brain temperature.