Evaluation of a Balloon Implant for Simultaneous Magnetic Nanoparticle Hyperthermia and High-Dose-Rate Brachytherapy of Brain Tumor Resection Cavities

Previous work has reported the design of a novel thermobrachytherapy (TBT) balloon implant to deliver magnetic nanoparticle (MNP) hyperthermia and high-dose-rate (HDR) brachytherapy simultaneously after brain tumor resection, thereby maximizing their synergistic effect. This paper presents an evaluation of the robustness of the balloon device, compatibility of its heat and radiation delivery components, as well as thermal and radiation dosimetry of the TBT balloon. TBT balloon devices with 1 and 3 cm diameter were evaluated when placed in an external magnetic field with a maximal strength of 8.1 kA/m at 133 kHz. The MNP solution (nanofluid) in the balloon absorbs energy, thereby generating heat, while an HDR source travels to the center of the balloon via a catheter to deliver the radiation dose. A 3D-printed human skull model was filled with brain-tissue-equivalent gel for in-phantom heating and radiation measurements around four 3 cm balloons. For the in vivo experiments, a 1 cm diameter balloon was surgically implanted in the brains of three living pigs (40–50 kg). The durability and robustness of TBT balloon implants, as well as the compatibility of their heat and radiation delivery components, were demonstrated in laboratory studies. The presence of the nanofluid, magnetic field, and heating up to 77 °C did not affect the radiation dose significantly. Thermal mapping and 2D infrared images demonstrated spherically symmetric heating in phantom as well as in brain tissue. In vivo pig experiments showed the ability to heat well-perfused brain tissue to hyperthermic levels (≥40 °C) at a 5 mm distance from the 60 °C balloon surface

The potential for using combined electrical impedance and ultrasound measurements for the non-invasive determination of temperature in deep body tumours during mild hyperthermia

The effectiveness of mild hyperthermia in improving the outcome of radiotherapy and chemotherapy treatment is well established for surface tumours (e.g. an average improvement of 20% in the 5 years survival rate using mild hyperthermia in conjunction with radiotherapy). However, to apply this technique to deep body solid tumours clinically, a non-invasive thermometry method is needed. Several approaches have been proposed for non-invasive thermometry in the past but none were capable of providing 3D temperature distributions in-vivo with the required accuracy. In this thesis, the potential for determining the temperature in a deep body solid tumour during mild hyperthermia by combining ultrasound propagation velocity and electrical impedance measurement techniques has been investigated. Simultaneous ultrasound propagation velocity and electrical impedance measurements were made in-vitro on liver, fat and layered fat-liver samples as the temperature was increased to mild hyperthermia levels (45°C max.). From the ultrasound measurements a linear correlation was found between the percentage of fat in the sample and the change in ultrasound propagation velocity with temperature (-0.12ms-1°C-1%-1, r2 = 0.93). Analysis of the data from the multi-frequency electrical impedance measurements showed that the magnitude of the electrical impedance measured at 256kHz normalised to the magnitude of the electrical impedance measured at 8kHz gave a linear correlation with the percentage of fat in the sample (0.003 %-1, r2 = 0.72) but no statistically significant correlation between the fat content and the temperature coefficient at 256kHz (r2 = 0.007, p >0.05). These results support an approach of using high to low frequency impedance ratios to determine the percentage of fat in the tissue and then this together with an ultrasound propagation velocity measure to detect the change in the temperature of the tissue. Application of this technique is limited by the variation in the change in ultrasound propagation velocity with temperature between tissue samples found in this study but the origins of this are unclear. In addition, further improvements in the spatial sensitivity of the tetrapolar impedance measurements are necessary to ensure an adequate spatial determination of fat content