Preclinical prototype validation and characterization of a thermobrachytherapy system for interstitial hyperthermia and high-dose-rate brachytherapy.

Background and purpose: Integrating simultaneous interstitial hyperthermia in high-dose-rate brachytherapy treatments (HDR-BT) is expected to lead to enhanced therapeutic effect. However, there is currently no device available for such an integration. In this study, we presented and validated the thermobrachytherapy (TBT) preclinical prototype system that is able to seamlessly integrate into the HDR-BT workflow. Materials and methods: The TBT system consisted of an advanced radiofrequency power delivery and control system, dual-function interstitial applicators, and integrated connection and impedance matching system. The efficiency and minimum heating ability of the system was calculated performing calorimetric experiments. The effective-heating-length and heating pattern was evaluated using single-applicator split phantom experiments. The heating independence between applicators, the ability of the system to adaptable and predictable temperature steering was evaluated using multi-applicator split phantom experiments. Results: The system satisfied interstitial hyperthermia requirements. It demonstrated 50 % efficiency and ability to reach 6 °C temperature increase in 6 min. Effective-heating-length of the applicator was 43.7 mm, following the initial design. Heating pattern interference between applicators was lower than recommended. The system showed its ability to generate diverse heating patterns by adjusting the phase and amplitude settings of each electrode, aligning well with simulations (minimum agreement of 88 %). Conclusions: The TBT preclinical prototype system complied with IHT requirements, and agreed well with design criteria and simulations, hence performing as expected. The preclinical prototype TBT system can now be scaled to an in-vivo validation prototype, including an adaptable impedance matching solution, appropriate number of channels, and ensuring biocompatibility and regulatory compliance.

Magnetic resonance thermometry for hyperthermia in the oropharynx region.

Magnetic resonance thermometry (MRT) can measure in-vivo 3D-temperature changes in real-time and noninvasively. However, for the oropharynx region and the entire head and neck, motion potentially introduces large artifacts. Considering long treatment times of 60-90 min, this study aims to evaluate whether MRT around the oropharynx is clinically feasible for hyperthermia treatments and quantify the effects of breathing and swallowing on MRT performance. A 3D-ME-FGRE sequence was used in a phantom cooling down and around the oropharynx of five volunteers over ∼75 min. The imaging protocol consisted of imaging with acceleration (ARC = 2), number of image averages (NEX = 1,2 and 3). For volunteers, the acquisitions included a breath-hold scan and scans with deliberate swallowing. MRT performance was quantified in neck muscle, spinal cord and masseter muscle, using mean average error (MAE), mean error (ME) and spatial standard deviation (SD). In phantom, an increase in NEX leads to a significant decrease in SD, but MAE and ME were unchanged. No significant difference was found in volunteers between the different scans. There was a significant difference between the regions evaluated: neck muscle had the best MAE (=1.96 °C) and SD (=0.82 °C), followed by spinal cord (MAE = 3.17 °C, SD = 0.92 °C) and masseter muscle (MAE = 4.53 °C, SD = 1.16 °C). Concerning the ME, spinal cord did best, then neck muscle and masseter muscle, with values of -0.64 °C, 1.15 °C and -3.05 °C respectively. Breathing, swallowing, and different ways of imaging (acceleration and NEX) do not significantly influence the MRT performance in the oropharynx region. The ROI selected however, leads to significant differences.

Adapting Temperature Predictions to MR Imaging in Treatment Position to Improve Simulation-Guided Hyperthermia for Cervical Cancer.

Hyperthermia treatment consists of elevating the temperature of the tumor to increase the effectiveness of radiotherapy and chemotherapy. Hyperthermia treatment planning (HTP) is an important tool to optimize treatment quality using pre-treatment temperature predictions. The accuracy of these predictions depends on modeling uncertainties such as tissue properties and positioning. In this study, we evaluated if HTP accuracy improves when the patient is imaged inside the applicator at the start of treatment. Because perfusion is a major uncertainty source, the importance of accurate treatment position and anatomy was evaluated using different perfusion values. Volunteers were scanned using MR imaging without ("planning setup") and with the MR-compatible hyperthermia device ("treatment setup"). Temperature-based quality indicators were used to assess the differences between the standard, apparent and the optimized hyperthermia dose. We conclude that pre-treatment imaging can improve HTP predictions accuracy but also, that tissue perfusion modelling is crucial if temperature-based optimization is applied.

Magnetic hybrid Pd/Fe-oxide nanoparticles meet the demands for ablative thermo-brachytherapy.

OBJECTIVE: To investigate the potential of hybrid Pd/Fe-oxide magnetic nanoparticles designed for thermo-brachytherapy of breast cancer, considering their specific loss power (SLP) and clinical constraints in the applied magnetic field. METHODS: Hybrid nanoparticles consisting of palladium-core and iron oxide shell of increasing thickness, were suspended in water and their SLPs were measured at varying magnetic fields (12-26 mT peak) and frequencies (50-730 kHz) with a commercial alternating magnetic field generator (magneTherm™ Digital, nanoTherics Ltd.). RESULTS: Validation of the heating device used in this study with commercial HyperMag-C nanoparticles showed a small deviation (±4%) over a period of 1 year, confirming the reliability of the method. The integration of dual thermometers, one in the center and one at the bottom of the sample vial, allowed monitoring of homogeneity of the sample suspensions. SLPs measurements on a series of nanoparticles of increasing sizes showed the highest heating for the diameter of 21 nm (SLP = 225 W/g) at the applied frequencies of 346 and 730 kHz. No heating was observed for the nanoparticles with the size <14 nm, confirming the importance of the size-parameter. The heating ability of the best performing Pd/Fe-oxide-21 was calculated to be sufficient to ablate tumors with a radius ±4 and 12 mm using 10 and 1 mg/mL nanoparticle concentration, respectively. CONCLUSIONS: Nanoparticles consisting of non-magnetic palladium-core and magnetic iron oxide shell are suitable for magnetic hyperthermia/thermal ablation under clinically safe conditions of 346 kHz and 19.1 mT, with minimal eddy current effects in combination with maximum SLP.