Design and base validation of a small-animal hyperthermia applicator.

OBJECTIVE: The design and base-validation of a small-animal microwave hyperthermia applicator for the adaptation of the clinically used BSD-500 hyperthermia device to function with mice. APPROACH: We iteratively designed and tested a 3D-printable applicator, using mouse cadavers as well as the life sciences simulation software Sim4life to optimise the applicator. The applicator uses an agarose phantom to couple the antenna to the tissue, and we determined the dielectric and thermal properties thereof. To monitor the temperatures in the cadavers during the experiments, electromagnetically stable 4-wire sensors from the clinical device were read out independently. MAIN RESULTS: The agarose coupling phantom was characterised dielectrically and thermally and closely approximated muscle tissue (ϵr = 51.91, σ = 0.99Sm-1 at 915MHz) and cp = (2592 ± 40)Jkg-1K-1. The independent sensor readout achieved 3Hz data collection with a sensor standard deviation from the reference thermometer smaller than 0.01◦C. In each of the validation experiments visual positioning was by itself sufficient to ensure the tumour- surrogate reached therapeutic temperatures (40 ◦C-43◦C) using only a control sensor in the agarose gel in contact with the mouse body. Extrapolating from our data, the highest temperature should occur in the gel at the antenna tip, reaching approximately 43◦C. The therapeutic zone extends to a depth of 9.3mm to 17.6mm (95% CI). The electromagnetic simulation predicted the heating-rate distribution well and was robust to changes in material properties and problem geometry. Perfusion-aware simulations based on the Pennes bioheat equation predicted at most an ≈21% reduction in tumour heating under physiological conditions, indicating that therapeutic temperatures should remain achievable in vivo. SIGNIFICANCE: This work substantially narrows the gap towards an accessible, easy-to-use small-animal hyperthermia applicator and provides the base-validation needed before progressing to in vivo experiments.