Large-volume focused-ultrasound mild hyperthermia for improving blood-brain tumor barrier permeability application

[[abstract]]Mild hyperthermia can locally enhance permeability of the blood-tumor barrier in brain tumors, improving delivery of antitumor nanodrugs. However, a clinical transcranial focused ultrasound (FUS) system does not provide this modality yet. The study aimed at the development of the transcranial FUS technique dedicated for large-volume mild hyperthermia in the brain. Acoustic pressure, multiple-foci, temperature and thermal dose induced by FUS were simulated in the brain through the skull. A 1-MHz, 114-element, spherical helmet transducer was fabricated to verify large-volume hyperthermia in the phantom. The simulated results showed that two foci were simultaneously formed at (2, 0, 0) and (-2, 0, 0) and at (0, 2, 0) and (0, -2, 0), using the phases of focusing pattern 1 and the phases of focusing pattern 2, respectively. Switching two focusing patterns at 5 Hz produced a hyperthermic zone with an ellipsoid of 7 mm × 6 mm × 11 mm in the brain and the temperature was 41-45 °C in the ellipsoid as the maximum intensity was 150 W/cm(2) and sonication time was 3 min. The phased array driven by switching two mode phases generated a 41 °C-contour region of 10 ± 1 mm × 8 ± 2 mm × 13 ± 2 mm in the phantom after 3-min sonication. Therefore, we have demonstrated our developed FUS technique for large-volume mild hyperthermia