Large-Volume Focused-Ultrasound Mild Hyperthermia for Improving Blood-Brain Tumor Barrier Permeability Application

Area of Science:

• Biomedical Engineering
• Medical Physics
• Oncology

Background:

• Mild hyperthermia can increase blood-tumor barrier permeability, enhancing nanodrug delivery for brain tumors.
• Current clinical transcranial focused ultrasound (FUS) systems lack the capability for large-volume mild hyperthermia.
• Developing such a system is crucial for improving targeted drug delivery in brain tumor treatment.

Purpose of the Study:

• To develop and validate a transcranial focused ultrasound (FUS) technique for achieving large-volume mild hyperthermia in the brain.
• To simulate and experimentally verify the FUS system's ability to induce therapeutic hyperthermia.
• To assess the potential of this technique for enhancing the delivery of antitumor nanodrugs.

Main Methods:

• Simulated acoustic pressure, multiple foci, temperature, and thermal dose distribution in the brain through the skull using FUS.
• Fabricated a 1-MHz, 114-element spherical helmet transducer for experimental verification.
• Employed switching between two focusing patterns at 5 Hz to create a sustained hyperthermic zone.

Main Results:

• Simulations predicted simultaneous foci formation and demonstrated the feasibility of creating a hyperthermic zone (7 mm × 6 mm × 11 mm) at 41-45 °C.
• Experimental verification in a phantom confirmed a 41 °C-contour region of approximately 10 mm × 8 mm × 13 mm after 3-min sonication.
• The developed phased array FUS technique successfully generated large-volume mild hyperthermia.

Conclusions:

• The developed transcranial FUS technique is effective for inducing large-volume mild hyperthermia in the brain.
• This technology holds promise for improving the efficacy of nanodrug delivery in treating brain tumors.
• Further clinical translation of this FUS system is warranted for enhanced brain tumor therapy.