Design of a defocused transducer for targeted cancer drug delivery by ultrasound-mediated hyperthermia

A major challenge in chemotherapy is that the systemic delivery of drugs to both healthy tissue as well as the tumour results in unwanted side effects. Thermosensitive liposomal carriers are designed to release their payload when they are exposed to mild hyperthermia (a few degrees above body temperature). If a tumour can be locally heated, thermosensitive liposomes can provide triggered and localised delivery of the drug which should reduce systemic toxicity. Ultrasound is a noninvasive modality which can be used to produce localised heating at depth. However, most clinically approved high-intensity focused ultrasound (HIFU) systems are designed for tumour ablation and exhibit a focal volume which typically spans 1-3mm in width and 10-15mm in length, generating temperatures in excess of 50◦C for a few seconds to directly kill tissue within the focal volume. Hyperthermia-triggered drug release usually requires maintaining a tumour volume which often spans several centimetres in size at a consistent therapeutic temperature of 39.5-42◦C for durations up to an hour. This is difficult to achieve for most current HIFU transducers due to their small focal volume. The approach employed here is to design an acoustic lens that retrofits onto a clinical HIFU system to produce a focal volume better suited for mild hyperthermia. 3D printing is employed in this work to produce the lenses, and sectored lenses which enable a single-element transducer to produce acoustic fields with multiple foci in an annular pattern are investigated. Experimental measurements of the pressure and temperature using a small therapeutic transducer are consistent with simulations, and the simulated -3dB free-field focal volume of the transducer was increased from 9.6mm3 to 90.9mm3. Finite element software is used to perform 3D linear full-wave simulations of an acoustic lens in a human liver target derived from a segmented CT dataset. The computational challenges with performing large 3D finite element simulations are addressed by dividing the simulation domain into several subregions. A phase-conjugate lens combined with masking transducer locations associated with ribs is explored as a solution to address aberrations in the acoustic field caused by tissue inhomogeneity. Experiments with a sectored acoustic lens on a clinical HIFU system showed the radial location of the free-field focus was shifted from 0mm to ±2.8mm in an annular pattern. This work shows that retrofitting a HIFU system with an acoustic lens is a practical approach to broadening the focal spot.

Keywords: Acoustic Hydrophone
Finite Element Modelling
3D Printing
Fibre Optic Hydrophone
Biomedical Acoustics
PZFlex
JC200
Ultrasound Mediated Drug Delivery
Patient Specific Acoustic Lens
HIFU
Acoustic Field
Patient Specific
Sonic Concepts
Sector Vortex Acoustic Lens
Spherically Focused Transducers
Tumour Targeting
Tumour Drug Delivery
Tissue Mimicking Material
Tissue Mimicking Phantom
Ultrasound
Chongqing Haifu
Ultrasound Simulation
Sector Vortex Transducers
Therapeutic Ultrasound
Ultrasound Transducer Design
Transducers
Tissue Properties
Sector Vortex
Ultrasound Mediated Hyperthermia
Focused Ultrasound
Thermosensitive Liposomes
Thermocouple Measurements
OnScale
Mild Hyperthermia
Patient Specific Modelling
Acoustic Lenses
High Intensity Focused Ultrasound
Single Element Transducer
Acoustic Tissue Properties
TARDOX
Advisor: Coussios, CC
Cleveland, RO