Sound-Speed Modifying Acoustic Metasurfaces for Acoustic Holography.

Acoustic metasurfaces offer unique capabilities to steer and direct acoustic fields, though these are generally composed of complex 3D structures, complicating their fabrication and applicability to higher frequencies. Here, an ultrathin metasurface approach is demonstrated, wherein planarized micropillars in a discretized phase array are utilized. This subwavelength metasurface is easily produced via a single-step etching process and is suitable for megahertz-scale applications. The flexibility of this approach is further demonstrated in the production of complex acoustic patterns via acoustic holography. This metasurface approach, with models used to predict their behavior, has broad potential in applications where robust, high-frequency acoustic manipulation is required, including microfluidics, cell/tissue engineering, and medical ultrasound.

Holographic Focused Ultrasound Hyperthermia System for Uniform Simultaneous Thermal Exposure of Multiple Tumor Spheroids.

Hyperthermia is currently used to treat cancer due to its ability to radio- and chemo-sensitize and to stimulate the immune response. While ultrasound is non-ionizing and can induce hyperthermia deep within the body non-invasively, achieving uniform and volumetric hyperthermia is challenging. This work presents a novel focused ultrasound hyperthermia system based on 3D-printed acoustic holograms combined with a high-intensity focused ultrasound (HIFU) transducer to produce a uniform iso-thermal dose in multiple targets. The system is designed with the aim of treating several 3D cell aggregates contained in an International Electrotechnical Commission (IEC) tissue-mimicking phantom with multiple wells, each holding a single tumor spheroid, with real-time temperature and thermal dose monitoring. System performance was validated using acoustic and thermal methods, ultimately yielding thermal doses in three wells that differed by less than 4%. The system was tested in vitro for delivery of thermal doses of 0-120 cumulative equivalent minutes at 43 °C (CEM43) to spheroids of U87-MG glioma cells. The effects of ultrasound-induced heating on the growth of these spheroids were compared with heating using a polymerase chain reaction (PCR) thermocycler. Results showed that exposing U87-MG spheroids to an ultrasound-induced thermal dose of 120 CEM43 shrank them by 15% and decreased their growth and metabolic activity more than seen in those exposed to a thermocycler-induced heating. This low-cost approach of modifying a HIFU transducer to deliver ultrasound hyperthermia opens new avenues for accurately controlling thermal dose delivery to complex therapeutic targets using tailored acoustic holograms. Spheroid data show that thermal and non-thermal mechanisms are implicated in the response of cancer cells to non-ablative ultrasound heating.

Numerical Study of Acoustic Holograms for Deep-Brain Targeting through the Temporal Bone Window.

Acoustic holograms can encode complex wavefronts to compensate the aberrations of a therapeutical ultrasound beam propagating through heterogeneous tissues such as the skull, and simultaneously, they can generate diffraction-limited acoustic images, that is, arbitrary shaped focal spots. In this work, we numerically study the performance of acoustic holograms focusing at the thalamic nuclei when the source is located at the temporal bone window. The temporal window is the thinnest area of the lateral skull and it is mainly hairless, so it is a desirable area through which to transmit ultrasonic waves to the deep brain. However, in targeting from this area the bilateral thalamic nuclei are not aligned with the elongated focal spots of conventional focused transducers, and in addition, skull aberrations can distort the focal spot. We found that by using patient-specific holographic lenses coupled to a single-element 650-kHz-frequency 65-mm-aperture source, the focal spot can be sharply adapted to the thalamic nuclei in a bilateral way while skull aberrations are mitigated. Furthermore, the performance of these holograms was studied under misalignment errors between the source and the skull, concluding that for misalignments up to 5°, acoustic images are correctly restored. This work paves the way to designing clinical applications of transcranial ultrasound such as blood-brain barrier opening for drug delivery or deep-brain neuromodulation using this low-cost and personalized technology, presenting desirable aspects for long-term treatments because the patient's head does not need to be shaved completely and skull heating is low.