Development of Visually Indistinguishable Acoustic Coupling Pads for Double-Blind Focused Ultrasound Neuromodulation...

Low intensity focused ultrasound (LIFU) is an emerging noninvasive neuromodulation modality with the ability to target deep brain structures with high spatial precision. Despite its promise, rigorous evaluation of its efficacy is limited by the absence of reliable, fully double-blind sham methodologies.

To develop and validate a pair of visually and mechanically indistinguishable acoustic coupling pads that enable true double-blind LIFU neuromodulation studies by providing either efficient ultrasound transmission or robust ultrasound blocking without altering participant or operator experience.

Two coupling pads were engineered: a transmitting pad designed to allow <5% pressure amplitude loss relative to free-water propagation to the intended focal region, and a non-transmitting pad designed to attenuate ultrasound by ≥40 dB in the same focal plane. Both pads used a Dragon Skin 10 NV silicone base and were identical in size, appearance, flexibility, and handling. The non-transmitting pad incorporated an encapsulated air-based blocking layer using a polyethylene foam insert. Acoustic performance was evaluated in a water tank using a 650 kHz BrainSonix transducer and a calibrated needle hydrophone including both waveform and spatial measurements. Sound speed of the silicone material was measured using pulse-echo techniques.

Twenty-three matched transmitting and non-transmitting pad pairs were fabricated and tested. Transmitting pads demonstrated a mean attenuation of -0.41 ± 0.53 dB, satisfying the design criterion of minimal acoustic loss. Non-transmitting pads demonstrated a mean attenuation of -48.61 ± 4.33 dB, exceeding the required -40 dB threshold for effective sham conditions. The Dragon Skin 10 NV substrate exhibited a sound speed of 964.72 m/s and produced <2 mm axial focal shift for standard pad thicknesses, with no measurable change in focal width. Non-transmitting pads produced a diffused beam profile in the focal plane, with no clear focal location. Both pad types were visually and tactually indistinguishable, could not be differentiated by experienced operators or participants, and maintained mechanical integrity after repeated cleaning.

These acoustically engineered coupling pads provide a practical and validated solution for achieving true single- and double-blind conditions in LIFU neuromodulation studies. By preserving identical sensory and procedural experiences while enabling precise control over ultrasound transmission, this approach addresses a critical methodological gap in human ultrasound neuromodulation research.