Feasibility Study for a High-Frequency Flexible Ultrasonic Cuff for High-Precision Vagus Nerve Ultrasound Neuromodulation.

In the emerging research field of bioelectronic medicine, it has been indicated that neuromodulation of the Vagus Nerve (VN) has the potential to treat various conditions such as epilepsy, depression, and autoimmune diseases. In order to reduce side effects, as well as to increase the effectiveness of the delivered therapy, sub-fascicle stimulation specificity is required. In the electrical domain, increasing spatial selectivity can only be achieved using invasive and potentially damaging approaches like compressive forces or nerve penetration. To avoid these invasive methods while obtaining a high spatial selectivity, a 2 mm diameter extraneural cuff-shaped proof-of-concept design with integrated Lead Zirconate Titanate (PZT) based ultrasound (US) transducers is proposed in this paper. For the development of the proposed concept, wafer-level microfabrication techniques are employed. Moreover, acoustic measurements are performed on the device, in order to characterize the ultrasonic beam profiles of the integrated PZT-based US transducers. A focal spot size of around 200 µm by 200 µm is measured for the proposed cuff. Moreover, the curvature of the device leads to constructive interference of the US waves originating from multiple PZT-based US transducers, which in turn leads to an increase of 45% in focal pressure compared to the focal pressure of a single PZT-based US transducer. Integrating PZT-based US transducers in an extraneural cuff-shaped design has the potential to achieve high-precision US neuromodulation of the Vagus Nerve without requiring intraneural implantation.

A 2D Ultrasound Phased-Array Transmitter ASIC for High-Frequency US Stimulation and Powering.

Ultrasound (US) neuromodulation and ultrasonic power transfer to implanted devices demand novel ultrasound transmitters capable of steering focused ultrasound waves in 3D with high spatial resolution and US pressure, while having a miniaturized form factor. Meeting these requirements needs a 2D array of ultrasound transducers directly integrated with a high-frequency 2D phased-array ASIC. However, this imposes severe challenges on the design of the ASIC. In order to avoid the generation of grating lobes, the elements in the 2D phased-array should have a pitch of half of the ultrasound wavelength, which, as frequency increases, highly reduces the area available for the design of high-voltage beamforming channels. This article addresses these challenges by presenting the system-level optimization and implementation of a high-frequency 2D phased-array ASIC. The system-level study focuses on the optimization of the US transmitter toward high-frequency operation while minimizing power consumption. This study resulted in the implementation of two ASICs in TSMC 180 nm BCD technology: firstly, an individual beamforming channel was designed to demonstrate the tradeoffs between frequency, driving voltage, and beamforming capabilities. Finally, a 12-MHz pitch matched 12 × 12 phased-array ASIC working at 20-V amplitude and 3-bit phasing was designed and experimentally validated, to demonstrate high-frequency phased-array operation. The measurement results verify the phasing functionality of the ASIC with a maximum DNL of 0.35 LSB. The CMOS chip consumes 130 mW and 26.6 mW average power during the continuous pulsing and delivering 200-pulse bursts with a PRF of 1 kHz, respectively.

Stent with Piezoelectric Transducers for High Spatial Resolution Ultrasound Neuromodulation- a Finite Element Analysis.

Deep brain stimulation is currently the only technique used in the clinical setting to modulate the neural activity of deep brain nuclei. Recently, low-intensity transcranial focused ultrasound (LIFU) has been shown to reversibly modulate brain activity through a transcranial pathway. Transcranial LIFU requires a low-frequency ultrasound of around 0.5 MHz due to skull attenuation, thus providing poor axial and lateral resolution. This paper proposes a new conceptual device that would use a stent to place a high-frequency ultrasound array within the brain vasculature to achieve high axial and lateral spatial resolution. The first part of this work identified the most commonly treated deep brain nuclei and examined the human brain vasculature for stent placement. Next, a finite element analysis was carried out using a piezoelectric array that follows the blood vessels curvature, and its ability to focus ultrasound waves in clinically relevant brain nuclei was evaluated. The analytical solution provided promising results for deep brain stimulation via a stent with ultrasound transducers for high spatial resolution neuromodulation.

Energy efficiency of pulse shaping in electrical stimulation: the interdependence of biophysical effects and circuit design losses.

Power efficiency in electrical stimulator circuits is crucial for developing large-scale multichannel applications like bidirectional brain-computer interfaces and neuroprosthetic devices. Many state-of-the-art papers have suggested that some non-rectangular pulse shapes are more energy-efficient for exciting neural excitation than the conventional rectangular shape. However, additional losses in the stimulator circuit, which arise from employing such pulses, were not considered. In this work, we analyze the total energy efficiency of a stimulation system featuring non-rectangular stimuli, taking into account the losses in the stimulator circuit. To this end, activation current thresholds for different pulse shapes and durations in cortical neurons are modeled, and the energy required to generate the pulses from a constant voltage supply is calculated. The proposed calculation reveals an energy increase of 14%-51% for non-rectangular pulses compared to the conventional rectangular stimuli, instead of the decrease claimed in previous literature. This result indicates that a rectangular stimulation pulse is more power-efficient than the tested alternative shapes in large-scale multichannel electrical stimulation systems.