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Low-intensity focused ultrasound (LI-FUS) clinical trials exploit either the neural activity modulating, or the blood-brain barrier opening, capacity of this stimulation modality. However, LI-FUS currently is applied only transcranially which means that it is conducive only for episodic and intermittent stimulation, although, clinical data shows that in numerous neurological and psychiatric applications, chronic and continuous stimulation is required for long-term, stable therapeutic effect. The paper presents experimental data on a novel and innovative approach describing an implantable, epidural focus ultrasound (eFUS) device, designed for continuous, chronic and multi-site steerable neuromodulation. The miniaturized eFUS device consists of a two-dimensional piezoelectric transducer array directly integrated onto a custom ASIC, specifically engineered for proof-of-principle neuromodulation studies in the rat brain. The system generates electronically steerable focused ultrasound with software-defined focal coordinates, sufficient to stimulate neuronal activity in deep brain structures. In vitro acoustic characterization confirmed accurate beam steering and focusing, while in vivo validation demonstrated reliable stimulation of a deep subcortical target with measurable physiological effects. eFUS-mediated targeting of the ventral tegmental area in awake and freely moving rats produced increase in dopamine release in the nucleus accumbens as confirmed using fiber photometry recordings. Post-mortem histological analysis of the target regions showed the absence of inflammatory markers, although the epidural placement of the eFUS device was associated with mild tissue damage. Overall, the study provides in vitro data demonstrating the energy efficiency, and steerability of the technology, and in vivo physiological evidence of neuromodulatory ability of a deep, subcortical brain structure.
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Low-intensity focused ultrasound (LI-FUS) clinical trials exploit either the neural activity modulating, or the blood-brain barrier opening, capacity of this stimulation modality. However, LI-FUS currently is applied only transcranially which means that it is conducive only for episodic and intermittent stimulation, although, clinical data shows that in numerous neurological and psychiatric applications, chronic and continuous stimulation is required for long-term, stable therapeutic effect. The paper presents experimental data on a novel and innovative approach describing an implantable, epidural focus ultrasound (eFUS) device, designed for continuous, chronic and multi-site steerable neuromodulation. The miniaturized eFUS device consists of a two-dimensional piezoelectric transducer array directly integrated onto a custom ASIC, specifically engineered for proof-of-principle neuromodulation studies in the rat brain. The system generates electronically steerable focused ultrasound with software-defined focal coordinates, sufficient to stimulate neuronal activity in deep brain structures. In vitro acoustic characterization confirmed accurate beam steering and focusing, while in vivo validation demonstrated reliable stimulation of a deep subcortical target with measurable physiological effects. eFUS-mediated targeting of the ventral tegmental area in awake and freely moving rats produced increase in dopamine release in the nucleus accumbens as confirmed using fiber photometry recordings. Post-mortem histological analysis of the target regions showed the absence of inflammatory markers, although the epidural placement of the eFUS device was associated with mild tissue damage. Overall, the study provides in vitro data demonstrating the energy efficiency, and steerability of the technology, and in vivo physiological evidence of neuromodulatory ability of a deep, subcortical brain structure.
Emerging biomedical ultrasound applications such as pulsed neurostimulation and shear-wave imaging demand single-pulse focused ultrasound waves with MPa-range acoustic pressures. Achieving high pressures typically involves driving transducers with high voltages, necessitating bulky power amplifiers. Recently, phased arrays have emerged to miniaturize these focused transducers. However, they often exhibit poor power efficiency and heat dissipation. To address this, we explore acoustic amplification through acoustic energy storage and release, where, with minimal voltage, high-amplitude ultrasound waves are produced. Prior work has shown the principle using bulky apparatus with limited applicability. In this work, we explore the theory and perform finite element modeling (FEM) to investigate this mechanism with miniaturized and micro-electro-mechanical systems (MEMS)-compatible materials and geometries.
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Emerging biomedical ultrasound applications such as pulsed neurostimulation and shear-wave imaging demand single-pulse focused ultrasound waves with MPa-range acoustic pressures. Achieving high pressures typically involves driving transducers with high voltages, necessitating bulky power amplifiers. Recently, phased arrays have emerged to miniaturize these focused transducers. However, they often exhibit poor power efficiency and heat dissipation. To address this, we explore acoustic amplification through acoustic energy storage and release, where, with minimal voltage, high-amplitude ultrasound waves are produced. Prior work has shown the principle using bulky apparatus with limited applicability. In this work, we explore the theory and perform finite element modeling (FEM) to investigate this mechanism with miniaturized and micro-electro-mechanical systems (MEMS)-compatible materials and geometries.
Piezoelectric Micromachined Ultrasonic Transducers (PMUT) and Capacitive Micromachined Ultrasonic Transducers (CMUT) have seen great developments in recent years, both in terms of performance and scope of applications within the biomedical ultrasound domain. This paper presents a review of the state-of-the-art of PMUT and CMUT technologies, focusing on their principle of operation, microfabrication techniques and use in different biomedical imaging and therapeutic applications. The advantages and drawbacks of PMUT and CMUT technologies in comparison with conventional bulk transducers are highlighted, the trade-offs among PMUTs and CMUTs are discussed, and their relevance in the current landscape of medical diagnostics and therapeutic uses is outlined, thus providing a clear overview of these promising technologies for the present and the next generation biomedical ultrasound applications.
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Piezoelectric Micromachined Ultrasonic Transducers (PMUT) and Capacitive Micromachined Ultrasonic Transducers (CMUT) have seen great developments in recent years, both in terms of performance and scope of applications within the biomedical ultrasound domain. This paper presents a review of the state-of-the-art of PMUT and CMUT technologies, focusing on their principle of operation, microfabrication techniques and use in different biomedical imaging and therapeutic applications. The advantages and drawbacks of PMUT and CMUT technologies in comparison with conventional bulk transducers are highlighted, the trade-offs among PMUTs and CMUTs are discussed, and their relevance in the current landscape of medical diagnostics and therapeutic uses is outlined, thus providing a clear overview of these promising technologies for the present and the next generation biomedical ultrasound applications.
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