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Transcranial focused ultrasound (tFUS) is increasingly used in experimental neuroscience due to its neuromodulatory effectiveness in animal studies. However, achieving multitarget tFUS in small animals is typically limited by transducer size, energy transfer efficiency, and brain volume. The objective of this work was to construct an ultrasound system for multitarget neuromodulation in small animals. First, a miniaturized high-powered 2-D array transducer was developed. The phase delay of each array element was calculated based on the multifocal time-reversal method, generating multiple foci simultaneously in a 3-D field. The effects of the axial focal length, interfocus spacing (lateral distance between the two focal centers), and the number of foci on the focal properties of the pressure field were examined through numerical simulations. In-vitro ultrasonic measurements and transcranial simulations on a rat skull were conducted. The minimum interfocus spacing separating two −6-dB foci and the peak full-width at half-maximum were positively correlated with axial focal length; the relative relationship between the interfocus spacing and pressure field properties was similar for each axial focal length. The maximum acoustic pressure and spatial average intensity at focus in deionized water were 2.21 MPa and 133 W/cm2, respectively. The simulated and experimental results were compared, demonstrating agreement in both peak position and focus shape. The ultrasound system can provide a neuroscientific platform for evaluating the feasibility of multitarget ultrasound stimulation treatment protocols, thus improving the understanding of functional neuroanatomy. [ABSTRACT FROM AUTHOR]

Transcranial ultrasound therapy has become a noninvasive method for treating neurological and psychiatric disorders, and studies have further demonstrated that multitarget transcranial ultrasound therapy is a better solution. At present, multitarget transcranial ultrasound therapy in small animals can only be achieved by the multitransducer or phased array. However, multiple transducers may cause spatial interference, and the phased array system is complicated, expensive, and especially unsuitable for small animals. This study is the first to design and fabricate a miniature acoustic holography lens for multitarget transcranial ultrasound therapy in rats. The acoustic holographic lens, working at a frequency of 1.0 MHz, with a size of 10.08 mm $\times10.08$ mm and a pixel resolution of 0.72 mm, was designed, optimized, and fabricated. The dual-focus transcranial ultrasound generated based on the lens was measured; the full-width at half-maximum (FWHM) of the focal spots in the ${y}$ -direction was 2.15 and 2.27 mm and in the ${z}$ -direction was 2.3 and 2.36 mm. The focal length was 5.4 mm, and the distance between the two focuses was 5.6 mm, close to the desired values of 5.4 and 6.0 mm. Finally, the multiple-target blood–brain barrier opening in rats’ bilateral secondary visual cortex (mediolateral area, V2ML) was demonstrated using the transcranial ultrasound therapy system based on the lens. These results demonstrate the good performance of the multitarget transcranial ultrasound therapy system for small animals, including high spatial resolution, small size, and low cost. [ABSTRACT FROM AUTHOR]

• A head-mounted transcranial ultrasound stimulation system for mice was built. • Ultrasound stimulation of DRN safely increased c-fos gene expression in the DRN. • Ultrasound stimulation of DRN increased 5-hydroxytryptamine levels in DRN. • Ultrasound stimulation of DRN promoted recovery from anesthesia and improved cognition in mice. • Antagonizing the 5-HT 2A receptor inhibited anesthesia recovery and cognition in mice after ultrasound stimulation of DRN. Delayed arousal and cognitive dysfunction are common, especially in older patients after general anesthesia (GA). Elevating central nervous system serotonin (5-HT) levels can promote recovery from GA and increase synaptic plasticity to improve cognition. Ultrasound neuromodulation has become a noninvasive physical intervention therapy with high spatial resolution and penetration depth, which can modulate neuronal excitability to treat psychiatric and neurodegenerative diseases. This study aims to use ultrasound to noninvasively modulate the brain 5-HT levels of mice to promote recovery from GA and improve cognition in mice. The dorsal raphe nucleus (DRN) of mice during GA was stimulated by the 1.1 MHz ultrasound with a negative pressure of 356 kPa, and the liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) method was used to measure the DRN 5-HT concentrations. The mice's recovery time from GA was assessed, and the cognition was evaluated through spontaneous alternation Y-maze and novel object recognition (NOR) tests. After ultrasound stimulation, the mice's DRN 5-HT levels were significantly increased (control: 554.0 ± 103.2 ng/g, anesthesia + US: 664.2 ± 84.1 ng/g, *p = 0.0389); the GA recovery time (return of the righting reflex (RORR) emergence latency time) of mice was significantly reduced (anesthesia: 331.6 ± 70 s, anesthesia + US: 223.2 ± 67.7 s, *p = 0.0215); the spontaneous rotation behavior score of mice was significantly increased (anesthesia: 59.46 ± 5.26 %, anesthesia + US: 68.55 ± 5.24 %; *p = 0.0126); the recognition index was significantly increased (anesthesia: 55.02 ± 6.23 %, anesthesia + US: 78.52 ± 12.21 %; ***p = 0.0009). This study indicates that ultrasound stimulation of DRN increases serotonin levels, accelerates recovery from anesthesia, and improves cognition, which could be an important strategy for treating delayed arousal, postoperative delirium, or even lasting cognitive dysfunction after GA. [ABSTRACT FROM AUTHOR]

[Display omitted] • The influencing mechanism of ultrasound on the size of Cu nanoparticles is studied. • The mean size and size dispersion are significantly reduced ultrasound treatment. • A competition model between surface energy and ultrasonic force is proposed. • An exponential relation of between particle size and ultrasonic power is revealed. • Ultrasonic power and surface energy are keys to control the final particle size. Ultrasonic treatment is an effective method for size refinement and dispersion of nanomaterials during their synthesis process. However, the quantitative relationship between ultrasonic conditions and particle size in the synthesis of metal nanoparticles has not been fully revealed. In this study, Cu nanoparticles were synthesized via the wet-chemical redox method under ultrasonic treatment, and statistical analysis on the evolution of particle size distribution was carried out. It was found that the particle size decreased exponentially with increasing ultrasonic power. A quantitative model was then proposed to describe the influence of ultrasonic power on the size distribution of metal nanoparticles from the perspective of the competition between the surface energy and the ultrasonic force. A relational expression of R c ∝ γ 4 7 P - 3 7 was revealed, and it was proved to fit well with the experimental results. Our study provides new experimental basis and theoretical method for understanding the mechanism of ultrasonic-induced size refinement of metal nanoparticles. [ABSTRACT FROM AUTHOR]