BACKGROUND: Parkinson\'s disease (PD) is a common neurodegenerative disease. Transcranial magnetoacoustic stimulation (TMAS) is a new therapy that combines a transcranial focused acoustic pressure field with a magnetic field to excite or inhibit neurons in targeted area, which suppresses the abnormally elevated beta band amplitude in PD states, with high spatial resolution and non-invasively.
OBJECTIVE: To study the effective stimulation parameters of TMAS mononuclear and multinuclear stimulation for the treatment of PD with reduced beta band energy, improved abnormal synchronization, and no thermal damage.
METHODS: The TMAS model is constructed based on the volunteer\'s computed tomography, 128 arrays of phase-controlled transducers, and permanent magnets. A basal ganglia-thalamic (BG-Th) neural network model of the PD state was constructed on the basis of the Izhikevich model and the acoustic model. An ultrasound stimulation neuron model is constructed based on the Hodgkin-Huxley model. Numerical simulations of transcranial focused acoustic pressure field, temperature field and induced electric field at single and dual targets were performed using the locations of STN, GPi, and GPe in the human brain as the main stimulation target areas. And the acoustic and electric parameters at the focus were extracted to stimulate mononuclear and multinuclear in the BG-Th neural network.
RESULTS: When the stimulating effect of ultrasound is ignored, TMAS-STN simultaneously inhibits the beta-band amplitude of the GPi nucleus, whereas TMAS-GPi fails to simultaneously have an inhibitory effect on the STN. TMAS-STN&GPi can reduce the beta band amplitude. TMAS-STN&GPi&GPe suppressed the PD pathologic beta band amplitude of each nucleus to a greater extent. When considering the stimulatory effect of ultrasound, lower sound pressures of ultrasound do not affect the neuronal firing state, but higher sound pressures may promote or inhibit the stimulatory effect of induced currents.
CONCLUSIONS: At 9 T static magnetic field, 0.5-1.5 MPa and 1.5-2.0 MPa ultrasound had synergistic effects on individual STN and GPi neurons. TMAS multinuclear stimulation with appropriate ultrasound intensity was the most effective in suppressing the amplitude of pathological beta oscillations in PD and may be clinically useful.

Non-invasive ultrasound neuromodulation (USNM) is a powerful tool to explore neural circuits and treat neurological disorders. Due to the heterogeneity of the skull and regional variations in modulation and treatment objectives, it is necessary to develop an efficient and spatially controllable neuromodulation approach. Recently, transcranial focused ultrasound (tFUS) combined with external biomicro/nanomaterials for brain stimulation has garnered significant attention. This study focused on tFUS combined with perfluoropentane (PFP) nanodroplets (NDs) to improve the efficacy and spatial controllability of USNM. The developed two-stage variable pulse tFUS sequence that include the acoustic droplet vaporization (ADV) pulse for vaporizing PFP NDs into microbubbles (MBs) and the USNM sequence for inducing mechanical oscillations of the formed MBs to enhance neuronal activity. Further, adjusting the acoustic pressure of the ADV pulse generated the controllable vaporization regions, thereby achieving spatially controllable neuromodulation. The results showed that the mean densities of c-fos+ cells expression in the group of PFP NDs with ADV (109 ± 19 cells/mm2) were significantly higher compared to the group without ADV (37.34 ± 8.24 cells/mm2). The acoustic pressure of the ADV pulse with 1.98 MPa and 2.81 MPa in vitro generated the vaporization regions of 0.146 ± 0.032 cm2 and 0.349 ± 0.056 cm2, respectively. Under the same stimulation conditions, a larger vaporization region was also obtained with higher acoustic pressure in vivo, inducing a broader region of neuronal activation. Therefore, this study will serve as a valuable reference for developing the efficient and spatially controllable tFUS neuromodulation strategy.

Transcranial focused ultrasound ablation has emerged as a promising technique for treating neurological disorders. The clinical system exclusively employed the ray tracing method to compute phase aberrations induced by the human skull, taking into account computational time constraints. However, this method compromises slightly on accuracy compared to simulation-based methods. This study evaluates a fast simulation method that simulates the time-harmonic pressure field within the region of interest for effective phase correction. Experimental validation was carried out using a 512-element, 670 kHz hemispherical transducer for fourex vivoskulls. The ray tracing method achieved a restoration ratio of 64.81% ± 4.33% of acoustic intensity normalized to hydrophone measurements. In comparison, the rapid simulation method demonstrated improved results with a restoration ratio of 73.10% ± 7.46%, albeit slightly lower than the full-wave simulation which achieved a restoration ratio of 75.87% ± 5.40%. The rapid simulation methods exhibited computational times that were less than five minutes for parallel computation with 8 threads. The incident angle was calculated, and a maximum difference of 6.8 degrees was found when the fixed position of the skull was changed. Meanwhile, the restoration ratio of acoustic intensity was validated to be above 70% for different target positions away from the geometrical focus of the transducer. The favorable balance between time consumption and correction accuracy makes this method valuable for clinical treatment applications.

UNASSIGNED: As a non-invasive method for brain diseases, transcranial focused ultrasound (tFUS) offers higher spatial precision and regulation depth. Due to the altered path and intensity of sonication penetrating the skull, the focus and intensity in the skull are difficult to determine, making the use of ultrasound therapy for cancer treatment experimental and not widely available. The deficiency can be effectively addressed by numerical simulation methods, which enable the optimization of sonication modulation parameters and the determination of precise transducer positioning.
UNASSIGNED: A 3D skull model was established using binarized brain CT images. The selection of the transducer matrix was performed using the radius positioning (RP) method after identifying the intracranial target region. Simulations were performed, encompassing acoustic pressure (AP), acoustic field, and temperature field, in order to provide compelling evidence of the safety of tFUS in sonication-induced thermal effects.
UNASSIGNED: It was found that the angle of sonication path to the coronal plane obtained at all precision and frequency models did not exceed 10° and 15° to the transverse plane. The results of thermal effects illustrated that the peak temperatures of tFUS were 43.73°C, which did not reach the point of tissue degeneration. Once positioned, tFUS effectively delivers a Full Width at Half Maximum (FWHM) stimulation that targets tumors with diameters of up to 3.72 mm in a one-off. The original precision model showed an attenuation of 24.47 ± 6.13 mm in length and 2.40 ± 1.42 mm in width for the FWHM of sonication after penetrating the skull.
UNASSIGNED: The vector angles of the sonication path in each direction were determined based on the transducer positioning results. It has been suggested that when time is limited for precise transducer positioning, fixing the transducer on the horizontal surface of the target region can also yield positive results for stimulation. This framework used a new transducer localization method to offer a reliable basis for further research and offered new methods for the use of tFUS in brain tumor-related research.

Transcranial focused ultrasound is a novel technique for the noninvasive treatment of brain diseases. The success of the treatment greatly depends on achieving precise and efficient intraoperative focus. However, compensating for aberrated ultrasound waves caused by the skull through numerical simulation-based phase corrections is a challenging task due to the significant computational burden involved in solving the acoustic wave equation. In this article, we propose a promising strategy using the coupling of the boundary integral equation method (BIEM) and the finite element method (FEM) to overcome the above limitation. Specifically, we adopt the BIEM to obtain the Robin-to-Dirichlet maps on the boundaries of the skull and then couple the maps to the FEM matrices via a dual interpolation technique, resulting in a computational domain including only the skull. Three simulation experiments were conducted to evaluate the effectiveness of the proposed method, including a convergence test and two skull-induced aberration corrections in 2D and 3D ultrasound. The results show that the method\'s convergence is guaranteed as the element size decreases, leading to a decrease in pressure error. The computation times for simulating a 500 kHz ultrasound field on a regular desktop computer were found to be 0.47 ± 0.01 s in the 2D case and 43.72 ± 1.49 s in the 3D case, provided that lower-upper decomposition (approximately 13 s in 2D and 2.5 h in 3D) was implemented in advance. We also demonstrated that more accurate transcranial focusing can be achieved by phase correction compared to the noncorrected results (with errors of 1.02 mm vs. 6.45 mm in 2D and 0.28 mm vs. 3.07 mm in 3D). The proposed strategy is valuable for enabling online ultrasound simulations during treatment, facilitating real-time adjustments and interventions.

BACKGROUND: Low-intensity transcranial focused ultrasound (tFUS) has gained considerable attention as a promising noninvasive neuromodulatory technique for human brains. However, the complex morphology of the skull hinders scholars from precisely predicting the acoustic energy transmitted and the region of the brain impacted during the sonication. This is due to the fact that different ultrasound frequencies and skull morphology variations greatly affect wave propagation through the skull.
OBJECTIVE: Although the acoustic properties of human skull have been studied for tFUS applications, such as tumor ablation using a multielement phased array, there is no consensus about how to choose a single-element focused ultrasound (FUS) transducer with a suitable frequency for neuromodulation. There are interests in exploring the magnitude and dimension of tFUS beam through human parietal bone for modulating specific brain lobes. Herein, we aim to investigate the wave propagation of tFUS on human skulls to understand and address the concerns above.
METHODS: Both experimental measurements and numerical modeling were conducted to investigate the transmission efficiency and beam pattern of tFUS on five human skulls (C3 and C4 regions) using single-element FUS transducers with six different frequencies (150-1500 kHz). The degassed skull was placed in a water tank, and a calibrated hydrophone was utilized to measure acoustic pressure past it. The cranial computed tomography scan data of each skull were obtained to derive a high-resolution acoustic model (grid point spacing: 0.25 mm) in simulations. Meanwhile, we modified the power-law exponent of acoustic attenuation coefficient to validate numerical modeling and enabled it to be served as a prediction tool, based on the experimental measurements.
RESULTS: The transmission efficiency and -6 dB beamwidth were evaluated and compared for various frequencies. An exponential decrease in transmission efficiency and a logarithmic decrease of -6 dB beamwidth with an increase in ultrasound frequency were observed. It is found that a >750 kHz ultrasound leads to a relatively lower tFUS transmission efficiency (<5%), whereas a <350 kHz ultrasound contributes to a relatively broader beamwidth (>5 mm). Based on these observations, we further analyzed the dependence of tFUS wave propagation on FUS transducer aperture size.
CONCLUSIONS: We successfully studied tFUS wave propagation through human skulls at different frequencies experimentally and numerically. The findings have important implications to predict tFUS wave propagation for ultrasound neuromodulation in clinical applications, and guide researchers to develop advanced ultrasound transducers as neural interfaces.

Transcranial-focused ultrasound (tFUS) has potential for both neuromodulation and neuroimaging. Due to the influence of head tissue, especially the skull, its attenuation is a key issue affecting precise focusing. The objective of the present study was to construct a mathematical model of ultrasound attenuation inclusive of skull thickness. First, combined with real skull phantom experiments and simulation experiments, tFUS attenuation of different head tissues was investigated. Furthermore, based on the system identification method, a mathematical model of ultrasound attenuation was constructed taking skull thickness into account. Finally, the performance of the mathematical model was tested, and its potential applications were investigated. For different head tissues, including scalp, skull, and brain tissue, the skull was found to be the biggest influencing factor for ultrasound attenuation, the attenuation caused by it being 4.70 times and 7.06 times that of attenuation caused by the brain and scalp, respectively. Consistent with the results of both the simulation and phantom experiments, the attenuation of the mathematical model increased as the skull thickness increased. The average error of the mathematical model was 1.87% in the phantom experiment. In addition, the experimental results show that the devised mathematical model is suitable for different initial pressures and different skulls with correlation coefficients higher than 0.99. Both simulation and phantom experiments validated the effectiveness of the proposed mathematical model. It can be concluded from this experiment that the proposed mathematical model can accurately calculate the tFUS attenuation and can significantly contribute to further research and application of tFUS.

Non-invasive neuromodulation technology is important for the treatment of brain diseases. The effects of focused ultrasound on neuronal activity have been investigated since the 1920s. Low intensity transcranial focused ultrasound (tFUS) can exert non-destructive mechanical pressure effects on cellular membranes and ion channels and has been shown to modulate the activity of peripheral nerves, spinal reflexes, the cortex, and even deep brain nuclei, such as the thalamus. It has obvious advantages in terms of security and spatial selectivity. This technology is considered to have broad application prospects in the treatment of neurodegenerative disorders and neuropsychiatric disorders. This review synthesizes animal and human research outcomes and offers an integrated description of the excitatory and inhibitory effects of tFUS in varying experimental and disease conditions.

Transcranial focused ultrasound (tFUS) has great potential in brain imaging and therapy. However, the structural and acoustic differences of the skull will cause a large number of technical problems in the application of tFUS, such as low focus energy, focal shift, and defocusing. To have a comprehensive understanding of the skull effect on tFUS, this study investigated the effects of the structural parameters (thickness, radius of curvature, and distance from the transducer) and acoustic parameters (density, acoustic speed, and absorption coefficient) of the skull model on tFUS based on acrylic plates and two simulation methods (self-programming and COMSOL). For structural parameters, our research shows that as the three factors increase the unit distance, the attenuation caused from large to small is the thickness (0.357 dB/mm), the distance to transducer (0.048 dB/mm), and the radius of curvature (0.027 dB/mm). For acoustic parameters, the attenuation caused by density (0.024 dB/30 kg/m3) and acoustic speed (0.021 dB/30 m/s) are basically the same. Additionally, as the absorption coefficient increases, the focus acoustic pressure decays exponentially. The thickness of the structural parameters and the absorption coefficient of the acoustic parameters are the most important factors leading to the attenuation of tFUS. The experimental and simulation trends are highly consistent. This work contributes to the comprehensive and quantitative understanding of how the skull influences tFUS, which further enhances the application of tFUS in neuromodulation research and treatment.