Transcranial Focused Ultrasound Neuromodulation: A Review of the Excitatory and Inhibitory Effects on Brain Activity in Human and Animals

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.

The Effects of the Structural and Acoustic Parameters of the Skull Model on Transcranial Focused Ultrasound

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.

Investigation of the Therapeutic Effect of Doxorubicin Combined With Focused Shockwave on Glioblastoma

BackgroundGlioblastoma multiforme (GBM) is currently the most devastating brain tumor globally and produces a high mortality rate. GBM is also challenging to eradicate using surgery due to its invasive characteristics. Moreover, the blood-brain barrier (BBB) increases the difficulty of transporting most therapeutic drugs to tumor sites. The use of transcranial focused ultrasound (FUS) has recently been investigated for opening the BBB to facilitate drug delivery. A special form of FUS, the shockwave (SW), has also been shown to open BBB efficiently. SW has several advantages including no heating effect, less reactive oxygen species production, good transcranial ability, and no need to supply microbubbles.MethodsWe employed a commercial SW device, which is a common tool used for musculoskeletal disorders, to improve doxorubicin delivery across the BBB and evaluated its therapeutic efficacy on GBM rat models. SW emits relatively short but stronger mechanical pulses comparing with FUS.ResultsThe results demonstrated that doxorubicin combined with SW treatment substantially inhibited tumor growth and prolonged overall survival.ConclusionsThe present study shows the non-invasive transcranial SW may have potential for the treatment of GBM in future clinical setting.