PDF(Pubmed)
Abstract：
Transcranial focused ultrasound enables precise and non-invasive manipulations of deep brain circuits in humans, promising to provide safe and effective treatments of various neurological and mental health conditions. Ultrasound focused to deep brain targets can be used to modulate neural activity directly or localize the release of psychoactive drugs. However, these applications have been impeded by a key barrier-the human skull, which attenuates ultrasound strongly and unpredictably. To address this issue, we have developed an ultrasound-based approach that directly measures and compensates for the ultrasound attenuation by the skull. No additional skull imaging, simulations, assumptions, or free parameters are necessary; the method measures the attenuation directly by emitting a pulse of ultrasound from an array on one side of the head and measuring with an array on the opposite side. Here, we apply this emerging method to two primary future uses-neuromodulation and local drug release. Specifically, we show that the correction enables effective stimulation of peripheral nerves and effective release of propofol from nanoparticle carriers through an ex vivo human skull. Neither application was effective without the correction. Moreover, the effects show the expected dose-response relationship and targeting specificity. This article highlights the need for precise control of ultrasound intensity within the skull and provides a direct and practical approach for addressing this lingering barrier.
摘要：
经颅聚焦超声能够精确和非侵入地操作人类的脑深部回路，有望为各种神经和精神健康状况提供安全有效的治疗方法。聚焦到深部脑目标的超声可用于直接调节神经活动或定位精神活性药物的释放。然而,这些应用受到了一个关键屏障——人类头骨的阻碍，它强烈且不可预测地衰减超声波。为了解决这个问题，我们开发了一种基于超声的方法，可以直接测量和补偿颅骨的超声衰减。没有额外的颅骨成像，模拟,假设,或自由参数是必要的;该方法通过从头部一侧的阵列发射超声脉冲并在相对侧的阵列测量来直接测量衰减。这里,我们将这种新兴方法应用于两个主要的未来用途-神经调节和局部药物释放。具体来说,我们表明，矫正能够有效刺激周围神经，并通过离体人颅骨从纳米颗粒载体中有效释放异丙酚。没有校正,两种应用都不有效。此外，这些效应显示了预期的剂量-反应关系和靶向特异性.本文强调了精确控制颅骨内超声强度的必要性，并为解决这一挥之不去的障碍提供了一种直接实用的方法。
