Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Sci Transl Med. 2024 May 29;16(749):eadj3143. doi: 10.1126/scitranslmed.adj3143.
Visualization of human brain activity is crucial for understanding normal and aberrant brain function. Currently available neural activity recording methods are highly invasive, have low sensitivity, and cannot be conducted outside of an operating room. Functional ultrasound imaging (fUSI) is an emerging technique that offers sensitive, large-scale, high-resolution neural imaging; however, fUSI cannot be performed through the adult human skull. Here, we used a polymeric skull replacement material to create an acoustic window compatible with fUSI to monitor adult human brain activity in a single individual. Using an in vitro cerebrovascular phantom to mimic brain vasculature and an in vivo rodent cranial defect model, first, we evaluated the fUSI signal intensity and signal-to-noise ratio through polymethyl methacrylate (PMMA) cranial implants of different thicknesses or a titanium mesh implant. We found that rat brain neural activity could be recorded with high sensitivity through a PMMA implant using a dedicated fUSI pulse sequence. We then designed a custom ultrasound-transparent cranial window implant for an adult patient undergoing reconstructive skull surgery after traumatic brain injury. We showed that fUSI could record brain activity in an awake human outside of the operating room. In a video game "connect the dots" task, we demonstrated mapping and decoding of task-modulated cortical activity in this individual. In a guitar-strumming task, we mapped additional task-specific cortical responses. Our proof-of-principle study shows that fUSI can be used as a high-resolution (200 μm) functional imaging modality for measuring adult human brain activity through an acoustically transparent cranial window.
可视化人类大脑活动对于理解正常和异常的大脑功能至关重要。目前可用的神经活动记录方法具有高侵入性、低灵敏度，并且不能在手术室之外进行。功能超声成像（fUSI）是一种新兴技术，可提供敏感、大规模、高分辨率的神经成像；然而，fUSI 无法通过成人颅骨进行。在这里，我们使用聚合颅骨替代材料创建了一个与 fUSI 兼容的声窗，以在单个个体中监测成人的大脑活动。我们使用体外脑血管模型来模拟脑血管，并使用体内啮齿动物颅缺损模型，首先，我们通过不同厚度的聚甲基丙烯酸甲酯（PMMA）颅骨植入物或钛网植入物评估了 fUSI 信号强度和信噪比。我们发现，使用专用的 fUSI 脉冲序列，可以通过 PMMA 植入物以高灵敏度记录大鼠大脑神经活动。然后，我们为一名因创伤性脑损伤而接受重建颅骨手术的成年患者设计了一个定制的超声透明颅骨窗口植入物。我们表明，fUSI 可以在手术室外记录清醒人类的大脑活动。在一个“连线”视频游戏任务中，我们证明了在该个体中可以对任务调制的皮质活动进行映射和解码。在弹吉他任务中，我们绘制了额外的特定于任务的皮质反应。我们的原理验证研究表明，fUSI 可以用作通过声学透明颅骨窗口测量成人大脑活动的高分辨率（200μm）功能成像方式。
