用于超声成像和神经调控的双模面阵换能器技术研究

Imaging guided ultrasonic neuromodulation is quite potential in brain academic fundamental research and clinical diagnosis and therapy of brain diseases due to its many merits, such as non-invasive stimulation, precise stimulation, and multi-focus stimulation. Compare to MRI guidance, ultrasonic imaging guidance has many advantages such as low cost, convenience, and precise guidance information because of the same ultrasound transmission path in imaging and neuromodulation mode. However, most ultrasound transducers used in previous research are single element transducers, which cannot realize multi-focus stimulation. And the distortion of ultrasonic field due to the skull influence the ultrasonic imaging quality and ultrasonic neuromodulation accuracy. Ultrasound 2D array can realize multi-focus stimulation and compensate the distorted ultrasonic field by electronical method. However, the reported ultrasound 2D arrays for ultrasonic imaging cannot be excited by long pulse signal, thus unsuitable for ultrasonic neuromodulation; and the reported ultrasound 2D arrays for therapy are not suitable for ultrasonic imaging because of their low imaging resolution. In this project, therefore, dual-mode ultrasound 2D array is going to be designed and fabricated for both ultrasonic imaging guidance and ultrasonic neuromodulation. The materials, structures and sizes of the dual-mode ultrasound 2D array would be designed and optimized to increase the imaging resolution and transcranial ultrasonic intensity. And the effect of the skull on ultrasonic field is going to be investigated in detail. The parameters of ultrasonic imaging mode and ultrasonic neuromodulation mode would be optimized after transcranial ultrasonic field compensation to improve the ultrasonic imaging quality and ultrasonic neuromodulation accuracy. The developing dual-mode ultrasound 2D array technology in this project is significant to the development of ultrasonic imaging guided ultrasonic neuromodulation technology for brain academic fundamental research and clinical diagnosis and therapy of brain diseases.

成像引导下超声神经调控技术以其无创、精准、可多点刺激等优点在脑科学基础研究和脑功能性疾病诊疗等领域展示了重大应用前景。相比于磁共振成像引导，超声成像引导以其成本低、使用方便并且能够模拟超声路径提供更准确的引导信息显示了更大优势。但是目前相关研究都是使用单阵元换能器，无法实现多点刺激。而且颅骨对超声声场的畸变会影响成像质量和调控精度。采用面阵换能器可进行多点刺激以及穿颅后声场补偿。但是已研究报道的用于成像的面阵换能器不支持长序列脉冲发送，不适于神经调控应用；用于治疗的面阵换能器带宽低，超声成像质量差。因此，本项目拟设计制备能同时用于超声成像和神经调控的双模面阵换能器，从换能器制备材料选择，结构尺寸设计等方面提高穿颅后超声强度和成像分辨率；并研究颅骨对超声声场的影响，对穿颅后超声声场进行补偿，提高超声成像质量和神经调控精度，为超声成像引导下超声神经调控技术发展奠定基础，具有重要医学科学价值。

帕金森病、癫痫和抑郁症等脑功能性疾病的有效干预和治疗是重大医学难题。发展无创、精准的脑神经调控技术和工具是脑疾病研究的重大需求。成像引导下基于面阵超声换能器的超声神经调控技术以其无创、精准、可多靶点刺激等优点在脑科学基础研究和脑功能性疾病干预治疗等方面展示了重大应用前景。相比于磁共振成像引导，基于双模面阵换能器的超声成像引导以其成本低、便携、能够实时优化超声路径并提供更准确引导信息等优点显示了更大优势。但是传统用于成像的面阵换能器不支持长序列脉冲发送，不适于神经调控应用；用于治疗的面阵换能器带宽低，超声成像质量差。另外颅骨对超声声场的衰减和畸变会影响成像质量和调控精度。因此，本项目设计制备了能同时用于超声成像和神经调控的高性能双模面阵超声换能器，从换能器制备材料选择，结构尺寸设计等方面提高面阵换能器输出声压和成像分辨率；并研究了颅骨及颅骨与面阵换能器相对位置对面阵超声声场的影响。研究结果表明，本项目基于新型Sm掺杂PMN-PT压电陶瓷（Sm-PMN-PT）研制的面阵超声换能器输出声压是传统压电材料的2倍，同时声束在较大角度范围偏转无栅瓣，面阵换能器的-6dB带宽为61.6%，具备了可同时用于超声三维成像和三维神经调控的能力。另外，无论在声束有无偏转情况下小鼠颅骨对二维面阵超声换能器的超声声场分布基本没有影响，但是会使焦点处最大输出声压幅值大概降低20%。聚焦点位置越近，颅骨对焦点区域输出声压的衰减越大；在聚焦点位置不变的情况下，随着颅骨离面阵换能器的距离增大，颅骨对焦点区域输出声压的衰减先增大后减小。同时优化了面阵三维成像方法，并研究了颅骨对超声成像的影响，发现在超声图像中大脑信号相对于颅骨太弱。因此本研究提出并验证了一种基于颅骨超声图像结构特征定位脑区的方法，实现了对穿颅靶点的精准定位，并验证了基于双模面阵超声换能器的超声引导下神经调控技术可行性，对超声神经调控技术发展有着重要指导意义，具有重要医学科学价值。