碳纳米管提高脑起搏器电极MRI相容性的研究

Deep brain stimulation (DBS) is currently a hot topic in clinical application and basic research. However, the implantable lead would interact with the radio frequency (RF) field in magnetic resonance imaging (MRI), resulting in severe heating near the stimulating contacts of the lead. This brings safety concerns to the patients, hinders the spread of DBS and the patients’ needs for MRI examination, and denies the application of MRI and functional MRI to study the brain network after implantation of DBS. Earlier a ‘shielding’method to use macroscopic carbon nanotube films to cover the outer wall of the lead was developed, and found to be effective in reduing the lead heating under MRI. An invention patent and USA patents were applied for. Based on it, the project is to take full advantage of the unique physical and chemical properties of carbon nanotubes, combine many years’ experience of developing DBS lead, by means of phantom test and numerical simulaiton, comparatively study mechanisms underlying lead heating reduction by carbon nanotube coating, explore the influence of the electrical, thermal and tissue interfacial properties of carbon nanotube on the ‘shielding’ effect, as well as its relation to preparation and treatment methods, improve the lead wrapping method, and optimize MRI compatibility of carbon nanotube coated lead. This work is at present a blank both at home and abroad. The new lead will reform the DBS therapy, and contribute to the wide use of DBS under MRI, and has significant value in clinical application and research.

脑起搏器是目前临床应用和基础研究的热点，但是其植入电极会在核磁（MRI）下因为射频磁场耦合而在前端触点产生严重的发热，带来安全隐患，制约了脑起搏器推广和植入患者的MRI检查，也妨碍了应用MRI以及功能核磁（fMRI）研究植入脑起搏器后的大脑网络。前期提出了用宏观碳纳米管薄膜包裹电极外壁的“屏蔽”方法，能有效抑制MRI下的电极发热，并申请了发明专利和美国专利。拟在此基础上，充分挖掘碳纳米管独特的物理、化学性质，结合多年研发脑起搏器电极经验，通过体外模型、数值仿真等对比研究碳纳米管包裹抑制电极发热的作用机制，探索碳纳米管材料电、热以及组织界面特性对“屏蔽”效果的影响规律，及其与制备、后处理方法的关联，改进电极包裹方法，优化碳纳米管包裹电极的MRI相容性。该项工作目前在国内外是一项空白，新的电极将革新脑起搏器疗法，使脑起搏器在MRI下广泛应用，具有重大临床应用价值和研究意义。

帕金森病等脑疾病成为最严重的社会负担之一。脑起搏器通过埋植在胸前的刺激器向植入大脑特定靶点的电极发送电脉冲来调节大脑功能，能治疗多种脑疾病。作为唯一能精确调控大脑的手段，也是研究大脑运行机理的利器。核磁是研究大脑的主要手段之一。电极射频发热带来的安全问题限制了脑起搏器在核磁下应用，从而阻碍了脑研究的发展。.本项目提出共振偶极子天线理论，分析了电极结构对射频温升的影响规律，揭示了包裹方法抑制温升的机制；建立了数值模型，验证了电极射频温升的长度共振效应，并验证了包裹方法抑制温升的可行性。实现大面积、高质量碳纳米管薄膜制备和处理，探索了激光加工碳纳米管方法，改进了包裹工艺，形成良好包覆；测试了其射频温升性能，体现了良好的温升抑制。开发了超弹性Ni-Ti合金丝编织网工艺，研究了处理方法对其力学性能的影响；提出了Ni-Ti网包覆电极结构和制造方法，研究了覆盖率、长度等包覆参数对射频温升的影响规律；通过构造不同结构电极，验证了电极射频温升的长度共振效应，证明了电极射频温升机制，并通过编织屏蔽实现了电极温升的有效抑制。基于编织包覆方法，开发了核磁相容脑起搏器系统，通过体模和动物实验验证了安全性，开展了临床试验，完成了6个月随访，初步证明了本项目研制的核磁相容脑起搏器在核磁下应用的安全性。.本项目提出的共振偶极子天线理论，是分析脑起搏器电极在核磁下的射频温升机制研究的重要突破。在此基础上提出导电包覆方法，从碳纳米管薄膜包覆出发，发展出超弹性Ni-Ti丝编织包覆结构和方法，实现了电极射频温升的有效抑制，并最终开展了临床试验。这是全球首个能够兼容3.0T高场核磁的脑起搏器电极及系统，实现了我国在这一领域的创新引领。在临床试验中采集到了一批丰富而珍贵的帕金森病患者在不同时间和不同状态下的核磁影像数据，为分析大脑网络以及脑起搏器刺激影响奠定了基础，对推动我国在脑科学和脑疾病研究方面有重要意义。