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类型 应用研究 预答辩日期 2018-01-23
开始(开题)日期 2014-12-15 论文结束日期 2017-12-05
地点 东南大学四牌楼校区李文正楼北412室 论文选题来源 国家自然科学基金项目     论文字数 8 (万字)
题目 植入式神经肌肉功能电刺激电子系统设计与实验研究
主题词 脊髓损伤,膀胱功能障碍,胃食管反流病,植入式,神经肌肉电刺激
摘要 脊髓损伤(Spinal Cord Injury, SCI)导致损伤部位以下的运动和感觉功能的丧失,因而也经常导致膀胱功能部分或完全的丧失。SCI患者往往同时面临着膀胱贮尿和排尿双重功能障碍,如果不及时治疗最终可能导致肾衰竭,这也是导致 SCI患者后期死亡的第一位原因。SCI后膀胱功能障碍的患者数目众多、发病率高,严重影响患者的生活质量、心理和社会交往,对患者家庭和社会造成沉重的经济负担。因此,恢复与重建SCI患者的膀胱功能,对于提高这些患者的生活质量、降低死亡率具有十分重要意义。 胃食管反流病(Gastro-esophageal Reflux Disease, GERD)被定义为胃内容物反流入食管,导致一系列的不适症状和(或)并发症的一种疾病。GERD是全世界最常见的消化道疾病之一,而且在人群中发病率高。据统计,全世界范围内,大约有2.5亿个GERD患者。GERD不仅严重影响患者的生活质量,还造成了沉重的经济和社会负担,其治疗方法也成为了全世界关注和研究的热点。 基于课题组前期实行的“先外周后中枢”和“先体外后体内”研究路线,目前肌电桥(EMGB)系统(“体外”)已进入临床认证阶段,所以在前期的工作基础上,本文主要围绕应用于SCI后膀胱功能重建和治疗GERD相关的植入式(“体内”)神经肌肉电刺激电子系统设计以及实验开展研究。主要研究内容如下: 1) 电极配置选择和刺激波形参数优化实验研究。通过实验探索合适的电极配置和刺激参数,旨在不改变系统的软硬件设计的前提下,进一步地提高刺激器的性能。为此,本文讨论不同电极配置、不同脉宽比和不同IPG(Interphase Gap)对神经电刺激的影响,为植入NMES系统电路系统设计提供实验指导。 2) 用于膀胱功能控制的神经刺激器电路设计。采用集成电路设计的方法设计刺激器,能够产生满足治疗SCI后膀胱功能障碍的刺激脉冲。刺激器电路设计主要包括DAC、电流驱动电路和开关网络电路。 3) 用于膀胱功能重建的神经信号探测前端电路设计。采用集成电路设计的方法设计神经信号探测前端电路,用于骶神经神经信号探测,识别膀胱状态信息。探测前端电路设计主要包括OTA设计和反馈伪电阻设计。另外,从理论上分析神经探测前端的噪声。 4) 体内无源型食管下括约肌电刺激系统设计和实验研究。基于信号无线跨皮传输技术,设计用于治疗GERD的体内无源型食管下括约肌电刺激系统。然后,利用生物相容性材料对系统的体内部分进行封装,并对封装后系统的信号特性和位置失匹配进行测试。最后,利用所设计的系统进行LES电刺激实验和体内植入实验,验证系统的安全性和有效性。 本文所涉及的创新点如下: 1) 研究不同电极配置、不同脉宽比和不同IPG对神经电刺激的影响,得出以下结论:纵向三极电极配置所需的刺激阈值电流最低,这一点对植入式刺激器的低功耗设计非常有利;横向电极配置的选择性比纵向配置的好,因为横向电极配置拥有较大的动态范围可供调节。从肌肉力量精细控制角度考虑,横向电极配置更适合。脉宽比为1:6的非对称双相电荷平衡脉冲很好地结合单相脉冲阈值低和双相脉冲电荷平衡二者的优点。为了使随后的阳极相不影响阴极相所引起的动作电位的传播,需要在两个刺激相间加个IPG,实验得到阴极脉宽为50 μs时最佳的IPG为300 μs,因为此时具有较低的阈值,同时还获得较大的最大EMG响应幅度和最大的动态范围。这些结论为植入NMES系统电路系统设计提供了验指导。 2) 刺激器一方面采用电流型DAC和电流驱动直接实现电流模式刺激,不需要电压-电流转换电路,显著地降低了刺激器的功耗;另一方面采用同一个电流源和一个开关网络来实现双相刺激电流脉冲,消除了用两个独立电流源分别生成阴极和阳极电流,节省了芯片面积且减少了控制信号互连线。另外,采用对称可调的共源共栅电流镜作为电流驱动电路。该方法结合了压控电阻技术和电流镜的线性两者的优点,能够获得高的电压容限和高的输出阻抗,确保有效地发送电荷到生物组织上。 3) 神经探测前端电路采用了两级全差分电容耦合的运放结构。全差分结构具有高的共模抑制比和高的电源抑制比,能够抑制共模噪声和源自电源纹波和数字电路干扰。采用两级信号放大是为了获得足够大的增益,且保证良好的线性度。采用电容耦合放大器结构是了隔断电极-组织接口电化学反应引起的直流偏移。第一级采用套筒式共源共栅结构运放降低系统的噪声,而第二级采用折叠共源共栅结构优化摆幅。与先前研究相比,该神经信号探测前端电路具有低噪声、低功耗等优点。 4) 设计了一种体内无源型食管括约肌电刺激系统。该系统采用信号无线跨皮传输技术,刺激信号是通过体外发射电路经线圈耦合的方式传输到体内,具有电路结构简单、系统可靠性好、体积小、寿命长和成本低的特点。体内设计成无源的结构,解决了传统植入式器件电池供电所带来的问题。另外,医生可依据患者的情况,通过无线程序控制及时有效地调整刺激参数,以便对不同患者进行个性化的治疗。
英文题目 Electronic System Design and Experimental Study for Implantable Neuromuscular Functional Electrical Stimulation
英文主题词 Spinal Cord Injury, Bladder Dysfunction, Gastro-esophageal Reflux Disease, Implantable, Neuromuscular Electrical Stimulation
英文摘要 Spinal cord injury (SCI) leads to the loss of motor and sensory function below lesion, and thus often causes the loss of partial or complete bladder function. The patients after SCI are often faced with the double dysfunction of bladder storage and urination at the same time. If not treated in time, it might eventually lead to kidney failure which is the first cause of death of SCI patients. Patients with bladder dysfunction after SCI are numerous and high incidence. Bladder dysfunction after SCI seriously affects the patient’s quality of life, psychological and social relations, and gives rise to a heavy economic burden to their family and social. Therefore, the restoration and rebuilding of bladder function has great significance for improving the quality of life and reducing the mortality rate of SCI patients. Gastro-esophageal Reflux Disease (GERD) is defined as “a condition which develops when the reflux of stomach contents causes troublesome symptoms and/or complications”. GERD is one of the most common gastrointestinal diseases around the world, and has a high incidence. According to statistics, there are about 250 million GERD patients around the world. GERD is not only seriously affecting the patient’s quality of life, but also causing the heavy burden of economy and society. Therefore, treatment methods of GERD have become a worldwide concern and research hot spot. Based on the previous research route of “From peripheral to central nervous” and “From in vitro to in vivo”, the system (“in vitro”) of Electromyographic Bridge (EMGB) has entered the stage of clinical certification. This paper mainly focuses on the reconstruction of bladder dysfunction after SCI and treatment of GERD associated with electronic system design and experimental research for implantable (“in vivo”) neuromuscular electrical stimulation. The specific works of this paper are presented as follows: 1) The experiment research of electrode configuration choice and the stimulating waveform parameters optimization: The suitable electrode configurations and stimulation parameters are explored by experiments, which aims to further improve the performance of the stimulator under the condition of not changing circuit hardware and software design. This paper discussed the effects of the different electrode configuration, the pulse width ratio and interphase gap (IPG) for nerve electrical stimulation. 2) The design of nerve stimulator circuit for controlling the bladder function: The method of integrated circuit design was adopted for the design of stimulator which can generate stimulus pulse for the treatment of bladder dysfunction after SCI. The design of stimulator circuit mainly includes the DAC circuit, current driver circuit and switch network. 3) The design of nerve signal detection front-end circuit for the reconstruction of bladder function: The method of integrated circuit design was adopted for the design of nerve signal detection front-end circuit which was used for sacral nerve signal detection to identify the bladder status information. The design of detection front-end circuit mainly includes the OTAs and pseudo feedback resistance. In addition, the noise of the detection front-end circuit is analyzed theoretically. 4) The passive type of implantable system design and experimental research for esophageal lower sphincter electrical stimulation: Based on RF-wireless across skin transmission technology, the passive type of implantable system was designed for the treatment of GERD. Then, a kind of biocompatible material was used to encapsulate the body part of the system, and the encapsulation system was tested by the signal characteristics and the mismatch position. Finally, the system was used to the LES electrical stimulation experiment and implantation experiment. The specific novel ideas of this paper are presented as follows: 1) By studying the effects of the different electrode configuration, the pulse width ratio and interphase gap (IPG) for nerve electrical stimulation, we can draw the following conclusion: the longitudinal tripolar electrode configuration with lowest threshold appear to be well suitable for the low power design of implantable stimulator; the transverse configurations with gentle slope and large dynamic range are suitable for the muscle force fine control. The1:6 of pulse width ratio well combines the advantages of the single-phase pulse with low threshold and the biphasic pulse with charge balance. In order to the subsequent anode phase not affect the action potential propagation caused by cathode phase, it needs to add an interphase gap between two phases. The best IPG is 300 μs corresponding to the cathode pulse width of 50 μs, because it can obtain a lower threshold, a larger biggest EMG response and the maximum dynamic range at the same time. These results can provide the experiment instruction for the design of implantable NMES system circuit system. 2) On the one hand, a current type DAC and a current driver were adopted to realize the current mode stimulus, which do not need the voltage-current convert circuit that significantly reduces the power consumption of the stimulator. On the other hand, using the same current source and switch network implement biphasic stimulation current pulses which eliminate to use two independent current sources for generating cathode and anode current that saved the chip area and reduces the control signal interconnect. In addition, using a symmetrical regulated cascode with a current mirror as a current driver circuit, the method combines the advantages of the voltage-controlled resistor technology and current mirror, which can obtain a high voltage tolerance and high output impedance that make sure to send the charge to the tissue effectively. 3) The front-end circuit for nerve signal detection adopts two-stage fully differential amplifiers with a high common mode rejection ratio and a high power supply rejection ratio which can restrain the common-mode noise interference, the power supply ripple and the digital circuit. The two-stage signal amplification is utilized for achieving a high gain and a good linearity. The capacitively coupled amplifiers are used as the neural recording circuit for injecting DC offset introduced by the electrochemical reaction at electrode tissue interface. The first stage adopts telescopic-cascode OTA for reducing the noise of the system, while the second stage adopts folded-cascode OTA for obtaining a high output swing. Compared with previous research, the neural signal detection front-end circuit has the advantages of low noise and low power consumption. 4) A passive type of implantable system is designed for esophageal lower sphincter electrical stimulation. The RF-wireless signal across skin transmission technology was used for the design of this system which has the characteristics of simple circuit structure, good reliability, small volume, long service life and low cost. The stimulating signal from in vitro transmitted to in vivo is coupled by the coils in the transmission circuit. The passive structure in vivo was adopted to solve the problem that the traditional implantable devices need batteries. In addition, according to the situation of patients, doctors can effectively adjust the stimulation parameters in time by radio program control, in order to undertake personalized treatment.
学术讨论
主办单位时间地点报告人报告主题
射光所/生电国重联合课题组 2012.10.15 李文正楼四楼会议室 陶万军 膀胱刺激系统调研报告
射光所/生电国重联合课题组 2013.05.09 李文正楼南409 陶万军 膀胱功能控制电刺激系统设计方案讨论
射光所/生电国重联合课题组 2014.06.16 李文正楼四楼会议室 陶万军 清华大学李路明教授脑起搏器调研报告
射光所/生电国重联合课题组 2015.05.14 李文正楼四楼会议室 陶万军 Design of Nerve Stimulator Circuit for Controlling the Bladder Function
射光所 2016.08.29 李文正楼四楼会议室 Prof. Scheytt illimeter-Wave- and Electronic-Photonic System-on-Chip Design
射光所 2016.12.21 李文正楼南409 Tong Zhang Integrated Wideband Self-interference Cancellation Techniques for FDD, Full-duplex Wireless Communication
射光所/生电国重联合课题组 2017.04.21 李文正楼南409 陶万军 胃食管反流工作研究进展
射光所 2017.10.15 钟山宾馆三楼大会堂 杨守军 FMCW毫米波雷达产业化发展
     
学术会议
会议名称时间地点本人报告本人报告题目
IEEE EMBS协会 2015.4.22-24 法国蒙彼利埃 Effects of Different Configurations of Multi-contact Cuff Electrode on Recruitment Characteristics of Nerve Stimulation
中国生物医学工程学会 2015.10.16-19 中国南京 不同脉宽比和相间距脉冲对电刺激神经募集响应的影响
神经再生协同创新中心 2016.7.16-18 中国南通 植入式膀胱功能控制电刺激电路系统设计与研究
     
代表作
论文名称
Design of Integrated Neural Stimulating and Recording Frontend for Bladder Control Prosthesis
Effects of different configurations of multi-contact cuff electrode on recruitment characteristics
 
答辩委员会组成信息
姓名职称导师类别工作单位是否主席备注
郭宇锋 正高 教授 博导 南京邮电大学
乔庐峰 正高 教授 硕导 解放军理工大学
孟桥 正高 教授 博导 东南大学
李文渊 正高 教授 博导 东南大学
樊祥宁 正高 教授 博导 东南大学
      
答辩秘书信息
姓名职称工作单位备注
王科平 副高 副教授 东南大学