颅内血肿水肿的生物电阻抗检测技术及初步实验研究

发布时间：2018-04-29 22:38

本文选题：生物电阻抗 + 无创监测　；参考：《第四军医大学》2007年博士论文

【摘要】： 颅内疾病如脑出血、脑梗塞及各种原因引起的脑水肿,严重威胁患者的生命安全,具有较高的致残率和致死率,早诊断、早治疗是改善预后、降低致残致死率的关键。但是,目前还缺乏一种无创的辅助诊断技术与设备,用于对颅内血肿水肿进行早期、实时的监测。既往研究已表明,颅内血肿水肿时颅内组织的电阻抗将发生改变,显示出应用生物电阻抗测量技术检测颅内血肿水肿的研究价值和应用潜力。但由于颅骨的电阻率较高,在颅外只能无创检测到微弱的电阻抗变化,增加了检测的难度。目前国外的研究大都在开颅状态下进行动物实验,没有设计专门的电阻抗测量系统;虽然国内有研究者设计了一套测量系统,但是该系统采用两电极法测量电阻抗,电极皮肤接触阻抗对测量结果有较大影响。因此,在现有的研究基础上,克服电极皮肤接触阻抗的影响,提高测量系统的检测精度,并将其应用于颅内血肿水肿的监测,成为进一步研究的关键问题。本论文以应用无创生物电阻抗技术检测颅内血肿水肿为研究对象,在分析国内外研究现状的基础上,针对头部无创生物电阻抗检测技术中存在的关键问题,结合本课题组的实际情况与工作需要,主要进行了三方面的研究工作:通过仿真研究,提出了一种较为适用于头部电阻抗测量的电极配置方案;基于四电极电阻抗测量方法,设计了一套电阻抗测量系统;并应用该系统,进行了初步的动物和人体实验。具体包括: ○1 .对电极配置方案进行了软件仿真研究。设计了两种电极配置方案,方案一采用四电极法测量电阻抗,共有6个电极,将激励电极配置在头部正中线、两个通道的测量电极分别对称配置在激励电极的左右两侧;方案二采用两电极法测量电阻抗,共有4个电极,电极同时作为激励和测量电极,将这些电极对称配置在头部的左右两侧。软件仿真结果表明,方案一对测量区域内的电阻抗变化更为敏感;而且方案二采用两电极法测量电阻抗,受到电极-皮肤接触阻抗的影响较大,而方案一则采用四电极电阻抗测量法,可以减少电极皮肤接触阻抗的影响,所以本研究采用电极配置方案一,应用四电极法测量头部双侧的电阻抗。在软件仿真研究的基础上,还提出了两个数据分析指标,用于对颅内的电阻率扰动进行动态的分析和评估。 ○2 .针对目前已有设备采用两电极法测量电阻抗、受到接触阻抗影响较大这一问题,基于四电极电阻抗测量方法,设计了一套双通道的、具有较高测量精度的多频电阻抗测量系统。该系统具有以下的特性: 1)设计有两个测量通道,可以测量头部两侧的生物电阻抗; 2)采用直接数字频率合成技术设计激励信号源,采用正交数字解调技术解调生物电阻抗信息,提高了系统的测量精度; 3)激励信号工作频率可以在5~300kHz之间程控选择,激励电流强度可以在0~1mA之间程控选择; 4)在全部的工作频率范围内,系统的共模抑制比可以达到80dB以上; 5)整个系统集成在一个机箱内,实现了系统的一体化、小型化,便于移动和进行床旁检测,配合专门编写的应用软件,具备很强的实用性。 ○3 .使用设计的电阻抗测量系统,进行了初步的动物实验。实验动物采用家兔,主要进行了两种动物实验: 1)脑出血动物模型实验。使测量系统的两个测量通道分别测量动物头部左右两侧的、体表电极提取的电阻抗变化。采用自体血注入法制作脑出血动物模型,观察注入血液前后,头部两侧的电阻抗变化。结果表明,注入血液后,注血侧的电阻抗上升了大约0.91%,而对侧的电阻抗上升了大约0.45%。 2)脑水肿动物模型实验。使测量系统的两个测量通道分别测量动物头部左右两侧的电阻抗变化,使用固定在颅骨上的颅钉,作为测量电极。采用光化学诱导法制作脑梗塞动物模型,观察脑梗塞及随后的脑水肿过程中的电阻抗变化。可以观察到光照15分钟后,电阻抗开始升高,光照30分钟后停止,光照侧的电阻抗上升了大约1.5%,之后电阻抗持续上升,90分钟后光照侧的电阻抗上升了大约4%,对侧的电阻抗也呈现出上升的趋势,上升幅度大约是光照侧的一半。通过脑出血和脑水肿模型实验,表明颅内血肿水肿时,电阻抗呈现出上升的趋势,这就提示了应用本测量系统、无创检测颅内血肿水肿发展程度的可行性。 ○4 .使用设计的电阻抗测量系统,进行了初步的健康人体头部电阻抗测量实验。实验结果表明,该系统可以测量到健康人的头部电阻抗的变化。由于健康人不存在颅内血肿水肿等病变,所以没有直接观察到由颅内血肿水肿引起的电阻抗变化;但是,该系统可以检测到由人体的心脏跳动、深呼吸引起的微弱的头部电阻抗变化,为将该系统应用于颅内血肿水肿病人的临床检测打下了基础。本论文的主要特色与创新之处包括: 对电极配置方案进行了仿真研究,提出了一种较为适合于头部电阻抗测量的电极方案。基于四电极电阻抗测量方法,针对检测颅内血肿水肿的需要,研制了一套高性能、双通道多频电阻抗测量系统。并在设计过程中,提出了一种自动动态调整模拟放大倍数的方法,和校准电阻抗测量结果的方法。在软件仿真的基础上,提出了2个反映电阻率扰动的数据分析指标:总体变化指数和对称变化指数。经过初步的动物实验证实,可以使用这两个指标,依据相应的评判标准,对颅内血肿水肿的发展程度进行评估。本论文在软件仿真研究的基础上,提出了一种较为适合于头部电阻抗测量的电极配置方案和2个反映电阻率扰动的数据分析指标:总体变化指数和对称变化指数。基于四电极电阻抗测量方法,针对检测颅内血肿水肿的需要,研制了一套高性能、双通道多频电阻抗测量系统。初步的动物实验表明,可以应用本测量系统无创、灵敏的检测到颅内血肿水肿引起的电阻抗变化。在健康人体试验中,使用本系统可以观察到由人体的心脏跳动和深呼吸引起的电阻抗波动,表明无创生物电阻抗测量技术也可以应用于人体的头部电阻抗测量。本论文的研究成果为应用无创生物电阻抗技术监测颅内血肿水肿打下了坚实的基础。
[Abstract]:Intracranial diseases such as cerebral hemorrhage , cerebral infarction and cerebral edema caused by various causes seriously threaten the life safety of patients , have higher disability rate and death rate , early diagnosis , early treatment is the key to improve prognosis and reduce disability mortality . However , there is still a lack of noninvasive auxiliary diagnosis technique and equipment for early and real - time monitoring of intracranial hematoma edema .

Previous studies have shown that the electrical impedance of the intracranial tissues will change when the intracranial hematoma is edema , showing the research value and application potential of using bioelectrical impedance measurement technique to detect the edema of intracranial hematoma . However , because of the high resistivity of the skull , only slight changes in electrical impedance can be detected outside the skull , and the difficulty of detection is increased .

At present , most of the researches abroad are carried out in animal experiments under the open - cranial state , and no special electrical impedance measurement system is designed ; however , the system adopts two - electrode method to measure the electrical impedance , and the contact impedance of the electrode skin has a great influence on the measurement result .

Based on the analysis of the present situation of non - invasive bioelectrical impedance technology , the paper presents a kind of electrode configuration scheme which is suitable for the measurement of head electrical impedance . Based on the research of simulation , a kind of electrode configuration scheme is proposed , which is suitable for the measurement of head electrical impedance . Based on the four - electrode electrical impedance measurement method , a set of electrical impedance measurement system is designed , and the system is applied to carry out preliminary animal and human experiments .

1 . Two kinds of electrode configuration schemes are designed . Two kinds of electrode configuration schemes are designed . A four - electrode method is adopted to measure the electrical impedance . The two electrodes are symmetrically arranged on the left and right sides of the excitation electrode .

On the basis of software simulation research , two data analysis indexes are proposed for dynamic analysis and evaluation of the resistivity disturbance of intracranial .

02 . According to the four - electrode electrical impedance measurement method , a multi - frequency electric impedance measurement system with high measurement accuracy is designed aiming at the problem that the current device adopts two - electrode method to measure the electrical impedance , and a multi - frequency electric impedance measurement system with high measurement accuracy is designed based on the four - electrode electrical impedance measurement method .

1 ) two measuring channels are designed , and the bioelectrical impedance on two sides of the head can be measured ;

2 ) designing an excitation signal source by adopting a direct digital frequency synthesis technology , demodulating the bioelectrical impedance information by adopting an orthogonal digital demodulation technique , and improving the measurement accuracy of the system ;

3 ) the operating frequency of the excitation signal can be selected by programming between 5 and 300 kHz , and the excitation current intensity can be selected by programming between 0 and 1 mA ;

4 ) the common mode rejection ratio of the system can reach more than 80 dB in all operating frequency ranges ;

5 ) the whole system is integrated in one chassis , the integration of the system is realized , the miniaturization is realized , the mobile terminal is convenient to move and the bedside detection is carried out , the special writing application software is matched , and the system has strong practicability .

03 . A preliminary animal experiment was conducted using the designed electrical impedance measurement system . The experimental animals used rabbits , mainly two animal experiments :

1 ) Animal model of cerebral hemorrhage . Two measuring channels of the measuring system were used to measure the changes of electrical impedance of the body surface electrodes on the left and right sides of the animal ' s head . The changes of electrical impedance at both sides of the head were made by using autologous blood injection method . The results showed that the electrical impedance at the side of the head increased by about 0.91 % before and after the injection of blood , while the electrical impedance on the opposite side increased by about 0.45 % .

2 ) Animal model of cerebral edema . Two measuring channels of the measuring system were used to measure the changes of electrical impedance on the left and right sides of the animal ' s head . The electrical impedance of the cerebral infarction and the subsequent cerebral edema was observed . After 15 minutes of illumination , the electrical impedance of the illumination side increased by about 1.5 % . After 30 minutes of illumination , the electrical impedance of the light side increased by about 4 % . The electrical impedance on the opposite side also increased , and the rise was about half of the light side .

Through the experiment of cerebral hemorrhage and cerebral edema model , indicating that intracranial hematoma edema , the electrical impedance presents a rising trend , which suggests the feasibility of applying the measurement system and non - invasive detection of edema development degree of intracranial hematoma .

04 . The experimental results show that the system can measure the changes of the electrical impedance of the head of the healthy person . The results show that the system can measure the changes of the electrical impedance caused by the edema of the intracranial hematoma . However , the system can detect the changes of the electrical impedance of the head caused by the beating of the heart and deep breath of the human body , and the system can be used for the clinical detection of the patients with intracranial hematoma edema .

The main features and innovations of this thesis include :

The electrode configuration scheme is simulated and studied , and a kind of electrode scheme is proposed which is suitable for the measurement of the electrical impedance of the head .

Based on the four - electrode electrical impedance measurement method , a high - performance and dual - channel multi - frequency impedance measurement system is developed for the purpose of detecting the edema of intracranial hematoma . In the design process , a method for automatically dynamically adjusting the analog amplification factor and the method of calibrating the electrical impedance measurement result are presented .

On the basis of software simulation , two data analysis indexes reflecting the resistivity disturbance are presented : the general change index and the symmetry change index . After the preliminary animal experiment , the two indexes can be used , and the degree of development of intracranial hematoma edema can be evaluated according to the corresponding evaluation criteria .

Based on the research of software simulation , this paper presents an electrode configuration scheme and two data analysis indexes which reflect resistivity disturbance : general change index and symmetry change index . Based on the four - electrode electrical impedance measurement method , a set of high - performance and dual - channel multi - frequency electrical impedance measurement system is developed for detecting the edema of intracranial hematoma .

【学位授予单位】：第四军医大学
【学位级别】：博士
【学位授予年份】：2007
【分类号】：R35;R651.15

【引证文献】