本文選題：視神經(jīng)假體　切入點(diǎn)：Oozeer視神經(jīng)纖維模型　出處：《天津醫(yī)科大學(xué)》2012年碩士論文

【摘要】：研究目的： 電極刺激視神經(jīng)是用于恢復(fù)盲人視覺的一種實(shí)現(xiàn)方式。利用這種方式形成的視覺假體稱為視神經(jīng)假體。為了了解電極刺激視神經(jīng)的作用機(jī)制,設(shè)計(jì)視神經(jīng)假體和指導(dǎo)視神經(jīng)假體臨床應(yīng)用,Oozeer等人根據(jù)文獻(xiàn)中視神經(jīng)生理參數(shù)提出了一種視神經(jīng)模型來模擬哺乳動(dòng)物視神經(jīng)動(dòng)作電位變化,稱為Oozeer視神經(jīng)纖維模型。本文以MATLAB為平臺(tái),研究了Oozeer視神經(jīng)纖維模型在不同刺激下視神經(jīng)纖維離子通道特性和膜特性,和在圓柱形視神經(jīng)容積導(dǎo)體模型內(nèi)刺激參數(shù)對(duì)Oozeer視神經(jīng)纖維模型響應(yīng)的影響,為視神經(jīng)假體的設(shè)計(jì)和臨床應(yīng)用提供一種計(jì)算支持。 研究方法： 1.基于Oozeer視神經(jīng)纖維模型的離子通道特性分析 (1)膜離子通道特性分析。分析模型在外加刺激下的動(dòng)作電位響應(yīng),分析模型被激活時(shí)膜離子通道隨時(shí)間響應(yīng)。 (2)相平面分析。使用相圖法探討視神經(jīng)纖維動(dòng)作電位變化規(guī)律,觀察整個(gè)動(dòng)作電位階段的動(dòng)態(tài)變化。 (3)強(qiáng)度—時(shí)間曲線的研究。分析整個(gè)模型在胞外電刺激下的電流-時(shí)間關(guān)系。 2.胞外電刺激下視神經(jīng)纖維模型的響應(yīng)的仿真 (1)建立一個(gè)視神經(jīng)導(dǎo)體模型,計(jì)算出在刺入式電極刺激下,視神經(jīng)內(nèi)各處電勢(shì)分布,利用建立的視神經(jīng)纖維模型計(jì)算不同深度纖維的刺激閾值,分析Oozeer視神經(jīng)纖維模型在視神經(jīng)導(dǎo)體內(nèi)的響應(yīng)。 (2)用激活函數(shù)和組織激活區(qū)來表征外加刺激的作用于視神經(jīng)的效果。 (3)分析纖維的直徑對(duì)刺激效果的影響。 (4)分析刺激脈沖參數(shù)對(duì)刺激效果的影響。 研究結(jié)果： 1.刺激下視神經(jīng)纖離子通道特性 (1)四種離子通道：速鈉離子(INa)、快速鉀離子(IK)、慢鉀離子(Is)和持續(xù)鈉離子(Ip)在動(dòng)作電位的形成過程中作用階段和大小各不相同,對(duì)動(dòng)作電位的形成所起作用不也同。 (2)相圖法分析動(dòng)作電位的動(dòng)態(tài)變化可知,不同強(qiáng)度閾上刺激,視神經(jīng)纖維上產(chǎn)生的動(dòng)作電位發(fā)放時(shí)間不同,動(dòng)作電位能沿軸突無衰減傳播,單個(gè)動(dòng)作電位持續(xù)時(shí)間無明顯變化。 (3)由模型強(qiáng)度-時(shí)間曲線可知,當(dāng)時(shí)間t足夠大時(shí),激活纖維所需電流強(qiáng)度不再改變,脈沖持續(xù)時(shí)間短于時(shí)值時(shí)斜率漸漸接近1/τ,與動(dòng)物實(shí)驗(yàn)中所測(cè)量得到強(qiáng)度-時(shí)間關(guān)系一致。Oozeer視神經(jīng)纖維模型穩(wěn)定,能夠正確反映胞外電刺激視神經(jīng)纖維的電流-時(shí)間關(guān)系。 2.胞外電刺激對(duì)視神經(jīng)纖維作用效應(yīng) (1)激活距離電極0.2mm處纖維,刺入式電極刺激閾值為14gA,比袖套電極激活同一距離纖維閾值要小得多。處于容積導(dǎo)體內(nèi)部視的神經(jīng)纖維,電極-纖維距離由0.2mm逐步增加到1.5mm過程中,纖維刺激閾值由14μA增加至0260μA。 (2)纖維直徑由1μm逐步增加到6μm,深度為0.5mm處纖維刺激閾值由36μA減小至24μA,；深度為1mm纖維刺激閾值由104gA減小至52μA。直徑由1μm增加到2μm時(shí),刺激閾值減小程度最大。 (3)將單相矩形波脈寬從0.1ms逐步增加到1.0ms,深度為0.5mm纖維刺激閾值由45gA減小至34gA；深度為1.0mm纖維刺激閾值由166gA減小至104A。0.1ms增加到0.2ms時(shí),刺激閾值的減小程度最大 結(jié)論： 1.仿真結(jié)果表明,所建立的視神經(jīng)纖維模型能正確反映視神經(jīng)纖維被胞外刺激激活的動(dòng)作電位特性,在動(dòng)作電位的過程中各個(gè)離子通道作用時(shí)間不同,對(duì)動(dòng)作電位形成的影響也不同。 2.相平面分析表明,閾上不同強(qiáng)度的刺激電流刺激下,Oozeer視神經(jīng)纖維模型放電時(shí)間不同,動(dòng)作電位在各個(gè)階段的變化速度不同。 3.Oozeer視神經(jīng)纖維模型的強(qiáng)度-時(shí)間曲線表明,胞外刺激下模型的強(qiáng)度-時(shí)間曲線與胞內(nèi)刺激不同,Oozeer視神經(jīng)纖維模型的電流-時(shí)間關(guān)系與實(shí)驗(yàn)所得的結(jié)論一致。 4.容積導(dǎo)體內(nèi)纖維能被刺入式電極施加的電流刺激成功激活,并比袖套電極有更小的激活閾值。容積導(dǎo)體內(nèi)不同位置上的視神經(jīng)纖維具有不同的刺激閾值,距離電極越遠(yuǎn)的電極刺激閾值越大。 5.不同直徑的纖維具有不同的刺激閾值,纖維直徑越大,視神經(jīng)纖維刺激閾值越小 6.改變刺激脈沖的脈寬和強(qiáng)度能產(chǎn)生不同的激活效應(yīng)。纖維的位置、直徑、刺激脈沖的寬度和強(qiáng)度等,可以成為實(shí)現(xiàn)視神經(jīng)選擇性激活重要參考量。所得結(jié)論對(duì)以后視神經(jīng)選擇性刺激實(shí)驗(yàn)以及基于視神經(jīng)刺激的視覺假體的研究具有一定的指導(dǎo)意義。
[Abstract]:The purpose of the study is:
Electrical stimulation of the optic nerve is a method for restoring the vision of the blind. Visual prosthesis by this way is called optic nerve prosthesis. In order to understand the mechanism of stimulation of the optic nerve, optic nerve prosthesis design and clinical application of optic nerve prosthesis guidance, Oozeer et al. According to the literature in neural physiological parameters, proposes a simulation the mammalian optic nerve in the optic nerve action potential model was called Oozeer optic nerve fiber model. Using MATLAB as a platform to study Oozeer optic nerve fiber model of optic nerve fiber ion channel characteristics and membrane characteristics under different stimulation, and in a cylindrical volume conductor model of optic nerve stimulation parameters on Oozeer nerve fiber model response the calculation provides a support for the design and clinical application of optic nerve prosthesis.
Research methods:
1. analysis of ion channel characteristics based on Oozeer optic nerve fiber model
(1) analysis of membrane ion channel characteristics. The action potential response of the model under external stimulation is analyzed. The response of the membrane ion channel to time is analyzed when the model is activated.
(2) phase plane analysis. The changes in the action potential of optic nerve fibers were studied by phase diagram method, and the dynamic changes of the whole action potential stage were observed.
(3) the study of the intensity time curve and the analysis of the current time relation of the whole model under the exo electric stimulation.
Simulation of the response of the optic nerve fiber model under 2. extracellular electrical stimulation
(1) establish a model of optic nerve conductors, calculate the potential distribution in the optic nerve under the stimulation of puncture electrodes, calculate the threshold of different depths of fiber using the established optic nerve fiber model, and analyze the echo of Oozeer optic nerve fiber in the optic nerve conductor.
(2) use the activation function and the tissue activation area to characterize the effect of external stimulation on the optic nerve.
(3) the influence of the diameter of the fiber on the stimulation effect is analyzed.
(4) the effect of stimulation pulse parameters on the stimulation effect is analyzed.
The results of the study:
Properties of optic fiber ion channel under 1. stimulation
(1) four kinds of ion channels: fast sodium ion (INa), fast potassium ion (IK), slow potassium ion (Is) and continuous sodium ion (Ip), which act differently in the formation of action potential, and play a similar role in the formation of action potential.
(2) the dynamic change of action potential is analyzed by phase diagram method. We can see that different intensity suprathreshold stimulation can produce different action potential time on optic nerve fiber, action potential can propagate along axons, and there is no significant change in duration of single action potential.
(3) by the time intensity curve model shows that when t is large enough, the activation of fiber required current intensity does not change, the pulse duration is shorter than the slope gradually close to 1/ and tau, the measured intensity in animal experiment time consistent.Oozeer optic nerve fiber model is stable, it can correctly reflect the cell stimulation of optic nerve fiber current time relationship.
Effect of 2. extracellular electrical stimulation on optic nerve fiber
(1) the activation of 0.2mm fiber electrode distance, penetrating electrode stimulation threshold is 14gA, the same distance is much smaller than the threshold fiber cuff electrode activation. In optic nerve fibers of the inner conductor and the electrode fiber distance by 0.2mm gradually increased to 1.5mm in the process of fiber stimulation threshold by 14. A increased to 0260 A.
(2) the fiber diameter increased gradually from 1 m to 6 m, at a depth of 0.5mm fiber stimulation threshold by 36. A reduced to 24 A, depth of 1mm; fiber stimulation threshold is reduced from 104gA to 52 A. diameter increased from 1 m to 2 m, the largest decrease of stimulus threshold.
(3) the single phase square wave pulse width increased from 0.1ms to 1.0ms, and the depth of 0.5mm fiber decreased from 45gA to 34gA. When the depth of 1.0mm fiber was reduced from 166gA to 104A.0.1ms to 0.2ms, the threshold of stimulation decreased to a maximum.
Conclusion:
1. simulation results show that the established optic nerve fiber model can correctly reflect the action potential characteristics of optic nerve fiber stimulated by extracellular stimuli, and the action time of each ion channel is different during action potential, and the effect on action potential is also different.
The 2. phase plane analysis showed that when the threshold intensity was stimulated by different stimuli, the Oozeer optic nerve fiber model had different discharge time and the action potential varied at different stages.
The intensity time curve of 3.Oozeer optic nerve fiber model shows that the intensity time curve of extracellular stimulus is different from that of intracellular stimulation. The current time relationship of Oozeer optic nerve fiber model is consistent with the experimental conclusion.
The 4. volume conductor fiber current stimulation electrode piercing applied successfully activated, and cuff electrodes have smaller activation threshold. The volume conductor in different positions on the optic nerve fibers with different stimulation threshold, electrode electrode distance farther stimulation threshold more.
5. the fibers with different diameters have different stimulation thresholds. The greater the diameter of the fibers, the smaller the threshold of the optic nerve fibers is.
The pulse width and intensity change of 6. stimulus pulse can produce different activation effects. The position of the fiber, diameter, pulse width and intensity, can become the optic nerve selective activation of an important reference. The conclusion of the optic nerve after selective stimulation experiment and has guiding significance to the study of visual prosthesis based on optic nerve stimulation.

【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R318.0

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本文編號(hào)：1726086