基于FPGA的多通道视皮层电刺激器的设计
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摘要
随着医学与工程学的发展,基于功能性电刺激的人工视觉假体技术的研究及其成果为失明患者带来希望。人工视觉假体技术是将微电极阵列植入视觉通路中的某段神经处,电刺激器把视觉信息转换为电脉冲信号通过微电极阵列刺激相邻的神经节细胞,神经节细胞再将信息传入大脑,使患者感知到图像。各种视觉假体刺激的部位不同,但是基本功能是相同的,都需要将外界的光信号转换为可用的电流脉冲,通过微电极阵列刺激相关部位产生光幻视。电刺激器是视觉假体的关键部分,其功能是连接图像处理系统与刺激电极阵列,将图像信号转变为电流脉冲。
本文设计了一款应用于视皮层假体的多通道电刺激器,实现将图像编码信号转换为电流脉冲的功能。采用FPGA作为主控芯片,在FPGA内部设计了刺激脉冲发生器,多路选择器和串并转换器。刺激脉冲发生器通过对FPGA的系统时钟计数,能够产生各种形式的脉冲信号,输入到多路选择器的信号输入端。在74164宏功能函数的基础上增加触发器级数实现了32位的串/并转换功能,通过读取图像处理系统传入的图像编码信号并将其转换为并行信号,同时控制16个多路选择器,从而实现16个通道的信号转换。为了将FPGA输出的电压信号转换为电流信号,设计了外围电压/电流转换电路,外围转换电路由多个压控双向恒流源单元电路构成。经测试,本文所设计的电压/电流转换电路具较好的转换线性和恒流特性。在EP1C6核心板的基础上制作了十六通道电刺激器初级样机,利用十六通道电刺激器初级样机与图像处理系统搭建了视皮层假体系统初级样机,并进行了图像测试。测试结果表明,系统初级样机可以将获取到的图像信息进行相应的处理并转化为相应的电流脉冲,对于变换的图像信息能够作出及时的反应,达到了预期的目标。本文采用多通道刺激器的样机进行了动物验证实验。采用猫作为实验对象,在猫的视皮层硬脑膜外左右两侧植入微电极,左侧接入刺激信号,右侧记录脑电,实验结果显示,视皮层能够响应来自对硬脑膜的电刺激,验证了本文所设计的刺激器是可行的。
As the developing of medicine and engineering, artificial vision prosthesis based on functional electrical stimulation brings hopes to the blind. Artificial vision prosthesis technology implants a micro-electrode array in the visual pathway of certain nerve. An electrical stimulator is able to convert visual information into electronic pulses to stimulate the adjacent ganglion cells by micro-electrode array. Ganglion cells then pass the information the brain, so that patients can perceive the image. All visual prostheses have the same function: converting outside optical signal to certain current pulses and stimulating the relevant parts by the micro-electrode array to generated phosphenes. Electrical stimulator is to convert image information to current pulse in the vision prostheses.
This paper designed a multi-channel electrical stimulator for the visual cortex prosthesis to convert image information to stimulation current. It uses FPGA as its main control chip. The FPGA comprises a spike generator, a serial-to-parallel converter and some multiplexers. The spike generator can generate various forms of pulse signal by counting the system clock, and put them into the signal input end of all multiplexers. The 32 bits serial-to-parallel converter is realized by increasing the trigger progression of macro function 74164. Serial-to-parallel converter can read the coded image signals and convert them to parallel signals to control 16 multiplexers simultaneously. Then the FPGA converts image signals to electrical pulse. In order to convert the output voltage signals to current signals, we designed peripheral conversion circuit. The peripheral conversion circuit contains some voltage-controlled bidirectional constant current source units. These voltage / current conversion circuits show good linearity and constant-current characteristics of conversion in testing. We made an initial prototype of 16-channel electrical stimulator based on the EP1C6 kernel board. And a system initial prototype of visual cortex prosthesis is made by the initial prototype of 16-channel electrical stimulator and an image process system. Result of testing shows that the system initial prototype can process image information correspondingly and convert image information to corresponding current pulse. And the prototype can make timely responses to the transformation of the image information. We performed the experimental evaluation by the initial prototype of 16-channel electrical stimulator. Put two electrode chips out of the left and right dura of cortex of a cat. Electrical stimulation was connected to the left one. Record the visual electrically evoked potential (EEP) by the right one. The results of experiment on cat’s cortex show that the cortex can respond to the current stimulation, and the initial prototype is feasible.
本文设计了一款应用于视皮层假体的多通道电刺激器,实现将图像编码信号转换为电流脉冲的功能。采用FPGA作为主控芯片,在FPGA内部设计了刺激脉冲发生器,多路选择器和串并转换器。刺激脉冲发生器通过对FPGA的系统时钟计数,能够产生各种形式的脉冲信号,输入到多路选择器的信号输入端。在74164宏功能函数的基础上增加触发器级数实现了32位的串/并转换功能,通过读取图像处理系统传入的图像编码信号并将其转换为并行信号,同时控制16个多路选择器,从而实现16个通道的信号转换。为了将FPGA输出的电压信号转换为电流信号,设计了外围电压/电流转换电路,外围转换电路由多个压控双向恒流源单元电路构成。经测试,本文所设计的电压/电流转换电路具较好的转换线性和恒流特性。在EP1C6核心板的基础上制作了十六通道电刺激器初级样机,利用十六通道电刺激器初级样机与图像处理系统搭建了视皮层假体系统初级样机,并进行了图像测试。测试结果表明,系统初级样机可以将获取到的图像信息进行相应的处理并转化为相应的电流脉冲,对于变换的图像信息能够作出及时的反应,达到了预期的目标。本文采用多通道刺激器的样机进行了动物验证实验。采用猫作为实验对象,在猫的视皮层硬脑膜外左右两侧植入微电极,左侧接入刺激信号,右侧记录脑电,实验结果显示,视皮层能够响应来自对硬脑膜的电刺激,验证了本文所设计的刺激器是可行的。
As the developing of medicine and engineering, artificial vision prosthesis based on functional electrical stimulation brings hopes to the blind. Artificial vision prosthesis technology implants a micro-electrode array in the visual pathway of certain nerve. An electrical stimulator is able to convert visual information into electronic pulses to stimulate the adjacent ganglion cells by micro-electrode array. Ganglion cells then pass the information the brain, so that patients can perceive the image. All visual prostheses have the same function: converting outside optical signal to certain current pulses and stimulating the relevant parts by the micro-electrode array to generated phosphenes. Electrical stimulator is to convert image information to current pulse in the vision prostheses.
This paper designed a multi-channel electrical stimulator for the visual cortex prosthesis to convert image information to stimulation current. It uses FPGA as its main control chip. The FPGA comprises a spike generator, a serial-to-parallel converter and some multiplexers. The spike generator can generate various forms of pulse signal by counting the system clock, and put them into the signal input end of all multiplexers. The 32 bits serial-to-parallel converter is realized by increasing the trigger progression of macro function 74164. Serial-to-parallel converter can read the coded image signals and convert them to parallel signals to control 16 multiplexers simultaneously. Then the FPGA converts image signals to electrical pulse. In order to convert the output voltage signals to current signals, we designed peripheral conversion circuit. The peripheral conversion circuit contains some voltage-controlled bidirectional constant current source units. These voltage / current conversion circuits show good linearity and constant-current characteristics of conversion in testing. We made an initial prototype of 16-channel electrical stimulator based on the EP1C6 kernel board. And a system initial prototype of visual cortex prosthesis is made by the initial prototype of 16-channel electrical stimulator and an image process system. Result of testing shows that the system initial prototype can process image information correspondingly and convert image information to corresponding current pulse. And the prototype can make timely responses to the transformation of the image information. We performed the experimental evaluation by the initial prototype of 16-channel electrical stimulator. Put two electrode chips out of the left and right dura of cortex of a cat. Electrical stimulation was connected to the left one. Record the visual electrically evoked potential (EEP) by the right one. The results of experiment on cat’s cortex show that the cortex can respond to the current stimulation, and the initial prototype is feasible.
引文
[1]张文斌,黄世建,单藕琦等.我国眼病患者调查与统计分析[J].中国卫生统计. 2002. 19(1).
[2]姚泰,吴博威.生理学[M].北京:人民卫生出版社, 2005:246.
[3]邵轶彬.基于有限元分析方法的视觉假体微电极阵列的设计与测试[D].上海:上海交通大学,2009.
[4]袁启明,功能性电刺激装置及其临床应用前景[J].上海生物医学工程.1997.18(1):52-54.
[5] Foerster O. Beitrage zur Pathophysiologie der Sehbahn und der Spehsphare [J]. J Psychol Neurol, 1929, 39: 435-463.
[6] Button J, Putnam T: Visual responses to cortical stimulation in the blind [J]. Iowa St Med Soc, 1962, 52:17–21.
[7] Brindley G S, Lewin W S. The visual sensations produced by electrical stimulation of the medial occipital cortex [J]. Physiol, 1968, 194:54–55.
[8] Brindley G, Rushton D. Implanted stimulators of the visual cortex as visual prosthetic devices [J]. Trans Am Acad Ophthalmol Otolaryngol, 1974, 78:741–745.
[9] Schmidt E M, Bak M J, Hambrecht F T, et al. Feasibility of a visual prosthesis for the blind based on intracortical microstimulation of the visual cortex [J]. Brain, 1996, 119:507–522.
[10] Bak M, Girvin J P, Hambrecht F T, et al. Visual sensations produced by intracortical microstimulation of the human occipital cortex [J]. Med Biol Eng Comput, 1990, 28:257–259.
[11] Richard A. Normann.“Visual Neuroprosthetics Functional Vision for the Blind”[J], IEEE ENGINEERING IN MEDICINE AND BIOLOGY 0739.51 75/95/1995.
[12] Merabet LB, Rizzo JF, Amedi A, et al. What blindness can tell us about seeing again: Merging neuroplasticity and neuroprostheses [J]. Nature Reviews Neuroscience. 2005, 6: 71-77.
[13]邓亲恺,现代医学仪器设计原理[M],北京:科学出版社,2004:433.
[14]桂福如,电刺激在医疗中的应用与展望[J].中国医疗器械信息,1996,2(1):9-11.
[15]秦明新,王宏山等,可编程刺激器[J].中国医疗器械杂志,1991.15(1):9-12.
[16]谢翔.张春.王志华.微电子技术在生物医学中的应用与发展[J].电路与系统学报.2003,8(2):80-83.
[17]冯正权,植入式神经肌肉电刺激器的电路研究[D],重庆大学,光电工程学院,2007.
[18]柯江华,杨光.人工电子耳蜗[J].科学, 2003, 8:76-77.
[19]王洪良,视觉假体微电流刺激器控制及反馈系统的研究[D].上海交通大学,生命科学技术学院.2009.
[20] Liu Wentai, Sankar Mohana, etc. Implantable Biomimetic Microelectronic [J]. Engineering inMedicine and Biology Magazine, IEEE. 2005, 24(5):66–74.
[21] Weiland J D, Humayun M S. A biomimetic retinal stimulating array [J]. Biomimetic systems, 2005, 9 :14-21.
[22] Eckmiller R. Learning retina implants with epiretinal contacts [J]. Ophthalmic Res , 1997, 29:281–289.
[23] Li L, Hayashida Y, Yagi T. Temporal properties of retinal ganglion cell responses to local transretinal current stimuli in the frog retina [J]. Vision research, 2005, 45(2): 263-273.
[24] Chow A Y, Chow V Y. Subretinal electrical stimulation of the rabbit retina [J]. Neurosci Lett, 1997, 225:13-16.
[25] Chow AY, Peyman GA, Pulido J. Safety and feasibility of subretinal Artificial Silicon Retina (TM) retinal prosthesis for the treatment of patients with retinitis pigmentosa [J]. Investigative Ophthalmology & Visual Science, 2001, 42(4): 5042
[26] Gekeler F, Zrenner E. Status of the subretinal implant project-an overview [J]. Ophthalmologe, 2005, 102 (10): 941.
[27]周业,牛金海,刘易非,等.视觉功能修复方法[J].中国生物医学工程学报, 2008, 27(4):615-620.
[28] Veraart C, Wanet-Defalque MC, Gérard B, et al. Pattern recognition with the optic nerve visual prosthesis [J]. Artificial Organs, 2003, 27(11): 996-1004.
[29] De Michele G.A., Troyk P.R., Integrated Multi-Channel Wireless Biotelemetry System [A]. Proceeding of the 25th Annual International Conference of the IEEE EMBS, Cancun, Mexico, 2003, 17–21:3372–3375.
[30] Rousche P J, Normann R A. Chronic recording capability of the uath intracortical electrode array in cat sensory cortex [J]. Journal of neuroscience methods. 1998, 82: 1-15.
[31] Normann R A, Maynard E M, Rousche P J, et al. A neural interface for a cortical vision prosthesis [J]. Vision Res, 1999, 39:2577–2587.
[32] Christian M, Samuel R, Antonio M, et al. A neuroengineering suite of computational tools for visual prosthesis [J]. Neurocomputing, 2007, 70: 2817-2827.
[33] Chowdhury V, Morley JW, Coroneo MT. Surface stimulation of the brain with a prototype array for a visual cortex prosthesis [J]. Journal of Clinical Neuroscience, 2004, 11(7): 750-755.
[34] Dobelle WH. Artificial Vision for the Blind by Connecting a Television Camera to the Visual Cortex [J]. ASAIO Journal, 2000, 46(1): 3-9.
[35] [B/OL]http://en.wikipedia.org/wiki/Brodmann_area.
[36] [B/OL]http://en.wikipedia.org/wiki/Cerebral_cortex.
[37] [B/OL]http://thebrain.mcgill.ca/flash/a/a_02/a_02_cl/a_02_cl_vis/a_02_cl_vis.html.
[38]周扬,王健.视皮层分区及其fMRI研究进展[J].现代生物医学进展, 2006, 6(9): 79-81.
[39]牛金海,刘易非,任秋实,等.视觉假体:带给盲人光明的电子设备[J].中国科学( E辑:信息科学). 2007, 37(10): 1354-1362.
[40]吕国蔚,神经电刺激的方法学问题[J].生理科学, 1986,6(2):78-84.
[41]郭冰冰,侯文生,阴正勤,等.一种经硬脑膜的多通道视觉诱发电位实验测试系统的设计[J].仪器仪表学报, 2009, 30(6)增刊: 204-207.
[42] Mesut S, Yanmei T. Non-rectangular waveforms for neural stimulation with practical electrodes [J]. Neural engineering, 2007, 4:227-233.
[43] Schmidt E M, Bak M J, Hambrecht F T, et al. Feasibility of a visual prosthesis for the blind based on intracortical microstimulation of the visual cortex [J]. Brain, 1996, 119:507–522.
[44]夏露,一种经硬脑膜的视皮层电刺激装置的设计与实验研究[D].重庆大学:生物工程学院, 2009.
[45]杨华,基于FPGA的实时图像采集与处理系统研究[D].长春理工大学,2009.
[46]王诚,吴继华,范丽珍,薛宁. Altera FPGA/ CPLD设计[M].人民邮电出版社,2005.
[47]朱永强,王辉林,仪垂杰.可编程逻辑器件及其在DSP系统中的应用[J].山东工程学院学报,2002,16(2):38-41.
[2]姚泰,吴博威.生理学[M].北京:人民卫生出版社, 2005:246.
[3]邵轶彬.基于有限元分析方法的视觉假体微电极阵列的设计与测试[D].上海:上海交通大学,2009.
[4]袁启明,功能性电刺激装置及其临床应用前景[J].上海生物医学工程.1997.18(1):52-54.
[5] Foerster O. Beitrage zur Pathophysiologie der Sehbahn und der Spehsphare [J]. J Psychol Neurol, 1929, 39: 435-463.
[6] Button J, Putnam T: Visual responses to cortical stimulation in the blind [J]. Iowa St Med Soc, 1962, 52:17–21.
[7] Brindley G S, Lewin W S. The visual sensations produced by electrical stimulation of the medial occipital cortex [J]. Physiol, 1968, 194:54–55.
[8] Brindley G, Rushton D. Implanted stimulators of the visual cortex as visual prosthetic devices [J]. Trans Am Acad Ophthalmol Otolaryngol, 1974, 78:741–745.
[9] Schmidt E M, Bak M J, Hambrecht F T, et al. Feasibility of a visual prosthesis for the blind based on intracortical microstimulation of the visual cortex [J]. Brain, 1996, 119:507–522.
[10] Bak M, Girvin J P, Hambrecht F T, et al. Visual sensations produced by intracortical microstimulation of the human occipital cortex [J]. Med Biol Eng Comput, 1990, 28:257–259.
[11] Richard A. Normann.“Visual Neuroprosthetics Functional Vision for the Blind”[J], IEEE ENGINEERING IN MEDICINE AND BIOLOGY 0739.51 75/95/1995.
[12] Merabet LB, Rizzo JF, Amedi A, et al. What blindness can tell us about seeing again: Merging neuroplasticity and neuroprostheses [J]. Nature Reviews Neuroscience. 2005, 6: 71-77.
[13]邓亲恺,现代医学仪器设计原理[M],北京:科学出版社,2004:433.
[14]桂福如,电刺激在医疗中的应用与展望[J].中国医疗器械信息,1996,2(1):9-11.
[15]秦明新,王宏山等,可编程刺激器[J].中国医疗器械杂志,1991.15(1):9-12.
[16]谢翔.张春.王志华.微电子技术在生物医学中的应用与发展[J].电路与系统学报.2003,8(2):80-83.
[17]冯正权,植入式神经肌肉电刺激器的电路研究[D],重庆大学,光电工程学院,2007.
[18]柯江华,杨光.人工电子耳蜗[J].科学, 2003, 8:76-77.
[19]王洪良,视觉假体微电流刺激器控制及反馈系统的研究[D].上海交通大学,生命科学技术学院.2009.
[20] Liu Wentai, Sankar Mohana, etc. Implantable Biomimetic Microelectronic [J]. Engineering inMedicine and Biology Magazine, IEEE. 2005, 24(5):66–74.
[21] Weiland J D, Humayun M S. A biomimetic retinal stimulating array [J]. Biomimetic systems, 2005, 9 :14-21.
[22] Eckmiller R. Learning retina implants with epiretinal contacts [J]. Ophthalmic Res , 1997, 29:281–289.
[23] Li L, Hayashida Y, Yagi T. Temporal properties of retinal ganglion cell responses to local transretinal current stimuli in the frog retina [J]. Vision research, 2005, 45(2): 263-273.
[24] Chow A Y, Chow V Y. Subretinal electrical stimulation of the rabbit retina [J]. Neurosci Lett, 1997, 225:13-16.
[25] Chow AY, Peyman GA, Pulido J. Safety and feasibility of subretinal Artificial Silicon Retina (TM) retinal prosthesis for the treatment of patients with retinitis pigmentosa [J]. Investigative Ophthalmology & Visual Science, 2001, 42(4): 5042
[26] Gekeler F, Zrenner E. Status of the subretinal implant project-an overview [J]. Ophthalmologe, 2005, 102 (10): 941.
[27]周业,牛金海,刘易非,等.视觉功能修复方法[J].中国生物医学工程学报, 2008, 27(4):615-620.
[28] Veraart C, Wanet-Defalque MC, Gérard B, et al. Pattern recognition with the optic nerve visual prosthesis [J]. Artificial Organs, 2003, 27(11): 996-1004.
[29] De Michele G.A., Troyk P.R., Integrated Multi-Channel Wireless Biotelemetry System [A]. Proceeding of the 25th Annual International Conference of the IEEE EMBS, Cancun, Mexico, 2003, 17–21:3372–3375.
[30] Rousche P J, Normann R A. Chronic recording capability of the uath intracortical electrode array in cat sensory cortex [J]. Journal of neuroscience methods. 1998, 82: 1-15.
[31] Normann R A, Maynard E M, Rousche P J, et al. A neural interface for a cortical vision prosthesis [J]. Vision Res, 1999, 39:2577–2587.
[32] Christian M, Samuel R, Antonio M, et al. A neuroengineering suite of computational tools for visual prosthesis [J]. Neurocomputing, 2007, 70: 2817-2827.
[33] Chowdhury V, Morley JW, Coroneo MT. Surface stimulation of the brain with a prototype array for a visual cortex prosthesis [J]. Journal of Clinical Neuroscience, 2004, 11(7): 750-755.
[34] Dobelle WH. Artificial Vision for the Blind by Connecting a Television Camera to the Visual Cortex [J]. ASAIO Journal, 2000, 46(1): 3-9.
[35] [B/OL]http://en.wikipedia.org/wiki/Brodmann_area.
[36] [B/OL]http://en.wikipedia.org/wiki/Cerebral_cortex.
[37] [B/OL]http://thebrain.mcgill.ca/flash/a/a_02/a_02_cl/a_02_cl_vis/a_02_cl_vis.html.
[38]周扬,王健.视皮层分区及其fMRI研究进展[J].现代生物医学进展, 2006, 6(9): 79-81.
[39]牛金海,刘易非,任秋实,等.视觉假体:带给盲人光明的电子设备[J].中国科学( E辑:信息科学). 2007, 37(10): 1354-1362.
[40]吕国蔚,神经电刺激的方法学问题[J].生理科学, 1986,6(2):78-84.
[41]郭冰冰,侯文生,阴正勤,等.一种经硬脑膜的多通道视觉诱发电位实验测试系统的设计[J].仪器仪表学报, 2009, 30(6)增刊: 204-207.
[42] Mesut S, Yanmei T. Non-rectangular waveforms for neural stimulation with practical electrodes [J]. Neural engineering, 2007, 4:227-233.
[43] Schmidt E M, Bak M J, Hambrecht F T, et al. Feasibility of a visual prosthesis for the blind based on intracortical microstimulation of the visual cortex [J]. Brain, 1996, 119:507–522.
[44]夏露,一种经硬脑膜的视皮层电刺激装置的设计与实验研究[D].重庆大学:生物工程学院, 2009.
[45]杨华,基于FPGA的实时图像采集与处理系统研究[D].长春理工大学,2009.
[46]王诚,吴继华,范丽珍,薛宁. Altera FPGA/ CPLD设计[M].人民邮电出版社,2005.
[47]朱永强,王辉林,仪垂杰.可编程逻辑器件及其在DSP系统中的应用[J].山东工程学院学报,2002,16(2):38-41.