第六讲 遗传病和人类基因组计划.ppt

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1、Session 4 Biosignal Processing 1.Introduction 2.Physiological Origins of Biosignals 3.Characteristics of Biosignals 4.Signal Acquisition 5.Frequency Domain Representation of Biosignals 1.Introduction Biosignal are space,time,or space-time records of a biological event such as a beating heart or a co

2、ntracting muscle.The electrical,chemical,and mechanical activity that occurs during this biological event often produces signals that can be measured and analyzed.Biosignals,therefore,contain information that can be used to explain the underlying physiological mechanisms of a specific biological eve

3、nt or system.Biosignals must be analyzed to retrieve the most relevant information from them.The basic methods of signal analysis,e.g.,amplification,filtering,digitization,processing,and storage,can be applied to many biosignals.Other signal processing methods include signal averaging,wavelet analys

4、is,and artificial intelligence techniques.2.Physiological Origins of Biosignals（1）Bioelectric Signals Nerve and muscle cells generate bioelectric signals that are the result of electrochemical changes within and between cells.If a nerve or muscle cell is stimulated by a stimulus that is strong enoug

5、h to reach a necessary threshold,the cell will generate an action potential.The action potential represents the flow of ions across the cell membrane and can be transmitted from one cell to adjacent cells.When many cells become excited,an electric field is generated and propagates through the biolog

6、ical medium.Changes in extracellular potential can be measured on the surface of the organ by using surface electrodes.(ECG,EEG,EMG)（2）Biomagnetic Signals Different organs,including the heart,brain,and lungs,generate magnetic fields that are weak compared to other events as electrical changes occur

7、in them.Biomagnetism is the measurement of the magnetic signals that are associated with specific physiological activity.Biomagnetic signals therefore can provide valuable additional information that is not usually contained in bioelectric signals.Furthermore,they can be used to obtain additional in

8、formation about intracellular activity.心磁图仪心磁图仪1.1.概述概述 心磁图（心磁图（Magnetocardiogram，MCG）是是低温超导与计算机技术相结合，以超导量子介低温超导与计算机技术相结合，以超导量子介入装置为探头，对心动周期中心脏电活动引起入装置为探头，对心动周期中心脏电活动引起的微小磁场进行测定的一项新型心脏无创伤性的微小磁场进行测定的一项新型心脏无创伤性检查。检查。与与ECG相比，相比，MCG具备以下特点：具备以下特点：信号高度保真。信号高度保真。心脏与体表心电图电极间的电心脏与体表心电图电极间的电场需通过几个不同的介质边界，它们每一

9、个都场需通过几个不同的介质边界，它们每一个都有不同的传导性和其他的电特性。有不同的传导性和其他的电特性。由于心脏产生电场的边界歪曲，心电电极由于心脏产生电场的边界歪曲，心电电极记录的电场特点与心脏产生的电场是不同的。记录的电场特点与心脏产生的电场是不同的。界面对磁场不产生太大歪曲，界面对磁场不产生太大歪曲，MCG资料因资料因此可提供更准确的心脏活动信息。此可提供更准确的心脏活动信息。对局部心肌电流高度敏感。对局部心肌电流高度敏感。MCG有更高的空有更高的空间分辨率，与间分辨率，与ECG相比，相比，MCG对局部电流有对局部电流有更高的空间敏感性。更高的空间敏感性。这些局部电流微弱，来自心肌边界，

10、有不这些局部电流微弱，来自心肌边界，有不同的电生理特点，即每个都有不同的动作电位同的电生理特点，即每个都有不同的动作电位间期。在磁场中，这些电流比在电场中反映得间期。在磁场中，这些电流比在电场中反映得更清晰。更清晰。2 2.心磁图测量原理心磁图测量原理（1 1）测量原理）测量原理 生物磁信号与生物电信号相比更为微弱，例生物磁信号与生物电信号相比更为微弱，例如心脏周围的磁场约为如心脏周围的磁场约为51011特斯拉（特斯拉（T），），心心磁图（磁图（MCG）的最大幅值为的最大幅值为1010特斯拉（特斯拉（T），），比地球磁场小一百万倍（地球磁场为比地球磁场小一百万倍（地球磁场为104 T量级）量级

11、），比城市的环境磁噪声（，比城市的环境磁噪声（107 T量级）小一万倍量级）小一万倍左右。左右。脑磁图（脑磁图（MEG）的信号更为微弱，在的信号更为微弱，在1012T量级，因此要采用磁通门来测量生物磁，尤其是量级，因此要采用磁通门来测量生物磁，尤其是心磁图及脑磁图等微弱信号是不可能的。心磁图及脑磁图等微弱信号是不可能的。在强的背景磁场（地磁场及环境磁场）测量微弱的在强的背景磁场（地磁场及环境磁场）测量微弱的生物磁信号，采用超导量子干涉仪（生物磁信号，采用超导量子干涉仪（Superconducting QUantum Interference Device，SQUID）来完成。来完成。SQUID

12、的灵敏度高达的灵敏度高达10141015T的量级，是磁通计、的量级，是磁通计、磁通门难以比拟的。磁通门难以比拟的。超导量子干涉仪有高的生物磁场检测灵敏度，是一超导量子干涉仪有高的生物磁场检测灵敏度，是一种非接触无创测量方法，不受被测对象表面状况的影响，种非接触无创测量方法，不受被测对象表面状况的影响，避免电测量中安置电极的麻烦，安全可靠，易实现空间避免电测量中安置电极的麻烦，安全可靠，易实现空间扫描，甚至可建立二维图像。扫描，甚至可建立二维图像。SQUID分为直流超导量子干涉仪（分为直流超导量子干涉仪（DC-SQUID）和交流超导量子干涉仪（和交流超导量子干涉仪（RF-SQUID），），它们利

13、用约瑟夫逊（它们利用约瑟夫逊（Joseffson）结结超导环，超导环，DC-SQUID多为双节超导环，而多为双节超导环，而RF-SQUID为单结超导环。为单结超导环。DC-SQUID的灵敏度比的灵敏度比RF-SQUID高，但高，但RF-SQUID的制造工艺、电路的制造工艺、电路与器件的耦合比较容易，因此实用中常采用与器件的耦合比较容易，因此实用中常采用RF-SQUID系统来实现弱磁信号的检测。系统来实现弱磁信号的检测。RF-SQUID的的系系统统（图图1.11-1）的的关关键键是是探探头头，探探头头内内含含磁磁通通变变换换器器、约约瑟瑟夫夫逊逊结结超超导导环环及及共共振振回回路路，它它们们处处

14、在在超超低低温温状状态态（5K左左右右)。利利用用超超低低温温超超导导状状态态下下的的量量子子干干扰扰现现象象来来检检测测体体内内弱弱磁磁场场，并并将将测测得得的的磁磁信信号号经经过过变变换换、放放大大、滤滤波波后后进进行行记记录录。通通过过对对心心电图电图ECG进行比较，分析生理和病理信息。进行比较，分析生理和病理信息。图图1.11-1 RF-SQUID1.11-1 RF-SQUID的系统框图的系统框图（2 2）心磁图的记录方法和测定部位）心磁图的记录方法和测定部位 在在接接受受心心磁磁图图测测定定前前，被被检检者者脱脱去去外外衣衣及及卸卸去身上的金属制品，平卧于检查床。去身上的金属制品，平

15、卧于检查床。SQUID磁磁强强计计检检测测部部分分（杜杜瓦瓦）的的前前端端放放在在被被检检者者胸胸前前壁壁，但但不不接接触触身身体体，并并与与胸胸前前壁壁保保持持垂直。垂直。一一般般多多采采用用在在胸胸前前壁壁作作多多点点栅栅极极系系统统式式描描记记法法。国国际际上上普普遍遍应应用用心心电电图图的的Einthoven氏氏命命名名法法对对MCG进进行行命命名名，即即P波波，QRS波波，T波波和和ST段段。3.3.临床应用临床应用 MCG除了能够检查大多数心脏疾病，如除了能够检查大多数心脏疾病，如心梗后的心衰预测、室颤的危险评估、心肌心梗后的心衰预测、室颤的危险评估、心肌缺血和成活率检测、缺血和成

16、活率检测、ECG无变化的冠心病检无变化的冠心病检测、左心室肥大的检测等外，还可用于胎儿测、左心室肥大的检测等外，还可用于胎儿心脏病学研究（心脏病学研究（fetal MCG，fMCG）、）、药理药理学测试、肝脏铁储量检查、恶性肿瘤检查等。学测试、肝脏铁储量检查、恶性肿瘤检查等。脑磁图仪脑磁图仪1.1.概述概述 脑磁图（脑磁图（Magnetoencephalogram，MEG）对对脑神经电流产生的微弱生物磁场的测量，对自发的脑神经电流产生的微弱生物磁场的测量，对自发的或受到外界刺激而产生的脑活动进行功能性成像。或受到外界刺激而产生的脑活动进行功能性成像。MEG没有侵害性和危险性，具有毫秒级的时没有

17、侵害性和危险性，具有毫秒级的时间分辨率，对电活动源的定位可达到间分辨率，对电活动源的定位可达到2mm的精度。的精度。MEG对脑生理活动研究具有较好空间灵敏度对脑生理活动研究具有较好空间灵敏度和时间灵敏度，操作简单，易于掌握。和时间灵敏度，操作简单，易于掌握。高温超导脑磁图测量系统高温超导脑磁图测量系统和高温超导冷却屏蔽罩和高温超导冷却屏蔽罩七个信道的高温超导七个信道的高温超导脑磁图测量系统脑磁图测量系统 2.2.脑脑磁磁图图仪仪的的组组成成原原理理 MEG系统的核心是系统的核心是由许多处于不同空间位置由许多处于不同空间位置的信号探测线圈（的信号探测线圈（Pickup Coil）和超导量子干涉器

18、和超导量子干涉器件（件（SQUID）两部分组成两部分组成每一个探测器是由磁场梯每一个探测器是由磁场梯度仪和把磁场信号转化成度仪和把磁场信号转化成电压信号的电压信号的SQUID通过电通过电磁感应而耦合在一起的。磁感应而耦合在一起的。上世纪八十年代上世纪八十年代MEG由单信道发展成由单信道发展成37信道传感器装置，用于癫痫诊断和其它脑功能信道传感器装置，用于癫痫诊断和其它脑功能方面的研究。方面的研究。九十年代初已研制出全头型的多信道九十年代初已研制出全头型的多信道MEG测量系统（探测位置数量已达到测量系统（探测位置数量已达到275个）。个）。现在，信号探测传感器可同时快速地收集和处现在，信号探测传

19、感器可同时快速地收集和处理整个大脑的数据，并通过抗外磁场干扰系统理整个大脑的数据，并通过抗外磁场干扰系统和计算机信息处理技术，将信号转换成脑磁曲和计算机信息处理技术，将信号转换成脑磁曲线图、等磁线图等，还可与线图、等磁线图等，还可与MRI或或CT等解剖等解剖影像信息融合，形成脑功能解剖学定位，准确影像信息融合，形成脑功能解剖学定位，准确地反映出脑功能瞬时变化状态。地反映出脑功能瞬时变化状态。3.MEG3.MEG临床应用临床应用v 癫痫病的早期检测定位癫痫病的早期检测定位v 脑脑外外科科手手术术前前得得到到病病人人脑脑功功能能严严重重损损伤伤区区域域的的空空间间位置位置v 对严重头部损伤昏迷的病

20、人醒后进行其脑神经功能对严重头部损伤昏迷的病人醒后进行其脑神经功能评价评价v 对受到轻微脑损伤的病人进行功能性检测以确定是对受到轻微脑损伤的病人进行功能性检测以确定是否出现并发症否出现并发症 许多受轻微脑损伤的病人都会有各种各样的并许多受轻微脑损伤的病人都会有各种各样的并发症出现，然而他们却有正常的发症出现，然而他们却有正常的MRI、CT和和EEG检测结果。只有在经过检测结果。只有在经过MEG检测后，才能发现这检测后，才能发现这些病人的异常脑神经功能。些病人的异常脑神经功能。（3）Biochemical Signals Biochemical signals contain informati

21、on about the levels and changes in various chemical in the body.For example,the concentration of various ions,such as calcium and potassium,in cells can be measured and recorded as can the changes in the partial pressures of oxygen(pO2)and carbon dioxide(pCO2)in the respiratory system or blood.All t

22、hese constitute biochemical signals.These biochemical signals can be used for a variety of purposes,such as determining levels of glucose(葡萄糖),lactate(乳酸盐),and metabolites(代谢物)and providing information about the function of various physiological systems.（4）Biomechanical Signals Mechanical functions

23、of biological systems,which include motion,displacement,tension,force,pressure,and flow,also produce biosignals.Blood pressure,for example,is a measurement of the force that blood exerts against the walls of blood vessels.Changes in blood pressure can be recorded as a waveform.The upstrokes in the w

24、aveform represent the contraction of the ventricles of the heart as blood is ejected from the heart into the body and blood pressure increases to the systolic(心脏收缩的)pressure.The downward portion of the waveform depicts ventricular relaxation as the blood pressure drops to the minimum value that is c

25、alled the diastolic(心脏舒张的)pressure.（5）Bioacoustic Signals Bioacoustic signals are a special subset of biomechanical signals that involve vibration(motion).Many biological events produce acoustic noise.For instance,the flow of blood through the valves(瓣膜)in the heart has a distinctive sound.Measureme

26、nts of the bioacoustic signal of a heart valve can be used to help determine whether or not it is operating properly.The respiratory system,joints,and muscles also generate bioacoustic signals that propagate through the biological medium and can often be measured at the skin surface by using acousti

27、c transducers such as microphones and accelerometers(加速度计).（6）Biooptical Signals Biooptical signals are generated by the optical attributes of biological systems.Biooptical signals may occur naturally or,in some cases,the signals may be induced using a biomedical technique.For example,information ab

28、out the health of a fetus may be obtained by measuring the fluorescence characteristics of the amniotic fluid(羊水).Estimation of cardiac output can be made by using the dye dilution method that involves monitoring the concentration of a dye as it recirculates through the bloodstream.3.Characteristics

29、 of Biosignals continuous signal discrete signaldeterministic signalrandom signalstationary signalnonstationary signal Real biosignals almost always have some unpredictable noise or change in parameters and,therefore,are not deterministic.The ECG of a normal heart rate at rest is an example of a sig

30、nal that appears to be almost periodic.The basic waveshape consists of the P wave,QRS complex,and T wave.However,the precise shapes of the P waves,QRS complexes,and T waves vary over time.The length of time between QRS complexes,which is known as the R-R intervals,also changes over time as a result

31、of heart rate variability(HRV).HRV is used as a diagnostic tool to predict the health of a heart that has experienced a heart attack.Patients with low HRV is generally worse than it is for patients with high HRV.Mathematical functions can not be used to precisely describe random signals.Random signa

32、ls often show distribution probabilities and can be expressed in terms of statistical properties.The EMG which is used for the diagnosis of neuromuscular disorders,is a random signal.Stationary random signals are signals for which the statistics or frequency spectra remain the same over time.Convers

33、ely,nonstationary random signals have statistical properties or frequency spectra that vary with time.The identification of stationary segments of random signals is important for signal processing and pattern analysis.Biosignals are often very small,contain unwanted noise,and can even be masked by o

34、ther biosignals.Throughout the data acquisition procedure,it is critical that the information in the original biosignal be preserved.Since these signals are often used to aid the diagnosis of pathological(病理的)disorders,the procedures of amplification,analog filtering and analog-to-digital(A/D)conver

35、sion should not cause misleading or imperceptible distortions in the biosignal.Distortions in the biosignal could lead to an improper diagnosis.4.Signal Acquisition Sampling an analog signal must be accomplished so that the digitized signal provides an accurate representation of the original analog

36、signal.Thus,the sampling rate is critical for the generation of an accurate digital signal.If the sampling rate is too low,distortions will occur in the digital signal.Nyquists theorem states that the minimum sampling rate should be twice the highest frequency in the original signal,that is Biosigna

37、ls can be represented in both the time domain and the frequency domain.The Fourier transform is a basic operation that is used to transform signals from the time domain into the frequency domain.For many different biosignal processing methods and applications,including filtering and spectral analysi

38、s,it is useful to have the frequency domain representations of the biosignals.Filtering operations can,in some cases,be applied more efficiently in the frequency domain,and spectral information about biosignals can be obtained from frequency representations of biosignals.5.Frequency Domain Representation of Biosignals再见！