遗传病和人类基因组计划专家讲座.pptx

Session 4 Biosignal Processing 1.Introduction 2.Physiological Origins of Biosignals 3.Characteristics of Biosignals 4.Signal Acquisition 5.Frequency Domain Representation of Biosignals遗传病和人类基因组计划第1页 1.Introduction Biosignal are space,time,or space-time records of a biological event such as a beating heart or a contracting 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 event 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 analysis,and artificial intelligence techniques.遗传病和人类基因组计划第2页 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 enough 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 biological medium.Changes in extracellular potential can be measured on the surface of the organ by using surface electrodes.(ECG,EEG,EMG)遗传病和人类基因组计划第3页遗传病和人类基因组计划第4页（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 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 information about intracellular activity.遗传病和人类基因组计划第5页心磁图仪心磁图仪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发入装置为探头，对心动周期中心脏电活动引发微小磁场进行测定一项新型心脏无创伤性检验。微小磁场进行测定一项新型心脏无创伤性检验。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电场心脏与体表心电图电极间电场需经过几个不一样介质边界，它们每一个都有需经过几个不一样介质边界，它们每一个都有不一样传导性和其它电特征。不一样传导性和其它电特征。遗传病和人类基因组计划第6页 因为心脏产生电场边界歪曲，心电电极统因为心脏产生电场边界歪曲，心电电极统计电场特点与心脏产生电场是不一样。计电场特点与心脏产生电场是不一样。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资料所资料所以可提供更准确心脏活动信息。以可提供更准确心脏活动信息。对局部心肌电流高度敏感。对局部心肌电流高度敏感。MCG有更高空间有更高空间分辨率，与分辨率，与ECG相比，相比，MCG对局部电流有更对局部电流有更高空间敏感性。高空间敏感性。这些局部电流微弱，来自心肌边界，有不这些局部电流微弱，来自心肌边界，有不一样电生理特点，即每个都有不一样动作电位一样电生理特点，即每个都有不一样动作电位间期。在磁场中，这些电流比在电场中反应得间期。在磁场中，这些电流比在电场中反应得更清楚。更清楚。遗传病和人类基因组计划第7页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，比生物磁信号与生物电信号相比更为微弱，比如心脏周围磁场约为如心脏周围磁场约为51011特斯拉（特斯拉（T），心磁），心磁图（图（MCG）最大幅值为）最大幅值为1010特斯拉（特斯拉（T），比地），比地球磁场小一百万倍（地球磁场为球磁场小一百万倍（地球磁场为104 T量级），量级），比城市环境磁噪声（比城市环境磁噪声（107 T量级）小一万倍左右。量级）小一万倍左右。脑磁图（脑磁图（MEG）信号更为微弱，在）信号更为微弱，在1012T量量级，所以要采取磁通门来测量生物磁，尤其是心级，所以要采取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。磁图及脑磁图等微弱信号是不可能。遗传病和人类基因组计划第8页 在强背景磁场（地磁场及环境磁场）测量微弱生物在强背景磁场（地磁场及环境磁场）测量微弱生物磁信号，采取超导量子干涉仪（磁信号，采取超导量子干涉仪（Superconducting QUantum Interference Device，SQUID）来完成。）来完成。SQUID灵敏度高达灵敏度高达10141015T量级，是磁通计、磁量级，是磁通计、磁通门难以比拟。通门难以比拟。超导量子干涉仪有高生物磁场检测灵敏度，是一个超导量子干涉仪有高生物磁场检测灵敏度，是一个非接触无创测量方法，不受被测对象表面情况影响，防非接触无创测量方法，不受被测对象表面情况影响，防止电测量中安置电极麻烦，安全可靠，易实现空间扫描，止电测量中安置电极麻烦，安全可靠，易实现空间扫描，甚至可建立二维图像。甚至可建立二维图像。遗传病和人类基因组计划第9页 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灵敏度比灵敏度比RF-SQUID高，但高，但RF-SQUID制造工艺、电路与制造工艺、电路与器件耦合比较轻易，所以实用中常采取器件耦合比较轻易，所以实用中常采取RF-SQUID系统来实现弱磁信号检测。系统来实现弱磁信号检测。遗传病和人类基因组计划第10页 RF-SQUID系系统统（图图1.11-1）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，它它们们处处于于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统统计计。经经过过对对心心电电图图ECG进进行比较，分析生理和病理信息。行比较，分析生理和病理信息。遗传病和人类基因组计划第11页图图1.11-1 RF-SQUID1.11-1 RF-SQUID系统框图系统框图 遗传病和人类基因组计划第12页（2 2）心磁图统计方法和测定部位）心磁图统计方法和测定部位 在在接接收收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金属制品，平卧于检验床。去身上金属制品，平卧于检验床。SQUID磁磁强强计计检检测测部部分分（杜杜瓦瓦）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垂直。直。普普通通多多采采取取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专专心心电电图图Einthoven氏氏命命名名法法对对MCG进行命名，即进行命名，即P波，波，QRS波，波，T波和波和ST段段。遗传病和人类基因组计划第13页3.3.临床应用临床应用 MCG除了能够检验大多数心脏疾病，如除了能够检验大多数心脏疾病，如心梗后心衰预测、室颤危险评定、心肌缺血心梗后心衰预测、室颤危险评定、心肌缺血和成活率检测、和成活率检测、ECG无改变冠心病检测、左无改变冠心病检测、左心室肥大检测等外，还可用于胎儿心脏病学心室肥大检测等外，还可用于胎儿心脏病学研究（研究（fetal MCG，fMCG）、药理学测试、）、药理学测试、肝脏铁储量检验、恶性肿瘤检验等。肝脏铁储量检验、恶性肿瘤检验等。遗传病和人类基因组计划第14页脑磁图仪脑磁图仪1.1.概述概述 脑磁图（脑磁图（Magnetoencephalogram，MEG）对对脑神经电流产生微弱生物磁场测量，对自发或受到脑神经电流产生微弱生物磁场测量，对自发或受到外界刺激而产生脑活动进行功效性成像。外界刺激而产生脑活动进行功效性成像。MEG没有侵害性和危险性，含有毫秒级时间没有侵害性和危险性，含有毫秒级时间分辨率，对电活动源定位可到达分辨率，对电活动源定位可到达2mm精度。精度。MEG对脑生理活动研究含有很好空间灵敏度对脑生理活动研究含有很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。遗传病和人类基因组计划第15页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高温超导七个信道高温超导脑磁图测量系统脑磁图测量系统 遗传病和人类基因组计划第16页2.2.脑磁图仪组成原理脑磁图仪组成原理 MEG系统关键是由系统关键是由许多处于不一样空间位置许多处于不一样空间位置信号探测线圈（信号探测线圈（Pickup Coil）和超导量子干涉器）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电压信号SQUID经过电磁经过电磁感应而耦合在一起。感应而耦合在一起。遗传病和人类基因组计划第17页 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，用于癫痫诊疗和其它脑功效信道传感器装置，用于癫痫诊疗和其它脑功效方面研究。方面研究。九十年代初已研制出全头型多信道九十年代初已研制出全头型多信道MEG测量系统（探测位置数量已到达测量系统（探测位置数量已到达275个）。现个）。现在，信号探测传感器可同时快速地搜集和处理在，信号探测传感器可同时快速地搜集和处理整个大脑数据，并经过抗外磁场干扰系统和计整个大脑数据，并经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线图、算机信息处理技术，将信号转换成脑磁曲线图、等磁线图等，还可与等磁线图等，还可与MRI或或CT等解剖影像信等解剖影像信息融合，形成脑功效解剖学定位，准确地反应息融合，形成脑功效解剖学定位，准确地反应出脑功效瞬时改变状态。出脑功效瞬时改变状态。遗传病和人类基因组计划第18页3.MEG3.MEG临床应用临床应用v 癫痫病早期检测定位癫痫病早期检测定位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效效严严重重损损伤伤区区域域空空间间位位置置v 对严重头部损伤昏迷病人醒后进行其脑神经功效评对严重头部损伤昏迷病人醒后进行其脑神经功效评价价v 对受到轻微脑损伤病人进行功效性检测以确定是否对受到轻微脑损伤病人进行功效性检测以确定是否出现并发症出现并发症 许多受轻微脑损伤病人都会有各种各样并发症许多受轻微脑损伤病人都会有各种各样并发症出现，然而他们却有正常出现，然而他们却有正常MRI、CT和和EEG检测结检测结果。只有在经过果。只有在经过MEG检测后，才能发觉这些病人检测后，才能发觉这些病人异常脑神经功效。异常脑神经功效。遗传病和人类基因组计划第19页（3）Biochemical Signals Biochemical signals contain information 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 these 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.遗传病和人类基因组计划第20页（4）Biomechanical Signals Mechanical functions 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 waveform 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)pressure.The downward portion of the waveform depicts ventricular relaxation as the blood pressure drops to the minimum value that is called the diastolic(心脏舒张)pressure.遗传病和人类基因组计划第21页遗传病和人类基因组计划第22页（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.Measurements 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 acoustic transducers such as microphones and accelerometers(加速度计).遗传病和人类基因组计划第23页（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 about 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.遗传病和人类基因组计划第24页3.Characteristics of Biosignals continuous signal discrete signaldeterministic signalrandom signalstationary signalnonstationary signal遗传病和人类基因组计划第25页 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 signal 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 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.遗传病和人类基因组计划第26页 Mathematical functions can not be used to precisely describe random signals.Random signals 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.Conversely,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.遗传病和人类基因组计划第27页 Biosignals are often very small,contain unwanted noise,and can even be masked by other 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)disorders,the procedures of amplification,analog filtering and analog-to-digital(A/D)conversion should not cause misleading or imperceptible distortions in the biosignal.Distortions in the biosignal could lead to an improper diagnosis.4.Signal Acquisition遗传病和人类基因组计划第28页遗传病和人类基因组计划第29页遗传病和人类基因组计划第30页 Sampling an analog signal must be accomplished so that the digitized signal provides an accurate representation of the original analog 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 遗传病和人类基因组计划第31页 Biosignals 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 analysis,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遗传病和人类基因组计划第32页遗传病和人类基因组计划第33页遗传病和人类基因组计划第34页遗传病和人类基因组计划第35页再见！遗传病和人类基因组计划第36页