第六讲 遗传病和人类基因组计划精选文档.ppt

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1、第六讲 遗传病和人类基因组计划本讲稿第一页，共三十六页 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 ana

2、lyzed.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,filterin

3、g,digitization,processing,and storage,can be applied to many biosignals.Other signal processing methods include signal averaging,wavelet analysis,and artificial intelligence techniques.本讲稿第二页，共三十六页 2.Physiological Origins of Biosignals（1）BioelectricSignals Nerve and muscle cells generate bioelectric

4、 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 memb

5、rane 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)本讲稿第三页，共三十六页本

6、讲稿第四页，共三十六页（2）BiomagneticSignals 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.B

7、iomagnetic 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.本讲稿第五页，共三十六页心磁图仪心磁图仪1.1.概述概述心磁图（心磁图（Magnetocardiogram，MCG）是低温是低温超导与计算机技术相结合，以超导量子介入

8、装置为探头，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的微小磁场进行测定的一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检查。项新型心脏无创伤性检查。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场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，它们每一个都有不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。同的传导性和其他的电特性。本讲稿第六页，共三十六页由于心脏产生电场的边界歪曲，心电电极记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

9、产生的电场是不同的。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资料因此资料因此可提供更准确的心脏活动信息。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有更高的空间分有更高的空间分辨率，与辨率，与ECG相比，相比，MCG对局部电流有更高的空间对局部电流有更高的空间敏感性。敏感性。这些局部电流微弱，来自心肌边界，有不同的电这些局部电流微弱，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间期。在磁生理特点，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更清晰。场中，这些电流比在电

10、场中反映得更清晰。本讲稿第七页，共三十六页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，例如心脏周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围的磁场约为51011特斯拉（特斯拉（T），心磁图（），心磁图（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），比地球磁场小一百万倍（地球磁场为倍（地球磁场为104T量级），比城市的环境磁噪声量级），比城市的环境磁噪声（107T量级）小一万倍左右。量级）小一万倍左右。脑磁图（脑磁图（MEG）的信号更为微弱，在）的信号更为微弱，在1012T量量级，因此要

11、采用磁通门来测量生物磁，尤其是心磁级，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。图及脑磁图等微弱信号是不可能的。本讲稿第八页，共三十六页在强的背景磁场（地磁场及环境磁场）测量微弱的生在强的背景磁场（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（物磁信号，采用超导量子干涉仪（SuperconductingQUantumInterferenceDevice，SQUID）来完成。）来完成。SQUID的灵的灵敏度高达敏度高达10141015T的量级，是磁通计、磁通门难以比拟的量级，是磁通计、磁通门难以比拟的。的。超导量子干涉仪有高的生物磁场检测灵敏度，是一种

12、非接触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，避免电测量中安无创测量方法，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，易实现空间扫描，甚至可建立二维图置电极的麻烦，安全可靠，易实现空间扫描，甚至可建立二维图像。像。本讲稿第九页，共三十六页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），它们利用约瑟夫逊（瑟夫逊（Joseffson）结超导环，）结超导环，DC-SQUID多为双多为双节超导环，而节超导环，而RF-SQU

13、ID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的的制造工艺、电路与器件的耦合比较容易，因此实用中常制造工艺、电路与器件的耦合比较容易，因此实用中常采用采用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。本讲稿第十页，共三十六页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

14、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。通过对心电图通过对心电图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。本讲稿第十一页，共三十六页图图1.11-1 RF-SQUID1.11-1 RF-SQUID的系统框图的系统框图 本讲稿第十二页，共三十六页（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去身身上上的的金属制品，平卧于检查床。金属制品，平卧于检查床。SQUID磁磁强强计计检检测测部部分分（杜杜瓦

15、瓦）的的前前端端放放在在被被检检者胸前壁，但不接触身体，并与胸前壁保持垂直。者胸前壁，但不接触身体，并与胸前壁保持垂直。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进进行行命名，即命名，即P波，波，QRS波，波，T波和波和ST段段。本讲稿第十三页，共三十六页3.3.临床应用临床应用MCG除了能够检查大多数心脏疾病，如心梗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、心肌缺血和成活后的心衰预测、室颤的危险评估、心肌缺血和成活率检测、率检测、ECG无变化的

16、冠心病检测、左心室肥大无变化的冠心病检测、左心室肥大的检测等外，还可用于胎儿心脏病学研究（的检测等外，还可用于胎儿心脏病学研究（fetalMCG，fMCG）、药理学测试、肝脏铁储量检查、）、药理学测试、肝脏铁储量检查、恶性肿瘤检查等。恶性肿瘤检查等。本讲稿第十四页，共三十六页脑磁图仪脑磁图仪1.1.概述概述脑磁图（脑磁图（Magnetoencephalogram，MEG）对脑神经对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。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，具有毫秒级的时间分没

17、有侵害性和危险性，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和时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。间灵敏度，操作简单，易于掌握。本讲稿第十五页，共三十六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本讲稿第十六页，共三十六页2.2.脑磁图仪的组成原理脑磁图仪的组成原理MEG系统的核心是由许系统的核心是由许多处于不同空间位置的信号探多处于不同空间位置的信号探测线圈（测

18、线圈（PickupCoil）和超）和超导量子干涉器件（导量子干涉器件（SQUID）两部分组成每一个探测器是两部分组成每一个探测器是由磁场梯度仪和把磁场信号由磁场梯度仪和把磁场信号转化成电压信号的转化成电压信号的SQUID通过电磁感应而耦合在一通过电磁感应而耦合在一起的。起的。本讲稿第十七页，共三十六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信道传信道传感器装置，用于癫痫诊断和其它脑功能方面的研究。感器装置，用于癫痫诊断和其它脑功能方面的研究。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2

19、75个）。现在，信个）。现在，信号探测传感器可同时快速地收集和处理整个大脑号探测传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和计算机信息的数据，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线图、等磁线图处理技术，将信号转换成脑磁曲线图、等磁线图等，还可与等，还可与MRI或或CT等解剖影像信息融合，形成脑等解剖影像信息融合，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。功能解剖学定位，准确地反映出脑功能瞬时变化状态。本讲稿第十八页，共三十六页3.3.MEG 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

20、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否出现并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发症许多受轻微脑损伤的病人都会有各种各样的并发症出现，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然而他们却有正常的MRI、CT和和EEG检测结果。只有在检测结果。只有在经过经过MEG检测后，才能发现这些病人的异常脑神经功能。检测后，才能发现这些病人的异常脑神经功能。本讲稿第十九页，共三十六页（3

21、）BiochemicalSignals 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 car

22、bon 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 physiologic

23、al systems.本讲稿第二十页，共三十六页（4）BiomechanicalSignals 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 i

24、n 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(心脏收缩的)pressure.The downward portion of the waveform depicts ventricular

25、relaxation as the blood pressure drops to the minimum value that is called the diastolic(心脏舒张的)pressure.本讲稿第二十一页，共三十六页本讲稿第二十二页，共三十六页（5）BioacousticSignals Bioacoustic signals are a special subset of biomechanical signals that involve vibration(motion).Many biological events produce acoustic noise.For

26、 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 propag

27、ate 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).本讲稿第二十三页，共三十六页（6）BioopticalSignals Biooptical signals are generated by the optical attributes of biological systems.Biooptical signals may occur

28、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 tha

29、t involves monitoring the concentration of a dye as it recirculates through the bloodstream.本讲稿第二十四页，共三十六页3.Characteristics of Biosignals continuous signal discrete signaldeterministic signalrandom signalstationary signalnonstationary signal本讲稿第二十五页，共三十六页 Real biosignals almost always have some unpr

30、edictable 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,an

31、d 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 gener

32、ally worse than it is for patients with high HRV.本讲稿第二十六页，共三十六页 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 neuromus

33、cular 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 r

34、andom signals is important for signal processing and pattern analysis.本讲稿第二十七页，共三十六页 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.

35、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)conversion should not cause misleading or imperceptible distortions in the biosignal.Distortions in the biosignal could lead to an improper

36、 diagnosis.4.Signal Acquisition本讲稿第二十八页，共三十六页本讲稿第二十九页，共三十六页本讲稿第三十页，共三十六页 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.I

37、f 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 本讲稿第三十一页，共三十六页 Biosignals can be represented in both the time domain and the frequency domain.The Fo

38、urier 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

39、.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本讲稿第三十二页，共三十六页本讲稿第三十三页，共三十六页本讲稿第三十四页，共三十六页本讲稿第三十五页，共三十六页再见！本讲稿第三十六页，共三十六页