遗传病和人类基因组计划专家讲座

Session4BiosignalProcessing

1.Introduction2.PhysiologicalOriginsofBiosignals

3.CharacteristicsofBiosignals4.SignalAcquisition5.FrequencyDomainRepresentationofBiosignals遗传病和人类基因组计划第1页

1.Introduction

Biosignalarespace,time,orspace-timerecordsofabiologicaleventsuchasabeatingheartoracontractingmuscle.Theelectrical,chemical,andmechanicalactivitythatoccursduringthisbiologicaleventoftenproducessignalsthatcanbemeasuredandanalyzed.Biosignals,therefore,containinformationthatcanbeusedtoexplaintheunderlyingphysiologicalmechanismsofaspecificbiologicaleventorsystem.Biosignalsmustbeanalyzedtoretrievethemostrelevantinformationfromthem.Thebasicmethodsofsignalanalysis,e.g.,amplification,filtering,digitization,processing,andstorage,canbeappliedtomanybiosignals.Othersignalprocessingmethodsincludesignalaveraging,waveletanalysis,andartificialintelligencetechniques.遗传病和人类基因组计划第2页

2.PhysiologicalOriginsofBiosignals

（1）BioelectricSignalsNerveandmusclecellsgeneratebioelectricsignalsthataretheresultofelectrochemicalchangeswithinandbetweencells.Ifanerveormusclecellisstimulatedbyastimulusthatisstrongenoughtoreachanecessarythreshold,thecellwillgenerateanactionpotential.Theactionpotentialrepresentstheflowofionsacrossthecellmembraneandcanbetransmittedfromonecelltoadjacentcells.Whenmanycellsbecomeexcited,anelectricfieldisgeneratedandpropagatesthroughthebiologicalmedium.Changesinextracellularpotentialcanbemeasuredonthesurfaceoftheorganbyusingsurfaceelectrodes.(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）BiomagneticSignalsDifferentorgans,includingtheheart,brain,andlungs,generatemagneticfieldsthatareweakcomparedtoothereventsaselectricalchangesoccurinthem.Biomagnetismisthemeasurementofthemagneticsignalsthatareassociatedwithspecificphysiologicalactivity.Biomagneticsignalsthereforecanprovidevaluableadditionalinformationthatisnotusuallycontainedinbioelectricsignals.Furthermore,theycanbeusedtoobtainadditionalinformationaboutintracellularactivity.遗传病和人类基因组计划第5页心磁图仪1.概述

心磁图（Magnetocardiogram，MCG）是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微小磁场进行测定一项新型心脏无创伤性检验。与ECG相比，MCG具备以下特点：①信号高度保真。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，MCG资料所以可提供更准确心脏活动信息。②对局部心肌电流高度敏感。MCG有更高空间分辨率，与ECG相比，MCG对局部电流有更高空间敏感性。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间期。在磁场中，这些电流比在电场中反应得更清楚。遗传病和人类基因组计划第7页2.心磁图测量原理（1）测量原理

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5×10－11特斯拉（T），心磁图（MCG）最大幅值为10－10特斯拉（T），比地球磁场小一百万倍（地球磁场为10－4T量级），比城市环境磁噪声（10－7T量级）小一万倍左右。脑磁图（MEG）信号更为微弱，在10－12T量级，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。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）测量微弱生物磁信号，采取超导量子干涉仪（SuperconductingQUantumInterferenceDevice，SQUID）来完成。SQUID灵敏度高达10－14~10－15T量级，是磁通计、磁通门难以比拟。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，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（DC-SQUID）和交流超导量子干涉仪（RF-SQUID），它们利用约瑟夫逊（Joseffson）结超导环，DC-SQUID多为双节超导环，而RF-SQUID为单结超导环。DC-SQUID灵敏度比RF-SQUID高，但RF-SQUID制造工艺、电路与器件耦合比较轻易，所以实用中常采取RF-SQUID系统来实现弱磁信号检测。遗传病和人类基因组计划第10页RF-SQUID系统（图1.11-1）关键是探头，探头内含磁通变换器、约瑟夫逊结超导环及共振回路，它们处于超低温状态（5K左右)。利用超低温超导状态下量子干扰现象来检测体内弱磁场，并将测得磁信号经过变换、放大、滤波后进行统计。经过对心电图ECG进行比较，分析生理和病理信息。遗传病和人类基因组计划第11页图1.11-1RF-SQUID系统框图

遗传病和人类基因组计划第12页（2）心磁图统计方法和测定部位在接收心磁图测定前，被检者脱去外衣及卸去身上金属制品，平卧于检验床。SQUID磁强计检测部分（杜瓦）前端放在被检者胸前壁，但不接触身体，并与胸前壁保持垂直。普通多采取在胸前壁作多点栅极系统式描记法。国际上普遍应专心电图Einthoven氏命名法对MCG进行命名，即P波，QRS波，T波和ST段。遗传病和人类基因组计划第13页3.临床应用

MCG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、心肌缺血和成活率检测、ECG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研究（fetalMCG，fMCG）、药理学测试、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1.概述

脑磁图（Magnetoencephalogram，MEG）对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。MEG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2mm精度。MEG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。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和高温超导冷却屏蔽罩七个信道高温超导脑磁图测量系统遗传病和人类基因组计划第16页2.

脑磁图仪组成原理

MEG系统关键是由许多处于不一样空间位置信号探测线圈（PickupCoil）和超导量子干涉器件（SQUID）两部分组成每一个探测器是由磁场梯度仪和把磁场信号转化成电压信号SQUID经过电磁感应而耦合在一起。遗传病和人类基因组计划第17页上世纪八十年代MEG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方面研究。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275个）。现在，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MRI或CT等解剖影像信息融合，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。遗传病和人类基因组计划第18页3.

MEG临床应用癫痫病早期检测定位脑外科手术前得到病人脑功效严重损伤区域空间位置对严重头部损伤昏迷病人醒后进行其脑神经功效评价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MRI、CT和EEG检测结果。只有在经过MEG检测后，才能发觉这些病人异常脑神经功效。遗传病和人类基因组计划第19页（3）BiochemicalSignals

Biochemicalsignalscontaininformationaboutthelevelsandchangesinvariouschemicalinthebody.Forexample,theconcentrationofvariousions,suchascalciumandpotassium,incellscanbemeasuredandrecordedascanthechangesinthepartialpressuresofoxygen(pO2)andcarbondioxide(pCO2)intherespiratorysystemorblood.Alltheseconstitutebiochemicalsignals.Thesebiochemicalsignalscanbeusedforavarietyofpurposes,suchasdetermininglevelsofglucose

(葡萄糖),lactate(乳酸盐),andmetabolites(代谢物)andprovidinginformationaboutthefunctionofvariousphysiologicalsystems.遗传病和人类基因组计划第20页（4）BiomechanicalSignalsMechanicalfunctionsofbiologicalsystems,whichincludemotion,displacement,tension,force,pressure,andflow,alsoproducebiosignals.Bloodpressure,forexample,isameasurementoftheforcethatbloodexertsagainstthewallsofbloodvessels.Changesinbloodpressurecanberecordedasawaveform.Theupstrokesinthewaveformrepresentthecontractionoftheventriclesoftheheartasbloodisejectedfromtheheartintothebodyandbloodpressureincreasestothesystolic(心脏收缩)pressure.Thedownwardportionofthewaveformdepictsventricularrelaxationasthebloodpressuredropstotheminimumvaluethatiscalledthediastolic(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）BioacousticSignalsBioacousticsignalsareaspecialsubsetofbiomechanicalsignalsthatinvolvevibration(motion).Manybiologicaleventsproduceacousticnoise.Forinstance,theflowofbloodthroughthevalves(瓣膜)inthehearthasadistinctivesound.Measurementsofthebioacousticsignalofaheartvalvecanbeusedtohelpdeterminewhetherornotitisoperatingproperly.Therespiratorysystem,joints,andmusclesalsogeneratebioacousticsignalsthatpropagatethroughthebiologicalmediumandcanoftenbemeasuredattheskinsurfacebyusingacoustictransducerssuchasmicrophonesandaccelerometers(加速度计).遗传病和人类基因组计划第23页（6）BioopticalSignalsBioopticalsignalsaregeneratedbytheopticalattributesofbiologicalsystems.Bioopticalsignalsmayoccurnaturallyor,insomecases,thesignalsmaybeinducedusingabiomedicaltechnique.Forexample,informationaboutthehealthofafetusmaybeobtainedbymeasuringthefluorescencecharacteristicsoftheamnioticfluid(羊水).Estimationofcardiacoutputcanbemadebyusingthedyedilutionmethodthatinvolvesmonitoringtheconcentrationofadyeasitrecirculatesthroughthebloodstream.遗传病和人类基因组计划第24页3.CharacteristicsofBiosignalscontinuoussignaldiscretesignaldeterministicsignalrandomsignalstationarysignalnonstationarysignal遗传病和人类基因组计划第25页Realbiosignalsalmostalwayshavesomeunpredictablenoiseorchangeinparametersand,therefore,arenotdeterministic.TheECGofanormalheartrateatrestisanexampleofasignalthatappearstobealmostperiodic.ThebasicwaveshapeconsistsofthePwave,QRScomplex,andTwave.However,thepreciseshapesofthePwaves,QRScomplexes,andTwavesvaryovertime.ThelengthoftimebetweenQRScomplexes,whichisknownastheR-Rintervals,alsochangesovertimeasaresultofheartratevariability(HRV).HRVisusedasadiagnostictooltopredictthehealthofaheartthathasexperiencedaheartattack.PatientswithlowHRVisgenerallyworsethanitisforpatientswithhighHRV.遗传病和人类基因组计划第26页Mathematicalfunctionscannotbeusedtopreciselydescriberandomsignals.Randomsignalsoftenshowdistributionprobabilitiesandcanbeexpressedintermsofstatisticalproperties.TheEMGwhichisusedforthediagnosisofneuromusculardisorders,isarandomsignal.Stationaryrandomsignalsaresignalsforwhichthestatisticsorfrequencyspectraremainthesameovertime.Conversely,nonstationaryrandomsignalshavestatisticalpropertiesorfrequencyspectrathatvarywithtime.Theidentificationofstationarysegmentsofrandomsignalsisimportantforsignalprocessingandpatternanalysis.遗传病和人类基因组计划第27页Biosignalsareoftenverysmall,containunwantednoise,andcanevenbemaskedbyotherbiosignals.Throughoutthedataacquisitionprocedure,itiscriticalthattheinformationintheoriginalbiosignalbepreserved.Sincethesesignalsareoftenusedtoaidthediagnosisofpathological(病理)disorders,theproceduresofamplification,analogfilteringandanalog-to-digital(A/D)conversionshouldnotcausemisleadingorimperceptibledistortionsinthebiosignal.Distortionsinthebiosignalcouldleadtoanimproperdiagnosis.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Samplingananalogsignalmustbeaccomplishedsothatthedigitizedsignalprovidesanaccuraterepresentationoftheorigin