遺傳病和人類基因組計劃課件

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.

2.PhysiologicalOriginsofBiosignals

（1）BioelectricSignalsNerveandmusclecellsgeneratebioelectricsignalsthataretheresultofelectrochemicalchangeswithinandbetweencells.Ifanerveormusclecellisstimulatedbyastimulusthatisstrongenoughtoreachanecessarythreshold,thecellwillgenerateanactionpotential.Theactionpotentialrepresentstheflowofionsacrossthecellmembraneandcanbetransmittedfromonecelltoadjacentcells.Whenmanycellsbecomeexcited,anelectricfieldisgeneratedandpropagatesthroughthebiologicalmedium.Changesinextracellularpotentialcanbemeasuredonthesurfaceoftheorganbyusingsurfaceelectrodes.(ECG,EEG,EMG)（2）BiomagneticSignalsDifferentorgans,includingtheheart,brain,andlungs,generatemagneticfieldsthatareweakcomparedtoothereventsaselectricalchangesoccurinthem.Biomagnetismisthemeasurementofthemagneticsignalsthatareassociatedwithspecificphysiologicalactivity.Biomagneticsignalsthereforecanprovidevaluableadditionalinformationthatisnotusuallycontainedinbioelectricsignals.Furthermore,theycanbeusedtoobtainadditionalinformationaboutintracellularactivity.心磁圖儀1.概述

心磁圖（Magnetocardiogram，MCG）是低溫超導與計算機技術相結合，以超導量子介入裝置為探頭，對心動周期中心臟電活動引起的微小磁場進行測定的一項新型心臟無創(chuàng)傷性檢查。與ECG相比，MCG具備以下特點：①信號高度保真。心臟與體表心電圖電極間的電場需通過幾個不同的介質邊界，它們每一個都有不同的傳導性和其他的電特性。由于心臟產生電場的邊界歪曲，心電電極記錄的電場特點與心臟產生的電場是不同的。界面對磁場不產生太大歪曲，MCG資料因此可提供更準確的心臟活動信息。②對局部心肌電流高度敏感。MCG有更高的空間分辨率，與ECG相比，MCG對局部電流有更高的空間敏感性。這些局部電流微弱，來自心肌邊界，有不同的電生理特點，即每個都有不同的動作電位間期。在磁場中，這些電流比在電場中反映得更清晰。2.心磁圖測量原理（1）測量原理

生物磁信號與生物電信號相比更為微弱，例如心臟周圍的磁場約為5×10－11特斯拉（T），心磁圖（MCG）的最大幅值為10－10特斯拉（T），比地球磁場小一百萬倍（地球磁場為10－4T量級），比城市的環(huán)境磁噪聲（10－7T量級）小一萬倍左右。腦磁圖（MEG）的信號更為微弱，在10－12T量級，因此要采用磁通門來測量生物磁，尤其是心磁圖及腦磁圖等微弱信號是不可能的。

在強的背景磁場（地磁場及環(huán)境磁場）測量微弱的生物磁信號，采用超導量子干涉儀（SuperconductingQUantumInterferenceDevice，SQUID）來完成。SQUID的靈敏度高達10－14~10－15T的量級，是磁通計、磁通門難以比擬的。超導量子干涉儀有高的生物磁場檢測靈敏度，是一種非接觸無創(chuàng)測量方法，不受被測對象表面狀況的影響，避免電測量中安置電極的麻煩，安全可靠，易實現空間掃描，甚至可建立二維圖像。SQUID分為直流超導量子干涉儀（DC-SQUID）和交流超導量子干涉儀（RF-SQUID），它們利用約瑟夫遜（Joseffson）結超導環(huán)，DC-SQUID多為雙節(jié)超導環(huán)，而RF-SQUID為單結超導環(huán)。DC-SQUID的靈敏度比RF-SQUID高，但RF-SQUID的制造工藝、電路與器件的耦合比較容易，因此實用中常采用RF-SQUID系統(tǒng)來實現弱磁信號的檢測。RF-SQUID的系統(tǒng)（圖1.11-1）的關鍵是探頭，探頭內含磁通變換器、約瑟夫遜結超導環(huán)及共振回路，它們處在超低溫狀態(tài)（5K左右)。利用超低溫超導狀態(tài)下的量子干擾現象來檢測體內弱磁場，并將測得的磁信號經過變換、放大、濾波后進行記錄。通過對心電圖ECG進行比較，分析生理和病理信息。圖1.11-1RF-SQUID的系統(tǒng)框圖

（2）心磁圖的記錄方法和測定部位在接受心磁圖測定前，被檢者脫去外衣及卸去身上的金屬制品，平臥于檢查床。SQUID磁強計檢測部分（杜瓦）的前端放在被檢者胸前壁，但不接觸身體，并與胸前壁保持垂直。一般多采用在胸前壁作多點柵極系統(tǒng)式描記法。國際上普遍應用心電圖的Einthoven氏命名法對MCG進行命名，即P波，QRS波，T波和ST段。3.臨床應用

MCG除了能夠檢查大多數心臟疾病，如心梗后的心衰預測、室顫的危險評估、心肌缺血和成活率檢測、ECG無變化的冠心病檢測、左心室肥大的檢測等外，還可用于胎兒心臟病學研究（fetalMCG，fMCG）、藥理學測試、肝臟鐵儲量檢查、惡性腫瘤檢查等。腦磁圖儀1.概述

腦磁圖（Magnetoencephalogram，MEG）對腦神經電流產生的微弱生物磁場的測量，對自發(fā)的或受到外界刺激而產生的腦活動進行功能性成像。MEG沒有侵害性和危險性，具有毫秒級的時間分辨率，對電活動源的定位可達到2mm的精度。MEG對腦生理活動研究具有較好空間靈敏度和時間靈敏度，操作簡單，易于掌握。高溫超導腦磁圖測量系統(tǒng)和高溫超導冷卻屏蔽罩七個信道的高溫超導腦磁圖測量系統(tǒng)2.

腦磁圖儀的組成原理

MEG系統(tǒng)的核心是由許多處于不同空間位置的信號探測線圈（PickupCoil）和超導量子干涉器件（SQUID）兩部分組成每一個探測器是由磁場梯度儀和把磁場信號轉化成電壓信號的SQUID通過電磁感應而耦合在一起的。上世紀八十年代MEG由單信道發(fā)展成37信道傳感器裝置，用于癲癇診斷和其它腦功能方面的研究。九十年代初已研制出全頭型的多信道MEG測量系統(tǒng)（探測位置數量已達到275個）?，F在，信號探測傳感器可同時快速地收集和處理整個大腦的數據，并通過抗外磁場干擾系統(tǒng)和計算機信息處理技術，將信號轉換成腦磁曲線圖、等磁線圖等，還可與MRI或CT等解剖影像信息融合，形成腦功能解剖學定位，準確地反映出腦功能瞬時變化狀態(tài)。3.

MEG臨床應用癲癇病的早期檢測定位腦外科手術前得到病人腦功能嚴重損傷區(qū)域的空間位置對嚴重頭部損傷昏迷的病人醒后進行其腦神經功能評價對受到輕微腦損傷的病人進行功能性檢測以確定是否出現并發(fā)癥許多受輕微腦損傷的病人都會有各種各樣的并發(fā)癥出現，然而他們卻有正常的MRI、CT和EEG檢測結果。只有在經過MEG檢測后，才能發(fā)現這些病人的異常腦神經功能。（3）BiochemicalSignals

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

(葡萄糖),lactate(乳酸鹽),andmetabolites(代謝物)andprovidinginformationaboutthefunctionofvariousphysiologicalsystems.（4）BiomechanicalSignalsMechanicalfunctionsofbiologicalsystems,whichincludemotion,displacement,tension,force,pressure,andflow,alsoproducebiosignals.Bloodpressure,forexample,isameasurementoftheforcethatbloodexertsagainstthewallsofbloodvessels.Changesinbloodpressurecanberecordedasawaveform.Theupstrokesinthewaveformrepresentthecontractionoftheventriclesoftheheartasbloodisejectedfromtheheartintothebodyandbloodpressureincreasestothesystolic(心臟收縮的)pressure.Thedownwardportionofthewaveformdepictsventricularrelaxationasthebloodpressuredropstotheminimumvaluethatiscalledthediastolic(心臟舒張的)pressure.（5）BioacousticSignalsBioacousticsignalsareaspecialsubsetofbiomechanicalsignalsthatinvolvevibration(motion).Manybiologicaleventsproduceacousticnoise.Forinstance,theflowofbloodthroughthevalves(瓣膜)inthehearthasadistinctivesound.Measurementsofthebioacousticsignalofaheartvalvecanbeusedtohelpdeterminewhetherornotitisoperatingproperly.Therespiratorysystem,joints,andmusclesalsogeneratebioacousticsignalsthatpropagatethroughthebiologicalmediumandcanoftenbemeasuredattheskinsurfacebyusingacoustictransducerssuchasmicrophonesandaccelerometers(加速度計).（6）BioopticalSignalsBioopticalsignalsaregeneratedbytheopticalattributesofbiologicalsystems.Bioopticalsignalsmayoccurnaturallyor,insomecases,thesignalsmaybeinducedusingabiomedicaltechnique.Forexample,informationaboutthehealthofafetusmaybeobtainedbymeasuringthefluorescencecharacteristicsoftheamnioticfluid(羊水).Estimationofcardiacoutputcanbemadebyusingthedyedilutionmethodthatinvolvesmonitoringtheconcentrationofadyeasitrecirculatesthroughthebloodstream.3.CharacteristicsofBiosignalscontinuoussignaldiscretesignaldeterministicsignalrandomsignalstationarysignalnonstationarysignalRealbiosignalsalmostalwayshavesomeunpredictablenoiseorchangeinparametersand,therefore,arenotdeterministic.TheECGofanormalheartrateatrestisanexampleofasignalthatappearstobealmostperiodic.ThebasicwaveshapeconsistsofthePwave,QRScomplex,andTwave.However,thepreciseshapesofthePwaves,QRScomplexes,andTwavesvaryovertime.ThelengthoftimebetweenQRScomplexes,whichisknownastheR-Rintervals,alsochangesovertimeasaresultofheartratevariability(HRV).HRVisusedasadiagnostictooltopredictthehealthofaheartthathasexperiencedaheartattack.PatientswithlowHRVisgenerallyworsethanitisforpatientswithhighHRV.Mathematicalfunctionscannotbeusedtopreciselydescriberandomsignals.Randomsignalsoftenshowdistributionprobabilitiesandcanbeexpressedintermsofstatisticalproperties.TheEMGwhichisusedforthediagnosisofneuromusculardisorders,isarandomsignal.Stationaryrandomsignalsaresignalsforwhichthestatisticsorfrequencyspectraremainthesameovertime.Conversely,nonstationaryrandomsignalshavestatisticalpropertiesorfrequencyspectrathatvarywithtime.Theidentificationofstationarysegmentsofrandomsignalsisimportantforsignalprocessingandpatternanalysis.Biosignalsareoftenverysmall,containunwantednoise,andcanevenbemaskedbyotherbiosignals.Throughoutthedataacquisitionprocedure,itiscriticalthattheinformationintheoriginalbiosignalbepreserved.Sincethesesignalsareoftenusedtoaidthediagnosisofpathological(病理的)disorders,theproceduresofamplification,analogfilteringandanalog-to-digital(A/D)conversionshouldnotcausemisleadingorimperceptibledistortionsinthebiosignal.Distortionsinthebiosignalcouldleadtoanimproperdiagnosis.4.

Signal

AcquisitionSamplingananalogsignalmustbeaccomplishedsothatthedigitizedsignalprovidesanaccurate