PHOSPHORUS-31INVIVOHUMANCARDIAC MAGNETICRESONANCESPECTROSCOPY: DEVELOPMENTOFMRSPECTROSCOPYTECHNIQUES By HEE-WONKIM ADISSERTATIONPRESENTEDTOTHEGRADUATESCHOOL OFTHEUNIVERSITYOFFLORIDAINPARTIALFULFILLMENT OFTHEREQUIREMENTSFORTHEDEGREEOF DOCTOROFPHILOSOPHY UNIVERSITYOFFLORIDA \ 1997 Thisdissertationisdedicatedto mymother,SoonRanKwon mywife,Jung-Hee anddaughters,Dah-SongandYeh-Song and SaengJiLee,mymother-in-law ofblessedmemory ACKNOWLEDGMENTS Allworkincludedinthisdissertationwouldnothavebeenpossible withouttheguidanceofKatherineScott,Ph.D.,myprincipaladvisor.Dr.Scott ismyscientificmentorandmotivator.Hergenuineenthusiasmforthepursuit ofscientificknowledgeandwarmheartedpatiencewerearealencouragement formeduringthewholeperiodofresearch. Iamobviouslygratefultoallthesupervisorycommitteemembersfor theirexcellentguidance,enduranceandprobingquestions.Jeffrey Fitzsimmons,Ph.D.,gaveanoverallpictureofthewholebodyimagingsystem wherethisresearchhasbeendoneandadvisedmetofollowthepropertrackof MRinstrumentation.RichardBriggs,Ph.D.,advisedmetoclarifythe assumptionsandthedataobtained.Hisrigorousproofreadingisalsomuch appreciated.ToJ.RayBallinger,M.D.,Ph.D.,Iamindebtednotonlyforhis adviceandsuggestionsforallinvivospectroscopicworkandmuchhelpatthe rightmoments,butalsoforhisfriendshipandgenerosity.DavidHintenlang, Ph.D.,gavehisthoughtfulcommentsonmyworks.ChrstineStopka,Ph.D., inspiredmewithherenthusiasticpersonalityandshapedmydissertationby keenreviews. Iamgratefultoallofmycolleaguesandfriendswhohavecontributedin somanywaystowardthecompletionofthisresearch.Iamdeeplyindebtedto HaejinKangPh.D.,forintroducingmetoDr.ScottandhelpingmesinceIfirst participatedintheNMRrealm.Hefurnishednotonlytechniquesnecessaryfor MRspectroscopybutalltheencouragementforlifeinGainesville.Fellow graduatestudent,AngelaBrunerhasgivenmanydaysofhertimetosearching outthemethodswelookedforandsharedthoughtsandtheexcitementduring manystudies.IwishtorecognizeDavidPetersonwhodealtwithdifficultiesin themiddleofengineeringproblemswhenIwastrappedduringbuildingthe secondMRprobe.HeisanexcellentRFcoilengineerandwellawareofKorean cultures.CarolSweeneyhassharedwithmelotsoftheexcitementand frustrationofMRspectroscopy.Iwishtothankherforencouragement,forhelp inconstructingphantomsandherthoughtfulpersonalitywhichwas sufficientlyinsightfultohelpmeoutofsomedifficulties.JimScottadvisedme inthedesignofthesecondprobeandgavemegoodinsight.Iamreallygrateful forhissuggestions,andIwasalwaysdelightedwithhiswarmpersonality. DianaGarside,Ph.D.,advisedmeinhandlingchemicalsubstances.Iwishto thankChrisHunterandTeresaLyles,M.S.,forasecretarialsupport.Teresa Lyles’enthusiasticpersonalitywasaninvigorationinGatorcountry.Jintong Mao,Ph.D.helpedmetostarttouseEPIC®programming.ToSoonNyung Huh,Ph.D.,whoprovidedsoundunderstandingtheRFcommunicationandto MarianBuszko,Ph.D.,whodiscussedmanyaspectsofMRtechniques,I expressmydeepthanks. Iappreciatethecommentsofferedbythefollowingexpertswho furnishedmanyhelpfulsuggestions.CecilCharles,Ph.D.,gaveaninsighton howtoimplementtheoutervolumesuppressionwithCSI.BenInglis,Ph.D., waswillingtosupportmewhenIsuggestedaplantoapplytheBIR-4pulseto 31Pspectroscopy.MichaelGarwood,Ph.D.,kindlysenttheBIR-4pulsefiles. NapaponSailasuta,Ph.D.andQingTan,M.S.,providedsourceprograms necessaryforEPIC®pulseprogramming.TomRaidy,Ph.D.,sharedhis expertiseinoutervolumesuppressionsandshortTespinecho.Iamgrateful fortheirkindandvaluablehelp.IthanktoHeungKyuLee,Ph.D.,for IV discussionsontheMRimagingsystem.Healwaysencouragedmethroughout theresearchperiod. Iwouldliketorecognizemyformerteachersandseniors.Inparticular,I ammuchobligedfortheencouragementofChangSoonKang,Ph.D.,myformer graduateadvisorinKorea,ChangKunLee,Ph.D.,JungEuiKuh,Ph.D.,and HaeRyongHwang,Ph.D.,whoalwaysregardmewithaffection. Ialsohavetoexpressmyappreciationtoallthevolunteerswhomadea specialefforttohelpmyusuallyrushedrequests.ThanksalsogotoDukWon Kim,M.S.,whospentalotoftimeinhelpingmeorganizethemanuscriptfiles. Iammostgratefultomyfamilyinmycountrywhosogenerously encouragedmetostudyabroadeveninadversity.Iamverymuchindebedto mymother,SoonRanKwon.Surely,herprayerwasresponded.Iowea tremendousdebtofgratitudetomysisters,HwaSeungandHaeJa,for encouragementandpatienceandforagooddealofmoralsupportthroughout mystudy.MyspecialthanksgotoMr.DongDuShinforrendering support andgivingmanydaysofhisprecioustimetome. Iwishtorecognizemyfather-in-law,ChunDukOh,forallhehasgiven sounselfishlyinthemostheartbreakingdaysinhislife,ashavemysister-in- lawJeeHeeOhandYoungHoonKimforencouragementwhenitwasmost needed. Nodoubtmygreatestdebtsaretomyfamily.MydaughtersDah-Song andYeh-SonghaveturnedourlivesintotrulyhappySongs.Withoutmywife, Jung-Hee,nothingwouldhavebeenpossible.Herlovemadeallmydaysa happyexperience.Igivehermylovingappreciation. v TABLEOFCONTENTS ACKNOWLEDGMENTS iii LISTOFTABLES viii LISTOFFIGURES ix SYMBOLSANDABBREVIATIONS xiii ABSTRACT xv INTRODUCTION 1 ExistingKnowledgeinThisArea 1 StatementoftheProblem 3 SpecificAimsoftheProposedResearch 4 FeasibilityofSurfaceCoilSpectroscopy 5 CardiacGatingMRExperiment 5 OuterVolumeSuppressionanditsHybrid 5 ChemicalShiftImagingwithOuterVolumeSuppression 6 Quantitation 6 SURFACECOILSPECTROSCOPY 7 ReviewoftheLiterature 7 DesignandBuildingofSurfaceCoils 8 COILA:Transmitter/ReceiverSurfaceCoil 9 DoublyTunedCircuit 10 COILB:SeparateTransmitterandReceiverCoil 11 CoilBuilding 13 LOCALIZATIONTECHNIQUESFORCARDIACSPECTROSCOPY 22 ReviewofLocalizationTechniquesforCardiacSpectroscopy 22 RotatingFrame 22 DepthResolvedSurfaceCoilSpectroscopy(DRESS) 23 ImageSelectiveInVivoSpectroscopy(ISIS) 23 SpectroscopicImaging 24 TheTechniquesDevelopedforThisStudy 24 OuterVolumeSuppressionPulse 24 OVSPulse 26 OVSpulsedesign(I):Cos-sincpulse 26 OVSpulsedesign(II):SLRsaturationpulse 31 2DOVS/IDISISHybrid 32 ShortTeSpinEcho 33 SpectroscopicImaging 33 vi 1 MATMERRISAyLsSteAmNDMETHODS ! 5522 PhantomStudy 52 InVivoCardiacSpectroscopy 54 HumanVolunteers 54 ECGCardiacGating 54 B0FieldShimming 56 ShimmingwiththeSTEAMsequence 57 InVivoSpectroscopyProtocol 60 RESULTSANDDISCUSSION 68 PhantomExperiments 68 TestsoftheCoils 68 COILA 68 COILB 69 ShortTeSpinEchoPulse 71 OVS-ISISLocalization 72 SpectroscopicImaging1 73 SpectroscopicImagingII 74 HumaninVivoCardiacSpectroscopy 76 31PMRCardiacSpectra 76 PCr/ATPRatio 77 BloodContamination 80 SUMMMRAPRrYobAeNDCONCLUSION 1Il1l LocalizationTechnique 112 Phosphorus-31CardiacMRinVivoSpectroscopy 113 APPENDIXA:Matlab®M-fileforSaturationPulseDesign 115 APPENDIXB:Cos-SineSaturationPulse 120 APPENDIXC:SLRMaximumPhaseSaturationPulse 125 APPENDIXD:PhaseModulatedBIR-4Pulse 129 LISTOFREFERENCES 134 vii LISTOFTABLES Table page Table2.1 ComparisonofCOILAandCOILB 15 Table5.1 SNRcomparisonfromMDPApeakbetweenthetwocoils ; 70 Table5.2 PartlysaturatedPCr/ATPratiofromhumanheartmuscle 78 Table5.3 PartlysaturatedPCr/ATPratiofromavoxeladjacent/exterior totheheartlayer 78 Table5.4 Partialsaturationcorrectionfactors 79 Table5.5 PCr/ATPratioadjustedbysaturationcorrectionfactors 80 viii LISTOFFIGURES Figure page Figure2.1 CircuitdiagramofCOILA 16 Figure2.2 Fieldstrengthvs.distancefromthecoil 17 Figure2.3 COILA:Doublytunedtransceivercoil 18 Figure2.4 CircuitdiagramofCOILB 19 Figure2.5 COILB:Separate-transmitter/receivercoil 20 Figure2.6 COILA(center),COILB(right)andlargetransceivercoil 21 Figure3.1(a) PhasemodulatedBIR4pulse 36 Figure3.1(b) BlochsimulationofBIR4pulse 37 Figure3.2 OutputoftheMatlab®pulsegenerationprogram 38 Figure3.3 Signalresponseofthecos-sincpulse 39 Figure3.4 Mzresponseofthecos-sincpulse 40 Figure3.5 MaximumphaseSLRsaturationpulse 41 Figure3.6 SignalresponseoftheSLRsaturationpulse 42 Figure3.7 MzresponseoftheSLRsaturationpulse 43 Figure3.8(a) BlochsimulationofGEstandardsaturationpulse 44 Figudreeph3.a8si(an1g) gBrlaodcihenstimulationofGEstandardsaturationpulsewith 45 Figure3.8(b) Blochsimulationof2kHzSLRMaximumPhasesaturation pulse 46 Figure3.8(b’) Blochsimulationof2kHzSLRMaximumPhase saturationpulsewithdephasinggradient 47 IX Figure3.8(c) Blochsimulationof5kHzSLRMaximumPhasesaturation pulse 48 Figure3.8(c’) Blochsimulationof5kHzSLRMaximumPhasesaturation pulsewithdephasinggradient 49 Figure3.9 DoubleOVS-ISIShybridpulsediagram 50 Figure3.10 CSIcombinedwithSLRMaximumPhasesaturationpulse diagram 51 Figure4.1 10mmsliceaxialimageofPHANTOM1 63 Figure4.2 10mmsliceaxialimageofPHANTOM2 64 Figure4.3 TypicalposteriorplacementoftheECGeleoctrode 65 Figure4.4 ProtonspectrumaftershimmingwithSTEAM 66 Figure4.5 ProtonspectrumwithB0shimmingwithAUTOSHIM 67 Figure5.1 Unlocalized31PspectrumfromPHANTOM2usingCOILB 82 Figure5.2(a) Signalfromthe5cmdeep25mmcoronalslicewitha1.8 msexcitationpulseusing7.5cmtransceiverCOILA 83 Figure5.2(b) Signalfromthe5cmdeep20mmcoronalslicewitha doubleamplitude3.6msexcitationpulseusingCOILA 83 Figure5.2(c) Signalfromthe5cmdeep20mmaxialslicewitha3.6ms excitationpulseusingCOILA 84 Figure5.2(d) Signalfromthe5cmdeep20mmaxialslicewithadouble amplitude3.6msexcitationpulseusingCOILA 84 Figure5.3(a) Signalfromthe5cmdeep25mmcoronalslicewitha1.8 msexcitationpulseusingseparatetransmitter/receiverCOILB 85 Figure5.3(b) Signalfromthe5cmdeep20mmcoronalslicewitha3.6 msexcitationpulseusingCOILB 85 Figure5.3(c) Signalfromthe5cmdeep20mmcoronalslicewitha doubleamplitude3.6msexcitationpulseusingCOILB 86 Figure5.3(d) Signalfromthe5cmdeep20mmaxialslicewitha3.6ms excitationpulseusingCOILB 86 Figure5.3(e) Signalfromthe5cmdeep20mmaxialslicewithadouble amplitude3.6msexcitationpulseusingCOILB 87 x