超声造影(Contrast-enhanced ultrasound)

超声造影（Contrast-enhancedultrasound）PrefaceReviewthehistoryofthedevelopmentofmedicalultrasound,weseethattheultrasoundrisein70s(real-timegrey-scaleultrasound)orBtypeultrasoundorgray-scaleultrasoundtomographytechnology,laidthefoundationofmodernultrasonicdiagnosis,pavingthewayfortheclinicalapplicationofultrasoundisverywide;colorDopplerimagingtechnologydevelopedinthe80s,themodernultrasonicimagingdiagnosisisverycharacteristicofnondestructiveexaminationandcardiovascularhemodynamicsandbloodflowofthebodyorgansandtissuestocreateanewfield;since90s,theemergenceofmanynewultrasoundtechnologyisoneofthemedicalultrasoundemergeinanendlessstream,themostinfluentialandcanfurtherimproveitsstatusinmodernimagingtechnology,thanultrasoundcontrastimaging.Thecontrast-enhancedultrasonography(contrastenhancedultrasound).Withthehelpofintravenouscontrastultrasoundandcontrastharmonicimagingtechnology,canclearlyshowthemicrobloodvesselsandtissueperfusion,increasetheimagecontrastresolution,greatlyimprovethesensitivityandspecificityofultrasounddetectedlesions.ThisisverysimilartotheenhancedCTscan.Nowadays,radiographynotonlyopensupthescopeofclinicalapplication,butalsoimprovesthediagnosticlevelofconventionalgreyscale/colorDopplerultrasonography,andhasagoodprospectintargetedtherapy.Inconclusion,CEUSisamajortechnologicalinnovationandresearchdirection,andisanewmilestoneinthedevelopmentofmedicalultrasound.Theconceptofcontrast-enhancedultrasoundBarryB.Goldbergisapioneerintheresearchanddevelopmentofnewultrasoundcontrastagentsintheworld.Hehasshowngreatinterestintheresearchandapplicationofvariousultrasoundcontrastagents.Goldbergetalcomparedmicrobubblestoultrasoundcontrastagents(vascularcontrast,agents)orvascularenhancedultrasoundcontrastagents,whicharedifferentfromoralcontrastagents(oralagents)commonlyusedingastrointestinalimaging.Therefore,ultrasoundcontrasthas2kindsofangiographyagentsandoralorenemacontrastagents,andtheformerisalsocalledmicrobubblecontrastmedium.Forthepastmorethan10years,contrastenhancedultrasoundorvascularcontrastenhancedultrasoundhasbeenthemostrapidlydeveloped.Microbubbleultrasoundcontrastagentintheinitialresearchstage,thefirstgasismainlyusedforimagingofairandoxygen,then,istoCO2astherepresentativeofthemicrobubbleshellmembranecontrastagentintravenousinjectionandtranscatheterarterialinjectionofcontrast-enhancedultrasound.In90s,anewtypeofultrasoundcontrastagentcameintobeing.ThemembranecontrastagentcontainingmicrobubbleswasrepresentedbyLevovist(LiFa),AlbunexandEchvist,whichiscalledthefirstgenerationofnewcontrastagents.Sincethen,moreinertgascontainingSonoVue(SonoVue)andOptionsangiographyastherepresentativeoftheshellmembranetypeagent,alsoknownasthesecondgenerationofnewcontrastagent.Theaveragediameterofthenewcontrastmicrobubblesisabout3~5m,whichcansuccessfullypassthroughthepulmonarycirculation,andrealizethecontrastenhancementoftheleftventricle,themyocardium,andtheorgans,tissuesandlesionsofthewholebody.Thesafetyofmicrobubbleultrasoundcontrastagents:alargenumberofexperimentalstudiesandmorethan10000casesofclinicalexperiencehaveprovedthatmicrobubblecontrastagentsaresafe.Accordingtoestimates,eachtimetheintravenousinjectionofultrasoundcontrastmicrobubblescontainingair/gasamountislessthan200L(0.2ml),anynodangerofairembolism;thecontrastagentlistedonlyinshellmembranewascomposedofacousticctose,thecontrastagentwithalbumin,phospholipidsorpolymer.Thatiseasyforhumanmetabolism,toxiceffectsonthehumanbodydoesnot.Therefore,itisanidealultrasoundcontrastagent.ThestudypointedoutthatthesecondgenerationofnewultrasoundcontrastagentwithhighmolecularweightandlowsolubilityandlowdispersionoffluorinecontaininginertgassuchasSF6,C3F8etc.,cansignificantlyextendthemicrobubblesinthehumanbodylife,increasethestabilityofmicrobubbles.Principleofcontrast-enhancedultrasoundStudyofultrasoundcontrastagenthasexperiencedthreestages,namelythefirstgenerationofCO2freemicroshellmembranetypebubblecontrastagentastherepresentative,withAlbunexandLevovist(Levovist)astherepresentativeofthesecondgenerationofaircontainingmicrobubbleshellmembranemodelandcontrastagent,containinganinertgasmicrobubblecontrastagentssuchasSonoVue,Optison,Echogenetc..Thebasicprincipleofthesecontrastagentsarebychangingthesoundattenuation,velocityandenhancedscattering,changethebasicroleofsonicandbetweenorganizations,namelytheabsorption,reflectionandrefraction,sothatthelocationoftheechosignalenhancement.Ultrasoundcontrastagentmicrobubblestoidealthroughsmalllung,heartandcapillarycirculation,sothattheperipheralintravenouscontrastcanbesimple,andcanstablymaintainitseffectinacousticimaging.Itisfoundthatlowsolubilityandlowdispersionofhighmoleculargas,suchasfluorinegas,canincreasethelifetimeofmicrobubblesinbloodandincreasestability.Withthedevelopmentofpolymerchemistry,someforeignscholarsusingbiodegradablepolymericmaterialstoreplacetheHumanAlbuminandothernaturalphospholipidsubstances,changingthecompositionofmicrobubbleshell,therebyavoidingtheproblemofacousticeffectcausedbythelimitationofthenatureofthematerialitselfisnotstable.Atpresentthedomesticandforeignresearchshowsthatpolymermicrobubbleultrasoundcontrastagentdevelopmentisthemostpromising,itcanchangethepolymerizationconditionstheacousticpropertiescanbedesignedfora"tailored"fortheimagingconditionofcontrastagent,maketheparticlesizedistributionismoreconcentrated,afterthesoundattenuationisweakandprolongedinvivotheremainingtimetobeusedindifferentphysiologicalandpathologicalconditionsandtargeteddrugdelivery.Withmicrobubblesespeciallyhalothanegasultrasoundcontrastagentwasdevelopedandusedinclinical,ultrasoundcontrastimagingtechnologyisinrapiddevelopment,fromthecolorDopplerimaging,intermittentharmonicgray-scaleultrasonography,contrast-enhancedultrasoundimagingqualityhasbeengreatlyimproved,theresolutionisobviouslyimproved,andgreatlyreducethetheartifacts,andcandisplayreal-timeperfusion.ClinicalapplicationofcontrastenhancedultrasoundThedevelopmentofultrasoundcontrastagentsandcontrast-enhancedultrasoundhaspromotedtheapplicationofcontrast-enhancedultrasoundinclinicaldiagnosisandtreatment.1.contrastechocardiography(contrast,echocar-diography):itisreportedthatroutineechocardiographyresultsintechnicaldifficultiesinsome10%to20%ofpatients.Microbubblecontrastechocardiographyisausefulmethodforimprovingendocardialfindingsandmakingcardiacfunctionmoreaccurate.Inaddition,itcanvisuallydisplaymyocardialperfusionandimprovethequantitativedeterminationofmyocardialviability,whichcanbesuccessfullyusedtodeterminemyocardialischemiaandnecrosis.Theroomofultrasonographyinthediagnosisofseptaldefectsensitivitywas97%,higherthanthesamegroupofpatientswithcardiaccatheterizationsensitivity.Itcanalsobeusedforthediagnosisofprimarypulmonaryhypertension,2.liverharmoniccontrastenhancedultrasonography:Theeffectofliverultrasoundcontrast:1.,improvethedetectionrateof2.,locationandqualitativechangesofthelesions,3.curativeeffectjudgment,4.portalveinbloodflowstudy.Contrastobservationcontents:1.enhancedmode:theoverallenhancedperipheralenhancedcentralenhanced(radial)enhanced2..Distributionafterthepeak:homogeneous,cyclic,homogeneousenhancementofthe3.phase:accordingtotheCTstagingcanbedividedintoarterialportalvenousphasedelay0-40S41-120S121-200S4.enhancedcontinuouslythetime.Alargenumberofstudieshaveconfirmedthatharmonicultrasoundisthemostsuccessfulclinicalapplicationintheliver,andhasmadeabreakthroughintheapplicationoflivertumors,andcanbecomparedwithCTangiography.Firstofall,thesensitivityofsmalltumorswasimprovedsignificantly,especiallyfortumorslessthan1cm.Secondly,thespecificitywasenhancedsignificantly.(1)livertumorsorlesionsofbenignandmalignantdifferentiation,includinghepatocellularcarcinoma(HCCandmetastasis),hemangioma,adenomaandfocalnodularhyperplasia(FNH)withnon-uniformdistributionoffattyliverandotheridentification;(2)livercancerpreoperativeroutineliverultrasound,andfurtherdeterminethesizeandscopeofinvasiontumormetastasis,therearenosmallhiddenintrahepaticormultifocaltumors;(3)applicationinthediagnosisoflivertumors:interventionalultrasoundcontrasthelpssmalltumorofliverinsuspiciousespeciallynodulebiopsypunctureecho;(4)theapplicationofinterventionaltherapyliverneoplasms:inhepaticarteryembolizationchemotherapyaftercontrast-enhancedultrasound,butalsointheRF,microwaveablation,HIFUimmediatelyaftertreatmentofbedsideultrasoundangiography,determinetheablationeffectandthereisnoresidualtumortissue,todeterminefurthertreatment,improvethecurativeeffect.Forwithoutfurthertreatmentinpatientswithlong-termfollow-up;(5)theapplicationofcontrast-enhancedultrasoundinlivercanceroperation:itisreportedthatintraoperativeangiographycandetect/exceptothersmallertumors,surgicaltreatmentorchangerangeofwaysintime;theprimarylesionresectionintointrahepaticmetastasisoccultexaminationandimmediatelydecidedtouseresectionorablation;evaluatethenatureandextentofliverinjury.Inaddition,inotherliverdiseasessuchaslivertransplantationwithoutvascularstenosisorocclusionofportalhypertensioninpatientswithTIPSstentpatencyandBuchashicomprehensiveultrasoundcolorDopplersyndromedetectionisdifficult,theapplicationvalueofcontrast-enhancedultrasoundhavecertainliver.3.renalcontrastradiography:renalarterystenosisisfrequentlyencounteredbyultrasonography.Renalcontrastangiographycanroutinelydisplayrenalartery,improvethedetectionrateofrenalarterystenosis,andmakeupforthedeficiencyofcolorDopplerultrasonography.ItisalsohelpfulforthecolorDopplerexaminationofrenalvessels.Animalstudieshaveshownthatradiographyhelpstodetectrenaltumorsmoresensitively,andtheclinicalsignificanceremainstobefurtherstudied.4.spleniccontrastultrasonography:CEUSishelpfulforthediagnosisofsplenictumor,splenictraumaandsplenicinfarctionandtheevaluationofitsrange.Chinesescholarshavebeguntoevaluatetheeffectofmicrowaveablationinthetreatmentofhypersplenism.5.contrast-enhancedultrasonographyofpancreaticmasses:reportsofLevovistultrasoundcontrastagentsinpancreatictumorshavebeenreportedbyDaiLuShu,whichincreasedbloodflowinthetumorbyupto100%.Malignanttumorsweremainlyvascularized,whereasbenigntumorswerelessvascular.Itimprovesthejudgmentofbenignandmalignanttumors.6.breasttumorultrasoundcontrast:bymeansofcontrast-enhancedultrasound,itcandisplaythecharacteristicsoftumormicrovasculardistribution,andcanbeusedtoidentifybenignandmalignanttumorsbyusingthetimeechointensitycurvematchedwithmicrobubbles.7.lymphoangiographyenhanced(contrast):experimentalstudieshaveconfirmedthatmicrobubbleultrasoundangiographyishelpfulinshowingdrainageoflymphvesselsandlymphnodes.CEUSishelpfulinidentifyinglymphnodemetastasisofcancer.Therefore,itispossibletohavesentinellymphnodemetastasisinpatientswithbreastcancer.Itisofpotentialclinicalvalue.8.contrastenhancedultrasonographyishelpfultoenhancetwo-dimensionaltranscranialDoppler(TCD)andcolorDopplerangiographyofintracranialvesselsanditsreal-timethree-dimensionaldisplay.9.microbubbleultrasoundcontrastcanbeusedtoevaluatethefunctionofliver,kidneyandhearttransplantationpatients.Applicationofcontrast-enhancedultrasoundinlivertransplantation:1.Preoperativeevaluationofportalstatus,directionofbloodflow,presenceofportalveinthrombosis,portalcavernousdegeneration,andhepaticarteryocclusion;2,whetherthepostoperativehepaticarterystenosisandocclusion(forpatientsafterlivertransplantation,two-dimensionalandcolorDopplercannotseethispoint,itisveryimportant,comparedtotheradiologydepartment,DSAandalotofconvenience)Isthereafalseaneurysm?.Theultrasoundcontrastsystemoftransplantedliverconsistsofselectivearterialcannulation(invasive)orbyperipheralvein(minimallyinvasive)injectionofultrasoundcontrastagent,whichformstheultrasonicinterfaceofliverandliverinlivertissue,andtheimageisdenseandstrongecho.CEUScanobservethechangesofthe3dynamicphasesoftheliverbloodflow,thatis,thearterialphase,theportalveinphase,andtheliverparenchymaphase.Therefore,CEUSishelpfultodetecttheabnormalbloodflowandintravascularlesionsandthedilatationofthesmallbileduct.Toobservethebloodsupplyofthehepaticarteryafterorthotopiclivertransplantationwithcontrast-enhancedultrasound,itisimportanttoevaluatetheprognosisafterorthotopiclivertransplantation.10.other:themicrobubblecontrastagentinjectedintothebladderwillhelptodiagnosebladderureterreflux;contrastagentsinjectedintotheuterinecavitywillhelptoconfirmthepatencyofthefallopiantubesininfertilewomen.ItisreportedthatCEUShasgoodeffectandisexpectedtoreplacetraditionalradiographicradiographywithradioactivity.GuYurongreportedthattheapplicationofultrasoundcontrastagentLevovistcanhelpCDFItoevaluatetumorbloodvesselsmoreaccurately,andisofgreatvalueinthediagnosis,differentialdiagnosisandtreatmentofovarianbenignandmalignanttumors..ApplicationofultrasoundcontrastagentsintargetedtherapyThebroadprospectsofmicrobubbleultrasoundcontrastagentshavebeenreported.Infact，Thetherapeuticeffectofthisnewmicrobubblecontrastagentisalsopromisingandhasattractedmuchattention.Ithasbecomeoneofthemostimportantresearchanddevelopmentdirections.Becausethemicrobubblemeandiameteroflessthanredbloodcells,canrunonthemicrocirculation,andbecauseofthesuccessfuldevelopmentofanewtypeoffluorineandsulfurorfluorocarbongascontrastagent,thecontrastagentinthemicrocirculationlivedsignificantlylonger(accordingtosomereportsoftissue-specificcontrastagentcanbekeptforseveralhoursinlivertissue),scholarsareactivelytoexploretheuseofultrasonicirradiationfortreatmentofnon-invasive.Forexample,intravascularthrombolysis,or/andthemicrobubbleasdrugorgenecarrierincombinationwithmicrobubbleorshellmembranesurface,withthehelpofultrasonicdrugorgenetransferintospecifictissues,theantitumoractivityandpromoteangiogenesis.Themechanismofultrasoundenhancedgenetransfectionandhowtofurtherimprovethegenetransfectionratehavealsobeenactivelyexplored,andalotofpositiveresultshavebeenachieved.Modernmedicalimagingtechniques,suchasCTandMR,havebeenwidelyusedandreliedoncontrastagentsformanyyears.Incontrast,ultrasoundstillrarelyexertsitsgreatpotentialwithcontrastmedia.Inrecentyears,microbubbleenhancedultrasoundimaginghasbeenwidelyappliedinclinicaldiagnosis,andhasshownuniqueadvantages.Microbubbleultrasoundhasanattractiveprospectintargetedtherapy.(SonoVue)isbolaikecompany(Bracco)pharmaceuticalcompanyproducesatpresentanewmedicalimagingagent.SonoVueisonthemarketallovertheworld,andhasbeenwidelyusedintheUnitedStatesandeurope.IntheUnitedStates,itismostlyusedinthestudyoftheheart,whileinEuropeitismainlyusedinthestudyoftheabdomen.ApprovedbytheStateDrugAdministrationreview,Chinaenteredthemarket,SonoVueenteredChinain2002March8,2004afterphaseIIIclinicalstudy;21hospitalfirstbegantouseYumproductstomatchtheuseofSonoVue.Developveryrapidly.Itisaneffectivetoolforclinicians.ComparedwithMRIandCT,thecostofultrasonicexaminationislowandhasverygoodmarketvalue.BraccoinShanghaiPudongpharmaceuticaljointventureBracco-SineJointVenture,ChinesenamedBraccoXinyiPharmaceuticalCo.Ltd.,beganoperatingthisyear,partofthejointventurebycontrastagentwillplanttoproduce.Therefore,theproductcanbepurchasedathome,thepriceofabout700yuan.Mostpatientscanaffordit.