4 Principles of high-intensity focused ultrasound

Добавил:

Sekretar kiopkiopkiop18@yandex.ru t.me/Prokururor I Вовсе не секретарь, но почту проверяю Опубликованный материал нарушает ваши авторские права? Сообщите нам.

Вуз:

Ростовский Государственный Медицинский Университет

Предмет:

Медицина общая

Файл:

Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3658_Библиотеки_им_академика_М_И_Перельмана.pdf

Скачиваний:

Добавлен:

30.08.2026

Размер:

49 Мб

Скачать

☆

<<< < Предыдущая 1 2 34 / 354 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 > Следующая >>>

Chapter3:Irreversible electroporation

20. NealRE2nd,SinghR,HatcherHC,etal.Treatmentofbreast cancerthroughtheapplicationofirreversibleelectroporation usinganovelminimallyinvasivesingleneedleelectrode.Breast Cancer Res Treat2010;123(1):295–301.

21. IvorraA,Al-SakereB,RubinskyB,etal.Invivoelectrical conductivitymeasurementsduringandaertumor electroporation:conductivitychangesreectthetreatment outcome.Phys Med Biol2009;54(19):5949–5963.

22. NealRE2nd,GarciaPA,RobertsonJL,etal.Experimental characterizationandnumericalmodelingoftissueelectrical conductivityduringpulsedelectriceldsforirreversible electroporationtreatmentplanning.IEEE Trans Biomed Eng 2012;59(4):1076–1085.

23. NealRE2nd,MillarJL,KavnoudiasH,etal.Invivo characterizationandnumericalsimulationofprostate propertiesfornon-thermalirreversibleelectroporationablation. Prostate2014;74(5):458–468.

24. AuJT,KinghamTP,JunK,etal.Irreversibleelectroporation ablationofthelivercanbedetectedwithultrasoundB-mode andelastography.Surgery2013;153(6):787–793.

25. AppelbaumL,Ben-DavidE,SosnaJ,etal.USndingsaer irreversibleelectroporationablation:radiologic–pathologic correlation.Radiology2012;262(1):117–125.

26. HjoujM,LastD,GuezD,etal.MRIstudyonreversibleand irreversibleelectroporationinducedbloodbrainbarrier disruption.PLoS ONE2012;7(8):e42817.

27. WendlerJJ,PorschM,HühneS,etal.Short-andmid-term eectsofirreversibleelectroporationonnormalrenal tissue:ananimalmodel.Cardiovasc Intervent Radiol2013;36 (2):512–520.

28. ZhangY,WhiteSB,NicolaiJR,etal.Multimodalityimagingto assessimmediateresponsetoirreversibleelectroporationina ratlivertumormodel.Radiology2014;18:130989.

29. RyanER,SofocleousCT,SchöderH,etal.Split-dosetechnique forFDGPET/CT-guidedpercutaneousablation:amethodto facilitatelesiontargetingandtoprovideimmediateassessment oftreatmenteectiveness.Radiology2013;268(1):288–295.

30. ScheerHJ,NielsenK,deJongMC,etal.Irreversible electroporationfornonthermaltumorablationintheclinical setting:asystematicreviewofsafetyandecacy.J Vasc Interv Radiol2014;pii:S1051–0443(14)00101–8.

31. CannonR,EllisS,HayesD,etal.Safetyandearlyecacyof irreversibleelectroporationforhepatictumorsinproximityto vitalstructures.J Surg Oncol2013;107(5):544–549.

32. MartinRC2nd,McFarlandK,EllisS,etal.Irreversible electroporationinlocallyadvancedpancreaticcancer:potential improvedoverallsurvival.Ann Surg Oncol2013;20Suppl 3:S443–S449.

33. NarayananG,HoseinPJ,AroraG,etal.Percutaneous irreversibleelectroporationfordownstagingandcontrolof unresectablepancreaticadenocarcinoma.J Vasc Interv Radiol 2012;23(12):1613–1621.

Chapter

Principles of high-intensity focused ultrasound

Aradhana M. Venkatesan and Bradford J.Wood

Introduction

High-intensityfocusedultrasound(HIFU),alsoknownasfocused ultrasound(US),isa non-invasiveimage-guidedtherapywhich hasbeenprimarilyemployedintheclinicalrealmfornon-invasive thermalablationofbenignandmalignantneoplasms. imagingguidance,treatmentmonitoring,andtherapycontrolare achievedwitheitherUS ormagnetic resonanceimaging(MRI) guidance.3 HIFU clinical experience has been described in the

1,2

Real-time

treatment of leiomyomata (uterine broids), prostate (benign prostatichypertrophyandcancer),breast,hepatic,renal,pancreatic,brain,andbonetumors,althoughformostofthesetumors, relativelysmallnumbersoftreatedpatientshavebeendescribed andwidespreadadoptionofHIFUthermoablationremainslimited.Ongoingtechnicalchallengesincludethefeasibilityoftreatinglargetumorswithinanite treatmenttime,treatingtumors pronetomotion,andaccessingtargetswhentheacousticwindow isrestrictedbyinterveninganatomy(e.g.,ribs,bowel).

ArangeofprovocativebioeectsoftherapeuticUSbeyond thermoablationhavethepotentialtobeleveragedinthecareof selectedoncologypatients.Hyperthermiceectscanpotentiate therelease of thermosensitive drugs, enhance the permeabilityandretention(“EPReect”)ofchemotherapeuticagentsor nanoparticles,sensitizetissuestoradiationeects,andpotentially augment therapeutic gene transfection within tumors. MechanicaleectsofHIFU,includingstableandinertialcavitationandradiationforces,alsoplayrolesinheat-sensitivedrug andgenedelivery,andtheenhancedpermeabilityoftherapeuticmolecules,anddisruptionoftheblood–brainbarrier(BBB). eseareareasofongoingandpromisingoncologicresearch.

ischapterwillprovideanoverviewoftheprinciplesand existingtherapeuticplatformsforHIFU,includingUSandMRI guidance, treatment planning, and monitoring capabilities. Asummaryofcurrentandpotentialfutureclinicalapplications isalsopresented.

a focused US system and executed preclinical testing in the brain.4Subsequently,inthe1950s,theFrybrothersdevelopeda clinicalHIFUdeviceintendedtotreatpatientswithneurological disorders likeParkinson’s disease.5 is systememployed radiography to determine target location in relation to the overlyingcalvariumandfocusedtheUSbeam throughacraniotomy.

5–7

e needtoremoveaportionoftheskullandthe absenceofhigh-resolutionneuroimaginglimitedfurtherdevelopmentofthisresearchatthattime.8Inthe1970s,theability offocusedUStoinducehyperthermiaintissue(i.e.,elevation oftissuetemperatureto43°C)wasoutlined.

8,9

Sincethe1990s, coincidentwith the maturationof US transducerdesignsand more precise intraprocedural targeting and monitoring with diagnosticUSandMRI,scienticinterestinHIFUforoncologicapplicationshasbeenrevitalized.

Thermal eects

Ablation

e principles governing diagnostic US and HIFU are the same. Representativetime-averaged intensities for diagnostic US (B-mode, pulsed, or continuous Doppler) may be up to 720mW/cm2accordingtoUSFoodandDrugAdministration (FDA)regulations.eintensityofHIFU,incontrast,isseveral timeshigher,from100to10,000W/cm2,withpeakcompression pressuresofupto70MPaandpeakrarefactionpressuresupto 20MPa.8HIFUablationutilizesapiezoelectrictransducerwith acenterfrequencytypicallyof1–7MHzwhichisinsonatedinto the body via acouplingmedia, such as a degassedwater–gel pad interfaceforextracorporeal systems or with a gel-coated water balloon surrounding the transducer for endocavitary approaches.

HIFU-treatedtissuesexperiencearapidelevationoftemperatureas a resultof acoustic energyabsorption at the target focus.

1,8,10

 e small volume heated rapidly results in a

well-demarcated focus of coagulativenecrosis, with the skin

HIFU principles and bioeects

History

HIFUisnotanewtechnology.Itsrstmedicallyapplicableuse wasdescribed by Lynn et al. in 1942;these authorsdesigned

andadditionaloverlyingtissue layersbeing either unaected or sustaining minimal temperatureelevation due to the low acoustic energy away from the US focus

1,10

(Figures 4.1 and

4.2).Aswithotherformsofthermoablation,thedegreeofther-

maldamagetothetissuedependsonthetemperaturereached andthedurationoftheexposure.6Tissuetemperatureelevated

Interventional Oncology, Second Edition, ed. Jean-François H.Geschwind and Michael C.Soulen. Published by Cambridge University Press. ©Cambridge University Press2016

Chapter4:High-intensity focused ultrasound

Figure 4.1 Intraprocedural magnetic resonance (MR)-guided high-intensity focused ultrasound (HIFU) monitoring and MR imaging and histopathologic ﬁndings

after leiomyoma ablation with MR-guided HIFU. Graphic user interface displays multiplanar three-dimensional T2-weighted imaging and overlaid temperature maps (A, B) as well as overlaid thermal dose estimates (C, D) during sonication of an anterior intramural leiomyoma within the body of the uterus. Accumulated thermal dose information in the treated volume is displayed at the end of each sonication as a thermal dose estimate. These thermal doses are reported in CEM43, with 30 CEM43 (beige polygon, C, D) corresponding to onset of tissue alteration and 240 CEM43 (white polygon, C, D) representing predicted territory of complete necrosis. Both 30 CEM43 and 240 CEM43 thermal dose estimates are updated after each sonication. Sagittal (E) and coronal (F) contrast-enhanced MR images after HIFU show non-enhancing treated region (arrows). (G) Bivalved gross uterine specimen shows hemorrhagic necrosis in the area of treatment (arrows). Low-magniﬁcation (4×) histologic images of margin (H), high-magniﬁcation (10×) images of margin (I), and high-magniﬁcation images of the center of the ablation zone (J) conﬁrm necrosis (asterisk) and narrow zone of transition (arrows) between viable and necrotic HIFU-treated tissue. (Reprinted as per Elsevier permissions requirements from Venkatesan AM, Partanen A, Pulanic TK, et al. Magnetic resonance imaging-guided volumetric ablation of symptomatic leiomyomata: correlation of imaging with histology. J Vasc Interv Radiol 2012; 23: 786–794.14)

tomorethan60°Cfor1secondwillgenerallyleadtoinstantaneousandirreversiblecelldeathviacoagulationnecrosis.8With longerHIFUexposures,perfusionresultsinareductionofthe temperaturegradientachieved. Tissues in proximity to large bloodvesselsexperienceconvectiveheatlossanalogoustothat encountered for other forms of thermoablation, particularly iftheHIFU energy delivery islongorslow.6Blood ow and perfusionvariabilitybaseduponanatomicsiteandtissuetype remainachallengeforecaciousHIFUtherapy,asthesecanbe associatedwithtreatmentinecienciesandvariabilityintreatment outcome.

6,11–14

 In addition to controlling the temperatureachievedand exposure duration, US beam focusingcan achievehigh acoustic intensities.

1,8

 Averageablation volumes

achievablewith individualHIFUsonicationsareabout1 mm indiameterandabout10mminlength,withanaveragevolumebetween50and300mm3.

1,8

Byperformingmultipleindividualshortexposures,larger compositeablation volumes,whichencompassasolidtumor andintendedtumor-freemargin,canbeachieved.1Pausesare oen required between sonications to prevent tissue boiling and bubble formation,which can reect and distort the US eld,resultinginunpredictablelesiongrowthand non-target thermal injury,or uncontrollable cavitation.1 To circumvent thepotentialforlongtreatmenttimesassociatedwiththisstrategy,specictechniqueshavebeendeveloped,includingtheuse ofinterleavemode,wherebysonicationorderisprescribedso

Section II:Principles of image-guided therapies

t Rt

=∆

−

Figure 4.2 Therapy planning for

magnetic resonance (MR)-guided high-intensity focused ultrasound leiomyoma ablation. Therapy-planning software enables delineation of the planned treatment volume (PTV) and individual sonications during treatment planning. Each sonication cell (either treatment cell or feedback cell) may be assigned its own acoustic power setting, sonication frequency, and cell diameter. (A) Individual sonications are delineated, and cumulative volume of individual planned sonications, known as a treatment cluster, is compared with PTV to determine the percentage of target volume to be ablated (in this example, 28%). Regulatory stipulations for this trial permitted ablation of 30% of target ﬁbroid volume. (B) Three-dimensional T2-weighted MR imaging allows for multiplanar assessment and treatment planning, with PTV (red ellipse) and

After populating PTV with intended sonication cells, the radiologist veriﬁes on all planes to conﬁrm that cells remain within the PTV outline. (Reprinted as per Elsevier permissions requirements from Venkatesan AM, Partanen A, Pulanic TK, et al. Magnetic resonance imaging-guided volumetric ablation of symptomatic leiomyomata: correlation of imaging with histology. J Vasc Interv Radiol 2012; 23: 786–794.14)

planned sonications (green ellipses) superpositioned on anatomic images.

astominimizesonicationoverlap,resultinginareductionin cooling times.6 Another method to achieve conuent, more time-ecientHIFUablationsemploysphased-arraytransducersandbeam-formingtechniqueswhichcanenlargetheeectiveUSfocalareawhilepreservingthefocusingcharacteristic oftheUS eld.

1,15

Volumetric ablation,in particular,employs phased-array transducers and driving electronics enabling rapidtemporalswitchingofthefocalpointlocationwithinthe treatedtissue.

12,14,16–19

Largertissuevolumesareheatedperunit timeusingthistechnique,whichtakesadvantageoflocalheat diusion.

1,12,14,16–19

Hyperthermia

ClinicallyrelevantthermaleectsoffocusedUSoccuratboth ablative(>60°C)andnon-ablativehyperthermictemperatures (typically40–45°C).Hyperthermiacansensitizetissuetoradiationorchemotherapyandthesearepotential emergingapplicationsforfocusedUS.

6,20,21

Activationof heat-sensitive genes usingHIFUisalsobeinginvestigated,wherebyHIFU has the potentialtoenablelocal, physical, andspatiotemporalcontrol oftransgeneexpression.

6,20,22

Chemotherapeuticagentsencapsulatedwithin thermosensitive liposomesmayalso be locally released within tumors using HIFU. Properties intrinsic to heat-sensitive liposomes include: (1) their increased bilayer permeabilityatagel-to-liquidcrystallinephasetransitiontemperaturecomparedwithboththe solidandliquidphases, and (2)theabilityofawater-solublecomponenttobereleasedfrom the bilayer as it begins to melt.23 In the hyperthermic range, heat-sensitive liposomes undergo a phase transition, from a solid-ordered to liquid-disordered phase, with resultantdrug

24,25

release.

Ultrasound eld generation and transducerdesign

HIFUtransducersvaryinsizedependingontheclinicalapplication,whichcanrangefromsupercialendocavitarytargetsto

deepabdominaltargetsthatnecessitategreateracousticpower forsuccessfulablation.

3,26

esimplestHIFUtransducerstypically consist of a single-element spherical or at transducer moved mechanically to ablate tissue using a point-by-point (rastering)sonicationapproach.Mostcommonly,thesetransducersareself-focusingpiezoceramictransducerswithaxed apertureandfocallength.1Morecomplexphased-arraytransducerscomprisemultipletransducerelements,witheach elementdrivenbyaseparateradiofrequencysignal withitsown phase, frequency, and amplitude. As a result, selective activation of individual elements and electronic beam steering of these transducers can be performed.1 For specic clinical applications,such as brain HIFU,the number of elements in phased-arraytransducerscan be in the thousands.

1,27

Topreventthermaldestructionofthetransducerduringhigh-power applications,activewatercoolingmaybeutilized.Giventheir morecomplexdesign,phased-arraytransducers are typically muchmoreexpensivethansingle-elementdevices,1butmaybe fasterandmoreversatileinapplications.

Thermal dose concept

Tissuethermaldamageathigh-temperatureHIFUexposures can be predicted via an Arrhenius analysis or, more commonly, by using the Sapareto–Dewey thermal dose model,

tfinal

−

(

)

∑

lentminutesat43.0°C,Tisthemeantemperatureduringtime Δt,andRisaconstantthatequals0.50above43.0°Cand0.25 below 43.0°C.28 e Sapareto–Dewey model describes tissue thermaldamageasapproximatelylinearlydependentonexposure time and exponentially dependent on the temperature elevation,withthethermaldoseexpressedinequivalentminutes at 43°C (EM43°C, CEM43°C, or t43). of120–240 minutesat43°Cresultin irreversible coagulative

, where t43 is the thermal dose in equiva-

8,29

 ermal doses

Chapter4:High-intensity focused ultrasound

necrosis, although the specic threshold for a given target will varydepending on tissue type,regional blood ow,and perfusion.

8,30

Mechanical eects

MechanicaleectsofHIFUaresustainedwhenacousticpulses at high intensitiesare utilized. includecavitation,microstreaming,andradiationforces.

Cavitation

Athigh-pressureUSamplitudes,microbubblesdevelopasfoci ofgas are drawn out of solution on the basisof US-induced local temperatureelevationsand alternating tissue compressionandrarefaction. tion,growth,andimplosivecollapseofthesebubblesandtheir interactionwithhigh-intensityUS.32Preformedmicrobubbles, availableclinicallyasUScontrastagents,canbeusedascavitationsitesatlower-intensityUSexposures. itationhave been described: stable and inertial cavitation. Stable(non-inertial)cavitationrefers tothe stableoscillation ofbubblesizewhenexposedtoalow-pressureacousticeld.8 Inertial(unstable)cavitationisassociatedwithviolentoscillationsofthebubble,rapidbubblegrowthduringtherarefaction phase, and subsequentimplosivebubblecollapse, which can resultincelldeathandtissuedamage.

HIFUmechanicaleects,usedin conjunctionwithHIFU thermal ablation, may result in larger tumor ablation volumes and reduced treatmenttimes.6 Histologic studies have also demonstrated disruption of the BBB, selective vascular damage, arterial occlusion, and disruptionof atherosclerotic plaquesandthrombiasaresultof cavitation. canalsoaectcellmembraneandvascularpermeability,which hasthepotentialtobeleveragedfortargeteddepositionofthermosensitivechemotherapeutics. alterthesafetyproleandmaybelesscontrollableortargetable thanstandardHIFUwithoutcavitation.Cavitation detection isavailableonsomeMRI-HIFUsystemsasasafetymeasure.

6,31

Acousticcavitationreferstotheforma-

8,31–33

 ese mechanical eects

6,33

Twoformsofcav-

35–37

6,38–42

Cavitation

6,43,44

However, cavitationmay

8,34

Histotripsy

HIFU mechanical eects on their own can result in precise ablativelesions. cavitation,wherebyshortpulses(1–2ms)ofveryhigh-intensity US(upto100MPa)andtheirresultantmechanicalbioeects, likely combined with high temperatures, achieve focal tissue vaporization and destruction. waytoevaluatetheutilityofhistotripsy-basedtissuedestruction for clinical applications, including tumor ablation and thrombolysis.

Microstreaming

Microstreamingistheresultofstablecavitation,whichgeneratesrapidmovementofuidnearmicrobubblesdue to their oscillatingmotion.8Microstreamingcanresultintheproductionofshear forcesthatcausecellmembranedisruptionand resultingcelldamage. microstreamingshearforcesmayfacilitateUS-enhanceddrug orgenedelivery.

8,31,45

Histotripsyreferstoacontrolledformof

6,8,31,46–48

 Eorts are under

8,31

Transientcellmembraneinjurydueto

8,49

Radiationforces

HIFUcancreateradiationforcesintissuesthatarethe result ofabsorptionand reectionofUSwaveenergy. associatedwithadditionaldestructivebioeects,includingcell membrane deformation and microstreaming. forcesoccurringalongthedirectionoftheUSbeam,delivered viapulsedsonications,havebeenimplicatedas a mechanism forHIFU-enhanceddrugdeliverytotumors.

31,50,51

6,52

31,49

eseare

 Radiation

HIFU system technology

Imagingguidance during HIFU oncologic therapy is critical forimmediatepretreatmentplanning,intraproceduraltargeting,andsafetymonitoring,andpostproceduralassessmentof therapeuticeect.CurrentlyHIFUimagingguidanceiseither US-guidedorMRI-guided,witheachmodalityhavingspecic advantagesanddisadvantages.

Ultrasound guidance



Worldwide,mostHIFUtreatmentsarebeingperformedunder USguidance.

6,53

US-guidedHIFUinvolvessuperimposingthe eldofthediagnostic transducerandtheeldoftherapeutic source.1AdvantagesofUSguidanceareitsrelativelylowcost andavailability.6Limitationsincludeitsdependenceonindividualoperatorskillanddicultieswithsonographicdelineationofthetumorinrelationtosurroundinganatomyduring ablation.DuringHIFU treatment,cloudsof gas bubbles will be visible as a region of echogenicity.1Whilethis echogenicityprovidesgeneralinformationaboutablationlocation,itcan alsoimpedetargetvisualization.Intraproceduraltemperatures alsocannotbereadilymeasuredwithcurrentUSimagingtechniques.6Reliablyreproducingthesameimageandtargetingthe same anatomic locationduring treatment with US guidance canalso be challenging.6Asnoted by Tempanyetal.,eorts toimproveUSoncologicimagingareongoing,includingthose directedtowardsthedevelopmentof US-based thermometry, USelastography,andothermethodsfordetectingtissuecoagulationduringHIFU.

6,54–56

MRI guidance

Advantagesof real-time MRI guidanceduringHIFUtherapy are its intrinsic resolution, multiplanar imaging capabilities, and the availability of intraprocedural temperature-sensitive MRI parameters. T1-weighted, proton density, and diusion-weightedimagingareall temperature-sensitiveand havebeenstudiedasameansforguidingthermalablation. emostwidelyusedmethodformonitoringMR-guidedthermal therapies is the proton resonance frequency(PRF) shi method.

theexternallyappliedmagneticeldofMRI, thusdecreasing theresonantfrequencyofprotons.Whenthetissuetemperaturerises,hydrogenbondingispartiallydisrupted,leadingto increasedelectronshieldingofprotonsandareductioninresonantfrequency.iseecthasbeenshowntobethesamefor allaqueoustissuesandlinearwithinthetemperaturerangeof interest,withatemperaturecoecient,α= 0.01ppm/°C.Use

Normally, hydrogen electrons shield the protons from

6,57–59



Section II:Principles of image-guided therapies

−

∅∅

∅

of this relationshipto measure temperature is referred to as PRFshithermometry.61Employingthismethod,tissuetemperaturechangesaredeterminedbythe changeinphaseofa seriesofgradientechoimagesandaredenedbythefollowing relationship:

∆

∝γ

BTE

wherethe echo time TE, theeld strength B0,and the gyromagnetic ratio γ are known,∅ is the phase in the current image, and

 is the phase of a baseline imageat a known temperature. e linearity and temperature dependence of thePRFanditsnearindependenceoftissuetypehavemade PRF-based phase-mapping methods the preferred choice for currentclinicalapplications.57Moreover,thetemperaturesensitivityofthePRFshimethoddoesnotdependonthechange intissuepropertiessustained duringthermalcoagulation.

62,63

DrawbacksofthePRFshi-basedthermometrymethodareits sensitivitytomotionanditsinaccuratetemperaturemeasurementsinfattissues.

Additional advantages of MRI guidance during HIFU are the ability to visualize the devascularized ablation zone attheendofthetreatmentsessionviagadolinium-enhanced sequences.Morerecentuseof3TMRIforMRI-guidedHIFU therapyoerspotentialimprovementsintumormargindelineation compared with imaging at 1.5 T, given the increased signal-to-noise ratio and imaging resolution at higher magneticeldstrengths.AdvancedMRI techniques used in conjunctionwithtumor-speciccontrastagentsmayalsoimprove tumordelineation and MRI-guided HIFU treatment ecacy in the future.6 Disadvantages of MRI-guided HIFU are the requirementforanMRI-compatibleUStransducer,theassociatedcostandrelativecomplexityofanintegratedsystem,lack ofwidespreadavailabilityforthesedevices,andthe increased safetyissuesmandatedinthesettingofanMRIenvironment.

HIFU devices

HIFU devices may be categorized as extracorporeal, endocavitary,andinterstitial.Extracorporealsystemsonthemarket include both MR-guidedand US-guided systems, with most US-guidedsystemsinusebeingemployedinAsia.31Interstitial HIFUdevicesindevelopmentemployHIFUapplicatorscapableof360°rotation.

8,64

esemaybeabletotreattumorsites notreadilytreatedwithmostextracorporealandendocavitary platforms, such as biliary, esophageal, and prostate malignancy(thelatterviaatransurethralapproach).

8,64

ereader isencouragedtoconsulttworecentreviewsbyTempanyetal. andZhou,eachofwhichincludesasummarytableofexisting HIFUdevicesandcurrentoncologicapplications.

6,8

Adetailed listofHIFU manufacturerscan also be foundathttp://www

.fusfoundation.org/the-technology/manufacturers.

TwointracavitaryHIFUdevicesarecurrentlyavailablefor clinical use: the Ablatherm(EDAP TMS, Lyon,France) and Sonablate 500 (SonaCareMedical, Charlotte, NC, previously FocusSurgery,Indianapolis,IN).31BothsystemsareUS-guided and employ water-cooled transrectal US transducers under robotic control. Both have been used primarily in clinical

trialsforthetreatmentofprostatecancer,althoughtheyhave thepotentialforadditionalapplicationsinthepelvis. AblathermdeviceemploysanHIFUprobewithdualUStransducerselementsforimagingvs.treatment.eSonablate500 employsasinglewater-cooledtransrectalUSapplicatorwith “split-beam”technology,allowingnear-simultaneousimaging andtreatment.

31,67

ExtracorporealHIFUdevicespossessalongerfocallength andgreaterworkingdepththanintracavitarydevicesandhave been used for a wider range of clinical applications.In general,extracorporealUS-guideddeviceshavebeenmorepopularinAsia.31eModelJC HIFU system (HaifuTechnology, Chongquing, China) has been used to treat several types of cancer, including liver and renal cancer.

31,68

US-guided HIFU devices include the HIFU-2001 (Sumo Corporation, Kowloon, Hong Kong), which has been used since2001 totreatcancerpatientsinChina,HongKong,and



Korea, the HIFUNIT-9000 tumor therapy system (Shanghai AishenTechnology,Shanghai,China)andtheFEP-BYTMsystem(YuandeBiomedicalEngineering,Beijing,China).31One oftwocommerciallyavailableMRI-guidedHIFUextracorporeal devices is the ExAblate system (InSightec, Haifa, Israel), which uses real-time thermometry under MRI guidance. It is currently used worldwide to treat uterine broids and in EuropeitisCE-approvedforthetreatmentofbonemetastases. StudiesareongoinginEurope,Asia,andIsraelemployingthe ExAblatesysteminthetreatmentofbreastcancerandadeno-

69,70

myosis.

emorerecentlydevelopedSonalleveMR-HIFU (PhilipsHealthcare,Vantaa, Finland) employs a 256-element phased-arrayextracorporealUStransducerintegratedintoan MRItabletopthatiscompatiblewithPhilipsMRIplatforms.31 etransduceriselectronicallysteeredemployingavolumetric ablationmethodologywherebycontinuousacoustic energy is appliedinconcentriccirclesatthetargetfocus,takingadvan-

1,6

tageofheatdiusion14(Figure4.3).eSonallevesystemhas receivedCEmarkingforthetreatmentofuterinebroidsand FDAapprovalis currently being sought in the USA for this application.e device has also received CE marking forthe palliationof bone metastases andclinical trials forthe same indication are under way in the USA. Additional oncologic investigationswhichareongoingwiththisdeviceincludethe treatmentofbreastandprostatecancer.

Extracorporealdevicesspecicallydesignedfortranscranial HIFUincludetheExAblateNeuro hemisphericphased-array HIFU system, which iscurrentlyused exclusively for neurosurgery research in the treatment of neuropathic pain and movementdisorderssuchasParkinson’sdiseaseandessential

31,71

tremor. particularlyinthetreatmentofessentialtremor.

Promisingearlyclinicalresultshavebeenobserved,

Clinical applications

US- and MRI-guided HIFUhavebeen utilized forthe treatment of a wide range of benign and malignant neoplasms. Treatedmalignancies include cancersof the breast, prostate, andliveraswellasboneandso-tissuemetastases.Smallclinical series have also described treatment of pancreatic and renalcellcarcinomas.

58,73–76

Althougha detailed review ofall

31,66

e

 Additional

Chapter4:High-intensity focused ultrasound

Figure 4.3 Magnetic resonance-guided

high-intensity focused ultrasound (HIFU) volumetric ablation. (A) Schematic of HIFU transducer and beam, applying focused acoustic energy in concentric circles within a treatment cell. (B) Treatment cells 4 mm, 8 mm, or 12 mm in diameter, with a ratio of cell diameter to length

4 mm

8 mm

Outwards-moving

concentric circles

4–12 mm

12 mm

of approximately 1:2.5. (Reprinted as per Elsevier permissions requirements from Venkatesan AM, Partanen A, Pulanic TK, et al. Magnetic resonance imaging-guided volumetric ablation of symptomatic leiomyomata: correlation of imaging with histology. J Vasc Interv Radiol 2012; 23: 786–794.14)

pertinentliteratureconcerningoncologicapplicationsofHIFU isbeyondthescopeofthischapter,thereaderisencouragedto consultrecentreviewswhichfocusonthissubject.

2,56

Prostate

eimpetustodevelopHIFU forfocaltreatmentofprostate cancerstemsfromthe risks associated with standard-of-care prostatecancertherapies,whichmaybeincurredaerradical prostatectomyaswellasaerexternal-beamradiation,brachytherapy,orhormonaltherapy.HIFUtreatmentofprostatecancerwasrstdescribedusingUSguidance,employingeitherthe Sonablateor Ablathermsystemsinpatientsunder eitherspinalorgeneral anesthesia

6,76–79

Literaturereviewsindicatethat US-guidedtransrectalHIFUhasbeenusedinatotalof3,018 publishedpatients,93%oftreatmentsforprimary-careprostate cancer,and7%forsalvagetreatment.78Five-year(biochemical) disease-freesurvivalratesarereportedas77%withuseofthe Ablathermdeviceand45–84%withtheSonablatedevice,with optimalratesofnegativebiopsyandlowprostate-specicantigenlevelassociatedwithlow-gradedisease.

Complications from US-guided transrectal HIFU include urinary tract infection,stress incontinence, urinary retention, bladder outlet obstruction, rectourethral stulae and, particularly in early studies, impotence.76 Recently, members of theGastroenterologyand UrologyPaneloftheFDA’sMedical Devices Advisory Committee voted against approval of the Ablatherm-HIFU device for the treatment of low-risk, localizedprostatecancerintheUSA,citingconcernsregardingproof ofsafetyandecacy.81Atpresent,analreviewofthedevice’s pre-marketapprovalapplicationispendingbytheFDA,which willundoubtedlyinuenceadoptionofthistreatmentmodality inthe USA.Ablatherm-HIFUis approvedandcommercialized inEuropeforthetreatmentofprostatecancer.

MRI-guided transrectal HIFU has been more recently described,performedinconjunctionwithreal-time intraproceduralMRthermometryandimaging ofthetargetandvulnerableregionalanatomy,includingtheneurovascularbundle and rectal wall.6 Earlyexperience by Napoli et al. described thefeasibilityofMRI-guidedtransrectalHIFUpriortoradical prostatectomyin5patientswithunifocalbiopsy-provenprostatecancerevidentonpreoperativemultiparametricimaging.3 Histopathology conrmed extensive coagulative necrosis,with no residual tumorin the ablated area.3MRI-guided

transurethral HIFU of the prostate is also being explored, potentially oering an even greater safety prole.82 We and othershavepursuedpreclinicalstudiesemployingMRI-guided transurethralHIFUinacaninemodelforfocalprostateablation (Figures 4.4 and 4.5).

82,83

 A clinical feasibility study by Chopra et al. employed transurethral MRI-guided HIFU in 8 patientswith localizedprostatecancer(Gleasonscore≤ 7, prostate-specicantigenlevel<15μg/L)priortoradicalprostatectomy.84isstudyconrmed thesafetyandfeasibilityof this treatment,with a mean tissuetreatmentrateof0.5mL/ min,andspatialtargetingaccuracyof–1.0±2.6mm.

High-qualityevidence ontheecacyandsafetyofHIFU in prostatecanceris still needed,asmost clinical studies to date are clinical series lacking a control arm. Randomized controlledtrialsofsucientsizecomparingHIFUwithconventionalsurgicalandnon-surgicaltreatmentortonotreatment (active surveillance) are necessary. Data on overall survival,prostatecancer-specicsurvival,adverseevents,and quality-of-lifemetricsarecritical.80Continuedclinicalexperienceandtechnical improvementsareanticipatedtoimprove theaccuracyandecacyofHIFUtherapyforprostatecancer inthefuture.

Breast

AdvantagesofutilizingHIFUinthebreastincludetargetproximitytothetransducer,presenceofaso-tissueacousticwindow,andtheabilitytoimmobilizethetargettissue.emain argumentagainstnon-invasivebreastcancertherapies,includingHIFU,isthatmarginstatuscannotbeassessedduetolack ofa pathologicalspecimen.TechnicalchallengesforHIFUin thebreastincludetherisksofinjurytoskin,rib,andlungsand the relative insensitivityof existing PRF-based thermometry infattissues.31Technicaldevelopmentswhichmaysurmount these challenges include device designs enabling focal point correctionsinthesettingoftissueheterogeneity.

ere remains ongoing interest in breast HIFU as a breast-conservingalternativetherapy(Figures4.6,4.7,and4.8). Prior preclinical and clinical series suggest HIFU is feasible andmaybeecaciousin the breast,althoughmoreresearch in this areais needed andthe exact role for HIFU in breast cancerisyettobewelldened.Gianfeliceetal.describedfeasibilityofMRI-guidedHIFUin24patientswithbiopsy-proven breast cancer who refused surgery and underwent HIFU as

31,85,86

Section II:Principles of image-guided therapies

Figure 4.4 Planning and temperature

mapping for a focal prostate ablation using magnetic resonance imaging-guided ultrasound (US) therapy. (A, B) Prostate was clearly identiﬁed on the T2-weighted axial and sagittal planning images, and a temperature feedback control point within the prostate was prescribed (green circle). The red overlay shows the position of the US applicator, and the dashed yellow lines depict the position of the imaging slices ((A) shows the slice position in (B), and (B) shows the slice position in (A).) Depiction of applicator within the prostate is meant to be illustrative. (C, D) Color-coded temperature maps overlaid on dynamic magnitude images during a sonication (using four transducer elements), showing typical temperature distribution at the end of a 124-second sonication. Temperature monitoring and control were achieved in the target location with fast-ﬁeld echo (FFE)-echo planar imaging (EPI) sequence, using the proton resonance frequency shift (PRFS) method for temperature mapping, and by using a binary temperature feedback algorithm. (B) and (D) are the sagittal image planes corresponding to (A) and (C), respectively. (Reprinted with permission from Partanen A, Yerram NK, Trivedi H, et al. Magnetic resonance imaging (MRI)-guided transurethral ultrasound therapy of the prostate: a preclinical study with radiological and pathological correlation using customized MRI-based moulds. BJU Int 2013; 508–516.82)

an adjunct to tamoxifen therapy.87 Nineteen of 24 patients (79%) had negative biopsy results aer either one or two treatmentsessions.87Furusawaet al. treated 21 patientswith biopsy-provenductalcarcinomawiththeExAblatedevice.One recurrencewasobservedin21patientsoveramedianfollow-up of14months.69Wuet al.treated22patientswithbreastcancerwhoreceivedchemotherapy,radiation,andtamoxifen,followingHIFU using the ModelJC HIFU system,with 5-year disease-freesurvivalandrecurrence-freesurvivalratesof95% and 89%, respectively.88 Subsequently, Wu et al. described treatmentof23patientswith histologically conrmed breast cancerwhounderwentHIFUoftheirtumorsandanintended

1.5–2-cm tumor-free margin followed by modied mastectomy1–2weeksaerHIFU.89Ablationzonesizessignicantly largerthanthetargetedtumorswereachieved,withcomplete necrosisofthetreatedregionsconrmedathistopathology.

Liver

EortsareunderwaytoutilizeHIFUforhepaticmalignancy, particularly in patients with unresectable hepatocellular carcinoma (HCC) or surgical comorbidities (Figures 4.9 and

4.10).90OngoingHIFUtechnicalchallengesduringliverabla-

tionincluderespiratorymotion,dicultywithadequateenergy delivery through or between ribs, and long treatment times associatedwithlargetumors. mentsincluderespiratorygatingandselectiveelementactivationtoenableintercostalablation.93Complicationsdescribed asa result of HIFU liver tumorablationinclude ribfracture

31,91,92

Potentialtechnicaldevelop-

and necrosis, diaphragmatic rupture, biliary obstruction, pleural eusion, pneumothorax,and stula formation.94 e majorityofclinicalexperienceandresearchconcerningHIFU fortreatmentoflivertumorshasdevelopedinAsia,wherethe prevalenceofHCCremainshigh.31Ngetal.describedtheoutcomeof49patientswithunresectableHCCtreatedwithHIFU using the JC HIFU system (Chongqing Haifu Technology, Chongqing,China).95 Median size of thetreated tumors was

2.2 cm (range 0.9–8 cm). A primary technique eectiveness rateof79.5%(39of49patients)wasobserved,withtumorsize (≥3.0cm)beingthesignicantriskfactoraectingcomplete ablation rate and Child–Pugh liver function grading being the signicant prognosticfactor inuencing overall survival. One- and 3-year overall survival rates of 87.7% and 62.4%, respectively, were observed, leading the authors to conclude that HIFU is an eective treatment modality with favorable survival outcome.95 Combined treatment with transarterial chemoembolization (TACE) and HIFU in the treatment of HCC has also been described. Wuet al. treated 50 consecutivepatientswithstageIVaHCCrandomizedtoeitherTACE aloneorHIFUusingtheModelJCHIFUsystem followedby TACE4–6weekslater.96Treatedtumorswere4–14cmindiameter(mean10.5cm).PatientstreatedwithTACEandUSablationhad higher survivalratesthan those treated with TACE alone(P=0.007,log-ranktest).96emediansurvivaltimewas

11.3 monthsin the TACE+HIFUgroupand4.0 months in theTACE-onlygroup(P=0.004).e 6-monthsurvival rate was80.4–85.4%intheTACE+HIFUgroupand13.2%inthe

Chapter4:High-intensity focused ultrasound

Figure 4.5 Imaging to histopathologic

correlation after transurethral magnetic resonance imaging (MRI)-guided high-intensity focused ultrasound. Representative examples of contrast-enhanced imaging showing non-perfused regions (A), diﬀusion-weighted imaging (DWI) (b-value = 2000) showing restricted diﬀusion in ablated regions (B), CK-8-stained tissue showing areas of non-viable tissue (C), and real-time cumulative thermal dose estimates (D). Ablated volumes on histology appear slightly distorted compared with MRI due to diﬀerences in tissue slice position

and shrinkage secondary to formalin ﬁxation. (Reprinted with permission from Partanen A, Yerram NK, Trivedi H, et al. Magnetic resonance imaging (MRI)-guided transurethral ultrasound therapy of the prostate: a preclinical study with radiological and pathological correlation using customized MRI-based moulds. BJU Int 2013; 508–516.82)

Figure 4.6 A 45-year-old woman with

ductal cancer (T1 N0 M0) of the left breast. At pretreatment planning (A), T2-weighted axial image shows the nodule and its distance from the pectoralis muscle (red dashed line), and (B) T2-weighted axial image with fat saturation shows high signal intensity of the pathologic nodule. (Reprinted with permission from Napoli A, Anzidei M, Ciolina F, et al. MR-guided high-intensity focused ultrasound: current

A B

TACE-onlygroup(P=0.003),andthe1-yearsurvivalratewas

42.9%and0%,respectively.

US-guidedHIFUhasbeenemployedinthetreatmentofprimary bone tumors and MRI-guided HIFU for palliation of

status of an emerging technology. Cardiovasc Interv Radiol 2013; 36: 1190–1203.3)

painfulbonemetastases.

Bone

ermalablationinboneisfacilitatedbyitsabsorptivecapacity,withapproximately30%oftheenergyneededforso-tissue ablationbeingnecessaryforeectiveablationinbone.6Todate,

Chenetal.describedaprospectiveclinicaltrialemploying theJCHIFUsystemtotreatpatientswithprimarybonemalignancies.97Atotalof80patientsweretreated,62withUS-guided HIFUpluschemotherapy,and14patientstreatedwithHIFU

Section II:Principles of image-guided therapies

Figure 4.7 Breast magnetic

resonance-guided focused ultrasound surgery (MRgFUS) pretreatment imaging. (A) Breast MRgFUS pretreatment evaluation completed with MR spectroscopy. (B) Dynamic gadolinium-enhanced T1-weighted images for perfusion. (C) Diﬀusion-weighted image for molecular restriction. (D) Apparent diﬀusion coeﬃcient map. All are indicative of malignancy. (Reprinted with permission from Napoli A, Anzidei M, Ciolina F, et al. MR-guided high-intensity focused ultrasound: current status of an emerging technology. Cardiovasc Interv Radiol 2013; 36: 1190–1203.3)

only. Complete tumor ablation delineated on follow-up CT, MRI,andsingle-photonemissionCTimagingwasobservedin 69of80patients,with5of69 patients(7%) whounderwent completeablation experiencing local recurrences during the follow-upperiod.

Promisingresultshavebeendescribedforthe palliation ofpainfulbonetumorswithHIFU.HIFUtreatmentgoalsfor pain palliationdier from those needed to achieve tumor ablation.ForHIFUbonepainpalliation,theUSfocalpoint isintentionallyplacedbeyondthebonesurface,withthermal energylocalizedtothe periostealbone–sotissueinterface

andpalliationattributedtodenervationofperiostealnerves.6 Liberman et al. reported results from a multicenter trial employing the ExAblate MR thermometry-guided focused US(MRgFUS)systemto evaluate thesafetyandecacyof MRI-guidedHIFUinthepalliativetreatmentofbonemetastases.98irty-sixprocedureswereperformedon31patients, with72%ofevaluablepatients(18/25)reportingsignicant painimprovement,denedasareductionintheirvisualanalogscalescoreof>2points.Averagevisualanalogscalescore reductionsfrom 5.9 priorto treatment to 1.8 at 3 months posttreatment were observed. In all, 67% of patients with

Figure 4.8 Breast magnetic

resonance-guided focused ultrasound surgery (MRgFUS) pre- and posttreatment imaging. (A) Gadolinium-enhanced T1 gradient-echo fat-saturated axial image shows the malignant highly vascular breast nodule before MRgFUS. (B) After MRgFUS treatment, no residual enhancement of ablated lesion is detectable. (Reprinted with permission from Napoli A, Anzidei M, Ciolina F, et al. MR-guided high-intensity focused ultrasound: current status of an emerging technology. Cardiovasc Interv Radiol 2013; 36: 1190–1203.3)

<<< < Предыдущая 1 2 34 / 354 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 > Следующая >>>

Соседние файлы в папке Библиотека им академика М.И. Перельмана

#
30.08.202651 Мб0Книга_3653_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202650 Мб0Книга_3654_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202649 Мб0Книга_3655_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202649 Мб0Книга_3656_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202649 Мб0Книга_3657_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202649 Мб0Книга_3658_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202649 Мб0Книга_3659_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202649 Мб0Книга_3660_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202648 Мб0Книга_3661_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202648 Мб0Книга_3662_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202648 Мб0Книга_3663_Библиотеки_им_академика_М_И_Перельмана.pdf