Perfusion in ENT imaging

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CONTINUING

EDUCATION

PROGRAM:

FOCUS

.

.

.

Perfusion

in

ENT

imaging

S.

Espinoza

,

D.

Malinvaud ,

N.

Siauve ,

P.

Halimi

Georges-PompidouEuropeanHospital,20,rueLeblanc,75015Paris,France

KEYWORDS PerfusionMRI; PerfusionCT; Salivarygland tumors; ENTcancers

Abstract PerfusionMRIisanessentialpartofcharacterizingsalivaryglandtumors.Theshape

ofthecurvescanprovideaguideastothetypeoflesion:benign(ascendingplateau)or

malig-nant(descendingplateau),andcanalsooccasionallystronglysuggestahistologicaltypesuchas

aWarthintumor(intense,rapidcontrastenhancementwithwashout>30%).Perfusionimaging

(CTorMRI)forotherheadandnecktumorsiscurrentlybeingdevelopedandisbeingassessed.

Itshouldbeatooltoassistinchoosingthemostappropriateinitialtreatment(chemotherapy,

radiotherapyorsurgery)andshouldalsoallowpoorresponderstoconservativetreatmentto

beidentifiedandrecurrencestobedetectedinpost-treatmentdamagedtissues.Aims:(a)to

determinewhentoperformperfusionMRI;(b)todeterminethetypeofperfusiontocarryout:

CT,T1-weightedMRI;(c)todeterminehowtopositiontheregionofinteresttoplotthe

per-fusioncurve;(d)toknowhowtointerpretMRIcurvesforsalivaryglandtumors;(e)toknow

howtointerprettheinformationobtainedfromperfusionCTorMRIfortheupperaerodigestive

tract.

©2013Éditionsfrançaisesderadiologie.PublishedbyElsevierMassonSAS.Allrightsreserved.

Perfusionimaging,withCTorMRI,canprovidenon-invasiveaccesstothemicrocirculatory features of tissuelesions.The twomethods which can beusedin ENT imagingareCT perfusionandT1-weightedperfusionMRI.

Clinicians’requirements differdependingonthediseaseandtherelatedproblemsin treatingthemwhichareraised.Perfusionmethodsseektoanswerthesepracticalpatient careproblems.Theytherefore havedifferingmerits,dependingonthetypeandsiteof theheadandnecktumor.

The question facedby thesurgeonfor asalivary glandtumoris whethertooperate or not.The answertothisdependsonthetypeandsiteof thelesion.Wewillseethat perfusionMRIprovideswhathavebecomeessentialanswersforthesurgeonfromtheinitial diagnosticandpre-treatmentassessment.

Correspondingauthor.

E-mailaddress:sophie.espinoza@gmail.com(S.Espinoza).

2211-5684/$—seefrontmatter©2013Éditionsfrançaisesderadiologie.PublishedbyElsevierMassonSAS.Allrightsreserved.

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• canwe predict which patients will benefitfroma con-servative radiochemotherapy approach from the initial CTorMRIinvestigationbeforeanytreatmentisoffered? Also,itispossibletopredictwhichpatientswho,onthe otherhand,willnotrespondandwillbenefitfromsurgery fromthebeginning?Salvagesurgeryisextremelydifficult, particularlyafterradiotherapy,andcarriesahighriskof complicationsandlocalfailure.Itisthereforevery impor-tanttoidentify,whereverpossiblefromthestart,which patients need surgery as, although it is mutilating, ini-tialsurgerycarrieslessriskandoffers agreaterchance oflocalcontrolofthediseasewhenitisperformedfirst line;

• isitpossibletopredicttheresponsetoconservative treat-ments(radiotherapy,chemotherapyor acombinationof both),inordertodeterminetheoptimaltreatmentonan individualcasebasis?Dowehaveinformationtosuggest thatapatientwillrespondwell,andwhatisthepatient’s likelihoodofachievingacompleteresponseafter conser-vativetreatment?

• canweobjectivelyquantifyandmonitortheresponseto conservativetreatments?

• canwedetectpoorresponderstoconservativetreatment early? In particular, can we detect poor responders to radiotherapy and then stop the radiotherapy, todirect thepatienttosurgerymorequickly?

• canwedetectrecurrencesaftertreatmentearly,and dis-tinguish these from inflammatory changes or radiation necrosis?

• canweobtaininformationwhichwouldallowusto opti-mallyassess lymphnodesunderacentimeter insize so thatthelymphnodesareonlyremovediftheyare gen-uinelydiseased?

Weshallexaminethefollowingissuesinsuccessioninthis article:

• routineperfusionMRItechniqueswhichareessentialfor characterizingsalivarytumors,inorder:toestablishwhen to perform a perfusion sequence, todecide whattype ofperfusiontoperform,howtoacquireandanalyzethe images,howtopositiontheregionsofinterestandhowto plottheperfusioncurveinsignificantareasandbeable tointerprettheMRIcurvestocharacterizesalivarygland tumors;

• techniques which are currently being developed and assessedusingCTandMRIforUADTcarcinomas,inorder: toestablishwhentocarryoutaperfusionsequence, to

• benigntumorswhich,dohoweverneedtobeexcised sur-gicallybecauseoftheriskofmalignantdegeneration:this isthecaseforpleomorphicadenomas;

• benign tumors which usually do not need any surgery: thisisthecaseforWarthintumorswhicharenottreated surgicallyprovidedthatformalevidenceofthetumor is obtainedbyfineneedleaspirationandMRI.Theyarethen onlytreatedsurgicallyforaestheticorcomfortreasons; • low-, intermediate- or high-grade malignant tumors

whichalwaysrequiresurgicalexcision:muco-epidermoid squamous cell carcinomas, cystic adenoid carcinomas, adenocarcinomas,squamouscellcarcinomas,and undif-ferentiatedcarcinomas;

• malignant tumorswhich require systemictherapy: lym-phomas;

• rare benign tumors which do not require surgery: branchial cysts, HIV lympho-epithelial cysts, oncocy-tomas,hemolymphangiomasandlipomas.

Thefirstquestionthesurgeonneedstoansweris there-forewhether or nothe/sheneeds tooperate.Oneof the merits ofMRI andfine needleaspirationisthat theyhave allowedustoavoidalwaysresortingtosurgerytoestablish thetypeof lesion.Thesecond questionthe surgeonfaces is therisk ofmalignancy.In parotidtumors,surgeonsalso wanttoassesstherisktothefacialnerve.Inthiscase,the aimsofMRIaretodeterminetheexactsiteofthelesionand toprovideinformationinordertocharacterizeit,toassist thesurgeoninhis/herdecisionofwhetherornotto oper-ateandtohelphimtowarnpatientsoftheincreasedrisk oftemporaryorpermanentpostoperativefacialparalysisif malignantdiseaseisassumedfromMRIfindings.

Inthissituation,perfusionMRI providesessential infor-mationfor preoperative characterizationof salivarygland lesions,providedthatitisperformedandinterpreted rigor-ously.

Technique

and

image

processing

The aim of MRI investigation of a salivary gland lesion is to determine the site, size, margins and T1- and T2-weighted signal characteristics of the lesion (without fat saturation).Ithasnowbeenclearlyestablishedthat diffu-sionimagingisessentialandprovidesinformationaboutthe cellularityof thelesionanditsmalignantpotential[1—3]. However,thediagnosticaccuracyofdiffusion-weightedMRI either alone or combined with conventional T1- and T2-weightedsequencesisinadequate[4].This‘‘conventional’’

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approach has particular failings in Warthin tumors and cellular pleomorphic adenomas, both of which can con-tainahypercellularcomponentwithnoduleswhichgreatly reducesdiffusion,incorrectlysuggestingamalignanttumor which requires surgical excision. As we have seen above, Warthintumorsdonotrequiresurgeryastheycarrynorisk whatsoeverofmalignantdegeneration.Withcellular pleo-morphicadenomas,evenifsurgeryisrequired,theriskto thefacialnerveandtheprognosisaredifferentfromthose ofmalignanttumors.

Although conventional sequencinganddiffusion can be ineffective for Warthin tumors and cellular pleomorphic adenomas, it has now been clearly established that they have highlysuggestive and specificenhancement features onT1-weightedperfusion[5,6].

A full investigation of a salivary gland tumor must, therefore,includeT1-weightedperfusionMRIsequencesin additiontotheconventionalT1-,T2-weightedand diffusion-weightedsequences[2,7,8].

We shall notdescribe theT1 perfusion techniquehere andreferthereadertothetechniqueschapter.

Wewouldlikesimplytodrawreaders’attentiontoafew specificfeaturesofsalivaryglandimaging:

• itisveryimportanttotellthepatientthattheymustnot swallow;

• theFOVmustbesuitableforthecervicalregion:asmall FOV,i.e.28cm;

• thematrixalsoneedstobeincreased:192×192; • section thickness must be suitable for the anatomical

region:4mm.

AdetailedacquisitionprotocolisproposedinBoxedtext 1.

In imageprocessing,itis importanttounderstand that salivary glandtumors are heterogeneous andmade upof differentcomponents(greaterorlessercelldensity,a myx-oidcomponent,a calcifiedcomponentand amore orless hemorrhagicfluidcontent).T1-andT2-weightedsignalsand diffusionrestrictionandcontrastenhancementvary accord-ingtothetypeofthesedifferentcomponents.The choice oftheregionofinterestinwhichtheperfusioncurveis con-structed(andsimilarlymeasurementoftheapparentrADC diffusioncoefficient)isthereforefundamental:

• clearly the perfusion curve shouldnot beplotted for a non-tissueportionwhichdoesnotenhance.Hemorrhagic areasorthosemadeupofhighproteincontentfluidwhich

Boxedtext1 AcquisitionparametersforMR perfusionsequence.

MRperfusionsequence

Injection:0.2mmol/kgviaapowerinjectoratarate of 4mL/s, followed by injection of 20mL of normal saline SPGR3D;8slices Sectionthickness:4mm 40phases Temporalresolution:3—4s Matrix:192×192 FOV:28cm

arehyperintenseonanunenhancedT1sequenceareseen verycommonlyinWarthintumorsandmustthereforebe excluded (Fig. 1). It is also essential not to place the regionof interest innecrotic areas,which are hyperin-tenseonT2andproducevariablesignalsonT1sequences. Thesearecommoninmalignanttumors.Itisalso impor-tanttobeawareofcalcifiedacellularareasorthosemade upofamyxoidmatrix,whichareverycommonin pauci-cellularpleomorphicadenomas;

• therefore, it is preferable to use areas which are hypointenseonT2andnothyperintenseonT1sequences inordertodeterminethepositionoftheregionofinterest (Fig.2).

Finally, ascontrastis used,we suggest that the inves-tigationbecompletedby T1-weighted sequenceswithfat saturationaftercontrastinjection.

Interpretation

of

MRI

images

In light of the above, MRI characterization of a salivary glandtumorshouldincorporatealloftheanatomical,signal andfunctionalinformation(diffusionandperfusion)which itprovides[9].

Morphologyofthelesion

Thesizeandpositionofthelesion(superficialordeeppart ofthegland), relationshipswiththestylomastoidforamen andtheretrocondylarveins(whichareamarkerforthepath ofthefacialnerve),wellorpoorlydemarcatedoutlinesand anypotential extension tothe subcutaneous tissues (par-ticularlyfat)andmassetermuscleshouldbereported.The reportshouldstatethepresenceorabsenceofa contralat-erallesion (suggestive ofWarthin’s tumor or lymphnodal tumors).LymphadenopathyinzoneIIshouldalsobe investi-gated.

Signalfromthelesion

T1: the main benefit of this sequence is that it allows us toinvestigate for an unenhanced T1 hyperintensity in the lesion. These T1 hyperintensities are due to a pro-teincomponentwithinthelesionorthepresenceofblood, both of which suggest a diagnosis of Warthin’s tumor,

Figure1. Incorrectchoiceofthepositionoftheregionof inter-est(ROI).a:axialT1-weightedMRI:unenhancedT1hyperintensity (blackarrow)representingbleedingwithinthelesion;b: uninfor-mative,flatperfusioncurve.

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Figure2. Correctchoiceofthepositionoftheregionofinterest.a:axialT1-weightedMRI;b:axialT2-weightedMRI.GreenROIpositioned inthetissueportionswhicharehypointenseonT1-andT2-weightedsequences.c:informativeenhancementcurve.

even if they are limited to within the lesion. Also, it is importanttoidentifytheseareasbeforecontrast enhance-ment in order not to be misled by increased uptake and tocentre the perfusion sequence away from these areas (Fig.1).

T2 sequence without fat saturation: this sequence is usedtostudy thesignal from thelesion comparedtothe healthy parotid parenchyma. A strong T2 hyperintensity compared to the healthy parotid parenchyma suggests a benigntumor(pleomorphicadenoma,Fig.3).An interme-diary T2-weighted signal may represent either a cellular pleomorphicadenoma (Fig.4a),or an intermediary-grade malignanttumor (Fig.4b).AstrongT2hypointensity com-pared to the healthy parenchyma suggests a malignant tumor(Fig.5).

In a diffusion-weighted sequence with rADC measure-ment,thesignalfromthelesionshouldbecomparedtothe healthy neighboring or contralateral parotid parenchyma andtheresultexpressedasanapparentdiffusioncoefficient ratio(rADC) comparedtothe healthyparenchyma (tumor ADC/healthyparotidADC).Astronghyperintensetumoron adiffusion-weighted sequence withan apparent diffusion coefficient ratio of under 1, suggestsa high-grade malig-nant lesion (Fig. 6a) whereas a tumor with an apparent

Figure3. HyperintenseT2signal.T2axialMRI:rightintraparotid tumor with a pronounced T2-weighted hyperintensity which is greaterthantheglandularparenchymaand suggestiveofa pleo-morphicadenoma.

diffusioncoefficientratioofover1.3suggestsabenign pleo-morphicadenoma(Fig.6b).AnADCratioofbetween1and 1.3mayrepresenteitheracellularpleomorphicadenomaor anintermediary-grademalignanttumor(Fig.6c).

Figure4. IntermediaryT2-weightedsignal.a:axialT2-weightedMRI:intermediaryT2signalfromarightparotidcellularpleomorphic adenoma;b:axialT2-weightedMRI:intermediaryT2signalfromanintermediary-grademalignantleftparotidtumor.

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Figure 5. Low T2 signal. Axial T2-weighted MRI: pronounced hypointense T2 sequence compared to the normal glandular parenchyma,suggestiveofahigh-grademalignancytumor.

InaT1-weightedsequenceaftergadoliniuminjectionand fatsaturation,theinvestigationcanclearlydemarcatethe lesionandalsodistinguishcysticandnecroticcomponents which donot enhance (Fig.7),which should beexcluded retrospectively from the ROI in calculating the rADC and in tracingthe perfusioncurve —tissuecomponentswhich enhancelateandcanbeusedtocalculatetherADCandto obtaintheperfusioncurve.

Finally, the enhancement curve from the perfusion sequence:onthistypeofT1-weightedperfusionsequence, a pleomorphic adenoma (regardless of its cellularity) has extensive contrast uptake with an ascending plateau (Fig. 8a), a Warthin tumor has intense and rapid con-trast uptake with a high washout of over 30% (Fig. 8b) andintermediary-grademalignanttumorshaveintense con-trastuptakewithahorizontalordescendingplateaubuta washoutofunder30%(Fig.8c).

Figure7. Necroticareainthetumor.AxialT1-weightedMRIafter gadoliniumwith fat saturation, showinga large central portion whichdoesnotenhance.Thislesionisverydifficultto character-izeinaperfusionsequencebecauseoftheextensivecysticchanges whichmakeunequivocalpositioningoftheROIdifficultinprinciple (beforeinjection)inapartofthetissue.

TheplaceandlimitationsofperfusionMRI

It has now been clearly established that MRI for the investigation of a salivary gland tumor should include a T1-weighted perfusion sequence with recording of the enhancementcurve and that theseshould be interpreted jointly,takingaccountofalloftheinformationprovided.

PerfusionMRIaloneisinsufficientfor:

• tumors containing a largely cystic component in which positioningtheregionof interest isdifficult or impossi-ble(Fig.1).rADCmeasurementhasthesamelimitations inthissituation;

• the specificity of the threetypes of curves obtained is extremelyhigh,butisnotpathognomonicfora histolog-icaltypeof tumor (it hasa specificityof 80 to91% for malignancydetectionand90to100%foraWarthintumor)

[5];

Figure6. DiffusionmappingwithrADCmeasurementin3differentpatients.a:diffusionmappingshowingaverylowADCratiobetween thetumorandnormalparotid(0.55)suggestiveofamalignanttumor;b:diffusionmappingshowingaveryhighADCratiobetweenthe tumorandnormalparotid(1.4)suggestiveofabenignpleomorphicadenomatumor;c:diffusionmappingshowinganintermediaryADC ratiobetweenthetumorandnormalparotid(0.9)whichmayrepresenteitheracellularpleomorphicadenomaoranintermediary-grade malignanttumor.

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Figure8. Thethreepossibleperfusioncurves:a:ascendingplateau:curvesuggestiveofabenignpleomorphicadenomatumor;b:peak withwashoutmorethan30%typicalofaWarthintumor;c:descendingplateauwithwashoutlessthan30%:thiscurveissuggestiveofa malignanttumor.

• tumorsunder10mminsizearedifficulttocharacterizeon perfusionMRI,althoughtheyarealsodifficultingeneral evenwhenallofthesequencesareconsidered,because oftheirsmallsizeandprobablyalsobecausetheydonot yetexpressasufficientnumberoffunctionalcomponents. Asaresult,asalivaryglandMRIinvestigationshould con-tainthefollowingthreefeatures:

• aT2-weightedsequencewithoutfatsaturation;

• adiffusion-weightedsequencewithmeasurementofthe ADCratio;

• aperfusionsequencewithrecordingoftheenhancement curve.

Ifitdoesnot,theinvestigationdoesnotprovideallofthe essentialinformationtocharacterizethelesion,andreduces itsdiagnosticaccuracy.

Interpretationalgorithm

ThisisshowninFig.9.

High T1 signal ? No Yes Perfusion : type B curve High T2 signal? Yes Diffusion:

rCDA >1.3 type A curve Perfusion:

Pleomorphic Adenoma No Diffusion: rCDA: 1 - 1.3 Perfusion: type C curve Perfusion: type A curve Cellular Pleomorphic Adenoma Malignant tumor Diffusion: rCDA: <1 Perfusion: type C curve High grade Malignant tumor

Parotid gland Tumor > 1 cm

Non cystic lesion, regular margins

Perfusion : type B curve Warthin’s tumor Warthin’s tumor

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Diagnosis

Thediagnosisshouldbemadeconsistentwiththefeatures ofthelesionswhichareshowninTable1andinFigs.10—14.

Summary

An MRI for the investigation of a salivary gland tumor shouldcontainaT1-weightedperfusionsequence.However,

this sequence alone is not sufficient and the inter-pretation should incorporate anatomical features, a T2 sequence without fat saturation, the apparent diffusion coefficient ratio (rADC) and the lesion’s T1 enhancement curve.

Whentheseproceduresarecarriedout,MRIcanpredict thehistologicaldiagnosisof parotidlesionsinover 80%of cases.

Table1 Diagnosticcriteria.

T2 ADCratio Perfusion Others

Whartin’stumor HypoorIso 0.8—1 Wash-out

>30% HighT1 Bilateral Inferiorpart Man>50y Smoker

Pleomorphicadenoma High >1.3 Ascendingplateau

Cellularpleomorphicadenoma Iso 1—1.3 Ascendingplateau Malignanttumor:lowgrade IsoorHypo 1—1.3 Wash-out

<30%

Malignanttumor:highgrade Hypo <1 Descendingplateau Ill-definedmargins

Figure10. Typicalpleomorphicadenoma.Tissuestructureinthesuperficialpartoftheleftparotidgland,measuring35mminsize.a: axialT2-weightedMRI:thelesionshowsapronouncedhyperintensesignal;b:axialT1-weightedMRIwithgadoliniumandfatsaturation: intensecontrastenhancement;c:mappingtheapparentdiffusioncoefficient:rADC=1.7;d:perfusioncurveshowingintenseenhancement, withanascendingplateau.

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Figure11. TypicalWarthintumor.Tissuelesionacentimeterinsizeinthesuperficialpartoftherightparotidgland.a:axialT1-weighted MRI:thelesioncontainssmallhyperintensespotswithoutenhancementontheT1-weightedMRI;b:axialT2-weightedMRI:thelesionis hypointenseontheT2-weightedsequence;c:mappingoftheapparentdistributioncoefficient:rADC=0.8;d:perfusioncurveshowingrapid intensecontrastenhancementwithawashoutofover30%.

Perfusion

imaging

for

UADT

cancers

General

details

Untilnow,thechoiceofENToncologytreatmentshasbeen basedoncohortstudies’statistics.Therecentdevelopment of targeted molecules and the wide range of treatments whicharenowavailable(chemotherapy, radiotherapyand surgery)makeitessentialtodeveloptoolswiththree objec-tives:

• to predict whether a given tumor is or is not likely to respondtoaparticulartypeofnon-surgicaltreatment; • tomonitorandassessresponseduringtreatmentinorder

toadjustthetreatmentassoonaspossible.Ifapatient failstorespondadequatelyordoesnotrespondto treat-ment, early detection of the treatment failure allows thecaretobechanged.Thismayinvolveincreasingthe doses ofchemotherapy or radiotherapy or adding adju-vantchemotherapy.Itmayalsoinvolveswitchingsooner tosurgery:whilstthisisdefinitelymutilating,itismore likely toachieve satisfactory local controland a lower likelihood of complications if it is carried out on non-irradiatedtissue;

• todetectthepresenceofresidualtumororarecurrence afterconservativetreatmentasearlyaspossible,inorder toorganizesalvagesurgeryassoonaspossible.

The imaging questions which arise at present are not therefore only anatomicalones but areincreasingly func-tional(suchasdetectionofviablemalignanttissuewithin thescarredtissue).Themainpurposeofthisistoincrease local control and survival, at the same time reducing treatment-related complications. This is the context in whichperfusionimaging(CTorMRI)isbeingdevelopedfor UADTcarcinomas,andinwhichthisnewtechniqueisbeing assessed.

Perfusion imaging provides non-invasive access to the microcirculatory properties of tumors. The perfusion sequence, both in CT and MRI, can be used tocalculate microcirculatoryparameterswhichreflecttumor microvas-cularization. Both CT and MRI can quantify whether the temporal resolution and acquisition time are sufficient, togetherwithtissueblood flow(TBF),tissuebloodvolume (TBV), mean transit time (MTT) and surface permeability (SP)[10—16].

In the following sections, we will examine how tumor imagingcanassistinthefollowing byassessingthe micro-circulatorypropertiesoftumors:

• the choice of initial treatment which will have most likelihoodof success ina given patient(chemotherapy, radiotherapyorsurgery);

• identifyingpoorrespondersinordertoadjusttreatment morequickly;

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Figure12. Cellularpleomorphicadenoma.Tissuelesion inthesuperficiallobeoftheright parotidgland,measuring2cminsize.a: axialT2-weightedMRI:isointenselesion;b:axialT1-weightedMRIaftergadoliniumwithfatsaturation:intensecontrastenhancement;c: mappingoftheapparentdiffusioncoefficient:rADC=1.09;d:perfusioncurveshowingintensecontrastenhancementwithanascending plateau.

• quantitative (objective) monitoring of treatment response;

• early detection of recurrences in post-treatment dam-agedtissue.

Technique

and

image

processing

WewillnotdescribetheCTorMRItechniquehere,andrefer thereadertothetechniqueschapter.

Wewouldsimplyliketodrawthereader’sattentiontoa fewspecificfeaturesofheadandneckimaging.

Choiceofmethod,CTorMRI

This is usually dictatedby the site of the primarytumor, the patient’s past imaginghistory and the question being asked by the clinician. It should not further complicate thepre-treatmentassessment ofpatientswhoarealready goingthrougha relativelycomplexstagingprocess(initial CTand/orMRIimagingdependingonthesite,PETCT inves-tigatingforasecondprimary,biopsy).

Lesions ofthe cavum,oropharynx,oral cavityand pos-teriorpharyngealwallshouldpreferablybeinvestigatedby MRI.TheperfusionMRIsequenceisonlyanadditionalphase oftheinvestigation(Fig.15).

Lesions of the hypopharynx and larynx areonly inves-tigated by CT (unless there is an exception) and it is reasonabletouseaCTperfusionsequence(Fig.16).

The initialassessment offacialtumorsusuallyrequires both MRI (to demarcate the tumor, identify perineural or even intracranial extensions, and to distinguish it from neighboringinflammatoryreactions)andCT(toidentify cor-tical bone structures in the facial bone and base of the craniumwhichareinvolved).Inthissituation,thechoiceof methodis guidedby the radiologist’spersonal experience andthepatient’spastradiologicalhistory.

SpecificfeaturesoftheENTperfusionsequence

OnCT[17]:

• 80kV acquisition withdose modulation (angular and z) between 20 and 100mA, 2.5mm sections, FOV=20cm, softfilterreconstruction;

• injection:40mLat5mL/sbypulsedbolus,concentration 320mgI/mL;

• acquisition:5safterthestartoftheinjection,minimum time60s,temporalresolution:1/s;

• gentlebreathingwithoutswallowing.

OnMRI andCT,for UADTcarcinomas,theissue of den-talartifactsarises:thepatientshouldbetiltedtominimize these.

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Figure13. Intermediary-grademalignanttumor.Tissuelesioninthesuperficialpartoftherightparotidgland.a:axialT2-weightedMRI: hypointense;b:axialT1-weightedMRIaftergadoliniumwithfatsaturation:moderateenhancement;c:mappingoftheapparentdiffusion coefficient:rADC=1.1;d:perfusioncurveshowingearlycontrastenhancementwithwashoutofunder30%.

Boxedtext2 AcquisitionparametersforCT perfusionsequence.

Injection: 40mL via a power injector at a rate of 4mL/s,followedbyinjectionof40mLofnormalsaline

80kV/80mAs

Sectionthickness:2.5mm

Temporalresolution:1/sduringthefirstmin Acquisitionduration:4min30s

Matrix:192×192 FOV:28cm

Choice of arterial input functional ROI: there is no consensusonthis.Itwouldseemreasonabletopositionthis intheipsilateralexternalcarotidartery,ascloseaspossible tothelesion(Boxedtext2).

Interpretation

of

microcirculation

indices

Pre-treatment

Theaimhereistopredictthelikelihoodoflocalcontroland completeresponsetoconservativetreatment. Ithasbeen demonstratedthat:

• TBFand TBV predict thelevel of chemosensitivity. The higher these indices are, the more chemosensitive the

lesionis[15,18].Inparticular,ahighpre-treatmentTBV isamarkerof goodresponsetonon-surgicaltreatment, with a greater likelihood of complete response with radiochemotherapy[15];

• TBF,calculatedfromtheperfusionCT,isanindependent markeroffailureof radiotherapy:hypoperfused tumors respondlesswelltoradiotherapy,astheyarepoorly oxy-genated[19];

• SP predicts the likelihood of local control after non-surgicaltreatment[18].

Italsoappearsthat:

• theMTTcorrelateswiththelevelofmalignancy[13,14]. AnMTToflessthan3.5sisevidenceofamalignantlesion, whereasanMTTmorethan5.5ssignifiesabenignlesion. Thisreductionisduetoneoangiogenesis,withraised per-fusionpressureandraisedcapillarypermeability; • TBFandTBVcorrelatewithmicrovasculardensity[16]; • resultsforSParediscordant,andadditionalstudiesare

requiredtoestablishwhetherSPisorisnotamarkerof neoangiogenesis[13,16].

Quantitativeassessmentofresponsetotreatments andmonitoringresponsetonon-surgical

treatments

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Figure14. High-grademalignanttumor.Tissuestructureinthesuperficiallobeoftheleftparotidgland,measuring3cminsize.a:axial T2-weightedMRI:isointense;b:axialT1-weightedMRIaftergadoliniumwithfatsaturation:moderatecontrastenhancement;c:diffusion mapping:rADC=0.5;d:perfusioncurveshowingadescendingplateauwithwashoutofunder30%.

Figure15. CTversusMRIofthecavum.a:CT:sagittalreconstructioncenteredonthecavum;b:MRI:sagittalT1-weightedsequencewith gadoliniumandfatsaturationcenteredonthecavum.NotethattheenhancementresolutionisbetteronMRI.

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Figure16. CTversusMRIofthelarynx.a:MRI:coronalT1-weightedsequenceaftergadoliniumwithfat saturationcenteredonthe larynx.Rightsupra-glottalstructurewithperipheralenhancement;b:CT:coronalreconstructionofthelarynx.Notethatthedifferentiation betweenthelesion(blackasterisk)andthethyroidcartilage(blackarrow)isbetter,andvisualizationofthefatinthehyo-thyro-epiglottic cavity(whiteasterisk)isclearonCT.

• thechangeinTBVisagoodindicatorofresponse:a20% fallcorrelateswithan endoscopicresponseofover 50%

[20];

• asuccessivefallinTBVandTBF[21]isanobjective, quan-titativemethodtodetecttumorswhichhaveresponded toneo-adjuvantchemotherapy;

• arepeatedpersistent fall in TBV during treatment is a predictorofresponse[21];

• a progressive rise in TBV is characteristic of non-responderstoradiochemotherapy[21].

Detectionofrecurrences

The best detection method for detecting recurrences appears tobe PETCT withMRI [22], although these pre-liminaryfindingsneedtobeconfirmedinstudiesonlarger numbers.

A new rise in TBF after radiochemotherapy treatment wouldappeartohelptodetectrelapsewithinnon-specific post-treatmenttissuechanges[23,24].

Themainestablishedvaluesformicrocirculation param-etersaresummarizedinTable2.

AnexampleoftheuseofMRIisshowninFig.17.

Characterizationoflymphnodesundera centimeterinsize[22]

There is still a majorproblem withcharacterizing lymph nodesunderacentimeterin size.Combining PETCTwith diffusion-weighted MRI currently appears to be the best optiontodetectsmallinvadedlymphnodes[22].Perfusion

imagingdoesnotperformwell inthissituationbecauseof thesmallnumberofsectionswhichcanbeinvestigatedand theneedtodecideonthelymphnodestobeexamined in advance.

Summary

CT or MRI perfusion imaging can identify the microcir-culatory features of tumors. Initial work suggests that this method should help to predict response to non-surgicaltreatment inordertooptimallyadjustit,monitor response to the treatment quantitatively and detect relapses after conservative treatment early [25]. Validat-ing thistechnique therefore appears tobe thefirst stage towards dose modulation for each investigation, allow-ingindividuallycustomizedtreatment.Technicaldifficulties remain, however, and are described in the most recent publications which have returned to the physical bases and principles of calculating microcirculatory parameters

[26,27].

Conclusion

Perfusionimaging hasbecome a routineMRI toolfor sali-varyglandtumors.AgoodinvestigationshouldincludeaT2 sequence combinedwithdiffusion-weightedand perfusion sequence.Undertheseconditions,MRIcanpredictthetype oflesioninover80%ofcases.

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Figure17. Monitoringaleftsubmaxillarytumor.Firstline:beforetreatment:a:perfusioncurvebeforetreatmentshowingadescending plateausuggestingamalignanttumor;b:mappingofthepositiveenhancementintegralbeforetreatment:notetheperipheralhypervascular crownshowninyellowandred,indicatingextensivevascularizationwithinthelesion;c:ADCmappingbeforetreatment:lowrADCof1.1. Secondline:aftertreatment:d:perfusioncurveaftertreatmentshowinganascendingplateau;e:mappingofthepositiveenhancement integralaftertreatment:notethedisappearanceoftheperipheralhypervascularcrowninyellowandred,indicatingareductioninthe vascularizationwithinthelesion;f:ADCmappingaftertreatment:highrADCof1.45.

Table2 Literaturedata.

MTT TBF TBV PS

Beforetreatment Chemosensitivewhen

highvalue

Chemosensitivewhen highvalue

Predictivelocal control Duringtreatment Decreasewithresponse Decreasewithresponse

Increasewithno response Other Correlatedto malignancy Correlatedto malignancyand microvasculardensity Correlatedto malignancyand microvasculardensity Correlatedto malignancy

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• thechoiceofROIisveryimportant.This shouldbe positioned:

◦ outsideofcysticandhemorrhagicareas, ◦ outsideofT1hyperintenseareas, ◦ insideT1andT2hypointenseareas;

• thecurvecanonlybeinterpretedinconjunctionwith conventionalimaging:

◦ a washout of over 30% is highly suggestive of a Warthintumor,

◦ anascendingplateauwithnowashoutsuggestsa pleomorphicadenoma,

◦ adescendingplateausuggestsamalignanttumor; • afullinvestigationprotocolshouldincludeT1andT2 sequenceswithout fat saturation, T1diffusion and perfusionsequencesandafatsaturationgadolinium enhancedT1-weightedsequence;

• interpretation should take all of the anatomical, signal abnormality and functional findings into account.

UADTcarcinomas:

• the perfusion sequence appears to be useful for selectingandmonitoringtreatments;

• theperfusionsequence canbeperformed byCTor T1-weightedMRI;

• thespatialresolutionshouldbe: ◦ onesetofimagespersecondbyCT, ◦ onesetofimagesevery3to4sbyMRI;

• TBVand TBF are the bestpredictive indicators of responsetoconservativetreatmentandcanbeused tomonitorlesionswhicharecurrentlybeingtreated.

Clinical

case

report

This 79-year-old patient is being followed up for bladder cancer.PETCTshows rightparotiduptake withan SUVof 5.3(Fig.18).ThisishisMRI(Fig.19).

Questions

1.DescribetheabnormalitiesonMRI.

2.Whatquestionshouldthepatientbeasked? 3.Whatisyourdiagnosis?

4.Howdoyouconfirmit?

a30%washout.

2.The question toaskthe patientis: ‘‘Haveyoudone a needle aspiration of the lesion?’’ A needle aspiration beforetheMRIcouldcausebleedinginsidethelesion.The T1-weightedhyperintensityisnotsignificantifaneedle aspi-rationwastakenbeforetheMRI.Inthiscase,theMRIwould needtoberepeatedamonthlater.Inthiscase,noneedle aspirationhadbeenperformedbeforetheMRI.

3. The diagnosis is that of a typical Warthin tumor becauseofanunenhancedT1-weightedhyperintensityand 30%washout.TheselesionsoftenhaveanrADCofbetween 0.6and1:thisisnotthereforeincompatiblewiththe diag-nosis.In addition,thelesionsshowintenseuptake onPET CT.Thisisanincreasinglycommondiagnosisbecauseofthe increased useof this typeof investigation in all oncology assessments,particularlyinENT.

4.The diagnosismustbeconfirmedbyaneedle aspira-tion,whichdidconfirmthisdiagnosis.

5.Thisisabenigntumorwithnoriskofmalignant degen-erationandsurgeryisnotindicated. MRImonitoringalone maybesufficient,althoughisnotreallyessential.Thelesion may change in size and signal as a result of episodes of inflammationorbleedingwithinthelesion.

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Figure19. MRI: a:axialT1-weightedMRI; b:axialT2-weightedMRI; c:diffusionmapping;d:T1-weightedperfusion curve;e:axial T1-weightedMRIafterenhancementwithfatsaturation;f:coronalT1-weightedMRIafterenhancementwithfatsaturation.

Disclosure

of

interest

Theauthorsdeclarethattheyhavenoconflictsofinterest concerningthisarticle.

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