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MARIE SKLODOWSKA-CURIE ACTIONS

Co-funding of regional, national and international programmes (COFUND)

DOC2AMU THESIS PROJECT 2018 CALL FOR APPLICATIONS

Quantitative Ultrasonic Imaging in Diagnosis of Children Bone Diseases

1. GENERAL INFORMATION

Call 2018-1

Topic Imaging

Keywords Quantitative, Ultrasonic Imaging, Numerical Modeling, Experimental, Signal processing, Children Bone Diseases

2. THESIS DIRECTOR(S), RESEARCH UNITS AND DOCTORAL SCHOOLS

Thesis director Philippe LASAYGUES

Research Unit Laboratoire de Mécanique et d’Acoustique

Doctoral school ED 353 - Sciences pour l'Ingénieur : Mécanique, Physique, Micro et Nanoélectronique

Thesis co-director Philippe PETIT

Research Unit Santé Publique et Maladies Chroniques : Qualité de Vie Concepts, Usages et Limites, Déterminants

Doctoral school ED 062 - Sciences de la Vie et de la Santé

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MARIESKLODOWSKA-CURIEACTIONS

Co-fundingofregional,nationalandinternationalprogrammes(COFUND)

DOC2AMUTHESISPROJECT2018CALLFORAPPLICATIONS

QuantitativeUltrasonicImaginginDiagnosisofChildrenBoneDiseases

1. DESCRIPTIONOFTHEPHDTHESISPROJECT

1.1OBJECTIVESOFTHEPROJECTBASEDONTHECURRENTSTATEOFTHEART

Forchildren’sbonepathologies(tumors,non-unionfractures,distraction,physispathologies),thedevelopmentofultrasonic imagingmodalitiesandprotocolsare importantchallenges inordertoprovideanalternativetoothersimagingtechnics.ConventionalmodalitiessuchasX-rayradiologyorComputedTomography(CT)whichmustbe limitedduetotheirradiationhazard.MagneticResonance Imaging isamajortoolbutrequiremorefrequentlyanesthesia[1]thanCTandgivepoorcorticalinformation.Nowadays,theB-modeultrasoundisthefirst-lineexaminationforthediagnosisofmanychildren’sdiseases.Duetoitsefficiency,theB-modeultrasoundisparticularlydedicatedtopediatricuse,allowingtoincreasethenumberofprocedureswithoutharmfuleffects.However,B-modeultrasoundhasdifficultypenetratingboneand,therefore,canonlyseetheoutersurfaceofbonystructures,andnotwhatlieswithinthem.Currently,densitometrymethodsarethemostcommonlyusedtoassessskeletalstatusinmetabolicbonediseases.InvestigationsaremainlyperformedusingDualEnergyX-ray Absorptiometry (DXA). DXA provides information on quantitative content of hydroxyapatite calcium inmeasuredbones.Thus,DXAwidelyused ina clinicalpracticedoesnotprovideanydataonbonequalitativefeatures. It iswellknownthatbiomechanicscompetenceoftheskeletonisdependentbothonbonemineraldensity (BMD)measured by DXA and qualitative features of bone like elasticity ormicroarchitecture. Somemethodsmaygiveadditionaldataonbonetissueandamongthemarequantitativeultrasound(QUS).QUSusedsincemid-eightiesshowsseveralimportantadvantages:anabilitytoassesssomequalitativefeaturesofbonetissue,relativelylowcostsandsmallsizesofequipment.QUShasalsosomedisadvantagesinvolvingdifficultyinprecisedeterminationofmeasuredbonetissuefeatures,skeletalsiteslimitedonlytoperipheralskeletonandrelatively poor precision. Commercially available QUS machines measure several peripheral skeletal sites:calcaneus, phalanges, or patella, and there is no general solution for the others. Commonly, in reviewsconcerningQUS[2]inthescopeofinterestweremainlyosteoporoticpopulations.It’sobviousthatosteoporosisisthemostcommonmetabolicbonediseasebutthereareseveralotherareaswhere isanecessitytofollowbone status, especially in children. Skeletal status changes during the whole life in physiologic (growth,involution)orpathologicstates(endocrinedisorders,sideeffectsofsomemedicationsetc.).Theroleofchildren'sbonequality iscurrentlywidelyaccepted inaclinicalcontext.But there isurgentneedtodevelopultrasonicmethodsabletoassessnotonlychildren'sbonequantity.B-modeultrasounddoesnotallowthischaracterizationofthechildren'sbonemicroarchitecture.Theimageisnotquantitative;thegrayscalelevelsarenotlinkedtoanysignificant physical parameters of the organs, such as speed of sound or attenuation.A new and relevantresearchaxisisthenproposedinthisPhDthesis:todevelopanultrasonicdiagnosticmodalityforpediatricboneimagingwithaparametriccharacterizationofbonelesion.

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For several years, the "Wave & Imaging" group of Laboratory of Mechanics and Acoustics (LMA, CNRS)associatedwiththePublicAssistance–HospitalsofMarseille(APHM)andtheEuropeanCenterforResearchinMedicalImaging(CERIMED)hasbeenstudyingthediffraction-modeultrasonicimagingofbiologicaltissues,suchasbreast tissues [3]–[5]. Thedevelopedmethodsarebasedon theultrasonic computed tomography (USCT)principlesprovideimagesofsoftmedium.Theacquisitiongeometryofthesignalsisnolongerlinearnorsectoral,asinB-modeultrasound,butcircularintheorthogonalplane,andbasedonamulti-channelandmulti-frequencyantenna.ThemaindifficultyoftheUSCTappliedinthecaseofboneimagingisthelargeimpedancecontrastbetween echogenic structures and the surrounding soft tissues. In that context, approximation methods

commonly for soft tissuesfailtoprovidequantitativeimages, except whenadapted but timeconsuming algorithmssuch as compound USCTfor instance are used [6].Wehavethensuggestedapurely numerical non-linear inversionalgorithm,and the minimizationprocedure between thefull recorded and

simulateddataissolvedusingaconjugate-gradientmethod[7],[8].ThemainobjectiveofthePhDthesisistodeveloparealprototypeofpredictiveanalysisanddiagnosisofthepediatricskeletonbasedonUSCT.Thelocksassociatedwith an in-vivo configuration are still numerous: the number of transducers, the power and theintensityofthewave,theimageresolutionandthecontrastinthedeepzone,theaccessibilityofnon-peripheralskeletalsites,orinbetweenthetwolegandarmbones,andthemuscleandsofttissueeffectintermofdispersionandattenuationofthewave.

Tasksarebasedoncombiningnumerical(taskno1)andexperimentalbenchmarktests(taskno2) inordertooptimize the signal processing (task no3). The work will begin with academic models and then the in-vivoparametersandthemorphologyof thecompleteanatomical structure (skin,muscle,bone),willbegraduallyintegratedtoachievearealisticclinicalmodel(taskno4).

1.2METHODOLOGY

(Taskno1)Modellinganalysisofinteractionwave/bone:Thenumericalmodellingisofprimeinteresttotacklemultiphysicsissues.Thesimulationofultrasonicwavespropagationthroughbiologicaltissuesisanefficientwaytogaininsightintoboneimaging.Inthisproject,anumericalmodelisdevelopedoncommercialfiniteelementsoftwareComsolMultiphysics®inordertosimulatetheexperimentalsetup.Thegoalistooptimizethedeviceconfigurationandtheultrasonicparameters.Thenumericalmodelcouldalsoprovideabetterunderstandingofthesignalsrecordedintheexperimentalsetupandimprovethesignalprocessingandtheinterpretationofthedata. After validating this model on in-vitro testing, it could integrate all the complexity of the in-vivoconfigurationtoextrapolatetheresultstoclinicalapplications:muscleandsofttissues,pairedboneetc.ThistaskwillbecarriedoutjointlywithCécileBaron'steamfromtheInstituteofMovementSciences.

(Taskno2)Laboratoryvalidationtests:Afteraseriesoftestsonnumerically-generatedsyntheticdata,weplanto test these approaches on real experimental data, for calibrated and academic objects (non-circularhomogeneouscylindersandtubes),forbonemimickingphantomsaswellasrealanimalandhumanbones.Wewilluseanewmechanicalultrasonic3D-scannersdevelopedaspartofacontract financedby theProvence-

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Alpes-Côted'Azur(PACA)RegionalCouncil(ProjectCOSTOS,2017-2018).Theideaistoimprovespecificityoftheultrasonic systems both from the electro-acoustic setup and signal processing points of view. Starting frommodificationsoftheexistingelectro-acousticsystem(pulsetransmitter,1MHz-transducers),wewillgoonwithone-element probes centered on different frequencies (500kHz, 1MHz and 2MHz) and with an ultrasonicwideband128-elementsensor(dominantfrequency3MHz[0.5–5]MHz),allowingelectronicsteeringandbeamforming. Comparative tests based on clinical B-mode ultrasound and X-ray imaging devices and preclinicalexperimentsonanimalandhumanmodelswillbecarriedoutbythedoctoralcandidateatTimoneChildren’sHospitalinMarseille,respectingthefavorableopinionofthehospitalconvention(CPP).

(Taskno3)Signalprocessing:AnotherpointofinterestrelatedtotheUSCTbreakthroughdealswiththechoiceof thecenter frequencyofprobes.TheclinicalB-modeultrasound is ratherhigh frequency (>3MHz)and inpediatricsuntil10MHz.Actually,theresultantimageadmitsagoodresolutionfortheweakdepthsoftissuesproportionallyintheacousticimpedancecontrastbetweenthemedia.Inthecaseofthebonetheuseoflowerfrequencies(<3MHz)wouldallowtosolvesomemultiplescatteringproblems.Decreasingthefrequencyofthetransmittedwavesallowswinning inpenetrationdepth in thediaphysis.But thenwe lose in spatiotemporalresolutionandfinallyinimageresolution.Topassthisdifficulty,wehaveappealtosignalprocessingmethods,notablythedeconvolutionofthesignalsbythetransferfunctionofthedevice(technologicallimitoftheclinicalB-mode ultrasound device). In this task, wewill propose to investigate a processingmethod, which can beoptimizedbysimultaneouslyanalyzingthetimeandfrequencyparameters.Forthispurpose,analgorithmbasedonawaveletcoded-excitationmethod,willbeusedtodeterminethevelocityoftheultrasonicwave,andthewavepathacrossthethicknessofthediaphysis[9]andtoenhancetheContrast-to-NoiseRatio[10].Themethodwillbeadaptedtoone-elementprobesandtothe128-elementsensor.

(Taskno4)Clinicalvalidationtests:Inthelongrun,theaimistoproduceanultrasonicdeviceofin-vivobones.The development of protocols and a prototype for clinical use should be done in close collaboration withclinicians and radiologists. The doctoral candidatewill bework in theDepartment of Pediatric and PrenatalRadiology at Timone Children’s Hospital in Marseille (APHM). These collaborations will provide clinical andmedicalexpertise,andwillalsoprovidebonesamplesforex-vivoexperiments.Severalex-vivomeasurementsonhumanbonesofdifferentsizeswillbecompletedusingofadult'sand/orchildren'sbones.Thesebonescanbeincludedinagarorgelatin-basedsoftsolidsmimickingthesofttissuessurroundingthebones.Theresultswillneedtobevalidatedfromageometricalandalsomechanicalpointofview.Realandcompleteanatomicalparttests(muscle,skin,bone)willthenbecarriedoutjointlyinthelaboratoryandclinictocompareconventionalmethods with USCT. Depending on the degree of progress, trials on patients in real-life conditionsmay beperformed.

1.3WORKPLAN

Intermsofworkflow,wehaveorganizedthePhDthesisaccordingtotheGanttchart.

Tasks Year 1 Year 2 Year 3 Months 6 12 18 24 30 36

Task1:Modellinganalysisofinteractionwave/bone(LMA) Task2:Laboratoryvalidationtests(LMA-APHM) Task3:Signalprocessing(LMA) Task4:Clinicalvalidationtests(APHM–LMA)

1.4 SUPERVISORSANDRESEARCHGROUPSDESCRIPTION

TheprojectofthePhDthesis isapartofamajorresearchprogramoncharacterizationand imagingofbonetissue inchildrenfinancedbytheFrenchNationalResearchAgency(ANRBioGMID,2007-2010;ANRMalice,

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2012-2016), the Institut Carnot STAR (Croissance, 2015-2016) and the Provence-Alpes-Côte d'Azur – PACARegional Council (Project COSTOS, 2017-2018), involving several national and international laboratories:Institute ofMovement Sciences (ISM, CNRS-AMU),University Institute of Industrial Thermal Systems (IUSTI,CNRS-AMU),LaboratoryofVibrationandAcoustics(LVA,INSALyon),LaboratoryofPathophysiology,Diagnosis&TreatmentsofBone(Lyos,INSERMLyon),MultiscaleModelingandSimulationLaboratory(MSME,CNRS-UPEC-UPEM,Marne-la-Vallée),BiologyInstituteofValrose(iBV,INSERMNice),TimoneChildren'sHospitalAPHMandthe European Center for Research in Medical Imaging (CERIMED), University of Alberta, Canada, CharitéUniversity,Germany,UniversityofMonastir,Tunisia,andNationalUniversityofColombia,Bogota,Colombia.LMA,APHM,ISM,MSMEandiBVhaveproposetocontinueunderanAAPGANR2018program,ofwhichLMAwillbetheleader.Thethesiswillbecomethemainthrustofthisprogramifaccepted.

Philippe Lasaygues (IRHC,HDR),whichwill be the thesis Supervisor and theProject Coordinator, isworkingattheLaboratoryofMechanicsandAcoustics(LMA),Marseille.LMAisaresearchunitoftheCNRS(UPR7051)attachedtotheInstituteforEngineeringandSystemsSciences(INSIS),toAix-MarseilleUniversity(AMU)andCentralMarseille.Theresearchonmedicalfieldofthe"Wave&Imaging"groupisfocusedontheultrasoniccharacterizationandimagingofbiologicalmedium/materialsuchashard(bones)andsoft(cells,blood,breast)tissues.Someof researchers in the"Wave& Imaging" teamhave interests innumerical studyofacousticorseismicwave propagation in complexmedia, with associated effects related to strong local heterogeneitiesand/or steep topography. LMA is oneof the four laboratories involved in theResearch Federation Fabri dePeiresc(FR3515)andsupportsthemechanicalcharacterizationplatform(micro-tomography,thermalimaging,ultrasonicimaging,mechanicalengineeringandmodelling).ThelaboratoryisamainpartnerofCERIMED,sinceitscreation.LMAisinvolved,forexample,intheClearPEMSonicproject(Europeangrants),intheNOVUSBIOproject (A*MIDEX grants), and in the DHU-Imaging project (A*MIDEX grants, Jules Plisson' engineeringinternship,2017).LMAisinvolvedinFranceLifeImaging,inwhichPhilippeLasayguesistheregionalinstitutionalrepresentative.

Prof.Dr.PhilippePetit(PU-PH),whichwillbethethesisco-Supervisor,istheHeadoftheDepartmentofPediatricandPrenatalRadiology,"Timone"Children-HospitalAPHM,andmemberoftheSPMCLaboratory(PublicHealthandChronicDiseases:QualityofLife,Concepts,UsesandLimitations,Determinants,Aix-MarseilleUniversity,FacultyofMedicine,EA3279).Prof.Dr.PhilippePetitisassociatedwiththeprojectofchildren'sboneimaging using USCT, since the beginning of the research program. Prof. Dr. Philippe Petit regularly acts forvalidationexperimentsonanimalorhumanmodels,inthelaboratoryastheclinic.Prof.Dr.PhilippePetitwilldefine the clinical context of the study and the bone pathologies in the child. He will participate in theexperimentalframeworkdefinedduringthethesisbythedoctoralcandidate,andwilltrainandguidethestudentintheclinicalpracticeofultrasound,andwillsupervisehimorherfortheclinicaltests.Allcontrolimagingtests,includingX-rayandultrasound,willbeperformedinhisdepartmentunderhisguidance.

2.3IDIMENSIONSANDOTHERASPECTSOFTHEPROJECT

2.1 INTERDISCIPLINARYDIMENSION

ThePhDstudentwillworkbothinacademicandclinicalteams.Withinthetwoentities,heorshewillbenefitfrom all the scientific andmedical skills needed to complete his or her thesis. The LMAhas very significantexpertiseinultrasonicexperimentaldevelopments,includinghigh-performanceinformationprocessingmethodstoproducehigh-qualityaswellasreferencedata.TheDepartmentofPediatricandPrenatalRadiologyoftheTimone Children's Hospital is specialized in diagnostic and interventional imaging, carrying out all theexplorations of pre- and post-natal imaging. This department has a complete modern technical platformincludingUltrasound,X-rayandMRIScanners,ConventionalRadiology,InterventionalRadiology.Theprojectwilllead to important breakthroughs: progress towards the development of a biomechanicalmodel and elastic

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constitutiverelationsincaseofbonediseases;andprogresstowardsthediagnosticofspecificchildren'sbonepathologies. The challenges addressed in this project will induce substantial developments in scientific,technological and clinical domains, and the research groupbrings amajor contribution to thepreventionofchildren’sbonediseases.Thenumberofidentifiedosseousdiseaseswillincreaseduetobetterknowledgeofthemechanismsofchildren'sbonemodelling.Suchadvanceswillallowforabetterclinicalmanagementofpatients.Furthermore,ultrasonicwavescanbeusedasatherapeuticvectorinthecontextofbonerepair.Whenthebonedefect is properly detected and characterized thanks to the quantitative ultrasonic imaging, the therapeutictreatmentofthislesioncouldbeoptimizedusingultrasonictools.ThisapproachisthemainresearchschemeoftheCecileBaron'steamfromISM,associatedwithLMA,MSMEandiBVlaboratories.Anotheraxisconcernstheimplementationofgeophysicalmodellingfortheinversionofexperimentaldata.The"SeismicsandSeismology"groupofLMAproposesaveryinnovativeapproachwhichwillconsistinimportingthemostsophisticatedimagingtechniquesthatareattheforefrontinthefieldofgeophysics,inanattempttoadaptthemtothefieldofmedicalbone imaging [8]. Ultrasonic wave therapy and geophysical modelling are two very promising original newapproachesaswellasdifficult.Thedoctoralcandidatewillnotworkonthesepartsdirectlybecausetheyrequireaverybroadanddeepspectrumofskillsinthefieldsofbiologyandgeophysics.Butheorshewillbenefitfrombothcommunities,andfromexchangeswithresearchersworkingonthesesubjects.Resultsaregoingtobethefruitofacomprehensiveinterdisciplinaryconcertationbyphysiciananddoctors.

2.2INTERSECTORALDIMENSION:Today,severalresultsinacademicconfigurationsmatchpredictionsexpectedforUSCT.Theproofofconceptisestablished.Thecomponentandthehardwaremodulesweredraftedandvalidatedinlaboratoryenvironment.Regardingtheeconomicmodel,theprojectisinalevelofTRL3-4(TechnologyReadinessLevel).Thegoalofthisthesisistoupgradetheexperimentalsetuptovalidateitinamorerelevantclinicalenvironment(uptoTRL5-6)Aneconomicpositioningstudyoftheprojectwilltargetindustrialpartnersandfuturephasesfortechnologicaltransfer (partnershipwith theSATTSud-Est).Thesocietaland financial impactof this researchproject in thelongerrunliesinthefactthattheuseofultrasoundsinthecaseofchildrenclinicalexaminationishighlybeneficialbecauseultrasonicwavesarea formofmechanical energy that isnot ionizing,not invasiveandnotpainful.Ultrasonic-baseddevices are a lower-costmeanof examination.UltrasonicComputedTomography couldbeviewedasafurtherexaminationforconventionalB-modeultrasoundbecauseitwillhaveincreasedaccuracyandwillprovideparametricimaging,withoutanyknownrisktothepatient."

IndustrialpartnersCR PACA brings together several businesses in the ultrasonic area, potentially concerned by the aim of thisproject. For example, Supersonic Imaging Inc., company based in Aix-en-Provence, develops the Aixplorer®deviceusedbytheLMAforelastography-basedmeasures.Inthesameway,theEurosonic-MistrasInc.(DavidMarlot),basedinVitrolles, isworkingwiththeLMAtodevelopexperimentaldevices(ANAÏSandTON'US)forultrasoniccomputedtomographyofchildren'sbones[11],andbreasts[12].

Asfarasscientificcommunicationisconcerned,theoriginalresearchbroughtoutbythisthesisshouldleadtorankjournalpublications.Resultswillalsobepresentedininternationalconferencesgatheringultrasoundsandacoustics,andbiomechanicalandbioengineeringcommunities.

2.2 INTERNATIONALDIMENSION:

TheresearchgroupconsistingoftheLMA,ISMandtheDept.ofPediatricandPrenatalRadiologycollaborateswithseveralinternationalteams.Weareco-workingwiththeteamoftheProf.LaurenceH.Le,DepartmentofRadiologyandDiagnosticImaging,andDr.RuiZheng,DepartmentofSurgery,UniversityofAlberta,Edmonton,Canada.Theseteamsare involved inclinical researchutilizingultrasoundtostudybonestructures.Withthisteam,weareworkingonsignalprocessingandinversemodelsforultrasonicimaging[9],[13],[14].Ourresearch

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groupisalsoco-workingwiththeProf.KayRaum,CenterforRegenerativeTherapies(BCRT),CharitéUniversity,Berlin,Germany.Themaingoalofthisgroupistocombinenumericalmodelling,acousticalandbiomechanicalcompetences of musculoskeletal tissues to evaluate normal and pathological conditions. Our collaborationfocusedonthemultimodalnumericalapproachformechanicalcharacterizationofbones[15].Ourgroupisco-working with the Dr. Wajih Elhadj Youssef, Laboratory of Electronics and Micro-electronics, University ofMonastir,Tunisia.Thislaboratoryismainlyspecializinginthedevelopmentofreal-timeelectronicsystems,andisinterestedinultra-fastimageprocessingmethods.OurcollaborationonimageprocessingisthemainsubjectofthePhDthesisofMsFradiMarwa[16].Forseveralyears,wehavebeencollaboratingwiththeteamofDr.Flavio Prieto-Ortiz and the team of Dr Diego Alexander Garzón-Alvarado from the National University ofColombia, in Bogota (ECOS-Nord program, 2017-2018). Our common topics are signal processing andoptimizationmethodsforelectrotechnicsprocess(adaptedforbiologicalandnaturalmaterialsuchasboneandwood),whichisthespecialtyofthisColombiangroup[17].

3.RECENTPUBLICATIONS

[1] P.Petitetal.,“RateofAbnormalOsteoarticularRadiographicFindingsinPediatricPatients,”Am.J.Roentgenol.,vol.176,no.4,pp.987–990,Apr.2001.

[2] P.LaugierandG.Haïat,Bonequantitativeultrasound.Dordrecht;NewYork:SpringerScience,2011.

[3] B.Frisch,“DevelopmentofClearPEM-Sonic&#x2014;Amultimodalpositronemissionmammographandultrasoundscanner,”2011,pp.2267–2272.

[4] G.Cucciatietal.,“DevelopmentofClearPEM-Sonic,amultimodalmammographysystemforPETandUltrasound,”J.Instrum.,vol.9,no.03,pp.C03008–C03008,Mar.2014.

[5] M.Pizzichemietal.,“157:ClearPEM-Sonic:amultimodalPET-ultrasoundmammographysystem,”Radiother.Oncol.,vol.110,pp.S76–S77,Feb.2014.

[6] P.Lasaygues,E.Ouedraogo,J.-P.Lefebvre,M.Gindre,M.Talmant,andP.Laugier,“Progresstowardsinvitroquantitativeimagingofhumanfemurusingcompoundquantitativeultrasonictomography,”Phys.Med.Biol.,vol.50,no.11,pp.2633–2649,Jun.2005.

[7] R.Guillermin,P.Lasaygues,andG.Rabau,“QuantitativeUltrasonicImagingofBones,”inThe22ndInternationalCongressonSoundandVibration,Florence,Italy,2015,pp.1–6.

[8] S.Bernard,V.Monteiller,D.Komatitsch,andP.Lasaygues,“Ultrasoniccomputedtomographybasedonfull-waveforminversionforbonequantitativeimaging,”Phys.Med.Biol.,vol.62,no.17,pp.7011–7035,Aug.2017.

[9] K.Metwally,E.Lefevre,C.Baron,R.Zheng,M.Pithioux,andP.Lasaygues,“Measuringmassdensityandultrasonicwavevelocity:Awavelet-basedmethodappliedinultrasonicreflectionmode,”Ultrasonics,Sep.2015.

[10] P.Lasayguesetal.,“ContrastresolutionenhancementofUltrasonicComputedTomographyusingawavelet-basedmethod–Preliminaryresultsinboneimaging,”inProceedingsoftheInt.WorkshoponMedicalUltrasoundTomography,Speyer,Germany,2017.

[11] P.Lasayguesetal.,“AdvancedUltrasonicTomographofChildren’sBones,”inAcousticalImaging,vol.31,A.Nowicki,J.Litniewski,andT.Kujawska,Eds.Dordrecht:SpringerNetherlands,2012,pp.31–38.

[12] J.Rouyer,S.Mensah,E.Franceschini,P.Lasaygues,andJ.-P.Lefebvre,“Conformalultrasoundimaging

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systemforanatomicalbreastinspection,”IEEETrans.Ultrason.Ferroelectr.Freq.Control,vol.59,no.7,pp.1457–1469,Jul.2012.

[13] R.ZhengandP.Lasaygues,“Simultaneousassessmentofbonethicknessandvelocityforultrasoniccomputedtomographyusingtransmission-echomethod,”2013,pp.2084–2087.

[14] R.Zheng,E.Lefevre,C.Baron,andP.Lasaygues,“Thinbonesampleassessmentusingultrasonictransmittedsignalsbasedonwaveletprocessingmethod,”in2013InternationalCongressonUltrasonics,Singapore,2013,pp.1–5.

[15] Q.Leguillette,J.-P.Berteau,C.Baron,andR.Kay,“Mechanicalandstructuralcharacterizationofthespinalentheses:amultimodalapproach,”JuliusWolffInstitute,Berlin,Germany,MasterThesis,2012.

[16] F.Marwa,Y.WajihElhadj,P.Lasaygues,andM.Mohsen,“Theimageprocessingofultrasoniccomputedtomographyofchildbone,”inProceedingsofthe2ndInternationalConferenceonAdvancedSystemsandElectricalTechnologies,Hammamet,Tunisia,2018,pp.1–6.

[17] A.Arciniegas,F.Prieto,L.Brancheriau,andP.Lasaygues,“Literaturereviewofacousticandultrasonictomographyinstandingtrees,”Trees,Aug.2014.

4.EXPECTEDPROFILEOFTHECANDIDATE

SuitablecandidateswillhaveaM.Sc.(MasterofResearch)orequivalentdegree,fromareputableUniversityorEngineering School and have strong interests in conducting research in the areas of (bio)mechanical and/oracousticalapplications,withtheoretical,numericalandexperimentalaspects.Previousexperience inmedicalfieldisadvisablebutnotrequired.

Wearelookingforhighlymotivatedstudentswhocantacklescientificproblemsonultrasonicsystems-orientedapproaches. We offer excellent research facilities, interdisciplinary scientific training, and a comprehensivecomplementarytrainingprograminaninternationalenvironment.Candidateswillhaveexcellentwrittenandverbalcommunicationskills,abilitytoworkharmoniouslyinacollaborativeresearchteam,andtopresentalargeautonomyinthework,responsibilities,dynamismandavailability.GoodknowledgeofspokenFrenchorEnglishaswellofwrittenEnglishisrequired.

5.SUPERVISORS’PROFILES

PhilippeLasayguesreceivedaPhDdegreesinAcousticfromtheAix-MarseilleUniversity,in1992.HeisworkingfortheFrenchNationalCentreforScientificResearch(CNRS)attheLaboratoryofMechanicsandAcoustics(LMAUPR7051),Marseille,France,asSeniorResearchEngineer(IRHC).Hisinterestsincludeultrasounds,ultrasonicimaging and tomography, bio-engineering, medical applications, signal processing and experimentaldevelopments.HeisheadingtheUltrasonicplatformoftheLMAandoftheAix-MarseilleUniversityeducationplatform on ultrasounds. He teaches courses on ultrasound, B-mode imaging and wave physics at the Aix-Marseille University. He is involved in several research programs as coordinatorwith regional, national andInternationalpartners(France,Canada,USA,Germany,Tunisia,Colombia).Hehasbeencoordinatorforindustrialprograms(BFSystems,Mistras).HewasproposalcoordinatorofanANR’sprojects“BioGMID–BiologicalGrowthMediumIntegrityDiagnosesusingbi-modalitytomographies”,(2007-2010)and"MALICE-MultiscaleAnaLysIsofChildren's bonE growth: both advanced ultrasonic cross-sectional imaging and biomechanics model" (2012–2016).HeisproposalcoordinatorofaprojectsupportedbytheProvence-Alpes-Côted'Azur(PACA)RegionalCouncil"COSTOS-COntrôle,SuivietperspectivesTheragnostiquesdemaladiesOSseuseschezl'enfant"(2017-

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2018).Hehassupervisedandco-supervised,9PhDstudents(nonecurrentlysupervised),5Postdoctoralfellows,and70Trainingcourses&master'sdegree.Everyyear,hecarriesoutseveralexpertsurveysinthedomainofacoustics,ultrasounds,medical imaging,non-destructive testing, signalprocessing, for regional,national andinternationalcouncils,and/oreditorialboards.HeismemberoftheInstituteofElectrical&ElectronicEngineers(IEEE),oftheEuropeanAcousticsAssociation(EAA-BoardoftheTechnicalCommitteeonUltrasound,TC-ULT),and of the French Acoustical Society (SFA - French Acoustical Society - Board of the Physical acoustics,Underwateracoustics,UltrasonicGAPSUS-group).Morethan60publicationsreferenced;WebofScience,h-index=9.-(recent)Honorthesis-DIONGM.Lamine(2015-Statisticaloptimizationalgorithmsappliedtoinverseproblemsinelectromagnetismandacoustical imaging),currently inpost-doctoralposition, ISAE,Toulouse,ARCINIEGASAndrés(2014-Ultrasoniccomputedtomographyofstandingtrees),currentlyinpost-doctoralposition,SATIESLab., Cergy-Pontoise - BERTEAU Jean-Philippe (2011 - Children Bone characterization), currently AssistantProfessor,CUNYGraduateCenter,New-York,USA.

Prof.Dr.PhilippePetitisUniversityprofessorandHospitalpractitioner(PU-PH).HeisamemberoftheSPMCLaboratory(PublicHealthandChronicDiseases:QualityofLife,Concepts,UsesandLimitations,Determinants,Aix-Marseille University, Faculty of Medicine, EA3279). Since 2004, he has been Head of the Pediatric andPrenatalImagingDepartmentattheTimoneEnfantsHospitalinMarseille.MemberoftheFrancophonePediatricandPrenatalImagingSociety,heistheTreasurerfrom2002to2008.Since2012,hehasbeenamemberoftheboardof theCollègedesEnseignantsdeFrance(CERF).He isamemberof theEuropeanSocietyofPediatricRadiology(ESPR)andhasbeentheTreasurersince2015.Morethan100publicationsreferencedinthecurrentcontents;WebofScience,h-index=12.

AVISDESDIRECTEURSDESLABORATOIRESCONCERNESPARLEPROJETDETHESE

Avisdudirecteurdulaboratoiredudirecteurdethèse,M.LEBONFrédéric

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Avisdudirecteurdulaboratoireduco-directeurdethèse,M.AUQUIERPascal

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