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MARIE SKLODOWSKA-CURIE ACTIONS

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

DOC2AMU THESIS PROJECT 2018 CALL FOR APPLICATIONS

SCRUM: Spinal cord and Cerebral tissue alterations encountered in Rugby –

Use of Magnetic resonance imaging, Mobility, bioMechanical simulations and

external Markers to characterize the Microtraumatisms

1. GENERAL INFORMATION

Call 2018-28

Topic Imaging

Keywords Magnetic Resonance Imaging, Biomechanics, Spinal Cord, Rugby

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

Thesis director Virginie CALLOT

Research Unit Centre de Résonance Magnétique Biologique et Médicale

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

Thesis co-director Morgane EVIN

Research Unit Laboratoire de Biomécanique Appliquée

Doctoral school ED 463 - Sciences du Mouvement Humain

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MARIESKLODOWSKA-CURIEACTIONS

Co-fundingofregional,nationalandinternationalprogrammes(COFUND)

DOC2AMUTHESISPROJECT2018CALLFORAPPLICATIONS

SCRUM:SpinalcordandCerebraltissuealterationsencounteredinRugby–UseofMagneticresonanceimaging,Mobility,bioMechanicalsimulationsand

externalMarkerstocharacterizetheMicrotraumatisms

BRIEF SUMMARY: this PhD project is proposed within the frame of the iLab-Spine International AssociatedLaboratory (LIA) research group that involves CRMBM (V. Callot’s team) and LBA (PJ. Arnoux’s team) inMarseille, and 4 Canadian institutions in Montréal, on the topics of spine biomechanics and imaging. Theproject focuses on the characterization ofmicrotraumas encountered in the rugby union practice and theirshort and long term effects on the central nervous system (brain and spinal cord). The project will beperformedincollaborationwiththeFrenchRugbyFederation,NationalLeague,andassociateregionalamateurandprofessionalclubs.

1. DESCRIPTIONOFTHEPHDTHESISPROJECT

1.1OBJECTIVESOFTHEPROJECTBASEDONTHECURRENTSTATEOFTHEARTCONTEXTRugby(orrugbyfootball)isoneofthethreemostpopularteamcontactsports;itispracticedinmore

than100countriesacross5continents.Sincetherugbyunionprofessionalism(in1995inFrancewhererugbyunioniscalledrugbyàXV),rugbyhasfurthergainednationalandinternationalpopularity.Withplayersbecomingprofessional,andgivenrugby’son-fieldcompetitiveness,theplayeranthropometryhasevolved, and the levels of play, speed, game intensity and workloads have also considerably enhanced,contributingtoanincreaseininjuryincidence.Themajorityoftheseinjuriesarejointtraumainvolvingmuscles,ligaments and cartilage structures [1]. But the spine and head have also been reported as common sites ofinjury.Strainorforcepulsesappliedonthebrainandthecervicalspinecanactuallyleadtoseriousaccidents(concussions,acuteinjuries,fractures,vertebraldisplacements)withpotentialdevastatingconsequences,uptotetraplegia.Nonetheless,thankstospecificpreventionprogramsandlawchanges,spineinjuriesandtraumashavenotablydecreased[2],andmedical follow-upoftheathleteswithconcussion isbecomingprogressivelyspecialized[3].However, cervical spine, spinal cord and brain are also subjected tomicrotraumas induced by the physicalconstraintsregularlyencounteredduringthegameortraining(impact,scrum,tackle,cyclic loadings, ...).Therepetitionofsuchmicrotraumascanleadtospinedegeneration(reductionofthevertebralcanal,osteophyte,

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cervicalspondylosis,…),asalreadyreportedinafewstudiescomparingprofessionalrugbyplayersandgeneralpopulation [4,5].Concerningthespinalcord,whichensuresmotorandsensorynervemessages transmissionbetweenthebrainandtherestofthebody, little isknownaboutmicrotraumaconsequences,althoughtheymay leadtomanydysfunctionsandpain (paresthesia,gaitdisorder,neurapraxia). Impactonthebrain tissuehasnotyetbeenextensivelydetailedeither[6]andshouldthusalsobeconsidered.WithanincreasingnumberofplayersintheFrenchrugbyfederationeachyear,theintensificationofpracticefor youngerplayer aswell as changes in equipment and impactpostures, tounderstand the impactof suchmicrotraumasappearsasanecessity.

Byusingcutting-edgeimagingtechnologies(highandultrahighfield)aswellasmovementandsportbiomechanicsmethodologies,suchasdevelopedatCRMBM-CEMEREMandLBA,ourmainobjective inthisprojectistodescribetheimpactofmicrotraumaencounteredduringthepracticeofrugby,intermsofearlyaging,degeneration,orrestructurationofbothbrainandspinalcordtissues.

RELEVANCEOFLABRESEARCHAXISWITHTHEPROJECT(ANDVICE-VERSA)Thanks to the technical progresses made over the last ten years in the field of medical imaging,

magneticresonanceimaging(MRI)nowoffershugeopportunitiesforbrainandspinalcordcharacterization.Amorepreciseandanearlyassessmentofbothbrainandcordalterationmechanismsmaybeachievedthroughhighqualityandspatialresolutionimagingtechniquesofferedbyhighfieldsystems(3Tand7T)andexplorationofnewbiologicalmechanisms(axonalloss,neuronalimpairment,demyelination,...),

Of particular interest for this project, the advanced MRI techniques that have been developed atCRMBM-CEMEREM (Marseille) during the last years [7-9] have shown promising results for the study ofdifferentpathophysiologicalmechanisms(cordatrophyanddegenerationoccurringwithnormalaging,specificpattern of destructuration in cervicarthrosic myelopathy, regional impairment in multiple sclerosis oramyotrophic lateralsclerosis) [10-11]. Inparallel,humanmodellingthroughVirtualHumanresearchtopicsatLBA (Marseille) have also brought new knowledge. In strong relation with the current research project,advancedtechniquestocharacterizetherangeofcervicalmotionhaveforinstancerecentlybeencoupledwithfiniteelementbasednumericalsimulationandusedtoprovideobjectivecharacterizationofmotorbikehelmetcomforts [12], head impact biomechanical analysis in snowboarding [13-14] or to quantify the effects ofcervical manipulations in osteopathy [15]; motion analysis protocols on football players have also beendevelopedwithintheiLab-Spine,toanalysetraumaticbraininjuriesduringpracticesandgames[16].

Appliedinthefieldofrugby,thetechniquesdevelopedatLBAandCRMBM-CEMEREMshouldhencealso be valuable tools that could help answering different questions. In particular, does the repetition ofmicrotraumascausevulnerabilityandearlyagingof the spinal cordandbrain?Does thepracticeof rugbychange the natural restingcervicalspinealignment and activecervicalspinerange of motion as anadaptation to rugby training or playing? Do professional or amateur players present different damagepatterns related to their training load or physical preparation? Do tissue modifications (recovery ordegeneration)occurovertime?Canwebetterdescribetheimpactandmechanismsofmicrotrauma? Conversely, the applications of MR techniques so far dedicated to the study of SC and brainpathologiestothedomainofsportisauniqueopportunityfortheCRMBM-CEMEREMtodevelopanewrangeofactivityandtoincreaseitsattractivity.ThesameholdsforthebiomechanicaltechnologiesdevelopedatLBA,whichweresofarmainlydirectedtowarddirectclinicalapplicationsorindustrialdevelopmentswithdedicatedsafetyequipmentforplayers.

MAINGOALSThemainobjectiveofthisprojectisthustobetterdescribetheimpactofmicrotraumasencountered

during the practice of rugby at the level of the central nervous system. The PhD project will consequentlyfocusedon:

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- the improvement of quantitative MR techniques so as to be able to probe specific and subtleinformationrelativetoacuteandchronicalterationsoftherugbymanbrain,spine,andspinalcord,

- the optimization of indirectmarker techniques allowing further correlationswith tissue alterations,namelyactivecervicalrangeofmotion,aswellasGPS-andheadbandsensors-deriveddatacollection,

- theidentificationofrelationshipbetweenbiomechanicalspineloadingsandtheoccurrenceofmicro-traumathroughthedescriptionandsimulationofalterationphenomenon,andfinally

- theapplicationofsuchtechniquestodifferentgroupsofrugbymanplayers,soastodefinedifferentgrades of alterations, provide objective elements for player follow-up and aptitude assessment, possiblyidentifynewriskfactors,andeventuallyprovidenewknowledgethatcouldbeusedtoimprovethesafetyandhealthoftheplayers.

1.2METHODOLOGY

To assess relevant characterizationof brain andoverall spinal cord tissuedamage,whichhas neverbeendescribed,thePhDprojectwill relyonmultiparametrichighandultra-highfield (3T/7T)MRtechniquesproviding complementary physiological information (advanced diffusion, microstructural characterization,metabolism, ..), aswell asonbiomechanical investigationscombiningnumerical simulation (SpineModel forSafety and Surgery, …) to dedicated experimental investigations using motion tracking and measurementtechniques(Codamotion-,GPS-andbrainbandsensor-basedtechnology).

The proposed methodology for the thesis project being subject to potential patents, it could not bescientificallydetailedhere.Briefly,itwillconsiston:

- theoptimizationofquantitativeMRtechniqueacquisitionstrategies(morphological,structuralandfunctional characterization of both white and gray matter and surrounding tissues, adequatesensitivitytoallowsubtleacuteorchroniceffectdetection,…),

- theoptimizationofexternalmarkertechniquesallowingfurthercorrelationswithtissuealterations,mainlyactivecervicalrangeofmotion(adaptationtothesubjectanthropometry,determinationofpotential compensatory effect, adaptation to rugby workload, hypo/hyper mobility) and datacollectedonthefield(impactforce,velocity,…)usingGPS-andheadbandsensors,and

- theexplorationofspecificgroupsofplayers(junior,seniorandretiredprofessionalfrontandrearlines, amateurs, non rugby players) using these technologies so as to identify different damagepatterns and potential acute and long-term effects (dysregulation, degeneration, early aging,remodeling) in relation with their global or individual workload, level of practice, and physicalpreparation.

Upon completion, this project should provide objective elements for player follow-up and aptitudeassessment, informationaboutage-relatedneckproblems, it shouldalsoallow the identificationofnew riskfactorsandnewknowledgetobeusedtoimprovethesafetyandhealthoftheplayers.Toachievetheseobjectives,thePhDprojectwillbecarriedoutatCRMBM-CEMEREMandLBA,withintheiLab-Spineframe*(see1.4).Inadditiontocutting-edgeequipments(whole-body7Tsystem,SpineModelforSafetyand Surgerymodel, ..), theprojectwill be supportedby amultidisciplinary partnership involving local rugbyamateur clubs, regional rugby professional clubs, the French Rugby Federation (FFR), the National RugbyLeague(LNR),theToulonUniversity(UFRSTAPS,AixMarseilleProvenceMéditerranée),aswellasclinicalandscientificexpertiseatthelocalandinternationallevelsthatguaranteefavorableoutcomesfortheproject.It isworth noting that the project is focusing here on rugby union players specifically, however the generalstudydesignisnotlimitedtothissportpracticeandcouldopenlargerperspectiveofinvestigationsinthesportdomain.

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1.3WORKPLANPROJECTFLOWSCHEDULE Year1 Year2 Year3

(months) 6 12 18 24 30 36

TASK1–Technicaldevelopments(MR/mobility/impact)

TASK2–Technicalvalidations(MR/mobility/impact)

TASK3–Controlinvestigations(normal/retired/amateur)

TASK3–Chronic/long-termphaseinvestigations(professional)

TASK4–Acutephaseinvestigations(professional)

Publication/valorization(M/A:Methodology/Application)

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1.4 SUPERVISORSANDRESEARCHGROUPSDESCRIPTIONThe PhDprojectwill be carried out under the supervision of Virginie Callot at CRMBM-CEMEREM1 and

Morgane Evin at LBA2 (see profiles on paragraph 5). The PhD project is part of the iLab-Spine3 program.Thereby,itwillbenefitfromlong-termandfruitfulpartnershipinvolvingclinical,industrialandinterdisciplinaryscientificexpertiseatthelocal,nationalandinternationallevels.

1 : TheCentre de RésonanceMagnétique Biologique etMédicale (CRMBM,UMR7339,CNRS/Aix-MarseilleUniversity, directed by M. Bernard) and CEMEREM (AP-HM, Hôpital de la Timone, directed by Pr. Guye)dedicatetheirresearchestoMRdevelopmentsandapplicationsforcardiovascular,neuromuscularandcentralnervoussystem(includingbrainandspinalcord)pathologies.TheCRMBM-CEMEREMisequippedwithaquiteunique technicalplatform, including4.7,7and11.75TMRsystems foranimal studies,and1.5,3and7TMRsystems dedicated to clinical research. The Spinal Cord imaging team is among the 10 internationallyrecognizedleadergroupsofthedomain.2:TheLaboratoiredeBiomécaniqueAppliquée(LBA,UMRT24,IFSTTAR/Aix-MarseilleUniversity,directedbyPJ.Arnoux)dedicatesitsresearchestoonescientificobjectiveandonesinglepriority:theVirtualHuman.Theappliedresearchactivitiessustainthedevelopmentofnewknowledgeontraumaevents(andtheireffectsonthehumanbody),ontraumaprevention(forthedesignofsafetysystems)andinjurymanagement(includingthedesignofmedicaldevices).3 : The iLab-Spine is an international associated laboratory (LIA) founded in 2014 (A*MIDEX foundationsupport), labeled by the CNRS in 2015, and gathering LBA (PJ. Arnoux), CRMBM (V. Callot) and AP-HM inFrance,aswellETS (Y.Petit),EPM(CE.Aubin),HSCM,HSJ inCanada.So far, the iLab-SpineandourprojectshavereceiveddirectfinancialsupportsfromA*midexfoundation,CNRS,FondationSécuritéRoutière,DomaineSkiabledeFrance,Fédération InternationaledeMoto,Salomon, InstitutCarnotSTARandAssociationpour laRecherchesurlaScléroseenPlaques.

REFERENCES:[1]KaplanKM,etal.Rubgyinjuries:areviewofconceptsandcurrentliterature.BullNYUHospJtDis.2008;66(2):86-93[2]ReboursiereE,etal.BrJSportsMed2016;0:1–5.doi:10.1136/bjsports-2016-096122[3]https://www.ffr.fr/Au-coeur-du-jeu/Comite-Medical/Commotions-Cerebrales[4]BergeJ,etal.,Age-relatedchangesinthecervicalspinesoffront-linerugbyplayers.AmJSportsMed27:422–429,1999[5]D.Brauge,etal.,Clinicalandradiologicalcervicalspineevaluationinretiredprofessionalrugbyplayers,JNeurosurgSpine23:551–557,2015[6]GalloV,etal.BMJOpen2017;7:e017990.doi:10.1136/bmjopen-2017-017990[7]O.Girard, et al,Magnetization Transfer from InhomogeneouslyBroadened Lines (ihMT): Improved Imaging Strategy for Spinal CordApplications,MagnResonMed,2017,77(2):581-591[8] A.Massire,M. Taso, P. Besson,M. Guye, JP. Ranjeva, V. Callot, High-resolutionmulti-parametric quantitative magnetic resonanceimagingofthehumancervicalspinalcordat7T,Neuroimage,2016,143,58-59

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[9]A.Massire,etal,Multi-levelmulti-anglediffusiontensorimagingofthehumancervicalspinalcordat7T,MRM,2017,inpress.[10]M.Tasoetal,Tract-specificandage-relatedvariationsofthespinalcordmicrostructure:amulti-parametricMRIstudyusingdiffusiontensorimaging(DTI)andinhomogeneousmagnetizationtransfer(ihMT),NMRinBiomed,2016,29(6):817-32[11]H.Rasoanandrianinaetal,Region-specificimpairmentofthecervicalspinalcord(SC)inamyotrophiclateralsclerosis:afeasibilitystudyusingSCtemplatesandquantitativeMRI(DTI/ihMT)),NMRBiomed,2017,30(12):doi:10.1002/nbm.3801[12]RJBianco,etal.Assessingtheglobalrangeofmotionofthehelmetedheadthroughrotationalandtranslationalmeasurements,TobesubmittedtoTrafficInjuryPrevention.[13]BaillyN.,etal,2017.AnalysisofInjuryMechanismsinHeadInjuriesinSkiersandSnowboarders.MedSciSportsExerc49,1–10.https://doi.org/10.1249/MSS.0000000000001078[14]BaillyN.,etal,2016.Headimpactinasnowboardingaccident.ScandJMedSciSports.https://doi.org/10.1111/sms.12699[15]NiewiadomskiC.,etal.2017.Lesstratégiesdemobilitécervicalesetimpactd’unetechniqueostéopathiquemyotensive.11èmeSymposiumostéopathiqueinternationaldeNantes.[16]LecoursC.,2017.Analysebiomécaniquedurisquedetraumatismecrânio-cérébrallégerlorsdelapratiquedusoccer.

2.3IDIMENSIONSANDOTHERASPECTSOFTHEPROJECT

2.1 INTERDISCIPLINARYDIMENSION

The interdisciplinary dimension is brought by the complementary approaches that are beingdevelopedbetweenCRMBM-CEMEREMandLBAwithintheiLab-Spine,togetherwiththeirclinicalpartnerships(such as AP-HM) and the recent collaboration setup with sport institutions (FFR, LNR) and their medicalcommittees and staffs. The multidisciplinary aspects of the project involve MR physics, imaging,neuroscience,dataanalysis,sportbiomechanicsandscienceofhumanbodymovement.

Virginie Callot, research director at CNRS and head of the spinal cord MR imaging group, willsupervisedthePhDprojectwithMorganeEvin,researcherinbiomechanicsatLBA,withinPierre-JeanArnoux’steam.V.CallotandPJ.ArnouxhavebeenparticularlycollaboratingonmultiphysicsapproachescombiningMRIandbiomechanicsformorethan5yearsnow(with1on-goingand1finishingPhDs,aswellas2successfullyachieved student co-directions onmorphologicalMRI, its integration within the biomechanical spinemodelSM2S,anditsusetodescribefundamentalknowledge(seee.g.[1,2]),andmorphologicalMRIcombinedwithbiomechanicalsimulationtoenhanceourvisiononcervicalmyelopathy(seee.g.[3,4]).TherecentrecruitmentofMorganeEvin,whose interests focusonspinebiomechanics(andspecifically fluidbiomechanicsandspinemobility)enlargesthepossibilitiesofinteractionwithinCRMBM-CEMEREMandLBAandinsidetheiLab-Spine.TheproposedCOFUNDPhDprojectsupervisedbyV.CallotandM.EvinwillbeconductedonthesamebasesthanpreviouslyperformedwithPJ.Arnoux,withalternateresidenciesofthePhDbetweenbothlabs.

It is finallyworthnoting that theproposedprojectwillbeconductedwith thecollaborationofFFRandLNR,therebyfurtherbroadeningtheinterdisciplinarydimension,especiallyinthemedicalandsportdomains.[1]L.Fradet,PJ.Arnoux,JP.Ranjeva,Y.Petit,V.Callot,MorphometricsoftheentirehumanspinalcordandspinalcanalmeasuredfrominvivohighresolutionanatomicalMRI,Spine,2014;[2]L.Fradet,PJArnoux,VCallot,YPetit,Contributionofwhiteandgraymattersaffectsthebiomechanicsofspinalcordinjuriesmorethanthearachnoidspace,AIME,2016;[3]M.Taso,A.LeTroter,M.Sdika,J.Cohen-Adad,PJ.Arnoux,M.Guye,JP.Ranjeva,V.Callot,Areliablespatiallynormalized templateof thehumanspinal cord -Applications toautomatedwhitematter/graymatter segmentationandTensor-BasedMorphometry (TBM)mappingofgraymatteralterationsoccurringwithage,Neuroimage,2015;[4]M.Taso,L.Fradet,V.Callot,PJ.Arnoux,Anteroposteriorcompressionofthespinalcordleadingtocervicalmyelopathy:afiniteelementanalysis.ComputMethodsBiomechBiomedEngin.,2015.

2.2INTERSECTORALDIMENSION

The intersectoral dimension is brought by recent but already strong relationships with FédérationFrançaisedeRugby(FFR)atthenationallevel,LigueNationaledeRugby(LNR)andmoreparticularlywiththeLiguePACA(ProvenceAlpesCôted’Azur)attheregionallevel,togetherwithcoachesandmedicalstaffsfromregionalprofessionalclubs(ProvenceRugby(Fédérale1)andRacingClubToulonnais(TOP14)).

WithintheframeofthisphDproject,Dr. Jean-BaptisteGrisoli (RacingClubToulonnaismedicalstaff,Sport Medicine Department AP-HM) has been identified as the major intersectoral partner. Former rugbyplayer, former physician from XV de France national team, physician at RCT and in the Sport MedicineDepartment of AP-HM, he is at the heart of the project andwill provide excellent training opportunities to

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apprehendthemajormedicalissuesoftheproject.Hewillalsoprovidementorshiptothecandidatethroughregularmeetings,offeringhim/herthepossibilitytoexperimentandcollectinformationfromthefieldtruth.

The proposed PhD project also enters within the regional and national RIS3 strategies (researchinnovation strategies for smart specialization), allowinggreat perspectives in the domains of “Health” and“RisksandSecurity”byofferingobjectiveelementsforplayerfollow-up,aptitudeassessment,riskfactorsandnew knowledge to be used to improve the safety and health of the players. The elements could provideguidelinesbeneficialtobothfederalinstitutionandsportphysiciannetworks,aswellassportindustry.

InvolvingMRandbiomechanicalinvestigationsofsportrelatedinjuries,thisprojectisalsoanexcellentopportunity to create local synergy and strengthen relationships with the Luminy Technosport, labsconnectedtotheInstitutCarnotSTARandtheassociationofinstitutionsAix-Marseille-Provence-Méditerranée.

2.2 INTERNATIONALDIMENSION:

Theinternationaldimensionisbroughtby:

- first, an international consortium. Performedwithin the frame of the iLab-Spine (Marseille/Montréal), thisproject relies on a high level consortium endorsed by complementary recognized experts in imaging andbiomechanics domains and belonging to high ranked universities (Ecole de Technologie Supérieure andPolytechnique de Montréal, Aix-Marseille University). More particularly, the candidate will have theopportunitytocloselyinteractwithandbetrainedbytheETSteaminMontréal(E.Wagnac,Y.Petit),whosetup an experimental protocol relying on head and body sensors for the detection of brainmicrotrauma forfootballplayers,whichcouldbeadaptedtorugbypractice.

-an internationalcontextassociatedtothepracticeofrugby itselfallaroundtheworld.Uponcompletionoftheproject,multicentricstudiesincollaborationwithWorldRugbycouldindeedbeconsideredtoreinforcethestatisticalpoweroftheobservations.ItisworthmentioningthatFrancewillhosttheRugbyWorldCupin2023,ie.2yearsafterthethesiscompletion,henceopeninggreatperspectivestoconsiderfurtherinvestigations.

- and, an international opening: spinal cordMRI being a rapidly evolving domain, but underrepresented ascomparedtobrain,resultsthatwillderivedfromthisPhDthesisshouldreceivepositiveattentionfromtheMRscientific and clinical community. Similarly, prevention, health and security of the players being highlyconsidered nowadays, the subject should also receive positive attention from the sport biomechanicscommunity. Participation to the International Society ofMagnetic Resonance inMedicine (ISMRM)meetingand International Conference in Biomechanics in Sport (ICBS) with presentation of on-going and innovativeworksareinherentlyexpected,alongwithpublicationsininternationalpeer-reviewjournals.

Theprojectismoreover,anddefacto, intendedtopromotethe internationalvisibilityandattractivenessofAMU,asitinvolvestheultrahighfieldMRsystem(7T)launchedbyanEquipex(7TAMI)andan«Emergenceand innovation» A*MIDEX (7T AMIstart, 2014-2016) grants; as well as the iLab-Spine, supported by an«International»A*midexgrant(2014-2016);andiswithinthescopeofInstitutCarnotSTARactivities.

Finally,basedonoriginalandcomplementaryapproaches,relyingonamultidisciplinaryresearchteamhavingalready built strong and efficient collaborations and having international recognition, relying on variousimagingandbiomechanicalfullyoperationalandinnovativeaspectsandsophisticatedtools,theprojectisnotonly feasible, it should lead to rapid publications of methods and results improving the description of thecentralnervoussystemandmoreparticularlyofthespinalcordalterationsencounteredduringthepracticeofsport, and more particularly rugby. Skills developed during the PhD, richness and complementarity of thehuman relations encountered during the 3-year PhD period, should foster career opportunities andprofessionalintegrationforthecandidate,withinbothacademicornonacademicsectors.

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3.RECENTPUBLICATIONS(LAST5YEARS)

By includingmultimodalMRI of the spinal cord and brain at high and ultra high field, post-processing toolsdedicated to the analysis of spinal cord MRI, motion range characterization and multiphysic approachescombiningMRIandbiomechanics,thefollowingpublicationsareconnectedtothethesisproject.Co-directorsofthecurrentphDproposition(V.Callot,M.Evin/PJ.Arnoux)arehighlightedinbold.

• Massire,H.Rasoanandrianina,M.Taso,M.Guye,JP.Ranjeva,T.FeiweierV.Callot,Multi-levelmulti-anglediffusiontensorimagingofthehumancervicalspinalcordat7T,MRM,2017,inpress.

• H.Rasoanandrianina,AM.Grapperon,M.Taso,OM.Girard,G.Duhamel,M.Guye,JP.Ranjeva,S.Attarian,A. Verschueren, V. Callot, Region-specific impairment of the cervical spinal cord (SC) in amyotrophiclateral sclerosis: a feasibility studyusing SC templates andquantitativeMRI (DTI/ihMT)),NMRBiomed,2017,30(12):doi:10.1002/nbm.3801

• M.Fournely,Y.Petit,E.Wagnac,J.Laurin,V.Callot,PJ.Arnoux,High-speedvideoanalysisimprovestheaccuracyof spinal cordcompressionmeasurement inamousecontusionmodel,Acompressioncriteriashouldbepreferredoveraforcecriteriatoquantifythelevelofinjuryinaspinalcordcontusionmodel,J.NeurosciMethods,2017,293:1-5

• O. Girard, V. Callot, V. Prevost, B. Robert, M. Taso, G. Ribeiro, G. Varma, N. Rangwala, D. Alsop, G.Duhamel, Magnetization Transfer from Inhomogeneously Broadened Lines (ihMT): Improved ImagingStrategyforSpinalCordApplications,MagnResonMed,2017,77(2):581-591

• DeLeener,S.Lévy,V.S.Fonov,N.Stikov,L.D.Collins,V.Callot,J.Cohen-AdadSCT:SpinalCordToolbox,anopen-sourcesoftwareforprocessingspinalcordMRIdata,Neuroimage,2017,145,24-43

• Bailly, N., Afquir, S., Laporte, J.-D., Melot, A., Savary, D., Seigneuret, E., Delay, J.-B., Donnadieu, T.,Masson,C.,Arnoux,P.-J.AnalysisofInjuryMechanismsinHeadInjuriesinSkiersandSnowboarders.MedSciSportsExerc,2017,49,1–10.

• Bailly, N., Llari,M., Donnadieu, T.,Masson, C.,Arnoux, P.J., Head impact in a snowboarding accident.ScandJMedSciSports.2016,https://doi.org/10.1111/sms.12699

• EvinM,BroadhouseKM,CallaghanFM,McGrathRT,GlastrasS,KozorR,HockingSL,LamyJ,RedheuilA,KachenouraN,FulcherGR,FigtreeGA,GrieveSM.ImpactofobesityandepicardialfatonearlyleftatrialdysfunctionassessedbycardiacMRIstrainanalysis.CardiovascDiabetol.2016,15(1):164.

• EvinM,RedheuilA, SoulatG,Perdrix L,AshrafpoorG,GironA, Lamy J,DefranceC,RouxC,HatemSN,DieboldB,MousseauxE,KachenouraN.Leftatrialaging:acardiacmagnetic resonance feature-trackingstudy.AmJPhysiolHeartCircPhysiol.2016,310(5):H542-9.

• L.Fradet,PJArnoux,VCallot,YPetit,Contributionofwhiteandgraymattersaffectsthebiomechanicsofspinalcordinjuriesmorethanthearachnoidspace,AIME,2016,8(8):1-8

• Massire,M.Taso,P.Besson,M.Guye,JP.Ranjeva,V.Callot,High-resolutionmulti-parametricquantitativemagneticresonanceimagingofthehumancervicalspinalcordat7T,Neuroimage,2016,143,58-59;

• M.Taso,O.Girard,G.Duhamel,A.LeTroter,T.Feiweier,M.Guye, JP.Ranjeva,V. Callot,Tract-specificandage-relatedvariationsofthespinalcordmicrostructure:amulti-parametricMRIstudyusingdiffusiontensor imaging (DTI) and inhomogeneous magnetization transfer (ihMT), NMR in Biomed, 2016,29(6):817-32

• DeLeener,M.Taso,J.Cohen-Adad,V.Callot,Segmentationofthehumanspinalcord,«Specialissueontissuesegmentation»,MAGMA,Magn.Reson.Mater.Phy,2016,29(2):125-53

• M. Taso, L. Fradet, V. Callot, PJ. Arnoux, Anteroposterior compression of the spinal cord leading tocervicalmyelopathy: a finite element analysis. Comput Methods Biomech Biomed Engin. 2015 Oct;18Suppl1:2070-1.

• S.Lévy,M.Benhamou;C.Naaman,P.Rainville,V.Callot,J.Cohen-AdadWhitematteratlasofthehumanspinalcordwithestimationofpartialvolumeeffect,Neuroimage,2015;119:262-71.

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• M. Taso, A. Le Troter,M. Sdika, J. Cohen-Adad,PJ. Arnoux,M.Guye, JP. Ranjeva,V. Callot, A reliablespatially normalized templateof thehuman spinal cord -Applications to automatedwhitematter/graymatter segmentation and Tensor-Based Morphometry (TBM) mapping of gray matter alterationsoccurringwithage,Neuroimage,2015,117:20-8.

• L.Fradet,PJ.Arnoux,JP.Ranjeva,Y.Petit,V.Callot,MorphometricsoftheentirehumanspinalcordandspinalcanalmeasuredfrominvivohighresolutionanatomicalMRI,Spine,2014,39(4):E262-9,

• M.Taso,A.LeTroter,M.Sdika,JP.Ranjeva,M.Guye,M.Bernard,V.Callot,ConstructionofaSpinalCordIn Vivo Atlas based on high resolution MR images at cervical and thoracic levels: preliminary results,MAGMA,Magn.Reson.Mater.Phy,2014,27,257-267

• S.Fellah,D.Caudal,A.MauesdePaula,P.Dory-Lautrec,D.Figarella-Branger,O.Chinot,P.Metellus,PJ.Cozzone, S. Confort-Gouny, B. Ghattas, V. Callot, N. Girard,MultimodalMRI (Diffusion, Perfusion andSpectroscopy):Isitpossibletopredictoligodendroglialtumorsgradeandgenotypeinthepre-therapeuticdiagnosis,AJNRAmJNeuroradiol,2013,34:1326-1333

• M.Tachrount,G.Duhamel,J.Laurin,T.Marqueste,A.MauesdePaula,P.Decherchi,PJ.Cozzone,V.Callot,InvivoshortTE localized1HMRspectroscopyofmousecervical spinal cordatveryhighmagnetic field(11.75T),MagnResonMed,2013,69(5):1225-36

• Sun, J.,Rojas,A.,Bertrand,P.,Petit,Y.,Kraenzler,R.,Arnoux, P.J. InvestigationofMotorcyclistCervicalSpineTraumaUsingHUMOSModel.TrafficInjuryPrevention,2012,13,519–528.

4.EXPECTEDPROFILEOFTHECANDIDATE

GiventhemultidisciplinaryaspectsoftheprojectstraddlingMRphysics,neuroscience,dataanalysis,sportbiomechanicsandscienceofhumanbodymovement,weseekforacandidatewithstrongskillsinthesedomains, good track records, capacity to invest in new research field, and strong ability to interactwith aninterdisciplinarycommunity.

Moreparticularly, thecandidatewillbe inchargeof theMRandmobilityprotocoloptimization, thetechnicalvalidationsandmethodologicalapplicationsonthedifferentcohorts,withpost-processinganddataanalyses,togetherwithcontributiontonumericalsimulationvalidation.He/shewillstronglyinteractwiththerugbyunionclubs,physicians,MRmethodologistsandbiomechanicians.

Consequently,thecandidateshouldideallypossessamasterdegreeoranengineerdiplomainanappropriatediscipline, such as general or biophysical engineering. Good expertise in MR imaging and image analysis,numericalsimulations,aswellasinterestinsportpracticewouldbeadvantageous.

Westronglysuggestthecandidatetocontacttheco-directors,sendingabriefCVandamotivationletter.

5.SUPERVISORS’PROFILES

ThethesiswillbesupervisedbyV.CallotandcosupervisedbyM.EvinandPJ.Arnoux

VirginieCALLOT,aged43,isaCNRSresearcherdirector,trainedinPhysics.ShecurrentlyheadstheSpinalCordMRI research group at CRMBM-CEMEREM. Her project relies on both methodological developments andpathologicalinvestigations,frommousemodelstoclinicalandultra-highfieldresearches.Shehasalong-termpartnership with both academic and industrial collaborators, from both local and international origins(Siemens, Ecole Polytechnique de Montréal, AP-HM, …). For more details, see http://crmbm.univ-amu.fr/CALLOT-Virginieorcontactvirginie.callot@univ-amu.fr

V.Callothad2patents,morethan40publications,amongwhichthemajorityqualifiedwithintheQ1quartileof their category (here mostly ‘Radiology, Nuclear Medicine & Medical Imaging’). She has coordinated 8projectsasprincipalinvestigators,amongwhichdifferentnationalcalls(ANR,IRME,ARSEP..)

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Sheisintheexecutiveandscientificboardoftheinternationallab“iLab-Spine”(directedbyPJ.Arnoux,LBA),for which she is also principal investigator for MRI, as well as in the scientific board of Institut pour laRecherchesurlaMoelleépinièreetl’Encéphale(IRME).Shehasenteredthescientificandadministrativeboardof the SFMRMB in 2013 (French society of magnetic resonance imaging in biology and medicine) and is amemberofISMRM.

Shehaspreviouslysupervisedabout15masters,2post-doctoralfellowsnowengineeratUCLondon(England)andself-entrepreneur inMontreal (Canada), respectively.Shealsosupervised3 theses: SlimFellah (EDSVS,fromseptember2009toDecember2012,3peer-reviewedpublicationsas1stauthorand1asco-author,nowina research assistant position inMemphis, USA); Manuel Taso (ED SMH, co-direction with PJ. Arnoux, fromoctober 2013 to april 2016, 4 peer-reviewed publications as 1st author and 5 as co-author, now in apostdoctoralpositioninBoston,USA);HenitsoaRasoanandrianina(EDSMH,fromOctober2015toSeptember2018,1peerreviewedpublicationas1stauthor,3tobesubmittedas1stauthorand2as2ndco-author).Onepostdoctoral fellow (starting date october 2014) and one phD student (starting date october 2017) arecurrentlyunderhersupervision.

Morgane Evin, aged 32, is a researcher recruited at IFSTTAR in 2016 after two post-doctoral positions incardiovascular biomechanics (Paris, Sydney). Her main area of research is fluid dynamics applied for thediagnosisandsimulationofphysiologyandpathologyinhumanbody.Herrecentworkontherangeofmotionassociatedtothespineaswellasonthesimulationofthecerebrospinalfluidcouldbeanassettothisproject.Part of the international lab “iLab-Spine”, her current work is in line with both imaging and simulationobjectives for the Virtual Human project. Previously involved in several interdisciplinary projects includingexperimental,imagingandnumericalparts,validationanddevelopmentofdiagnosistoolsusingavailabledataand gathering different cutting edge techniques have been performed with her collaboration (heart valvediagnosis throughcardiovascularduplicator, leftatrium functionalMRdiagnosisandcurrently cerebro-spinalfluid roles in post-traumatic recovery). Even though at the early stage of her career, her motivation andorganizationaswellasheravailabilitycouldhelpanyPhDstudentrecruitedforthisproject.OnePhDstudent(startingdateoctober2017)iscurrentlyunderhersupervision.

Pierre-Jean Arnoux, aged 45 is a researcher director in Biomechanic and Human Modelling from the“Laboratoire de Biomécanique Appliquée (LBA)” at IFSTTAR. His main research activities are related tobiomechanicsandhumanmodelling,andconcernthedesignandvalidationofhumanmodels,theanalysisoftraumaoccurrence, thedesignofdevicestoprevent injuryandthecontributiontopathologiesmanagementincludingmedicaldevicesdesignuporsurgicalplanning…).RecentlynameddirectorofLBA,PJ.Arnouxisalsoleading the International Laboratory – Spine Imaging andBiomechanics (iLab-Spine).Hehaspublishedmorethan 75 articles in peer-reviewed scientific journals, and co-authored 1 patent. He was involved in thesupervision of more than 30 master degrees, supervised 5 post-doctoral fellows and supervised or co-supervisedmorethan20PhDtheses.Allofthesestudentsretainimportantacademicandindustrialpositionsin France and Canada in the field of humanmodelling or numerical simulation. He has also coordinated 6collaborativeprojectsasprincipalinvestigatorsandmanaged12bilateralcooperationswithcompanies.

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AVISDESDIRECTEURSDESLABORATOIRESCONCERNESPARLEPROJETDETHESE

Avisdudirecteurdulaboratoiredudirecteurdethèse,MmeBERNARDMonique

xFavorable□Défavorable

Commentaires:Monavisesttrèsfavorablepourceprojetderecherchequis’intègredansunethématiquepharedulaboratoireàfortevisibilité,etestparfaitementenphaseaveclesobjectifsscientifiquesduCRMBMetlacollaborationbienétablieavecleLBAetleséquipescanadiennesàtraversleLIAiLab-Spine.Ceprojetpermettradeplusd’ouvrirunnouveauchampd’applicationpourl’imageriedelamoelleépinièredansledomainedestraumatismesliésausport.FaitàMarseille,le06/01/18Signature

Avis du directeur du laboratoire du co-directeurdethèse,MrARNOUXPierre-Jean

xFavorable□Défavorable

Commentaires: Ce projet de recherches’inscritpleinementdanslesthématiquesduLBA et du Laboratoire International iLab-Spine et contribue largement à structurernoscollaborationsavecleCRMBM.MonavisestdonctrèsfavorableFaitàMarseille,le06/01/18Signature

Pôle de Médecine Physique et de Réadaptation – Médecine du Sport Unité de Médecine du Sport – Hôpital Salvator

Pr A. DELARQUE Pr J.M. VITON Pr L. BENSOUSSAN Dr. J.M. COUDREUSE    

               

Marseille, le 06/01/2018  

 

Je soussigné Jean-Baptiste Grisoli, médecin au Pôle de Médecine Physique et de Réadaptation (Unité

de Médecine du Sport de l’Hôpital Salvator à Marseille), médecin du Rugby Club Toulonnais, ancien médecin du XV de France, apporte mon entier soutien au projet de thèse « SCRUM » soumis par Virginie Callot, directrice de recherche au CRMBM-CEMEREM, et Morgane Evin, chargée de recherche au LBA, dans le cadre du programme doctoral COFUND DOC2AMU.

Ce projet de thèse porte sur l’étude des microtraumatismes du rachis et de la moelle épinière liés à la

pratique du rugby à haut niveau. Il repose sur des approches innovantes en Imagerie par Résonance Magnétique et en Biomécanique du Sport et vise à apporter des réponses utiles tant au niveau du bilan d’aptitude des joueurs professionnels, que sur les mécanismes de blessure mis en jeu. Alors que les études concernant les commotions cérébrales sont en plein essor, peu d’études sont actuellement réalisées au niveau médullaire, plaçant ainsi le projet dans une position très favorable au niveau de la visibilité internationale, et dans un contexte médical à moyen terme. Virginie Callot, Pierre-Jean Arnoux, et moi-même collaborons sur la mise en place de ce sujet depuis 2016 (Morgane Evin nous a récemment rejoint sur ce sujet) ; nous avons depuis rencontré un ensemble de partenaires au niveau local (équipes Rugby Amateur), régional (équipes Rugby Professionnel) et national (Ligue Nationale de Rugby, Fédération Française de Rugby) pour discuter de sa faisabilité et de son intérêt. L’appel à projets de thèse COFUND DOC2AMU 2018 est une opportunité particulièrement intéressante pour concrétiser sa réalisation.

Dans ce contexte, en complément des recherches menées au sein des laboratoires CRMBM, LBA et iLab-Spine, l’étudiant(e) retenu(e) pour ce projet de thèse interagira étroitement avec mon activité professionnelle. Outre l’étude de cas pathologiques et d’occurrence de blessures médullaires qui donnera une réalité de terrain aux développements réalisés, le candidat validera ses méthodes sur les sujets sportifs que nous aurons recrutés ensemble et qui seront sujets aux explorations IRM et aux simulations biomécaniques. Le candidat aura également la possibilité d’interagir avec l’ensemble des médecins du pôle et du staff technique du RCT, de manière à renforcer ses connaissances et la pertinence de ses recherches.  

Attachés : Dr COLLETTE Philippe Dr DESSART Benjamin Dr GRISOLI Jean-Baptiste Dr LAGRANGE Gérard Dr MARZIALE Dominique Dr REQUIER Pierre Dr REQUIER Charlotte Dr RENZULLI Jean Dr SCHVIRTZ Erica Dr SERRA Jean-Michel Dr TRAPE Christian