2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 1 Development of Complex Curricula for Molecular Bionics and Infobionics Programs within a consortial* framework** Consortium leader PETER PAZMANY CATHOLIC UNIVERSITY Consortium members SEMMELWEIS UNIVERSITY, DIALOG CAMPUS PUBLISHER The Project has been realised with the support of the European Union and has been co-financed by the European Social Fund *** **Molekuláris bionika és Infobionika Szakok tananyagának komplex fejlesztése konzorciumi keretben ***A projekt az Európai Unió támogatásával, az Európai Szociális Alap társfinanszírozásával valósul meg. PETER PAZMANY CATHOLIC UNIVERSITY SEMMELWEIS UNIVERSITY sote_logo.jpg dk_fejlec.gif INFOBLOKK 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 2 Peter Pazmany Catholic University Faculty of Information Technology BIOMEDICAL IMAGING RecentAdvancesinMagneticResonanceImaging www.itk.ppke.hu (Orvosbiológiaiképalkotás) (Legújabb trendek a mágneses rezonancia képalkotásban) LAJOS R. KOZÁK, VIKTOR GÁL 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 3 www.itk.ppke.hu Diffusion Tensor Imaging (DTI) Diffusion Weighted Imaging (DWI) Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 4 Diffusion Thewatermoleculesareinconstantmotion • Randomrotationsbythermalmotions• Leadingtolocalmagneticfieldvariationsandthus • T2effects • Randomdisplacementsordiffusion• RandomwalkorBrownianmotion • Inasufficientlybigcompartmenttheprobabilityofmovinginagivendirectionisequalacrossdirections(isotropy) 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 4 diff_single.png www.itk.ppke.hu Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 5 Diffusion Duetothecompleterandomnessofmotion,agroupofmoleculesstartingfromroughlythesamelocationspreadoutovertime •ThevarianceofthespreadovertimealongagivenspatialaxisiswhereDisthediffusioncoefficient •Astheyareequallylikelytomoveinanydirection,themeandisplacementofthemoleculesis0 •Diffusionisalocaleffect,thedisplacementispresentovershortdistances 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 5 diff_multiple_iso.png www.itk.ppke.hu Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 6 Diffusion anisotropy Ifmolecularmotionislimitedbynon-permeablewalls,thepatternofdiffusionbecomesanisotropic,i.e.thereisahigherprobabilityofdiffusionalongdirectionsparallelwiththeboundariesthanalongdirectionsperpendiculartothem. Diffusion in the cerebral gray matter is isotropic. Diffusion in the cerebral white matter is anisotropic. 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 6 diff_multiple_aniso.png diff_multiple_iso.png Isotropic diffusion Anisotropic diffusion www.itk.ppke.hu Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 7 Diffusion anisotropy in the human brain Theaxonsofneuronsaresurroundedbyamyelinsheath •extendedandmodifiedplasmamembraneofSchwanncellswrappedaroundtheaxoninaspiralfashion • protectstheaxons • facilitatessignaltransduction • impermeabletowater 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 7 single_neuron.png cell body axon myelin sheath Ranvier’s node axon terminals www.itk.ppke.hu Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 8 neuron_bundle.png Diffusion anisotropy in the human brain Bundledaxonslimitthediffusionofwateralongtheaxonalaxis. Thereare3maintypesofaxonalbundlesfoundinthewhitematterofthehumanbrain •Commissuralbundlesprovideconnectionbetweenthehemispheres •Associationbundlesprovidelongitudinalconnectionswithinhemispheres •Projectionbundlesprovideconnectionstotheperipheralnervoussystem 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 8 diffusion_along_nerve_fibers.png neural fiber tract diffusion along axons in a neural fiber tract www.itk.ppke.hu Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 9 Diffusion anisotropy in the human brain Commissural bundles 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 9 DTI_fiber_bundles_in_the_brain_commissural.png Patient examination @ MRKK in 2010, LR Kozák, MD, PhD www.itk.ppke.hu Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 10 Diffusion anisotropy in the human brain Projection bundles 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 10 DTI_fiber_bundles_in_the_brain_projection.png Patient examination @ MRKK in 2010, LR Kozák, MD, PhD www.itk.ppke.hu Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 11 Diffusion anisotropy in the human brain Association bundles 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 11 DTI_fiber_bundles_in_the_brain_association.png Patient examination @ MRKK in 2010, LR Kozák, MD, PhD www.itk.ppke.hu Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 12 Diffusion anisotropy in the human brain Commissural bundles Projection bundles Association bundles 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 12 DTI_fiber_bundles_in_the_brain_all.png Patient examination @ MRKK in 2010, LR Kozák, MD, PhD www.itk.ppke.hu Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 13 Diffusion weighted MRI (DWI) Usesaspin-echopulsesequencewithtwoadditionalgradientsappliedduringthesequence Pulsed-GradientSpinEcho(PGSE) EOStejskal,JETanner:SpinDiffusionMeasurements:SpinEchoesinthePresenceofaTime-dependentFieldGradient,JChemPhys,42:288-292,1965 •Firstgradientdisruptsthemagneticphasesofallprotons •Secondgradientrestoresthephasesofstationaryprotons 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 13 diffusion_sequence.png www.itk.ppke.hu Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 14 Diffusion weighted MRI (DWI) cont’d •Butthesecondgradientdoesnotcompletelyre-phasethespins •Therestorationofsignalisincompleteforprotonsthathavemoved(diffused)duringtheelapsedtime Thissequenceisverysensitivetobulkheadmovement,aswell •Diffusionineachvoxelcanbecalculatedfromthesignaldecayknowingtheacquisitionparameterb 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 14 diffusion_sequence.png www.itk.ppke.hu Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 15 Diffusion weighted MRI (DWI) cont’d •OntheexampleDWIs(diffusionsensitivegradientsappliedinthreedirectionsallwiththesameb-value)darkareasrepresentareaswithhighdegreeofdiffusion •Usingasingleb=0referenceimage,i.e.animagewithoutdiffusionweighting(S0) •Dcanbecalculatedvoxelwise,andpresentedasanapparentdiffusioncoefficient(ADC)image 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 15 DWIs S0 ADC Patient examination @ MRKK in 2010, LR Kozák, MD, PhD www.itk.ppke.hu Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 16 Diffusion weighted MRI (DWI) cont’d Asgradientsencodedirectionsinthemagnet,diffusioncanbemeasuredinarbitrarydirections. Thisflexibilityprovidesameansfordescribingneuraltractorientationsbymeasuringdiffusionanisotropy. The32diffusiondirectionvectorsofthestandardhighresolutionDTIsequenceusedattheSemmelweisUniversityMRResearchCenter(MRKK)isvisibleontheright. 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 16 www.itk.ppke.hu Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 17 Types of diffusion anisotropy 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 17 diffusion_isotropy_anisotropy.png isotropic planar linear www.itk.ppke.hu Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 18 The diffusion tensor •Diffusive properties can be described with a 3 X 3 symmetric tensor matrix 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 18 .X .Z .Y tensor www.itk.ppke.hu Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 19 FAs.png Fractional anisotropy (FA) •Direction independent measure of anisotropy •FA maps can be color coded according to the direction of highest diffusion:• LEFT-RIGHT • ANTERIOR-POSTERIOR • FEET-HEAD 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 19 FA=0 FA=0.52 FA=0.7 www.itk.ppke.hu Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 20 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 20 FA map FA map color coded according to the direction of highest diffusion Patient examination @ MRKK in 2010, LR Kozák, MD, PhD www.itk.ppke.hu Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 21 Diffusion tensor imaging (DTI) •Diffusiontensorscanbecalculatedandvisualizedvoxelwise •Theprimarydirectioncalculatedfromthetensorcanbeusedasinputfortractography 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 21 Patient examination @ MRKK in 2010, LR Kozák, MD, PhD www.itk.ppke.hu Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 22 Tractography Tractsarebuiltfromacollectionofconnectedvoxelsduringtractography.Duringstreamlinetractographyneighboringvoxelsareconnectedifthetensorinonepointstowardstheother. DTIvoxelsareonthescaleof2x2x2mm,whileneuronalfibersareonthescaleofmicrons,thereforetensorsprovideaggregatedinformation. Thusconnectivitymustbemodeled •Withadiscretemodeloftensors(toprow)connectionsordirectionscanbemissedormisinterpreted •Withacontinuousmodeloftensors(bottomrow)theresultsaremorerealistic. 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 22 tracto_disc_cont.png www.itk.ppke.hu Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 23 Tractography ProbabilistictractographyusesaBayesianapproachtoestimatethemostprobableconnections • Timedemanding • Hardwaredemanding •Cannotfullysolvecrossingfiberandkissingfiberuncertainties• Althoughaprioriinformationhelpsinsomecases 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 23 tracto_probabilistic.png www.itk.ppke.hu Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 24 crossin-kissing.png Tractography pitfalls Due to the low resolution of DTI,especially compared to the size of neural axons,uncertainties arise when: • fibers cross within a voxel •fibers come to close vicinity within a voxel (kissing fibers) •fiber direction changes in an acute angle 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 24 crossingfibers kissingfibers kissingfibers, acute angle www.itk.ppke.hu Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 25 Ways to improve DTI DTI uncertainties can be decreased using special sequences and special post processing methods: • increasing the number of diffusion directions (HARDI)• very time consuming, not appropriate in a clinical setting • increased probability of head movement artifacts • modeling higher order tensors• needs HARDI data • time consuming • computationally intensive • modeling two (or more) tensors simultaneously• Needs HARDI data • computationally intensive 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 25 Tuch et al., 2002Descoteaux et al., 2006 www.itk.ppke.hu Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 26 Ways to improve DWI/DTI Pulse-triggeringimprovesDWI/DTIimagequality TheDWIsequenceisverysensitivetotissuemotion,buttissuemotionisnotlimitedtobulkheadmovements. CSFpulsationcanalsocausemovementartifacts,whichcanbemoreprominentinthepediatricpopulation. 20imagesrecordedinthefeet-headdiffusiondirectionisshownontheright;thevariabilityintheimagesisclearlyvisible. Kozak et al., ESNR 2010 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 26 www.itk.ppke.hu Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 27 Ways to improve DWI/DTI Pulse-triggering improves DWI/DTI image quality Pulsatileartifactsareoftenvisuallyidentifiablewhenpulsetriggeringisnotused. Contrarytowhathasbeenshowninadults,thepulsationartifactscanbeobservedthroughoutthebraininthepediatricpopulation. Kozak et al., ESNR 2010 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 27 www.itk.ppke.hu Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 28 Ways to improve DWI/DTI Pulse-triggering improves DWI/DTI image quality Theseartifactscanstronglyinfluencecalculatedtensorparameters,suchasfractionalanisotropyand/oreigenvectors. Usingpulsetriggeredacquisitionscaneliminatepulsatileartifacts. PulsetriggeringisfeasibleforDWIininfantsbecauseitdoesnotincreasetheacquisitiontimesubstantiallygiventheinfants’relativelyhigherheartrateandsmallerbrainsize. Kozaketal.,ESNR2010 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 28 www.itk.ppke.hu Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 29 Clinical applications of DWI/DTI Stroke Primarycauseisinterruptionofbloodflowtobrainregionischemicinjury,infarction. ItisdifficulttodifferentiatebetweenacuteandchronicischemiausingstandardMRsequences. As“timemeanslife”incaseofstroke,DWIisaveryimportantclinicaltool. 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 29 FLAIR Patient examination @ MRKK in 2010, Courtesy of IZsigmond, MD www.itk.ppke.hu Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 30 AcuteandchronicstrokecanbedifferentiatedusingdiffusionMRI. AcutestrokeisseenasreductioninADC(decreasedsignalintesityontheADCimage,andincreasedsignalintensityontheDWI),whilechronicischemiahasincreasedADC(increasedsignalintensityonADC,anddecreasedintensityonDWI). Thereductionindiffusivityisduetocellswellingandincreasedtortuosityofextracellularfluidspaces. 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 30 ADC DWI Acute Acute Chronic Chronic Patient examination @ MRKK in 2010, Courtesy of IZsigmond, MD Patient examination @ MRKK in 2010, Courtesy of IZsigmond, MD www.itk.ppke.hu Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 31 Epilepsies DTI can be useful for describing epileptogenic neural circuits in epilepsy patients. Lymphomas & extracranial tumors DWIBS (Diffusion Weighted whole body Imaging with Background Suppression) are usefulfortumor viability assessment, itspredictive value matches that of PET-CT’s. e.g Kwee et al., Eur Radiol, 2008 Clinical applications of DWI/DTI Brain tumors DWIcan help in tumor grading • high cellular density (lymphomas, dysembryoplastic neuroepithelial tumors)low ADC • cellular density increases with degree of malignancy in gliomas DTI is useful for pre-surgical evaluation andtreatment planning in brain tumor patients. Fiber tractography can estimate the relationship between the tumor and nerve fiber bundles especially important for the quality of life (corticospinal tract, arcuate fasciculus, callosal fibers, etc.). 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 31 www.itk.ppke.hu Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 32 BoththeleftcorticospinaltractandthearcuatefasciculusaredisplacedbythelargetemporaltumorvisibleasadecreasedsignalintensityregionontheT1Wcoronalimage. 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 32 Patient examination @ MRKK in 2010, LR Kozák, MD, PhD www.itk.ppke.hu Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 33 The tumor not only displaces the arcuate fasciculus, but also separates it into an upper and lower bundle. 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 33 Patient examination @ MRKK in 2010, LR Kozák, MD, PhD www.itk.ppke.hu Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 34 Diffusion restriction in case of a brain metastasis of pulmonary origin. 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 34 Patient examination @ MRKK in 2010, LR Kozák, MD, PhD DWI ADC www.itk.ppke.hu Patient examination @ MRKK, images courtesy of G Rudas, MD, PhD. Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 35 Future clinical applications DTI-based temperature measurements Thecerebrospinalfluidcanfreelymovewithinthelateralventricles. •Incaseofnon-limiteddiffusivitythediffusionconstantofwaterdependsonlyonthetemperature. •CSFisalmostpurewater,containingonlysomeionsinnormalconditions •UsingartificialCSFcontainingphantoms,therelationshipbetweentemperatureandCSFdiffusivitycanbecalculated Kozak et al., Acta Paed, 2010 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 35 www.itk.ppke.hu Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 36 Future clinical applications DTI-based temperature measurements UponcalibrationandCSF-pulsationcorrection,ventriculartemperaturescanbeestimatedinvivo. Thiscanbeespeciallyusefulincasesofhypothermictreatmentfollowing: • perinatal brainischemia • traumatic brain injury Kozak et al., Acta Paed, 2010 Yamada et al., showed increased temperature in Moyamoya patients using this method (NeuroReport, 2010). 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 36 www.itk.ppke.hu Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 37 DWI/DTI summary Diffusionweightedimagingiscapabletomeasurewaterdiffusivityinvivo.Thesemeasurementscangiveinformationbothonstructureandfunction. Structuralaspects Asthemaindiffusiondirectionofwaterisstrictlyrestrictedalongtheaxonsinthecerebralwhitematter,DTIcandepictneuralconnectionsinhealthysubjectsandpatients. Functionalaspects Aswaterdiffusivitydependsonthebalanceofextracellularandintracellularfactors,anypathologyaffectingthesecompartments(e.g.stroke,lymphoma,etc.)cancausechangesindiffusivity,thusDWIcanbeusedfordiagnosticandprognosticpurposes. 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 37 www.itk.ppke.hu Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 38 www.itk.ppke.hu Arterial Spin Labeling (ASL) Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 39 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 39 Measuring (local) cerebral perfusion/cerebral blood flow (CBF) Invasive: contrastperfusion MRIwith contrast materials (Dynamic-susceptibilityContrast perfusion, DSC) Noninvasive: Arterial Spin Labelling (ASL) www.itk.ppke.hu D:\temp\fmri\syringe.png D:\temp\fmri\gado.gif G:\vision_projects\richter\asl\func_1-2\selslice.png Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 40 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 40 Principles of ASL www.itk.ppke.hu •PET-like for direct CBF measurement(but not CBV as with vascular contrast agents) • Measurement of slow neural changes • Absolute quantification of blood flow G:\vision_projects\richter\asl\output_func1-func2.tif Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 41 Principles of ASL: acquiring tagged image •Tag/label (with inversion) water in the blood proximalof imaging plane • Wait predefined period of time for blood to arrive • Acquire tagged image 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 41 www.itk.ppke.hu Label slab Scan slab time Label: inversion pulse Image: scan Blood flow TI Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 42 Principles of ASL: acquiring control image •Do not tag(or use altered, ineffective tag ) water in the blood proximal of imaging plane • Wait predefined period of time for blood to arrive • Acquire control image 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 42 www.itk.ppke.hu time No label Image: scan Blood flow Scan slab Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 43 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 43 Principles of ASL • Subtractlabeled and unlabeled images gives a blood flow (perfusion) weighted image www.itk.ppke.hu - = Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 44 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 44 Pulsed ASL (PASL) variants www.itk.ppke.hu Label slab Scan slab Labeled Control FAIR EPISTAR Label slab Scan slab Label slab Scan slab Label slab Scan slab Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 45 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 45 Pulsed ASL (PASL) Simple No special MR hardware required Low signal Fast acquisition www.itk.ppke.hu Label slab Inversion pulse ON Inversion pulse OFF Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 46 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 46 ContinuousASL (CASL) Special sequence-programming requirements Special (advanced) MR hardware for continues RF generation Higher SNR than PASL Slow acquisition www.itk.ppke.hu Label plane Inversion RF ON Inversion RF ON Inversion RF ON Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 47 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 47 www.itk.ppke.hu Labelled Control BOLD baseline baseline task Parallel acquisitionof ASL and BOLD data • Interleaved •Averaging of labelled and unlabelled scans (provided the sequence is BOLD type) Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 48 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 48 www.itk.ppke.hu Quantitative, independent measurements, white noise, less drifts ASL is better than BOLD •Reduced between-subject variability •Reduced within-subject, inter-session variability• Longitudinal studies •Low frequency neural activity (drug response) •Better functional spatial localization (capillaries) Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 49 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 49 www.itk.ppke.hu Low SNR comparedtoBOLD (intraditionalexperiments) ASL has problems Partialbraincoverage & Thickslices(>4mm) Reducedtemporalresolution(>4sec/volumesample) Violation of single TI(time-to-inversion)assumptions Standardization is not solved Complexpreprocessing Dozensof possiblecombinations Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 50 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 50 www.itk.ppke.hu Preprocessing and analysis: main issues Motion correction • separate (labelled-unlabelled) • combined Spatial smoothing & normalization• before or after subtraction Global spike elimination Normalization by CBF (calculation based onintesity difference)• global signal as covariate Spike (jump in average intensity) detection and clean-up based on• motion parameters • global CBF Biomedical Imaging: RecentAdvancesinMRI 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 51 2011.10.04.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 51 www.itk.ppke.hu Clinical example:amnestic mild cognitive impairment (aMCI). Direct comparison of patient and healthy group Hypo-perfusion(aMCIs4min) single subject studies High frequency stimulation (<4min) Low frequency stimulation (>4min) ASL + + BOLD ++ +/- Group level ASL ++ ++ Group level BOLD + +/- ASL fMRI with very low task frequencyConclusion Biomedical Imaging: RecentAdvancesinMRI