2024
PET imaging of M4 muscarinic acetylcholine receptors in rhesus macaques using [11C]MK-6884: Quantification with kinetic modeling and receptor occupancy by CVL-231 (emraclidine), a novel positive allosteric modulator
Belov V, Guehl N, Duvvuri S, Iredale P, Moon S, Dhaynaut M, Chakilam S, MacDonagh A, Rice P, Yokell D, Renger J, Fakhri G, Normandin M. PET imaging of M4 muscarinic acetylcholine receptors in rhesus macaques using [11C]MK-6884: Quantification with kinetic modeling and receptor occupancy by CVL-231 (emraclidine), a novel positive allosteric modulator. Cerebrovascular And Brain Metabolism Reviews 2024, 44: 1329-1342. PMID: 38477292, PMCID: PMC11342722, DOI: 10.1177/0271678x241238820.Peer-Reviewed Original ResearchConceptsPositive allosteric modulatorsReceptor occupancyNon-human primatesBinding potentialPositron emission tomographyMuscarinic acetylcholine receptorsAllosteric modulatorsNon-human primate brainM4 muscarinic acetylcholine receptorStriatal hyperdopaminergiaAcetylcholine receptorsBrain regionsCaudate nucleusTotal volume of distributionDose-dependent blockReference regionVolume of distributionPositron emission tomography imagingEmission tomographyReceptor levelsFunction of dosePET scansClinical trialsBlood-basedRhesus macaques
2023
Simulation results for limited-angle ultra-high time-of-flight resolution PET system
Marin T, Zhuo Y, Orehar M, Razdevšekc G, Dolenec R, Mounime I, Alamo J, Benlloch J, Chemli Y, Fernández-Tenllado J, Gascon D, Gola A, Gomez S, Grogg K, Guberman D, Korpar S, Krizan P, Majewski S, Manera R, Mariscal-Castilla A, Mauricio J, Merzi S, Morera C, Normandin M, Pavon G, Penna M, Seljak A, Studen A, Pestotnik R, Fakhri G. Simulation results for limited-angle ultra-high time-of-flight resolution PET system. 2023, 00: 1-1. DOI: 10.1109/nssmicrtsd49126.2023.10337821.Peer-Reviewed Original ResearchResolution PET systemsPET systemAxial fieldPositron emission tomography systemPositron emission tomography scannerTotal-body PET systemsLong axial fieldTOF resolutionNovel detectorNumerical phantomHigh-sensitivity systemMonte-Carlo simulationsSpatial resolutionPositron emission tomographyMonte-CarloSystem sensitivityImage resolutionImage qualityScintillationReconstruction engineFWHMResolutionTOFPhantomScannerTau Positron Emission Tomography and Neurocognitive Function Among Former Professional American-Style Football Players
Dhaynaut M, Grashow R, Normandin M, Wu O, Marengi D, Terry D, Sanchez J, Weisskopf M, Speizer F, Taylor H, Guehl N, Seshadri S, Beiser A, Daneshvar D, Johnson K, Iverson G, Zafonte R, Fakhri G, Baggish A. Tau Positron Emission Tomography and Neurocognitive Function Among Former Professional American-Style Football Players. Journal Of Neurotrauma 2023, 40: 1614-1624. PMID: 37282582, PMCID: PMC10458363, DOI: 10.1089/neu.2022.0454.Peer-Reviewed Original ResearchConceptsPositron emission tomographyDistribution volume ratioNeuropsychological testsNeurocognitive functionStandardized uptake value ratioControl participantsMeasures of neurocognitive functionStructural magnetic resonance imagingMeasures of memoryDepressive symptom severityMale control participantsEmission tomographyCerebellar gray matterNeuropsychological measuresTau positron emission tomographyExecutive functionSymptom severityBrain regionsEntorhinal cortexRepetitive head impactsP-tauReference regionFormer playersRepetitive head impact exposureMale controlsImpact of motion correction on [18F]-MK6240 tau PET imaging
Tiss A, Marin T, Chemli Y, Spangler-Bickell M, Gong K, Lois C, Petibon Y, Landes V, Grogg K, Normandin M, Becker A, Thibault E, Johnson K, Fakhri G, Ouyang J. Impact of motion correction on [18F]-MK6240 tau PET imaging. Physics In Medicine And Biology 2023, 68: 105015. PMID: 37116511, PMCID: PMC10278956, DOI: 10.1088/1361-6560/acd161.Peer-Reviewed Original ResearchConceptsMotion correctionPET quantitationImpact of motion correctionList-mode reconstructionMotion correction methodList-mode dataMotion-corrected imagesEffect of motion correctionVoxel displacementsPhantom experimentsOptical tracking dataLong acquisitionBrain PET scansSlow motionImage qualityPET imagingPositron emission tomographyCorrectionMotionCorrection methodRates of tau accumulationHead motionMotion metricsPhantomPositronSuper-resolution in brain positron emission tomography using a real-time motion capture system
Chemli Y, Tétrault M, Marin T, Normandin M, Bloch I, El Fakhri G, Ouyang J, Petibon Y. Super-resolution in brain positron emission tomography using a real-time motion capture system. NeuroImage 2023, 272: 120056. PMID: 36977452, PMCID: PMC10122782, DOI: 10.1016/j.neuroimage.2023.120056.Peer-Reviewed Original ResearchConceptsBrain positron emission tomographySuper-resolutionEvent-by-event basisReal-time motion capture systemSR reconstruction methodTracking cameraVisualization of small structuresPET reconstruction algorithmMoving phantomMeasure target motionLine profilesPET/CT scannerMeasured shiftsImprove image resolutionMotion capture systemMotion tracking devicePositron emission tomographyReconstruction algorithmSpatial resolutionMeasured linesPhantomReal-timeEstimation frameworkIncreased spatial resolutionReconstruction method
2022
Radiochemical Synthesis and Evaluation of 3‑[11C]Methyl-4-aminopyridine in Rodents and Nonhuman Primates for Imaging Potassium Channels in the CNS
Sun Y, Guehl N, Zhou Y, Takahashi K, Belov V, Dhaynaut M, Moon S, Fakhri G, Normandin M, Brugarolas P. Radiochemical Synthesis and Evaluation of 3‑[11C]Methyl-4-aminopyridine in Rodents and Nonhuman Primates for Imaging Potassium Channels in the CNS. ACS Chemical Neuroscience 2022, 13: 3342-3351. PMID: 36417797, PMCID: PMC9732819, DOI: 10.1021/acschemneuro.2c00364.Peer-Reviewed Original ResearchConceptsRegional brain time-activity curvesBrain time-activity curvesOne-tissue compartment modelBlood-brain barrierConsistent with <i>inNonhuman primatesTime-activity curvesPositron emission tomographySpinal cord injuryDemyelinated neuronsNeurological symptomsPotassium channelsNeuronal conductionBrain uptakeEmission tomographyStille cross-couplingMultiple sclerosisCord injurySlow kineticsBrain permeabilityTraumatic brainMyelin sheathStronger binding affinityNeuronsBrainPET imaging studies to investigate functional expression of mGluR2 using [11C]mG2P001
Yuan G, Dhaynaut M, Guehl N, Neelamegam R, Moon S, Qu X, Poutiainen P, Afshar S, Fakhri G, Normandin M, Brownell A. PET imaging studies to investigate functional expression of mGluR2 using [11C]mG2P001. Cerebrovascular And Brain Metabolism Reviews 2022, 43: 296-308. PMID: 36172629, PMCID: PMC9903221, DOI: 10.1177/0271678x221130387.Peer-Reviewed Original ResearchConceptsPositive allosteric modulatorsPositron emission tomographyNon-human primatesMGluR2 positive allosteric modulatorPositron emission tomography imagingPositive allosteric modulator of mGluR2Metabotropic glutamate receptor 2Positron emission tomography imaging studiesExpression of mGluR2Glutamate receptor 2MGluR2 functionPsychiatric disordersMGluR2 expressionTissue glutamate concentrationMGluR2Expressing mGluR2Allosteric modulatorsRat brainTransfected CHO cellsReceptor 2Glutamate concentrationEmission tomographyImaging studiesPharmacological effectsImaging ligandsSynthesis and Characterization of 5‑(2-Fluoro-4‑[11C]methoxyphenyl)-2,2-dimethyl-3,4-dihydro‑2H‑pyrano[2,3‑b]pyridine-7-carboxamide as a PET Imaging Ligand for Metabotropic Glutamate Receptor 2
Yuan G, Dhaynaut M, Lan Y, Guehl N, Huynh D, Iyengar S, Afshar S, Jain M, Pickett J, Kang H, Wang H, Moon S, Ondrechen M, Wang C, Shoup T, Fakhri G, Normandin M, Brownell A. Synthesis and Characterization of 5‑(2-Fluoro-4‑[11C]methoxyphenyl)-2,2-dimethyl-3,4-dihydro‑2H‑pyrano[2,3‑b]pyridine-7-carboxamide as a PET Imaging Ligand for Metabotropic Glutamate Receptor 2. Journal Of Medicinal Chemistry 2022, 65: 2593-2609. PMID: 35089713, PMCID: PMC9434702, DOI: 10.1021/acs.jmedchem.1c02004.Peer-Reviewed Original ResearchConceptsNegative allosteric modulatorsMetabotropic glutamate receptor 2Positron emission tomographyGlutamate receptor 2MGluR2 functionNeuropsychiatric disordersDrug effectsBrain heterogeneityReceptor 2Allosteric modulatorsMGluR2Nonhuman primatesBrain imagingPositron emission tomography imagingPositron emission tomography imaging ligandsHigh molar activityEmission tomographyExcellent radiochemical purityImaging ligandsBlocking agentsPET imagingMolar activityTherapeutic targetMetabotropicDisorders
2021
Quantification of Myocardial Mitochondrial Membrane Potential Using PET
Pelletier-Galarneau M, Detmer F, Petibon Y, Normandin M, Ma C, Alpert N, El Fakhri G. Quantification of Myocardial Mitochondrial Membrane Potential Using PET. Current Cardiology Reports 2021, 23: 70. PMID: 33970353, PMCID: PMC8443083, DOI: 10.1007/s11886-021-01500-8.Peer-Reviewed Original ResearchThe cortical origin and initial spread of medial temporal tauopathy in Alzheimer’s disease assessed with positron emission tomography
Sanchez J, Becker J, Jacobs H, Hanseeuw B, Jiang S, Schultz A, Properzi M, Katz S, Beiser A, Satizabal C, O'Donnell A, DeCarli C, Killiany R, El Fakhri G, Normandin M, Gómez-Isla T, Quiroz Y, Rentz D, Sperling R, Seshadri S, Augustinack J, Price J, Johnson K. The cortical origin and initial spread of medial temporal tauopathy in Alzheimer’s disease assessed with positron emission tomography. Science Translational Medicine 2021, 13 PMID: 33472953, PMCID: PMC7978042, DOI: 10.1126/scitranslmed.abc0655.Peer-Reviewed Original ResearchConceptsPositron emission tomographyTemporal lobeMedial temporal lobe tauAlzheimer's diseaseMedial temporal lobeStudy of normal agingAssociated with baseline measuresMolecular positron emission tomographyTau-PET signalDegree of clinical impairmentEmission tomographyModel of Alzheimer's diseaseTemporal lobe anatomyCognitive declineClinical impairmentNormal agingAdult participantsStudy of AgingRhinal sulcusBrain pathologyExtratemporal regionsPET measurementsLongitudinal studyTau progressionClinically normal people
2020
Positron annihilation localization by nanoscale magnetization
Gholami Y, Yuan H, Wilks M, Josephson L, El Fakhri G, Normandin M, Kuncic Z. Positron annihilation localization by nanoscale magnetization. Scientific Reports 2020, 10: 20262. PMID: 33219274, PMCID: PMC7680104, DOI: 10.1038/s41598-020-76980-9.Peer-Reviewed Original ResearchConceptsNanoscale magnetsSpatial resolution of PET imagesImproved dose localizationPositron emitting sourcesResolution of PET imagesPositron emission tomography instrumentationSpatial resolutionPositron emission tomographyAnnihilation quantaPhoton pairsPositron rangeDose localizationPositron annihilationCharged particlesOrtho-positroniumAnnihilationSuperparamagnetic iron oxide nanoparticlesCancer theranostic strategyPositron emission tomography scanPositronElectronic placesImage blurringPET imagingPET-MRITreatment outcomesJoint Direct Parametric Reconstruction for Pet Receptor Occupancy Mapping
Marin T, Ouyang J, Fakhri G, Normandin M, Petibon Y. Joint Direct Parametric Reconstruction for Pet Receptor Occupancy Mapping. 2020, 00: 1-4. DOI: 10.1109/nss/mic42677.2020.9507742.Peer-Reviewed Original ResearchCentral nervous systemPositron emission tomographyVariable splitting techniqueReceptor occupancyBayesian reconstruction frameworkDenoising problemDose-occupancy relationshipReconstruction frameworkCentral nervous system drugsDevelopment of central nervous systemEstimation of receptor occupancyOptimization problemDrug brain penetrationLow precisionMeasure occupancyDrug AdministrationBrain penetrationRadiation exposureSplitting techniqueEmission tomographyDynamic dataTracer bindingNervous systemConventional approachesTarget engagementPenalized Parametric PET Image Estimation Using Local Linear Fitting
Kim K, Gong K, Moon S, Fakhri G, Normandin M, Li Q. Penalized Parametric PET Image Estimation Using Local Linear Fitting. IEEE Transactions On Radiation And Plasma Medical Sciences 2020, 4: 750-758. DOI: 10.1109/trpms.2020.3024123.Peer-Reviewed Original ResearchReconstructed framesImage estimationGraphical modelsFull-dose imagesStatic imagesParametric imaging methodFunction extractionPhysiological informationImagesPositron emission tomographyLogan graphical modelConventional methodsPatient studiesKinetic parametersSuboptimalityFrameDynamic imagingTwo-tissue compartment modelPET imaging of neurotransmission using direct parametric reconstruction
Petibon Y, Alpert N, Ouyang J, Pizzagalli D, Cusin C, Fava M, Fakhri G, Normandin M. PET imaging of neurotransmission using direct parametric reconstruction. NeuroImage 2020, 221: 117154. PMID: 32679252, PMCID: PMC7800040, DOI: 10.1016/j.neuroimage.2020.117154.Peer-Reviewed Original ResearchConceptsSignal-to-noise ratioImage reconstructionPositron emission tomography image reconstructionLow signal-to-noise ratioPoisson log-likelihood functionScattered coincidencesDetector sensitivityPET sinogramsStatistical fluctuationsEstimate parametric imagesGradient-based optimizationParametric reconstructionLog-likelihood functionEffects of head movementVoxel scalePositron emission tomographySimplified reference region modelActivity concentration dataIn-vivo Imaging of Mitochondrial Depolarization of Myocardium With Positron Emission Tomography and a Proton Gradient Uncoupler
Alpert N, Pelletier-Galarneau M, Kim S, Petibon Y, Sun T, Ramos-Torres K, Normandin M, Fakhri G. In-vivo Imaging of Mitochondrial Depolarization of Myocardium With Positron Emission Tomography and a Proton Gradient Uncoupler. Frontiers In Physiology 2020, 11: 491. PMID: 32499721, PMCID: PMC7243673, DOI: 10.3389/fphys.2020.00491.Peer-Reviewed Original ResearchMitochondrial membrane potentialPositron emission tomographyProton gradient uncouplerMembrane potentialIntracoronary infusionEmission tomographyPositron emission tomography scanBolus plus infusionVolume of distributionMitochondrial membraneCellular membrane potentialBAM15InfusionPreliminary dose-response experimentsMaximum depolarizationDose-response experimentsIn vivo imagingSecular equilibriumA Radio-Nano-Platform for T1/T2 Dual-Mode PET-MR Imaging
Gholami Y, Yuan H, Wilks M, Maschmeyer R, Normandin M, Josephson L, Fakhri G, Kuncic Z. A Radio-Nano-Platform for T1/T2 Dual-Mode PET-MR Imaging. International Journal Of Nanomedicine 2020, 15: 1253-1266. PMID: 32161456, PMCID: PMC7049573, DOI: 10.2147/ijn.s241971.Peer-Reviewed Original ResearchConceptsLine spread functionPET-MR imagingSignal-to-noise ratioFull-width half-maximum (FWHMPET-MRHalf-maximum (FWHMSpatial resolutionTransmission electron microscopyImage quality gainSimultaneous positron emission tomographyContrast-enhanced diagnostic imagingAtom adsorptionPhantom imagesPositron emission tomographySpatial resolution of MRHybrid PET-MRRadio-isotopesSpread functionMulti-modal imaging techniquesSensitivity of positron emission tomographyMagnetic resonanceCo-registeredTransmission electron microscopy analysisSuper paramagnetic iron oxide nanoparticlesContrast agentsPreclinical Validation of a Single-Scan Rest/Stress Imaging Technique for 13N-Ammonia Positron Emission Tomography Cardiac Perfusion Studies
Guehl N, Pelletier-Galarneau M, Wooten D, Guerrero J, Kas A, Normandin M, Fakhri G, Alpert N. Preclinical Validation of a Single-Scan Rest/Stress Imaging Technique for 13N-Ammonia Positron Emission Tomography Cardiac Perfusion Studies. Circulation Cardiovascular Imaging 2020, 13: e009407. PMID: 31959009, PMCID: PMC7205554, DOI: 10.1161/circimaging.119.009407.Peer-Reviewed Original ResearchConceptsMyocardial blood flowPerfusion imagingMyocardial perfusion imaging proceduresSCAN-ALeft anterior descending arteryDose of adenosineAbsolute myocardial blood flowStress perfusion imagingAnterior descending arteryCardiac perfusion studiesMyocardial blood flow measurementsBland-Altman analysisNonstationary kinetic modelPositron emission tomographyMeasurement of restMyocardial blood flow valuesPharmacological stressorDescending arteryPreclinical validationMyocardial blood flow estimatesSingle-scan acquisitionPerfusion studiesVariable dosesImaging sessionMicrosphere MBF measurements
2019
Assessment of Striatal Dopamine Transporter Binding in Individuals With Major Depressive Disorder
Pizzagalli D, Berretta S, Wooten D, Goer F, Pilobello K, Kumar P, Murray L, Beltzer M, Boyer-Boiteau A, Alpert N, Fakhri G, Mechawar N, Vitaliano G, Turecki G, Normandin M. Assessment of Striatal Dopamine Transporter Binding in Individuals With Major Depressive Disorder. JAMA Psychiatry 2019, 76: 854-861. PMID: 31042280, PMCID: PMC6495358, DOI: 10.1001/jamapsychiatry.2019.0801.Peer-Reviewed Original ResearchConceptsMajor depressive disorderDA transporter availabilityVentral tegmental areaDA transporterDAT availabilityTegmental areaDepressive disorderDA signalingPositron emission tomographyDAT expressionMcLean HospitalHealthy controlsMajor depressive disorder groupsNumbers of depressive episodesStriatal dopamine transporter bindingDA transporter levelsLevels of DAT expressionStriatal DAT expressionStriatal DAT availabilityDA transporter densityDAT binding potentialDopamine transporter bindingOlder healthy controlsMesolimbic pathwayDA clearanceNovel radioligands for imaging sigma-1 receptor in brain using positron emission tomography (PET)
Lan Y, Bai P, Chen Z, Neelamegam R, Placzek M, Wang H, Fiedler S, Yang J, Yuan G, Qu X, Schmidt H, Song J, Normandin M, Ran C, Wang C. Novel radioligands for imaging sigma-1 receptor in brain using positron emission tomography (PET). Acta Pharmaceutica Sinica B 2019, 9: 1204-1215. PMID: 31867166, PMCID: PMC6900558, DOI: 10.1016/j.apsb.2019.07.002.Peer-Reviewed Original ResearchPositron emission tomographySigma-1 receptorCentral nervous systemPET/CT imagingEmission tomographyOrgans of micePositron emission tomography tracersNeuropsychiatric disordersNon-invasive quantificationBrain regionsNoninvasive toolSigma-1RadioligandDisease pathophysiologyNervous systemNovel radioligandMiceMouse brainPathological conditionsBrainReceptorsTomographyIntracellular proteinsTarget validationPET/CT
2017
Lessons learned about [F-18]-AV-1451 off-target binding from an autopsy-confirmed Parkinson’s case
Marquié M, Verwer E, Meltzer A, Kim S, Agüero C, Gonzalez J, Makaretz S, Siao Tick Chong M, Ramanan P, Amaral A, Normandin M, Vanderburg C, Gomperts S, Johnson K, Frosch M, Gómez-Isla T. Lessons learned about [F-18]-AV-1451 off-target binding from an autopsy-confirmed Parkinson’s case. Acta Neuropathologica Communications 2017, 5: 75. PMID: 29047416, PMCID: PMC5648451, DOI: 10.1186/s40478-017-0482-0.Peer-Reviewed Original ResearchConceptsPositron emission tomographyBasal gangliaBinding to neuromelaninPositron emission tomography studiesDementia of AD typeInferior temporal cortexParkinson's diseaseTau pathologyPositron emission tomography scanAlzheimer's diseaseMild cognitive impairmentTemporal cortexAutoradiographic bindingBrain regionsNeurofibrillary tau pathologyOccipital cortexPositron emission tomography signalCognitive impairmentPostmortem materialEntorhinal cortexSubstantia nigraParenchymal hemorrhagePD diagnosisAutoradiography experimentsChoroid plexus