2024
Head-to-head comparison of [18F]-Flortaucipir, [18F]-MK-6240 and [18F]-PI-2620 postmortem binding across the spectrum of neurodegenerative diseases
Aguero C, Dhaynaut M, Amaral A, Moon S, Neelamegam R, Scapellato M, Carazo-Casas C, Kumar S, El Fakhri G, Johnson K, Frosch M, Normandin M, Gómez-Isla T. Head-to-head comparison of [18F]-Flortaucipir, [18F]-MK-6240 and [18F]-PI-2620 postmortem binding across the spectrum of neurodegenerative diseases. Acta Neuropathologica 2024, 147: 25. PMID: 38280071, PMCID: PMC10822013, DOI: 10.1007/s00401-023-02672-z.Peer-Reviewed Original ResearchConceptsNon-AD tauopathiesTau aggregationTau PET tracersDNA-binding proteinsBinds to neurofibrillary tanglesSecond-generation tau tracersTransactive response DNA-binding proteinSpectrum of neurodegenerative diseasesNeurofibrillary tanglesTau lesionsMelanin-containing cellsTDP-43Binding signalTauopathiesBinding targetsCerebral amyloid angiopathyOff-target bindingB-amyloidBinding patternsNeurodegenerative diseasesTau tracersTauBinding to areasBinding profilesBinding
2023
Association of Pathologic and Volumetric Biomarker Changes With Cognitive Decline in Clinically Normal Adults
Hanseeuw B, Jacobs H, Schultz A, Buckley R, Farrell M, Guehl N, Becker J, Properzi M, Sanchez J, Quiroz Y, Vannini P, Sepulcre J, Yang H, Chhatwal J, Gatchel J, Marshall G, Amariglio R, Papp K, Rentz D, Normandin M, Price J, Healy B, El Fakhri G, Sperling R, Johnson K. Association of Pathologic and Volumetric Biomarker Changes With Cognitive Decline in Clinically Normal Adults. Neurology 2023, 101: e2533-e2544. PMID: 37968130, PMCID: PMC10791053, DOI: 10.1212/wnl.0000000000207962.Peer-Reviewed Original ResearchConceptsAssociated with cognitive declineOlder adultsNon-AD pathologyCognitive declineHippocampal volumeCognitive dataPreclinical Alzheimer Cognitive CompositeInferior temporal tauProspective cohort studyClinically normal older adultsHarvard Aging Brain StudyPittsburgh compound B PET scansOvert cognitive impairmentAnalyzed dataNormal older adultsAging Brain StudyClinically normal adultsLongitudinal associationsAlzheimer's diseaseCohort studyMemory impairmentCognitive compositeCognitive impairmentHippocampal atrophyCognitionAssociation of Novelty-Related Locus Coeruleus Function With Entorhinal Tau Deposition and Memory Decline in Preclinical Alzheimer Disease
Prokopiou P, Engels-Domínguez N, Schultz A, Sepulcre J, Koops E, Papp K, Marshall G, Normandin M, El Fakhri G, Rentz D, Sperling R, Johnson K, Jacobs H. Association of Novelty-Related Locus Coeruleus Function With Entorhinal Tau Deposition and Memory Decline in Preclinical Alzheimer Disease. Neurology 2023, 101: e1206-e1217. PMID: 37491329, PMCID: PMC10516269, DOI: 10.1212/wnl.0000000000207646.Peer-Reviewed Original ResearchConceptsLC activityMemory declineLocus coeruleusCognitive declineEC tauHarvard Aging Brain StudyHuman neuroimaging studiesSteeper memory declineNoradrenergic brainstem nucleiLongitudinal cognitive dataFunctional MRI dataTau depositionAging Brain StudyPreclinical Alzheimer's diseaseTau progressionCortical tau depositionElevated beta-amyloidInterventions promoting resilienceMild cognitive impairmentExecutive dysfunctionExecutive functionNeuroimaging studiesTau spreadingTemporal cortexCognitive compositeTau 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 metricsPhantomPositronMeasurement of Cerebral Perfusion Indices from the Early Phase of [18F]MK6240 Dynamic Tau PET Imaging
Guehl N, Dhaynaut M, Hanseeuw B, Moon S, Lois C, Thibault E, Fu J, Price J, Johnson K, El Fakhri G, Normandin M. Measurement of Cerebral Perfusion Indices from the Early Phase of [18F]MK6240 Dynamic Tau PET Imaging. Journal Of Nuclear Medicine 2023, 64: 968-975. PMID: 36997330, PMCID: PMC10241011, DOI: 10.2967/jnumed.122.265072.Peer-Reviewed Original ResearchConceptsTime-activity curvesCerebral perfusionMetabolite-corrected arterial input functionBrain time-activity curvesEarly phaseRegional time-activity curvesIndices of cerebral perfusionDynamic [<sup>18</sup>FBlood-brain barrierPlasma to brain tissueStatistically significant differenceArterial blood samplesForty-nine subjectsCNArterial input functionPathophysiological mechanismsPerfusion indicatorsPET imagingBlood samplesSignificant differenceSurrogate indexNoninvasive estimationAnatomical informationCompound BForty-nine
2022
Kinetic evaluation and assessment of longitudinal changes in reference region and extracerebral [18F]MK-6240 PET uptake
Fu J, Lois C, Sanchez J, Becker J, Rubinstein Z, Thibault E, Salvatore A, Sari H, Farrell M, Guehl N, Normandin M, Fakhri G, Johnson K, Price J. Kinetic evaluation and assessment of longitudinal changes in reference region and extracerebral [18F]MK-6240 PET uptake. Cerebrovascular And Brain Metabolism Reviews 2022, 43: 581-594. PMID: 36420769, PMCID: PMC10063833, DOI: 10.1177/0271678x221142139.Peer-Reviewed Original ResearchConceptsPartial volume correctionLongitudinal changesReference regionStandardized uptake valueFollow-up scansExtracerebral signalsAssessment of longitudinal changesCross-sectional effect sizesUptake valuePET uptakeDistribution volumeRegional uptakeArterial samplesExtracerebral contaminationOne-yearCognitively-normalEffect sizePonsGroup differentiationVolume correctionSubject levelSubjectsHuman biodistribution and radiation dosimetry of the demyelination tracer [18F]3F4AP
Brugarolas P, Wilks M, Noel J, Kaiser J, Vesper D, Ramos-Torres K, Guehl N, Macdonald-Soccorso M, Sun Y, Rice P, Yokell D, Lim R, Normandin M, El Fakhri G. Human biodistribution and radiation dosimetry of the demyelination tracer [18F]3F4AP. European Journal Of Nuclear Medicine And Molecular Imaging 2022, 50: 344-351. PMID: 36197499, PMCID: PMC9816249, DOI: 10.1007/s00259-022-05980-w.Peer-Reviewed Original ResearchConceptsRadiation dosimetryTime-activity curvesAdverse eventsEffective doseMultiple bed positionsComprehensive metabolic panelNonhuman primatesHealthy human volunteersNo adverse eventsDynamic PET scansVoltage-gated potassiumAnimal models of neurological diseasesNonhuman primate studiesModels of neurological diseasesHuman biodistributionAverage effective doseMetabolic panelDosimetryOLINDA softwareHealthy volunteersUrinary bladderPET scansDemyelinating lesionsBed positionAnimal modelsImpact of 40 Hz Transcranial Alternating Current Stimulation on Cerebral Tau Burden in Patients with Alzheimer’s Disease: A Case Series1
Dhaynaut M, Sprugnoli G, Cappon D, Macone J, Sanchez J, Normandin M, Guehl N, Koch G, Paciorek R, Connor A, Press D, Johnson K, Pascual-Leone A, Fakhri G, Santarnecchi E. Impact of 40 Hz Transcranial Alternating Current Stimulation on Cerebral Tau Burden in Patients with Alzheimer’s Disease: A Case Series1. Journal Of Alzheimer's Disease 2022, 85: 1667-1676. PMID: 34958021, PMCID: PMC9023125, DOI: 10.3233/jad-215072.Peer-Reviewed Original ResearchConceptsMicroglia activationGamma spectral powerDecrease of microglia activationNo adverse eventsTranscranial alternating current stimulationSlow disease progressionPlacebo-controlled conditionsPreclinical dataCase seriesAdverse eventsGamma oscillationsElectrophysiological assessmentP-tauMouse modelDisease progressionMesial regionMild to moderate ADAnimal modelsPatientsPET imagingAlzheimer's diseaseSpectral powerAD mouse modelAD patientsProtein clearanceA multi-pronged investigation of option generation using depression, PET and modafinil
Ang Y, Cusin C, Petibon Y, Dillon D, Breiger M, Belleau E, Normandin M, Schroder H, Boyden S, Hayden E, Levine M, Jahan A, Meyer A, Kang M, Brunner D, Gelda S, Hooker J, Fakhri G, Fava M, Pizzagalli D. A multi-pronged investigation of option generation using depression, PET and modafinil. Brain 2022, 145: 1854-1865. PMID: 35150243, PMCID: PMC9166534, DOI: 10.1093/brain/awab429.Peer-Reviewed Original ResearchConceptsD2/D3 receptor availabilitySelf-generated optionsDepressive disorderDepressed individualsReceptor availabilityDopamine D2/D3 receptor availabilityNon-depressed adultsEffects of modafinilPutamen of patientsAssociated with uniquenessOption generationD2/D3 receptorsDopaminergic activityClinical depressionBinding potentialModafinilHealthy participantsPutamenPlacebo-controlledSamples of healthy peopleDouble-blindDisordersSelf-generationHealthy controlsDopamine
2021
Near-Infrared Fluorescence Imaging of Carotid Plaques in an Atherosclerotic Murine Model
Wu X, Ulumben A, Long S, Katagiri W, Wilks M, Yuan H, Cortese B, Yang C, Kashiwagi S, Choi H, Normandin M, Fakhri G, Zaman R. Near-Infrared Fluorescence Imaging of Carotid Plaques in an Atherosclerotic Murine Model. Biomolecules 2021, 11: 1753. PMID: 34944397, PMCID: PMC8698491, DOI: 10.3390/biom11121753.Peer-Reviewed Original ResearchIn vivo and neuropathology data support locus coeruleus integrity as indicator of Alzheimer’s disease pathology and cognitive decline
Jacobs H, Becker J, Kwong K, Engels-Domínguez N, Prokopiou P, Papp K, Properzi M, Hampton O, d'Oleire Uquillas F, Sanchez J, Rentz D, El Fakhri G, Normandin M, Price J, Bennett D, Sperling R, Johnson K. In vivo and neuropathology data support locus coeruleus integrity as indicator of Alzheimer’s disease pathology and cognitive decline. Science Translational Medicine 2021, 13: eabj2511. PMID: 34550726, PMCID: PMC8641759, DOI: 10.1126/scitranslmed.abj2511.Peer-Reviewed Original ResearchConceptsLC integrityLongitudinal cognitive measuresCognitive measuresLocus coeruleusIndicators of Alzheimer's disease pathologyLocus coeruleus integrityMedial temporal lobeTangle densityRush Memory and Aging ProjectBraak stageMemory and Aging ProjectHyperphosphorylated tau aggregatesAlzheimer's diseaseB-amyloidAD-related processesMemory declineCognitive dysfunctionDisease pathologyCognitive trajectoriesTemporal lobeLC neuronsPostmortem correlationsCognitive declineEntorhinal cortexPreclinical ADNeurovascular imaging with QUTE-CE MRI in APOE4 rats reveals early vascular abnormalities
Leaston J, Ferris C, Kulkarni P, Chandramohan D, van de Ven A, Qiao J, Timms L, Sepulcre J, Fakhri G, Ma C, Normandin M, Gharagouzloo C. Neurovascular imaging with QUTE-CE MRI in APOE4 rats reveals early vascular abnormalities. PLOS ONE 2021, 16: e0256749. PMID: 34449808, PMCID: PMC8396782, DOI: 10.1371/journal.pone.0256749.Peer-Reviewed Original ResearchConceptsVascular abnormalitiesAPOE-e4Contrast-enhanced magnetic resonance imagingBlood-brain-barrier leakageNeurovascular dysfunctionSmall vessel abnormalitiesMagnetic resonance imagingTri-synaptic circuitBlood-brain-barrierCross-sectional studyFemale ratsSignificant signal increaseHyper-vascularizationCerebrovascular abnormalitiesVessel abnormalitiesNeurovascular imagingQUTE-CEBrain volumeAnimal modelsPathological causesAbnormalitiesHistological validationImaging modalitiesResonance imagingIn vivo imaging of mGlu5 receptor expression in humans with Fragile X Syndrome towards development of a potential biomarker
Mody M, Petibon Y, Han P, Kuruppu D, Ma C, Yokell D, Neelamegam R, Normandin M, Fakhri G, Brownell A. In vivo imaging of mGlu5 receptor expression in humans with Fragile X Syndrome towards development of a potential biomarker. Scientific Reports 2021, 11: 15897. PMID: 34354107, PMCID: PMC8342610, DOI: 10.1038/s41598-021-94967-y.Peer-Reviewed Original ResearchConceptsFragile X syndromeFragile X mental retardation proteinX syndromeLoss of fragile X mental retardation proteinMGlu5 receptor expressionMetabotropic glutamate subtype 5 receptorsDrug occupancy studiesSignificant group differencesFragile X mental retardationHealthy controlsAnterior cingulateMGluR5 availabilityVisuospatial processingMGlu5 receptorsOlfactory cortexBrain areasGroup differencesRetardation proteinGlutamate signalingImages of maleNeurodevelopmental disordersExcessive glutamate signalingGender-matched controlsDisordersMGluR5Quantification 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 outcomesIn vivo quantitative mapping of human mitochondrial cardiac membrane potential: a feasibility study
Pelletier-Galarneau M, Petibon Y, Ma C, Han P, Kim S, Detmer F, Yokell D, Guehl N, Normandin M, El Fakhri G, Alpert N. In vivo quantitative mapping of human mitochondrial cardiac membrane potential: a feasibility study. European Journal Of Nuclear Medicine And Molecular Imaging 2020, 48: 414-420. PMID: 32719915, PMCID: PMC7839097, DOI: 10.1007/s00259-020-04878-9.Peer-Reviewed Original ResearchConceptsMembrane potentialBolus injectionHealthy subjectsHematocrit levelsSerial venous blood samplesT1 mapping imagesVenous blood samplesExtracellular space fractionMethodsThirteen healthy subjectsDynamic PET acquisitionCellular membrane potentialGadolinium injectionPrognostic informationVentricular arrhythmiasHeart failureMyocardial hypertrophyMitochondrial membrane potentialCardiac diseaseIn vitro assessmentTherapy monitoringBlood concentrationsPET acquisitionImaging protocolBlood samplesPlasma tracer concentrationPET 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 dataReply to: Fitting of late dynamic [18F]MK6240 PET scans for in vivo tau quantification
Guehl N, Wooten D, El Fakhri G, Normandin M. Reply to: Fitting of late dynamic [18F]MK6240 PET scans for in vivo tau quantification. European Journal Of Nuclear Medicine And Molecular Imaging 2020, 47: 2947-2949. PMID: 32556399, PMCID: PMC8015946, DOI: 10.1007/s00259-020-04927-3.Peer-Reviewed Original Research