2024
Associations of Plasma Tau with Amyloid and Tau PET: Results from the Community-Based Framingham Heart Study
Ramos-Cejudo J, Scott M, Tanner J, Pase M, McGrath E, Ghosh S, Osorio R, Thibault E, Fakhri G, Johnson K, Beiser A, Seshadri S. Associations of Plasma Tau with Amyloid and Tau PET: Results from the Community-Based Framingham Heart Study. Journal Of Alzheimer's Disease 2024, 100: 487-494. PMID: 38875034, DOI: 10.3233/jad-231320.Peer-Reviewed Original ResearchConceptsCommunity-based Framingham Heart StudyFramingham Heart StudyHeart StudyCross-sectional associationsPlasma total tauMiddle-aged participantsRisk of ADCognitively healthy individualsCommunity-basedCompound B (PiB)-PETMiddle-agedPositive associationPlasma tauParticipantsTau-PETAssociationTotal tau levelsAD brain pathologyTotal-tauHealthy individualsAPOEe4Tau levelsBurdenRhinal cortexPrecuneus regions
2023
Association of Sleep Duration and Change Over Time With Imaging Biomarkers of Cerebrovascular, Amyloid, Tau, and Neurodegenerative Pathology
Baril A, Kojis D, Himali J, Decarli C, Sanchez E, Johnson K, El Fakhri G, Thibault E, Yiallourou S, Himali D, Cavuoto M, Pase M, Beiser A, Seshadri S. Association of Sleep Duration and Change Over Time With Imaging Biomarkers of Cerebrovascular, Amyloid, Tau, and Neurodegenerative Pathology. Neurology 2023, 102: e207807. PMID: 38165370, PMCID: PMC10834132, DOI: 10.1212/wnl.0000000000207807.Peer-Reviewed Original ResearchConceptsHigher WMH burdenSelf-reported sleep durationLong sleep durationNeuroimaging metricsSleep durationAssociated with incident dementiaNeurodegenerative trajectoriesSleep duration categoriesNeuroimaging markersTAU outcomesIncident dementiaNeuroimagingSleep duration changesNeuroimaging testsLinear regression modelsDuration changesMRI metricsAlzheimer's diseaseAssociation 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 compositeImpact 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 metricsPhantomPositron
2022
Impact 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 clearance
2019
Attenuation correction using 3D deep convolutional neural network for brain 18F-FDG PET/MR: Comparison with Atlas, ZTE and CT based attenuation correction
Blanc-Durand P, Khalife M, Sgard B, Kaushik S, Soret M, Tiss A, Fakhri G, Habert M, Wiesinger F, Kas A. Attenuation correction using 3D deep convolutional neural network for brain 18F-FDG PET/MR: Comparison with Atlas, ZTE and CT based attenuation correction. PLOS ONE 2019, 14: e0223141. PMID: 31589623, PMCID: PMC6779234, DOI: 10.1371/journal.pone.0223141.Peer-Reviewed Original ResearchConceptsZero echo timeAC mapsAttenuation correctionPET attenuation correctionCT-based ACComputed tomographyAC methodPhoton attenuationZTE-ACInvestigation of suspected dementiaMR imagingBrain computed tomographyAtlas-ACBrain metabolismZTE-MRIConvolutional neural networkEcho timeHead atlasFDG-PET/MRPET imagingLow biasRegions-of-interestPatientsCorrectionNeural networkMulti-Modal Signatures of Tau Pathology, Neuronal Fiber Integrity, and Functional Connectivity in Traumatic Brain Injury
Wooten D, Ortiz-Terán L, Zubcevik N, Zhang X, Huang C, Sepulcre J, Atassi N, Johnson K, Zafonte R, Fakhri G. Multi-Modal Signatures of Tau Pathology, Neuronal Fiber Integrity, and Functional Connectivity in Traumatic Brain Injury. Journal Of Neurotrauma 2019, 36: 3233-3243. PMID: 31210098, PMCID: PMC6857466, DOI: 10.1089/neu.2018.6178.Peer-Reviewed Original ResearchConceptsTraumatic brain injuryTraumatic brain injury subjectsDistribution volume ratioWhite matter integrityFunctional connectivityDiffusion tensor imagingPositron emission tomographyTBI subjectsResting-state functional magnetic resonance imagingResting state functional connectivityFunctional magnetic resonance imagingFractional anisotropyDecreased white matter integrityGroup of TBI subjectsIncreased functional connectivityFunctional MRI resultsGraph theory metricsBrain injuryLiving human brainMagnetic resonance imagingNoninvasive neuroimaging techniquesBrain regionsFunctional MRINeuroimaging techniquesDiffusion tractography imagingEvaluation of pharmacokinetic modeling strategies for in-vivo quantification of tau with the radiotracer [18F]MK6240 in human subjects
Guehl N, Wooten D, Yokell D, Moon S, Dhaynaut M, Katz S, Moody K, Gharagouzloo C, Kas A, Johnson K, El Fakhri G, Normandin M. Evaluation of pharmacokinetic modeling strategies for in-vivo quantification of tau with the radiotracer [18F]MK6240 in human subjects. European Journal Of Nuclear Medicine And Molecular Imaging 2019, 46: 2099-2111. PMID: 31332496, PMCID: PMC6709592, DOI: 10.1007/s00259-019-04419-z.Peer-Reviewed Original ResearchConceptsReference tissue methodDistribution volume ratioTissue methodIn vivo quantificationPharmacokinetic modeling strategiesArterial plasma input functionMultilinear reference tissue methodsTwo-tissue compartment modelBlood:plasma ratioTissue-to-plasmaPlasma input functionPlasma concentration time courseBlood-based methodMethodsThirty-five subjectsSUV ratioBlood-based analysesData setsArterial input functionPET scansControl subjectsMild cognitive impairmentPlasma ratioRadiometabolite analysisHealthy controlsConcentration time courseVisual cognition in non-amnestic Alzheimer's disease: Relations to tau, amyloid, and cortical atrophy
Putcha D, Brickhouse M, Touroutoglou A, Collins J, Quimby M, Wong B, Eldaief M, Schultz A, Fakhri G, Johnson K, Dickerson B, McGinnis S. Visual cognition in non-amnestic Alzheimer's disease: Relations to tau, amyloid, and cortical atrophy. NeuroImage Clinical 2019, 23: 101889. PMID: 31200149, PMCID: PMC6562373, DOI: 10.1016/j.nicl.2019.101889.Peer-Reviewed Original ResearchConceptsVisual cognitive testsNeuropsychological batteryAssociated with tauVariant of ADCortical atrophyCognitive testsLogopenic variant primary progressive aphasiaVariant primary progressive aphasiaMagnetic resonance imagingPrimary progressive aphasiaStructural magnetic resonance imagingVentral occipitotemporal cortexSuperior parietal cortexCognitive test performanceVisual cognitive dysfunctionCognitive task performanceNon-amnestic variantsSpatial patterns of tauAlzheimer's diseasePosterior cortical dysfunctionVisual cortical regionsOccipital association corticesAmyloid PETAmyloid-positive patientsPosterior cortical atrophyAutoradiography validation of novel tau PET tracer [F-18]-MK-6240 on human postmortem brain tissue
Aguero C, Dhaynaut M, Normandin M, Amaral A, Guehl N, Neelamegam R, Marquie M, Johnson K, El Fakhri G, Frosch M, Gomez-Isla T. Autoradiography validation of novel tau PET tracer [F-18]-MK-6240 on human postmortem brain tissue. Acta Neuropathologica Communications 2019, 7: 37. PMID: 30857558, PMCID: PMC6410510, DOI: 10.1186/s40478-019-0686-6.Peer-Reviewed Original ResearchConceptsIn vivo detection of neurofibrillary tanglesNeurofibrillary tanglesDetection of neurofibrillary tanglesAlzheimer's diseaseTDP-43Binds to neurofibrillary tanglesFrontotemporal lobar degeneration-tauOff-target bindingDNA-binding protein 43Binding patternsNon-Alzheimer tauopathiesHuman postmortem brain tissueTau aggregationPostmortem brain tissueBinding signalBinding targetsCerebral amyloid angiopathyIn vivo detectionB-amyloidNeurodegenerative diseasesHuman brain tissueTauTau positron emission tomographyBindingMK-6240
2018
[18F]Fluorocholine and [18F]Fluoroacetate PET as Imaging Biomarkers to Assess Phosphatidylcholine and Mitochondrial Metabolism in Preclinical Models of TSC and LAM
Verwer E, Kavanagh T, Mischler W, Feng Y, Takahashi K, Wang S, Shoup T, Neelamegam R, Yang J, Guehl N, Ran C, Massefski W, Cui Y, El-Chemaly S, Sadow P, Oldham W, Kijewski M, Fakhri G, Normandin M, Priolo C. [18F]Fluorocholine and [18F]Fluoroacetate PET as Imaging Biomarkers to Assess Phosphatidylcholine and Mitochondrial Metabolism in Preclinical Models of TSC and LAM. Clinical Cancer Research 2018, 24: 5925-5938. PMID: 30054282, PMCID: PMC6816044, DOI: 10.1158/1078-0432.ccr-17-3693.Peer-Reviewed Original ResearchMeSH KeywordsAgedAnimalsBiomarkersCholineDisease Models, AnimalFemaleFluoroacetatesHeterograftsHumansImage Processing, Computer-AssistedImmunohistochemistryLipid MetabolismLymphangioleiomyomatosisMaleMiceMice, TransgenicMitochondriaOxygen ConsumptionPhosphatidylcholinesPositron-Emission TomographyRatsTuberous SclerosisConceptsTuberous sclerosis complexMetabolic imaging biomarkersPreclinical modelsImaging biomarkersTSC2-deficient cellsStandardized uptake valueTuberous sclerosis complex manifestationsModels of tuberous sclerosis complexAutosomal dominant disorderPotential clinical interestBenign tumorsOvariectomized miceUptake valueSubcutaneous tumorsPreclinical studiesPulmonary nodulesCystic destructionLymphangioleiomyomatosisDominant disorderProliferative lesionsInactivating mutationsTumorMetabolic reprogrammingNeurocognitive impairmentPET imagingMagnetic resonance imaging based anatomical assessment of tongue impairment due to amyotrophic lateral sclerosis: A preliminary study
Lee E, Xing F, Ahn S, Reese T, Wang R, Green J, Atassi N, Wedeen V, El Fakhri G, Woo J. Magnetic resonance imaging based anatomical assessment of tongue impairment due to amyotrophic lateral sclerosis: A preliminary study. The Journal Of The Acoustical Society Of America 2018, 143: el248-el254. PMID: 29716267, PMCID: PMC5895467, DOI: 10.1121/1.5030134.Peer-Reviewed Original ResearchConceptsDiffusion tensor imagingHigh-resolution magnetic resonance imagingMagnetic resonance imagingResonance imagingEffects of amyotrophic lateral sclerosisAmyotrophic lateral sclerosisTensor imagingAmyotrophic lateral sclerosis patientsFiber connectionsSpeechNeurological disordersLateral sclerosis
2017
Hierarchical Organization of Tau and Amyloid Deposits in the Cerebral Cortex
Sepulcre J, Grothe M, Sabuncu M, Chhatwal J, Schultz A, Hanseeuw B, Fakhri G, Sperling R, Johnson K. Hierarchical Organization of Tau and Amyloid Deposits in the Cerebral Cortex. JAMA Neurology 2017, 74: 813-820. PMID: 28558094, PMCID: PMC5710537, DOI: 10.1001/jamaneurol.2017.0263.Peer-Reviewed Original ResearchConceptsHeteromodal areasTemporal lobeHarvard Aging Brain StudyHeteromodal association regionsAging Brain StudyCognitively normal participantsElderly brainsPositron emission tomographicPrimary somatomotor cortexDistribution volume ratioAlzheimer's diseaseTau depositionStandardized uptake value ratioVisual regionsNormal participantsAb depositionSomatomotor cortexTemporal areaPittsburgh compound BCarbon 11-labeled Pittsburgh Compound BBrain studiesAssociation regionsHuman brainPathological hallmarks of Alzheimer's diseaseCortical distributionTau and amyloid β proteins distinctively associate to functional network changes in the aging brain
Sepulcre J, Sabuncu M, Li Q, Fakhri G, Sperling R, Johnson K. Tau and amyloid β proteins distinctively associate to functional network changes in the aging brain. Alzheimer's & Dementia 2017, 13: 1261-1269. PMID: 28366797, PMCID: PMC5623176, DOI: 10.1016/j.jalz.2017.02.011.Peer-Reviewed Original ResearchConceptsAging brainFunctional connectivityAlzheimer's disease-related pathologyCognitively normal individualsPositron emission tomography scanHyperconnected regionsFunctional network changesMisfolded tauDisease-related pathologyBrain areasEmission tomography scanAmyloid-bFunctional reorganizationB proteinHuman brainNeuronal circuitsTauBrainNeuronal functionNegative associationAmyloidCortical patternsNetwork changesElderly subjectsPositive association
2016
Pharmacokinetic Evaluation of the Tau PET Radiotracer 18F-T807 (18F-AV-1451) in Human Subjects
Wooten D, Guehl N, Verwer E, Shoup T, Yokell D, Zubcevik N, Vasdev N, Zafonte R, Johnson K, Fakhri G, Normandin M. Pharmacokinetic Evaluation of the Tau PET Radiotracer 18F-T807 (18F-AV-1451) in Human Subjects. Journal Of Nuclear Medicine 2016, 58: 484-491. PMID: 27660144, PMCID: PMC5334185, DOI: 10.2967/jnumed.115.170910.Peer-Reviewed Original ResearchConceptsDistribution volume ratioTraumatic brain injuryMetabolite-corrected arterial input functionPET imagingPlasma radioactivity concentrationsTemporal cortexDynamic PET imagesTotal volume of distributionVolume of distributionTraumatic brain injury subjectsMesial temporal cortexArterial blood samplesPosterior cingulate gyrusFocal uptakeSUV ratioHuman subjectsArterial input functionPosterior corpus callosumBolus injectionPharmacokinetic evaluation
2015
Pulmonary imaging using respiratory motion compensated simultaneous PET/MR
Dutta J, Huang C, Li Q, El Fakhri G. Pulmonary imaging using respiratory motion compensated simultaneous PET/MR. Medical Physics 2015, 42: 4227-4240. PMID: 26133621, PMCID: PMC4474958, DOI: 10.1118/1.4921616.Peer-Reviewed Original ResearchConceptsRespiratory motionContrast-to-noise ratioClinical patient studiesPulse sequenceHigh-intensity featuresXCAT studyLow proton densityXCAT simulationPatient studiesXCAT phantomAttenuation mapBiograph mMRComplete data acquisitionSimultaneous PET/MRNonrigid registrationPET/MR scannersPET/magnetic resonanceMagnetic susceptibilityProton densityQuantitative accuracyRelaxation timePulmonary imagingLung lesionsBlurring artifactsDeformation fieldA Spectral Graph Regression Model for Learning Brain Connectivity of Alzheimer’s Disease
Hu C, Cheng L, Sepulcre J, Johnson K, Fakhri G, Lu Y, Li Q. A Spectral Graph Regression Model for Learning Brain Connectivity of Alzheimer’s Disease. PLOS ONE 2015, 10: e0128136. PMID: 26024224, PMCID: PMC4449104, DOI: 10.1371/journal.pone.0128136.Peer-Reviewed Original ResearchConceptsNetwork featuresAlzheimer's diseaseConsistent with known pathologyUnknown graphConnection weightsReconstruction networkCortical hubsDegree statisticsData modelSmooth signalsFeatures of brain pathologyOptimization frameworkAmyloid-bPartial correlation estimationImage dataNetworkGraphGlobal connectivity measuresPositron emission tomographyConnectivity measuresNeurodegenerative diseasesConnectivity patternsSample correlationClinical ADSimulated data
2014
Relative role of motion and PSF compensation in whole‐body oncologic PET‐MR imaging
Petibon Y, Huang C, Ouyang J, Reese T, Li Q, Syrkina A, Chen Y, Fakhri G. Relative role of motion and PSF compensation in whole‐body oncologic PET‐MR imaging. Medical Physics 2014, 41: 042503. PMID: 24694156, PMCID: PMC3971824, DOI: 10.1118/1.4868458.Peer-Reviewed Original ResearchConceptsPoint spread function modelRespiratory motionPoint spread functionPET-MR scannersPencil-beam navigator echoesPET-MRMeasurement of respiratory motionPSF modelRespiratory motion correctionDetector blur effectsModel respiratory motionLung-liver interfacePatient studiesLesion contrastSimultaneous PET-MRSource of image degradationWhole-body PET imagingPET reconstruction algorithmMoving lesionsPhantom experiment resultsPET eventsContrast recoveryNavigator echoesIterative reconstruction processMotion correction
2009
Quantitative relationship between coronary calcium content and coronary flow reserve as assessed by integrated PET/CT imaging
Curillova Z, Yaman B, Dorbala S, Kwong R, Sitek A, El Fakhri G, Anagnostopoulos C, Di Carli M. Quantitative relationship between coronary calcium content and coronary flow reserve as assessed by integrated PET/CT imaging. European Journal Of Nuclear Medicine And Molecular Imaging 2009, 36: 1603-1610. PMID: 19387640, PMCID: PMC3117296, DOI: 10.1007/s00259-009-1121-1.Peer-Reviewed Original ResearchConceptsCoronary artery calcium scoreCoronary artery calciumCoronary vasodilator functionCoronary flow reserveCoronary artery diseaseHyperemic myocardial blood flowMyocardial blood flowVasodilator functionWeak inverse correlationCAC scoreCoronary artery calcium contentFlow reserveIncreasing CAC scorePer-vessel basisPer-patient basisInverse correlationBody mass indexCoronary calcium contentCoronary risk factorsCoronary vascular resistancePET/CT imagingConclusionIn patientsArtery calciumVascular resistanceMass index