2024
Associations of Physical Activity Engagement with Cerebral Amyloid-β and Tau from Midlife
Gonzales M, Kojis D, Spartano N, Thibault E, DeCarli C, Fakhri G, Johnson K, Beiser A, Seshadri S. Associations of Physical Activity Engagement with Cerebral Amyloid-β and Tau from Midlife. Journal Of Alzheimer's Disease 2024, 100: 935-943. PMID: 39031362, DOI: 10.3233/jad-240322.Peer-Reviewed Original ResearchConceptsPhysical activity indexPhysical activity engagementAssociated with lower dementia riskPhysical activity index scoreAssociation of physical activityActive engagementPhysical activity levelsFramingham Heart StudyCross-sectional associationsCommunity-based cohortCardiovascular risk factorsDementia riskPhysical activityLifestyle interventionHeart StudyLinear regression modelsStratified analysisTau-PET retentionSelf-reportSex disparitiesActivity levelsLate lifeTau positron emission tomographyRisk factorsAge groupsAssociations 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 regionsAccelerated 3D metabolite T1 mapping of the brain using variable‐flip‐angle SPICE
Zhao Y, Li Y, Guo R, Jin W, Sutton B, Ma C, Fakhri G, Li Y, Luo J, Liang Z. Accelerated 3D metabolite T1 mapping of the brain using variable‐flip‐angle SPICE. Magnetic Resonance In Medicine 2024, 92: 1310-1322. PMID: 38923032, DOI: 10.1002/mrm.30200.Peer-Reviewed Original ResearchConceptsLow-rank tensor modelGeneralized series modelMetabolite TExperimental resultsBrain metabolitesClinically acceptable scan timeEfficient encodingPhantom experimental resultsAcceptable scan timeNoisy dataSparse samplingImaging problemsData processingHealthy subject dataVariable flip angleFlip angleTensor modelSaturation effectsQuantitative metabolic imagingMRSI techniquePhantomScan timeData acquisitionMetabolic imagingT1 mappingPET 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
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 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 controls
2022
Human 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 clearanceSynthesis 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
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 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 controlsDisordersMGluR5Synthesis and Characterization of [18F]JNJ-46356479 as the First 18F-Labeled PET Imaging Ligand for Metabotropic Glutamate Receptor 2
Yuan G, Guehl N, Zheng B, Qu X, Moon S, Dhaynaut M, Shoup T, Afshar S, Kang H, Zhang Z, El Fakhri G, Normandin M, Brownell A. Synthesis and Characterization of [18F]JNJ-46356479 as the First 18F-Labeled PET Imaging Ligand for Metabotropic Glutamate Receptor 2. Molecular Imaging And Biology 2021, 23: 527-536. PMID: 33559035, PMCID: PMC8277681, DOI: 10.1007/s11307-021-01586-0.Peer-Reviewed Original ResearchConceptsNon-human primatesIn vivo PET imaging studiesNucleus accumbensGlutamate receptor 2PET imaging ligandsImaging ligandsParietal cortexBrain regionsPET imaging studiesPET radioligandIn vivo PET imaging experimentsVolume of distributionMGluR2C57BL/6 J micePET imaging experimentsPET studiesBrainSprague-Dawley ratsAlzheimer's diseaseBrain permeabilityPre-treatment studyImaging studiesDisordersRat studiesReversible kinetics
2020
Evaluation of the potassium channel tracer [18F]3F4AP in rhesus macaques
Guehl N, Ramos-Torres K, Linnman C, Moon S, Dhaynaut M, Wilks M, Han P, Ma C, Neelamegam R, Zhou Y, Popko B, Correia J, Reich D, Fakhri G, Herscovitch P, Normandin M, Brugarolas P. Evaluation of the potassium channel tracer [18F]3F4AP in rhesus macaques. Cerebrovascular And Brain Metabolism Reviews 2020, 41: 1721-1733. PMID: 33090071, PMCID: PMC8221756, DOI: 10.1177/0271678x20963404.Peer-Reviewed Original ResearchConceptsFocal brain injuryMyelin repair therapyContributions of demyelinationDrivers of disabilityImaging demyelinationBrain injuryMeasurements of molecular changesTool's sensitivity to changesLower myelin contentDemyelinating lesionsNeuronal conductionImpaired conductionDemyelinationBrain penetrationGold standardRhesus macaquesInjured areaMultiple sclerosisMolecular changesMyelin sheathNeurological diseasesHigh metabolic stabilityMRI methodsMRIInjurySynthesis and Characterization of Fluorine-18-Labeled N‑(4-Chloro-3-((fluoromethyl‑d 2)thio)phenyl)picolinamide for Imaging of mGluR4 in Brain
Wang J, Qu X, Shoup T, Yuan G, Afshar S, Pan C, Zhu A, Choi J, Kang H, Poutiainen P, Fakhri G, Zhang Z, Brownell A. Synthesis and Characterization of Fluorine-18-Labeled N‑(4-Chloro-3-((fluoromethyl‑d 2)thio)phenyl)picolinamide for Imaging of mGluR4 in Brain. Journal Of Medicinal Chemistry 2020, 63: 3381-3389. PMID: 32081008, PMCID: PMC7261135, DOI: 10.1021/acs.jmedchem.0c00201.Peer-Reviewed Original ResearchConceptsDrug-like propertiesMethylthio analoguePotential ligandsMetabolic stabilityPositron emission tomographyRadiochemical yieldMolar activityDose-dependent blocking effectPositron emission tomography imaging studiesMethylthioPAM activityBrain regionsMale Sprague Dawley ratsLigandEx vivo biodistribution studiesRadiosynthesisSprague Dawley ratsBrainMGluR4SynthesisAnaloguesEmission tomographyImaging studies
2019
Renal clearable nanochelators for iron overload therapy
Kang H, Han M, Xue J, Baek Y, Chang J, Hu S, Nam H, Jo M, El Fakhri G, Hutchens M, Choi H, Kim J. Renal clearable nanochelators for iron overload therapy. Nature Communications 2019, 10: 5134. PMID: 31723130, PMCID: PMC6853917, DOI: 10.1038/s41467-019-13143-z.Peer-Reviewed Original ResearchConceptsIron overloadIntravenous injectionDaily sc injectionsUrinary iron excretionSecondary iron overloadIron-overloaded miceAdverse side effectsIron chelatorsIron overload disordersGastrointestinal bleedingSC injectionIron excretionLiver fibrosisSide effectsKidney damageKidney failureIron overload therapyIron levelsToxic ironPharmacokinetic propertiesDeferoxamineNanochelatorKidneyExcretionInjectionAttenuation 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 imagingAssessment 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 clearance