2025
Elevated serum cortisol associated with early‐detected increase of brain amyloid deposition in Alzheimer's disease imaging biomarkers among menopausal women: The Framingham Heart Study
Salardini A, Himali J, Abdullah M, Chaudhari R, Young V, Zilli E, McGrath E, Gonzales M, Thibault E, Salinas J, Aparicio H, Himali D, Ghosh S, Buckley R, Satizabal C, Johnson K, DeCarli C, Fakhri G, Vasan R, Beiser A, Seshadri S. Elevated serum cortisol associated with early‐detected increase of brain amyloid deposition in Alzheimer's disease imaging biomarkers among menopausal women: The Framingham Heart Study. Alzheimer's & Dementia 2025, 21: e70179. PMID: 40271551, PMCID: PMC12019305, DOI: 10.1002/alz.70179.Peer-Reviewed Original ResearchConceptsPost-menopausal womenFramingham Heart Study participantsIncreased risk of ADFramingham Heart StudyRisk of ADNo significant associationHeart StudyEarly risk factorsStudy participantsMenopausal statusMultivariate regression analysisApolipoprotein E4Significant associationAlzheimer's diseaseIncreased riskRisk factorsCognitive impairmentMenopausal womenBrain amyloid depositionRegression analysisWomenAnalyzed dataPositron emission tomographyIncreased amyloid depositionBurdenOptimizing imaging modalities for sarcoma subtypes in radiation therapy: State of the art
Beddok A, Kaur H, Khurana S, Dercle L, El Ayachi R, Jouglar E, Mammar H, Mahe M, Najem E, Rozenblum L, Thariat J, El Fakhri G, Helfre S. Optimizing imaging modalities for sarcoma subtypes in radiation therapy: State of the art. Critical Reviews In Oncology/Hematology 2025, 211: 104708. PMID: 40139581, DOI: 10.1016/j.critrevonc.2025.104708.Peer-Reviewed Original ResearchConceptsMagnetic resonance imagingRadiation therapyComputed tomographyRT planningImaging modalitiesSarcoma managementSarcoma subtypesAssessment of tumor extentIntegration of magnetic resonance imagingAlveolar soft part sarcomaSuperior soft tissue contrastSoft part sarcomaCombination of magnetic resonance imagingContext of radiation therapyIntegration of imaging modalitiesMetabolically active regionsActive regionPositron emission tomographyRT deliveryDose escalationSoft tissue contrastUterine sarcomaTumor extentTumor marginsOsseous involvement[18F]MK-6240 Radioligand Delivery Indices as Surrogates of Cerebral Perfusion: Bias and Correlation Against [15O]Water.
Fu J, Juttukonda M, Garimella A, Salvatore A, Lois C, Ranasinghe A, Efthimiou N, Sari H, Aye W, Guehl N, El Fakhri G, Johnson K, Dickerson B, Izquierdo-Garcia D, Catana C, Price J. [18F]MK-6240 Radioligand Delivery Indices as Surrogates of Cerebral Perfusion: Bias and Correlation Against [15O]Water. Journal Of Nuclear Medicine 2025, 66: 410-417. PMID: 39947916, PMCID: PMC11876731, DOI: 10.2967/jnumed.124.268701.Peer-Reviewed Original ResearchPreliminary Evidence for Perturbation‐Based tACS‐EEG Biomarkers of Gamma Activity in Alzheimer's Disease
Palmisano A, Pezanko L, Cappon D, Tatti E, Macone J, Koch G, Smeralda C, Romanella S, Ruffini G, Rivolta D, Press D, Pascual‐Leone A, El‐Fakhri G, Santarnecchi E. Preliminary Evidence for Perturbation‐Based tACS‐EEG Biomarkers of Gamma Activity in Alzheimer's Disease. International Journal Of Geriatric Psychiatry 2025, 40: e70025. PMID: 39799469, DOI: 10.1002/gps.70025.Peer-Reviewed Original ResearchConceptsPeripheral neuroinflammationIdentification of novel biomarkersResponse to TACPatient's clinical phenotypeSpectral powerGABAergic dysfunctionNo significant correlationPrognostic valueInhibitory circuitryClinical severityClinical phenotypeAnimal modelsCognitive statusNeuroinflammatory markersAlzheimer's diseaseHuman patientsNeuroinflammatory biomarkersNovel biomarkersPatientsDisease severityTherapeutic targetGamma activityBiomarkersMild to moderate dementiaSignificant correlation
2024
Investigating muscle coordination patterns with Granger causality analysis in protrusive motion from tagged and diffusion MRI
Park H, Xing F, Stone M, Kang H, Liu X, Zhuo J, Fels S, Reese T, Wedeen V, Fakhri G, Prince J, Woo J. Investigating muscle coordination patterns with Granger causality analysis in protrusive motion from tagged and diffusion MRI. JASA Express Letters 2024, 4: 095201. PMID: 39240196, PMCID: PMC11384280, DOI: 10.1121/10.0028500.Peer-Reviewed Original ResearchAssociations 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 regionsAssociations 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, PMCID: PMC12050109, 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 groupsAdvances and Insights in Positron Emission Tomography Tracers for Metabotropic Glutamate Receptor 4 Imaging
Wang J, Li Y, Fakhri G. Advances and Insights in Positron Emission Tomography Tracers for Metabotropic Glutamate Receptor 4 Imaging. Journal Of Medicinal Chemistry 2024, 67: 10517-10529. PMID: 38924702, PMCID: PMC11290609, DOI: 10.1021/acs.jmedchem.3c02431.Peer-Reviewed Original ResearchConceptsPositive allosteric modulatorsPositron emission tomographyPositron emission tomography radioligandsAllosteric modulatorsMGluR4 positive allosteric modulatorsMetabotropic glutamate receptor subtype 4PET ligandNeurological disordersPositron emission tomography tracersEmission tomographySubtype 4Molecular imaging modalitiesEffective treatmentMetabotropicDisordersParent drugImaging modalitiesPET tracersMGluR4Therapeutic targetPositron emitting radioisotopesSelection of lead compoundsLiving subjectsPositronQuantitative accuracyAccelerated 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, PMCID: PMC12120684, 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 mappingHead-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 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 atrophyCognitionPET image denoising based on denoising diffusion probabilistic model
Gong K, Johnson K, El Fakhri G, Li Q, Pan T. PET image denoising based on denoising diffusion probabilistic model. European Journal Of Nuclear Medicine And Molecular Imaging 2023, 51: 358-368. PMID: 37787849, PMCID: PMC10958486, DOI: 10.1007/s00259-023-06417-8.Peer-Reviewed Original ResearchConceptsDenoising diffusion probabilistic modelPET image denoisingDiffusion probabilistic modelImage denoisingDenoising methodNonlocal meansNetwork inputGenerative adversarial networkData consistency constraintsProbabilistic modelLearning-based modelsAdversarial networkData distributionDenoisingRefinement stepsIterative refinementFlexible frameworkImage qualityPhysical degrading factorsUNetNetworkDatasetImagesInputNoise levelTau-PET abnormality as a biomarker for Alzheimer’s disease staging and early detection: a topological perspective
Ding J, Shen C, Wang Z, Yang Y, Fakhri G, Lu J, Liang D, Zheng H, Zhou Y, Sun T, Study F. Tau-PET abnormality as a biomarker for Alzheimer’s disease staging and early detection: a topological perspective. Cerebral Cortex 2023, 33: 10649-10659. PMID: 37653600, DOI: 10.1093/cercor/bhad312.Peer-Reviewed Original ResearchConceptsStandardized uptake value ratioMild cognitive impairmentBrain regionsCognitive impairmentPositron emission tomographyMedial temporal lobeAlzheimer's diseaseVisual-related regionsTopological perspectiveTau positron emission tomographyMode networkTau PET imagingTopological featuresIndependent data cohortsTemporal lobeConnection strengthExtract topological featuresTau networksAbnormal networkProgression of Alzheimer's diseaseAbnormal protein accumulationAssociation 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 compositeLongitudinal Imaging in a Patient With Opioid-associated Amnestic Syndrome
Barash J, Schmahmann J, Xie Z, Lev M, Fakhri G. Longitudinal Imaging in a Patient With Opioid-associated Amnestic Syndrome. Cognitive And Behavioral Neurology 2023, 36: 194-197. PMID: 37389894, PMCID: PMC10527331, DOI: 10.1097/wnn.0000000000000347.Peer-Reviewed Original ResearchConceptsOpioid-associated amnestic syndromeFluid-attenuated inversion recoveryPositron emission tomographyAmnestic syndromeHistory of attention-deficit hyperactivity disorderAttention-deficit hyperactivity disorderBrain regions of individualsSubstance use disordersOpioid misuseMild memory lossN-acetyl aspartate/creatineUrine toxicology screenFollow-up imagingHistory of opioid misuseRegions of individualsTau depositionTau positron emission tomographyHyperactivity disorderIntravenous heroinRight hippocampusAnterograde amnesiaRestricted diffusionBrain regionsHippocampal abnormalitiesLongitudinal imagingTau 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 controlsAttentive continuous generative self-training for unsupervised domain adaptive medical image translation
Liu X, Prince J, Xing F, Zhuo J, Reese T, Stone M, El Fakhri G, Woo J. Attentive continuous generative self-training for unsupervised domain adaptive medical image translation. Medical Image Analysis 2023, 88: 102851. PMID: 37329854, PMCID: PMC10527936, DOI: 10.1016/j.media.2023.102851.Peer-Reviewed Original ResearchConceptsUnsupervised domain adaptationImage translationProblem of domain shiftSelf-trainingImage modality translationLabeled source domainTarget domain dataSelf-attention schemeAlternating optimization schemeHeterogeneous target domainContinuous value predictionPseudo-labelsDomain adaptationUDA methodsDomain shiftSoftmax probabilitiesSource domainTarget domainVariational BayesBackground regionsTranslation tasksTraining processDomain dataGeneration taskOptimization schemeImpact 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
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