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 regionsAdvances 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, 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 macaquesHead-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
Evaluation of trans- and cis-4‑[18F]Fluorogabapentin for Brain PET Imaging
Zhou Y, Normandin M, Belov V, Macdonald-Soccorso M, Moon S, Sun Y, Fakhri G, Guehl N, Brugarolas P. Evaluation of trans- and cis-4‑[18F]Fluorogabapentin for Brain PET Imaging. ACS Chemical Neuroscience 2023, 14: 4208-4215. PMID: 37947793, PMCID: PMC11485007, DOI: 10.1021/acschemneuro.3c00593.Peer-Reviewed Original ResearchConceptsNeuropathic painRodent models of neuropathic painSubunit of voltage-dependent calcium channelsModel of neuropathic painTreatment of neuropathic painMetabolite-corrected arterial input functionVoltage-dependent calcium channelsMultilinear analysis 1Brain uptakePET imagingDose of gabapentinOne-tissue compartment modelRegional time-activity curvesAdult rhesus macaquesPlasma protein bindingTime-activity curvesModerate brain uptakeCalcium channelsInjured nerveArterial input functionGabapentinRodent modelsAnticonvulsant medicationBrain PET imagingRhesus macaquesTau-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 accumulationB1 inhomogeneity‐corrected T1 mapping and quantitative magnetization transfer imaging via simultaneously estimating Bloch‐Siegert shift and magnetization transfer effects
Jang A, Han P, Ma C, Fakhri G, Wang N, Samsonov A, Liu F. B1 inhomogeneity‐corrected T1 mapping and quantitative magnetization transfer imaging via simultaneously estimating Bloch‐Siegert shift and magnetization transfer effects. Magnetic Resonance In Medicine 2023, 90: 1859-1873. PMID: 37427533, PMCID: PMC10528411, DOI: 10.1002/mrm.29778.Peer-Reviewed Original ResearchConceptsBloch-Siegert shiftBloch-SiegertMagnetization transfer effectsMonte Carlo simulationsSpin-lattice relaxationSpin-bath modelMagnetization transferBinary spin-bath modelCarlo simulationsProton fractionOff-resonance irradiationIn vivo brain studiesBloch simulationsPhantom experimentsMagnetizationEstimationTransmitted fieldQuantitative magnetization transferMethod performanceMT effectSignal equationLongitudinal 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 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 metricsPhantomPositronArterial spin labeled perfusion imaging with balanced steady-state free precession readout and radial sampling
Han P, Marin T, Zhuo Y, Ouyang J, El Fakhri G, Ma C. Arterial spin labeled perfusion imaging with balanced steady-state free precession readout and radial sampling. Magnetic Resonance Imaging 2023, 102: 126-132. PMID: 37187264, PMCID: PMC10524790, DOI: 10.1016/j.mri.2023.05.005.Peer-Reviewed Original ResearchConceptsOff-resonance effectsBalanced steady-state free precessionPhase-cycling techniqueTemporal SNRBalanced steady-state free precession acquisitionRadial sampling schemeSpoiled gradient-recalled acquisitionRadial samplingCartesian sampling schemeBalanced steady-state free precession readoutK-space dataSampling schemeSpin labelingSteady-state free precessionK-spaceImage readoutBanding artifactsMotion-related artifactsReadoutFree precessionArterial spin labelingImage reconstructionParallel imagingImaging timePerfusion-weighted imagingMeasurement 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-nineSuper-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 affinityNeuronsBrainJoint spectral quantification of MR spectroscopic imaging using linear tangent space alignment‐based manifold learning
Ma C, Han P, Zhuo Y, Djebra Y, Marin T, Fakhri G. Joint spectral quantification of MR spectroscopic imaging using linear tangent space alignment‐based manifold learning. Magnetic Resonance In Medicine 2022, 89: 1297-1313. PMID: 36404676, PMCID: PMC9892363, DOI: 10.1002/mrm.29526.Peer-Reviewed Original ResearchConceptsSubspace-based methodsManifold learningIntrinsic low-dimensional structureGlobal coordinationLearning-based methodsNumerical simulation dataSpatial smoothness constraintSparsity constraintSpace alignmentSubspace modelSmoothness constraintSuperior performanceRoot mean square errorLinear transformationMechanical simulationsLow-dimensionalSquare errorSubspaceExperimental dataSpectroscopic imagingQuantum mechanical simulationsCoordinate alignmentMR spectroscopic imagingSpectral quantificationSimulated dataNetwork Tau spreading is vulnerable to the expression gradients of APOE and glutamatergic-related genes
Montal V, Diez I, Kim C, Orwig W, Bueichekú E, Gutiérrez-Zúñiga R, Bejanin A, Pegueroles J, Dols-Icardo O, Vannini P, El-Fakhri G, Johnson K, Sperling R, Fortea J, Sepulcre J. Network Tau spreading is vulnerable to the expression gradients of APOE and glutamatergic-related genes. Science Translational Medicine 2022, 14: eabn7273. PMID: 35895837, PMCID: PMC9942690, DOI: 10.1126/scitranslmed.abn7273.Peer-Reviewed Original ResearchConceptsTau spreadingIntracellular accumulation of tau proteinAccumulation of tau proteinAlzheimer's diseasePathological tau accumulationGenetic gradientGenetic dataTau proteinNeurofibrillary tanglesSynaptic genesTau accumulationGenetic traitsGenesDrug development strategiesExpression gradientIntracellular accumulationTauExpressionCognitively normal older participantsHuman brain cortexTanglesProteinApoTraitsAlzheimerDesign, Synthesis, and Characterization of [18F]mG2P026 as a High-Contrast PET Imaging Ligand for Metabotropic Glutamate Receptor 2
Yuan G, Dhaynaut M, Guehl N, Afshar S, Huynh D, Moon S, Iyengar S, Jain M, Pickett J, Kang H, Ondrechen M, Fakhri G, Normandin M, Brownell A. Design, Synthesis, and Characterization of [18F]mG2P026 as a High-Contrast PET Imaging Ligand for Metabotropic Glutamate Receptor 2. Journal Of Medicinal Chemistry 2022, 65: 9939-9954. PMID: 35802702, PMCID: PMC9434700, DOI: 10.1021/acs.jmedchem.2c00593.Peer-Reviewed Original ResearchConceptsPositive allosteric modulatorsMetabotropic glutamate receptor 2Glutamate receptor 2Cu-mediated radiofluorinationPET imaging ligandsReceptor 2High molar activityExcellent radiochemical purityGloSensor assayPositron emission tomography radiotracersClasses of positive allosteric modulatorsNon-human primatesJNJ-46356479Radiochemical yieldBrain heterogeneityAllosteric modulatorsBrain uptakeMGluR2Molar activityLigandBrainBrain permeabilityImaging ligandsBinding kineticsMetabotropicBrain MR Atlas Construction Using Symmetric Deep Neural Inpainting
Xing F, Liu X, Kuo C, Fakhri G, Woo J. Brain MR Atlas Construction Using Symmetric Deep Neural Inpainting. IEEE Journal Of Biomedical And Health Informatics 2022, 26: 3185-3196. PMID: 35139030, PMCID: PMC9250592, DOI: 10.1109/jbhi.2022.3149754.Peer-Reviewed Original ResearchConceptsImage inpainting methodInpainting methodDeep learning-based image inpainting methodsBrain Tumor Segmentation ChallengeMultimodal Brain Tumor Segmentation ChallengeReduce reconstruction errorAtlas constructionStatistical brain atlasInpainted regionsInpainted dataImage registration methodReconstruction errorTumor regionMutual informationSimilarity scoresSegmentation ChallengeSymmetry constraintsImage dataRegistration methodMagnetic resonance imagingTumor locationStatistical atlasDistribution of lesionsCross-correlationPatient population