2024
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
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
Tau-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 accumulationLongitudinal 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 controls
2021
Synthesis 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
Design, Synthesis, and Characterization of Benzimidazole Derivatives as Positron Emission Tomography Imaging Ligands for Metabotropic Glutamate Receptor 2
Yuan G, Qu X, Zheng B, Neelamegam R, Afshar S, Iyengar S, Pan C, Wang J, Kang H, Ondrechen M, Poutiainen P, Fakhri G, Zhang Z, Brownell A. Design, Synthesis, and Characterization of Benzimidazole Derivatives as Positron Emission Tomography Imaging Ligands for Metabotropic Glutamate Receptor 2. Journal Of Medicinal Chemistry 2020, 63: 12060-12072. PMID: 32981322, PMCID: PMC8629109, DOI: 10.1021/acs.jmedchem.0c01394.Peer-Reviewed Original ResearchConceptsPotential positron emission tomographyBenzimidazole derivativesPositron emission tomography imaging ligandsExcellent selectivityImaging ligandsPositive allosteric modulatorsRadiochemical yieldBinding affinityMetabotropic glutamate receptor 2C]methyl iodideMolar activityLigandDerivativesRadiochemical purityGlutamate receptor 2Brain regionsAllosteric modulatorsPositron emission tomographyC]methylationRadiochemicalIodideBrain uptakeMGluR subtypesCompoundsBindingSynthesis 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
Multi-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 imaging
2018
Sequence Alterations of Cortical Genes Linked to Individual Connectivity of the Human Brain
Xin Q, Ortiz-Terán L, Diez I, Perez D, Ginsburg J, Fakhri G, Sepulcre J. Sequence Alterations of Cortical Genes Linked to Individual Connectivity of the Human Brain. Cerebral Cortex 2018, 29: 3828-3835. PMID: 30307489, PMCID: PMC6686751, DOI: 10.1093/cercor/bhy262.Peer-Reviewed Original ResearchConceptsGenetic sequence alterationsGene expression profilesSequence alterationsGenetic expression dataExpression profilesBrain regionsFunctional connectivity variabilityCortical genesCortical regionsAllen Brain AtlasExpression dataGenetic variationGenetic signaturesFunctional connectivity magnetic resonance imagingCortical areasDiscrete cortical regionsGenesGraph theory analysisFunctional profilesNeurobiological underpinningsSequenceDegree of individual variabilityBrain areasBrain individualizationBrain organization