2024
Diffusion-based Bayesian posterior distribution prediction of kinetic parameters in dynamic PET
Djebra Y, Liu X, Marin T, Tiss A, Dhaynaut M, Guehl N, Johnson K, Fakhri G, Ma C, Ouyang J. Diffusion-based Bayesian posterior distribution prediction of kinetic parameters in dynamic PET. 2024, 00: 1-1. DOI: 10.1109/nss/mic/rtsd57108.2024.10657955.Peer-Reviewed Original ResearchConditional variational autoencoderEfficient deep learning-based approachMarkov chain Monte CarloDenoising diffusion probabilistic modelDeep learning-based approachDiffusion probabilistic modelLearning-based approachApproximate posterior distributionPosterior distributionVariational autoencoderHeavy computationTau protein aggregationBayesian inferenceProbabilistic modelData-drivenStudy molecular processesBayesian posterior distributionProtein aggregationMetropolis-Hastings Markov chain Monte CarloMolecular processesAlzheimer's diseaseNeurodegenerative diseasesKinetic parametersEstimate posterior distributionsAutoencoderPET mapping of receptor occupancy using joint direct parametric reconstruction
Marin T, Belov V, Chemli Y, Ouyang J, Najmaoui Y, Fakhri G, Duvvuri S, Iredale P, Guehl N, Normandin M, Petibon Y. PET mapping of receptor occupancy using joint direct parametric reconstruction. IEEE Transactions On Biomedical Engineering 2024, PP: 1-15. PMID: 39446540, DOI: 10.1109/tbme.2024.3486191.Peer-Reviewed Original ResearchCentral nervous systemReceptor occupancyLow-binding regionsPET scansSimulation resultsPreclinical in vivo experimentsDynamic PET scansPairs of baselineEstimation of receptor occupancyEstimation frameworkPET neuroimagingReconstruction frameworkModulating drugsTime activity curvesParametric reconstructionDevelopment of drugsEffects of List-Mode Based Intra-Frame Motion Correction in Dynamic Brain PET Imaging
Tiss A, Chemli Y, Guehl N, Marin T, Johnson K, Fakhri G, Ouyang J. Effects of List-Mode Based Intra-Frame Motion Correction in Dynamic Brain PET Imaging. IEEE Transactions On Radiation And Plasma Medical Sciences 2024, PP: 1-1. DOI: 10.1109/trpms.2024.3432322.Peer-Reviewed Original ResearchDiffusion Model-Based Posterior Distribution Prediction for Kinetic Parameter Estimation in Dynamic PET
Djebra Y, Liu X, Marin T, Tiss A, Dhaynaut M, Guehl N, Johnson K, Fakhri G, Ma C, Ouyang J. Diffusion Model-Based Posterior Distribution Prediction for Kinetic Parameter Estimation in Dynamic PET. 2024, 00: 1-5. DOI: 10.1109/isbi56570.2024.10635805.Peer-Reviewed Original ResearchPosterior distributions of kinetic parametersDenoising diffusion probabilistic modelHyperphosphorylated tauP-tauDiffusion probabilistic modelAlzheimer's diseaseNeurodegenerative diseasesKinetic parametersPosterior distributionInference efficiencyComputational needsEstimate kinetic parametersProbabilistic modelComputation timeRadiosynthesis automation, non-human primate biodistribution and dosimetry of K+ channel tracer [11C]3MeO4AP
Zhou Y, Wilks M, Dhaynaut M, Guehl N, Vesper D, Moon S, Rice P, El Fakhri G, Normandin M, Brugarolas P. Radiosynthesis automation, non-human primate biodistribution and dosimetry of K+ channel tracer [11C]3MeO4AP. EJNMMI Research 2024, 14: 43. PMID: 38683467, PMCID: PMC11058135, DOI: 10.1186/s13550-024-01092-8.Peer-Reviewed Original ResearchRadiation dosimetryAverage effective doseWhole-body biodistributionTotal scan timeNon-decayEffective doseNon-human primatesSymptomatic treatment of multiple sclerosisIn vivo binding affinityBed positionTreatment of multiple sclerosisHigh-resolution CTDynamic acquisition protocolDosimetryPET dataAdult rhesus macaquesScan timeImaging demyelinationOLINDA softwareRadiationAcquisition protocolsPreclinical studiesNo significant changesHigh dosesPET imagingPET 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 macaquesAcute Stress Increases Striatal Connectivity With Cortical Regions Enriched for μ and κ Opioid Receptors
Zhukovsky P, Ironside M, Duda J, Moser A, Null K, Dhaynaut M, Normandin M, Guehl N, El Fakhri G, Alexander M, Holsen L, Misra M, Narendran R, Hoye J, Morris E, Esfand S, Goldstein J, Pizzagalli D. Acute Stress Increases Striatal Connectivity With Cortical Regions Enriched for μ and κ Opioid Receptors. Biological Psychiatry 2024, 96: 717-726. PMID: 38395372, PMCID: PMC11339240, DOI: 10.1016/j.biopsych.2024.02.005.Peer-Reviewed Original ResearchMajor depressive disorderFunctional connectivityEffects of stressAcute stressK-opioid receptorsStriatal connectivityEtiology of major depressive disorderCortical regionsMontreal Imaging Stress TaskEffects of acute stressGlobal FCIncreased striatal connectivityVentral attention/salience networkAllen Human Brain AtlasDefault mode networkCortical connectivityHuman Brain AtlasMDD studiesDepressive disorderFrontoparietal networkNeurobiological effectsMode networkStress taskDimensional approachMDD risk
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 macaquesAssociation 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 atrophyCognitionInjectable ice slurry for reducing pericardial adipose tissue
Shuhaiber J, Tuchayi S, Bijari F, Guehl N, Wang Y, Farinelli W, Arkun K, Fakhri G, Anderson R, Garibyan L. Injectable ice slurry for reducing pericardial adipose tissue. Lasers In Surgery And Medicine 2023, 55: 674-679. PMID: 37464943, DOI: 10.1002/lsm.23709.Peer-Reviewed Original ResearchConceptsPericardial adipose tissuePericardial adipose tissue volumeChest computed tomographyPAT volumeBaseline chest computed tomographyAnimal modelsSubcutaneous adipose tissue volumesCardiovascular diseaseHigh risk of cardiovascular diseaseAdipose tissueLow patient complianceRisk of cardiovascular diseaseWeight lossPreclinical large animal modelAdipose tissue volumeLarge animal modelBariatric surgeryComputed tomographyPatient complianceHigh riskNovel treatmentTreated groupCT imagesTissue volumeCryolipolysisTau 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 controlsMeasurement 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-nineCorrection to: Evaluation 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, Fakhri G, Normandin M. Correction to: 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 2023, 50: 1273-1273. PMID: 36604327, DOI: 10.1007/s00259-022-06102-2.Peer-Reviewed Original Research
2022
Kinetic evaluation and assessment of longitudinal changes in reference region and extracerebral [18F]MK-6240 PET uptake
Fu J, Lois C, Sanchez J, Becker J, Rubinstein Z, Thibault E, Salvatore A, Sari H, Farrell M, Guehl N, Normandin M, Fakhri G, Johnson K, Price J. Kinetic evaluation and assessment of longitudinal changes in reference region and extracerebral [18F]MK-6240 PET uptake. Cerebrovascular And Brain Metabolism Reviews 2022, 43: 581-594. PMID: 36420769, PMCID: PMC10063833, DOI: 10.1177/0271678x221142139.Peer-Reviewed Original ResearchConceptsPartial volume correctionLongitudinal changesReference regionStandardized uptake valueFollow-up scansExtracerebral signalsAssessment of longitudinal changesCross-sectional effect sizesUptake valuePET uptakeDistribution volumeRegional uptakeArterial samplesExtracerebral contaminationOne-yearCognitively-normalEffect sizePonsGroup differentiationVolume correctionSubject levelSubjectsRadiochemical 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 affinityNeuronsBrainHuman 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 modelsPET imaging studies to investigate functional expression of mGluR2 using [11C]mG2P001
Yuan G, Dhaynaut M, Guehl N, Neelamegam R, Moon S, Qu X, Poutiainen P, Afshar S, Fakhri G, Normandin M, Brownell A. PET imaging studies to investigate functional expression of mGluR2 using [11C]mG2P001. Cerebrovascular And Brain Metabolism Reviews 2022, 43: 296-308. PMID: 36172629, PMCID: PMC9903221, DOI: 10.1177/0271678x221130387.Peer-Reviewed Original ResearchConceptsPositive allosteric modulatorsPositron emission tomographyNon-human primatesMGluR2 positive allosteric modulatorPositron emission tomography imagingPositive allosteric modulator of mGluR2Metabotropic glutamate receptor 2Positron emission tomography imaging studiesExpression of mGluR2Glutamate receptor 2MGluR2 functionPsychiatric disordersMGluR2 expressionTissue glutamate concentrationMGluR2Expressing mGluR2Allosteric modulatorsRat brainTransfected CHO cellsReceptor 2Glutamate concentrationEmission tomographyImaging studiesPharmacological effectsImaging ligandsDesign, 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 kineticsMetabotropicPET imaging of mitochondrial function in acute doxorubicin-induced cardiotoxicity: a proof-of-principle study
Detmer F, Alpert N, Moon S, Dhaynaut M, Guerrero J, Guehl N, Xing F, Brugarolas P, Shoup T, Normandin M, Pelletier-Galarneau M, El Fakhri G, Petibon Y. PET imaging of mitochondrial function in acute doxorubicin-induced cardiotoxicity: a proof-of-principle study. Scientific Reports 2022, 12: 6122. PMID: 35414642, PMCID: PMC9005533, DOI: 10.1038/s41598-022-10004-6.Peer-Reviewed Original ResearchConceptsLeft anterior descending coronary arteryDoxorubicin-induced cardiotoxicityCardiac membrane potentialDoxorubicin infusionMembrane potentialAnimal modelsAcute doxorubicin-induced cardiotoxicityLeft anterior descending coronary artery territoryAcute cardiotoxic effectsAnterior descending coronary arteryControl saline infusionDescending coronary arteryDoxorubicin doseSaline infusionTest infusionCardiotoxic effectsMitochondrial membrane potentialInfusion catheterCoronary arteryInfusionMitochondrial functionDoxorubicinMyocardial areaPET imagingIntracoronary catheterImpact 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