Featured Publications
Imaging synaptic density in the living human brain
Finnema SJ, Nabulsi NB, Eid T, Detyniecki K, Lin SF, Chen MK, Dhaher R, Matuskey D, Baum E, Holden D, Spencer DD, Mercier J, Hannestad J, Huang Y, Carson RE. Imaging synaptic density in the living human brain. Science Translational Medicine 2016, 8: 348ra96. PMID: 27440727, DOI: 10.1126/scitranslmed.aaf6667.Peer-Reviewed Original ResearchConceptsSynaptic densityPositron emission tomographyPET imagingSynaptic vesicle glycoprotein 2ATemporal lobe epilepsyNumerous brain disordersCentral nervous systemNumber of synapsesJ PET imagingHuman brainHuman PET studiesPredominant neuronsSurgical resectionSynaptic lossLobe epilepsyPsychiatric disordersNervous systemBrain disordersPresynaptic boutonsAlzheimer's diseaseBrain tissueEmission tomographyNeuron contactsTherapeutic monitoringPET studiesFirst-in-Human Evaluation of 18F-SynVesT-1, a Radioligand for PET Imaging of Synaptic Vesicle Glycoprotein 2A
Naganawa M, Li S, Nabulsi N, Henry S, Zheng MQ, Pracitto R, Cai Z, Gao H, Kapinos M, Labaree D, Matuskey D, Huang Y, Carson RE. First-in-Human Evaluation of 18F-SynVesT-1, a Radioligand for PET Imaging of Synaptic Vesicle Glycoprotein 2A. Journal Of Nuclear Medicine 2020, 62: 561-567. PMID: 32859701, PMCID: PMC8049363, DOI: 10.2967/jnumed.120.249144.Peer-Reviewed Original ResearchConceptsC-UCBSynaptic densityRegional time-activity curvesTime-activity curvesDistribution volumeMetabolite-corrected arterial input functionPET imagingMultilinear analysis 1Synaptic vesicle glycoprotein 2AAntiepileptic drug levetiracetamTotal distribution volumeNondisplaceable distribution volumeCentrum semiovaleBlocking doseHealthy volunteersHuman studiesDrug levetiracetamLassen plotNeuropsychiatric disordersPET radioligandArterial input functionNonhuman primatesLevetiracetamReference regionRadioligandAssessing Synaptic Density in Alzheimer Disease With Synaptic Vesicle Glycoprotein 2A Positron Emission Tomographic Imaging
Chen MK, Mecca AP, Naganawa M, Finnema SJ, Toyonaga T, Lin SF, Najafzadeh S, Ropchan J, Lu Y, McDonald JW, Michalak HR, Nabulsi NB, Arnsten AFT, Huang Y, Carson RE, van Dyck CH. Assessing Synaptic Density in Alzheimer Disease With Synaptic Vesicle Glycoprotein 2A Positron Emission Tomographic Imaging. JAMA Neurology 2018, 75: 1215-1224. PMID: 30014145, PMCID: PMC6233853, DOI: 10.1001/jamaneurol.2018.1836.Peer-Reviewed Original ResearchConceptsPositron emission tomographic imagingSynaptic vesicle glycoprotein 2ASynaptic densityAlzheimer's diseaseEmission tomographic imagingHigh-resolution PET scanningPET scanningCognitive impairmentDisease-modifying therapiesDisease-modifying treatmentsNormal participantsCross-sectional studyPittsburgh compound BMajor structural correlateAmnestic mild cognitive impairmentMagnetic resonance imagingMild cognitive impairmentJ PET imagingRestoration of synapsesSpecific bindingNeurologic evaluationSynaptic lossDisease stagePostmortem studiesOutcome measuresLower synaptic density is associated with depression severity and network alterations
Holmes SE, Scheinost D, Finnema SJ, Naganawa M, Davis MT, DellaGioia N, Nabulsi N, Matuskey D, Angarita GA, Pietrzak RH, Duman RS, Sanacora G, Krystal JH, Carson RE, Esterlis I. Lower synaptic density is associated with depression severity and network alterations. Nature Communications 2019, 10: 1529. PMID: 30948709, PMCID: PMC6449365, DOI: 10.1038/s41467-019-09562-7.Peer-Reviewed Original ResearchConceptsMajor depressive disorderPost-traumatic stress disorderLower synaptic densitySynaptic densityPositron emission tomographyFunctional connectivityNetwork alterationsSynaptic vesicle glycoprotein 2ASymptoms of depressionSynaptic lossDepressive disorderHealthy controlsNerve terminalsDepressive symptomsDepression severityUnmedicated individualsSynaptic connectionsEmission tomographyStress disorderVivo evidenceSymptomsDepressionSeverityDisordersAlterations
2024
11C-UCB-J PET imaging is consistent with lower synaptic density in autistic adults
Matuskey D, Yang Y, Naganawa M, Koohsari S, Toyonaga T, Gravel P, Pittman B, Torres K, Pisani L, Finn C, Cramer-Benjamin S, Herman N, Rosenthal L, Franke C, Walicki B, Esterlis I, Skosnik P, Radhakrishnan R, Wolf J, Nabulsi N, Ropchan J, Huang Y, Carson R, Naples A, McPartland J. 11C-UCB-J PET imaging is consistent with lower synaptic density in autistic adults. Molecular Psychiatry 2024, 1-7. PMID: 39367053, DOI: 10.1038/s41380-024-02776-2.Peer-Reviewed Original ResearchPositron emission tomographySynaptic densityAutistic adultsBrain regionsAutistic featuresClinical phenotype of autismNon-autistic participantsPhenotype of autismNon-autistic individualsRelationship to clinical characteristicsSynaptic vesicle glycoprotein 2AAssociated with clinical measuresPost-mortem studiesPositron emission tomography scanPrefrontal cortexClinician ratingsAutism groupNeural basisBrain areasNeural processesBetween-group differencesVolumetric differencesBinding potentialDensity of synapsesAutismValidation of a Simplified Tissue-to-Reference Ratio Measurement Using SUVR to Assess Synaptic Density Alterations in Alzheimer Disease with [11C]UCB-J PET
Young J, O’Dell R, Naganawa M, Toyonaga T, Chen M, Nabulsi N, Huang Y, Cooper E, Miller A, Lam J, Bates K, Ruan A, Nelsen K, Salardini E, Carson R, van Dyck C, Mecca A. Validation of a Simplified Tissue-to-Reference Ratio Measurement Using SUVR to Assess Synaptic Density Alterations in Alzheimer Disease with [11C]UCB-J PET. Journal Of Nuclear Medicine 2024, 65: jnumed.124.267419. PMID: 39299782, PMCID: PMC11533916, DOI: 10.2967/jnumed.124.267419.Peer-Reviewed Original ResearchDistribution volume ratioSUV ratioSynaptic densityEffect sizeAlzheimer's diseaseLongitudinal study of Alzheimer's diseaseMethods:</b> ParticipantsLongitudinal studyMeasure synaptic densityAD participantsStudy of Alzheimer's diseaseNormal cognitionReference regionOlder adultsMulticenterDensity alterationsChallenges and rewards of in vivo synaptic density imaging, and its application to the study of depression
Asch R, Abdallah C, Carson R, Esterlis I. Challenges and rewards of in vivo synaptic density imaging, and its application to the study of depression. Neuropsychopharmacology 2024, 50: 153-163. PMID: 39039139, PMCID: PMC11525584, DOI: 10.1038/s41386-024-01913-3.Peer-Reviewed Original ResearchStudies of depressionAnimal models of chronic stressPositron emission tomographyModel of chronic stressSV2A imagingSynaptic densitySignificant depressive symptomsDevelopment of novel radiotracersDepressive symptomsNeuropsychiatric disordersSymptom severityChronic stressDrug challengeSynaptic vesicle glycoprotein 2 ANeural markersAnimal modelsSynaptic alterationsSynaptogenesis in vivoPreliminary findingsIn vivo quantificationCentral nervous systemDepressionEmission tomographySV2ASV2A positron emission tomographySynaptic density patterns in early Alzheimer’s disease assessed by independent component analysis
Fang X, Raval N, O’Dell R, Naganawa M, Mecca A, Chen M, van Dyck C, Carson R. Synaptic density patterns in early Alzheimer’s disease assessed by independent component analysis. Brain Communications 2024, 6: fcae107. PMID: 38601916, PMCID: PMC11004947, DOI: 10.1093/braincomms/fcae107.Peer-Reviewed Original ResearchMedial temporal brain regionsAlzheimer's diseaseTemporal brain regionsCognitive deficitsBrain regionsCognitive impairmentPostmortem studiesBinds to SV2ASynaptic densityReduction of synaptic densityIndependent component analysisSynaptic lossAlzheimerDeficitsImpairmentBrainNeocortexComponent analysisPrimary pathologySV2ASynaptic loss and its association with symptom severity in Parkinson’s disease
Holmes S, Honhar P, Tinaz S, Naganawa M, Hilmer A, Gallezot J, Dias M, Yang Y, Toyonaga T, Esterlis I, Mecca A, Van Dyck C, Henry S, Ropchan J, Nabulsi N, Louis E, Comley R, Finnema S, Carson R, Matuskey D. Synaptic loss and its association with symptom severity in Parkinson’s disease. Npj Parkinson's Disease 2024, 10: 42. PMID: 38402233, PMCID: PMC10894197, DOI: 10.1038/s41531-024-00655-9.Peer-Reviewed Original ResearchSynaptic density lossPositron emission tomographyBinds to synaptic vesicle glycoprotein 2AAssociated with symptom severityParkinson's diseaseHigh-resolution positron emission tomographySynaptic vesicle glycoprotein 2ADuration of illnessPositron emission tomography scanBrain perfusionIllness durationSymptom severitySeverity of symptomsHC groupSubstantia nigraSynaptic densityLiving brainPD individualsClinical insightsDensity lossPD patientsEmission tomographyBrainSynaptic lossSynapse lossA pilot study to evaluate the effect of CT1812 treatment on synaptic density and other biomarkers in Alzheimer’s disease
van Dyck C, Mecca A, O’Dell R, Bartlett H, Diepenbrock N, Huang Y, Hamby M, Grundman M, Catalano S, Caggiano A, Carson R. A pilot study to evaluate the effect of CT1812 treatment on synaptic density and other biomarkers in Alzheimer’s disease. Alzheimer's Research & Therapy 2024, 16: 20. PMID: 38273408, PMCID: PMC10809445, DOI: 10.1186/s13195-024-01382-2.Peer-Reviewed Original ResearchConceptsMild to moderate dementiaPositron emission tomographyAlzheimer's diseaseVolumetric MRIModerate dementiaClinical rating scalesSynaptic vesicle glycoprotein 2ACerebrospinal fluidMouse model of ADPharmacodynamic effectsPlacebo-controlled phase 1 clinical trialBiomarkers of AD pathologyClinical trialsCognitive measuresNominally significant differencesPhase 1 clinical trialModel of ADHippocampal cortexPhase 1/2 studyRating ScaleParallel-group trialSynaptic densityTrial registrationThe clinical trialPlacebo-controlledSigma-2 receptor ligands
2023
The regional pattern of age-related synaptic loss in the human brain differs from gray matter volume loss: in vivo PET measurement with [11C]UCB-J
Toyonaga T, Khattar N, Wu Y, Lu Y, Naganawa M, Gallezot J, Matuskey D, Mecca A, Pittman B, Dias M, Nabulsi N, Finnema S, Chen M, Arnsten A, Radhakrishnan R, Skosnik P, D’Souza D, Esterlis I, Huang Y, van Dyck C, Carson R. The regional pattern of age-related synaptic loss in the human brain differs from gray matter volume loss: in vivo PET measurement with [11C]UCB-J. European Journal Of Nuclear Medicine And Molecular Imaging 2023, 51: 1012-1022. PMID: 37955791, DOI: 10.1007/s00259-023-06487-8.Peer-Reviewed Original ResearchSynaptic densityAge-related decreaseMagnetic resonance imagingBlood flowAge-related synaptic lossGray matter volume lossSynaptic density lossPositron emission tomography (PET) ligandSynaptic vesicle glycoprotein 2AVivo PET measurementsMedial occipital cortexGray matter volumeAge-related neurodegenerationGray matter regionsCognitive normal subjectsAge-related changesSynaptic lossNerve terminalsWide age rangeOccipital cortexTomography ligandNormal subjectsGM volumeAge-related functional lossesMatter volumeSynaptic PET Imaging in Neurodegeneration
Chen M, Matuskey D, Finnema S, Carson R. Synaptic PET Imaging in Neurodegeneration. 2023, 157-167. DOI: 10.1007/978-3-031-35098-6_10.ChaptersAlzheimer's diseaseSynaptic densityProgressive supranuclear palsySynaptic vesicle glycoprotein 2ALarge patient cohortPositron emission tomography (PET) biomarkersInitial PET studiesMultiple neurodegenerative diseasesSupranuclear palsyCorticobasal degenerationLewy bodiesPatient cohortSynapse densityTomography biomarkersClinical valueParkinson's diseaseNeurological diseasesBrain regionsFrontotemporal dementiaPET studiesDiseaseNeurodegenerative diseasesHuntington's diseaseMultiple centersSynaptic vesicle membraneAssessment of Gray Matter Microstructure and Synaptic Density in Alzheimer's Disease: A Multimodal Imaging Study With DTI and SV2A PET
Silva-Rudberg J, Salardini E, O'Dell R, Chen M, Ra J, Georgelos J, Morehouse M, Melino K, Varma P, Toyonaga T, Nabulsi N, Huang Y, Carson R, van Dyck C, Mecca A. Assessment of Gray Matter Microstructure and Synaptic Density in Alzheimer's Disease: A Multimodal Imaging Study With DTI and SV2A PET. American Journal Of Geriatric Psychiatry 2023, 32: 17-28. PMID: 37673749, PMCID: PMC10840732, DOI: 10.1016/j.jagp.2023.08.002.Peer-Reviewed Original ResearchSynaptic densityAlzheimer's diseaseMean diffusivitySynaptic lossGray matter microstructureGray matter mean diffusivityDisease pathologyHippocampal synaptic densityMajor pathological correlateSetting of ADAD-related neuropathologySynaptic vesicle glycoprotein 2AHippocampal mean diffusivityAlzheimer's disease pathologyAmyloid-positive participantsMatter mean diffusivityPositron emission tomography (PET) imagingEmission Tomography ImagingGray matter structuresPathological correlatesPositive participantsInverse associationAD groupCognitive impairmentDiseaseLinking resting-state network fluctuations with systems of coherent synaptic density: A multimodal fMRI and 11C-UCB-J PET study
Fang X, Volpi T, Holmes S, Esterlis I, Carson R, Worhunsky P. Linking resting-state network fluctuations with systems of coherent synaptic density: A multimodal fMRI and 11C-UCB-J PET study. Frontiers In Human Neuroscience 2023, 17: 1124254. PMID: 36908710, PMCID: PMC9995441, DOI: 10.3389/fnhum.2023.1124254.Peer-Reviewed Original ResearchSynaptic densityRSN activityResting-state network connectivityRSN functional connectivityAnterior default mode networkJ PET studyResting-state fMRIBrain functional organizationDefault mode networkHealthy adult participantsExecutive control networkRSN connectivityFunctional organizationPsychiatric disordersMedial prefrontalSalience networkPET studiesFunctional connectivityHealthy agingFractional amplitudeLow-frequency fluctuationsNeurophysiological linkSynaptic architectureAdult participantsDefault-mode activity
2022
A 3D atlas of functional human brain energetic connectome based on neuropil distribution
Yu Y, Akif A, Herman P, Cao M, Rothman D, Carson R, Agarwal D, Evans A, Hyder F. A 3D atlas of functional human brain energetic connectome based on neuropil distribution. Cerebral Cortex 2022, 33: 3996-4012. PMID: 36104858, PMCID: PMC10068297, DOI: 10.1093/cercor/bhac322.Peer-Reviewed Original ResearchConceptsSynaptic densityCortical regionsHigher synapse densityHuman cortical circuitsFunctional imaging studiesCortical activity mapsVivo PET imagingNeuropil distributionGlucose oxidationSynapse densityCortical circuitsMetabolic rateSynaptic connectionsCortical energeticsImaging studiesHuman cortexPET imagingHistological stainingRecent evidenceCortexHuman brainBrainVoxel levelActivity ratesAtlasReversal of synapse loss in Alzheimer mouse models by targeting mGluR5 to prevent synaptic tagging by C1Q
Spurrier J, Nicholson L, Fang XT, Stoner AJ, Toyonaga T, Holden D, Siegert TR, Laird W, Allnutt MA, Chiasseu M, Brody AH, Takahashi H, Nies SH, Pérez-Cañamás A, Sadasivam P, Lee S, Li S, Zhang L, Huang YH, Carson RE, Cai Z, Strittmatter SM. Reversal of synapse loss in Alzheimer mouse models by targeting mGluR5 to prevent synaptic tagging by C1Q. Science Translational Medicine 2022, 14: eabi8593. PMID: 35648810, PMCID: PMC9554345, DOI: 10.1126/scitranslmed.abi8593.Peer-Reviewed Original ResearchConceptsPositron emission tomographySilent allosteric modulatorsAlzheimer's diseaseMouse modelPhospho-tau accumulationAged mouse modelAlzheimer mouse modelImmune-mediated attackSAM treatmentMicroglial mediatorsSynaptic engulfmentSynaptic lossAD miceComplement component C1qSynapse lossGlutamate responseSynaptic densityDrug washoutSynaptic localizationTherapeutic benefitCognitive impairmentAllosteric modulatorsEmission tomographyNonhuman primatesComponent C1qImaging of Synaptic Density in Neurodegenerative Disorders
Carson RE, Naganawa M, Toyonaga T, Koohsari S, Yang Y, Chen MK, Matuskey D, Finnema SJ. Imaging of Synaptic Density in Neurodegenerative Disorders. Journal Of Nuclear Medicine 2022, 63: 60s-67s. PMID: 35649655, DOI: 10.2967/jnumed.121.263201.Peer-Reviewed Original ResearchConceptsSynaptic densityAlzheimer's diseaseNeurodegenerative disordersNeurodegenerative diseasesSynaptic vesicle protein 2APotential reference regionsSynaptic density lossLewy body dementiaProgressive supranuclear palsyDisease-modifying therapiesSpecific brain proteinsLarge patient cohortAntiepileptic drug levetiracetamPET imaging resultsMultiple neurodegenerative disordersSynaptic lossSupranuclear palsyCorticobasal degenerationNeuropathologic diseasePatient cohortRat modelClinical valueF-FDGParkinson's diseaseEfficacy assessmentImaging the fetal nonhuman primate brain with SV2A positron emission tomography (PET)
Rossano S, Toyonaga T, Berg E, Lorence I, Fowles K, Nabulsi N, Ropchan J, Li S, Ye Y, Felchner Z, Kukis D, Huang Y, Benveniste H, Tarantal AF, Groman S, Carson RE. Imaging the fetal nonhuman primate brain with SV2A positron emission tomography (PET). European Journal Of Nuclear Medicine And Molecular Imaging 2022, 49: 3679-3691. PMID: 35633376, PMCID: PMC9826644, DOI: 10.1007/s00259-022-05825-6.Peer-Reviewed Original ResearchConceptsPositron emission tomographySynaptic densityFetal brainThird trimesterEmission tomographyBrain developmentGravid rhesus monkeysPost-mortem brain tissueEarly neonatal periodNonhuman primate brainLate gestational periodSubset of subjectsPostnatal brain developmentPost-mortem samplesGestational ageNeonatal periodPregnant monkeysSynapse numberGestational periodPrimary motorPrimate brainBrain growthSubcortical regionsBrain tissueCortical regionsFeasibility of imaging synaptic density in the human spinal cord using [11C]UCB-J PET
Rossano S, Toyonaga T, Bini J, Nabulsi N, Ropchan J, Cai Z, Huang Y, Carson RE. Feasibility of imaging synaptic density in the human spinal cord using [11C]UCB-J PET. EJNMMI Physics 2022, 9: 32. PMID: 35503134, PMCID: PMC9065222, DOI: 10.1186/s40658-022-00464-0.Peer-Reviewed Original ResearchFull spinal cordSpinal cord injuryHuman spinal cordSpinal cordAmyotrophic lateral sclerosisDistribution volume ratioCervical SCSynaptic densitySynaptic vesicle protein 2ACervical spinal cordBrain gray matterUse of PETBaseline VTWhole-body imagesSynapse lossCord injuryLateral sclerosisInjury severityGray matterNeurodegenerative disordersCordProtein 2AHuman dataDVR valuesCurrent standardPET Imaging of Synaptic Density: Challenges and Opportunities of Synaptic Vesicle Glycoprotein 2A PET in Small Animal Imaging
Toyonaga T, Fesharaki-Zadeh A, Strittmatter SM, Carson RE, Cai Z. PET Imaging of Synaptic Density: Challenges and Opportunities of Synaptic Vesicle Glycoprotein 2A PET in Small Animal Imaging. Frontiers In Neuroscience 2022, 16: 787404. PMID: 35345546, PMCID: PMC8957200, DOI: 10.3389/fnins.2022.787404.Peer-Reviewed Original ResearchAnimal modelsPET imaging studiesPET imagingImaging studiesSynaptic vesicle glycoprotein 2ADisease animal modelsOngoing clinical investigationsDifferent injection routesSynaptic densityClinical investigationPharmacological effectsRodent brainNovel interventionsInjection routeNeurodegenerative disordersNeuropsychiatric diseasesPET studiesBrainMultiple diseasesPET centersDiseaseInjectable volumeImagingSmaller brainsPET