2025
Venous blood sampling for less invasive in vivo quantification of synaptic density with constant infusion of [18F]SynVesT-1 and PET
Asch R, Naganawa M, Moisieienko K, Weed M, Kapinos M, Zheng M, Hillmer A, Carson R, Pietrzak R, Esterlis I. Venous blood sampling for less invasive in vivo quantification of synaptic density with constant infusion of [18F]SynVesT-1 and PET. EJNMMI Research 2025, 15: 8. PMID: 39900828, PMCID: PMC11790547, DOI: 10.1186/s13550-025-01200-2.Peer-Reviewed Original Research
2024
An In Vivo Examination of the Relationship Between Metabotropic Glutamate 5 Receptor and Suicide Attempts in People With Borderline Personality Disorder
Davis M, Asch R, Weiss E, Wagner A, Fineberg S, Nabulsi N, Matuskey D, Carson R, Esterlis I. An In Vivo Examination of the Relationship Between Metabotropic Glutamate 5 Receptor and Suicide Attempts in People With Borderline Personality Disorder. Biological Psychiatry Cognitive Neuroscience And Neuroimaging 2024, 10: 324-332. PMID: 39613160, DOI: 10.1016/j.bpsc.2024.11.014.Peer-Reviewed Original ResearchBorderline personality disorderPathophysiology of borderline personality disorderSuicide attemptsPersonality disorderPositron emission tomographyAssociated with history of suicide attemptBorderline personality disorder symptomsBPD pathophysiologyPositron emission tomography outcomes measurementsHistory of suicide attemptsMetabotropic glutamate receptor type 5Metabotropic glutamate receptor 5Glutamate receptor 5Comprehensive clinical assessmentFrontolimbic circuitsMDD groupDepressive disorderEmotion regulationPsychiatric conditionsCognitive functionMGlu5Comparison controlsMDDSuicideAssociated with history11C-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, 30: 1610-1616. 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 synapsesAutismMicroglia-mediated neuroimmune suppression in PTSD is associated with anhedonia
Bonomi R, Hillmer A, Woodcock E, Bhatt S, Rusowicz A, Angarita G, Carson R, Davis M, Esterlis I, Nabulsi N, Huang Y, Krystal J, Pietrzak R, Cosgrove K. Microglia-mediated neuroimmune suppression in PTSD is associated with anhedonia. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2406005121. PMID: 39172786, PMCID: PMC11363315, DOI: 10.1073/pnas.2406005121.Peer-Reviewed Original ResearchConceptsPTSD groupPrefrontal-limbic circuitsNeuroimmune responseAssociated with anhedoniaPosttraumatic stress disorderPositron emission tomography brain imagingTranslocator protein availabilityBrain immune functionAnhedonic symptomsStress disorderPeripheral immune dysfunctionPTSDGroup differencesSeverity of symptomsPsychiatric diseasesTranslocator proteinBrain imagingAdministration of lipopolysaccharideSymptomsMicroglial markersLPS-induced increaseCompared to controlsImmune functionSickness symptomsAnhedoniaChallenges 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 tomographyDeficits in prefrontal metabotropic glutamate receptor 5 are associated with functional alterations during emotional processing in bipolar disorder
Asch R, Worhunsky P, Davis M, Holmes S, Cool R, Boster S, Carson R, Blumberg H, Esterlis I. Deficits in prefrontal metabotropic glutamate receptor 5 are associated with functional alterations during emotional processing in bipolar disorder. Journal Of Affective Disorders 2024, 361: 415-424. PMID: 38876317, PMCID: PMC11250898, DOI: 10.1016/j.jad.2024.06.025.Peer-Reviewed Original ResearchMetabotropic glutamate receptor 5Bipolar disorderGlutamate receptor 5Positron emission tomographyFear processingEmotional processingAssociated with greater activationEmotion processing taskAssociated with impulsivityFunctional brain differencesAssociated with functional alterationsParietal brain regionsPathology of BDIncreased cortical activityAssociated with difficultiesDepressive disorderHealthy comparisonReceptor availabilityBrain differencesPre/postcentral gyriAttention difficultiesGreater activationBrain regionsPsychomotor functionTreatment developmentSynaptic 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 loss
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 volumeEvaluating infusion methods and simplified quantification of synaptic density in vivo with [11C]UCB-J and [18F]SynVesT-1 PET
Asch R, Naganawa M, Nabulsi N, Huan Y, Esterlis I, Carson R. Evaluating infusion methods and simplified quantification of synaptic density in vivo with [11C]UCB-J and [18F]SynVesT-1 PET. Cerebrovascular And Brain Metabolism Reviews 2023, 43: 2120-2129. PMID: 37669455, PMCID: PMC10925870, DOI: 10.1177/0271678x231200423.Peer-Reviewed Original ResearchLinking 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 activityInvestigating CNS distribution of PF‐05212377, a P‐glycoprotein substrate, by translation of 5‐HT6 receptor occupancy from non‐human primates to humans
Sawant‐Basak A, Chen L, Lockwood P, Boyden T, Doran A, Mancuso J, Zasadny K, McCarthy T, Morris E, Carson R, Esterlis I, Huang Y, Nabulsi N, Planeta B, Fullerton T. Investigating CNS distribution of PF‐05212377, a P‐glycoprotein substrate, by translation of 5‐HT6 receptor occupancy from non‐human primates to humans. Biopharmaceutics & Drug Disposition 2023, 44: 48-59. PMID: 36825693, DOI: 10.1002/bdd.2351.Peer-Reviewed Original ResearchConceptsNon-human primatesBrain penetrationPositron emission tomographyReceptor occupancyUnbound concentrationsPre-clinical evidenceVivo brain penetrationConcentration-dependent increaseP-glycoprotein substratesPlasma ECsP-gpAlzheimer's diseaseEmission tomographyRat BBBTarget engagementCumulative evidenceDependent increaseTransporter substratesCNS distributionBBBRatsDiseasePrimatesSpecies differencesHumans
2022
Differences in Quantification of the Metabotropic Glutamate Receptor 5 Across Bipolar Disorder and Major Depressive Disorder
Holmes S, Asch R, Davis M, DellaGioia N, Pashankar N, Gallezot J, Nabulsi N, Matuskey D, Sanacora G, Carson R, Blumberg H, Esterlis I. Differences in Quantification of the Metabotropic Glutamate Receptor 5 Across Bipolar Disorder and Major Depressive Disorder. Biological Psychiatry 2022, 93: 1099-1107. PMID: 36764853, PMCID: PMC10164841, DOI: 10.1016/j.biopsych.2022.10.018.Peer-Reviewed Original ResearchConceptsMajor depressive disorderMetabotropic glutamate receptor 5Glutamate receptor 5MGluR5 availabilityBipolar disorderPositron emission tomographyHC groupDepressive disorderReceptor 5Emission tomographyHealthy control individualsPossible treatment targetsGlutamate transmissionBD depressionTreatment strategiesBD groupMGluR5Depressive symptomsNovel treatmentsCognitive alterationsTreatment targetsSynaptic plasticityControl individualsAccurate diagnosisSignificant negative correlation
2021
Lower prefrontal cortical synaptic vesicle binding in cocaine use disorder: An exploratory 11C‐UCB‐J positron emission tomography study in humans
Angarita GA, Worhunsky PD, Naganawa M, Toyonaga T, Nabulsi NB, Li C, Esterlis I, Skosnik PD, Radhakrishnan R, Pittman B, Gueorguieva R, Potenza MN, Finnema SJ, Huang Y, Carson RE, Malison RT. Lower prefrontal cortical synaptic vesicle binding in cocaine use disorder: An exploratory 11C‐UCB‐J positron emission tomography study in humans. Addiction Biology 2021, 27: e13123. PMID: 34852401, PMCID: PMC8891080, DOI: 10.1111/adb.13123.Peer-Reviewed Original ResearchConceptsCocaine use disorderAnterior cingulate cortexRecent cocaine useSynaptic densityMedial orbitofrontal cortexPrefrontal cortexCocaine useOrbitofrontal cortexUse disordersVentromedial prefrontal cortexPositron emission tomography scanPositron emission tomography studyEmission tomography scanSynaptic vesicle glycoprotein 2AHealthy control subjectsVolume of distributionEmission tomography studiesAcute cocaineControl subjectsTomography scanCocaine exposurePreclinical studiesHC subjectsDendritic spinesLifetime cocaine useIn vivo evidence of lower synaptic vesicle density in schizophrenia
Radhakrishnan R, Skosnik PD, Ranganathan M, Naganawa M, Toyonaga T, Finnema S, Hillmer AT, Esterlis I, Huang Y, Nabulsi N, Carson RE, D’Souza D. In vivo evidence of lower synaptic vesicle density in schizophrenia. Molecular Psychiatry 2021, 26: 7690-7698. PMID: 34135473, DOI: 10.1038/s41380-021-01184-0.Peer-Reviewed Original ResearchConceptsSynaptic vesicle densityHealthy controlsVesicle densityHigh-resolution research tomographySynaptic densitySCZ patientsVivo measuresNovel positron emission tomography (PET) ligandGender-matched healthy controlsCumulative antipsychotic exposurePositron emission tomography (PET) ligandSynaptic spine densityPsychosis symptom severityGray matter volumeJ bindingAntipsychotic exposureSpine densityDisease progressionFrontal cortexOccipital cortexTomography ligandTemporal cortexAnterior cingulateVivo findingsParietal cortexIdentifying brain networks in synaptic density PET (11C-UCB-J) with independent component analysis
Fang XT, Toyonaga T, Hillmer AT, Matuskey D, Holmes SE, Radhakrishnan R, Mecca AP, van Dyck CH, D’Souza D, Esterlis I, Worhunsky PD, Carson RE. Identifying brain networks in synaptic density PET (11C-UCB-J) with independent component analysis. NeuroImage 2021, 237: 118167. PMID: 34000404, PMCID: PMC8452380, DOI: 10.1016/j.neuroimage.2021.118167.Peer-Reviewed Original ResearchConceptsSynaptic densityResting-state functional magnetic resonance imagingSynaptic vesicle protein 2ALevel-dependent signal fluctuationsBrain networksFunctional magnetic resonance imagingMagnetic resonance imagingAge-related changesHealthy controlsResonance imagingRs-fMRIEffects of sexProtein 2AMultiple comparisonsHuman brainAgePotential utilitySexFirst evidenceCovariance patternsPET Imaging Estimates of Regional Acetylcholine Concentration Variation in Living Human Brain
Smart K, Naganawa M, Baldassarri SR, Nabulsi N, Ropchan J, Najafzadeh S, Gao H, Navarro A, Barth V, Esterlis I, Cosgrove KP, Huang Y, Carson RE, Hillmer AT. PET Imaging Estimates of Regional Acetylcholine Concentration Variation in Living Human Brain. Cerebral Cortex 2021, 31: 2787-2798. PMID: 33442731, PMCID: PMC8355478, DOI: 10.1093/cercor/bhaa387.Peer-Reviewed Original ResearchConceptsACh concentrationHuman volunteersHigh ACh concentrationsMuscarinic antagonist scopolamineHealthy human volunteersHuman brainCholinergic receptorsNicotine challengeAntagonist scopolaminePreclinical studiesStriatal regionsPET scansEndogenous neurotransmittersNeuropsychiatric diseasesNonhuman primatesWhole-brain imagesDrug occupancyNicotinic ligandsClinical populationsBrainAcetylcholineDistinct functional rolesStriatumVolunteersFunctional role
2020
PET Imaging of Synaptic Vesicle Protein 2A
Finnema S, Li S, Cai Z, Naganawa M, Chen M, Matuskey D, Nabulsi N, Esterlis I, Holmes S, Radhakrishnan R, Toyonaga T, Huang Y, Carson R. PET Imaging of Synaptic Vesicle Protein 2A. 2020, 993-1019. DOI: 10.1007/978-3-030-53176-8_29.ChaptersSynaptic vesicle protein 2APositron emission tomographyAntiepileptic drug levetiracetamInitial PET studiesPET imagingPET studiesSynaptic densityDrug levetiracetamHigh-affinity SV2A ligandsBrain regionsSynaptic density lossNeuropathological diseasesDisease-modifying therapiesLarge patient cohortMajor depressive disorderProtein 2APET imaging resultsPosttraumatic stress disorderPatient groupPatient cohortDepressive disorderClinical valueParkinson's diseaseEfficacy assessmentSynaptic vesicle proteinsSimplified Quantification of 11C-UCB-J PET Evaluated in a Large Human Cohort
Naganawa M, Gallezot JD, Finnema SJ, Matuskey D, Mecca A, Nabulsi NB, Labaree D, Ropchan J, Malison RT, D'Souza DC, Esterlis I, Detyniecki K, van Dyck CH, Huang Y, Carson RE. Simplified Quantification of 11C-UCB-J PET Evaluated in a Large Human Cohort. Journal Of Nuclear Medicine 2020, 62: 418-421. PMID: 32646875, PMCID: PMC8049341, DOI: 10.2967/jnumed.120.243949.Peer-Reviewed Original ResearchPTSD is associated with neuroimmune suppression: evidence from PET imaging and postmortem transcriptomic studies
Bhatt S, Hillmer AT, Girgenti MJ, Rusowicz A, Kapinos M, Nabulsi N, Huang Y, Matuskey D, Angarita GA, Esterlis I, Davis MT, Southwick SM, Friedman MJ, Duman R, Carson R, Krystal J, Pietrzak R, Cosgrove K. PTSD is associated with neuroimmune suppression: evidence from PET imaging and postmortem transcriptomic studies. Nature Communications 2020, 11: 2360. PMID: 32398677, PMCID: PMC7217830, DOI: 10.1038/s41467-020-15930-5.Peer-Reviewed Original ResearchMeSH KeywordsAcetamidesAdaptor Proteins, Signal TransducingAdultBrainCase-Control StudiesFemaleGene Expression ProfilingHealthy VolunteersHumansMaleMicrogliaMiddle AgedPositron-Emission TomographyPyridinesRadiopharmaceuticalsReceptors, GABAReceptors, Tumor Necrosis Factor, Member 14Sex FactorsStress Disorders, Post-TraumaticYoung AdultConceptsPosttraumatic stress disorderPeripheral immune activationImmune activationHigher C-reactive protein levelsC-reactive protein levelsTSPO availabilityTranslocator proteinBrain microglial activationTomography brain imagingStress-related pathophysiologyPositron emission tomography (PET) brain imagingNeuroimmune activationMicroglial activationPTSD symptom severityImmunologic regulationPostmortem studiesPTSD subgroupHealthy individualsSymptom severityTrauma exposurePTSD groupStress disorderLower relative expressionBrain imagingPET imaging
2019
Measuring the effects of ketamine on mGluR5 using [18F]FPEB and PET
Holmes SE, Gallezot JD, Davis MT, DellaGioia N, Matuskey D, Nabulsi N, Krystal JH, Javitch JA, DeLorenzo C, Carson RE, Esterlis I. Measuring the effects of ketamine on mGluR5 using [18F]FPEB and PET. Cerebrovascular And Brain Metabolism Reviews 2019, 40: 2254-2264. PMID: 31744389, PMCID: PMC7585925, DOI: 10.1177/0271678x19886316.Peer-Reviewed Original ResearchConceptsEffects of ketamineKetamine infusionGlutamate transmissionMetabotropic glutamate receptor 5Ketamine-induced effectsKetamine-induced changesGlutamate receptor 5Promising treatment targetDrug challenge studiesTwo-tissue compartment modelMGluR5 radioligandBlood pressureMGluR5 availabilityBaseline scanOutcome measuresHealthy subjectsHeart ratePsychiatric disordersReceptor 5Modulatory effectsMGluR5Treatment targetsChallenge studiesArterial input functionChallenge paradigm
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