Featured Publications
EM reconstruction algorithms for emission and transmission tomography.
Lange K, Carson R. EM reconstruction algorithms for emission and transmission tomography. Journal Of Computer Assisted Tomography 1984, 8: 306-16. PMID: 6608535.Peer-Reviewed Original ResearchConceptsEM algorithmGood physical modelTransmission image reconstructionTransmission tomographyMaximum likelihood estimatesAlgebraic schemeRelevant physical featuresNon-negativity constraintsGlobal convergenceIterative techniquePoisson natureLikelihood estimatesParameter estimatesCounting noiseMaximum likelihoodDetector geometryPhysical modelAccurate incorporationEM reconstruction algorithmPhysical featuresSpecific algorithmsImage reconstructionAlgorithmReconstruction algorithmActual reconstructionImaging 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 studiesConsensus Nomenclature for in vivo Imaging of Reversibly Binding Radioligands
Innis RB, Cunningham VJ, Delforge J, Fujita M, Gjedde A, Gunn RN, Holden J, Houle S, Huang SC, Ichise M, Iida H, Ito H, Kimura Y, Koeppe RA, Knudsen GM, Knuuti J, Lammertsma AA, Laruelle M, Logan J, Maguire RP, Mintun MA, Morris ED, Parsey R, Price JC, Slifstein M, Sossi V, Suhara T, Votaw JR, Wong DF, Carson RE. Consensus Nomenclature for in vivo Imaging of Reversibly Binding Radioligands. Cerebrovascular And Brain Metabolism Reviews 2007, 27: 1533-1539. PMID: 17519979, DOI: 10.1038/sj.jcbfm.9600493.Peer-Reviewed Original ResearchFirst-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 measuresReduced synaptic vesicle protein 2A binding in temporal lobe epilepsy: A [11C]UCB‐J positron emission tomography study
Finnema SJ, Toyonaga T, Detyniecki K, Chen M, Dias M, Wang Q, Lin S, Naganawa M, Gallezot J, Lu Y, Nabulsi NB, Huang Y, Spencer DD, Carson RE. Reduced synaptic vesicle protein 2A binding in temporal lobe epilepsy: A [11C]UCB‐J positron emission tomography study. Epilepsia 2020, 61: 2183-2193. PMID: 32944949, DOI: 10.1111/epi.16653.Peer-Reviewed Original ResearchConceptsMedial temporal lobe sclerosisTemporal lobe epilepsyTLE subjectsPositron emission tomographyLobe epilepsyJ BPSynaptic vesicle protein 2APartial volume correctionTemporal lobe sclerosisPositron emission tomography studyEmission tomography studiesSeizure onset zonePromising biomarker approachJ bindingPresurgical selectionSclerotic hippocampusHippocampal asymmetryTLE patientsRegional binding patternsControl subjectsCentrum semiovaleContralateral regionsEpilepsy patientsOutcome measuresOnset zoneLower 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 evidenceSymptomsDepressionSeverityDisordersAlterationsNoise Reduction in the Simplified Reference Tissue Model for Neuroreceptor Functional Imaging
Wu Y, Carson RE. Noise Reduction in the Simplified Reference Tissue Model for Neuroreceptor Functional Imaging. Cerebrovascular And Brain Metabolism Reviews 2002, 22: 1440-1452. PMID: 12468889, DOI: 10.1097/01.wcb.0000033967.83623.34.Peer-Reviewed Original ResearchComparison of Bolus and Infusion Methods for Receptor Quantitation: Application to [18F]Cyclofoxy and Positron Emission Tomography
Carson R, Channing M, Blasberg R, Dunn B, Cohen R, Rice K, Herscovitch P. Comparison of Bolus and Infusion Methods for Receptor Quantitation: Application to [18F]Cyclofoxy and Positron Emission Tomography. Cerebrovascular And Brain Metabolism Reviews 1993, 13: 24-42. PMID: 8380178, DOI: 10.1038/jcbfm.1993.6.Peer-Reviewed Original ResearchQuantification of Amphetamine-Induced Changes in [11C] Raclopride Binding with Continuous Infusion
Carson R, Breier* A, de Bartolomeis* A, Saunders† R, Su* T, Schmall B, Der M, Pickar* D, Eckelman W. Quantification of Amphetamine-Induced Changes in [11C] Raclopride Binding with Continuous Infusion. Cerebrovascular And Brain Metabolism Reviews 1997, 17: 437-447. PMID: 9143226, DOI: 10.1097/00004647-199704000-00009.Peer-Reviewed Original Research
2024
Challenges 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, 1-11. PMID: 39039139, 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 developmentPilot PET study of vaginally administered bioadhesive nanoparticles in cynomolgus monkeys: Kinetics and safety evaluation
Grun M, Honhar P, Wang Y, Rossano S, Khang M, Suh H, Fowles K, Kliman H, Cavaliere A, Carson R, Marquez‐Nostra B, Saltzman W. Pilot PET study of vaginally administered bioadhesive nanoparticles in cynomolgus monkeys: Kinetics and safety evaluation. Bioengineering & Translational Medicine 2024 DOI: 10.1002/btm2.10661.Peer-Reviewed Original ResearchVaginal dosage formsBioadhesive nanoparticlesCynomolgus monkeysAnalysis of inflammatory biomarkersVaginal microbicidesVaginal canalMultiple dosesInflammatory biomarkersTherapeutic efficacyVaginal fluidSystemic circulationLong-term deliveryNoninvasive imagingClinical translationDosage formsNon-human primatesDelivery vehiclesMonkeysDeliveryVaginitisUterusMicrobicidesSafety evaluationBiodistributionDosePopulation-based deep image prior for dynamic PET denoising: A data-driven approach to improve parametric quantification
Liu Q, Tsai Y, Gallezot J, Guo X, Chen M, Pucar D, Young C, Panin V, Casey M, Miao T, Xie H, Chen X, Zhou B, Carson R, Liu C. Population-based deep image prior for dynamic PET denoising: A data-driven approach to improve parametric quantification. Medical Image Analysis 2024, 95: 103180. PMID: 38657423, DOI: 10.1016/j.media.2024.103180.Peer-Reviewed Original ResearchDeep Image PriorImage priorsSupervised modelsNoise reductionIntrinsic image featuresDeep learning techniquesU-Net architectureNovel denoising techniqueQuality of parametric imagesDenoising modelDenoising techniquesStatic datasetsBaseline techniquesEffective noise reductionData-driven approachLearning techniquesDynamic datasetsOptimization processPrior informationStatic imagesHigh noise levelsImage featuresDatasetPrior imagePET datasetsAuthor Correction: Synaptic 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. Author Correction: Synaptic loss and its association with symptom severity in Parkinson’s disease. Npj Parkinson's Disease 2024, 10: 55. PMID: 38472206, PMCID: PMC10933370, DOI: 10.1038/s41531-024-00674-6.Peer-Reviewed Original ResearchSynaptic 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 lossFirst-in-Human Study of 18F-SynVesT-2: An SV2A PET Imaging Probe with Fast Brain Kinetics and High Specific Binding
Drake L, Wu Y, Naganawa M, Asch R, Zheng C, Najafzadeh S, Pracitto R, Lindemann M, Li S, Ropchan J, Labaree D, Emery P, Dias M, Henry S, Nabulsi N, Matuskey D, Hillmer A, Gallezot J, Carson R, Cai Z, Huang Y. First-in-Human Study of 18F-SynVesT-2: An SV2A PET Imaging Probe with Fast Brain Kinetics and High Specific Binding. Journal Of Nuclear Medicine 2024, 65: jnumed.123.266470. PMID: 38360052, PMCID: PMC10924160, DOI: 10.2967/jnumed.123.266470.Peer-Reviewed Original ResearchFirst-in-human studyPlasma free fractionTime-activity curvesCentrum semiovaleNonhuman primate's resultsFirst-in-humanFree fractionNondisplaceable binding potentialRegional time-activity curvesLow nonspecific uptakeRegional distribution volumesHigh-resolution research tomograph scannerTest-retest reproducibilityCerebral blood flowSynaptic vesicle glycoprotein 2AHealthy volunteersArterial input functionNonspecific uptakePET imaging probeDistribution volumeSynapse densityIndividual MR imagesHighest specific bindingMR imagingPET imagingA 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
PET Imaging of Rho‐Associated Protein Kinase 2 in A Mouse Model of Alzheimer’s Disease
Zheng C, Nicholson L, Chen B, Toyonaga T, Liu M, Strittmatter S, Carson R, Huang Y, Cai Z. PET Imaging of Rho‐Associated Protein Kinase 2 in A Mouse Model of Alzheimer’s Disease. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.075782.Peer-Reviewed Original ResearchAPP/PS1 micePS1 miceWT miceCentral nervous systemTime-activity curvesAlzheimer's diseaseAPP/PS1 transgenic miceAPP/PS1 transgenic AD miceMouse brainAge-matched WT controlsPS1 transgenic miceAPP/PS1Transgenic AD miceDynamic PET imaging dataROCK2 protein expressionAD drug discoveryHigh tracer uptakeMin post injectionPET imaging resultsExpression levelsReference tissue model 2PET imaging dataProtein expression levelsAD miceMouse model