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
Association 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 atrophyCognitionAssociation of Novelty-Related Locus Coeruleus Function With Entorhinal Tau Deposition and Memory Decline in Preclinical Alzheimer Disease
Prokopiou P, Engels-Domínguez N, Schultz A, Sepulcre J, Koops E, Papp K, Marshall G, Normandin M, El Fakhri G, Rentz D, Sperling R, Johnson K, Jacobs H. Association of Novelty-Related Locus Coeruleus Function With Entorhinal Tau Deposition and Memory Decline in Preclinical Alzheimer Disease. Neurology 2023, 101: e1206-e1217. PMID: 37491329, PMCID: PMC10516269, DOI: 10.1212/wnl.0000000000207646.Peer-Reviewed Original ResearchConceptsLC activityMemory declineLocus coeruleusCognitive declineEC tauHarvard Aging Brain StudyHuman neuroimaging studiesSteeper memory declineNoradrenergic brainstem nucleiLongitudinal cognitive dataFunctional MRI dataTau depositionAging Brain StudyPreclinical Alzheimer's diseaseTau progressionCortical tau depositionElevated beta-amyloidInterventions promoting resilienceMild cognitive impairmentExecutive dysfunctionExecutive functionNeuroimaging studiesTau spreadingTemporal cortexCognitive composite
2022
Human 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 modelsImpact 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 clearanceSynthesis and Characterization of 5‑(2-Fluoro-4‑[11C]methoxyphenyl)-2,2-dimethyl-3,4-dihydro‑2H‑pyrano[2,3‑b]pyridine-7-carboxamide as a PET Imaging Ligand for Metabotropic Glutamate Receptor 2
Yuan G, Dhaynaut M, Lan Y, Guehl N, Huynh D, Iyengar S, Afshar S, Jain M, Pickett J, Kang H, Wang H, Moon S, Ondrechen M, Wang C, Shoup T, Fakhri G, Normandin M, Brownell A. Synthesis and Characterization of 5‑(2-Fluoro-4‑[11C]methoxyphenyl)-2,2-dimethyl-3,4-dihydro‑2H‑pyrano[2,3‑b]pyridine-7-carboxamide as a PET Imaging Ligand for Metabotropic Glutamate Receptor 2. Journal Of Medicinal Chemistry 2022, 65: 2593-2609. PMID: 35089713, PMCID: PMC9434702, DOI: 10.1021/acs.jmedchem.1c02004.Peer-Reviewed Original ResearchConceptsNegative allosteric modulatorsMetabotropic glutamate receptor 2Positron emission tomographyGlutamate receptor 2MGluR2 functionNeuropsychiatric disordersDrug effectsBrain heterogeneityReceptor 2Allosteric modulatorsMGluR2Nonhuman primatesBrain imagingPositron emission tomography imagingPositron emission tomography imaging ligandsHigh molar activityEmission tomographyExcellent radiochemical purityImaging ligandsBlocking agentsPET imagingMolar activityTherapeutic targetMetabotropicDisorders
2019
Assessment of Striatal Dopamine Transporter Binding in Individuals With Major Depressive Disorder
Pizzagalli D, Berretta S, Wooten D, Goer F, Pilobello K, Kumar P, Murray L, Beltzer M, Boyer-Boiteau A, Alpert N, Fakhri G, Mechawar N, Vitaliano G, Turecki G, Normandin M. Assessment of Striatal Dopamine Transporter Binding in Individuals With Major Depressive Disorder. JAMA Psychiatry 2019, 76: 854-861. PMID: 31042280, PMCID: PMC6495358, DOI: 10.1001/jamapsychiatry.2019.0801.Peer-Reviewed Original ResearchConceptsMajor depressive disorderDA transporter availabilityVentral tegmental areaDA transporterDAT availabilityTegmental areaDepressive disorderDA signalingPositron emission tomographyDAT expressionMcLean HospitalHealthy controlsMajor depressive disorder groupsNumbers of depressive episodesStriatal dopamine transporter bindingDA transporter levelsLevels of DAT expressionStriatal DAT expressionStriatal DAT availabilityDA transporter densityDAT binding potentialDopamine transporter bindingOlder healthy controlsMesolimbic pathwayDA clearanceEvaluation 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, El Fakhri G, Normandin M. 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 2019, 46: 2099-2111. PMID: 31332496, PMCID: PMC6709592, DOI: 10.1007/s00259-019-04419-z.Peer-Reviewed Original ResearchConceptsReference tissue methodDistribution volume ratioTissue methodIn vivo quantificationPharmacokinetic modeling strategiesArterial plasma input functionMultilinear reference tissue methodsTwo-tissue compartment modelBlood:plasma ratioTissue-to-plasmaPlasma input functionPlasma concentration time courseBlood-based methodMethodsThirty-five subjectsSUV ratioBlood-based analysesData setsArterial input functionPET scansControl subjectsMild cognitive impairmentPlasma ratioRadiometabolite analysisHealthy controlsConcentration time courseAutoradiography validation of novel tau PET tracer [F-18]-MK-6240 on human postmortem brain tissue
Aguero C, Dhaynaut M, Normandin M, Amaral A, Guehl N, Neelamegam R, Marquie M, Johnson K, El Fakhri G, Frosch M, Gomez-Isla T. Autoradiography validation of novel tau PET tracer [F-18]-MK-6240 on human postmortem brain tissue. Acta Neuropathologica Communications 2019, 7: 37. PMID: 30857558, PMCID: PMC6410510, DOI: 10.1186/s40478-019-0686-6.Peer-Reviewed Original ResearchConceptsIn vivo detection of neurofibrillary tanglesNeurofibrillary tanglesDetection of neurofibrillary tanglesAlzheimer's diseaseTDP-43Binds to neurofibrillary tanglesFrontotemporal lobar degeneration-tauOff-target bindingDNA-binding protein 43Binding patternsNon-Alzheimer tauopathiesHuman postmortem brain tissueTau aggregationPostmortem brain tissueBinding signalBinding targetsCerebral amyloid angiopathyIn vivo detectionB-amyloidNeurodegenerative diseasesHuman brain tissueTauTau positron emission tomographyBindingMK-6240
2018
[18F]Fluorocholine and [18F]Fluoroacetate PET as Imaging Biomarkers to Assess Phosphatidylcholine and Mitochondrial Metabolism in Preclinical Models of TSC and LAM
Verwer E, Kavanagh T, Mischler W, Feng Y, Takahashi K, Wang S, Shoup T, Neelamegam R, Yang J, Guehl N, Ran C, Massefski W, Cui Y, El-Chemaly S, Sadow P, Oldham W, Kijewski M, Fakhri G, Normandin M, Priolo C. [18F]Fluorocholine and [18F]Fluoroacetate PET as Imaging Biomarkers to Assess Phosphatidylcholine and Mitochondrial Metabolism in Preclinical Models of TSC and LAM. Clinical Cancer Research 2018, 24: 5925-5938. PMID: 30054282, PMCID: PMC6816044, DOI: 10.1158/1078-0432.ccr-17-3693.Peer-Reviewed Original ResearchMeSH KeywordsAgedAnimalsBiomarkersCholineDisease Models, AnimalFemaleFluoroacetatesHeterograftsHumansImage Processing, Computer-AssistedImmunohistochemistryLipid MetabolismLymphangioleiomyomatosisMaleMiceMice, TransgenicMitochondriaOxygen ConsumptionPhosphatidylcholinesPositron-Emission TomographyRatsTuberous SclerosisConceptsTuberous sclerosis complexMetabolic imaging biomarkersPreclinical modelsImaging biomarkersTSC2-deficient cellsStandardized uptake valueTuberous sclerosis complex manifestationsModels of tuberous sclerosis complexAutosomal dominant disorderPotential clinical interestBenign tumorsOvariectomized miceUptake valueSubcutaneous tumorsPreclinical studiesPulmonary nodulesCystic destructionLymphangioleiomyomatosisDominant disorderProliferative lesionsInactivating mutationsTumorMetabolic reprogrammingNeurocognitive impairmentPET imaging
2017
Frontostriatal and Dopamine Markers of Individual Differences in Reinforcement Learning: A Multi-modal Investigation
Kaiser R, Treadway M, Wooten D, Kumar P, Goer F, Murray L, Beltzer M, Pechtel P, Whitton A, Cohen A, Alpert N, Fakhri G, Normandin M, Pizzagalli D. Frontostriatal and Dopamine Markers of Individual Differences in Reinforcement Learning: A Multi-modal Investigation. Cerebral Cortex 2017, 28: 4281-4290. PMID: 29121332, PMCID: PMC6454484, DOI: 10.1093/cercor/bhx281.Peer-Reviewed Original ResearchConceptsDA transporterRL behaviourVentral striatumDA clearanceFunctional connectivityBinding potentialLevel of neurocognitive functioningIncreased intrinsic functional connectivityMulti-modal neuroimaging studiesResting-state functional connectivityPhasic DA activityStriatal DA transporterIntrinsic functional connectivityReinforcement learning behaviorMulti-modal investigationsFrontostriatal circuitsFrontostriatal connectivityFrontostriatal regionsOrbitofrontal cortexDA activityNeuroimaging studiesOrbitofrontal regionsDopamine markersNeurocognitive functionDopamineLessons learned about [F-18]-AV-1451 off-target binding from an autopsy-confirmed Parkinson’s case
Marquié M, Verwer E, Meltzer A, Kim S, Agüero C, Gonzalez J, Makaretz S, Siao Tick Chong M, Ramanan P, Amaral A, Normandin M, Vanderburg C, Gomperts S, Johnson K, Frosch M, Gómez-Isla T. Lessons learned about [F-18]-AV-1451 off-target binding from an autopsy-confirmed Parkinson’s case. Acta Neuropathologica Communications 2017, 5: 75. PMID: 29047416, PMCID: PMC5648451, DOI: 10.1186/s40478-017-0482-0.Peer-Reviewed Original ResearchConceptsPositron emission tomographyBasal gangliaBinding to neuromelaninPositron emission tomography studiesDementia of AD typeInferior temporal cortexParkinson's diseaseTau pathologyPositron emission tomography scanAlzheimer's diseaseMild cognitive impairmentTemporal cortexAutoradiographic bindingBrain regionsNeurofibrillary tau pathologyOccipital cortexPositron emission tomography signalCognitive impairmentPostmortem materialEntorhinal cortexSubstantia nigraParenchymal hemorrhagePD diagnosisAutoradiography experimentsChoroid plexus[F-18]-AV-1451 binding correlates with postmortem neurofibrillary tangle Braak staging
Marquié M, Siao Tick Chong M, Antón-Fernández A, Verwer E, Sáez-Calveras N, Meltzer A, Ramanan P, Amaral A, Gonzalez J, Normandin M, Frosch M, Gómez-Isla T. [F-18]-AV-1451 binding correlates with postmortem neurofibrillary tangle Braak staging. Acta Neuropathologica 2017, 134: 619-628. PMID: 28612291, PMCID: PMC5772971, DOI: 10.1007/s00401-017-1740-8.Peer-Reviewed Original ResearchConceptsNeurofibrillary tanglesNeurofibrillary tau pathologyTau burdenBraak stageStaging of neurofibrillary tanglesBrain regionsAccurate diagnosis of Alzheimer's diseaseTau pathologyPhospho-tauStereotyped spatiotemporal patternBraak NFT stageNeurofibrillary tangle Braak stagePhosphor-screen autoradiographyAlzheimer's diseaseMild cognitive impairmentTau measuresNFT stageCognitively normal controlsObserved patternBraakCognitive impairmentWestern blottingBindingDiagnosis of Alzheimer's diseaseBraak staging of neurofibrillary tangles
2016
Differences in IV alcohol-induced dopamine release in the ventral striatum of social drinkers and nontreatment-seeking alcoholics
Yoder K, Albrecht D, Dzemidzic M, Normandin M, Federici L, Graves T, Herring C, Hile K, Walters J, Liang T, Plawecki M, O'Connor S, Kareken D. Differences in IV alcohol-induced dopamine release in the ventral striatum of social drinkers and nontreatment-seeking alcoholics. Drug And Alcohol Dependence 2016, 160: 163-169. PMID: 26832934, PMCID: PMC5074339, DOI: 10.1016/j.drugalcdep.2016.01.001.Peer-Reviewed Original ResearchConceptsSample of social drinkersNontreatment-seeking alcoholicsSocial drinkersVentral striatumDopamine releaseAlcohol intoxicationAlcohol-induced dopamine releaseVoxel-wise binding potentialTarget breath alcohol concentrationEffects of alcohol intoxicationRight ventral striatumInduce dopamine releaseStriatal DA systemIntravenous alcohol infusionAlcohol use disorderResponse to alcoholBreath alcohol concentrationDA responseStriatal dopamineDA systemTarget BrACAlcohol clampUse disorderDependent drinkersAlcohol infusion
2015
Validating novel tau positron emission tomography tracer [F‐18]‐AV‐1451 (T807) on postmortem brain tissue
Marquié M, Normandin M, Vanderburg C, Costantino I, Bien E, Rycyna L, Klunk W, Mathis C, Ikonomovic M, Debnath M, Vasdev N, Dickerson B, Gomperts S, Growdon J, Johnson K, Frosch M, Hyman B, Gómez-Isla T. Validating novel tau positron emission tomography tracer [F‐18]‐AV‐1451 (T807) on postmortem brain tissue. Annals Of Neurology 2015, 78: 787-800. PMID: 26344059, PMCID: PMC4900162, DOI: 10.1002/ana.24517.Peer-Reviewed Original ResearchConceptsTau filamentsAlzheimer brainsTDP-43Paired helical filamentsDNA-binding proteinsIn vitro binding assaysFrontotemporal lobar degeneration-tauBinding to tau lesionsDNA-binding protein 43Tauopathy brainsHelical filamentsBrain tau pathologyTau pathologyTau lesionsSubstrate-specificBinding proteinPostmortem brain tissueCerebral amyloid angiopathyPhosphor-screen autoradiographyOff-target bindingB-amyloidAlzheimer's diseaseBinding assaysTauProtein 43Imaging PEG-Like Nanoprobes in Tumor, Transient Ischemia, and Inflammatory Disease Models
Wilks M, Normandin M, Yuan H, Cho H, Guo Y, Herisson F, Ayata C, Wooten D, Fakhri G, Josephson L. Imaging PEG-Like Nanoprobes in Tumor, Transient Ischemia, and Inflammatory Disease Models. Bioconjugate Chemistry 2015, 26: 1061-1069. PMID: 25971846, PMCID: PMC5378316, DOI: 10.1021/acs.bioconjchem.5b00213.Peer-Reviewed Original ResearchImaging the Cannabinoid CB1 Receptor in Humans with [11C] OMAR: Assessment of Kinetic Analysis Methods, Test–Retest Reproducibility, and Gender Differences
Normandin MD, Zheng MQ, Lin KS, Mason NS, Lin SF, Ropchan J, Labaree D, Henry S, Williams WA, Carson RE, Neumeister A, Huang Y. Imaging the Cannabinoid CB1 Receptor in Humans with [11C] OMAR: Assessment of Kinetic Analysis Methods, Test–Retest Reproducibility, and Gender Differences. Cerebrovascular And Brain Metabolism Reviews 2015, 35: 1313-1322. PMID: 25833345, PMCID: PMC4528005, DOI: 10.1038/jcbfm.2015.46.Peer-Reviewed Original ResearchConceptsTest-retest reliabilityCannabinoid type 1 receptorType 1 receptorCannabinoid CB1 receptorsPositron emission tomography (PET) imagingTest-retest reproducibilityEmission Tomography ImagingGender differencesTwo-tissue compartment modelCerebral uptakePresent studyCB1 receptorsCB1R availabilityInjected doseVascular componentBody weightReceptor availabilityNeuropsychiatric disordersMultilinear analysis methodRegional volumesReceptor bindingTomography imagingParent fractionOne-tissueHuman subjects
2013
Elevated brain cannabinoid CB1 receptor availability in post-traumatic stress disorder: a positron emission tomography study
Neumeister A, Normandin MD, Pietrzak RH, Piomelli D, Zheng MQ, Gujarro-Anton A, Potenza MN, Bailey CR, Lin SF, Najafzadeh S, Ropchan J, Henry S, Corsi-Travali S, Carson RE, Huang Y. Elevated brain cannabinoid CB1 receptor availability in post-traumatic stress disorder: a positron emission tomography study. Molecular Psychiatry 2013, 18: 1034-1040. PMID: 23670490, PMCID: PMC3752332, DOI: 10.1038/mp.2013.61.Peer-Reviewed Original ResearchMeSH KeywordsAdultAmidesAnalysis of VarianceArachidonic AcidsBrainEndocannabinoidsEthanolaminesFemaleGlyceridesHumansHydrocortisoneImidazolesLogistic ModelsMalePalmitic AcidsPiperidinesPolyunsaturated AlkamidesPyrazolesRadionuclide ImagingReceptor, Cannabinoid, CB1Stress Disorders, Post-TraumaticYoung AdultConceptsPost-traumatic stress disorderVolume of distributionCB1 receptor availabilityPositron emission tomographyHC groupReceptor availabilityTC groupCannabinoid type 1 receptorStress disorderPositron emission tomography studyEvidence-based pharmacotherapyEtiology of PTSDType 1 receptorEmission tomography studiesAnandamide concentrationsElevated brainPeripheral levelsHealthy controlsCB1 receptorsUntreated individualsPET scansAnimal modelsCortisol levelsLifetime historyEmission tomography
2012
In Vivo Imaging of Endogenous Pancreatic β-Cell Mass in Healthy and Type 1 Diabetic Subjects Using 18F-Fluoropropyl-Dihydrotetrabenazine and PET
Normandin MD, Petersen KF, Ding YS, Lin SF, Naik S, Fowles K, Skovronsky DM, Herold KC, McCarthy TJ, Calle RA, Carson RE, Treadway JL, Cline GW. In Vivo Imaging of Endogenous Pancreatic β-Cell Mass in Healthy and Type 1 Diabetic Subjects Using 18F-Fluoropropyl-Dihydrotetrabenazine and PET. Journal Of Nuclear Medicine 2012, 53: 908-916. PMID: 22573821, PMCID: PMC3737743, DOI: 10.2967/jnumed.111.100545.Peer-Reviewed Original ResearchConceptsType 1 diabetes mellitusVesicular monoamine transporter type 2Pancreatic β-cell massStandardized uptake valueΒ-cell massDiabetes mellitusUptake valueType 1 diabetic subjectsΒ-cell densityHealthy control subjectsInsulin secretion capacityΒ-cell functionPathophysiology of diabetesTransporter type 2Nondisplaceable uptakeDiabetic subjectsControl subjectsDisease progressionClinical assessmentVMAT2 bindingRenal cortexTotal pancreasDTBZ PETEarly diagnosisInjected dose
2011
Striatal dopamine transporter availability in unmedicated bipolar disorder
Anand A, Barkay G, Dzemidzic M, Albrecht D, Karne H, Zheng Q, Hutchins G, Normandin M, Yoder K. Striatal dopamine transporter availability in unmedicated bipolar disorder. Bipolar Disorders 2011, 13: 406-413. PMID: 21843280, DOI: 10.1111/j.1399-5618.2011.00936.x.Peer-Reviewed Original ResearchConceptsDopamine transporter availabilityBipolar disorderDopamine transporterPositron emission tomographyNeuropathology of bipolar disorderStriatal dopamine transporter availabilityEtiology of bipolar disorderMultilinear reference tissue modelUnmedicated BPD patientsBilateral dorsal caudatePresynaptic dopamine functionStructural magnetic resonance imagingStriatal binding potentialReceptor imaging studiesReference tissue modelMagnetic resonance imagingBPD patientsDopamine functionDopamine neurotransmissionDopamine systemDorsal caudateSynaptic dopamineBPD subjectsDopaminergic systemDepressive phase