Abstract
Purpose
The aim of this study was to assess striatal dopamine transporter (DAT) availability in a large group of normal subjects.
Methods
The study included 122 healthy subjects, aged 18–83 years, recruited in the multicentre ‘ENC-DAT’ study (promoted by the European Association of Nuclear Medicine). Brain single photon emission computed tomography (SPECT) was acquired by means of dual-head cameras 3 h after [123I]FP-CIT administration. Specific to nondisplaceable binding ratios (SBRs) in the basal ganglia were computed using the ‘BasGan’ software, allowing automatic value extraction with partial volume effect correction. Multicentre camera inhomogeneity was taken into account by calibrating values on basal ganglia phantom data. SBR in each caudate nucleus (C) and putamen (P) were the dependent variables in a repeated measures general linear model analysis; age, gender, handedness and body mass index (BMI) were the independent variables.
Results
SBR values in C and P were significantly associated with age (mean rate decrease with age: 0.0306 per year, or 0.57 % of the general mean; p < 0.0001) and gender (women had higher values; p = 0.015), while no significant effect was found for handedness and BMI. A significant interaction was found between age and region (p < 0.0001) as the age-related decline was 0.028 for left C, 0.026 for right C and 0.034 for both P. P/C ratio analysis confirmed that age-related SBR decrease was stronger in P than in C (p < 0.0001). No significant effect was found for season or time of the day when the scan was acquired by analysing the residual of SBR values in C and P, after subtraction of age and gender effects.
Conclusion
This study confirms the dependency of DAT on ageing and highlights the gender differences in a large sample of healthy subjects, while it does not support the dependency of DAT on BMI, handedness, circadian rhythm or season.
Similar content being viewed by others
References
Benamer TS, Patterson J, Grosset DG, Booij J, de Bruin K, van Royen E, et al. Accurate differentiation of parkinsonism and essential tremor using visual assessment of [123I]-FP-CIT SPECT imaging: the [123I]-FP-CIT study group. Mov Disord 2000;15:503–10.
O’Brien JT, Colloby S, Fenwick J, Williams ED, Firbank M, Burn D, et al. Dopamine transporter loss visualized with FP-CIT SPECT in the differential diagnosis of dementia with Lewy bodies. Arch Neurol 2004;61:919–25.
Chouker M, Tatsch K, Linke R, Pogarell O, Hahn K, Schwarz J. Striatal dopamine transporter binding in early to moderate advanced Parkinson’s disease: monitoring of disease progression over 2 years. Nucl Med Commun 2001;22:721–5.
Parkinson Study Group. Dopamine transporter brain imaging to assess the effects of pramipexole vs levodopa on Parkinson disease progression. JAMA 2002;287:1653–61.
Acton PD, Pilowsky LS, Kung HF, Ell PJ. Automatic segmentation of dynamic neuroreceptor single-photon emission tomography images using fuzzy clustering. Eur J Nucl Med 1999;26:581–90.
Acton PD, Mozley PD, Kung HF. Logistic discriminant parametric mapping: a novel method for the pixel-based differential diagnosis of Parkinson’s disease. Eur J Nucl Med 1999;26:1413–23.
Koole M, Laere KV, de Walle RV, Vandenberghe S, Bouwens L, Lemahieu I, et al. MRI guided segmentation and quantification of SPECT images of the basal ganglia: a phantom study. Comput Med Imaging Graph 2001;25:165–72.
Habraken JBA, Booij J, Slomka P, Sokole EB, van Royen EA. Quantification and visualization of defects of the functional dopaminergic system using an automatic algorithm. J Nucl Med 1999;40:1091–7.
Radau PE, Linke R, Slomka PJ, Tatsch K. Optimization of automated quantification of 123I-IBZM uptake in the striatum applied to parkinsonism. J Nucl Med 2000;41:220–7.
Koch W, Radau PE, Hamann C, Tatsch K. Clinical testing of an optimized software solution for an automated, observer-independent evaluation of dopamine transporter SPECT studies. J Nucl Med 2005;46:1109–18.
Tatsch K, Poepperl G. Quantitative approaches to dopaminergic brain imaging. Q J Nucl Med Mol Imaging 2012;56:27–38.
Calvini P, Rodriguez G, Inguglia F, Mignone A, Guerra UP, Nobili F. The basal ganglia matching tools package for striatal uptake semi-quantification: description and validation. Eur J Nucl Med Mol Imaging 2007;34:1240–53.
Derogatis LR, Unger R. Symptom checklist-90-revised. The Corsini encyclopedia of psychology. Hoboken: Wiley; 2010. p. 1–2.
Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry 1961;4:561–71.
Fazekas F, Niederhorn K, Schmidt R, Offenbacher H, Horner S, Bertha G, et al. White matter signal abnormalities in normal individuals: correlation with carotid ultrasonography, cerebral blood flow measurements, and cerebrovascular risk factors. Stroke 1988;19:1285–8.
Tossici-Bolt L, Dickson JC, Sera T, de Nijs R, Bagnara MC, Jonsson C, et al. Calibration of gamma camera systems for a multicentre European 123I-FP-CIT SPECT normal database. Eur J Nucl Med Mol Imaging 2011;38:1529–40.
Dickson JC, Tossici-Bolt L, Sera T, de Nijs R, Booij J, Bagnara MC, et al. Proposal for the standardisation of multi-centre trials in nuclear medicine imaging: prerequisites for a European 123I-FP-CIT SPECT database. Eur J Nucl Med Mol Imaging 2012;39:188–97.
Electronic Statistics Textbook. (Electronic Version): StatSoft, Inc. (2011). Tulsa, OK: StatSoft. WEB: http://www.statsoft.com/textbook/.(Printed Version): Hill, T. & Lewicki, P. (2007). STATISTICS: Methods and Applications. StatSoft, Tulsa, OK.
Badiavas K, Molyvda E, Iakovou I, Tsolaki M, Psarrakos K, Karatzas N. SPECT imaging evaluation in movement disorders: far beyond visual assessment. Eur J Nucl Med Mol Imaging 2011;38:764–73.
Pagan L, Tranfaglia C, Galli S, Lucchi G, Novi B, Fagioli G, et al. A comparison between the conventional manual ROI method and an automatic algorithm for semi quantitative analysis of SPECT studies. International Conference on Image Optimisation in Nuclear Medicine (OptiNM) J Phys: Conference Series 317 (2011) 012004.
Isaias IU, Marotta G, Pezzoli G, Sabri O, Schwarz J, Crenna P, et al. Enhanced catecholamine transporter binding in the locus coeruleus of patients with early Parkinson disease. BMC Neurol 2011;11:88.
Caobelli F, Paghera B, Giubbini R. Is the time ripe to adopt semiquantitative analysis of SPECT evaluation in movement disorders as a standard? Eur J Nucl Med Mol Imaging 2011;38:596–7.
Nobili F, Campus C, Arnaldi D, De Carli F, Cabassi G, Brugnolo A, et al. Cognitive-nigrostriatal relationships in de novo, drug-naïve Parkinson’s disease patients: a [I-123]FP-CIT SPECT study. Mov Disord 2010;25:35–43.
Nobili F, Arnaldi D, Campus C, Ferrara M, De Carli F, Brugnolo A, et al. Brain perfusion correlates of cognitive and nigrostriatal functions in de novo Parkinson’s disease. Eur J Nucl Med Mol Imaging 2011;38:2209–18.
Arnaldi D, Campus C, Ferrara M, Famà F, Picco A, De Carli F, et al. What predicts cognitive decline in de novo Parkinson’s disease? Neurobiol Aging 2012;33:1127.e11–20.
Darcourt J, Booij J, Tatsch K, Varrone A, Vander Borght T, Kapucu OL, et al. EANM procedure guidelines for brain neurotransmission SPECT using (123)I-labelled dopamine transporter ligands, version 2. Eur J Nucl Med Mol Imaging 2010;37:443–50.
Lavalaye J, Booij J, Reneman L, Habraken JBA, van Royen EA. Effect of age and gender on dopamine transporter imaging with [123I]FP-CIT SPECT in healthy volunteers. Eur J Nucl Med 2000;27:867–9.
de Rijk MC, Launer LJ, Berger K, Breteler MM, Dartigues JF, Baldereschi M, et al. Prevalence of Parkinson’s disease in Europe: a collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group. Neurology 2000;54(11 Suppl 5):S21–3.
Staley JK, Krishnan-Sarin S, Zoghbi S, Tamagnan G, Fujita M, Seibyl JP, et al. Sex differences in [123I]beta-CIT SPECT measures of dopamine and serotonin transporter availability in healthy smokers and nonsmokers. Synapse 2001;41:275–84.
Mozley LH, Gur RC, Mozley PD, Gur RE. Striatal dopamine transporters and cognitive functioning in healthy men and women. Am J Psychiatry 2001;158:1492–9.
de Rijk MC, Tzourio C, Breteler MM, Dartigues JF, Amaducci L, Lopez-Pousa S, et al. Prevalence of parkinsonism and Parkinson’s disease in Europe: the EUROPARKINSON Collaborative Study. European Community Concerted Action on the Epidemiology of Parkinson’s disease. J Neurol Neurosurg Psychiatry 1997;62:10–5.
Ryding E, Lindström M, Brådvik B, Grabowski M, Bosson P, Träskman-Bendz L, et al. A new model for separation between brain dopamine and serotonin transporters in 123I-beta-CIT SPECT measurements: normal values and sex and age dependence. Eur J Nucl Med Mol Imaging 2004;31:1114–8.
Gunning-Dixon FM, Head D, McQuain J, Acker JD, Raz N. Differential aging of the human striatum: a prospective MR imaging study. AJNR Am J Neuroradiol 1998;19:1501–7.
van Dyck CH, Seibyl JP, Malison RT, Laruelle M, Zoghbi SS, Baldwin RM, et al. Age-related decline in dopamine transporters: analysis of striatal subregions, nonlinear effects, and hemispheric asymmetries. Am J Geriatr Psychiatry 2002;10:36–43.
Kazumata K, Dhawan V, Chaly T, Antonini A, Margouleff C, Belakhlef A, et al. Dopamine transporter imaging with fluorine-18-FPCIT and PET. J Nucl Med 1998;39:1521–30.
Rinne JO, Sahlberg N, Ruottinen H, Någren K, Lehikoinen P. Striatal uptake of the dopamine reuptake ligand [11C]beta-CFT is reduced in Alzheimer’s disease assessed by positron emission tomography. Neurology 1998;50:152–6.
Ishibashi K, Ishii K, Oda K, Kawasaki K, Mizusawa H, Ishiwata K. Regional analysis of age-related decline in dopamine transporters and dopamine D2-like receptors in human striatum. Synapse 2009;63:282–90.
Gibb WR, Lees AJ. Anatomy, pigmentation, ventral and dorsal subpopulations of the substantia nigra, and differential cell death in Parkinson’s disease. J Neurol Neurosurg Psychiatry 1991;54:388–96.
Szabo J. Organization of the ascending striatal afferents in monkeys. J Comp Neurol 1980;189:307–21.
Koch W, Pogarell O, Pöpperl G, Hornung J, Hamann C, Gildehaus FJ, et al. Extended studies of the striatal uptake of 99mTc-NC100697 in healthy volunteers. J Nucl Med 2007;48:27–34.
Carpenter MB, Peter P. Nigrostriatal and nigrothalamic fibers in the rhesus monkey. J Comp Neurol 1972;144:93–116.
Nomoto M, Kaseda S, Iwata S, Shimizu T, Fukuda T, Nakagawa S. The metabolic rate and vulnerability of dopaminergic neurons, and adenosine dynamics in the cerebral cortex, nucleus accumbens, caudate nucleus, and putamen of the common marmoset. J Neurol 2000;247 Suppl 5:V16–22.
Chen PS, Yang YK, Yeh TL, Lee I-H, Yao WJ, Chiu NT, et al. Correlation between body mass index and striatal dopamine transporter availability in healthy volunteers—a SPECT study. Neuroimage 2008;40:275–9.
Ruhé HG, Booij J, Reitsma JB, Schene AH. Serotonin transporter binding with [123I]beta-CIT SPECT in major depressive disorder versus controls: effect of season and gender. Eur J Nucl Med Mol Imaging 2009;36:841–9.
Kalbitzer J, Erritzoe D, Holst KK, Nielsen FA, Marner L, Lehel S, et al. Seasonal changes in brain serotonin transporter binding in short serotonin transporter linked polymorphic region-allele carriers but not in long-allele homozygotes. Biol Psychiatry 2010;67:1033–9.
Eisenberg DP, Kohn PD, Baller EB, Bronstein JA, Masdeu JC, Berman KF. Seasonal effects on human striatal presynaptic dopamine synthesis. J Neurosci 2010;30:14691–4.
Sleipness EP, Sorg BA, Jansen HT. Diurnal differences in dopamine transporter and tyrosine hydroxylase levels in rat brain: dependence on the suprachiasmatic nucleus. Brain Res 2007;1129:34–42.
Varrone A, Dickson J, Tossici-Bolt L, Sera T, Asenbaum S, Booij J, et al. European multicentre database of healthy controls for [(123)I]FP-CIT SPECT (ENC-DAT): age-related effects, gender differences and evaluation of different methods of 3 analysis. Eur J Nucl Med Mol Imaging. doi:10.1007/s00259-012-2276-8.
Acknowledgments
The participating centres thank GE Healthcare and the German Parkinson Association for their financial contribution to this study, ABX-CRO for managing the network activities and the Executive Committee of the EANM for establishing the EANM Research Ltd. (EARL) as an administrative framework for this project. The authors also thank the personnel from each Nuclear Medicine Centre responsible for the quality controls and acquisition of the SPECT data.
Conflicts of interest
Prof. Jan Booij is a consultant for GE Healthcare.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Nobili, F., Naseri, M., De Carli, F. et al. Automatic semi-quantification of [123I]FP-CIT SPECT scans in healthy volunteers using BasGan version 2: results from the ENC-DAT database. Eur J Nucl Med Mol Imaging 40, 565–573 (2013). https://doi.org/10.1007/s00259-012-2304-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00259-012-2304-8