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Physiological Whole-Brain Distribution of [18F]FDOPA Uptake Index in Relation to Age and Gender: Results from a Voxel-Based Semi-quantitative Analysis

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Abstract

Purpose

6-[18F]fluoro-l-DOPA ([18F]FDOPA), a positron emission tomography (PET) amino-acid tracer of brain decarboxylase activity, is used to assess the brain dopaminergic system. Using a voxel-based semi-quantitative analysis, this study aimed to determine whether a current brain uptake index of [18F]FDOPA, expressed relative to the occipital background level, varies according to age and gender.

Procedures

One hundred and seventy-seven subjects were retrospectively included. A whole-brain statistical parametric mapping analysis of the [18F]FDOPA uptake index in parametric PET images was performed at a voxel threshold of p < 0.05 (corrected) and p < 0.005 (uncorrected, k cluster > 125).

Results

Striatal uptake indices were influenced by age, negatively for the caudate nucleus and positively for the putamen, as well as by gender, with a lower left putaminal uptake index in women. Extra-striatal uptake indices were influenced by age, negatively for the frontal cortex and brainstem and positively for the occipital cortex and cerebellum, as well as by gender (diffuse increase in women).

Conclusions

The uptake index of [18F]FDOPA exhibited significant physiological variations according to age and gender and should therefore be considered for PET interpretation.

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References

  1. Darcourt J, Schiazza A, Sapin N, Dufour M, Ouvrier MJ, Benisvy D, Fontana X, Koulibaly PM (2014) 18F-FDOPA PET for the diagnosis of parkinsonian syndromes. Q J Nucl Med Mol Imaging 58:355–365

    CAS  PubMed  Google Scholar 

  2. Ikemoto S (2010) Brain reward circuitry beyond the mesolimbic dopamine system: a neurobiological theory. Neurosci Biobehav Rev 35:129–150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Kumakura Y, Cumming P (2009) PET studies of cerebral levodopa metabolism: a review of clinical findings and modeling approaches. Neuroscientist 15:635–650

    Article  CAS  PubMed  Google Scholar 

  4. Lopes Alves I, Meles SK, Willemsen AT et al (2017) Dual time point method for the quantification of irreversible tracer kinetics: a reference tissue approach applied to [18F]-FDOPA brain PET. J Cereb Blood Flow Metab 37:3124–3134

    Article  CAS  PubMed  Google Scholar 

  5. Kuwabara H, Cumming P, Reith J, Léger G, Diksic M, Evans AC, Gjedde A (1993) Human striatal L-dopa decarboxylase activity estimated in vivo using 6-[18F]fluoro-dopa and positron emission tomography: error analysis and application to normal subjects. J Cereb Blood Flow Metab 13:43–56

    Article  CAS  PubMed  Google Scholar 

  6. Jaimini A, Tripathi M, D’Souza MM, Panwar P, Sharma R, Mehta S, Pandey S, Saw S, Singh D, Solanki Y, Mishra AK, Mondal A (2013) Utility of intrastriatal ratios of FDOPA to differentiate idiopathic Parkinson’s disease from atypical parkinsonian disorders. Nucl Med Commun 34:426–431

    Article  CAS  PubMed  Google Scholar 

  7. Struck AF, Hall LT, Kusmirek JE, Gallagher CL, Floberg JM, Jaskowiak CJ, Perlman SB (2012) 18F-DOPA PET with and without MRI fusion, a receiver operator characteristics comparison. Am J Nucl Med Mol Imaging 2:475–482

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Chang I-C, Lue K-H, Hsieh H-J, Liu SH, Kao CHK (2011) Automated striatal uptake analysis of 18F-FDOPA PET images applied to Parkinson’s disease patients. Ann Nucl Med 25:796–803

    Article  PubMed  Google Scholar 

  9. Jokinen P, Helenius H, Rauhala E, Bruck A, Eskola O, Rinne JO (2009) Simple ratio analysis of 18F-fluorodopa uptake in striatal subregions separates patients with early Parkinson disease from healthy controls. J Nucl Med 50:893–899

    Article  PubMed  Google Scholar 

  10. Gispert JD, Pascau J, Reig S, Martínez-Lázaro R, Molina V, García-Barreno P, Desco M (2003) Influence of the normalization template on the outcome of statistical parametric mapping of PET scans. NeuroImage 19:601–612

    Article  CAS  PubMed  Google Scholar 

  11. Dhawan V, Ma Y, Pillai V, Spetsieris P, Chaly T, Belakhlef A, Margouleff C, Eidelberg D (2002) Comparative analysis of striatal FDOPA uptake in Parkinson’s disease: ratio method versus graphical approach. J Nucl Med 43:1324–1330

    PubMed  Google Scholar 

  12. Eusebio A, Azulay J-P, Ceccaldi M, Girard N, Mundler O, Guedj E (2012) Voxel-based analysis of whole-brain effects of age and gender on dopamine transporter SPECT imaging in healthy subjects. Eur J Nucl Med Mol Imaging 39:1778–1783

    Article  CAS  PubMed  Google Scholar 

  13. Cordes M, Snow BJ, Cooper S, Schulzer M, Pate BD, Ruth TJ, Calne DB (1994) Age-dependent decline of nigrostriatal dopaminergic function: a positron emission tomographic study of grandparents and their grandchildren. Ann Neurol 36:667–670

    Article  CAS  PubMed  Google Scholar 

  14. Eidelberg D, Takikawa S, Dhawan V, Chaly T, Robeson W, Dahl R, Margouleff D, Moeller JR, Patlak CS, Fahn S (1993) Striatal 18F-dopa uptake: absence of an aging effect. J Cereb Blood Flow Metab 13:881–888

    Article  CAS  PubMed  Google Scholar 

  15. Sawle GV, Colebatch JG, Shah A, Brooks DJ, Marsden CD, Frackowiak RSJ (1990) Striatal function in normal aging: implications for Parkinson’s disease. Ann Neurol 28:799–804

    Article  CAS  PubMed  Google Scholar 

  16. Martin WR, Palmer MR, Patlak CS, Calne DB (1989) Nigrostriatal function in humans studied with positron emission tomography. Ann Neurol 26:535–542

    Article  CAS  PubMed  Google Scholar 

  17. Laakso A, Vilkman H, Bergman J, Haaparanta M, Solin O, Syvälahti E, Salokangas RKR, Hietala J (2002) Sex differences in striatal presynaptic dopamine synthesis capacity in healthy subjects. Biol Psychiatry 52:759–763

    Article  CAS  PubMed  Google Scholar 

  18. Gallagher CL, Bell B, Palotti M, Oh J, Christian BT, Okonkwo O, Sojkova J, Buyan-Dent L, Nickles RJ, Harding SJ, Stone CK, Johnson SC, Holden JE (2015) Anterior cingulate dopamine turnover and behavior change in Parkinson’s disease. Brain Imaging Behav 9:821–827

    Article  PubMed  PubMed Central  Google Scholar 

  19. Li CT, Palotti M, Holden JE, Oh J, Okonkwo O, Christian BT, Bendlin BB, Buyan-Dent L, Harding SJ, Stone CK, DeJesus OT, Nickles RJ, Gallagher CL (2014) A dual-tracer study of extrastriatal 6-[18F]fluoro-m-tyrosine and 6-[18F]-fluoro-L-dopa uptake in Parkinson’s disease. Synapse 68:325–331

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Jokinen P, Karrasch M, Brück A, Johansson J, Bergman J, Rinne JO (2013) Cognitive slowing in Parkinson’s disease is related to frontostriatal dopaminergic dysfunction. J Neurol Sci 329:23–28

    Article  CAS  PubMed  Google Scholar 

  21. Van Der Gucht A, Verger A, Guedj E et al (2015) Age-related changes in FDG brain uptake are more accurately assessed when applying an adaptive template to the SPM method of voxel-based quantitative analysis. Ann Nucl Med 29:921–928

    Article  Google Scholar 

  22. Hoffman JM, Melega WP, Hawk TC, Grafton SC, Luxen A, Mahoney DK, Barrio JR, Huang SC, Mazziotta JC, Phelps ME (1992) The effects of carbidopa administration on 6-[18F]fluoro-L-DOPA kinetics in positron emission tomography. J Nucl Med 33:1472–1477

    CAS  PubMed  Google Scholar 

  23. García-Gómez FJ, García-Solís D, Luis-Simón FJ, Marín-Oyaga VA, Carrillo F, Mir P, Vázquez-Albertino RJ (2013) Elaboration of the SPM template for the standardization of SPECT images with 123I-Ioflupane. Rev Esp Med Nucl E Imagen Mol 32:350–356

    Google Scholar 

  24. Whitford TJ, Rennie CJ, Grieve SM, Clark CR, Gordon E, Williams LM (2007) Brain maturation in adolescence: concurrent changes in neuroanatomy and neurophysiology. Hum Brain Mapp 28:228–237

    Article  PubMed  Google Scholar 

  25. Sowell ER, Peterson BS, Thompson PM, Welcome SE, Henkenius AL, Toga AW (2003) Mapping cortical change across the human life span. Nat Neurosci 6:309–315

    Article  CAS  PubMed  Google Scholar 

  26. Grieve SM, Clark CR, Williams LM, Peduto AJ, Gordon E (2005) Preservation of limbic and paralimbic structures in aging. Hum Brain Mapp 25:391–401

    Article  PubMed  Google Scholar 

  27. Taki Y, Thyreau B, Kinomura S, Sato K, Goto R, Kawashima R, Fukuda H (2011) Correlations among brain gray matter volumes, age, gender, and hemisphere in healthy individuals. PLoS One 6:e22734. https://doi.org/10.1371/journal.pone.0022734

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Long X, Liao W, Jiang C, Liang D, Qiu B, Zhang L (2012) Healthy aging: an automatic analysis of global and regional morphological alterations of human brain. Acad Radiol 19:785–793

    Article  PubMed  Google Scholar 

  29. Driscoll I, Davatzikos C, An Y, Wu X, Shen D, Kraut M, Resnick SM (2009) Longitudinal pattern of regional brain volume change differentiates normal aging from MCI. Neurology 72:1906–1913

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Fjell AM, Westlye LT, Amlien I, Espeseth T, Reinvang I, Raz N, Agartz I, Salat DH, Greve DN, Fischl B, Dale AM, Walhovd KB (2009) High consistency of regional cortical thinning in aging across multiple samples. Cereb Cortex 19:2001–2012

    Article  PubMed  PubMed Central  Google Scholar 

  31. Bauer E, Toepper M, Gebhardt H, Gallhofer B, Sammer G (2015) The significance of caudate volume for age-related associative memory decline. Brain Res 1622:137–148

    Article  CAS  PubMed  Google Scholar 

  32. Madsen SK, Ho AJ, Hua X, Saharan PS, Toga AW, Jack CR Jr, Weiner MW, Thompson PM, Alzheimer's Disease Neuroimaging Initiative (2010) 3D maps localize caudate nucleus atrophy in 400 Alzheimer’s disease, mild cognitive impairment, and healthy elderly subjects. Neurobiol Aging 31:1312–1325

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Hosp JA, Luft AR (2013) Dopaminergic meso-cortical projections to m1: role in motor learning and motor cortex plasticity. Front Neurol 4:145

    Article  PubMed  PubMed Central  Google Scholar 

  34. Giompres P, Delis F (2005) Dopamine transporters in the cerebellum of mutant mice. Cerebellum 4:105–111

    Article  CAS  PubMed  Google Scholar 

  35. Houk JC, Wise SP (1995) Distributed modular architectures linking basal ganglia, cerebellum, and cerebral cortex: their role in planning and controlling action. Cereb Cortex 5:95–110

    Article  CAS  PubMed  Google Scholar 

  36. Varrone A, Dickson JC, Tossici-Bolt L, Sera T, Asenbaum S, Booij J, Kapucu OL, Kluge A, Knudsen GM, Koulibaly PM, Nobili F, Pagani M, Sabri O, Vander Borght T, van Laere K, Tatsch K (2013) European multicentre database of healthy controls for [123I]FP-CIT SPECT (ENC-DAT): age-related effects, gender differences and evaluation of different methods of analysis. Eur J Nucl Med Mol Imaging 40:213–227

    Article  CAS  PubMed  Google Scholar 

  37. Yoshizawa H, Gazes Y, Stern Y, Miyata Y, Uchiyama S (2014) Characterizing the normative profile of 18F-FDG PET brain imaging: sex difference, aging effect, and cognitive reserve. Psychiatry Res 221:78–85

    Article  PubMed  Google Scholar 

  38. Willis MW, Ketter TA, Kimbrell TA, George MS, Herscovitch P, Danielson AL, Benson BE, Post RM (2002) Age, sex and laterality effects on cerebral glucose metabolism in healthy adults. Psychiatry Res 114:23–37

    Article  CAS  PubMed  Google Scholar 

  39. Ragland JD, Coleman AR, Gur RC, Glahn DC, Gur RE (2000) Sex differences in brain-behavior relationships between verbal episodic memory and resting regional cerebral blood flow. Neuropsychologia 38:451–461

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Verger A, Stegmayr C, Galldiks N et al (2018) Evaluation of factors influencing 18F-FET uptake in the brain. Neuroimage Clin 17:491

    Article  PubMed  Google Scholar 

  41. Niven E, Thompson M, Nahmias C (2001) Absorbed dose to the adult male and female brain from 18F-fluorodeoxyglucose. Health Phys 80:62–66

    Article  CAS  PubMed  Google Scholar 

  42. Kordower JH, Olanow CW, Dodiya HB, Chu Y, Beach TG, Adler CH, Halliday GM, Bartus RT (2013) Disease duration and the integrity of the nigrostriatal system in Parkinson’s disease. Brain J Neurol 136:2419–2431

    Article  Google Scholar 

  43. Gallagher CL, Oakes TR, Johnson SC, Chung MK, Holden JE, Bendlin BB, McLaren DG, Xu G, Nickles RJ, Pyzalski R, DeJesus O, Brown WD (2011) Rate of 6-[18F]fluoro-L-dopa uptake decline in striatal subregions in Parkinson’s disease. Mov Disord 26:614–620

    Article  PubMed  PubMed Central  Google Scholar 

  44. Soret M, Bacharach SL, Buvat I (2007) Partial-volume effect in PET tumor imaging. J Nucl Med 48:932–945

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors thank Pierre Pothier for the critical review of the manuscript.

Author information

Authors and Affiliations

  1. Department of Nuclear Medicine & Nancyclotep Imaging Platform, CHRU Nancy, Lorraine University, Nancy, France

    Sinn-Rithy Toch, Sylvain Poussier, Elodie Chevalier, Pierre-Yves Marie & Antoine Verger

  2. Lorraine University, INSERM, IADI, Nancy, France

    Sylvain Poussier, Emilien Micard & Antoine Verger

  3. Department of Nuclear Medicine, APHP Pitié Salpêtrière, Paris, France

    Marc Bertaux

  4. Departments of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Lausanne, Switzerland

    Axel Van Der Gucht

  5. INSERM, UMR 1116, Lorraine University, Nancy, France

    Pierre-Yves Marie

  6. Aix Marseille Univ, CNRS, Centrale Marseille, Institut Fresnel, Marseille, France

    Eric Guedj

  7. Department of Biophysics & Nuclear Medicine, APHM Timone, Marseille, France

    Eric Guedj

  8. European Research Center in Nuclear Medicine, CERIMED, Marseille, France

    Eric Guedj

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  1. Sinn-Rithy Toch
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  8. Eric Guedj
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  9. Antoine Verger
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Correspondence to Antoine Verger.

Ethics declarations

This retrospective study was approved on June 27, 2017 by the local institutional review board (IRB) and the Ethics Committee (CPP Est III).

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

For this type of study, formal consent is not required. Informed consent was obtained from all individual participants included in the study.

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Toch, SR., Poussier, S., Micard, E. et al. Physiological Whole-Brain Distribution of [18F]FDOPA Uptake Index in Relation to Age and Gender: Results from a Voxel-Based Semi-quantitative Analysis. Mol Imaging Biol 21, 549–557 (2019). https://doi.org/10.1007/s11307-018-1256-1

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  • DOI: https://doi.org/10.1007/s11307-018-1256-1

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