SPECT imaging evaluation in movement disorders: far beyond visual assessment

  • Kosmas BadiavasEmail author
  • Elisavet Molyvda
  • Ioannis Iakovou
  • Magdalini Tsolaki
  • Kyriakos Psarrakos
  • Nikolaos Karatzas
Review Article


Single photon emission computed tomography (SPECT) imaging with 123I-FP-CIT is of great value in differentiating patients suffering from Parkinson’s disease (PD) from those suffering from essential tremor (ET). Moreover, SPECT with 123I-IBZM can differentiate PD from Parkinson’s “plus” syndromes. Diagnosis is still mainly based on experienced observers’ visual assessment of the resulting images while many quantitative methods have been developed in order to assist diagnosis since the early days of neuroimaging. The aim of this work is to attempt to categorize, briefly present and comment on a number of semi-quantification methods used in nuclear medicine neuroimaging. Various arithmetic indices have been introduced with region of interest (ROI) manual drawing methods giving their place to automated procedures, while advancing computer technology has allowed automated image registration, fusion and segmentation to bring quantification closer to the final diagnosis based on the whole of the patient’s examinations results, clinical condition and response to therapy. The search for absolute quantification has passed through neuroreceptor quantification models, which are invasive methods that involve tracer kinetic modelling and arterial blood sampling, a practice that is not commonly used in a clinical environment. On the other hand, semi-quantification methods relying on computers and dedicated software try to elicit numerical information out of SPECT images. The application of semi-quantification methods aims at separating the different patient categories solving the main problem of finding the uptake in the structures of interest. The semi-quantification methods which were studied fall roughly into three categories, which are described as classic methods, advanced automated methods and pixel-based statistical analysis methods. All these methods can be further divided into various subcategories. The plethora of the existing semi-quantitative methods reinforces the feeling that visual assessment is still the base of image interpretation and that the unambiguous numerical results that will allow the absolute differentiation between the known diseases have not been standardized yet. Switching to a commonly agreed—ideally PC-based—automated software that may take raw or mildly processed data (checked for consistency and maybe corrected for attenuation and/or scatter and septal penetration) as input, work with basic operator’s inference and produce validated numerical results that will support the diagnosis is in our view the aim towards which efforts should be directed. After all, semi-quantification can improve sensitivity, strengthen diagnosis, aid patient’s follow-up and assess the response to therapy. Objective diagnosis, altered diagnosis in marginal cases and a common approach to multicentre trials are other benefits and future applications of semi-quantification.


Parkinson Neuroimaging SPECT 123I-FP-CIT 123I-IBZM Semi-quantification ROI analysis Statistical parametric mapping 


Conflicts of interest



  1. 1.
    Hornykiewicz O. Dopamine (3-hydroxytyramine) and brain function. Pharmacol Rev 1966;18:925–64.PubMedGoogle Scholar
  2. 2.
    Jankovic J. Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry 2008;79:368–76.PubMedCrossRefGoogle Scholar
  3. 3.
    Kung HF, Pan S, Kung MP, Billings J, Kasliwal R, Reilley J, et al. In vitro and in vivo evaluation of [123I]IBZM: a potential CNS D-2 dopamine receptor imaging agent. J Nucl Med 1989;30:88–92.PubMedGoogle Scholar
  4. 4.
    Kung HF, Alavi A, Chang W, Kung MP, Keyes JW, Velchik MG, et al. In vivo SPECT imaging of CNS D-2 dopamine receptors: initial studies with iodine-123-IBZM in humans. J Nucl Med 1990;31:573–9.PubMedGoogle Scholar
  5. 5.
    Brücke T, Podreka I, Angelberger P, Wenger S, Topitz A, Küfferle B, et al. Dopamine D2 receptor imaging with SPECT: studies in different neuropsychiatric disorders. J Cereb Blood Flow Metab 1991;11:220–8.PubMedGoogle Scholar
  6. 6.
    Tatsch K, Schwartz J, Oertel WH, Kirsch CM. SPECT imaging of dopamine D2 receptors with 123I-IBZM: initial experience in controls and patients with Parkinson’s syndrome and Wilson’s disease. Nucl Med Commun 1991;12:699–707.PubMedCrossRefGoogle Scholar
  7. 7.
    Seibyl JP, Wallace E, Smith EO, Stabin M, Baldwin RM, Zoghbi S, et al. Whole-body biodistribution, radiation absorbed dose and brain SPECT imaging with iodine-123-β-CIT in healthy human subjects. J Nucl Med 1994;35:764–70.PubMedGoogle Scholar
  8. 8.
    Booij J, Tissingh G, Boer GJ, Speelman JD, Stoof JC, Janssen AG, et al. [123I]FP-CIT SPECT shows a pronounced decline of striatal dopamine transporter labelling in early and advanced Parkinson’s disease. J Neurol Neurosurg Psychiatry 1997;62:133–40.PubMedCrossRefGoogle Scholar
  9. 9.
    Asenbaum S, Pirker W, Angelberger P, Bencsits G, Pruckmayer M, Brücke T. [123I]beta-CIT and SPECT in essential tremor and Parkinson’s disease. J Neural Transm 1998;105:1213–28.PubMedCrossRefGoogle Scholar
  10. 10.
    Gerasimou G, Tsolaki M, Bostanjopoulou S, Liaros G, Papanastasiou E, Balaris V, et al. Findings from molecular imaging with SPET camera and 123I-ioflupane in the differential diagnosis of Parkinsonism and essential tremor. Hell J Nucl Med 2005;8(2):81–5.PubMedGoogle Scholar
  11. 11.
    Marshall V, Grosset D. Role of dopamine transporter imaging in routine clinical practice. Mov Disord 2003;18(12):1415–23.PubMedCrossRefGoogle Scholar
  12. 12.
    Tatsch K, Asenbaum S, Bartenstein P, Catafau A, Halldin C, Pilowsky LS, et al. European Association of Nuclear Medicine procedure guidelines for brain neurotransmission SPET using (123)I-labelled dopamine D(2) receptor ligands. Eur J Nucl Med Mol Imaging 2002;29:BP23–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Van Laere K, Varone A, Booij J, Vander Borght T, Nobili F, Kapucu OL, et al. EANM procedure guidelines for brain neurotransmission SPECT/PET using dopamine D2 receptor ligands, version 2. Eur J Nucl Med Mol Imaging 2010;37:434–42. doi: 10.1007/s00259-009-1265-z.PubMedCrossRefGoogle Scholar
  14. 14.
    Tatsch K, Asenbaum S, Bartenstein P, Catafau A, Halldin C, Pilowsky LS, et al. European Association of Nuclear Medicine procedure guidelines for brain neurotransmission SPET using (123)I-labelled dopamine D(2) transporter ligands. Eur J Nucl Med Mol Imaging 2002;29:BP30–5.PubMedCrossRefGoogle Scholar
  15. 15.
    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. doi: 10.1007/s00259-009-1267-x.PubMedCrossRefGoogle Scholar
  16. 16.
    Koch W, Hamann C, Radau PE, Tatsch K. Does combined imaging of the pre- and postsynaptic dopaminergic system increase the diagnostic accuracy in the differential diagnosis of parkinsonism? Eur J Nucl Med Mol Imaging 2007;34:1265–73.PubMedCrossRefGoogle Scholar
  17. 17.
    Costa DC, Verhoeff NPLG, Cullum ID, Ell PJ, Syed GM, Barrett J, et al. In vivo characterization of 3-iodo-6-methoxybenzamide 123I in humans. Eur J Nucl Med 1990;16:813–6.PubMedCrossRefGoogle Scholar
  18. 18.
    Neumeyer JL, Wang S, Millius RA, Baldwin RM, Zia-Ponce Y, Hoffer PB, et al. [123I]-2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane: high-affinity SPECT radiotracer of monoamine reuptake sites in brain. J Med Chem 1991;34:3144–6.PubMedCrossRefGoogle Scholar
  19. 19.
    Kuikka JT, Bergström KA, Vanninen E, Laulumaa V, Hartikainen P, Länsimies E. Initial experience with single-photon emission tomography using iodine-123-labelled 2β-carbomethoxy-3β-(4-iodophenyl)tropane in human brain. Eur J Nucl Med 1993;20:783–6.PubMedCrossRefGoogle Scholar
  20. 20.
    Seibyl JP, Marek KL, Quinlan D, Sheff K, Zoghbi S, Zea-Ponce Y, et al. Decreased single-photon emission computed tomographic [123I]β-CIT striatal uptake correlates with symptom severity in Parkinson’s disease. Ann Neurol 1995;38:589–98.PubMedCrossRefGoogle Scholar
  21. 21.
    Kung HF, Kim HJ, Kung MP, Meegalla SK, Plössl K, Lee HK. Imaging of dopamine transporters in humans with technetium-99m TRODAT-1. Eur J Nucl Med 1996;23:1527–30.PubMedCrossRefGoogle Scholar
  22. 22.
    Booij J, Tissingh G, Winogrodzka A, van Royen EA. Imaging of the dopaminergic neurotransmission system using single-photon emission tomography and positron emission tomography in patients with parkinsonism. Eur J Nucl Med 1999;26:171–82.PubMedCrossRefGoogle Scholar
  23. 23.
    Innis RB, Seibyl JP, Scanley BE, Laruelle M, Abi-Dargham A, Wallace E, et al. Single photon emission computed tomographic imaging demonstrates loss of striatal dopamine transporters in Parkinson disease. Proc Natl Acad Sci U S A 1993;90:11965–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Booij J, Tissingh G, Winogrodzka A, Boer GJ, Stoof JC, Wolter EC, et al. Practical benefit of [123I]FP-CIT SPET in the demonstration of the dopaminergic deficit in Parkinson’s disease. Eur J Nucl Med 1997;24:68–71.PubMedCrossRefGoogle Scholar
  25. 25.
    Staffen W, Mair A, Unterrainer J, Trinka E, Ladurner G. Measuring the progression of idiopathic Parkinson’s disease with [123I] beta-CIT SPECT. J Neural Transm 2000;107:543–52.PubMedCrossRefGoogle Scholar
  26. 26.
    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.PubMedCrossRefGoogle Scholar
  27. 27.
    Asenbaum S, Brücke T, Pirker W, Podreka I, Angelberger P, Wenger S, et al. Imaging of dopamine transporters with iodine-123-β-CIT and SPECT in Parkinson’s disease. J Nucl Med 1997;38:1–6.PubMedGoogle Scholar
  28. 28.
    Verhoeff NP, Kapucu O, Sokole-Busemann E, van Royen EA, Janssen AG. Estimation of dopamine D2 receptor binding potential in the striatum with iodine-123-IBZM SPECT: technical and interobserver variability. J Nucl Med 1993;34:2076–84.PubMedGoogle Scholar
  29. 29.
    Ichise M, Meyer JH, Yonekura Y. An introduction to PET and SPECT neuroreceptor quantification models. J Nucl Med 2001;42:755–63.PubMedGoogle Scholar
  30. 30.
    Habraken JB, 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.PubMedGoogle Scholar
  31. 31.
    Booij J, Speelman JD, Horstink MWIM, Wolters EC. The clinical benefit of imaging striatal dopamine transporters with [123I]FP-CIT SPET in differentiating patients with presynaptic parkinsonism from those with other forms of parkinsonism. Eur J Nucl Med 2001;28:266–72.PubMedCrossRefGoogle Scholar
  32. 32.
    Seibyl JP, Marek K, Sheff K, Baldwin RM, Zoghbi S, Zea-Ponce Y, et al. Test/retest reproducibility of iodine-123-betaCIT SPECT brain measurement of dopamine transporters in Parkinson’s patients. J Nucl Med 1997;38:1453–9.PubMedGoogle Scholar
  33. 33.
    Baulieu JL, Ribeiro MJ, Levilon-Prunier C, Tranquart F, Chartier JR, Guilloteau D, et al. Effects of the method of drawing regions of interest on the differential diagnosis of extrapyramidal syndromes using 123I-iodolisuride SPET. Nucl Med Commun 1999;20:77–84.PubMedCrossRefGoogle Scholar
  34. 34.
    Badiavas K, Iakovou I, Molyvda E, et al. Creation of a customized normal database for 123I-FP-CIT SPECT studies in a major nuclear medicine department in Northern Greece. Eur J Nucl Med Mol Imaging 2010;37 Suppl 2:S399.Google Scholar
  35. 35.
    Seppi K, Schocke MFH. An update on conventional and advanced magnetic resonance imaging techniques in the differential diagnosis of neurodegenerative parkinsonism. Curr Opin Neurol 2005;18:370–5.PubMedCrossRefGoogle Scholar
  36. 36.
    Koole M, Laere KV, de Walle RV, Vandenberghe S, Bouwens L, Lernahieu 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.PubMedCrossRefGoogle Scholar
  37. 37.
    Rojas GM, Raff U, Quintana JC, Huete I, Hutchinson M. Image fusion in neuroradiology: three clinical examples including MRI of Parkinson disease. Comput Med Imaging Graph 2007;31:17–27.PubMedCrossRefGoogle Scholar
  38. 38.
    van der Wee NJ, van Veen JF, Stevens H, van Vliet IM, van Rijk PP, Westenberg HG. Increased serotonin and dopamine transporter binding in psychotropic medication-naïve patients with generalized social anxiety disorder shown by 123I-β-(4-iodophenyl)-tropane SPECT. J Nucl Med 2008;49:757–63.PubMedCrossRefGoogle Scholar
  39. 39.
    Fleming JS, Bolt L, Stratford JS, Kemp PM. The specific uptake size index for quantifying radiopharmaceutical uptake. Phys Med Biol 2004;49:N227–34.PubMedCrossRefGoogle Scholar
  40. 40.
    Tossici-Bolt L, Hoffmann SMA, Kemp PM, Mehta RL, Fleming JS. Quantification of [123I]FP-CIT SPECT brain images: an accurate technique for measurement of the specific binding ratio. Eur J Nucl Med Mol Imaging 2006;33:1491–9.PubMedCrossRefGoogle Scholar
  41. 41.
    Dobbeleir AA, Hambye AE, Vervaet AM, Ham HR. Quantification of iodine-123-FP-CIT SPECT with a resolution-independent method. World J Nucl Med 2005;4(4):252–61.Google Scholar
  42. 42.
    Goethals I, Dobbeleir A, Ham H, Santens P, D’Asseler Y. Validation of a resolution-independent method for the quantification of 123I-FP-CIT SPECT scans. Nucl Med Commun 2007;28:771–4.PubMedCrossRefGoogle Scholar
  43. 43.
    Løkkegaard A, Werdelin LM, Friberg L. Clinical impact of diagnostic SPET investigations with a dopamine re-uptake ligand. Eur J Nucl Med Mol Imaging 2002;29:1623–9.PubMedCrossRefGoogle Scholar
  44. 44.
    Morton RJ, Guy MJ, Marshall CA, Clarke EA, Hinton PJ. Variation of DaTSCAN quantification between different gamma camera types. Nucl Med Commun 2005;26:1131–7.PubMedCrossRefGoogle Scholar
  45. 45.
    Morton RJ, Guy MT, Clauss R, Hinton PJ, Marshall CA, Clarke EA. Comparison of different methods of DatSCAN quantification. Nucl Med Commun 2005;26:1139–46.PubMedCrossRefGoogle Scholar
  46. 46.
    Lee JD, Huang CH, Weng YH, Lin KJ, Chen CT. An automatic MRI/SPECT registration algorithm using image intensity and anatomical feature as matching characters: application on the evaluation of Parkinson’s disease. Nucl Med Biol 2007;34:447–57.PubMedCrossRefGoogle Scholar
  47. 47.
    Lee JD, Chen CW, Huang CH. Computer-aided evaluation system for Parkinson’s disease using image registration and labeling. Proceedings of the 29th Annual International Conference of the IEEE EMBS. 2007: 844–7.Google Scholar
  48. 48.
    Zubal IG, Early M, Yuan O, Jennings D, Marek K, Seibyl JP. Optimized, automated striatal uptake analysis applied to SPECT brain scans of Parkinson’s disease patients. J Nucl Med 2007;48:857–64.PubMedCrossRefGoogle Scholar
  49. 49.
    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.PubMedCrossRefGoogle Scholar
  50. 50.
    Talairach J, Tournoux P. Co-planar stereotaxic atlas of the human brain. New York: Thieme; 1988.Google Scholar
  51. 51.
    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.PubMedGoogle Scholar
  52. 52.
    Pöpperl G, Radau P, Linke R, Hahn K, Tatsch K. Diagnostic performance of a 3-D automated quantification method of dopamine D2 receptor SPECT studies in the differential diagnosis of parkinsonism. Nucl Med Commun 2005;26:39–43.PubMedCrossRefGoogle Scholar
  53. 53.
    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.PubMedGoogle Scholar
  54. 54.
    Hamilton D, List A, Butler T, Hogg S, Cawley M. Discrimination between parkinsonian syndrome and essential tremor using artificial neural network classification of quantified DaTSCAN data. Nucl Med Commun 2006;27:939–44.PubMedCrossRefGoogle Scholar
  55. 55.
    Friston KJ, Ashburner J, Frith CD, Poline JB, Heather JD, Frackowiak RS. Spatial registration and normalization of images. Hum Brain Mapp 1995;3:165–89.CrossRefGoogle Scholar
  56. 56.
    Friston KJ, Holmes AP, Worsley KJ, Poline JP, Frith CD, Frackowiak RS. Statistical parametric maps in functional imaging: a general linear approach. Hum Brain Mapp 1994;2:189–210.CrossRefGoogle Scholar
  57. 57.
    Scherfler C, Seppi K, Donnemiller E, Goebel G, Brenneis C, Virgolini I, et al. Voxel-wise analysis of [123I]β-CIT SPECT differentiates the Parkinson variant of multiple system atrophy from idiopathic Parkinson’s disease. Brain 2005;128:1605–12.PubMedCrossRefGoogle Scholar
  58. 58.
    Seppi K, Scherfler C, Donnemiller E, Virgolini I, Schocke MF, Goebel G, et al. Topography of dopamine transporter availability in progressive supranuclear palsy: a voxelwise [123I]β-CIT SPECT analysis. Arch Neurol 2006;63:1154–60.PubMedCrossRefGoogle Scholar
  59. 59.
    Colloby SJ, O’Brien JT, Fenwick JD, Firbank MJ, Burn DJ, McKeith IG, et al. The application of statistical parametric mapping to 123I-FP-CIT SPECT in dementia with Lewy bodies, Alzheimer’s disease and Parkinson’s disease. Neuroimage 2004;23(3):956–66.PubMedCrossRefGoogle Scholar
  60. 60.
    Minoshima S, Koeppe RA, Frey KA, Kuhl DE. Anatomic standardization: linear scaling and nonlinear warping of functional brain images. J Nucl Med 1994;35:1528–37.PubMedGoogle Scholar
  61. 61.
    Hosaka K, Ishii K, Sakamoto S, Sadato N, Fukuda H, Kato T, et al. Validation of anatomical standardization of FDG PET images of normal brain: comparison of SPM and NEUROSTAT. Eur J Nucl Med Mol Imaging 2005;32:92–7.PubMedCrossRefGoogle Scholar
  62. 62.
    Takada S, Yoshimura M, Shindo H, Saito K, Koizumi K, Utsumi H, et al. New semiquantitative assessment of 123I-FP-CIT by an anatomical standardization method. Ann Nucl Med 2006;20(7):477–84.PubMedCrossRefGoogle Scholar
  63. 63.
    Buchert R, Berding G, Wilke F, Martin B, von Borczyskowski D, Mester J, et al. IBZM tool: a fully automated expert system for the evaluation of IBZM SPECT studies. Eur J Nucl Med Mol Imaging 2006;33:1073–83.PubMedCrossRefGoogle Scholar
  64. 64.
    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.PubMedCrossRefGoogle Scholar
  65. 65.
    Habraken JB, Booji J, Slomka P, Sokole EB, van Royen EA. Quantification and visualization of defects of the functional dopaminergic system using an automated algorithm. J Nucl Med 1999;40:1091–7.PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Kosmas Badiavas
    • 1
    Email author
  • Elisavet Molyvda
    • 2
  • Ioannis Iakovou
    • 3
  • Magdalini Tsolaki
    • 4
  • Kyriakos Psarrakos
    • 2
  • Nikolaos Karatzas
    • 3
  1. 1.Medical Physics Department“Papageorgiou” General HospitalThessalonikiGreece
  2. 2.Medical Physics DepartmentAristotle UniversityThessalonikiGreece
  3. 3.3rd Nuclear Medicine DepartmentAristotle University, “Papageorgiou” General HospitalThessalonikiGreece
  4. 4.3rd Neurology ClinicAristotle University, “Papanikolaou” General HospitalThessalonikiGreece

Personalised recommendations