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Regional CBF changes in Parkinson’s disease: a correlation with motor dysfunction

Abstract

Purpose

The purpose of this study was to further localize cerebral perfusion abnormalities, and to better correlate these abnormalities with the clinical severity of Parkinson’s disease (PD).

Methods

A single-photon emission computed tomography (SPECT) study was performed on 27 patients with PD and 24 age-matched controls. SPECT images were spatially normalized, concatenated, and then decomposed using Infomax independent component analysis (ICA). The resulting image components were separated by logistic regression into two subspaces: “disease-related” components whose subject weights differed between groups, and “disease-unrelated” components. The resultant regional cerebral blood flow (rCBF) subspace images were normalized to global CBF for each subject, and then processed using statistical parametric mapping to compare rCBF values between PD and control subjects.

Results

In the disease-related image subspace, patients with PD exhibited significantly higher adjusted rCBF in the putamen, globus pallidum, thalamus, brainstem, and the anterior lobe of the cerebellum, and significant hypoperfusion in the parieto-temporo-occipital cortex, the dorsolateral prefrontal cortex, the insula, and the cingulate gyrus. The motor Unified Parkinson’s Disease Rating Scale scores correlated negatively with rCBF in the insula and cingulate gyrus. In the disease-unrelated image subspace, no brain voxels exhibited a significant group difference.

Conclusion

ICA-based separation of normalized images into disease-related and disease-unrelated subspaces revealed many disease-related group blood flow differences. The regions revealed by ICA are consistent with the current model of PD. These rCBF changes in PD have not been fully demonstrated in any single functional imaging study previously.

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References

  1. 1.

    Hornykiewcz O. Dopamine (3-hydroxytyramine) and brain function. Pharmacol Rev 1966;18:925–64.

    Google Scholar 

  2. 2.

    Albin RL, Young AB, Penney JB. The functional anatomy of basal ganglia disorders. Trends Neurosci 1989;12:366–75.

    PubMed  Article  CAS  Google Scholar 

  3. 3.

    Alexander GE, Crutcher MD. Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends Neurosci 1990;13:266–71.

    PubMed  Article  CAS  Google Scholar 

  4. 4.

    Holman BL, Johnson KA, Gerada B, Carvalho PA, Satlin A. The scintigraphic appearance of Alzheimer’s disease: a prospective study using technetium-99m-HMPAO SPECT. J Nucl Med 1992;32:181–5.

    Google Scholar 

  5. 5.

    Perlmutter JS, Raichle ME. Regional blood flow in hemiparkinsonism. Neurology 1985;35:1127–34.

    PubMed  CAS  Google Scholar 

  6. 6.

    Henriksen L, Boas J. Regional cerebral blood flow in hemiparkinsonian patients: emission computerized tompgraphy of inhaled 133Xenon before and after levodopa. Acta Neurol Scand 1985;71:257–66.

    PubMed  CAS  Article  Google Scholar 

  7. 7.

    Wolfson LI, Leenders KL, Brown LL, Jones T. Alterations of cerebral blood flow and oxygen metabolism in Parkinson’s disease. Neurology 1985;35:1399–405.

    PubMed  CAS  Google Scholar 

  8. 8.

    Pizzolato G, Dam M, Borsato N, Saitta B, Da Col C, Perlotto N, et al. 99mTc-HMPAO SPECT in Parkinson’s disease. J Cereb Blood Flow Metab 1988;8(suppl):S101–8.

    PubMed  CAS  Google Scholar 

  9. 9.

    Imon Y, Matsuda H, Ogawa M, Kogure D, Sunohara N. SPECT image analysis using statistical parametric mapping in patients with Parkinson’s disease. J Nucl Med 1999;40;1583–9.

    PubMed  CAS  Google Scholar 

  10. 10.

    Vaasinen V, Maguire RP, Hundemer HP, Leenders KL. Corticostriatal covariance patterns of 6-[F18]fluoro-L-dopa and [F18]fluorodeoxyglucose PET in Parkinson’s disease. J Neurol 2006;253:340–8.

    Article  Google Scholar 

  11. 11.

    Dujardin K, Defebvre L, Duhamel A, Lecouffe P, Rogelet P, Steinling M, et al. Cognitive and SPECT characteristics predict progression of Parkinson’s disease in newly diagnosed patients. J Neurol 2004;251:1383–92.

    PubMed  Article  Google Scholar 

  12. 12.

    Bell AJ, Sejnowski TJ. An information-maximization approach to blind separation and blind deconvolution. Neural Comput 1995;7(6):1129–59.

    PubMed  CAS  Google Scholar 

  13. 13.

    Jung T-P, Makeig S, McKeown MJ, Bell AJ, Lee T-W, Sejnowski TJ. Imaging brain dynamics using independent component analysis. Proc IEEE 2001;89:1107–22.

    Google Scholar 

  14. 14.

    McKeown MJ, Makeig S, Brown GG, Jung T-P, Kindermann SS, Sejnowski TJ. Analysis of fMRI by blind separation into independent spatial components. Hum Brain Mapp 1988:6:160–88.

    Article  Google Scholar 

  15. 15.

    Ward CD, Gibb WR. Research diagnostic criteria for Parkinson’s disease. Adv Neurol 1990;53:245–9.

    PubMed  CAS  Google Scholar 

  16. 16.

    Hoehn MM, Yahr MD. Parkinsonism: onset, progression and mortality. Neurology 1967;17:427–42.

    PubMed  CAS  Google Scholar 

  17. 17.

    Fahn S, Elton RL, Members of the UPDRS Development Committee. Unified Parkinson’s disease and movement disorders. In: Fahn S, Marsden CD, Calne DB, Goldstein M, editors. Recent developments in Parkinson’s disease vol 2. Florham Park: NJ Mcmillan Health Care Information; 1987. pp. 153–64.

    Google Scholar 

  18. 18.

    Chang LT. A method for attenuation correction in radionuclide computed tomography. IEEE Trans Nucl Sci 1978;25:638–43.

    Article  Google Scholar 

  19. 19.

    Duann JR, Jung TP, Kuo WJ, Yeh TC, Makeig S, Hsieh JC, et al. Single-trial variability in event-related BOLD signals. Neuroimage 2002;15:823–35.

    PubMed  Article  Google Scholar 

  20. 20.

    Makeig S, Jung TP, Bell AJ, Ghahremani D, Sejnowski TJ. Blind separation of auditory event-related brain responses into independent components. Proc Natl Acad Sci USA 1997;94:10979–84.

    PubMed  Article  CAS  Google Scholar 

  21. 21.

    Friston KJ, Frith CD, Liddle PF, Frackowiak RSJ. Comparing functional (PET) images: the assessment of significant change. J Cereb Blood Flow Metab 1991;11:690–9.

    PubMed  CAS  Google Scholar 

  22. 22.

    Friston KJ, Worsley KJ, Frackowiak RSJ, Mazziotta JC, Evans AC. Assessing the significance of focal activations using their spatial extent. Hum Brain Mapp 1994;1:214–20.

    Article  Google Scholar 

  23. 23.

    Kikuchi A, Takeda A, Kimpara T, Nakagawa M, Kawashima R, Sugiura M, et al. Hypoperfusion in the supplementary motor area, dorsolateral prefrontal cortex and insular cortex in Parkinson’s disease. J Neurol Sci 2001;193:29–36.

    PubMed  Article  CAS  Google Scholar 

  24. 24.

    Dogali M, Fazzini E, Kolodny E, Eidelberg D, Sterio D, Devinsky O, et al. Stereotactic ventral pallidotomy for Parkinson’s disease. Neurology 1995;45:753–61.

    PubMed  CAS  Google Scholar 

  25. 25.

    Alvarez L, Macias R, Lopez G, Alvarez E, Pavon N, Rodriguez-Oroz MC, et al. Bilateral subthalamotomy in Parkinson’s disease: initial and long-term response. Brain 2005;128:570–83.

    PubMed  Article  CAS  Google Scholar 

  26. 26.

    Antonini A, Vontobel P, Psylla M, Gunther I, Maguire PR, Missimer J, et al. Complememtary positron emsission tomographic studies of the striatal dopaminergic system in Parkinson’s disease. Arch Neurol 1995;52:1183–90.

    PubMed  CAS  Google Scholar 

  27. 27.

    Hilker R, Voges J, Weisenbach S, Kalbe E, Burghaus L, Ghaemi M, et al. Subthalamic nucleus stimulation restores glucose metabolism in associative and limbic cortices and in cerebellum: evidence from a FDG-PET study in advanced Parkinson’s disease. J Cereb Blood Flow Metab 2004;24:7–16.

    PubMed  Article  CAS  Google Scholar 

  28. 28.

    Ghaemi M, Raethjen J, Hilker R, Rudolf J, Sobesky J, Deuschl G, et al. Monosymptomatic resting tremor and Parkinson’s disease: a multitracer positron emission tomographic study. Mov Disord 2002;17:782–8.

    PubMed  Article  Google Scholar 

  29. 29.

    Goerendt IK, Lawrence AD, Mehta MA, Stern JS, Odin P, Brooks DJ. Distributed neural actions of anti-parkinsonian therapies as revealed by PET. J Neural Transm 2006;113:75–86.

    PubMed  Article  CAS  Google Scholar 

  30. 30.

    Oishi N, Udaka F, Kameyama M, Sawamoto N, Hashikawa K, Fukuyama H. Regional cerebral flow in Parkinson disease with nonpsychotic visual hallucinations. Neurology 2005;65:1708–15.

    PubMed  Article  CAS  Google Scholar 

  31. 31.

    Firbank MJ, Colloby SJ, Burn DJ, McKeith IG, O’Brien JT. Regional cerebral blood flow in Parkinson's disease with and without dementia. Neuroimage 2003;20:1309–19.

    PubMed  Article  CAS  Google Scholar 

  32. 32.

    Antonini A, De Notaris R, Benti R, De Gaspari D, Pezzoli G. Perfusion ECD/SPECT in the characterization of cognitive deficits in Parkinson’s disease. Neurol Sci 2001;22:47–8.

    PubMed  Article  CAS  Google Scholar 

  33. 33.

    Arahata Y, Hirayama M, Ieda T, Koike Y, Kato T, Tadokoro M, et al. Parieto-occipital glucose hypometabolism in Parkinson’s disease with autonomic failure. J Neurol Sci 1999;163:119–26.

    PubMed  Article  CAS  Google Scholar 

  34. 34.

    Mayberg HS, Starkstein SE, Sadzot B, Preziosi T, Andrezejewski PL, Dannals RF, et al. Selective hypometabolism in the inferior frontal lobe in depressed patients with Parkinson’s disease. Ann Neurol 1990;28:57–64.

    PubMed  Article  CAS  Google Scholar 

  35. 35.

    Berding G, Odin P, Brooks DJ, Nikkhah G, Matthies C, Peschel T, et al. Resting regional cerebral glucose metabolism in advanced Parkinson’s disease studied in the off and on conditions with [18F]FDG-PET. Mov Disord 2001;16:1014–22.

    PubMed  Article  CAS  Google Scholar 

  36. 36.

    Black KJ, Hershey T, Hartlein JM, Carl JL, Perlmutter JS. Levodopa challenge neuroimaging of levodopa-related mood fluctuations in Parkinson’s disease. Neuropsychopharmacology 2005;30:590–601.

    PubMed  Article  CAS  Google Scholar 

  37. 37.

    Sestini S, Scotto di Luzio A, Ammannati F, De Cristofaro MT, Passeri A, Martini S, et al. Changes in regional cerebral blood flow caused by deep-brain stimulation of the subthalamic nucleus in Parkinson’s disease. J Nucl Med 2002;43:725–32.

    PubMed  Google Scholar 

  38. 38.

    Lozza C, Marie RM, Baron JC. The metabolic substrates of bradykinesia and tremor in uncomplicated Parkinson’s disease. Neuroimage 2002;17:688–99.

    PubMed  Article  CAS  Google Scholar 

  39. 39.

    Nagano-Saito A, Kato T, Arahata Y, Washimi Y, Nakamura A, Abe Y, et al. Cognitive- and motor-related regions in Parkinson’s disease: FDOPA and FDG PET studies. Neuroimage 2004;22:553–61.

    PubMed  Article  Google Scholar 

  40. 40.

    Mito Y, Yoshida K, Yabe I, Makino K, Tashiro K, Kikuchi S, et al. Brain SPECT analysis by 3D-SSP and phenotype of Parkinson’s disease. J Neurol Sci 2006;241:67–72.

    PubMed  Article  CAS  Google Scholar 

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Acknowledgement

This study was sponsored by the Shin Kong Wu Ho-Su Memorial Hospital (SKH-8302-95-DR-16).

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Correspondence to Han-Cheng Wang.

Additional information

An editorial commentary on this paper is available at http://dx.doi.org/10.1007/s00259-007-0411-8

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Hsu, JL., Jung, TP., Hsu, CY. et al. Regional CBF changes in Parkinson’s disease: a correlation with motor dysfunction. Eur J Nucl Med Mol Imaging 34, 1458–1466 (2007). https://doi.org/10.1007/s00259-006-0360-7

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Keywords

  • SPECT
  • Parkinson’s disease
  • Regional cerebral blood flow
  • Independent component analysis
  • Statistical parametric mapping