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Brain, Vol. 122, No. 9, 1637-1650, September 1999
© 1999 Oxford University Press

Frontal, midbrain and striatal dopaminergic function in early and advanced Parkinson's disease A 3D [¹⁸F]dopa-PET study

J. S. Rakshi¹, T. Uema¹, K. Ito^1,4, D. L. Bailey¹, P. K. Morrish¹, J. Ashburner², A. Dagher¹, I. H. Jenkins¹, K. J. Friston² and D. J. Brooks^1,3

¹ MRC Cyclotron Unit, Hammersmith Hospital, ² The Wellcome Department of Cognitive Neurology and ³ Department of Clinical Neurology, Institute of Neurology, London, UK and ⁴ Department of Biofunctional Research, National Institute for Longevity Sciences, Obu, Japan

Correspondence to: Dr James S. Rakshi, MRC Cyclotron Unit, Hammersmith Hospital, Du Cane Rd, London W12 ONN, UK E-mail: james{at}wren.rpms.ac.uk

We have studied focal changes in dopaminergic function throughout the brain volume in early and advanced Parkinson's disease by applying statistical parametric mapping (SPM) to 3D [¹⁸F]dopa-PET. Data from seven early hemi-Parkinson's disease and seven advanced bilateral Parkinson's disease patients were compared with that from 12 normal controls. Parametric images of [¹⁸F]dopa influx rate constant (K_i^o) were generated for each subject from dynamic 3D [¹⁸F]dopa datasets and transformed into standard stereotactic space. Significant changes in mean voxel [¹⁸F]dopa K_i^o values between the normal control group and each Parkinson's disease group were localized with SPM. Conventional region of interest analysis was also applied to comparable regions on the untransformed image datasets. In early left hemi-Parkinson's disease, significant extrastriatal increases in [¹⁸F]dopa K_i^o were observed in the left anterior cingulate gyrus and the dorsal midbrain region (P < 0.05, corrected) along with decreases in striatal [¹⁸F]dopa K_i^o. In advanced Parkinson's disease, significant extrastriatal decreases in [¹⁸F]dopa K_i^o were observed in the ventral and dorsal midbrain regions (P < 0.05, corrected). No significant changes in [¹⁸F]dopa K_i^o were observed in the anterior cingulate region. In a direct comparison between the early and late Parkinson's disease groups, we observed relative [¹⁸F]dopa K_i^o reductions in ventral and dorsal midbrain, and dorsal pontine regions along with striatal [¹⁸F]dopa K_i^o reductions. Similiar results were found with a region of interest approach, on non-transformed data, except for the focal midbrain [¹⁸F]dopa K_i^o increase seen in early Parkinson's disease. In conclusion, using SPM with [¹⁸F]dopa-PET, we have objectively localized changes in extrastriatal, pre-synaptic dopaminergic function in Parkinson's disease. The significance of the increased dopaminergic activity of anterior cingulate in early Parkinson's disease remains unclear, but may be compensatory. The [¹⁸F]dopa signal in dorsal midbrain and pontine regions suggests that [¹⁸F]dopa is taken up by serotonergic and noradrenergic neurons which also degenerate in advanced Parkinson's disease. This suggests, therefore, that Parkinson's disease is a monoaminergic neurodegenerative disorder.

Parkinson's disease; 3D [¹⁸F]dopa; focal changes; extrastriatal; progression

AADC = aromatic amino acid decarboxylase activity; COMT = catechol-O-methyl transferase; K_i^o = influx rate constant; MTGA = multiple time graphical analysis; rCBF = regional cerebral blood flow; SPM = statistical parametric mapping; UPDRS = Unified Parkinson's Disease Rating Scale

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