title: Voxel-wise analysis of [123I]beta-CIT SPECT differentiates the Parkinson variant of multiple system atrophy from idiopathic Parkinson's disease.
abstract: To investigate the cerebral dopamine transporter status in the early stages of the parkinson-variant of multiple system atrophy (MSA-P), 15 patients with MSA-P and a disease duration up to 3 years were studied with [123I]beta-CIT single photon emission computed tomography (SPECT). Data were compared with 13 age-matched healthy control subjects and 15 patients with idiopathic Parkinson's disease (IPD), matched for age and disease duration. Parametric SPECT images of the specific-to-nondisplaceable equilibrium partition coefficient (V3''), which is proportional to the receptor density (Bmax) have been generated. To objectively localize focal changes in dopaminergic function throughout the entire brain volume without having to make an a priori hypothesis as to their location, statistical parametric mapping (SPM) was applied to our [123I]beta-CIT SPECT study. Both MSA-P and IPD patients showed significant decreases in striatal [123I]beta-CIT SPECT uptake. However, in MSA-P patients an additional reduction in midbrain [123I]beta-CIT signal was localized with SPM compared with control subjects (MSA-P, V3'': 0.89 +/- 0.37 versus controls V3'': 1.81 +/- 0.38; P < 0.001) and patients with IPD (V3'': 1.84 +/- 0.26; P < 0.001). Stepwise linear discriminant analysis of mean [123I]beta-CIT uptake in the putamen, caudate and midbrain identified the caudate and midbrain as indices to classify correctly 95.2% of subjects as either normal, patients with MSA-P or IPD. Voxel-wise analysis of [123I]beta-CIT SPECT revealed more widespread decline of monoaminergic transporter availability in MSA-P compared with IPD, matching the underlying pathological features. We suggest that the quantification of midbrain DAT signal should be included in the routine clinical analysis of [123I]beta-CIT SPECT in patients with uncertain parkinsonism.
authors.affiliation: Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. christoph.scherfler@uibk.ac.at
authors.forename: Christoph
authors.initials: C
authors.lastname: Scherfler
authors.forename: Klaus
authors.initials: K
authors.lastname: Seppi
authors.forename: Eveline
authors.initials: E
authors.lastname: Donnemiller
authors.forename: Georg
authors.initials: G
authors.lastname: Goebel
authors.forename: Christian
authors.initials: C
authors.lastname: Brenneis
authors.forename: Irene
authors.initials: I
authors.lastname: Virgolini
authors.forename: Gregor K
authors.initials: GK
authors.lastname: Wenning
authors.forename: Werner
authors.initials: W
authors.lastname: Poewe
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D002421:Caudate Nucleus / Q000378:metabolism*; D003042:Cocaine / Q000031:analogs & derivatives*; D003342:Corpus Striatum / Q000378:metabolism; D003937:Diagnosis, Differential; D016002:Discriminant Analysis; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008636:Mesencephalon / Q000378:metabolism*; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000000981:diagnostic imaging* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000378:metabolism; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; C493214:SLC6A3 protein, human; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D003042:Cocaine; D004298:Dopamine