Voxel-wise analysis of [123I]β-CIT SPECT differentiates the Parkinson variant of multiple system atrophy from idiopathic Parkinson's disease

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 [I-123]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 (V-3''), which is proportional to the receptor density (B-max) 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 [I-123]beta-CIT SPECT study. Both MSA-P and IPD patients showed significant decreases in striatal [I-123]beta-CIT SPECT uptake. However, in MSA-P patients an additional reduction in midbrain [I-123]beta-CIT signal was localized with SPM compared with control subjects (MSA-P, V-3'': 0.89 +/- 0.37 versus controls V-3'': 1.81 +/- 0.38; P < 0.001) and patients with IPD (V-3'': 1.84 +/- 0.26; P < 0.001). Stepwise linear discriminant analysis of mean [I-123]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 [I-123]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 [I-123]beta-CIT SPECT in patients with uncertain parkinsonism.