In vivo Detection of the Neuropathological Hallmarks in Different Parkinsonian Syndromes by Voxel-Based Magnetization Transfer Imaging

Objective: To determine whether a whole brain voxel-by-voxel analysis of magnetization transfer imaging (MTI) using statistical parametric mapping (SPM) detects the known neuropathological changes in idiopathic Parkinson's disease (IPD), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) in comparison to healthy controls. Background: Although much is known about the neuropathology of IPD, MSA and PSP from histological studies, the assessment of these changes in vivo remains difficult. MTI is an MRI technique which is more sensitive to neuropathological changes than conventional MRI and provides a quantitative measure of macrostructural integrity in vivo. It has previously been shown by our group to reveal changes which match the underlying pathological features of the different Parkinsonian disorders using an ROI approach (Eckert et al., 2004). By the use of SPM it is now possible to study the whole brain in an exploratory fashion without having to make a priori assumptions about the structures to be investigated. Methods: We investigated 15 IPD, 12 MSA, 10 PSP patients and 20 age-matched controls by means of voxel-based MTI (VBMTI) which was performed on a 1.5 T neuro-optimized GE-scanner. After calculation of the Magnetization Transfer Ratio (MTR), images were pre-processed and analyzed using a new approach adopted from voxel-based morphometry which included an optimized normalization procedure, automated removal from skull and CSF as well as smoothing. ANCOVA with total brain volume as confounding factor was performed to differentiate regional effects between the groups (p<0.05, corrected for multiple comparisons for the entire brain volume). Results: In comparison with controls, VBMTI revealed a significantly decreased MTR in IPD patients within the substantia nigra (SN) bilaterally. In MSA patients decreased MTRs were detected in the dorsolateral putamen, the SN and along the border of claustrum and putamen. PSP patients exhibited reduced MTR in the globus pallidus, the SN as well as the thalamus on both sides. Increases in MTR were not detected in any patient group compared to controls. Conclusions: Magnetization transfer imaging as analyzed by statistical parametric mapping was sensitive in visualizing the neuropathological hallmarks of the different Parkinsonian disorders in vivo. It may assist in early diagnosis and individually discriminate between IPD, MSA and PSP patients.