Midbrain iron content in early Parkinson disease - A potential biomarker of disease status

Background: Parkinson disease (PD) is a progressive neurodegenerative disorder in which the major pathologic substrate is a loss of dopaminergic neurons from the lateral substantia nigra pars compacta (SNc). Our objective was to determine whether, in patients with early PD, SNc changes evident on MRI sequences sensitive to iron content corresponded anatomically to the pathologic changes reported previously, and to correlate these changes to the duration and severity of clinical manifestations of PD. Methods: Twenty-six untreated patients with early PD and 13 age-and gender-matched control subjects had MRI with a 3 tesla magnet using a multiple gradient echo sequence designed for rapid single-scan mapping of the proton transverse relaxation rate (R(2)*). R(2)* was calculated for midbrain and forebrain basal ganglia regions. Clinical features were rated with the Unified Parkinson's Disease Rating Scale. Results: A difference in measured R(2)* values between patients and controls was observed in the lateral SNc (p <= 0.005). Linear regression indicated a correlation between the lateralized motor score from the clinically most affected side and R(2)* values from the opposite lateral SNc (p = 0.01). Conclusions: High field strength MRI demonstrates lateral substantia nigra pars compacta abnormalities in early Parkinson disease (PD) consistent with increased iron content and corresponding to the known distribution of neuronal loss occurring in this disorder. This may ultimately provide an imaging marker for disease progression in PD, although longitudinal studies are required.