Abstract
Parkinson's disease (PD) is a progressive neurodegenerative disorder in which the major pathologic substrate is a loss of dopaminergic neurons from the substantia nigra. Our main objective was to determine the correspondence between changes in the substantia nigra, evident in neuromelanin and iron sensitive magnetic resonance imaging (MRI), and dopaminergic striatal innervation loss in patients with PD. Eighteen patients and 18 healthy control subjects were included in the study. Using neuromelanin-MRI, we measured the volume of the substantia nigra and the contrast-to-noise-ratio between substantia nigra and a background region. The apparent transverse relaxation rate and magnetic susceptibility of the substantia nigra were calculated from dual-echo MRI. Striatal dopaminergic innervation was measured as density of dopamine transporter (DAT) by means of single-photon emission computed tomography and [123I] N-ω-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) tropane. Patients showed a reduced volume of the substantia nigra and contrast-to-noise-ratio and both positively correlated with the corresponding striatal DAT density. The apparent transverse relaxation rate and magnetic susceptibility values of the substantia nigra did not differ between patients and healthy controls. The best predictor of DAT reduction was the volume of the substantia nigra. Clinical and imaging correlations were also investigated for the locus coeruleus. Our results suggest that neuromelanin-MRI can be used for quantifying substantia nigra pathology in PD where it closely correlates with dopaminergic striatal innervation loss. Longitudinal studies should further explore the role of Neuromelanin-MRI as an imaging biomarker of PD, especially for subjects at risk of developing the disease.
Highlights
Parkinson’s disease (PD) is characterized by a loss of neuromelanin (NM) containing dopaminergic neurons in the substantia nigra (SN), with a consequent reduction of dopamine concentration in the putamen and caudate nucleus (Ehringer and Hornykiewicz, 1998), as well as iron deposition throughout the SN
It has been suggested that for every PD patient who presents with motor signs there may be 10 subclinical cases in the community (Golbe, 1993), as destruction of 60% of the NM-laden neurons in the SN is expected before motor symptoms are manifest (Fearnley and Lees, 1991)
This study aimed to investigate the correlations between magnetic resonance imaging (MRI) markers (NM-MRI, R2∗, susceptibility) of the SN and locus coeruleus (LC) of PD patients and the corresponding nigro-striatal dopaminergic innervation loss as measured by Single-photon emission computed tomography (SPECT) with fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) tropane (FP-CIT)
Summary
Parkinson’s disease (PD) is characterized by a loss of neuromelanin (NM) containing dopaminergic neurons in the substantia nigra (SN), with a consequent reduction of dopamine concentration in the putamen and caudate nucleus (Ehringer and Hornykiewicz, 1998), as well as iron deposition throughout the SN. To date, imaging measures of dopaminergic function, such as Single-photon emission computed tomography (SPECT) with [I-123] N-ω-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) tropane (FP-CIT), represent a robust biomarkers for early PD detection and assessing disease progression (Isaias et al, 2006, 2007; de la Fuente-Fernández et al, 2011). Such markers, are mainly indicative of dopamine nerve terminal activity which could be altered by compensatory mechanisms, both endogenous and in response to treatment (Brooks and Pavese, 2011; Stoessl et al, 2014) rather than SN cell counts
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