Depigmentation of the substantia nigra is a conspicuous pathological feature of Parkinson's disease and related to a loss of neuromelanin. Similar to melanin, neuromelanin has paramagnetic properties resulting in signal increase on specific T1-weighted magnetic resonance imaging. The aim of this study was to assess signal changes in the substantia nigra in patients with Parkinson's disease using an optimized neuromelanin-sensitive T1 scan. Ten patients with Parkinson's disease and 12 matched controls underwent high-resolution T1-weighted magnetic resonance imaging with magnetization transfer effect at 3T. The size and signal intensity of the substantia nigra pars compacta were determined as the number of pixels with signal intensity higher than background signal intensity+3 standard deviations and regional contrast ratio. Patients were subclassified as early stage (n=6) and late stage (n=4) using the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr Parkinson's disease staging scale. The T1 hyperintense area in the substantia nigra was substantially smaller in patients compared with controls (-60%, P<.01), and contrast was reduced (-3%, P<.05). Size reduction was even more pronounced in more advanced disease (-78%) than in early-stage disease (-47%). We present preliminary findings using a modified T1-weighted magnetic resonance imaging technique showing stage-dependent substantia nigra signal reduction in Parkinson's disease as a putative marker of neuromelanin loss. Our data suggest that reduction in the size of neuromelanin-rich substantia nigra correlates well with postmortem observations of dopaminergic neuron loss. Further validation of our results could potentially lead to development of a new biomarker of disease progression in Parkinson's disease.

There is increasing interest in developing a reliable, affordable and accessible disease biomarker of Parkinson's disease (PD) to facilitate disease modifying PD-trials. Imaging biomarkers using magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) can describe parameters such as fractional anisotropy (FA), mean diffusivity (MD) or apparent diffusion coefficient (ADC). These parameters, when measured in the substantia nigra (SN), have not only shown promising but also varying and controversial results.To clarify the potential diagnostic value of nigral DTI in PD and its dependency on selection of region-of-interest, we undertook a high resolution DTI study at 3 T. 59 subjects (32 PD patients, 27 age and sex matched healthy controls) were analysed using manual outlining of SN and substructures, and voxel-based analysis (VBA). We also performed a systematic literature review and meta-analysis to estimate the effect size (DES) of disease related nigral DTI changes.We found a regional increase in nigral mean diffusivity in PD (mean ± SD, PD 0.80 ± 0.10 vs. controls 0.73 ± 0.06 · 10− 3 mm2/s, p = 0.002), but no difference using a voxel based approach. No significant disease effect was seen using meta-analysis of nigral MD changes (10 studies, DES = + 0.26, p = 0.17, I2 = 30%). None of the nigral regional or voxel based analyses of this study showed altered fractional anisotropy. Meta-analysis of 11 studies on nigral FA changes revealed a significant PD induced FA decrease. There was, however, a very large variation in results (I2 = 86%) comparing all studies. After exclusion of five studies with unusual high values of nigral FA in the control group, an acceptable heterogeneity was reached, but there was non-significant disease effect (DES = − 0.5, p = 0.22, I2 = 28%).The small PD related nigral MD changes in conjunction with the negative findings on VBA and meta-analysis limit the usefulness of nigral MD measures as biomarker of Parkinson's disease. The negative results of nigral FA measurements at regional, sub-regional and voxel level in conjunction with the results of the meta-analysis of nigral FA changes question the stability and validity of this measure as a PD biomarker.

Purpose: To determine if tissue magnetic susceptibility is a more direct marker of tissue iron content than other MR markers of iron. This study presents the first quantitative, in vivo measurements of the susceptibility of the substantia nigra in patients with Parkinson's disease. Materials and Methods:Nine patients and 11 controls were studied at 7 Tesla. Susceptibility maps were created by inverting the filtered phase maps associated with T2* weighted images.Results: On average, patients showed an increase in susceptibility of the pars compacta compared with controls, which correlates with the predicted increase in brain iron in Parkinson's disease. A rostral-caudal gradient in susceptibility was also observed in controls and patients. PARKINSON's DISEASE (PD) is a common neurodegenerative disease that is associated with dopaminergic cell loss in the substantia nigra (SN). In normal aging or Parkinson's disease, loss of these neurons occurs concurrently with the accumulation of iron, which acts as a nidus for neuronal damage, leading to free radical formation and lipid peroxidation (1). The pars compacta (PC), the medial sub region of the SN, has the greatest concentration of dopaminergic neurons in the SN.There have been several attempts to use MRI to study changes in the SN in PD. Anatomical differences within the borders of the SN have been studied in patients with PD, and an increased latero-medial contrast gradient has been detected (2,3). Reduced fractional anisotropy of water self diffusion, consistent with axonal loss, has also been observed in the SN of PD patients (4-6) and DTI has indicated changes in neuronal connectivity of the SN in patients with PD (3,7).However, most attempts to study PD with MRI have been based on the changes in iron homeostasis in the SN in PD, and the sensitivity of various MRI parameters to iron. In the SN there is a relatively inhomogeneous distribution of iron (8) in the form of ferritin and a heterogeneous distribution of iron within neuromelanin and hemosiderin, which will cause inhomogeneities in the magnetic field within a sample. The transverse relaxation rates, R2 and R2*, decrease with increasing iron concentration, due to spin dephasing in the microscopic field inhomogeneities induced in regions of heterogeneous iron distribution. R2 is sensitive to diffusion in the inhomogeneous magnetic field, whereas R2* is also sensitive to static dephasing in the inhomogeneous field. Increased R2 (9-12) and R2* (10) has been observed in the pars compacta of the SN of patients with PD, particularly on the most affected side. However, some studies do not detect this effect, possibly because the value of R2 measured will depend on the echo time interval in multiple spin-echo sequences, or on the echo time regimen explored in single spin echo sequences, due to the effects of diffusion and exchange. It has been proposed that the field dependence of R2 is a direct measure of ferritin, and using this it was suggested that early onset PD patients had an increase in ferritin in the S...

We found a high false positive (17.4 to 26.1%) and negative rate (6.7 to 20%) for the diagnosis of PD. The diagnostic distinction of TDPD from dystonic tremor was reduced by the presence of dystonic features in treated and untreated PD patients.Clinical distinction of TDPD from atypical tremor, monosymptomatic rest tremor, and dystonic tremor can be difficult, due to the presence of parkinsonian features in tremulous SWEDD patients. The diagnosis of bradykinesia was particularly challenging. This study highlights the difficulty of differentiation of some cases of SWEDD from PD.