Neuromelanin-sensitive magnetic resonance imaging: a promising technique for depicting tissue characteristics containing neuromelanin.

Abstract

Idiopathic Parkinson's disease (IPD) is a progressive, neurodegenerative movement disorder characterized by bradykinesia, muscular rigidity, postural instability and tremor. IPD is usually diagnosed based on clinical findings, but diagnoses are only 75–90% accurate when compared with autopsy results. Improving diagnostic accuracy is critical for the early differentiation of IPD from other Parkinsonism-related disorders because of differences in their prognoses and treatment. Furthermore, IPD is clinically heterogeneous, with variable prognosis. Although the biological function of neuromelanin has not yet been determined, the selective vulnerability of neuromelanin-containing neurons in patients with IPD suggests a role for this pigment in neurodegeneration. Recently developed ultra-high-field magnetic resonance imaging (MRI) systems produce T1-weighted neuromelanin-sensitive images with very high spatial resolution, enabling the depiction of tissue containing neuromelanin. Here we review recent advances in neuromelanin-sensitive MRI in IPD and related conditions suggesting that neuromelanin may be a potential diagnostic biomarker for IPD. Neuromelanin is a dark polymer produced in specific populations of catecholaminergic neurons in the brain. Three main regions of the brain contain neuromelanin-producing cells: the substantia nigra (SN) of the midbrain, the locus coeruleus (LC) within the pons and the ventrolateral reticular formation and nucleus of the solitary tract in the medulla oblongata. Moreover, two of these regions, the SN and the LC, contain large clusters of pigmented neurons that appear macroscopically as darkened areas (Fedorow et al., 2005). Parkinsonian syndrome is a heterogeneous group of movement disorders, which can be subdivided into IPD, genetic forms of Parkinson's disease (PD) and atypical parkinsonian syndrome. In addition, several other neurodegenerative disorders may show clinical signs of parkinsonism. The etiology, histopathology, clinical manifestation and disease course of these disorders vary significantly. The loss of neuromelanin-containing cells within the SN and LC is a primary pathological diagnostic criterion for IPD. The presence of neuromelanin in these vulnerable cells suggests a role for this pigment in the neurodegenerative process of IPD. The amount of neuromelanin contained within the dopaminergic neurons of the midbrain has been reported to be inversely related to the relative vulnerability of these cells to IPD (Hirsch et al., 1988). In addition to the degree of neuromelanin pigmentation, the position of neuromelanin-containing cells within the nigral complex was also found to be a key factor for neuronal survival in IPD (Damier et al., 1999). Neuromelanin has a high chelating ability for iron, and has been shown to bind neurotoxic and toxic metals that could promote neurodegeneration, such as pesticides and MPP +, suggesting a neuroprotective role of neuromelanin (Zecca et al., 2001). Cell death observed in IPD may be partly due to oxidative stress. This oxidation may also be relieved by neuromelanin. Following its binding of iron, neuromelanin acts as a paramagnetic agent. Recently developed ultra-high-field magnetic resonance imaging (MRI) systems produce T1-weighted neuromelanin-sensitive images of very high spatial resolution (Enochs et al., 1997; Sasaki et al., 2006; Bolding et al., 2013). On these images, neuromelanin-containing tissues appear as foci of high signal intensity, with the intensity proportional to the neuromelanin concentration. Neuromelanin-sensitive MRI can be used to directly measure the volume or concentration of neuromelanin in the SN and LC, suggesting that this modality may be able to distinguish IPD from other related conditions. We review here the usefulness of neuromelanin MRI for the diagnosis of parkinsonian syndrome, with special reference to neuropathological findings.