In vivo imaging of dopaminergic and noradrenergic neurons using neuromelanin-sensitive MRI

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We attempted to visualize dopaminergic neurons within the substantia nigra pars compacts (SNc) and noradrenergic neurons within the locus ceruleus (LC) using a newly developed neuromelanin-sensitive MRI technique, and to quantitatively evaluate the signal alterations of the SNc and LC in Parkinson's disease, depression, and schizophrenia.By using the neuromelanin-sensitive MRI.(a high-resolution T1-weighted fast spin-echo technique at 3 Thsla), we can successfully depict the SNc and LC as high signal intensity areas that correspond well to the neuromelanin-related black areas in macroscopic specimens. In patients with Parkinson's disease, the contrast ratios (CRs) of the SNc and LC decreased significantly as compared with those in the age-matched controls, suggesting the existence of neuronal depletion in these nuclei, which has been proven pathologically. In patients with depression, the CRs of the rostral two-thirds of the LC diminished significantly as compared with those in the age-matched controls, suggesting a dysfunction in the ascending noradrenergic system, which is believed to be one of the pathogeneses of depression. In patients with schizophrenia, the CRs of the SNc increased significantly as compared with those in the age-matched depressive patients and controls; this suggests the hyperactivity of the dopaminergic system, which supports the classical dopamine hypothesis.The neuromelanin-sensitive MRI, which we have developed, enabled the in vivo visualization of neuromelanin-contsirting nuclei, such as the SNc and LC. Further, it can also be useful for measuring the pathological or functional alterations in the degenerative and psychiatric disorders affecting these nuclei.