The researchers first set out to determine whether NM-MRI could accurately detect regional variations in the concentration of neuromelanin in those without neurodegeneration of the substantia nigra. To examine the detection ability of NM-MRI, the researchers compared NM-MRI measurements of neuromelanin to chemical measurements of neuromelanin in post-mortem brain tissue. The researchers found, across all sections of tissue, that higher NM-MRI signal was associated with higher concentrations of neuromelanin. The results confirm, for the first time, the ability of NM-MRI to measure regional concentrations of neuromelanin. Furthermore, the results show that NM-MRI signal reflects concentrations of neuromelanin in tissue, rather than just the number of neuromelanin-containing neurons.

The researchers next sought to determine whether NM-MRI could capture variations in neuromelanin in smaller anatomical subregions within the substantia nigra. Since dopamine function is thought to differ significantly in different parts of the substantia nigra, researchers needed to determine the ability of this tool to capture these anatomical differences. So, the researchers examined NM-MRI data from patients diagnosed with Parkinson's disease and individuals without Parkinson's disease. The researchers found decreases in NM-MRI signal in those with Parkinson's disease in the lateral, posterior, and ventral areas of the substantia nigra -- findings that correspond to the known anatomical distribution of cell loss in this brain area in Parkinson's disease. These results confirm that NM-MRI can capture known topographical variability within this brain structure.


A next critical step was to show a connection between NM-MRI and dopamine function. The researchers collected measurements of dopamine release capacity (as measured using positron emission tomography (PET)) and NM-MRI data from people without neurodegenerative illnesses. Individuals with a higher NM-MRI signal had greater dopamine release capacity in the striatum (a core component of reward, motor, and cognitive systems). The researchers also found that NM-MRI signal in the substantia nigra was associated with functional MRI measures of regional cerebral blood flow.

Lastly, the researchers examined the link between NM-MRI signal and psychosis severity, finding that more severe symptoms of psychosis were associated with higher NM-MRI signals in the nigrostriatal pathway of individuals with schizophrenia and in those at-risk for schizophrenia. Psychosis is associated with dopamine system dysfunction, characterized by greater dopamine release and synthesis capacity in the striatum. The findings suggest that NM-MRI is capturing this dopamine dysfunction, supporting the role of NM-MRI as a potential biomarker for psychosis.

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