Tuesday 19 February 2019
Researchers have shown that a type of magnetic resonance imaging – called neuromelanin-sensitive MRI (MRI-NM) – is a potential biomarker of psychosis. The MRI-NM signal has been shown to be a marker of dopaminergic function in people with schizophrenia and an indicator of the severity of psychotic symptoms in people with this mental illness. The study, funded by the National Institute of Mental Health (NIMH), which is part of the National Institutes of Health, appears in the Proceedings of the National Academy of Sciences.
"Disturbances affecting the neurotransmitter dopamine are associated with a host of mental and neurological disorders, such as schizophrenia and Parkinson's disease," said Joshua A. Gordon, MD, Ph.D., director of NIMH. "Because of the role that dopamine plays in these disorders, the ability to measure dopamine activity is essential to deepen our understanding of these disorders, including the best way to diagnose and treat them."
Neuromelanin is a dark pigment created in the mid-brain dopaminergic neurons, particularly in the dark substance, a region of the brain that plays a role in reward and movement. Neuromelanin accumulates over the course of life and is eliminated from cells only after cell death, as occurs in neurodegenerative disorders such as Parkinson's disease. Researchers found that the MRI-NM signal was lower in the substantia nigra of people with Parkinson's disease, reflecting the cell death that occurs in these patients.
Despite the usefulness of this tool for detecting the loss of neurons in neurodegenerative diseases, it was not yet proven that MRI-NM was a marker of dopaminergic function, nor was its utility demonstrated. individuals not suffering from neurodegenerative disease. In this study, Guillermo Horga, MD, Ph.D., of Columbia University, New York, and his colleagues conducted a series of validation studies to show that the MRI-NM can serve as a marker of dopaminergic function in people without neurodegenerative disorders.
"The main advantages of this technique are that, compared with other established and more direct measures of dopaminergic function, neuromelanin-sensitive MRI does not rely on invasive procedures or radiation", said Dr. Horga. "This benefit makes it more suitable for pediatric populations and repeated scans, which could be useful for monitoring disease progression or response to treatment – and it only takes a short scan that can be done." implemented in most clinical scanners. It also offers a very high anatomic resolution compared to PET measurements, which is important for examining the functions or dysfunctions of specific parts of the substantia nigra. "
The researchers first investigated whether MRI-NM could accurately detect regional variations in neuromelanin concentration in patients without neurodegeneration. To examine the ability to detect MRI-NM, the researchers compared measurements of neuromelanin by MRI-NM to chemical measurements of neuromelanin in post-mortem brain tissue. The researchers found, in all tissue sections, that a higher MRI-NM signal was associated with higher concentrations of neuromelanin. The results confirm for the first time the ability of MRI-NM to measure regional concentrations of neuromelanin. In addition, the results show that the NM-MRI signal reflects neuromelanin concentrations in the tissues, rather than the number of neurons containing neuromelanin.
The researchers then sought to determine if MRI-NM could capture variations of neuromelanin in the smaller anatomical subregions of the substantia nigra. Since dopaminergic function differs significantly in different parts of substantia nigra, researchers needed to determine the ability of this tool to capture these anatomical differences. The researchers therefore examined NM-MRI data from patients with Parkinson's disease and individuals without Parkinson's disease. The researchers found a decrease in MRI-NM signal in patients with Parkinson's disease in the lateral, posterior and ventral areas of the substantia nigra – the results correspond to the known anatomical distribution of cell loss in this region of the brain in Parkinson's disease. These results confirm that MRI-NM can capture the known topographic variability within this brain structure.
A next critical step was to show a link between MRI-NM and dopaminergic function. The researchers collected measurements of dopamine release capacity (measured using positron emission tomography (PET)) and NM-MRI data of people without neurodegenerative disease. Individuals with a higher NMR-MRI signal had a greater capacity for dopamine release in the striatum (an essential component of the reward, motor and cognitive systems). The researchers also found that the NM-MRI signal in the substantia nigra was associated with functional measures of regional cerebral blood flow by MRI.
Finally, the researchers examined the link between the MRI-NM signal and the severity of psychosis, concluding that more severe symptoms of psychosis were associated with higher MRI-NM signals in the nigrostriatal pathway of schizophrenics and subjects at risk. Psychosis is associated with dysfunction of the dopaminergic system, characterized by increased dopamine release and increased capacity for synthesis in the striatum. The results suggest that MRI-NM captures this dysfunction of dopamine, which reinforces the role of MRI-NM as a potential biomarker of psychosis.
The results reported in this study, taken as a whole, validate the use of MRI-NM in populations other than those with neurodegenerative disorders, showing that it may serve as a measure of concentration. of neuromelanin and dopaminergic function in substantia nigra.
In describing the future directions of their research, Dr. Horga said, "We are now expanding this work to see if we can detect neuromelanin signal abnormalities that help us predict which individuals are more likely to develop psychotic disorder at home. those who already have early symptoms of psychosis. We also want to determine whether a neuromelanin-sensitive MRI could be used in the future to determine who could best benefit from dopaminergic treatments. "
About the National Institute of Mental Health (NIMH): The mission of NIMH is to transform the understanding and treatment of mental illness through fundamental and clinical research, paving the way for prevention, recovery and healing. For more information, visit the NIMH website.
About the National Institutes of Health (NIH):
The NIH, the country's medical research agency, has 27 institutes and centers and is part of the US Department of Health and Human Services. NIH is the lead federal agency that conducts and supports basic, clinical and translational medical research. She studies causes, treatments and cures for common and rare diseases. For more information on NIH and its programs, visit www.nih.gov.
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Cassidy, C., Zucca, F., Girgis, S., Baker, J., Weinstein, Sharp M., …, Horga, G. (in press). MRI sensitive to neuromelanin as a noninvasive indirect measure of dopaminergic function in the human brain. Proceedings of the National Academy of Sciences of the United States.