Neuromelanin-sensitive MRI as a noninvasive proxy measure of dopamine function in the human brain

Abstract

Neuromelanin-sensitive MRI (NM-MRI) purports to detect the content of neuromelanin (NM), a product of dopamine metabolism that accumulates with age in dopamine neurons of the substantia nigra (SN). Interindividual variability in dopamine function may result in varying levels of NM accumulation in the SN; however, the ability of NM-MRI to measure dopamine function in nonneurodegenerative conditions has not been established. Here, we validated that NM-MRI signal intensity in postmortem midbrain specimens correlated with regional NM concentration even in the absence of neurodegeneration, a prerequisite for its use as a proxy for dopamine function. We then validated a voxelwise NM-MRI approach with sufficient anatomical sensitivity to resolve SN subregions. Using this approach and a multimodal dataset of molecular PET and fMRI data, we further showed the NM-MRI signal was related to both dopamine release in the dorsal striatum and resting blood flow within the SN. These results suggest that NM-MRI signal in the SN is a proxy for function of dopamine neurons in the nigrostriatal pathway. As a proof of concept for its clinical utility, we show that the NM-MRI signal correlated to severity of psychosis in schizophrenia and individuals at risk for schizophrenia, consistent with the well-established dysfunction of the nigrostriatal pathway in psychosis. Our results indicate that noninvasive NM-MRI is a promising tool that could have diverse research and clinical applications to investigate in vivo the role of dopamine in neuropsychiatric illness.

Dopamine, Oxidative Stress and Protein–Quinone Modifications in Parkinson's and Other Neurodegenerative Diseases

“…Nowadays,t he availability of 7T scanners has increased and anumber of MRI studies of NM in LC have been reported. [183] This shows that MRI of NM is ar eliable marker of NM concentration, which in turn is am arker of CA neuron number. [51] As shown in Section 6, the Fe sites are heterogeneous in NM of SN and only am inor fraction of mononuclear iron(III) is EPR detectable at low temperature,a lthough also the EPR-silent Fe clusters may access excited paramagnetic states at physiological temperature and hence contribute to MRI signal amplification.…”

Neuromelanin Locus Coeruleus MRI Contrast in Migraine With Aura

“…High LC signal may be induced by abundant, intracellular water protons interacting with neuromelanin and other paramagnetic ions not associated with neuromelanin . However, histological studies in humans have consistently demonstrated a close correlation between neuromelanin concentration and T1 neuromelanin‐sensitive MRI intensity in substantia nigra and in LC . Furthermore, in substantia nigra, neuromelanin MRI hyperintensity was correlated to dopaminergic neurons activity as measured by PET …”

“…17 However, histological studies in humans have consistently demonstrated a close correlation between neuromelanin concentration and T1 neuromelanin-sensitive MRI intensity in substantia nigra and in LC. 15,22,23 Furthermore, in substantia nigra, neuromelanin MRI hyperintensity was correlated to dopaminergic neurons activity as measured by PET. 23 The segmentation of LC was challenging, as LC is a very small brainstem nucleus, close to the fourth ventricle and surrounded by partial volume artifacts on MRI.…”

“…15,22,23 Furthermore, in substantia nigra, neuromelanin MRI hyperintensity was correlated to dopaminergic neurons activity as measured by PET. 23 The segmentation of LC was challenging, as LC is a very small brainstem nucleus, close to the fourth ventricle and surrounded by partial volume artifacts on MRI. This nucleus has a rostro-caudal extent of…”

Dopamin, oxidativer Stress und Protein‐Chinonmodifikationen bei Parkinson und anderen neurodegenerativen Erkrankungen

“…[24] Angewandte Chemie Aufsätze 8. [183] MRTv on NM ist ein zuverlässiger Marker fürd ie NM-Konzentration und diese wiederum ein Marker fürdie Zahl der CA-Neuronen. [177]).…”