Imaging of the dopamine system with focus on pharmacological MRI and neuromelanin imaging

Abstract

The dopamine system in the brain is involved in a variety of neurologic and psychiatric disorders, such as Parkinson's disease, attention-deficit/hyperactivity disorder and psychosis. Different aspects of the dopamine system can be visualized and measured with positron emission tomography (PET) and single photon emission computed tomography (SPECT), including dopamine receptors, dopamine transporters, and dopamine release. New developments in MR imaging also provide proxy measures of the dopamine system in the brain, offering alternatives with the advantages MR imaging, i.e. no radiation, lower costs, usually less invasive and time consuming. This review will give an overview of these developments with a focus on the most developed techniques: pharmacological MRI (phMRI) and neuromelanin sensitive MRI (NM-MRI). PhMRI is a collective term for functional MRI techniques that administer a pharmacological challenge to assess its effects on brain hemodynamics. By doing so, it indirectly assesses brain neurotransmitter function such as dopamine function. NM-MRI is an upcoming MRI technique that enables in vivo visualization and semi-quantification of neuromelanin in the substantia nigra. Neuromelanin is located in the cell bodies of dopaminergic neurons of the nigrostriatal pathway and can be used as a proxy measure for long term dopamine function or degeneration of dopaminergic neurons. Both techniques are still primarily used in clinical research, but there is promise for clinical application, in particular for NM-MRI in dopaminergic neurodegenerative diseases like Parkinson's disease.

The role of tyrosine hydroxylase–dopamine pathway in Parkinson’s disease pathogenesis

“…The DA system in human brains can be visualized and quantitatively analyzed by advanced molecular functional magnetic resonance imaging (MRI) techniques. Positron emission tomography (PET) and single photon emission computed tomography (SPECT) techniques can quantitatively monitor and visualize different aspects of the DA system to improve the accuracy of the diagnosis, including DA receptors, DA transporters, and DA release in the brain [ 66 , 67 ], whereas the novel neuromelanin (NM)-sensitive MRI (NM-MRI) can visualize and semi-quantify NM in SN of human brains [ 66 ]. The NM is the end product of DA oxidation, which is formed via polymerization of DA-derived DAQ [ 45 ].…”

The motivation of aggression: A cognitive neuroscience approach and neurochemical speculations.

“…There have been suggestions that both increased (Buckholtz et al, 2010) and decreased (Matthys et al, 2013) dopaminergic functioning might be associated with an increased risk for aggression. This issue will be considered with respect to the model of reactive and instrumental aggression outlined in Figure 1 There is considerable dopaminergic innervation of systems implicated in the acute threat response (the amygdala; e.g., Kröner et al, 2005), stimulus-reinforcement decision-making (striatum and medial frontal cortex; e.g., Reneman et al, 2021), responsiveness to distress cues (the amygdala; e.g., Kröner et al, 2005) and response control (dorsomedial and anterior insular/inferior frontal cortex; Kutlu et al, 2013;Reneman et al, 2021). As such dopaminergic function can be expected to modulate both reactive and instrumental aggression.…”

“…There is considerable dopaminergic innervation of systems implicated in the acute threat response (the amygdala; e.g., Kröner et al, 2005), stimulus-reinforcement decision-making (striatum and medial frontal cortex; e.g., Reneman et al, 2021), responsiveness to distress cues (the amygdala; e.g., Kröner et al, 2005) and response control (dorsomedial and anterior insular/inferior frontal cortex; Kutlu et al, 2013; Reneman et al, 2021). As such dopaminergic function can be expected to modulate both reactive and instrumental aggression.…”

“…Matthys et al, 2013) might be expected to increase aggression by: Compromising reinforcement-based decision-making. As noted, there is considerable dopaminergic innervation of systems involved in reinforcement-based decision-making (e.g., Reneman et al, 2021). Indeed, the role of the dopaminergic system in responding to prediction errors and buttressing the representation of EV has received considerable attention (Daw et al, 2002; Dayan et al, 2014; Schultz et al, 1997).…”

Evidence for Dopamine Abnormalities Following Acute Methamphetamine Exposure Assessed by Neuromelanin-Sensitive Magnetic Resonance Imaging

“…Thus, NM-MRI can enhance the T1-related contrast between NM and the brain tissue ( Wengler et al, 2020 ), which allows NM-MRI to be used to detect NM accumulation. As NM is located in the cell bodies of dopaminergic neurons of the nigrostriatal pathway ( Reneman et al, 2021 ), NM-MRI can also be used as a proxy measure for DA function. It provides the possibility for indirect measurement of DA function in non-neurodegenerative conditions.…”