Multimodal database of dopaminergic neurotransmission functions in substantia nigra measured by MRI and PET

72 Objectives The central dopaminergic system is of major importance in the pathophysiology of Parkinson’s disease, schizophrenia, and other neuropsychiatric disorders. In the present study, the multimodal normal database of dopaminergic neurotransmission functions, neuromelanin, dopamine synthesis, dopamine transporters and dopamine D2 receptors, in the midbrain was constructed using magnetic resonance (MR) imaging and positron emission tomography (PET). Methods PET studies with L-[β-C-11]DOPA, [F-18]FE-PE2I and [C-11]FLB457 were performed on twenty one young healthy men to obtain parametric images of dopamine synthesis capacity, dopamine transporter and dopamine D2 receptor binding, respectively. MRI studies were also performed for all subjects to obtain parametric images of neuromelanin accumulation as the ratio of signal intensity in the midbrain to decussation of superior cerebellar peduncles. All MRI and PET images were transformed into standard brain size and shape by SPM8. The neuromelanin accumulation was compared with dopamine synthesis capacity, dopamine transporter and dopamine D2 receptor binding in the substantia nigra. Results Although neuromelanin is synthesized from DOPA and dopamine in dopaminergic neurons, neuromelanin accumulation was not correlated with dopamine synthesis capacity in variation for young healthy subjects. Although the role of dopamine transporters in the substantia nigra is considered to be the transport of dopamine into neurons, no significant correlation was observed between neuromelanin accumulation and dopamine transporter binding. A positive correlation between dopamine D2 receptor binding and neuromelanin accumulation was observed indicating that negative feedback by dopamine through the dopaminergic autoreceptors might increase neuromelanin synthesis. Discrepancies in regional distribution between these dopaminergic neurotransmission functions were observed in the substantia nigra relating to the differences in regional distribution of them between the substantia nigra pars compacta and pars reticularis. Conclusions The multimodal normal database of dopaminergic neurotransmission functions in the midbrain were constructed using MRI and PET. Such multimodal database of dopaminergic neurotransmission functions might be useful for diagnosis of neuropsychiatric diseases.