Parkinson’s disease (PD) a neurodegenerative condition characterized by the reduction of
the pigmented dopaminergic neurons of the substantia nigra pars compacta (SNc) and the
loss of the dopaminergic striatal terminals which in turn result in the cardinal motor
symptoms including bradykinesia, rigidity and tremor. Iron plays a deleterious role in the
pathophysiology of PD due to the generation of reactive oxidative species that leads to
oxidative stress and neurodegeneration. In addition neuromelanin is a complex pigment
contained in the dopaminergic neurons of the SNc that plays a toxic role in pro-oxidative
conditions such as PD. Magnetic resonance imaging (MRI) is a widely available nonionising technique allowing the study of structural properties of the SN such as iron
deposition or neuromelanin pigmentation load in PD. In this thesis I have used state of
the art neuroimaging to assess nigral iron accumulation and nigral depigmentation in PD, the correlation between neuromelanin decline and nigrostriatal terminal loss, and the potential clinical use of an iron chelation to improve clinical symptoms. The main
findings of this thesis are as follows: A) Increased nigral iron accumulation in PD
displays an ascendant stratification according to clinical severity at baseline and it is
associated with bradykinesia and rigidity symptoms in cross-sectional and longitudinal
settings. B) Nigral depigmentation in PD shows a descendant stratification according to disease duration at baseline and displays significant associations with motor severity at
baseline and with bradykinesia at follow-up visits. C) The pattern of nigral pigmentation
loss shows a ventro-medial pattern and there was a significant correlation between this
loss and nigrostriatal terminals decline in the most affected side, but not in the least
affected side. D) Finally, iron chelation with deferiprone in PD shows a trend of motor
improvement after six months of treatment being optimally monitored with iron-sensitive
MR imaging techniques. The results presented in this thesis support the application of
multimodal imaging protocols to further understand the dopaminergic pathophysiology of PD and their usefulness for monitoring the progression of the disease.