Magnetic resonance susceptibility imaging for the evaluation of subcortical iron loading in Parkinson's disease and its relationship with non-motor clinical presentation

Abstract

Iron is essential for normal metabolism of human body, yet it is also postulated to be involved indifferent neurodegenerative diseases. Parkinson’s disease, being one of the most common neurodegenerative diseases in the aged population, is often observed with abnormal iron deposition in the substantia nigra pars compacta. However, the exact pathophysiology and the underlying mechanism of neurodegeneration in Parkinson’s disease are uncertain. Development of in vivo iron imaging technique is therefore essential to identify the role of iron in neurodegeneration. Susceptibility Weighted Imaging (SWI) and Quantitative Susceptibility Mapping (QSM) are advanced Magnetic Resonance Imaging techniques that exploit the underlying magnetic susceptibility property of body tissues to generate image contrast. The two techniques are proven to be capable of in vivo iron quantification. In this study, we employed both SWI and QSM to evaluate the putative iron content in different subcortical and limbic brain nuclei of Parkinson’s disease patients. The objective of this work is to examine the association between brain iron accumulation and the expression of both motor and non-motor symptoms in the Parkinson’s disease patients. SWI and QSM are employed to evaluate iron content in the iron-rich subcortical deep grey matter nuclei. Findings with both SWI and QSM suggest elevated iron concentration in substantia nigra of the Parkinson’s disease patients. Voxel-wise and slice-by-slice region-of-interest analyses with QSM indicate that spatial distribution of iron inside the substantia nigra is highly inhomogeneous, with higher concentration of iron locate mainly in the pars compacta of the structure. This result confirms the post-mortem findings of abnormal iron accumulation in the substantia nigra pars compacta of Parkinson’s disease patients. QSM is then applied to examine the association between in vivo iron content and the expression of dementia symptom in Parkinson’s disease patients. Increased iron content is observed in hippocampus and amygdala of the demented Parkinson’s disease patients. Iron concentrations in these two structures are found to be negatively correlated with cognitive functions of the patients. This result suggests that abnormal iron accumulation in the limbic structures could possibly induce dementia symptom in Parkinson’s disease. Another study is performed with QSM to assess the association of in vivo iron content with psychotic expression of visual hallucination in Parkinson’s disease patients. Abnormal iron deposition is observed in thalamus, hippocampus and amygdala of the Parkinson’s disease patients with visual hallucination. Iron concentrations in these three structures are found to be positively correlated with the severity of the visual hallucination symptom of the patients. This result suggests that iron deposition could be related to the onset of visual hallucination in the Parkinson’s disease patients and severity of the symptom could depend on the iron content in these brain nuclei.

In conclusion, abnormal deposition of iron in different brain regions is confirmed to be associated with both motor and non-motor clinical manifestations of Parkinson’s disease patients. This study also demonstrates the feasibility of using SWI and QSM for in vivo iron quantification, and provides insights to future clinical applications of the two techniques in other iron-related neurodegenerative diseases.