Regionally progressive accumulation of iron in Parkinson's disease as measured by quantitative susceptibility mapping

Abstract

The progression of Parkinson’s disease (PD) seems to vary according to the disease stage, which greatly influences the management of PD patients. However, the underlying mechanism of progression in PD remains unclear. This study was designed to explore the progressive pattern of iron accumulation at different stages in PD patients. Sixty right-handed PD patients and 40 normal controls were recruited. According to the disease stage, 45 patients with Hoehn-Yahr stage ≤ 2.5 and 15 patients with Hoehn-Yahr stage ≥ 3 were grouped into early-stage PD (EPD) and late-stage PD (LPD) groups, respectively. The iron content in the cardinal subcortical nuclei covering the cerebrum, cerebellum and midbrain was measured using quantitative susceptibility mapping (QSM). The substantia nigra pars compacta (SNc) showed significantly increased QSM values in the EPD patients compared with the controls. In the LPD patients, while the SNc continued to show increased QSM values compared with the controls and EPD patients, the regions showing increased QSM values spread to include the substantia nigra pars reticulata (SNr), red nucleus (RN) and globus pallidus (GP). Our data also indicated that iron deposition in the GP internal segment (GPi) was more significant than in the GP external segment. No other regions showed significant changes in QSM values among the groups. Therefore, we were able to confirm a regionally progressive pattern of iron accumulation in the different stages of PD, indicating that iron deposition in the SNc is affected exclusively in the early stages of the disease while the SNr, RN and GP, and particularly the GPi segment, become involved in advanced stages of the disease. This is a preliminary study providing objective evidence of the iron-related progression in PD.

Quantitative Evaluation of Iron Content in Idiopathic Rapid Eye Movement Sleep Behavior Disorder

“…Excessive iron likely contributes to the dysfunction of the nigrostriatal pathway, which is heavily involved in the motor deficits seen in PD patients. We did not find a significant correlation between iron content and any of the clinical assessments in the PD group, which is inconsistent with some previous studies . However, a recent study also did not find a correlation between iron content and clinical data in PD patients .…”

Quantitative Susceptibility Mapping in Parkinson's Disease

“…Related studies have found regional susceptibility or R2* differences in single individual anatomical structures such as the putamen, caudate nucleus or the globus pallidus [17,34,35]. Extending these findings, we were able to demonstrate a more widespread involvement of the deep gray matter structures by applying QSM, including the substantia nigra, nucleus ruber, thalamus, and globus pallidus.…”

Meta-analysis of brain iron levels of Parkinson’s disease patients determined by postmortem and MRI measurements

“…Recently, quantitative susceptibility mapping (QSM), a potentially superior method to measuring iron content in vivo , has been applied to measure PD-related iron deposition and progression28. By this method, Guan et al 59. have recently reported a distinct pattern of iron accumulation according to disease stage, with iron spreading from the substantia nigra in early stages to the substantia nigra, red nucleus and globus pallidus in later stages.…”