Evaluation of abnormal iron distribution in specific regions in the brains of patients with Parkinson's disease using quantitative susceptibility mapping and R2* mapping

Abstract

The primary aim of the present study was to evaluate abnormal iron distribution in specific regions of the brains in patients with Parkinson's disease (PD) using quantitative susceptibility mapping (QSM) and R2 * mapping, and to compare the diagnostic performances of QSM and R2 * mapping in differentiating patients with PD with that in normal controls. A total of 25 patients with idiopathic PD and 28 sex-and age-matched normal controls were included in the present study and their brains investigated using a 3T scanner. Magnetic resonance imaging techniques, namely, QSM and R2 * mapping, were applied to generate susceptibility and R2 * values. The differences in susceptibility and R2 * values in deep grey matter nuclei between patients with PD and the normal controls were compared using independent samples t-tests. The abilities of QSM and R2 * mapping to classify patients with PD and normal controls were analyzed using receiver operating characteristic curves. Correlation analyses between imaging parameters (e.g. susceptibility and R2 * values) and clinical feature (disease severity assessed using the Hoehn and Yahr score) were performed. The intra-class correlation coefficient (ICC) for susceptibility (ICC= 0.977; P<0.001) and R2 * (ICC=0.945; P<0.001) values between two neuro-radiologists were >0.81, showing excellent inter-rater agreement. The susceptibility values were significantly increased in the substantia nigra (SN) and red nucleus, but were decreased in the putamen of patients with PD compared with that in the corresponding brain regions of normal controls. However, increased R2 * values were observed only in the SN in patients with PD. QSM showed higher sensitivity and specificity compared with R2 * mapping to separate the patients with PD from the normal controls. There were no significant correlations between the susceptibility/R2 * values and clinical features in all targeted regions of the brains in patients with PD. In conclusion, both QSM and R2 * mapping are feasible to calculate the iron levels in human brains, and QSM provides a more sensitive and accurate method to assess regional abnormal iron distribution in patients with PD.

Imaging the Substantia Nigra in Parkinson Disease and Other Parkinsonian Syndromes

“…This shows the close relationship between PD and iron deposition in the SN pars compacta. Similar findings show that QSM has a higher diagnostic performance than R2* mapping in patients with PD (74,90,91). Notably, patients with early PD showed higher susceptibility values in the bilateral SN on QSM images.…”

Cerebral Microstructural Alterations in Patients With Early Parkinson’s Disease Detected With Quantitative Magnetic Resonance Measurements

“…Increased iron, copper and manganese concentrations in the substantia nigra were reported in a mouse model of experimental Parkinsonism (Matusch et al, 2012). Several other studies also reported significantly increased iron concentrations in the substantia nigra of PD patients compared to healthy controls by quantitative susceptibility mapping (Langkammer et al, 2016;Wang et al, 2016;Chen et al, 2019;Cheng et al, 2020). In a study of patients with neurodegeneration with brain iron accumulation (NBIA), thalamic and mesencephalic iron accumulation was also detected (McNeill et al, 2012).…”

Pretreatment with Human Lactoferrin Had a Positive Effect on the Dynamics of Mouse Nigrostriatal System Recovery after Acute MPTP Exposure

“…Previous research has demonstrated iron accumulation in the brain of PD patients [ 13 , 14 ] and MPTP-treated mice [ 15 , 16 ]. Increased iron concentrations can induce oxidative stress through ROS generation and cause neuronal damage [ 15 , 17 , 18 ].…”