Original contribution
Quantifying brain iron deposition in patients with Parkinson's disease using quantitative susceptibility mapping, R2 and R2*

https://doi.org/10.1016/j.mri.2015.02.021Get rights and content

Abstract

Purpose

To evaluate the sensitivity and specificity of quantitative magnetic resonance (MR) iron mapping including R2, R2* and magnetic susceptibility to differentiate patients with Parkinson's disease (PD) from healthy controls.

Materials and Methods

Thirty (30) healthy controls (HC) (64 ± 7 years old) and 20 patients with idiopathic PD (66 ± 8 years old) were studied using a 3 T MR imaging scanner. R2 maps were generated from GRASE sequence while R2*, and quantitative susceptibility mapping (QSM) were obtained from a conventional multi-echo gradient-echo sequence. R2, R2* and relative susceptibility (Δχ) values of structures in the basal ganglia were measured for each patient and control. An analysis of sensitivity and specificity and unpaired t-test was applied to the two groups.

Results

A significant difference (p < 0.05) was found for R2 and ∆χ values in the substantia nigra as a whole and in the pars compacta for PD patients. The R2* values were different significantly (p < 0.05) only on the substantia nigra pars compacta. QSM presented the highest sensitivity and specificity to differentiate the two populations.

Conclusion

The QSM map was the most sensitive quantitative technique for detecting a significant increase of iron for PD. The highest significant difference between controls and patients was found in the substantia nigra pars compacta using QSM.

Introduction

The ability of iron to accept and donate electrons makes it essential for cellular homeostasis and various biological reactions. However, excess iron deposition in the brain may lead to deleterious effects by generating reactive oxygen species that cause oxidative stress [1]. Some cadaver brain studies have found higher iron concentration in the basal ganglia in Parkinson's disease (PD) patients [2], [3], [4], [5] than in healthy controls (HC).

Several in vivo magnetic resonance (MR) imaging studies have used transverse relaxation rates (R2 and R2*) to distinguish patients with PD from healthy controls [6], [7], [8], [9], [10], [11], [12], [13], [14]. However, other studies were not able to find significant differences between the groups using the same approach [15], [16]. These contradictory results could be explained by the different methodologies used in these studies (segmentation of the structures and image acquisition parameters (echo time, numbers of echo time and inter-echo spacing) [17]. The relaxometry rates are influenced by changes in water content, local water diffusion rates in inhomogeneous field [18] and macroscopic magnetic field inhomogeneities.

Recently, quantitative susceptibility mapping (QSM) has been proposed to investigate iron concentration in the brain [19], [20], [21], [22], [23], [24], because it is, in principle, more accurate than transverse relaxation rates in terms of iron quantification. QSM has shown superior sensitivity over R2* mapping in differentiating controls and multiple sclerosis patients in regions with iron accumulation in the brain [25]. Another study showed that QSM improved contrast of the subthalamic nucleus in patients with PD better than T2-weighted, T2*-weighted, R2* mapping, susceptibility-weighted and phase images [26]. The subthalamic nucleus appeared to have higher iron content than the surrounding tissues [27].

A recent study reported elevated magnetic susceptibility values in the substantia nigra (SN) of patients with PD [28]. However, this study only analyzed the SN and did not compare iron in other structures. The comparative study of the MR techniques for iron quantification in the basal ganglia for patients with Parkinson's disease may define the most sensitive quantitative technique to estimate the metal and possible marker of PD. In our study, we propose the use of different quantitative MR techniques including R2 mapping, R2* mapping and QSM to quantify putative iron in multiple regions in the basal ganglia.

Section snippets

Subjects

The local ethics committee approved this study, and all participants signed the consent form. Twenty [20] patients (66 ± 8 years old, 12 males and 8 females) with idiopathic PD and 30 HC (64 ± 7 years old, 9 males and 21 females) were recruited from the university hospital and from the local university. The PD patients were selected by two experienced neurologists with expertise in extrapyramidal diseases (more than 10 years clinical experience each). The inclusion criteria for PD patients included:

Results

The normal and patient groups were age matched, and therefore there was no significant difference with age (p = < 0.5).

All R2, R2* and Δχ maps for structures in the basal ganglia showed a high contrast to the surrounding tissue (Fig. 3, Fig. 4). From a qualitative point of view, in general, it is hard to differentiate the age matched PD patients and controls from the information in Fig. 3, Fig. 4. By means of the segmentations performed by the three observers (ICC values of 0.97), R2, R2* and Δχ

Discussion

According to a review article by Grog and Berg (2012), the studies on R2 and R2* differentiating controls from patients with Parkinson's disease are controversial. Only 4 of 8 studies [6], [7], [8], [9] with R2 values and 6 of 8 studies [8], [10], [11], [12], [13], [14] with R2* values, found significant differences between groups in the region of the substantia nigra. The inconsistency of the iron quantification results in the literature may be explained by the use of different imaging

Conclusion

Susceptibility measurements represent the most sensitive quantitative technique to detect a significant increase of iron in PD patients. The highest significant difference between controls and patients was found for the substantia nigra pars compacta.

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    Contract grant sponsor: CNPq: 136062/2011-3, FAPESP: 2005/56447-7, CAPES.

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