Elsevier

Magnetic Resonance Imaging

Volume 31, Issue 7, September 2013, Pages 1068-1073
Magnetic Resonance Imaging

Original contribution
Quantitative assessment of iron deposition in the midbrain using 3D-enhanced T2 star weighted angiography (ESWAN): A preliminary cross-sectional study of 20 Parkinson’s disease patients

https://doi.org/10.1016/j.mri.2013.04.015Get rights and content

Abstract

Conventional magnetic resonance imaging (MRI) assesses neurodegenerative structural changes in the cerebral anatomy of Parkinson's disease (PD) patients but cannot detect non-structural abnormalities; however, enhanced T2 star weighted angiography (ESWAN) can precisely indicate PD-related substantia nigra (SN) iron deposition. The differences in ESWAN-based parameters between different PD stages were assessed using midbrain iron deposits of 20 PD patients aged 64.3 ± 12.7 (41–85) years grouped by Hoehn and Yahr staging into minimal (stages ≤ 2.5) or moderate to severe (stages ≥ 3.0) motor impairment groups and 14 healthy control subjects. Conventional MRI and ESWAN measurements of mean phase value (MPV) and midbrain dimensions (width and diameter) revealed similar anatomical characteristics; however, ESWAN revealed the presence of smaller MPVs and SN pars compacta (SNc) (P < 0.01) and a negative correlation between reduction extent and motor impairment (P < 0.01). SNc width to midbrain diameter was reduced in moderate to severe impairment patients versus control and minimal impairment patients (both P < 0.01). A positive correlation was found between MPV and width or SNc width to midbrain diameter ratio (P < 0.01 and P < 0.05, respectively). Minimal impairment group mean MPV and substantia nigra pars reticulata (SNr) width evidenced no significant reduction, unlike significant reductions in the moderate to severe impairment group (P < 0.01). No significant changes were observed in MPV or width in the RN region (P > 0.05). ESWAN allows for early and accurate iron deposition determination in PD patients, particularly useful as a supplement to conventional MRI in early-stage PD patients.

Introduction

Progressive worsening of motor impairments associated with Parkinson’s disease (PD) has been linked with increasing iron deposition in the mesencephalon (midbrain), particularly in the substantia nigra (SN) region [1]. In addition, iron metabolism dysfunctions have also been linked with other disorders involving symptomatic multiple system degeneration with the classical features of PD, known as Parkinsonian syndromes [2]. As symptoms of these diseases become more pronounced, most patients experience difficulty walking, speaking, and completing normal activities of daily living [1]. In different populations, the average age on onset for PD ranges from age 40 to 67 years, though many cases begin long before neurodegeneration results in symptoms and diagnosis [3]. Particularly in PD associated with certain genetic mutations, the slow onset of signs and symptoms can make early-stage PD symptoms difficult to diagnose [3]. With conventional magnetic resonance imaging (MRI) and computed tomography (CT) methods, early-stage PD and Parkinsonian syndromes are often impossible to differentiate, particularly when complicated by other neurologic diseases [2]. Thus, modern techniques, such as enhanced T2 star weighted angiography (ESWAN), may be able to provide superior assessments of the differences in ESWAN-based parameters between different stages of PD, potentially leading to future improvements in PD diagnosis and prognosis based on a better understanding of the association between iron deposition and PD progression.

MRI methods are most commonly used for examination of the extent of dopaminergic neuron loss in the midbrain and abnormalities in the SN region [1]. Excessive iron deposition in the midbrain, first indicated by conventional MRI studies, has recently been identified as a critical factor in PD pathophysiology and is the subject of numerous contemporary research studies [1], [4]. Susceptibility-weighted imaging (SWI) is an MRI technique that leverages the magnetic susceptibility differences in various tissues [5]. Because tissues containing high levels of iron have very different susceptibilities than normal tissues, high-pass filtered SWI phase images have been used to identify cerebral tissues containing high levels of iron [6]. While some useful information is provided by SWI images, methods that accurately quantify iron levels in cerebral tissues are required for effective early diagnosis of PD patients that exhibit only minimal symptoms and small iron-containing plaques.

By examining specific regions of interest (ROIs) in the midbrain using SWI imaging, Zhang et al. [7] found that iron concentrations in the SN of PD patients were the most significantly associated with symptomatic progression. Conversely, other studies have indicated that concentrations in iron in the substantia nigra pars compacta (SNc), caudate nucleus (CN), and red nucleus (RN) of PD patients are significant [8]. While these studies have generated preliminary results, further quantitative investigation is necessary to confirm the iron levels in specific midbrain tissues of PD patients. Recently, three-dimensional (3D)-ESWAN has been suggested as a potential diagnostic technique for PD patients. ESWAN combines novel 3D T2 star-based multi-echo acquisition with a reconstruction algorithm that, unlike conventional SWI, generates exact, quantitative information on iron deposition in living tissues [9], [10].

In order to provide previously undocumented quantitative information pertaining to assessment of the differences in ESWAN-based parameters between different stages of PD, including midbrain iron deposition, ESWAN was used to assess the phase values and midbrain dimensions (width and diameter) of the substantia nigra (SN), substantia nigra pars compacta (SNc), and red nucleus (RN) of PD patients with minimal and moderate to severe symptoms, as indicated by Hoehn and Yahr stage. Using ESWAN, the current study was conducted to confirm the previously reported correlation between iron deposition in midbrain tissues and PD progression [7], [8] and demonstrate the diagnostic sensitivity of ESWAN for potential clinical application.

Section snippets

Patients

A prospective cross-sectional study of 20 PD patients (male:female, 10:10) with a mean age of 67.3 ± 10.7 years (ranging 46–84 years) treated at the First Hospital of China Medical University from April 2010 to April 2011 (experimental group). A total of 14 healthy sex- and age-matched volunteers with a mean age of 64.3 ± 12.7 years (ranging 41–85 years) were included in the control group. Written informed consent was obtained from all participants. The study protocol was approved by the Medical

Patient demographic and clinical data

No significant differences in sex and age were found among the minimal impairment group (Hoehn and Yahr Stages ≤ 2.5) (n = 13), the moderate to severe impairment group (Hoehn and Yahr Stages ≥ 3.0 (n = 7) and the healthy (control) group (n = 14) (P > 0.05). There was no significant differences between PD patients in the minimal impairment group exhibited a mean disease duration of 2.4 ± 2.3 years, ranging 0.5-8 years, and PD patients in the moderate to severe impairment group exhibited a mean disease

Discussion

Examination of the midbrain SNr, SNc, and RN ROIs in PD patients revealed similar iron deposition results between conventional MRI and ESWAN, though the latter provided much more detailed quantitative information using automated, computerized analysis. These findings confirm previous reports of the association between iron deposition and progressive symptom severity in PD patients [7], [8]. Because early diagnosis of PD using symptoms alone has been a persistent challenge in clinical settings,

Acknowledgments

The authors thank Wenge Sun, M.S., for his technical expertise, Yongfeng Wang, B.S., Zhaofeng Li, B.S., Yanliang Li, B.S., Xixun Qi, B.S., Tao LU, B.S., for their assistances with the study and the research subjects for their participation. This work was supported by the National Science Foundation of China, Grant no. 81171327.

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