Original contributionQuantitative 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
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.
References (22)
- et al.
Characterizing Iron Deposition in Parkinson’s Disease Using Susceptibility-weighted imaging: an in vivo MR study
Brain Res
(2010) - et al.
Susceptibility-weighted angiography (SWAN) of cerebral veins and arteries compared to TOF-MRA
Eur J Radiol
(2012) - et al.
Iron deposition of deep grey matter in patients with multiple sclerosis and neuromyelitis optica: a control quantitative study by 3D-enhanced susceptibility-weighted angiography (ESWAN)
Eur J Radiol
(2012) - et al.
Susceptibility weighted magnetic resonance sequences "SWAN, SWI and VenoBOLD":Technical aspects and clinical applications
J Neororadiol
(2012) - et al.
MRI assessment of basal ganglia iron deposition in Parkinson's disease
J Magn Reson Imaging
(2008) - et al.
Iron metabolism in Parkinsonian syndromes
Mov Disord
(2006) Etiology of Parkinson’s disease
Neurology
(2006)- et al.
MR of human postmortem brain tissue: correlative study between T2 and assays of iron and ferritin in Parkinson and Huntington disease
AJNR Am J Neuroradiol
(1993) - et al.
Susceptibility weighted imaging (SWI)
Magn Reson Med
(2004) - et al.
et a1. Contrast-enhanced, high-resolution, susceptibility-weighted imaging of the brain:dose-dependent optimization at 3 Tesla and 1.5 Tesla in healthy volunteers
Invest Radiol
(2006)
Determination of brain iron content in patients with Parkinson's disease using magnetic susceptibility imaging
Neurosci Bull
Cited by (32)
A review of diagnostic imaging approaches to assessing Parkinson's disease
2022, Brain DisordersMidbrain area for differentiating Parkinson's disease from progressive supranuclear palsy
2019, Clinical Neurology and NeurosurgeryIron-related nigral degeneration influences functional topology mediated by striatal dysfunction in Parkinson's disease
2019, Neurobiology of AgingCitation Excerpt :As reviewed previously (Guan et al., 2017c; Lotfipour et al., 2012), because of the limited resolution of the clinical MRI scanner, there were different definitions for SN substructures. For example, many studies defined the tier with low signal between iron rich (bright signal in QSM) red nucleus and SN (located in the ventrolateral to red nucleus) as SNc (Du et al., 2016; Guan et al., 2017b,d; Martin et al., 2008; Wang et al., 2013). Therefore, as a control, we equally segmented this predefined SNc into superior, middle, and inferior parts in the template space and the averaged bilateral magnetic susceptibility from each subregion of SNc was calculated (Fig. S1).
Astroglial and microglial contributions to iron metabolism disturbance in Parkinson's disease
2018, Biochimica et Biophysica Acta - Molecular Basis of DiseaseAssociation of freezing of gait with nigral iron accumulation in patients with Parkinson's disease
2017, Journal of the Neurological Sciences