Asymmetrical diffusion tensor imaging indices of the rostral substantia nigra in Parkinson's disease

doi:10.1016/j.parkreldis.2012.05.021

Parkinsonism & Related Disorders

Volume 18, Issue 9, November 2012, Pages 1029-1033

https://doi.org/10.1016/j.parkreldis.2012.05.021 Get rights and content

Abstract

Objective

Motor asymmetry in Parkinson's disease (PD) is evident clinically and on functional neuroimaging, but not reported in diffusion tensor imaging (DTI). We aim to determine if asymmetry in fractional anisotropy (FA) and apparent diffusion coefficient (ADC) can be detected in the substantia nigra (SN) of PD subjects.

Methods

DTI scans were performed on 11 PD and 12 healthy subjects. Regions of interest (ROIs) were drawn by 2 independent raters at the caudal, middle and rostral SN on each side. FA and ADC were extracted from the ROIs.

Results

Significant asymmetry was observed in the FA (p < 0.005) and ADC (p < 0.00005) at the rostral SN of PD subjects. The differences in FA and ADC across the left and right rostral SN were significantly different between PD and healthy subjects, p < 0.05 and p < 0.02 respectively. PD subjects had significantly higher ADC at the left rostral SN than healthy subjects (p < 0.01). Significant correlation between the Unified Parkinson's Disease Rating Scale (UPDRS) motor scores and the FA was noted in the left rostral SN (r = 0.7, p < 0.03).

Conclusions

Asymmetry in DTI indices was noted at the rostral SN of PD subjects. The relationship between FA in the SN and UPDRS motor score was studied. Our findings may provide a model for better understanding of the implication of FA reduction in the SN.

Introduction

Parkinson's disease (PD) is a neurodegenerative disorder characterized by nigrostriatal cell loss, resulting in striatal dopamine deficiency [1]. The motor symptoms such as bradykinesia, rigidity, and tremor appear when 80% of the striatal dopamine, or 50% of the nigral cells are lost [1], [2]. In general, one side of the body is affected more than the other, and the asymmetry persists throughout the course of the disease [3], [4]. Motor asymmetry is correlated with contralateral striatal dopamine deficiency [5] and contralateral ventricular enlargement [6]. However, the reason for the asymmetrical involvement is not known.

Diffusion tensor imaging (DTI) is a relatively new technique to study the fibre tracts in the brain through measurement of the directional and diffusivity of water molecules [7]. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) are two measurable DTI values which give the directionality (anisotropy) and magnitude (diffusivity) of water diffusion respectively [8].

The FA is a scalar value between 0 and 1, with higher values found in white matter due to orientation and organization of the fibres [9], [10]. A breakdown in fibre integrity should result in a lower FA due to isotropic flow, and a higher ADC due to increase magnitude of water diffusion. Various studies have reported a lower FA in the substantia nigra (SN) of PD subjects, and along the nigrostriatal projections into the frontal lobes, the premotor areas and the cingulum [11], [12]. One group has shown a trend towards higher ADC in the SN of PD subject [11]. Changes in FA can reveal the progressive degeneration in the SN and the ascending nigrostriatal fibres [11], [13]. Using high resolution DTI, reduced FA has been shown in the caudal, middle and rostral regions of the SN in early untreated PD patients, with high sensitivity and specificity in the caudal regions [13]. In a study on PD subjects on medication, Modrego et al. [14] found a significant correlation between the Unified Parkinson's Disease Rating Scale (UPDRS) motor score and the FA at the side of the rostral SN with a lower mean value, which indirectly suggests a possible asymmetry of FA at the rostral SN. However, significant asymmetry for FA or ADC in the SN of PD subjects has never been reported in the literature to date.

In this study, we aim to determine if asymmetry in FA and ADC can be detected in the SN of PD subjects in the early stages of the disease. The relationship between motor severity and the DTI indices is also studied.

Section snippets

Methods

We studied 11 clinically definite PD subjects (7 women, 4 men, mean age 60.4 ± 9.3 years) according to the diagnostic criteria of Calne et al. [3] and 12 normal subjects (6 women, 6 men, mean age 60.8 ± 8.5 years). All were right handed ethnic Chinese. Subjects with atypical parkinsonism, dementia, psychiatric illness, severe motor fluctuation, on dopamine blocking agents, or with contraindications to magnetic resonance imaging were excluded from the study. The PD subjects had mild to moderate

Results

There were no significant differences in the extracted FA and ADC at each respective ROI locations between the two raters (BDP, WLA). As such only values obtained by WLA were reported in this paper.

Discussion

Our study is the first to report significant asymmetry in FA and ADC at the SN in PD subjects, in particular the FA was lower and the ADC was higher at the left rostral SN compared to the right, regardless of the motor asymmetry. The FA asymmetry was seen mainly in the subgroup of PD subjects with HY < 2, in particular those with HY 1.5 (i.e. unilateral disease with slight postural instability). We also observed a similar negative correlation (although not statistically significant) between FA

Conclusions

Asymmetry in DTI indices was noted at the rostral SN of PD subjects, which did not correlate with the side of clinical involvement. The relationship between FA and UPDRS motor score was studied. Our findings may provide a model for better understanding of the implication of FA reduction in the SN. These novel findings will require future validation studies using a larger sample population with greater variations in age, disease severity, and handedness.

Acknowledgements

We would like to thank Ms Irene Seah for her assistance in recruiting subjects.

The study is supported by research grant from Singapore Millennium Foundation Limited.

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Asymmetrical diffusion tensor imaging indices of the rostral substantia nigra in Parkinson's disease

Abstract

Objective

Methods

Results

Conclusions

Introduction

Section snippets

Methods

Results

Discussion

Conclusions

Acknowledgements

J Neurol Sci

Biophys J

Acad Radiol

Comput Methods Programs Biomed

Lancet

Neuroscience

Horm Behav

Am J Geriatr Psychiatry

Neuroscience

Brain Res

Ageing and Parkinson's disease: substantia nigra regional selectivity

Brain

Criteria for diagnosing Parkinson's disease

Ann Neurol

Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases

J Neurol Neurosurg Psychiatry

Asymmetrical pre-synaptic and post-synpatic changes in the striatal dopamine projection in dopa naive parkinsonism. Diagnostic implications of the D2 receptor status

Brain

Asymmetrical lateral ventricular enlargement in Parkinson's disease

Eur J Neurol

Looking into the functional architecture of the brain with diffusion MRI

Nat Rev Neurosci