Asymmetrical diffusion tensor imaging indices of the rostral substantia nigra in Parkinson’s disease Bhaskaran David Prakash a, b , Yih-Yian Sitoh c , Louis C.S. Tan a, b , Wing Lok Au a, b, * a Department of Neurology, National Neuroscience Institute, Singapore b Parkinson’s Disease and Movement Disorders Centre, National Neuroscience Institute, Singapore c Department of Neuroradiology, National Neuroscience Institute, Singapore article info Article history: Received 20 January 2012 Received in revised form 22 March 2012 Accepted 13 May 2012 Keywords: Parkinson’s disease Left-right asymmetry Diffusion tensor imaging abstract Objective: Motor asymmetry in Parkinson’s disease (PD) is evident clinically and on functional neuro- imaging, 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 signif- icantly 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 ¼ 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. Ó 2012 Elsevier Ltd. All rights reserved. 1. Introduction Parkinson’s disease (PD) is a neurodegenerative disorder char- acterized 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 asym- metrical 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 magni- tude 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. * Corresponding author. Department of Neurology, National Neuroscience Insti- tute,11 Jalan Tock Seng, Singapore 308433, Singapore. Tel.: þ65 6357 7171; fax: þ65 6357 7137. E-mail address: wing_lok_au@nni.com.sg (W.L. Au). Contents lists available at SciVerse ScienceDirect Parkinsonism and Related Disorders journal homepage: www.elsevier.com/locate/parkreldis 1353-8020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved. doi:10.1016/j.parkreldis.2012.05.021 Parkinsonism and Related Disorders 18 (2012) 1029e1033