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. 2013 Jun 13;8(6):e66022.
doi: 10.1371/journal.pone.0066022. Print 2013.

Assessment of Global and Regional Diffusion Changes Along White Matter Tracts in Parkinsonian Disorders by MR Tractography

Free PMC article

Assessment of Global and Regional Diffusion Changes Along White Matter Tracts in Parkinsonian Disorders by MR Tractography

Yulia Surova et al. PLoS One. .
Free PMC article


Purpose: The aim of the study was to determine the usefulness of diffusion tensor tractography (DTT) in parkinsonian disorders using a recently developed method for normalization of diffusion data and tract size along white matter tracts. Furthermore, the use of DTT in selected white matter tracts for differential diagnosis was assessed.

Methods: We quantified global and regional diffusion parameters in major white matter tracts in patients with multiple system atrophy (MSA), progressive nuclear palsy (PSP), idiopathic Parkinson's disease (IPD) and healthy controls). Diffusion tensor imaging data sets with whole brain coverage were acquired at 3 T using 48 diffusion encoding directions and a voxel size of 2×2×2 mm(3). DTT of the corpus callosum (CC), cingulum (CG), corticospinal tract (CST) and middle cerebellar peduncles (MCP) was performed using multiple regions of interest. Regional evaluation comprised projection of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and the apparent area coefficient (AAC) onto a calculated mean tract and extraction of their values along each structure.

Results: There were significant changes of global DTT parameters in the CST (MSA and PSP), CC (PSP) and CG (PSP). Consistent tract-specific variations in DTT parameters could be seen along each tract in the different patient groups and controls. Regional analysis demonstrated significant changes in the anterior CC (MD, RD and FA), CST (MD) and CG (AAC) of patients with PSP compared to controls. Increased MD in CC and CST, as well as decreased AAC in CG, was correlated with a diagnosis of PSP compared to IPD.

Conclusions: DTT can be used for demonstrating disease-specific regional white matter changes in parkinsonian disorders. The anterior portion of the CC was identified as a promising region for detection of neurodegenerative changes in patients with PSP, as well as for differential diagnosis between PSP and IPD.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.


Figure 1
Figure 1. Schematic illustration of the method used to display the variation of the diffusion parameters along the tracts.
Projection of diffusion parameters to a mean track resulted in individual parameter-versus-position plots (A), which were associated to the positions of the landmarks, shown as letters a-b-c in circles along the x-axis. The positions were normalized by interpolating the data so that the interval lengths a–b and b–c became equal in all individuals (B). Finally, the apparent area coefficient (AAC) of the tracts was calculated from cross sections of the tracts, where each individual track point (C, blue points) contributed to the total area coefficient with a weight of πr2, with r = 0.5 mm. Only non-overlapping parts of the subareas contributed to the total area coefficient.
Figure 2
Figure 2. Comparisons between diffusion parameters and apparent area coefficient (AAC) in patients with Parkinsons’s disease (IPD – blue lines), multiple system atrophy (MSA – green lines), progressive supranuclear palsy (PSP – red lines) and controls (CTR – black lines).
The lines show the median of diffusion parameters as a function of distance. The colored area shows the 10–90% confidence interval of the median in CTR. Panel A-C show mean diffusivity (MD), fractional anisotropy (FA), radial diffusivity (RD) and AAC in the cingulum, corticospinal tract, middle cerebellar peduncles and the corpus callosum, respectively. Values for AAC could not be calculated for the corpus callosum (see Methods). Positions with significant difference from controls (P<0.05, Mann–Whitney U-test) along tracts are marked with horizontal bars placed just above the x-axis, color-coded according to disease. Significant differences extending continuously for more than five mm along a tract were found for AAC in the cingulum, MD in the corticospinal tract, and RD, MD and FA in the corpus callosum in PSP.
Figure 3
Figure 3. The plots show radial diffusivity (RD) and fractional anisotropy (FA) as functions of position along the cingulum (CG) (upper panels) and corticospinal tract (CST) (lower panels) from the right and left hemispheres in controls.
Measurements from the right hemisphere are shown in blue and from the left side in red lines, respectively. The dashed and solid black lines represent the median value in each position of the left and right hand side tracts, respectively. The horizontal axis shows the position along CG in anterior – posterior direction. Distances 0–6 cm correspond approximately to the frontal part of the CG and 6–9 cm corresponds to the parietal part of the CG. For CST the horizontal axis shows the position along CST in inferior – superior direction. Distances 0–3 cm correspond approximately to the infracallosal part of the CST and 3–5 cm corresponds to the supracallosal part of the CST.
Figure 4
Figure 4. Beeswarm box-plot comparing mean diffusivity and fractional anisotropy in the anterior part of corpus callosum between patients with Parkinson’s disease, multiple system atrophy, progressive supranuclear palsy and controls.
Horizontal lines that intersect the boxes are medians. The top of the boxes is the 75th percentile and the bottom the 25th percentile. The whiskers above and below boxes represent maximum and minimum values when there are no outliers. If outliers are present the whisker on the appropriate side is taken to 1.5×IQR from the quartile. Outliers are labeled with open circles.

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Grant support

This research was supported by the Swedish Parkinson foundation, the Swedish Science Council grants through the Linnaeus project BAGADILICO, the Swedish Parkinson Academy and research funds from province of Skåne University Hospital and state grants (inclusively ALF) and in part by the Swedish Cancer Society (GrantNo CAN 2009/1076 and CAN 2012/597). The funders had no role in study design, data collection and analysis, decision to publish and preparation of the manuscript.