Alterations of Diffusion Kurtosis and Neurite Density Measures in Deep Grey Matter and White Matter in Parkinson's Disease

PLoS One. 2016 Jun 30;11(6):e0157755. doi: 10.1371/journal.pone.0157755. eCollection 2016.


In Parkinson's disease (PD), pathological microstructural changes occur and such changes might be detected using diffusion magnetic resonance imaging (dMRI). However, it is unclear whether dMRI improves PD diagnosis or helps differentiating between phenotypes, such as postural instability gait difficulty (PIGD) and tremor dominant (TD) PD. We included 105 patients with PD and 44 healthy controls (HC), all of whom underwent dMRI as part of the prospective Swedish BioFINDER study. Diffusion kurtosis imaging (DKI) and neurite density imaging (NDI) analyses were performed using regions of interest in the basal ganglia, the thalamus, the pons and the midbrain as well as tractography of selected white matter tracts. In the putamen, the PD group showed increased mean diffusivity (MD) (p = .003), decreased fractional anisotropy (FA) (p = .001) and decreased mean kurtosis (MK), compared to HC (p = .024). High MD and a low MK in the putamen were associated with more severe motor and cognitive symptomatology (p < .05). Also, patients with PIGD exhibited increased MD in the putamen compared to the TD patients (p = .009). In the thalamus, MD was increased (p = .001) and FA was decreased (p = .032) in PD compared to HC. Increased MD and decreased FA correlated negatively with motor speed and balance (p < .05). In the superior longitudinal fasciculus (SLF), MD (p = .019) and fiso were increased in PD compared to HC (p = .03). These changes correlated negatively with motor speed (p < .002) and balance (p < .037). However, most of the observed changes in PD were also present in cases with either multiple system atrophy (n = 11) or progressive supranuclear palsy (n = 10). In conclusion, PD patients exhibit microstructural changes in the putamen, the thalamus, and the SLF, which are associated with worse disease severity. However, the dMRI changes are not sufficiently specific to improve the diagnostic work-up of PD. Longitudinal studies should evaluate whether dMRI measures can be used to track disease progression.

MeSH terms

  • Aged
  • Case-Control Studies
  • Diffusion Magnetic Resonance Imaging / methods*
  • Diffusion Tensor Imaging / methods*
  • Female
  • Gray Matter / diagnostic imaging*
  • Gray Matter / pathology
  • Humans
  • Male
  • Middle Aged
  • Neurites / pathology*
  • Parkinson Disease / diagnostic imaging*
  • Parkinson Disease / pathology
  • Prospective Studies
  • Putamen / diagnostic imaging
  • Putamen / pathology
  • Supranuclear Palsy, Progressive / pathology
  • Sweden
  • Thalamus / diagnostic imaging
  • Thalamus / pathology
  • White Matter / diagnostic imaging*
  • White Matter / pathology

Grants and funding

The study was supported by the European Research Council, the Swedish Research Council, The Parkinson Foundation of Sweden, the Swedish Brain Foundation, the Swedish Cancer Society (grant no. CAN 2009/1076), the Swedish Foundation for Strategic Research (AM13-0090), and the Swedish Federal Government under the ALF Agreement. The funding sources had no role in the design and conduct of the study; in the collection, analysis, interpretation of the data; or in the preparation, review, or approval of the manuscript.