Elsevier

NeuroImage

Volume 99, 1 October 2014, Pages 498-508
NeuroImage

Mapping track density changes in nigrostriatal and extranigral pathways in Parkinson's disease

https://doi.org/10.1016/j.neuroimage.2014.06.033Get rights and content
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Highlights

  • First whole-brain probabilistic tractography study in Parkinson's disease

  • High quality diffusion-weighted images (120 gradient directions, b = 2500 s/mm2)

  • Voxel-based group analysis comparing early-stage patients and controls

  • Abnormal reconstructed track density in the nigrostriatal pathway and brainstem

  • Track density also increased in limbic and cognitive circuits.

Abstract

In Parkinson's disease (PD) the demonstration of neuropathological disturbances in nigrostriatal and extranigral brain pathways using magnetic resonance imaging remains a challenge. Here, we applied a novel diffusion-weighted imaging approach—track density imaging (TDI).

Twenty-seven non-demented Parkinson's patients (mean disease duration: 5 years, mean score on the Hoehn & Yahr scale = 1.5) were compared with 26 elderly controls matched for age, sex, and education level. Track density images were created by sampling each subject's spatially normalized fiber tracks in 1 mm isotropic intervals and counting the fibers that passed through each voxel. Whole-brain voxel-based analysis was performed and significance was assessed with permutation testing.

Statistically significant increases in track density were found in the Parkinson's patients, relative to controls. Clusters were distributed in disease-relevant areas including motor, cognitive, and limbic networks. From the lower medulla to the diencephalon and striatum, clusters encompassed the known location of the locus coeruleus and pedunculopontine nucleus in the pons, and from the substantia nigra up to medial aspects of the posterior putamen, bilaterally.

The results identified in brainstem and nigrostriatal pathways show a large overlap with the known distribution of neuropathological changes in non-demented PD patients. Our results also support an early involvement of limbic and cognitive networks in Parkinson's disease.

Abbreviations

18F-DOPA
[18F]-l-dihydroxyphenylalanine
APM
average pathlength map
BA
Brodmann area
DA
dopamine
DTI
diffusion tensor imaging
DW
diffusion-weighted
DWI
diffusion-weighted imaging
FA
fractional anisotropy
FDG
18Fluorodeoxyglucose
FLASH
fast low-angle shot
FOD
fiber orientation distribution
IFO
inferior fronto-occipital fasciculus
ILF
inferior longitudinal fasciculus
LC
locus coeruleus
LEDD
levodopa equivalent daily dose
MD
mean diffusivity
MT
magnetization transfer
NSP
nigrostriatal pathway
PD
proton density
PDQ
Parkinson's disease questionnaire
PET
positron emission tomography
SCP
superior cerebellar peduncle
SLF
superior longitudinal fasciculus
SN
substantia nigra
TDI
track density imaging
TPM
total pathlength map
UPDRS
Unified Parkinson's Disease Rating Scale
VTA
ventral tegmental area

Keywords

Parkinson's disease
Tractography
Diffusion
White matter
Substantia nigra

Cited by (0)

Data for this article are available at: http://www.nitrc.org/projects/parktdi/.

1

These authors contributed equally to this work.