Elsevier

NeuroImage: Clinical

Volume 3, 2013, Pages 481-488
NeuroImage: Clinical

Diffusion tensor imaging of nigral degeneration in Parkinson's disease: A region-of-interest and voxel-based study at 3 T and systematic review with meta-analysis

https://doi.org/10.1016/j.nicl.2013.10.006Get rights and content
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Highlights

  • Investigating diagnostic accuracy of nigral diffusion MRI to diagnose Parkinson's

  • There is small, inconsistent increase of mean diffusivity of the substantia nigra.

  • There is no change in nigral fractional anisotropy (FA) in the case–control study.

  • Meta-analysis revealed nigral FA change is dependent on high FA in controls.

  • This questions the usefulness of nigral diffusion MRI as biomarker in Parkinson's.

Abstract

There is increasing interest in developing a reliable, affordable and accessible disease biomarker of Parkinson's disease (PD) to facilitate disease modifying PD-trials. Imaging biomarkers using magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) can describe parameters such as fractional anisotropy (FA), mean diffusivity (MD) or apparent diffusion coefficient (ADC). These parameters, when measured in the substantia nigra (SN), have not only shown promising but also varying and controversial results.

To clarify the potential diagnostic value of nigral DTI in PD and its dependency on selection of region-of-interest, we undertook a high resolution DTI study at 3 T. 59 subjects (32 PD patients, 27 age and sex matched healthy controls) were analysed using manual outlining of SN and substructures, and voxel-based analysis (VBA). We also performed a systematic literature review and meta-analysis to estimate the effect size (DES) of disease related nigral DTI changes.

We found a regional increase in nigral mean diffusivity in PD (mean ± SD, PD 0.80 ± 0.10 vs. controls 0.73 ± 0.06 · 10 3 mm2/s, p = 0.002), but no difference using a voxel based approach. No significant disease effect was seen using meta-analysis of nigral MD changes (10 studies, DES = + 0.26, p = 0.17, I2 = 30%). None of the nigral regional or voxel based analyses of this study showed altered fractional anisotropy. Meta-analysis of 11 studies on nigral FA changes revealed a significant PD induced FA decrease. There was, however, a very large variation in results (I2 = 86%) comparing all studies. After exclusion of five studies with unusual high values of nigral FA in the control group, an acceptable heterogeneity was reached, but there was non-significant disease effect (DES =  0.5, p = 0.22, I2 = 28%).

The small PD related nigral MD changes in conjunction with the negative findings on VBA and meta-analysis limit the usefulness of nigral MD measures as biomarker of Parkinson's disease. The negative results of nigral FA measurements at regional, sub-regional and voxel level in conjunction with the results of the meta-analysis of nigral FA changes question the stability and validity of this measure as a PD biomarker.

Abbreviations

PD
Parkinson's disease
MRI
Magnetic resonance imaging
DTI
Diffusion tensor imaging
MD
Mean diffusivity
ADC
Apparent diffusion coefficient
SN
Substantia nigra
SNc
Substantia nigra pars compacta
DES
Effect size of disease related nigral changes
VBA
Voxel based analysis
TCS
Transcranial sonography
ACE
Addenbrooke's cognitive examination test battery
UPDRS
Unified Parkinson's disease rating scale
EPI
Echo planar imaging
ROI
Region/regions of interest
ICC
Intraclass correlation coefficient

Keywords

Parkinson's disease
Parkinsonism
Diffusion weighted imaging
Magnetic resonance imaging
Substantia nigra
Fractional anisotropy

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