DTI analysis in patients with primary open-angle glaucoma: impact of registration on Voxel-Wise statistics

PLoS One. 2014 Jun 5;9(6):e99344. doi: 10.1371/journal.pone.0099344. eCollection 2014.


Background and purpose: Tract-based spatial statistics (TBSS) has been used to assess the integrity of the visual pathway in glaucoma patients. TBSS uses the subjects' FA data to create a mean FA skeleton of white matter tracts before running voxel-wise cross-subject statistics. We compared four different approaches of registration of FA maps to create the skeleton and evaluated alignment and subsequently the impact of the chosen registration on voxel-wise statistics.

Material and methods: Our study comprised 69 subjects, i.e. 46 patients with primary open angle glaucoma (POAG) and a healthy, age-matched control group of 23 subjects. Mean FA skeletons were created using the following registration approaches: registration to a standard template (T), registration to the group mean (GM), registration to a group-wise atlas (GW) and registration to the most typical subject (N). Subsequently, maps of standard deviation of the 4D images were created to assess the alignment. Voxel-wise statistics for each registration approach were performed.

Results: We found distinct differences in voxel-wise statistics depending on the chosen registration approach. Best alignment results were achieved by registration to a study specific template, i.e. to the group mean (GM) or to a group-wise atlas (GW). Overall alignment did not differ between these two approaches. However, voxel-wise statistics showed clusters of significantly decreased FA values in the T and GM approach, which were not significant after GW registration. These voxels of significantly decreased FA values after T and GM registration did not represent white matter tracts and correlated with higher standard deviation in FA maps across subjects, thus implying registration errors, especially in the optic radiation.

Conclusion: Registration to a study-specific template, i.e. to the group mean or a group-wise atlas seems to be the method of choice in TBSS-analysis of glaucoma patients as it shows better alignment of the optic radiation and helps to rule out registration errors due to misalignment.

MeSH terms

  • Aged
  • Diffusion Tensor Imaging*
  • Glaucoma, Open-Angle / diagnosis*
  • Healthy Volunteers
  • Humans
  • Intraocular Pressure
  • Middle Aged
  • Registries

Grant support

The authors have no support or funding to report.