Elsevier

NeuroImage: Clinical

Volume 11, 2016, Pages 291-301
NeuroImage: Clinical

Spatial regression analysis of serial DTI for subject-specific longitudinal changes of neurodegenerative disease

https://doi.org/10.1016/j.nicl.2016.02.009Get rights and content
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open access

Highlights

  • A nonparametric method for detecting subject-specific localized changes in longitudinal DTI

  • Obtain sufficient statistical power even with limited scans available

  • Various voxel-level test statistics for hypothesis tests among groups across time

  • Excellent at controlling false positive ratio with the model-based test statistics

Abstract

Quantitative measurement of localized longitudinal changes in brain abnormalities at an individual level may offer critical information for disease diagnosis and treatment. The voxel-wise permutation-based method SPREAD/iSPREAD, which combines resampling and spatial regression of neighboring voxels, provides an effective and robust method for detecting subject-specific longitudinal changes within the whole brain, especially for longitudinal studies with a limited number of scans. As an extension of SPREAD/iSPREAD, we present a general method that facilitates analysis of serial Diffusion Tensor Imaging (DTI) measurements (with more than two time points) for testing localized changes in longitudinal studies. Two types of voxel-level test statistics (model-free test statistics, which measure intra-subject variability across time, and test statistics based on general linear model that incorporate specific lesion evolution models) were estimated and tested against the null hypothesis among groups of DTI data across time. The implementation and utility of the proposed statistical method were demonstrated by both Monte Carlo simulations and applications on clinical DTI data from human brain in vivo. By a design of test statistics based on the disease progression model, it was possible to apportion the true significant voxels attributed to the disease progression and those caused by underlying anatomical differences that cannot be explained by the model, which led to improvement in false positive (FP) control in the results. Extension of the proposed method to include other diseases or drug effect models, as well as the feasibility of global statistics, was discussed. The proposed statistical method can be extended to a broad spectrum of longitudinal studies with carefully designed test statistics, which helps to detect localized changes at the individual level.

Keywords

Diffusion Tensor Imaging
Resampling
General linear model
White matter
Longitudinal study

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This work is supported in part by the University of Rochester Center for AIDS Research grant P30AI078498.

1

These authors contributed equally to this work.