title: Spatial regression analysis of serial DTI for subject-specific longitudinal changes of neurodegenerative disease.
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.
authors.affiliation: Electrical and Computer Engineering, University of Rochester, Rochester, NY, United States.
authors.forename: Bilan
authors.initials: B
authors.lastname: Liu
authors.affiliation: Biostatistics and Computational Biology, University of Rochester, Rochester, NY, United States.
authors.forename: Xing
authors.initials: X
authors.lastname: Qiu
authors.affiliation: Radiation Oncology, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhu
authors.affiliation: Imaging Sciences, University of Rochester, Rochester, NY, United States.
authors.forename: Wei
authors.initials: W
authors.lastname: Tian
authors.affiliation: Biostatistics and Computational Biology, University of Rochester, Rochester, NY, United States.
authors.forename: Rui
authors.initials: R
authors.lastname: Hu
authors.affiliation: Imaging Sciences, University of Rochester, Rochester, NY, United States.
authors.forename: Sven
authors.initials: S
authors.lastname: Ekholm
authors.affiliation: Imaging Sciences, University of Rochester, Rochester, NY, United States.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Schifitto
authors.affiliation: Imaging Sciences, University of Rochester, Rochester, NY, United States; Biomedical Engineering, University of Rochester, Rochester, NY, United States; Biomedical Engineering, Zhejiang University, Hangzhou, China. Electronic address: jianhui.zhong@rochester.edu.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Zhong
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging*; D056324:Diffusion Tensor Imaging / Q000379:methods*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008297:Male; D015233:Models, Statistical; D009010:Monte Carlo Method; D019636:Neurodegenerative Diseases / Q000000981:diagnostic imaging* / Q000473:pathology*; D000068916:Spatial Regression; D013997:Time Factors
keywords: Diffusion Tensor Imaging; General linear model; Longitudinal study; Resampling; White matter