Affiliations: [a] Department of Radiology & Medical Imaging, University of Virginia, Charlottesville, VA, USA
| [b] Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA, USA
| [c] Department of Statistics, University of California, Irvine, CA, USA
| [d] Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA
Correspondence:
[*]
Correspondence to: Nicholas J. Tustison, 211 Qureshey Research Lab, Irvine, CA 92697-3800, USA. E-mail: ntustison@virginia.edu.
Note: [1] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf
Abstract: Longitudinal studies of development and disease in the human brain have motivated the acquisition of large neuroimaging data sets and the concomitant development of robust methodological and statistical tools for quantifying neurostructural changes. Longitudinal-specific strategies for acquisition and processing have potentially significant benefits including more consistent estimates of intra-subject measurements while retaining predictive power. Using the first phase of the Alzheimer’s Disease Neuroimaging Initiative (ADNI-1) data, comprising over 600 subjects with multiple time points from baseline to 36 months, we evaluate the utility of longitudinal FreeSurfer and Advanced Normalization Tools (ANTs) surrogate thickness values in the context of a linear mixed-effects (LME) modeling strategy. Specifically, we estimate the residual variability and between-subject variability associated with each processing stream as it is known from the statistical literature that minimizing the former while simultaneously maximizing the latter leads to greater scientific interpretability in terms of tighter confidence intervals in calculated mean trends, smaller prediction intervals, and narrower confidence intervals for determining cross-sectional effects. This strategy is evaluated over the entire cortex, as defined by the Desikan-Killiany-Tourville labeling protocol, where comparisons are made with the cross-sectional and longitudinal FreeSurfer processing streams. Subsequent linear mixed effects modeling for identifying diagnostic groupings within the ADNI cohort is provided as supporting evidence for the utility of the proposed ANTs longitudinal framework which provides unbiased structural neuroimage processing and competitive to superior power for longitudinal structural change detection.
