Feasibility of Multi-site Clinical Structural Neuroimaging Studies of Aging Using Legacy Data
The application of advances in biomedical computing to medical imaging research is enabling scientists to conduct quantitative clinical imaging studies using data collected across multiple sites to test new hypotheses on larger cohorts, increasing the power to detect subtle effects. Given that many research groups have valuable existing (legacy) data, one goal of the Morphometry Biomedical Informatics Research Network (BIRN) Testbed is to assess the feasibility of pooled analyses of legacy structural neuroimaging data in normal aging and Alzheimer’s disease. The present study examined whether such data could be meaningfully reanalyzed as a larger combined data set by using rigorous data curation, image analysis, and statistical modeling methods; in this case, to test the hypothesis that hippocampal volume decreases with age and to investigate findings of hippocampal asymmetry. This report describes our work with legacy T1-weighted magnetic resonance (MR) and demographic data related to normal aging that have been shared through the BIRN by three research sites. Results suggest that, in the present application, legacy MR data from multiple sites can be pooled to investigate questions of scientific interest. In particular, statistical analyses suggested that a mixed-effects model employing site as a random effect best fits the data, accounting for site-specific effects while taking advantage of expected comparability of age-related effects. In the combined sample from three sites, significant age-related decline of hippocampal volume and right-dominant hippocampal asymmetry were detected in healthy elderly controls. These expected findings support the feasibility of combining legacy data to investigate novel scientific questions.
KeywordsMRI Hippocampus Asymmetry Image processing Statistical modeling
This research was supported by a grant (#U24 RR021382) to the Morphometry Biomedical Informatics Research Network (BIRN, http://www.nbirn.net), that is funded by the National Center for Research Resources at the National Institutes of Health, U.S.A. Additional support was provided by: the University of California, San Diego, Department of Medicine; San Diego ADRC NIA P50 AG05131; Washington University, St. Louis ADRC NIA P50 AG05681; NIA R01 AG12674, R01 AG06849, PO1 AG04953, and P01 AG03991; a Research Enhancement Award Program and VA Merit Review grant from the Department of Veterans Affairs Medical Research Service; Howard Hughes Medical Institute; NCRR R01 RR16594-01A1, M01 RR00827, P41 RR14075, and P41 RR13642; Mental Illness and Neuroscience Discovery (MIND) Institute; NINDS R01 NS052585-01; NIH Roadmap for Medical Research U54 EB005149; and NIBIB R01 EB002010. Anders M. Dale is a founder and holds equity in CorTechs Labs, Inc, and also serves on the Scientific Advisory Board. The terms of this arrangement have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies.
Work based on these MRI data have been published separately for studies performed within each site locally, including: UCSD (Jernigan et al. 2001a, b; Murphy et al. 2003; Jernigan and Fennema-Notestine 2004; Jernigan and Gamst 2005; Fennema-Notestine et al. 2006); MGH/BWH (Killiany et al. 2000, Killiany et al. 2002); and WashU (Buckner et al. 2004, 2005, Fotenos et al. 2005, Head et al. 2005). Preliminary findings related to the combined data analysis were presented at the Society for Neuroscience 2005 meeting (Fennema-Notestine et al. 2005); work related to the combined data has not been published elsewhere.
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