title: Insight from uncertainty: bootstrap-derived diffusion metrics differentially predict memory function among older adults.
abstract: Diffusion tensor imaging suffers from an intrinsic low signal-to-noise ratio. Bootstrap algorithms have been introduced to provide a non-parametric method to estimate the uncertainty of the measured diffusion parameters. To quantify the variability of the principal diffusion direction, bootstrap-derived metrics such as the cone of uncertainty have been proposed. However, bootstrap-derived metrics are not independent of the underlying diffusion profile. A higher mean diffusivity causes a smaller signal-to-noise ratio and, thus, increases the measurement uncertainty. Moreover, the goodness of the tensor model, which relies strongly on the complexity of the underlying diffusion profile, influences bootstrap-derived metrics as well. The presented simulations clearly depict the cone of uncertainty as a function of the underlying diffusion profile. Since the relationship of the cone of uncertainty and common diffusion parameters, such as the mean diffusivity and the fractional anisotropy, is not linear, the cone of uncertainty has a different sensitivity. In vivo analysis of the fornix reveals the cone of uncertainty to be a predictor of memory function among older adults. No significant correlation occurs with the common diffusion parameters. The present work not only demonstrates the cone of uncertainty as a function of the actual diffusion profile, but also discloses the cone of uncertainty as a sensitive predictor of memory function. Future studies should incorporate bootstrap-derived metrics to provide more comprehensive analysis.
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, P&S Box 16, 630 West 168th Street, New York, NY, 10032, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Vorburger
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, P&S Box 16, 630 West 168th Street, New York, NY, 10032, USA.|Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA.
authors.forename: Christian G
authors.initials: CG
authors.lastname: Habeck
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, P&S Box 16, 630 West 168th Street, New York, NY, 10032, USA.
authors.forename: Atul
authors.initials: A
authors.lastname: Narkhede
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, P&S Box 16, 630 West 168th Street, New York, NY, 10032, USA.
authors.forename: Vanessa A
authors.initials: VA
authors.lastname: Guzman
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, P&S Box 16, 630 West 168th Street, New York, NY, 10032, USA.|Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Manly
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, P&S Box 16, 630 West 168th Street, New York, NY, 10032, USA. amb2139@columbia.edu.|Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA. amb2139@columbia.edu.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Brickman
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology / Q000523:psychology; D000465:Algorithms; D001921:Brain / Q000473:pathology* / Q000503:physiopathology*; D001931:Brain Mapping / Q000379:methods*; D003198:Computer Simulation; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D006801:Humans; D008297:Male; D008568:Memory; D008569:Memory Disorders / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology / Q000523:psychology; D011237:Predictive Value of Tests; D012307:Risk Factors; D012815:Signal Processing, Computer-Assisted; D035501:Uncertainty
keywords: Bootstrap methods; Cone of uncertainty; Diffusion tensor imaging; Memory function; White matter