title: Accurate measurement of brain changes in longitudinal MRI scans using tensor-based morphometry.
abstract: This paper responds to Thompson and Holland (2011), who challenged our tensor-based morphometry (TBM) method for estimating rates of brain changes in serial MRI from 431 subjects scanned every 6 months, for 2 years. Thompson and Holland noted an unexplained jump in our atrophy rate estimates: an offset between 0 and 6 months that may bias clinical trial power calculations. We identified why this jump occurs and propose a solution. By enforcing inverse-consistency in our TBM method, the offset dropped from 1.4% to 0.28%, giving plausible anatomical trajectories. Transitivity error accounted for the minimal remaining offset. Drug trial sample size estimates with the revised TBM-derived metrics are highly competitive with other methods, though higher than previously reported sample size estimates by a factor of 1.6 to 2.4. Importantly, estimates are far below those given in the critique. To demonstrate a 25% slowing of atrophic rates with 80% power, 62 AD and 129 MCI subjects would be required for a 2-year trial, and 91 AD and 192 MCI subjects for a 1-year trial.
authors.affiliation: Laboratory of Neuro Imaging, Dept. of Neurology, UCLA School of Medicine, Los Angeles, CA, USA.
authors.forename: Xue
authors.initials: X
authors.lastname: Hua
authors.affiliation: Laboratory of Neuro Imaging, Dept. of Neurology, UCLA School of Medicine, Los Angeles, CA, USA.
authors.forename: Boris
authors.initials: B
authors.lastname: Gutman
authors.affiliation: Laboratory of Neuro Imaging, Dept. of Neurology, UCLA School of Medicine, Los Angeles, CA, USA.
authors.forename: Christina P
authors.initials: CP
authors.lastname: Boyle
authors.affiliation: Laboratory of Neuro Imaging, Dept. of Neurology, UCLA School of Medicine, Los Angeles, CA, USA.
authors.forename: Priya
authors.initials: P
authors.lastname: Rajagopalan
authors.affiliation: Dept. of Psychiatry, University of Illinois-Chicago, Chicago, IL, USA; Dept. of Bioengineering, University of Illinois-Chicago, Chicago, IL, USA; Community Psychiatry Associates, Sacramento, CA, USA.
authors.forename: Alex D
authors.initials: AD
authors.lastname: Leow
authors.affiliation: Laboratory of Neuro Imaging, Dept. of Neurology, UCLA School of Medicine, Los Angeles, CA, USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Yanovsky
authors.affiliation: Dept. of Bioengineering, University of Illinois-Chicago, Chicago, IL, USA.
authors.forename: Anand R
authors.initials: AR
authors.lastname: Kumar
authors.affiliation: Laboratory of Neuro Imaging, Dept. of Neurology, UCLA School of Medicine, Los Angeles, CA, USA.
authors.forename: Arthur W
authors.initials: AW
authors.lastname: Toga
authors.affiliation: Dept. of Radiology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.affiliation: Dept. of Radiology and Biomedical Imaging, UCSF, San Francisco, CA, USA; Dept. of Medicine, UCSF, San Francisco, CA, USA.
authors.forename: Norbert
authors.initials: N
authors.lastname: Schuff
authors.affiliation: Dept. Psychology and Evelyn F. McKnight Brain Institute, University of Arizona, Tucson, AZ, USA.
authors.forename: Gene E
authors.initials: GE
authors.lastname: Alexander
authors.affiliation: Banner Alzheimer's Institute and Banner Good Samaritan PET Center, Phoenix, AZ, USA; Dept. of Mathematics and Statistics, Arizona State University, Tempe, AZ, USA.
authors.forename: Kewei
authors.initials: K
authors.lastname: Chen
authors.affiliation: Banner Alzheimer's Institute and Banner Good Samaritan PET Center, Phoenix, AZ, USA; Dept. Psychiatry, University of Arizona, Phoenix, AZ, USA; Neurogenomics Division, Translational Genomics Research Institute and Arizona Alzheimer's Consortium, AZ, USA.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Reiman
authors.affiliation: Dept. of Radiology and Biomedical Imaging, UCSF, San Francisco, CA, USA; Dept. of Medicine, UCSF, San Francisco, CA, USA; Dept. of Psychiatry, UCSF, San Francisco, CA, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Weiner
authors.affiliation: Laboratory of Neuro Imaging, Dept. of Neurology, UCLA School of Medicine, Los Angeles, CA, USA. Electronic address: thompson@loni.ucla.edu.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Thompson