Improving the SIENA performance using BEaST brain extraction.

We present an improved image analysis pipeline to detect the percent brain volume change (PBVC) using SIENA (Structural Image Evaluation, using Normalization, of Atrophy) in populations with Alzheimer's dementia. Our proposed approach uses the improved brain extraction mask from BEaST (Brain Extraction based on nonlocal Segmentation Technique) instead of the conventional BET (Brain Extraction Tool) for SIENA. We compared four varying options of BET as well as BEaST and applied these five methods to analyze scan-rescan MRIs in ADNI from 332 subjects, longitudinal ADNI MRIs from the same 332 subjects, their repeat scans over time, and OASIS longitudinal MRIs from 123 subjects. The results showed that BEaST brain masks were consistent in scan-rescan reproducibility. The cross-sectional scan-rescan error in the absolute percent brain volume difference measured by SIENA was smallest (p≤0.0187) with the proposed BEaST-SIENA. We evaluated the statistical power in terms of effect size, and the best performance was achieved with BEaST-SIENA (1.2789 for ADNI and 1.095 for OASIS). The absolute difference in PBVC between scan-dataset (volume change from baseline to year-1) and rescan-dataset (volume change from baseline repeat scan to year-1 repeat scan) was also the smallest with BEaST-SIENA compared to the BET-based SIENA and had the highest correlation when compared to the BET-based SIENA variants. In conclusion, our study shows that BEaST was robust in terms of reproducibility and consistency and that SIENA's reproducibility and statistical power are improved in multiple datasets when used in combination with BEaST.
Competing Interests: The authors declare no conflict of interest relevant to the manuscript. Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Mes Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceutical Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transitio Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical site in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. Other disclosures: KN received research support from Biogen, Sanofi Genzyme, National Institutes of Health, and Department of Defense and received a license payment from Biogen; SFE received funding from The Danish Research Council for Independent Research, grant agreement number DFF-4004-00305; SN received grant funding from the Canadian Institutes of Health Research, personal compensation from NeuroRx Research for consulting activities, and a speaker’s honorarium from Novartis Canada. DLA has served on advisory boards, received speaker honoraria, or served as a consultant, for Acorda, Biogen, F. Hoffmann-La Roche Ltd, Medday, MedImmune, Mitsubishi, Novartis, Receptos/Celgene, and Sanofi- Aventis; has received grants from Biogen and Novartis; and has an equity interest in NeuroRx Research. DLC has received personal compensation for consulting & training for NeuroRx Inc. The funder provided support in the form of salaries or compensation for authors SN, DLA and DLC, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. The commercial affiliations do not alter our adherence to all PLOS ONE policies on sharing study data and/or materials. There are no patents, products in development or marketed products to declare.