Abstract
Purpose: Precise and reproducible hippocampus outlining is important to quantify hippocampal atrophy caused by neurodegenerative diseases and to spare the hippocampus in whole brain radiation therapy when performing prophylactic cranial irradiation or treating brain metastases. This study aimed to quantify systematic differences between methods by comparing regional volume and outline reproducibility of manual, FSL-FIRST and FreeSurfer hippocampus segmentations. Materials and methods: This study used a dataset from ADNI (Alzheimer's Disease Neuroimaging Initiative), including 20 healthy controls, 40 patients with mild cognitive impairment (MCI), and 20 patients with Alzheimer's disease (AD). For each subject back-to-back (BTB) T1-weighted 3D MPRAGE images were acquired at time-point baseline (BL) and 12 months later (M12). Hippocampi segmentations of all methods were converted into triangulated meshes, regional volumes were extracted and regional Jaccard indices were computed between the hippocampi meshes of paired BTB scans to evaluate reproducibility. Regional volumes and Jaccard indices were modelled as a function of group (G), method (M), hemisphere (H), timepoint (T), region (R) and interactions. Results: For the volume data the model selection procedure yielded the following significant main effects G, M, H, T and R and interaction effects G-R and M-R. The same model was found for the BTB scans. For all methods volumes reduces with the severity of disease. Significant fixed effects for the regional Jaccard index data were M, R and the interaction M-R. For all methods the middle region was most reproducible, independent of diagnostic group. FSL-FIRST was most and FreeSurfer least reproducible. Discussion/Conclusion: A novel method to perform detailed analysis of subtle differences in hippocampus segmentation is proposed. The method showed that hippocampal segmentation reproducibility was best for FSL-FIRST and worst for Freesurfer. We also found systematic regional differences in hippocampal segmentation between different methods reinforcing the need of adopting harmonized protocols.
| Original language | English |
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| Article number | e0166785 |
| Journal | PLoS ONE |
| Volume | 12 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 1 Feb 2017 |
Funding
HV has received research grants from Novartis, Teva, MerckSerono and Pfizer, commercial companies, for this study. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials. The authors thank Felix C. van Dommelen of the Image Analysis Center, VU University Medical Center, Amsterdam, The Netherlands for performing the manual hippocampal volume analyses, and Margo A. Pronk, of the same Image Analysis Center, for assistance in the visual inspection of segmentation outputs. Furthermore, we thank R. Schijndel and R.A. de Jong E. Mulder of the Image Analysis Center, VU University Medical Center, Amsterdam, The Netherlands for their support and previous work. 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 & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites 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. This research was also supported by NIH grants P30 AG010129 and K01 AG030514. H. Vrenken has received research grants from Novartis, Teva, MerckSerono and Pfizer, and a speaker honorarium from Novartis. All funds were paid directly to his institution.
| Funders | Funder number |
|---|---|
| DOD ADNI | |
| MerckSerono | |
| National Institutes of Health | U01 AG024904, K01 AG030514 |
| U.S. Department of Defense | W81XWH-12-2-0012 |
| National Institute on Aging | P30AG010129 |
| National Institute of Biomedical Imaging and Bioengineering | |
| Pfizer | |
| Novartis | |
| Teva Pharmaceutical Industries | |
| Alzheimer's Disease Neuroimaging Initiative |