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The human thalamus is a brain structure that comprises numerous, highly specific nuclei. Since these nuclei are known to have different functions and to be connected to different areas of the cerebral cortex, it is of great interest for the neuroimaging community to study their volume, shape and connectivity in vivo with MRI. In this study, we present a probabilistic atlas of the thalamic nuclei built using ex vivo brain MRI scans and histological data, as well as the application of the atlas to in vivo MRI segmentation. The atlas was built using manual delineation of 26 thalamic nuclei on the serial histology of 12 whole thalami from six autopsy samples, combined with manual segmentations of the whole thalamus and surrounding structures (caudate, putamen, hippocampus, etc.) made on in vivo brain MR data from 39 subjects. The 3D structure of the histological data and corresponding manual segmentations was recovered using the ex vivo MRI as reference frame, and stacks of blockface photographs acquired during the sectioning as intermediate target. The atlas, which was encoded as an adaptive tetrahedral mesh, shows a good agreement with previous histological studies of the thalamus in terms of volumes of representative nuclei. When applied to segmentation of in vivo scans using Bayesian inference, the atlas shows excellent test-retest reliability, robustness to changes in input MRI contrast, and ability to detect differential thalamic effects in subjects with Alzheimer's disease. The probabilistic atlas and companion segmentation tool are publicly available as part of the neuroimaging package FreeSurfer.The authors would like to thank Professor Karla Miller (Oxford) for
her help with the design of the ex vivo MRI acquisition; Ms. Mercedes
I~niguez de Onzo~no and Mr. Francisco Romero (UCLM) for their careful
technical laboratory help; and Mr. Gonzalo Artacho (UCLM) for his help
with the digitization and curation of his organization of histological data.
This project has received funding from the European Union's Horizon
2020 research and innovation program under the Marie Sklodowska-
Curie grant agreement No 654911 (project “THALAMODEL”) and by
the European Research Council (ERC) Starting Grant agreement No
677697 (“BUNGEE-TOOLS”). It was also funded by the Spanish Ministry
of Economy and Competitiveness(MINECO TEC-2014-51882-P, RYC-
2014-15440, PSI2015-65696, and SEV-2015-0490), the Basque Government
(PI2016-12), and UCLM Internal Research Groups grants.
Support for this research was also provided in part by the National
Institute of Biomedical Imaging and Bioengineering (P41EB015896,
1R01EB023281, R01EB006758, R21EB018907, R01EB019956), the
National Institute on Aging (5R01AG008122, R01AG016495), the National
Institute of Diabetes and Digestive and Kidney Diseases (1-R21-DK-
108277-01), the National Institute of Neurological Disorders and Stroke
(R01NS0525851, R21NS072652, R01NS070963, R01NS083534,
5U01NS086625), and was made possible by the resources provided by
Shared Instrumentation Grants 1S10RR023401, 1S10RR019307, and 1S-
10RR023043. Additional support was provided by the NIH Blueprint for
Neuroscience Research (5U01-MH093765), part of the multiinstitutional
Human Connectome Project. In addition, B.F. has a financial
interest in CorticoMetrics, a company whose medical pursuits focus
on brain imaging and measurement technologies. B.F.’s interests were
reviewed and are managed by Massachusetts General Hospital and
Partners HealthCare in accordance with their conflict of interest policies.
Data collection and sharing for this project was funded by the
Alzheimer's Disease Neuroimaging Initiative (National Institutes of
Health Grant U01 AG024904) and DOD ADNI (DOD 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, Alzheimers Association; Alzheimers 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 Alzheimers 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
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