title: Training labels for hippocampal segmentation based on the EADC-ADNI harmonized hippocampal protocol.
abstract: BACKGROUND
  The European Alzheimer's Disease Consortium and Alzheimer's Disease Neuroimaging Initiative (ADNI) Harmonized Protocol (HarP) is a Delphi definition of manual hippocampal segmentation from magnetic resonance imaging (MRI) that can be used as the standard of truth to train new tracers, and to validate automated segmentation algorithms. Training requires large and representative data sets of segmented hippocampi. This work aims to produce a set of HarP labels for the proper training and certification of tracers and algorithms.
  
  
  METHODS
  Sixty-eight 1.5 T and 67 3 T volumetric structural ADNI scans from different subjects, balanced by age, medial temporal atrophy, and scanner manufacturer, were segmented by five qualified HarP tracers whose absolute interrater intraclass correlation coefficients were 0.953 and 0.975 (left and right). Labels were validated as HarP compliant through centralized quality check and correction.
  
  
  RESULTS
  Hippocampal volumes (mm(3)) were as follows: controls: left = 3060 (standard deviation [SD], 502), right = 3120 (SD, 897); mild cognitive impairment (MCI): left = 2596 (SD, 447), right = 2686 (SD, 473); and Alzheimer's disease (AD): left = 2301 (SD, 492), right = 2445 (SD, 525). Volumes significantly correlated with atrophy severity at Scheltens' scale (Spearman's ρ = <-0.468, P = <.0005). Cerebrospinal fluid spaces (mm(3)) were as follows: controls: left = 23 (32), right = 25 (25); MCI: left = 15 (13), right = 22 (16); and AD: left = 11 (13), right = 20 (25). Five subjects (3.7%) presented with unusual anatomy.
  
  
  CONCLUSIONS
  This work provides reference hippocampal labels for the training and certification of automated segmentation algorithms. The publicly released labels will allow the widespread implementation of the standard segmentation protocol.
authors.affiliation: LENITEM (Laboratory of Epidemiology, Neuroimaging and Telemedicine) IRCCS - Centro S. Giovanni di Dio - Fatebenefratelli, Brescia, Italy. Electronic address: mboccardifbf@gmail.com.
authors.forename: Marina
authors.initials: M
authors.lastname: Boccardi
authors.affiliation: LENITEM (Laboratory of Epidemiology, Neuroimaging and Telemedicine) IRCCS - Centro S. Giovanni di Dio - Fatebenefratelli, Brescia, Italy; Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Bocchetta
authors.affiliation: Department of Radiology, Université Laval and Centre de Recherche de l'Institut universitaire de santé mentale de Québec, Quebec City, Canada; Imeka, Sherbrooke, Québec, Canada.
authors.forename: Félix C
authors.initials: FC
authors.lastname: Morency
authors.affiliation: McConnell Brain Imaging Center, Montreal Neurological Institute, McGill University, Montreal, Canada.
authors.forename: D Louis
authors.initials: DL
authors.lastname: Collins
authors.affiliation: Kawamura Gakuen Woman's University, Abiko-city, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Nishikawa
authors.affiliation: Department of Radiology, Université Laval and Centre de Recherche de l'Institut universitaire de santé mentale de Québec, Quebec City, Canada.
authors.forename: Rossana
authors.initials: R
authors.lastname: Ganzola
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany.
authors.forename: Michel J
authors.initials: MJ
authors.lastname: Grothe
authors.affiliation: Klinik für Psychiatrie und Psychotherapie, Johannes Gutenberg-Universität, Mainz, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Wolf
authors.affiliation: LENITEM (Laboratory of Epidemiology, Neuroimaging and Telemedicine) IRCCS - Centro S. Giovanni di Dio - Fatebenefratelli, Brescia, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Redolfi
authors.affiliation: LENITEM (Laboratory of Epidemiology, Neuroimaging and Telemedicine) IRCCS - Centro S. Giovanni di Dio - Fatebenefratelli, Brescia, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Pievani
authors.affiliation: LENITEM (Laboratory of Epidemiology, Neuroimaging and Telemedicine) IRCCS - Centro S. Giovanni di Dio - Fatebenefratelli, Brescia, Italy; Laboratory of Neuroimaging of Aging, Department of Psychiatry, HUG Belle-Idée, Geneva, Switzerland.
authors.forename: Luigi
authors.initials: L
authors.lastname: Antelmi
authors.affiliation: Klinik für Psychiatrie und Psychotherapie, Johannes Gutenberg-Universität, Mainz, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Fellgiebel
authors.affiliation: Integrative Brain Imaging Center, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsuda
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany; Integrative Brain Imaging Center, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Stefan
authors.initials: S
authors.lastname: Teipel
authors.affiliation: Department of Radiology, Université Laval and Centre de Recherche de l'Institut universitaire de santé mentale de Québec, Quebec City, Canada.
authors.forename: Simon
authors.initials: S
authors.lastname: Duchesne
authors.affiliation: Department of Diagnostic Radiology, Mayo Clinic and Foundation, Rochester, MN, USA.
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.affiliation: LENITEM (Laboratory of Epidemiology, Neuroimaging and Telemedicine) IRCCS - Centro S. Giovanni di Dio - Fatebenefratelli, Brescia, Italy; Laboratory of Neuroimaging of Aging, Department of Psychiatry, HUG Belle-Idée, Geneva, Switzerland; University of Geneva, Faculty of Medicine, Geneva, Switzerland.
authors.forename: Giovanni B
authors.initials: GB
authors.lastname: Frisoni
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000544:Alzheimer Disease / Q000473:pathology; D001284:Atrophy; D060825:Cognitive Dysfunction / Q000473:pathology; D005260:Female; D007839:Functional Laterality; D006624:Hippocampus / Q000033:anatomy & histology / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D021621:Imaging, Three-Dimensional / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging / Q000379:methods*; D009929:Organ Size; D010363:Pattern Recognition, Automated / Q000379:methods*; D015203:Reproducibility of Results; D013702:Temporal Lobe / Q000473:pathology
keywords: Algorithm training; Automated segmentation algorithms; Benchmark images; Harmonized protocol; Hippocampal segmentation; Hippocampus; MRI