title: Operationalizing protocol differences for EADC-ADNI manual hippocampal segmentation.
abstract: BACKGROUND
  Hippocampal volumetry on magnetic resonance imaging is recognized as an Alzheimer's disease (AD) biomarker, and manual segmentation is the gold standard for measurement. However, a standard procedure is lacking. We operationalize and quantitate landmark differences to help a Delphi panel converge on a set of landmarks.
  
  
  METHODS
  One hundred percent of anatomic landmark variability across 12 different protocols for manual segmentation was reduced into four segmentation units (the minimum hippocampus, the alveus/fimbria, the tail, and the subiculum), which were segmented on magnetic resonance images by expert raters to estimate reliability and AD-related atrophy.
  
  
  RESULTS
  Intra- and interrater reliability were more than 0.96 and 0.92, respectively, except for the alveus/fimbria, which were 0.86 and 0.77, respectively. Of all AD-related atrophy, the minimum hippocampus contributed to 67%; tail, 24%; alveus/fimbria, 4%; and the subiculum, 5%.
  
  
  CONCLUSIONS
  Anatomic landmark variability in available protocols can be reduced to four discrete and measurable segmentation units. Their quantitative assessment will help a Delphi panel to define a set of landmarks for a harmonized protocol.
authors.affiliation: Laboratory of Epidemiology, Neuroimaging and Telemedicine, IRCCS - S. Giovanni di Dio - Fatebenefratelli, Brescia, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Boccardi
authors.affiliation: Laboratory of Epidemiology, Neuroimaging and Telemedicine, IRCCS - S. Giovanni di Dio - Fatebenefratelli, Brescia, Italy; Associazione Fatebenefratelli per la Ricerca, Rome, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Bocchetta
authors.affiliation: Laboratory of Epidemiology, Neuroimaging and Telemedicine, IRCCS - S. Giovanni di Dio - Fatebenefratelli, Brescia, Italy.
authors.forename: Rossana
authors.initials: R
authors.lastname: Ganzola
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: Nicolas
authors.initials: N
authors.lastname: Robitaille
authors.affiliation: Laboratory of Epidemiology, Neuroimaging and Telemedicine, IRCCS - S. Giovanni di Dio - Fatebenefratelli, Brescia, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Redolfi
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: Laboratory of Epidemiology, Neuroimaging and Telemedicine, IRCCS - S. Giovanni di Dio - Fatebenefratelli, Brescia, Italy; University Hospitals and University of Geneva, Geneva, Switzerland. Electronic address: gfrisoni@fatebenefratelli.it.
authors.forename: Giovanni B
authors.initials: GB
authors.lastname: Frisoni
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology; D001284:Atrophy; D060825:Cognitive Dysfunction / Q000473:pathology; D003697:Delphi Technique; D005260:Female; 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; D059906:Neuroimaging / Q000379:methods*; D009929:Organ Size; D015203:Reproducibility of Results
keywords: Alzheimer's Disease Neuroimaging Initiative; Alzheimer's disease; Anatomic landmark; Atrophy; Degeneration; Harmonization; Hippocampal atrophy; Hippocampal volumetry; Hippocampus; Magnetic resonance; Manual segmentation protocol; Manual tracing; Medial temporal lobes; Neuroimaging; Standard operating procedures