title: Integrating longitudinal information in hippocampal volume measurements for the early detection of Alzheimer's disease.
abstract: BACKGROUND
  Structural MRI measures for monitoring Alzheimer's Disease (AD) progression are becoming instrumental in the clinical practice, and more so in the context of longitudinal studies. This investigation addresses the impact of four image analysis approaches on the longitudinal performance of the hippocampal volume.
  
  
  METHODS
  We present a hippocampal segmentation algorithm and validate it on a gold-standard manual tracing database. We segmented 460 subjects from ADNI, each subject having been scanned twice at baseline, 12-month and 24month follow-up scan (1.5T, T1 MRI). We used the bilateral hippocampal volume v and its variation, measured as the annualized volume change Λ=δv/year(mm(3)/y). Four processing approaches with different complexity are compared to maximize the longitudinal information, and they are tested for cohort discrimination ability. Reference cohorts are Controls vs. Alzheimer's Disease (CTRL/AD) and CTRL vs. Mild Cognitive Impairment who subsequently progressed to AD dementia (CTRL/MCI-co). We discuss the conditions on v and the added value of Λ in discriminating subjects.
  
  
  RESULTS
  The age-corrected bilateral annualized atrophy rate (%/year) were: -1.6 (0.6) for CTRL, -2.2 (1.0) for MCI-nc, -3.2 (1.2) for MCI-co and -4.0 (1.5) for AD. Combined (v, Λ) discrimination ability gave an Area under the ROC curve (auc)=0.93 for CTRL vs AD and auc=0.88 for CTRL vs MCI-co.
  
  
  CONCLUSIONS
  Longitudinal volume measurements can provide meaningful clinical insight and added value with respect to the baseline provided the analysis procedure embeds the longitudinal information.
authors.affiliation: Istituto Nazionale di Fisica Nucleare, Sezione di Genova, I-16146 Genova, Italy. Electronic address: andrea.chincarini@ge.infn.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Chincarini
authors.affiliation: Istituto Nazionale di Fisica Nucleare, Sezione di Genova, I-16146 Genova, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Sensi
authors.affiliation: Istituto Nazionale di Fisica Nucleare, Sezione di Genova, I-16146 Genova, Italy; Dipartimento di Fisica, Università degli Studi di Genova, I-16146 Genova, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Rei
authors.affiliation: Istituto Nazionale di Fisica Nucleare, Sezione di Genova, I-16146 Genova, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Gemme
authors.affiliation: Istituto Nazionale di Fisica Nucleare, Sezione di Genova, I-16146 Genova, Italy; Dipartimento di Fisica, Università degli Studi di Genova, I-16146 Genova, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Squarcia
authors.affiliation: Dipartimento di Fisica, Università degli Studi di Trieste, Italy; Istituto Nazionale di Fisica Nucleare, Sezione di Trieste, Italy.
authors.forename: Renata
authors.initials: R
authors.lastname: Longo
authors.affiliation: Dipartimento di Ingegneria e Architettura, Università degli Studi di Trieste, Italy; Istituto Nazionale di Fisica Nucleare, Sezione di Trieste, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Brun
authors.affiliation: Istituto Nazionale di Fisica Nucleare, Sezione di Bari, Italy.
authors.forename: Sabina
authors.initials: S
authors.lastname: Tangaro
authors.affiliation: Dipartimento Interateneo di Fisica, Università degli Studi di Bari, Italy; Istituto Nazionale di Fisica Nucleare, Sezione di Bari, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bellotti
authors.affiliation: Dipartimento Interateneo di Fisica, Università degli Studi di Bari, Italy; Istituto Nazionale di Fisica Nucleare, Sezione di Bari, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Amoroso
authors.affiliation: IRCCS Centro San Giovanni di Dio Fatebenefratelli, I-25125 Brescia, Italy; Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Bocchetta
authors.affiliation: IRCCS Centro San Giovanni di Dio Fatebenefratelli, I-25125 Brescia, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Redolfi
authors.affiliation: IRCCS Centro San Giovanni di Dio Fatebenefratelli, I-25125 Brescia, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bosco
authors.affiliation: IRCCS Centro San Giovanni di Dio Fatebenefratelli, I-25125 Brescia, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Boccardi
authors.affiliation: University Hospitals and University of Geneva, Geneva, Switzerland; IRCCS Centro San Giovanni di Dio Fatebenefratelli, I-25125 Brescia, Italy.
authors.forename: Giovanni B
authors.initials: GB
authors.lastname: Frisoni
authors.affiliation: Neurofisiologia Clinica, Dipartimento di Neuroscienze, Oftalmologia e Genetica, Azienda Ospedale-Università S. Martino, Genova I-16132, Italy.
authors.forename: Flavio
authors.initials: F
authors.lastname: Nobili
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000544:Alzheimer Disease / Q000175:diagnosis*; D042241:Early Diagnosis; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged
keywords: Alzheimer's disease; Hippocampus; Image analysis; Longitudinal measure; MRI