title: Predicting behavioral variant frontotemporal dementia with pattern classification in multi-center structural MRI data.
abstract: Frontotemporal lobar degeneration (FTLD) is a common cause of early onset dementia. Behavioral variant frontotemporal dementia (bvFTD), its most common subtype, is characterized by deep alterations in behavior and personality. In 2011, new diagnostic criteria were suggested that incorporate imaging criteria into diagnostic algorithms. The study aimed at validating the potential of imaging criteria to individually predict diagnosis with machine learning algorithms.
  
  
  
  Brain atrophy was measured with structural magnetic resonance imaging (MRI) at 3 Tesla in a multi-centric cohort of 52 bvFTD patients and 52 healthy control subjects from the German FTLD Consortium's Study. Beside group comparisons, diagnosis bvFTD vs. controls was individually predicted in each subject with support vector machine classification in MRI data across the whole brain or in frontotemporal, insular regions, and basal ganglia known to be mainly affected based on recent meta-analyses. Multi-center effects were controlled for with a new method, "leave one center out" conjunction analyses, i.e. repeatedly excluding subjects from each center from the analysis.
  
  
  
  Group comparisons revealed atrophy in, most consistently, the frontal lobe in bvFTD beside alterations in the insula, basal ganglia and temporal lobe. Most remarkably, support vector machine classification enabled predicting diagnosis in single patients with a high accuracy of up to 84.6%, where accuracy was highest in a region-of-interest approach focusing on frontotemporal, insular regions, and basal ganglia in comparison with the whole brain approach.
  
  
  
  Our study demonstrates that MRI, a widespread imaging technology, can individually identify bvFTD with high accuracy in multi-center imaging data, paving the road to personalized diagnostic approaches in the future.
authors.affiliation: Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Meyer
authors.affiliation: Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Mueller
authors.affiliation: Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Stuke
authors.affiliation: Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Bisenius
authors.affiliation: Clinic for Psychiatry and Psychotherapy, Technical University of Munich, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Diehl-Schmid
authors.affiliation: Clinic for Psychiatry and Psychotherapy, University Bonn, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Jessen
authors.affiliation: Clinic for Neurology, University of Ulm, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Kassubek
authors.affiliation: Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University Erlangen-Nuremberg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Kornhuber
authors.affiliation: Clinic for Neurology, University of Ulm, Germany.
authors.forename: Albert C
authors.initials: AC
authors.lastname: Ludolph
authors.affiliation: Department of Neurology, Rostock University Medical Center, Rostock, Germany; German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Prudlo
authors.affiliation: Clinic for Psychiatry and Psychotherapy, University of Goettingen, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Schneider
authors.affiliation: Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Schuemberg
authors.affiliation: Clinic for Nuclear Medicine, Technical University of Munich, Germany.
authors.forename: Igor
authors.initials: I
authors.lastname: Yakushev
authors.affiliation: Clinic for Neurology, University of Ulm, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Otto
authors.affiliation: Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; Clinic for Cognitive Neurology, University Hospital Leipzig, Germany.
authors.forename: Matthias L
authors.initials: ML
authors.lastname: Schroeter
mesh_terms: D000368:Aged; D001284:Atrophy / Q000000981:diagnostic imaging; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology; D001931:Brain Mapping; D015331:Cohort Studies; D005260:Female; D057180:Frontotemporal Dementia / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D060388:Support Vector Machine
keywords: Atrophy; Behavioral variant frontotemporal dementia; Diagnostic criteria; FEW, family wise error; FTLD, frontotemporal lobar degeneration; Frontotemporal lobar degeneration; GMD, gray matter density; MNI, Montreal Neurological Institute; MPRAGE, magnetization-prepared rapid gradient echo; MRI; MRI, magnetic resonance imaging; Pattern classification; SVM, support vector machine; VBM, voxel based morphometry; bvFTD, behavioral variant frontotemporal dementia