Fully automatic MRI-based hippocampus volumetry using FSL-FIRST: Intra-scanner test-retest stability, inter-field strength variability, and performance as enrichment biomarker for clinical trials using prodromal target populations at risk for Alzheimer's disease

Enrica Cavedo, Per Suppa, Catharina Lange, Roland Opfer, Simone Lista, Samantha Galluzzi, Adam J. Schwarz, Lothar Spies, Ralph Buchert, Harald Hampel

Research output: Contribution to journalArticle

Abstract

Background: MRI-based hippocampus volume is a core clinical biomarker for identification of Alzheimer's disease (AD). Objective: To assess robustness of automatic hippocampus volumetry with the freely available FSL-FIRST software with respect to short-term repeat and across field strength imaging. FSL-FIRST hippocampus volume (FIRST-HV) was also evaluated as enrichment biomarker for mild cognitive impairment (MCI) trials. Methods: Robustness of FIRST-HV was assessed in 51 healthy controls (HC), 74 MCI subjects, and 28 patients with AD dementia from ADNI1, each with two pairs of back-to-back scans, one at 1.5T one at 3T. Enrichment performance was tested in a second sample of 287 ADNI MCI subjects. Results: FSL-FIRST worked properly in all four scans in 147 out of 153 subjects of the first sample (49 HC, 72 MCI, 26 AD). In these subjects, FIRST-HV did not differ between the first and the second scan within an imaging session, neither at 1.5T nor at 3T (p≥0.302). FIRST-HV was on average 0.78% larger at 3T compared to 1.5T (p = 0.012). The variance of the FIRST-HV difference was larger in the inter-field strength setting than in the intra-scanner settings (p < 0.0005). Computer simulations suggested that the additional variability encountered in the inter-field strength scenario does not cause a relevant degradation of FIRST-HV's prognostic performance in MCI. FIRST-HV based enrichment resulted in considerably increased effect size of the 2-years change of cognitive measures. Conclusion: The impact of intra-scanner test-retest and inter-field strength variability of FIRST-HV on clinical tasks is negligible. In addition, FIRST-HV is useful for enrichment in clinical MCI trials.

Original languageEnglish
Pages (from-to)151-164
Number of pages14
JournalJournal of Alzheimer's Disease
Volume60
Issue number1
DOIs
Publication statusPublished - Jan 1 2017

Keywords

  • Alzheimer's disease
  • clinical trials
  • FSL-FIRST
  • hippocampus
  • mild cognitive impairment
  • reproducibility
  • test/retest

ASJC Scopus subject areas

  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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