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

J Alzheimers Dis. 2017;60(1):151-164. doi: 10.3233/JAD-161108.


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.

Keywords: Alzheimer’s disease; FSL-FIRST; clinical trials; hippocampus; mild cognitive impairment; reproducibility; test/retest.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / pathology*
  • Cognitive Dysfunction / diagnostic imaging
  • Cognitive Dysfunction / pathology*
  • Female
  • Hippocampus / diagnostic imaging*
  • Humans
  • Image Interpretation, Computer-Assisted
  • Longitudinal Studies
  • Magnetic Resonance Imaging*
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Prodromal Symptoms*
  • Reproducibility of Results