Standardization of hippocampus volumetry using automated brain structure volumetry tool for an initial Alzheimer's disease imaging biomarker

Acta Radiol. 2019 Jun;60(6):769-776. doi: 10.1177/0284185118795327. Epub 2018 Sep 5.


Background: One significant barrier to incorporate Alzheimer's disease (AD) imaging biomarkers into diagnostic criteria is the lack of standardized methods for biomarker quantification. The European Alzheimer's Disease Consortium-Alzheimer's Disease Neuroimaging Initiative (EADC-ADNI) Harmonization Protocol project provides the most authoritative guideline for hippocampal definition and has produced a manually segmented reference dataset for validation of automated methods.

Purpose: To validate automated hippocampal volumetry using AccuBrain™, against the EADC-ADNI dataset, and assess its diagnostic performance for differentiating AD and normal aging in an independent cohort.

Material and methods: The EADC-ADNI reference dataset comprise of manually segmented hippocampal labels from 135 volumetric T1-weighted scans from various scanners. Dice similarity coefficient (DSC), intraclass correlation coefficient (ICC), and Pearson's r were obtained for AccuBrain™ and FreeSurfer. The magnetic resonance imaging (MRI) of a separate cohort of 299 individuals (150 normal controls, 149 with AD) were obtained from the ADNI database and processed with AccuBrain™ to assess its diagnostic accuracy. Area under the curve (AUC) for total hippocampal volumes (HV) and hippocampal fraction (HF) were determined.

Results: Compared with EADC-ADNI dataset ground truths, AccuBrain™ had a mean DSC of 0.89/0.89/0.89, ICC of 0.94/0.96/0.95, and r of 0.95/0.96/0.95 for right/left/total HV. AccuBrain™ HV and HF had AUC of 0.76 and 0.80, respectively. Thresholds of ≤ 5.71 mL and ≤ 0.38% afforded 80% sensitivity for AD detection.

Conclusion: AccuBrain™ provides accurate automated hippocampus segmentation in accordance with the EADC-ADNI standard, with great potential value in assisting clinical diagnosis of AD.

Keywords: Alzheimer’s disease; biomarker; hippocampus; software validation; standardization.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnostic imaging*
  • Alzheimer Disease / pathology*
  • Biomarkers
  • Databases, Factual
  • Female
  • Hippocampus / diagnostic imaging*
  • Hippocampus / pathology*
  • Humans
  • Image Processing, Computer-Assisted / methods*
  • Magnetic Resonance Imaging / methods*
  • Male
  • Middle Aged
  • Neuroimaging / methods
  • Organ Size
  • Reproducibility of Results


  • Biomarkers