Steps to standardization and validation of hippocampal volumetry as a biomarker in clinical trials and diagnostic criterion for Alzheimer's disease

Clifford R. Jack, Frederik Barkhof, Matt A. Bernstein, Marc Cantillon, Patricia E. Cole, Charles Decarli, Bruno Dubois, Simon Duchesne, Nick C. Fox, Giovanni B. Frisoni, Harald Hampel, Derek L.G. Hill, Keith Johnson, Jean Franois Mangin, Philip Scheltens, Adam J. Schwarz, Reisa Sperling, Joyce Suhy, Paul M. Thompson, Michael WeinerNorman L. Foster

Research output: Contribution to journalComment/debate

133 Scopus citations

Abstract

Background: The promise of Alzheimer's disease biomarkers has led to their incorporation in new diagnostic criteria and in therapeutic trials; however, significant barriers exist to widespread use. Chief among these is the lack of internationally accepted standards for quantitative metrics. Hippocampal volumetry is the most widely studied quantitative magnetic resonance imaging measure in Alzheimer's disease and thus represents the most rational target for an initial effort at standardization. Methods and Results: The authors of this position paper propose a path toward this goal. The steps include the following: (1) Establish and empower an oversight board to manage and assess the effort, (2) adopt the standardized definition of anatomic hippocampal boundaries on magnetic resonance imaging arising from the European Alzheimer's Disease Centers-Alzheimer's Disease Neuroimaging Initiative hippocampal harmonization effort as a reference standard, (3) establish a scientifically appropriate, publicly available reference standard data set based on manual delineation of the hippocampus in an appropriate sample of subjects (Alzheimer's Disease Neuroimaging Initiative), and (4) define minimum technical and prognostic performance metrics for validation of new measurement techniques using the reference standard data set as a benchmark. Conclusions: Although manual delineation of the hippocampus is the best available reference standard, practical application of hippocampal volumetry will require automated methods. Our intent was to establish a mechanism for credentialing automated software applications to achieve internationally recognized accuracy and prognostic performance standards that lead to the systematic evaluation and then widespread acceptance and use of hippocampal volumetry. The standardization and assay validation process outlined for hippocampal volumetry was envisioned as a template that could be applied to other imaging biomarkers.

Original languageEnglish (US)
Pages (from-to)474-485.e4
JournalAlzheimer's and Dementia
Volume7
Issue number4
DOIs
StatePublished - Jul 2011

Keywords

  • Alzheimer's disease
  • Biomarker standards
  • Biomarkers
  • Hippocampus
  • Magnetic resonance imaging

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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    Jack, C. R., Barkhof, F., Bernstein, M. A., Cantillon, M., Cole, P. E., Decarli, C., Dubois, B., Duchesne, S., Fox, N. C., Frisoni, G. B., Hampel, H., Hill, D. L. G., Johnson, K., Mangin, J. F., Scheltens, P., Schwarz, A. J., Sperling, R., Suhy, J., Thompson, P. M., ... Foster, N. L. (2011). Steps to standardization and validation of hippocampal volumetry as a biomarker in clinical trials and diagnostic criterion for Alzheimer's disease. Alzheimer's and Dementia, 7(4), 474-485.e4. https://doi.org/10.1016/j.jalz.2011.04.007