Background
The
promise of Alzheimer’s disease (AD) 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 (MRI) measure in AD 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: 1) Establish and empower an oversight board to manage and
assess the effort, 2) Adopt the standardized definition of anatomic
hippocampal boundaries on MRI arising from the EADC-ADNI hippocampal
harmonization effort as a Reference Standard, 3) Establish a
scientifically appropriate, publicly available Reference Standard
Dataset based on manual delineation of the hippocampus in an appropriate
sample of subjects (ADNI), and 4) Define minimum technical and
prognostic performance metrics for validation of new measurement
techniques using the Reference Standard Dataset 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 is 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 is envisioned as a template that
could be applied to other imaging biomarkers.
