Pitfalls in the use of voxel-based morphometry as a biomarker: examples from huntington disease

AJNR Am J Neuroradiol. 2010 Apr;31(4):711-9. doi: 10.3174/ajnr.A1939. Epub 2009 Dec 24.


Background and purpose: VBM is increasingly used in the study of neurodegeneration, and recently there has been interest in its potential as a biomarker. However, although it is largely "automated," VBM is rarely implemented consistently across studies, and changing user-specified options can alter the results in a way similar to the very biologic differences under investigation.

Materials and methods: This work uses data from patients with HD to demonstrate the effects of several user-specified VBM parameters and analyses: type and level of statistical correction, modulation, smoothing kernel size, adjustment for brain size, subgroup analysis, and software version.

Results: The results demonstrate that changing these options can alter results in a way similar to the biologic differences under investigation.

Conclusions: If VBM is to be useful clinically or considered for use as a biomarker, there is a need for greater recognition of these issues and more uniformity in its application for the method to be both reproducible and valid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers
  • Brain / pathology*
  • Female
  • Genetic Carrier Screening
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Huntington Disease / diagnosis*
  • Huntington Disease / genetics*
  • Image Processing, Computer-Assisted / methods*
  • Longitudinal Studies
  • Magnetic Resonance Imaging / methods*
  • Male
  • Middle Aged
  • Organ Size / physiology
  • Reference Values
  • Sensitivity and Specificity
  • Software
  • Trinucleotide Repeats / genetics


  • Biomarkers