Jacobian integration method increases the statistical power to measure gray matter atrophy in multiple sclerosis

Neuroimage Clin. 2013 Oct 29;4:10-7. doi: 10.1016/j.nicl.2013.10.015. eCollection 2014.


Gray matter atrophy provides important insights into neurodegeneration in multiple sclerosis (MS) and can be used as a marker of neuroprotection in clinical trials. Jacobian integration is a method for measuring volume change that uses integration of the local Jacobian determinants of the nonlinear deformation field registering two images, and is a promising tool for measuring gray matter atrophy. Our main objective was to compare the statistical power of the Jacobian integration method to commonly used methods in terms of the sample size required to detect a treatment effect on gray matter atrophy. We used multi-center longitudinal data from relapsing-remitting MS patients and evaluated combinations of cross-sectional and longitudinal pre-processing with SIENAX/FSL, SPM, and FreeSurfer, as well as the Jacobian integration method. The Jacobian integration method outperformed these other commonly used methods, reducing the required sample size by a factor of 4-5. The results demonstrate the advantage of using the Jacobian integration method to assess neuroprotection in MS clinical trials.

Keywords: Atrophy; Gray matter; Jacobian integration; Magnetic resonance imaging; Multiple sclerosis; Sample size.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / therapeutic use
  • Atrophy / etiology
  • Cohort Studies
  • Cross-Sectional Studies
  • Female
  • Glatiramer Acetate
  • Gray Matter / drug effects
  • Gray Matter / pathology*
  • Humans
  • Image Processing, Computer-Assisted
  • Immunosuppressive Agents / therapeutic use
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Models, Statistical*
  • Multiple Sclerosis / complications
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / pathology*
  • Nonlinear Dynamics*
  • Peptides / therapeutic use
  • Prednisone / therapeutic use


  • Anti-Inflammatory Agents
  • Immunosuppressive Agents
  • Peptides
  • Glatiramer Acetate
  • Prednisone