Reducing MRI Inter-Scanner Variability Using 3D Superpixel ComBat

Chang Le Chen, Mahbaneh Eshaghzadeh Torbati, James D. Wilson, Davneet S. Minhas, Charles M. Laymon, Seong Jae Hwang, Pauline Maillard, Evan Fletcher, Charles S. DeCarli, Dana L. Tudorascu

Research output: Contribution to journalComment/debatepeer-review


Background: Inter-scanner variability hinders the direct comparability of multi-site/scanner MRI data for clinical research. The ComBat method is commonly used to reduce the variability based on an empirical Bayes framework1,2, harmonizing the data at the feature level (e.g., region-of-interest measures). However, directly harmonizing the scans at the voxel-level using ComBat has been relatively less explored. In this study, we investigated the performance of the voxel-wise ComBat. Also, going beyond voxels, we proposed a new ComBat approach which operates on a small group of voxels called superpixels3. Method: Eighteen subjects (10 patients with Alzheimer's disease and 8 controls; age: 68.0 [9.3] years; 10 females) participated in this study. For each subject, T1-weighted images were acquired on each of four 3T scanners with different manufacturers or models (i.e., GE, Philips, Siemens-Prisma, Siemens-Trio). After the standard image preprocessing including two-step registration by using the Statistical Parametric Mapping (SPM12)4, the unharmonized scans (Raw data) were aligned in the standard template space. To reduce the computational load for ComBat at the voxel level (Voxel-ComBat), we used a three-dimensional superpixel algorithm3 to parcellate the images into hundreds of superpixels based on the study-specific template, and then the ComBat was applied at the superpixel level (Figure 1). Compared to Voxel-Combat operating on about half million voxels (computation time >>10,000 seconds), this superpixel ComBat (SP-ComBat) operates on only a few hundred superpixels, significantly improving the computation efficiency (computation time < 5 seconds) while maintaining the harmonization performance. The harmonized scans were used to estimate cortical thickness by employing surface-based morphometry5, and the coefficients of variation of thickness measures were calculated to evaluate the harmonization performance. Result: The harmonized data provided similar contrasts across scanners compared to the Raw images in visual inspection (Figure 2) and had comparable distributions of the tissue-specific signal intensity between scanners for both Voxel-ComBat and SP-ComBat (Figure 3). Also, these two methods significantly reduced the inter-scanner variation (both p-values < 0.001) in terms of cortical thickness measures (Figure 4). Conclusion: This study evaluated the feasibility and effectiveness of Voxel-ComBat and proposed a new approach, SP-ComBat, to optimize the efficiency of ComBat harmonization at the voxel level.

Original languageEnglish
Article numbere065171
JournalAlzheimer's and Dementia
Issue numberS1
Publication statusPublished - 2022 Dec

Bibliographical note

Publisher Copyright:
© 2022 the Alzheimer's Association.

All Science Journal Classification (ASJC) codes

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


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