Intensity non-uniformity correction using N3 on 3-T scanners with multichannel phased array coils

Richard G. Boyes, Jeff L. Gunter, Chris Frost, Andrew L. Janke, Thomas Yeatman, Derek L.G. Hill, Matt A. Bernstein, Paul M. Thompson, Michael W. Weiner, Norbert Schuff, Gene E. Alexander, Ronald J. Killiany, Charles DeCarli, Clifford R. Jack, Nick C. Fox

Research output: Contribution to journalArticlepeer-review

100 Scopus citations


Measures of structural brain change based on longitudinal MR imaging are increasingly important but can be degraded by intensity non-uniformity. This non-uniformity can be more pronounced at higher field strengths, or when using multichannel receiver coils. We assessed the ability of the non-parametric non-uniform intensity normalization (N3) technique to correct non-uniformity in 72 volumetric brain MR scans from the preparatory phase of the Alzheimer's Disease Neuroimaging Initiative (ADNI). Normal elderly subjects (n = 18) were scanned on different 3-T scanners with a multichannel phased array receiver coil at baseline, using magnetization prepared rapid gradient echo (MP-RAGE) and spoiled gradient echo (SPGR) pulse sequences, and again 2 weeks later. When applying N3, we used five brain masks of varying accuracy and four spline smoothing distances (d = 50, 100, 150 and 200 mm) to ascertain which combination of parameters optimally reduces the non-uniformity. We used the normalized white matter intensity variance (standard deviation/mean) to ascertain quantitatively the correction for a single scan; we used the variance of the normalized difference image to assess quantitatively the consistency of the correction over time from registered scan pairs. Our results showed statistically significant (p < 0.01) improvement in uniformity for individual scans and reduction in the normalized difference image variance when using masks that identified distinct brain tissue classes, and when using smaller spline smoothing distances (e.g., 50-100 mm) for both MP-RAGE and SPGR pulse sequences. These optimized settings may assist future large-scale studies where 3-T scanners and phased array receiver coils are used, such as ADNI, so that intensity non-uniformity does not influence the power of MR imaging to detect disease progression and the factors that influence it.

Original languageEnglish (US)
Pages (from-to)1752-1762
Number of pages11
Issue number4
StatePublished - Feb 15 2008

ASJC Scopus subject areas

  • Neurology
  • Cognitive Neuroscience


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