Alternative diffusion anisotropy measures for the investigation of white matter alterations in 22q11.2 deletion syndrome

Julio E. Villalon-Reina, Christopher R.K. Ching, Deydeep Kothapalli, Daqiang Sun, Talia Nir, Amy Lin, Jennifer K. Forsyth, Leila Kushan, Ariana Vajdi, Maria Jalbrzikowski, Laura Hansen, Rachel K. Jonas, Therese Van Amelsvoort, Geor Bakker, Wendy R. Kates, Kevin M. Antshel, Wanda Fremont, Linda E. Campbell, Kathryn L. McCabe, Eileen DalyMaria Gudbrandsen, Clodagh Murphy, Declan Murphy, Michael Craig, Beverly Emanuel, Donna McDonald-Mcginn, Kosha Ruparel, David Roalf, Raquel E. Gur, J. Eric Schmitt, Tony J. Simon, Naomi J. Goodrich-Hunsaker, Courtney A. Durdle, Joanne Doherty, Adam C. Cunningham, Marianne Van Den Bree, David E.J. Linden, Michael Owen, Hayley Moss, Neda Jahanshad, Carrie E. Bearden, Paul M. Thompson

Research output: Chapter in Book/Entry/PoemConference contribution

3 Scopus citations


Diffusion MRI (dMRI) is widely used to study the brain's white matter (WM) microstructure in a range of psychiatric and neurological diseases. As the diffusion tensor model has limitations in brain regions with crossing fibers, novel diffusion MRI reconstruction models may offer more accurate measures of tissue properties, and a better understanding of the brain abnormalities in specific diseases. Here we studied a large sample of 249 participants with 22q11.2 deletion syndrome (22q11DS), a neurogenetic condition associated with high rates of developmental neuropsychiatric disorders, and 224 age-matched healthy controls (HC) (age range: 8-35 years). Participants were scanned with dMRI at eight centers worldwide. Using a meta-analytic approach, we assessed the profile of group differences in four diffusion anisotropy measures to better understand the patterns of WM microstructural abnormalities and evaluate their consistency across alternative measures. When assessed in atlas-defined regions of interest, we found statistically significant differences for all anisotropy measures, all showing a widespread but not always coinciding pattern of effects. The tensor distribution function fractional anisotropy (TDF-FA) showed largest effect sizes all in the same direction (greater anisotropy in 22q11DS than HC). Fractional anisotropy based on the tensor model (FA) showed the second largest effect sizes after TDF-FA; some regions showed higher mean values in 22q11DS, but others lower. Generalized fractional anisotropy (GFA) showed the opposite pattern to TDF-FA with most regions showing lower anisotropy in 22q11DS versus HC. Anisotropic power maps (AP) showed the lowest effect sizes also with a mixed pattern of effects across regions. These results were also consistent across skeleton projection methods, with few differences when projecting anisotropy values from voxels sampled on the FA map or projecting values from voxels sampled from each anisotropy map. This study highlights that different mathematical definitions of anisotropy may lead to different profiles of group differences, even in large, well-powered population studies. Further studies of biophysical models derived from multi-shell dMRI and histological validations may help to understand the sources of these differences. 22q11DS is a promising model to study differences among novel anisotropy/dMRI measures, as group differences are relatively large and there exist animal models suitable for histological validation.

Original languageEnglish (US)
Title of host publication14th International Symposium on Medical Information Processing and Analysis
EditorsNatasha Lepore, Eduardo Romero, Jorge Brieva
ISBN (Electronic)9781510626058
StatePublished - 2018
Event14th International Symposium on Medical Information Processing and Analysis, SIPAIM 2018 - Mazatlan, Mexico
Duration: Oct 24 2018Oct 26 2018

Publication series

NameProceedings of SPIE - The International Society for Optical Engineering
ISSN (Print)0277-786X
ISSN (Electronic)1996-756X


Conference14th International Symposium on Medical Information Processing and Analysis, SIPAIM 2018


  • 22q11.2 deletion syndrome
  • Diffusion MRI
  • dMRI
  • diffusion anisotropy
  • white matter

ASJC Scopus subject areas

  • Electronic, Optical and Magnetic Materials
  • Condensed Matter Physics
  • Computer Science Applications
  • Applied Mathematics
  • Electrical and Electronic Engineering


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