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Alternative diffusion anisotropy measures for the investigation of white matter alterations in 22q11.2 deletion syndrome
Author(s): 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 Daly; Maria 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
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Paper Abstract

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.

Paper Details

Date Published: 21 December 2018
PDF: 14 pages
Proc. SPIE 10975, 14th International Symposium on Medical Information Processing and Analysis, 109750U (21 December 2018); doi: 10.1117/12.2513788
Show Author Affiliations
Julio E. Villalon-Reina, The Univ. of Southern California (United States)
Christopher R. K. Ching, The Univ. of Southern California (United States)
Univ. of California, Los Angeles (United States)
Deydeep Kothapalli, The Univ. of Southern California (United States)
Daqiang Sun, Univ. of California, Los Angeles (United States)
Veterans Affairs Greater Los Angeles Healthcare System (United States)
Talia Nir, The Univ. of Southern California (United States)
Amy Lin, Univ. of California, Los Angeles (United States)
Jennifer K. Forsyth, Univ. of California, Los Angeles (United States)
Leila Kushan, Univ. of California, Los Angeles (United States)
Ariana Vajdi, Univ. of California, Los Angeles (United States)
Maria Jalbrzikowski, Univ. of Pittsburgh (United States)
Laura Hansen, Univ. of California, Los Angeles (United States)
Rachel K. Jonas, Univ. of California, Los Angeles (United States)
Therese van Amelsvoort, Maastricht Univ. (Netherlands)
Geor Bakker, Maastricht Univ. (Netherlands)
Wendy R. Kates, The State Univ. of New York, Upstate Medical Univ. (United States)
Kevin M. Antshel, Syracuse Univ. (United States)
Wanda Fremont, The State Univ. of New York, Upstate Medical Univ. (United States)
Linda E. Campbell, Newcastle Univ. (Australia)
Kathryn L. McCabe, Newcastle Univ. (Australia)
Eileen Daly, King's College London (United Kingdom)
Maria Gudbrandsen, King's College London (United Kingdom)
Clodagh Murphy, King's College London (United Kingdom)
Declan Murphy, King's College London (United Kingdom)
Michael Craig, King's College London (United Kingdom)
Bethlem Royal Hospital (United Kingdom)
Beverly Emanuel, Children's Hospital of Philadelphia, Univ. of Pennsylvania (United States)
Donna McDonald-McGinn, Children's Hospital of Philadelphia, Univ. of Pennsylvania (United States)
Kosha Ruparel, Univ. of Pennsylvania (United States)
David Roalf, Univ. of Pennsylvania (United States)
Raquel E. Gur, Univ. of Pennsylvania (United States)
J. Eric Schmitt, Univ. of Pennsylvania (United States)
Tony J. Simon, Univ. of California, Davis (United States)
Naomi J. Goodrich-Hunsaker, Univ. of California, Davis (United States)
Brigham Young Univ. (United States)
Courtney A. Durdle, Univ. of California, Davis (United States)
Joanne Doherty, Cardiff Univ. (United Kingdom)
Adam C. Cunningham, Cardiff Univ. (United Kingdom)
Marianne van den Bree, Cardiff Univ. (United Kingdom)
David E. J. Linden, Cardiff Univ. (United Kingdom)
Michael Owen, Cardiff Univ. (United Kingdom)
Hayley Moss, Cardiff Univ. (United Kingdom)
Neda Jahanshad, The Univ. of Southern California (United States)
Carrie E. Bearden, Univ. of California, Los Angeles (United States)
Paul M. Thompson, The Univ. of Southern California (United States)


Published in SPIE Proceedings Vol. 10975:
14th International Symposium on Medical Information Processing and Analysis
Eduardo Romero; Natasha Lepore; Jorge Brieva, Editor(s)

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