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 Martin Antshel, Wanda Fremont, Linda E. Campbell, Kathryn L. McCabe, Eileen Daly & 22 others 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

Research output: Chapter in Book/Report/Conference proceedingConference contribution

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.

Original languageEnglish (US)
Title of host publication14th International Symposium on Medical Information Processing and Analysis
EditorsNatasha Lepore, Eduardo Romero, Jorge Brieva
PublisherSPIE
ISBN (Electronic)9781510626058
DOIs
StatePublished - Jan 1 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
Volume10975
ISSN (Print)0277-786X
ISSN (Electronic)1996-756X

Conference

Conference14th International Symposium on Medical Information Processing and Analysis, SIPAIM 2018
CountryMexico
CityMazatlan
Period10/24/1810/26/18

Fingerprint

deletion
Deletion
Anisotropy
anisotropy
Alternatives
Magnetic resonance imaging
Tensors
Fractional
Tensor
Effect Size
tensors
brain
Distribution functions
Brain
Distribution Function
distribution functions
abnormalities
Fatty Acids
Voxel
Animal Model

Keywords

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

ASJC Scopus subject areas

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

Cite this

Villalon-Reina, J. E., Ching, C. R. K., Kothapalli, D., Sun, D., Nir, T., Lin, A., ... Thompson, P. M. (2018). Alternative diffusion anisotropy measures for the investigation of white matter alterations in 22q11.2 deletion syndrome. In N. Lepore, E. Romero, & J. Brieva (Eds.), 14th International Symposium on Medical Information Processing and Analysis [109750U] (Proceedings of SPIE - The International Society for Optical Engineering; Vol. 10975). SPIE. https://doi.org/10.1117/12.2513788

Alternative diffusion anisotropy measures for the investigation of white matter alterations in 22q11.2 deletion syndrome. / Villalon-Reina, Julio E.; Ching, Christopher R.K.; Kothapalli, Deydeep; Sun, Daqiang; Nir, Talia; Lin, Amy; Forsyth, Jennifer K.; Kushan, Leila; Vajdi, Ariana; Jalbrzikowski, Maria; Hansen, Laura; Jonas, Rachel K.; Van Amelsvoort, Therese; Bakker, Geor; Kates, Wendy R.; Antshel, Kevin Martin; Fremont, Wanda; Campbell, Linda E.; McCabe, Kathryn L.; Daly, Eileen; Gudbrandsen, Maria; Murphy, Clodagh; Murphy, Declan; Craig, Michael; Emanuel, Beverly; McDonald-Mcginn, Donna; Ruparel, Kosha; Roalf, David; Gur, Raquel E.; Schmitt, J. Eric; Simon, Tony J.; Goodrich-Hunsaker, Naomi J.; Durdle, Courtney A.; Doherty, Joanne; Cunningham, Adam C.; Van Den Bree, Marianne; Linden, David E.J.; Owen, Michael; Moss, Hayley; Jahanshad, Neda; Bearden, Carrie E.; Thompson, Paul M.

14th International Symposium on Medical Information Processing and Analysis. ed. / Natasha Lepore; Eduardo Romero; Jorge Brieva. SPIE, 2018. 109750U (Proceedings of SPIE - The International Society for Optical Engineering; Vol. 10975).

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Villalon-Reina, JE, Ching, CRK, Kothapalli, D, Sun, D, Nir, T, Lin, A, Forsyth, JK, Kushan, L, Vajdi, A, Jalbrzikowski, M, Hansen, L, Jonas, RK, Van Amelsvoort, T, Bakker, G, Kates, WR, Antshel, KM, Fremont, W, Campbell, LE, McCabe, KL, Daly, E, Gudbrandsen, M, Murphy, C, Murphy, D, Craig, M, Emanuel, B, McDonald-Mcginn, D, Ruparel, K, Roalf, D, Gur, RE, Schmitt, JE, Simon, TJ, Goodrich-Hunsaker, NJ, Durdle, CA, Doherty, J, Cunningham, AC, Van Den Bree, M, Linden, DEJ, Owen, M, Moss, H, Jahanshad, N, Bearden, CE & Thompson, PM 2018, Alternative diffusion anisotropy measures for the investigation of white matter alterations in 22q11.2 deletion syndrome. in N Lepore, E Romero & J Brieva (eds), 14th International Symposium on Medical Information Processing and Analysis., 109750U, Proceedings of SPIE - The International Society for Optical Engineering, vol. 10975, SPIE, 14th International Symposium on Medical Information Processing and Analysis, SIPAIM 2018, Mazatlan, Mexico, 10/24/18. https://doi.org/10.1117/12.2513788
Villalon-Reina JE, Ching CRK, Kothapalli D, Sun D, Nir T, Lin A et al. Alternative diffusion anisotropy measures for the investigation of white matter alterations in 22q11.2 deletion syndrome. In Lepore N, Romero E, Brieva J, editors, 14th International Symposium on Medical Information Processing and Analysis. SPIE. 2018. 109750U. (Proceedings of SPIE - The International Society for Optical Engineering). https://doi.org/10.1117/12.2513788
Villalon-Reina, Julio E. ; Ching, Christopher R.K. ; Kothapalli, Deydeep ; Sun, Daqiang ; Nir, Talia ; Lin, Amy ; Forsyth, Jennifer K. ; Kushan, Leila ; Vajdi, Ariana ; Jalbrzikowski, Maria ; Hansen, Laura ; Jonas, Rachel K. ; Van Amelsvoort, Therese ; Bakker, Geor ; Kates, Wendy R. ; Antshel, Kevin Martin ; Fremont, Wanda ; Campbell, Linda E. ; McCabe, Kathryn L. ; Daly, Eileen ; Gudbrandsen, Maria ; Murphy, Clodagh ; Murphy, Declan ; Craig, Michael ; Emanuel, Beverly ; McDonald-Mcginn, Donna ; Ruparel, Kosha ; Roalf, David ; Gur, Raquel E. ; Schmitt, J. Eric ; Simon, Tony J. ; Goodrich-Hunsaker, Naomi J. ; Durdle, Courtney A. ; Doherty, Joanne ; Cunningham, Adam C. ; Van Den Bree, Marianne ; Linden, David E.J. ; Owen, Michael ; Moss, Hayley ; Jahanshad, Neda ; Bearden, Carrie E. ; Thompson, Paul M. / Alternative diffusion anisotropy measures for the investigation of white matter alterations in 22q11.2 deletion syndrome. 14th International Symposium on Medical Information Processing and Analysis. editor / Natasha Lepore ; Eduardo Romero ; Jorge Brieva. SPIE, 2018. (Proceedings of SPIE - The International Society for Optical Engineering).
@inproceedings{2b32399ddcaa41d4a854990db54958e2,
title = "Alternative diffusion anisotropy measures for the investigation of white matter alterations in 22q11.2 deletion syndrome",
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.",
keywords = "22q11.2 deletion syndrome, diffusion anisotropy, Diffusion MRI, dMRI, white matter",
author = "Villalon-Reina, {Julio E.} and Ching, {Christopher R.K.} and Deydeep Kothapalli and Daqiang Sun and Talia Nir and Amy Lin and Forsyth, {Jennifer K.} and Leila Kushan and Ariana Vajdi and Maria Jalbrzikowski and Laura Hansen and Jonas, {Rachel K.} and {Van Amelsvoort}, Therese and Geor Bakker and Kates, {Wendy R.} and Antshel, {Kevin Martin} and Wanda Fremont and Campbell, {Linda E.} and McCabe, {Kathryn L.} and Eileen Daly and Maria Gudbrandsen and Clodagh Murphy and Declan Murphy and Michael Craig and Beverly Emanuel and Donna McDonald-Mcginn and Kosha Ruparel and David Roalf and Gur, {Raquel E.} and Schmitt, {J. Eric} and Simon, {Tony J.} and Goodrich-Hunsaker, {Naomi J.} and Durdle, {Courtney A.} and Joanne Doherty and Cunningham, {Adam C.} and {Van Den Bree}, Marianne and Linden, {David E.J.} and Michael Owen and Hayley Moss and Neda Jahanshad and Bearden, {Carrie E.} and Thompson, {Paul M.}",
year = "2018",
month = "1",
day = "1",
doi = "10.1117/12.2513788",
language = "English (US)",
series = "Proceedings of SPIE - The International Society for Optical Engineering",
publisher = "SPIE",
editor = "Natasha Lepore and Eduardo Romero and Jorge Brieva",
booktitle = "14th International Symposium on Medical Information Processing and Analysis",

}

TY - GEN

T1 - Alternative diffusion anisotropy measures for the investigation of white matter alterations in 22q11.2 deletion syndrome

AU - Villalon-Reina, Julio E.

AU - Ching, Christopher R.K.

AU - Kothapalli, Deydeep

AU - Sun, Daqiang

AU - Nir, Talia

AU - Lin, Amy

AU - Forsyth, Jennifer K.

AU - Kushan, Leila

AU - Vajdi, Ariana

AU - Jalbrzikowski, Maria

AU - Hansen, Laura

AU - Jonas, Rachel K.

AU - Van Amelsvoort, Therese

AU - Bakker, Geor

AU - Kates, Wendy R.

AU - Antshel, Kevin Martin

AU - Fremont, Wanda

AU - Campbell, Linda E.

AU - McCabe, Kathryn L.

AU - Daly, Eileen

AU - Gudbrandsen, Maria

AU - Murphy, Clodagh

AU - Murphy, Declan

AU - Craig, Michael

AU - Emanuel, Beverly

AU - McDonald-Mcginn, Donna

AU - Ruparel, Kosha

AU - Roalf, David

AU - Gur, Raquel E.

AU - Schmitt, J. Eric

AU - Simon, Tony J.

AU - Goodrich-Hunsaker, Naomi J.

AU - Durdle, Courtney A.

AU - Doherty, Joanne

AU - Cunningham, Adam C.

AU - Van Den Bree, Marianne

AU - Linden, David E.J.

AU - Owen, Michael

AU - Moss, Hayley

AU - Jahanshad, Neda

AU - Bearden, Carrie E.

AU - Thompson, Paul M.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - 22q11.2 deletion syndrome

KW - diffusion anisotropy

KW - Diffusion MRI

KW - dMRI

KW - white matter

UR - http://www.scopus.com/inward/record.url?scp=85060547360&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85060547360&partnerID=8YFLogxK

U2 - 10.1117/12.2513788

DO - 10.1117/12.2513788

M3 - Conference contribution

T3 - Proceedings of SPIE - The International Society for Optical Engineering

BT - 14th International Symposium on Medical Information Processing and Analysis

A2 - Lepore, Natasha

A2 - Romero, Eduardo

A2 - Brieva, Jorge

PB - SPIE

ER -