Body size and intracranial volume interact with the structure of the central nervous system: A multi-center in vivo neuroimaging study

René Labounek; Monica T Bondy; Amy L Paulson; Sandrine Bédard; Mihael Abramovic; Eva Alonso-Ortiz; Nicole T Atcheson; Laura R Barlow; Robert L Barry; Markus Barth; Marco Battiston; Christian Büchel; Matthew D Budde; Virginie Callot; Anna Combes; Benjamin De Leener; Maxime Descoteaux; Paulo Loureiro de Sousa; Marek Dostál; Julien Doyon; Adam V Dvorak; Falk Eippert; Karla R Epperson; Kevin S Epperson; Patrick Freund; Jürgen Finsterbusch; Alexandru Foias; Michela Fratini; Issei Fukunaga; Claudia A M Gandini Wheeler-Kingshott; GianCarlo Germani; Guillaume Gilbert; Federico Giove; Francesco Grussu; Akifumi Hagiwara; Pierre-Gilles Henry; Tomáš Horák; Masaaki Hori; James M Joers; Kouhei Kamiya; Haleh Karbasforoushan; Miloš Keřkovský; Ali Khatibi; Joo-Won Kim; Nawal Kinany; Hagen Kitzler; Shannon Kolind; Yazhuo Kong; Petr Kudlička; Paul Kuntke; Nyoman D Kurniawan; Slawomir Kusmia; Maria Marcella Laganà; Cornelia Laule; Christine S W Law; Tobias Leutritz; Yaou Liu; Sara Llufriu; Sean Mackey; Allan R Martin; Eloy Martinez-Heras; Loan Mattera; Kristin P O'Grady; Nico Papinutto; Daniel Papp; Deborah Pareto; Todd B Parrish; Anna Pichiecchio; Ferran Prados; Àlex Rovira; Marc J Ruitenberg; Rebecca S Samson; Giovanni Savini; Maryam Seif; Alan C Seifert; Alex K Smith; Seth A Smith; Zachary A Smith; Elisabeth Solana; Yuichi Suzuki; George W Tackley; Alexandra Tinnermann; Jan Valošek; Dimitri Van De Ville; Marios C Yiannakas; Kenneth A Weber Ii; Nikolaus Weiskopf; Richard G Wise; Patrik O Wyss; Junqian Xu; Julien Cohen-Adad; Christophe Lenglet; Igor Nestrašil

doi:10.1162/imag_a_00559

Body size and intracranial volume interact with the structure of the central nervous system: A multi-center in vivo neuroimaging study

René Labounek, Monica T Bondy, Amy L Paulson, Sandrine Bédard, Mihael Abramovic, Eva Alonso-Ortiz, Nicole T Atcheson, Laura R Barlow, Robert L Barry, Markus Barth, Marco Battiston, Christian Büchel, Matthew D Budde, Virginie Callot, Anna Combes, Benjamin De Leener, Maxime Descoteaux, Paulo Loureiro de Sousa, Marek Dostál, Julien DoyonAdam V Dvorak, Falk Eippert, Karla R Epperson, Kevin S Epperson, Patrick Freund, Jürgen Finsterbusch, Alexandru Foias, Michela Fratini, Issei Fukunaga, Claudia A M Gandini Wheeler-Kingshott, GianCarlo Germani, Guillaume Gilbert, Federico Giove, Francesco Grussu, Akifumi Hagiwara, Pierre-Gilles Henry, Tomáš Horák, Masaaki Hori, James M Joers, Kouhei Kamiya, Haleh Karbasforoushan, Miloš Keřkovský, Ali Khatibi, Joo-Won Kim, Nawal Kinany, Hagen Kitzler, Shannon Kolind, Yazhuo Kong, Petr Kudlička, Paul Kuntke, Nyoman D Kurniawan, Slawomir Kusmia, Maria Marcella Laganà, Cornelia Laule, Christine S W Law, Tobias Leutritz, Yaou Liu, Sara Llufriu, Sean Mackey, Allan R Martin, Eloy Martinez-Heras, Loan Mattera, Kristin P O'Grady, Nico Papinutto, Daniel Papp, Deborah Pareto, Todd B Parrish, Anna Pichiecchio, Ferran Prados, Àlex Rovira, Marc J Ruitenberg, Rebecca S Samson, Giovanni Savini, Maryam Seif, Alan C Seifert, Alex K Smith, Seth A Smith, Zachary A Smith, Elisabeth Solana, Yuichi Suzuki, George W Tackley, Alexandra Tinnermann, Jan Valošek, Dimitri Van De Ville, Marios C Yiannakas, Kenneth A Weber Ii, Nikolaus Weiskopf, Richard G Wise, Patrik O Wyss, Junqian Xu, Julien Cohen-Adad, Christophe Lenglet, Igor Nestrašil

Department of Psychology

Research output: Contribution to journal › Article › peer-review

1 Citation (SciVal)

Abstract

Clinical research emphasizes the implementation of rigorous and reproducible study designs that rely on between-group matching or controlling for sources of biological variation such as subject's sex and age. However, corrections for body size (i.e., height and weight) are mostly lacking in clinical neuroimaging designs. This study investigates the importance of body size parameters in their relationship with spinal cord (SC) and brain magnetic resonance imaging (MRI) metrics. Data were derived from a cosmopolitan population of 267 healthy human adults (age 30.1 ± 6.6 years old, 125 females). We show that body height correlates with brain gray matter (GM) volume, cortical GM volume, total cerebellar volume, brainstem volume, and cross-sectional area (CSA) of cervical SC white matter (CSA-WM; 0.44 ≤ r ≤ 0.62). Intracranial volume (ICV) correlates with body height (r = 0.46) and the brain volumes and CSA-WM (0.37 ≤ r ≤ 0.77). In comparison, age correlates with cortical GM volume, precentral GM volume, and cortical thickness (-0.21 ≥ r ≥ -0.27). Body weight correlates with magnetization transfer ratio in the SC WM, dorsal columns, and lateral corticospinal tracts (-0.20 ≥ r ≥ -0.23). Body weight further correlates with the mean diffusivity derived from diffusion tensor imaging (DTI) in SC WM (r = -0.20) and dorsal columns (-0.21), but only in males. CSA-WM correlates with brain volumes (0.39 ≤ r ≤ 0.64), and with precentral gyrus thickness and DTI-based fractional anisotropy in SC dorsal columns and SC lateral corticospinal tracts (-0.22 ≥ r ≥ -0.25). Linear mixture of age, sex, or sex and age, explained 2 ± 2%, 24 ± 10%, or 26 ± 10%, of data variance in brain volumetry and SC CSA. The amount of explained variance increased to 33 ± 11%, 41 ± 17%, or 46 ± 17%, when body height, ICV, or body height and ICV were added into the mixture model. In females, the explained variances halved suggesting another unidentified biological factor(s) determining females' central nervous system (CNS) morphology. In conclusion, body size and ICV are significant biological variables. Along with sex and age, body size should therefore be included as a mandatory variable in the design of clinical neuroimaging studies examining SC and brain structure; and body size and ICV should be considered as covariates in statistical analyses. Normalization of different brain regions with ICV diminishes their correlations with body size, but simultaneously amplifies ICV-related variance (r = 0.72 ± 0.07) and suppresses volume variance of the different brain regions (r = 0.12 ± 0.19) in the normalized measurements.

Original language	English
Journal	Imaging Neuroscience
Volume	3
Early online date	15 Apr 2025
DOIs	https://doi.org/10.1162/imag_a_00559
Publication status	Published - 7 May 2025

Data Availability Statement

All raw data are publicly available at: https://github.com/spine-generic/data-multi-subject (utilized release ID: r20231212). MRI protocols for all optimized manufacturers and scanner types are publicly available at: https://github.com/spine-generic/protocols. Tables with SCT and Freesurfer measurements are available at: https://github.com/umn-milab/spine-generic-body-size-results (utilized release ID: r20250226). Spinal Cord Toolbox is available at: https://github.com/spinalcordtoolbox/spinalcordtoolbox (utilized version: 6.1; git commit: git-master-c7a8072fd63a06a2775a74029c042833f0fce510). FreeSurfer is available at: https://surfer.nmr.mgh.harvard.edu (utilized version: 7.2). All computer code providing image and statistical analyses is available at: https://github.com/spine-generic/spine-generic (utilized release ID: height-weight-analysis-v1.2).

Acknowledgements

The Center for Magnetic Resonance Research (CMRR), Department of Radiology; the Center for Neurobehavioral Development (CNBD) at the Masonic Institute for the Developing Brain (MIDB), Department of Pediatrics; and the Minnesota Supercomputing Institute (MSI); all are part of the University of Minnesota and all provided laboratory space and computational support for this research project. The authors acknowledge the facilities, scientific and technical assistance of the National Imaging Facility, a National Collaborative Research Infrastructure Strategy (NCRIS) capability, at the Centre for Advanced Imaging, The University of Queensland. This work is based on experiments performed at the Swiss Center for Musculoskeletal Imaging, SCMI, Balgrist Campus AG, Zurich.

Funding

M.D. was supported by the University of Sherbrooke institutional research Chair in Neuroinformatics and his NSERC Discovery grant RGPIN-2020-04818. N.W. has received funding from the European Union’s Horizon 2020 research and innovation programme under the grant agreement No 681094. S.L. holds grants from the ISCIII [PI21/01189], AGAUR [021-SGR-01325], and research support from Bristol Myers Squibb. C.A.M.G.W.-K. receives funding from MRC (#MR/S026088/1), Ataxia UK, Rosetrees Trust (#PGL22/100041 and #PGL21/10079). The research reported in this publication was also supported by the National Natural Science Foundation of China (82072010); the Beijing Natural Science Foundation [IS23108]; the Swiss National Science Foundation [205321-207493]; the Ministry of Health, Czech Republic—conceptual development of research organization [FNBr, 65269705]; the Ministry of Education, Youth and Sports, Czech Republic [LM2018129 Czech-BioImaging], part of the Euro-BioImaging (www.eurobioimaging.eu) Advanced Light Microscopy and Medical Imaging Node (Brno, Czech Republic); the Max Planck Society and the European Research Council [ERC StG 758974, European Union’s Horizon 2020 research and innovation program 758974]; the University of Pennsylvania [MDBR-17-123-MPS - Million Dollar Bike Ride]; the Instituto Salud Carlos III—co-funded European Union [PI18/00823, PI22/01709]; the Ministry of Health of the Czech Republic [NU22-04-00024]; the European Union’s Horizon Europe research and innovation program under the Marie Skłodowska-Curie grant [101107932]; the American Heart Association [23CDA1054207]; the Fondation Courtois; the Natural Sciences and Engineering Research Council of Canada (NSERC), TransMedTech Institute, ICORD [RGPIN-2020–05242] and UBC; the Craig H. Neilsen Foundation; the “la Caixa” Foundation [ID 100010434; fellowship code LCF/BQ/PR22/11920010]; the Wings For Life charity [WFL-CH-19/20]; the International Foundation for Research [IRP-158]; the Czech Health Research Council [NV18-04-00159]; the National Institute for Health Research Biomedical Research Centre at UCL and UCLH; the German Research Foundation [TI 1110/1-1]; SpinalCure Australia; the BRC [BRC1130/HEI/RS/11041]; the European Union—NextGenerationEU under the Italian Ministry of University and Research (MUR) National Innovation Ecosystem [ECS00000041 - VITALITY - CUP D73C22000840006]; the Canada Research Chair in Quantitative Magnetic Resonance Imaging [CRC-2020-00179]; the Canadian Institute of Health Research [PJT-190258]; the Canada Foundation for Innovation [32454, 34824]; the Fonds de Recherche du Québec - Santé [322736, 324636]; the Natural Sciences and Engineering Research Council of Canada [RGPIN-2019-07244]; the Canada First Research Excellence Fund (IVADO and TransMedTech), the Courtois NeuroMod project; the Quebec BioImaging Network [5886, 35450]; the INSPIRED (Spinal Research, UK; Wings for Life, Austria; Craig H. Neilsen Foundation, USA); the Mila - Tech Transfer Funding Program; and the National Institutes of Health (NIH) through the National Institute of Neurological Disorders and Stroke and the National Institute of Biomedical Imaging and Bioengineering [P41EB027061, P30NS076408, K23NS104211, L30NS108301, R01NS128478, R01NS133305, K01NS105160, K01EB030039, 5R01NS109114, K24NS126781, R61NS118651, R00EB016689, R01EB027779, R21EB031211, R01NS109450, and R03NS139000]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1162/imag_a_00559Licence: CC BY

Cite this

Labounek, R., Bondy, M. T., Paulson, A. L., Bédard, S., Abramovic, M., Alonso-Ortiz, E., Atcheson, N. T., Barlow, L. R., Barry, R. L., Barth, M., Battiston, M., Büchel, C., Budde, M. D., Callot, V., Combes, A., De Leener, B., Descoteaux, M., de Sousa, P. L., Dostál, M., ... Nestrašil, I. (2025). Body size and intracranial volume interact with the structure of the central nervous system: A multi-center in vivo neuroimaging study. Imaging Neuroscience, 3. https://doi.org/10.1162/imag_a_00559

Labounek, R, Bondy, MT, Paulson, AL, Bédard, S, Abramovic, M, Alonso-Ortiz, E, Atcheson, NT, Barlow, LR, Barry, RL, Barth, M, Battiston, M, Büchel, C, Budde, MD, Callot, V, Combes, A, De Leener, B, Descoteaux, M, de Sousa, PL, Dostál, M, Doyon, J, Dvorak, AV, Eippert, F, Epperson, KR, Epperson, KS, Freund, P, Finsterbusch, J, Foias, A, Fratini, M, Fukunaga, I, Wheeler-Kingshott, CAMG, Germani, G, Gilbert, G, Giove, F, Grussu, F, Hagiwara, A, Henry, P-G, Horák, T, Hori, M, Joers, JM, Kamiya, K, Karbasforoushan, H, Keřkovský, M, Khatibi, A, Kim, J-W, Kinany, N, Kitzler, H, Kolind, S, Kong, Y, Kudlička, P, Kuntke, P, Kurniawan, ND, Kusmia, S, Laganà, MM, Laule, C, Law, CSW, Leutritz, T, Liu, Y, Llufriu, S, Mackey, S, Martin, AR, Martinez-Heras, E, Mattera, L, O'Grady, KP, Papinutto, N, Papp, D, Pareto, D, Parrish, TB, Pichiecchio, A, Prados, F, Rovira, À, Ruitenberg, MJ, Samson, RS, Savini, G, Seif, M, Seifert, AC, Smith, AK, Smith, SA, Smith, ZA, Solana, E, Suzuki, Y, Tackley, GW, Tinnermann, A, Valošek, J, Van De Ville, D, Yiannakas, MC, Weber Ii, KA, Weiskopf, N, Wise, RG, Wyss, PO, Xu, J, Cohen-Adad, J, Lenglet, C & Nestrašil, I 2025, 'Body size and intracranial volume interact with the structure of the central nervous system: A multi-center in vivo neuroimaging study', Imaging Neuroscience, vol. 3. https://doi.org/10.1162/imag_a_00559

@article{e92f3df9be404ca5a96cdb96a293246b,

title = "Body size and intracranial volume interact with the structure of the central nervous system: A multi-center in vivo neuroimaging study",

abstract = "Clinical research emphasizes the implementation of rigorous and reproducible study designs that rely on between-group matching or controlling for sources of biological variation such as subject's sex and age. However, corrections for body size (i.e., height and weight) are mostly lacking in clinical neuroimaging designs. This study investigates the importance of body size parameters in their relationship with spinal cord (SC) and brain magnetic resonance imaging (MRI) metrics. Data were derived from a cosmopolitan population of 267 healthy human adults (age 30.1 ± 6.6 years old, 125 females). We show that body height correlates with brain gray matter (GM) volume, cortical GM volume, total cerebellar volume, brainstem volume, and cross-sectional area (CSA) of cervical SC white matter (CSA-WM; 0.44 ≤ r ≤ 0.62). Intracranial volume (ICV) correlates with body height (r = 0.46) and the brain volumes and CSA-WM (0.37 ≤ r ≤ 0.77). In comparison, age correlates with cortical GM volume, precentral GM volume, and cortical thickness (-0.21 ≥ r ≥ -0.27). Body weight correlates with magnetization transfer ratio in the SC WM, dorsal columns, and lateral corticospinal tracts (-0.20 ≥ r ≥ -0.23). Body weight further correlates with the mean diffusivity derived from diffusion tensor imaging (DTI) in SC WM (r = -0.20) and dorsal columns (-0.21), but only in males. CSA-WM correlates with brain volumes (0.39 ≤ r ≤ 0.64), and with precentral gyrus thickness and DTI-based fractional anisotropy in SC dorsal columns and SC lateral corticospinal tracts (-0.22 ≥ r ≥ -0.25). Linear mixture of age, sex, or sex and age, explained 2 ± 2\%, 24 ± 10\%, or 26 ± 10\%, of data variance in brain volumetry and SC CSA. The amount of explained variance increased to 33 ± 11\%, 41 ± 17\%, or 46 ± 17\%, when body height, ICV, or body height and ICV were added into the mixture model. In females, the explained variances halved suggesting another unidentified biological factor(s) determining females' central nervous system (CNS) morphology. In conclusion, body size and ICV are significant biological variables. Along with sex and age, body size should therefore be included as a mandatory variable in the design of clinical neuroimaging studies examining SC and brain structure; and body size and ICV should be considered as covariates in statistical analyses. Normalization of different brain regions with ICV diminishes their correlations with body size, but simultaneously amplifies ICV-related variance (r = 0.72 ± 0.07) and suppresses volume variance of the different brain regions (r = 0.12 ± 0.19) in the normalized measurements.",

author = "Ren{\'e} Labounek and Bondy, \{Monica T\} and Paulson, \{Amy L\} and Sandrine B{\'e}dard and Mihael Abramovic and Eva Alonso-Ortiz and Atcheson, \{Nicole T\} and Barlow, \{Laura R\} and Barry, \{Robert L\} and Markus Barth and Marco Battiston and Christian B{\"u}chel and Budde, \{Matthew D\} and Virginie Callot and Anna Combes and \{De Leener\}, Benjamin and Maxime Descoteaux and \{de Sousa\}, \{Paulo Loureiro\} and Marek Dost{\'a}l and Julien Doyon and Dvorak, \{Adam V\} and Falk Eippert and Epperson, \{Karla R\} and Epperson, \{Kevin S\} and Patrick Freund and J{\"u}rgen Finsterbusch and Alexandru Foias and Michela Fratini and Issei Fukunaga and Wheeler-Kingshott, \{Claudia A M Gandini\} and GianCarlo Germani and Guillaume Gilbert and Federico Giove and Francesco Grussu and Akifumi Hagiwara and Pierre-Gilles Henry and Tom{\'a}{\v s} Hor{\'a}k and Masaaki Hori and Joers, \{James M\} and Kouhei Kamiya and Haleh Karbasforoushan and Milo{\v s} Ke{\v r}kovsk{\'y} and Ali Khatibi and Joo-Won Kim and Nawal Kinany and Hagen Kitzler and Shannon Kolind and Yazhuo Kong and Petr Kudli{\v c}ka and Paul Kuntke and Kurniawan, \{Nyoman D\} and Slawomir Kusmia and Lagan{\`a}, \{Maria Marcella\} and Cornelia Laule and Law, \{Christine S W\} and Tobias Leutritz and Yaou Liu and Sara Llufriu and Sean Mackey and Martin, \{Allan R\} and Eloy Martinez-Heras and Loan Mattera and O'Grady, \{Kristin P\} and Nico Papinutto and Daniel Papp and Deborah Pareto and Parrish, \{Todd B\} and Anna Pichiecchio and Ferran Prados and {\`A}lex Rovira and Ruitenberg, \{Marc J\} and Samson, \{Rebecca S\} and Giovanni Savini and Maryam Seif and Seifert, \{Alan C\} and Smith, \{Alex K\} and Smith, \{Seth A\} and Smith, \{Zachary A\} and Elisabeth Solana and Yuichi Suzuki and Tackley, \{George W\} and Alexandra Tinnermann and Jan Valo{\v s}ek and \{Van De Ville\}, Dimitri and Yiannakas, \{Marios C\} and \{Weber Ii\}, \{Kenneth A\} and Nikolaus Weiskopf and Wise, \{Richard G\} and Wyss, \{Patrik O\} and Junqian Xu and Julien Cohen-Adad and Christophe Lenglet and Igor Nestra{\v s}il",

year = "2025",

month = may,

day = "7",

doi = "10.1162/imag\_a\_00559",

language = "English",

volume = "3",

journal = "Imaging Neuroscience",

issn = "2837-6056",

publisher = "MIT Press",

}

TY - JOUR

T1 - Body size and intracranial volume interact with the structure of the central nervous system

T2 - A multi-center in vivo neuroimaging study

AU - Labounek, René

AU - Bondy, Monica T

AU - Paulson, Amy L

AU - Bédard, Sandrine

AU - Abramovic, Mihael

AU - Alonso-Ortiz, Eva

AU - Atcheson, Nicole T

AU - Barlow, Laura R

AU - Barry, Robert L

AU - Barth, Markus

AU - Battiston, Marco

AU - Büchel, Christian

AU - Budde, Matthew D

AU - Callot, Virginie

AU - Combes, Anna

AU - De Leener, Benjamin

AU - Descoteaux, Maxime

AU - de Sousa, Paulo Loureiro

AU - Dostál, Marek

AU - Doyon, Julien

AU - Dvorak, Adam V

AU - Eippert, Falk

AU - Epperson, Karla R

AU - Epperson, Kevin S

AU - Freund, Patrick

AU - Finsterbusch, Jürgen

AU - Foias, Alexandru

AU - Fratini, Michela

AU - Fukunaga, Issei

AU - Wheeler-Kingshott, Claudia A M Gandini

AU - Germani, GianCarlo

AU - Gilbert, Guillaume

AU - Giove, Federico

AU - Grussu, Francesco

AU - Hagiwara, Akifumi

AU - Henry, Pierre-Gilles

AU - Horák, Tomáš

AU - Hori, Masaaki

AU - Joers, James M

AU - Kamiya, Kouhei

AU - Karbasforoushan, Haleh

AU - Keřkovský, Miloš

AU - Khatibi, Ali

AU - Kim, Joo-Won

AU - Kinany, Nawal

AU - Kitzler, Hagen

AU - Kolind, Shannon

AU - Kong, Yazhuo

AU - Kudlička, Petr

AU - Kuntke, Paul

AU - Kurniawan, Nyoman D

AU - Kusmia, Slawomir

AU - Laganà, Maria Marcella

AU - Laule, Cornelia

AU - Law, Christine S W

AU - Leutritz, Tobias

AU - Liu, Yaou

AU - Llufriu, Sara

AU - Mackey, Sean

AU - Martin, Allan R

AU - Martinez-Heras, Eloy

AU - Mattera, Loan

AU - O'Grady, Kristin P

AU - Papinutto, Nico

AU - Papp, Daniel

AU - Pareto, Deborah

AU - Parrish, Todd B

AU - Pichiecchio, Anna

AU - Prados, Ferran

AU - Rovira, Àlex

AU - Ruitenberg, Marc J

AU - Samson, Rebecca S

AU - Savini, Giovanni

AU - Seif, Maryam

AU - Seifert, Alan C

AU - Smith, Alex K

AU - Smith, Seth A

AU - Smith, Zachary A

AU - Solana, Elisabeth

AU - Suzuki, Yuichi

AU - Tackley, George W

AU - Tinnermann, Alexandra

AU - Valošek, Jan

AU - Van De Ville, Dimitri

AU - Yiannakas, Marios C

AU - Weber Ii, Kenneth A

AU - Weiskopf, Nikolaus

AU - Wise, Richard G

AU - Wyss, Patrik O

AU - Xu, Junqian

AU - Cohen-Adad, Julien

AU - Lenglet, Christophe

AU - Nestrašil, Igor

PY - 2025/5/7

Y1 - 2025/5/7

N2 - Clinical research emphasizes the implementation of rigorous and reproducible study designs that rely on between-group matching or controlling for sources of biological variation such as subject's sex and age. However, corrections for body size (i.e., height and weight) are mostly lacking in clinical neuroimaging designs. This study investigates the importance of body size parameters in their relationship with spinal cord (SC) and brain magnetic resonance imaging (MRI) metrics. Data were derived from a cosmopolitan population of 267 healthy human adults (age 30.1 ± 6.6 years old, 125 females). We show that body height correlates with brain gray matter (GM) volume, cortical GM volume, total cerebellar volume, brainstem volume, and cross-sectional area (CSA) of cervical SC white matter (CSA-WM; 0.44 ≤ r ≤ 0.62). Intracranial volume (ICV) correlates with body height (r = 0.46) and the brain volumes and CSA-WM (0.37 ≤ r ≤ 0.77). In comparison, age correlates with cortical GM volume, precentral GM volume, and cortical thickness (-0.21 ≥ r ≥ -0.27). Body weight correlates with magnetization transfer ratio in the SC WM, dorsal columns, and lateral corticospinal tracts (-0.20 ≥ r ≥ -0.23). Body weight further correlates with the mean diffusivity derived from diffusion tensor imaging (DTI) in SC WM (r = -0.20) and dorsal columns (-0.21), but only in males. CSA-WM correlates with brain volumes (0.39 ≤ r ≤ 0.64), and with precentral gyrus thickness and DTI-based fractional anisotropy in SC dorsal columns and SC lateral corticospinal tracts (-0.22 ≥ r ≥ -0.25). Linear mixture of age, sex, or sex and age, explained 2 ± 2%, 24 ± 10%, or 26 ± 10%, of data variance in brain volumetry and SC CSA. The amount of explained variance increased to 33 ± 11%, 41 ± 17%, or 46 ± 17%, when body height, ICV, or body height and ICV were added into the mixture model. In females, the explained variances halved suggesting another unidentified biological factor(s) determining females' central nervous system (CNS) morphology. In conclusion, body size and ICV are significant biological variables. Along with sex and age, body size should therefore be included as a mandatory variable in the design of clinical neuroimaging studies examining SC and brain structure; and body size and ICV should be considered as covariates in statistical analyses. Normalization of different brain regions with ICV diminishes their correlations with body size, but simultaneously amplifies ICV-related variance (r = 0.72 ± 0.07) and suppresses volume variance of the different brain regions (r = 0.12 ± 0.19) in the normalized measurements.

AB - Clinical research emphasizes the implementation of rigorous and reproducible study designs that rely on between-group matching or controlling for sources of biological variation such as subject's sex and age. However, corrections for body size (i.e., height and weight) are mostly lacking in clinical neuroimaging designs. This study investigates the importance of body size parameters in their relationship with spinal cord (SC) and brain magnetic resonance imaging (MRI) metrics. Data were derived from a cosmopolitan population of 267 healthy human adults (age 30.1 ± 6.6 years old, 125 females). We show that body height correlates with brain gray matter (GM) volume, cortical GM volume, total cerebellar volume, brainstem volume, and cross-sectional area (CSA) of cervical SC white matter (CSA-WM; 0.44 ≤ r ≤ 0.62). Intracranial volume (ICV) correlates with body height (r = 0.46) and the brain volumes and CSA-WM (0.37 ≤ r ≤ 0.77). In comparison, age correlates with cortical GM volume, precentral GM volume, and cortical thickness (-0.21 ≥ r ≥ -0.27). Body weight correlates with magnetization transfer ratio in the SC WM, dorsal columns, and lateral corticospinal tracts (-0.20 ≥ r ≥ -0.23). Body weight further correlates with the mean diffusivity derived from diffusion tensor imaging (DTI) in SC WM (r = -0.20) and dorsal columns (-0.21), but only in males. CSA-WM correlates with brain volumes (0.39 ≤ r ≤ 0.64), and with precentral gyrus thickness and DTI-based fractional anisotropy in SC dorsal columns and SC lateral corticospinal tracts (-0.22 ≥ r ≥ -0.25). Linear mixture of age, sex, or sex and age, explained 2 ± 2%, 24 ± 10%, or 26 ± 10%, of data variance in brain volumetry and SC CSA. The amount of explained variance increased to 33 ± 11%, 41 ± 17%, or 46 ± 17%, when body height, ICV, or body height and ICV were added into the mixture model. In females, the explained variances halved suggesting another unidentified biological factor(s) determining females' central nervous system (CNS) morphology. In conclusion, body size and ICV are significant biological variables. Along with sex and age, body size should therefore be included as a mandatory variable in the design of clinical neuroimaging studies examining SC and brain structure; and body size and ICV should be considered as covariates in statistical analyses. Normalization of different brain regions with ICV diminishes their correlations with body size, but simultaneously amplifies ICV-related variance (r = 0.72 ± 0.07) and suppresses volume variance of the different brain regions (r = 0.12 ± 0.19) in the normalized measurements.

U2 - 10.1162/imag_a_00559

DO - 10.1162/imag_a_00559

M3 - Article

C2 - 40800833

SN - 2837-6056

VL - 3

JO - Imaging Neuroscience

JF - Imaging Neuroscience

ER -

Body size and intracranial volume interact with the structure of the central nervous system: A multi-center in vivo neuroimaging study

Abstract

Data Availability Statement

Acknowledgements

Funding

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