A Brain Morphometry Study with Across-Site Harmonization Using a ComBat-Generalized Additive Model in Children and Adolescents
Tadashi Shiohama,
Norihide Maikusa,
Masahiro Kawaguchi,
Jun Natsume,
Yoshiyuki Hirano,
Keito Saito,
Jun-ichi Takanashi,
Jacob Levman,
Emi Takahashi,
Koji Matsumoto,
Hajime Yokota,
Shinya Hattori,
Keita Tsujimura,
Daisuke Sawada,
Tomoko Uchida,
Tomozumi Takatani,
Katsunori Fujii,
Shinji Naganawa,
Noriko Sato,
Hiromichi Hamada
Affiliations
Tadashi Shiohama
Department of Pediatrics, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba-shi 260-8677, Chiba, Japan
Norihide Maikusa
Center for Evolutionary Cognitive Sciences, Graduate School of Art and Sciences, The University of Tokyo, Tokyo 108-8639, Japan
Masahiro Kawaguchi
Department of Pediatrics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Aichi, Japan
Jun Natsume
Department of Pediatrics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Aichi, Japan
Yoshiyuki Hirano
Research Center for Child Mental Development, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba-shi 260-8677, Chiba, Japan
Keito Saito
Department of Pediatrics and Pediatric Neurology, Tokyo Women’s Medical University Yachiyo Medical Center, 477-96 Owadashinden, Yachiyo-shi 276-8524, Chiba, Japan
Jun-ichi Takanashi
Department of Pediatrics and Pediatric Neurology, Tokyo Women’s Medical University Yachiyo Medical Center, 477-96 Owadashinden, Yachiyo-shi 276-8524, Chiba, Japan
Jacob Levman
Division of Newborn Medicine, Department of Medicine, Boston Children’s Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA
Emi Takahashi
Division of Newborn Medicine, Department of Medicine, Boston Children’s Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA
Koji Matsumoto
Department of Radiology, Chiba University Hospital, Inohana 1-8-1, Chuo-ku, Chiba-shi 260-8677, Chiba, Japan
Hajime Yokota
Diagnostic Radiology and Radiation Oncology, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba-shi 260-8677, Chiba, Japan
Shinya Hattori
Department of Radiology, Chiba University Hospital, Inohana 1-8-1, Chuo-ku, Chiba-shi 260-8677, Chiba, Japan
Keita Tsujimura
Group of Brain Function and Development, Neuroscience Institute of the Graduate School of Science, Nagoya University, Nagoya 466-8550, Aichi, Japan
Daisuke Sawada
Department of Pediatrics, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba-shi 260-8677, Chiba, Japan
Tomoko Uchida
Department of Pediatrics, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba-shi 260-8677, Chiba, Japan
Tomozumi Takatani
Department of Pediatrics, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba-shi 260-8677, Chiba, Japan
Katsunori Fujii
Department of Pediatrics, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba-shi 260-8677, Chiba, Japan
Shinji Naganawa
Department of Radiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Aichi, Japan
Noriko Sato
Department of Radiology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo 187-8551, Japan
Hiromichi Hamada
Department of Pediatrics, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba-shi 260-8677, Chiba, Japan
Regional anatomical structures of the brain are intimately connected to functions corresponding to specific regions and the temporospatial pattern of genetic expression and their functions from the fetal period to old age. Therefore, quantitative brain morphometry has often been employed in neuroscience investigations, while controlling for the scanner effect of the scanner is a critical issue for ensuring accuracy in brain morphometric studies of rare orphan diseases due to the lack of normal reference values available for multicenter studies. This study aimed to provide across-site normal reference values of global and regional brain volumes for each sex and age group in children and adolescents. We collected magnetic resonance imaging (MRI) examinations of 846 neurotypical participants aged 6.0–17.9 years (339 male and 507 female participants) from 5 institutions comprising healthy volunteers or neurotypical patients without neurological disorders, neuropsychological disorders, or epilepsy. Regional-based analysis using the CIVET 2.1.0. pipeline provided regional brain volumes, and the measurements were across-site combined using ComBat-GAM harmonization. The normal reference values of global and regional brain volumes and lateral indices in our study could be helpful for evaluating the characteristics of the brain morphology of each individual in a clinical setting and investigating the brain morphology of ultra-rare diseases.
