BRain development, Imaging trajectories and Deviations in brain morpholoGy in the pEdiatric population; BRIDGing thE gap (BRIDGE gap study)

Background information

Reference growth curves are an established concept in many fields of child development, used as standard of care in everyday clinical practice to detect deviations in typical patterns of growth. This is extremely beneficial for in-depth understanding of disease, treatment, and follow-up in children. However, there currently are no suitable growth charts that can be applied to assess trajectories of neurodevelopment.

The Generation R Study has one of the largest population-based samples of children with neuroimaging data. This brings us in a unique position to test the utility of direct comparison of clinical scans with  population-based derived normative data.

The primary goal of this project is to develop clinically relevant growth charts for global and regional brain regions in children. In addition, we analyze the robustness of these curves by comparing them to international reference populations derived from other population-based studies. To test the applicability of these growth charts in a clinical setting, we will use thecharts to depict deviations in neurodevelopment in different patient groups. The second goal is to evaluate variations in brain development to help decide in everyday practice whether a finding is a relevant abnormality in brain development or not.

The Generation R Study cohort will provide a bridge to the application of both neurodevelopment curves and prediction models in pediatric neuroradiology. The main aim of this cohort is to study normal and abnormal development and health of individuals from fetal life until young adulthood. The cohort is the largest population-based sample of children with over 7000 neuroimaging scans of children and adolescents. The neuroimaging data of the Generation R Study cohort will provide valuable information for the development of the growth charts for global and regional brain regions in children.

To construct ‘neurodevelopment curves’ for total and regional brain volumes in children and adolescents. Furthermore, focus on differences in gender and ethnicity to bridge the gap to the diversity of normal brain development. To be able to detect early deviations in brain development in specific patients groups. Age-related changes in brain morphology are crucial to better understanding the neurobiology of these clinical conditions and eventually bridge the gap to possible therapeutic targets. To gain knowledge on variations in brain development and evaluate the consequences of incidental findings to bridge the gap between widely accepted consensus and factual evidence-based medicine.

Erasmus MC Grant 2018

The general design of Generation R Study is made possible by financial support from the Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam, the Netherlands Organization for Health Research and Development (ZonMw), the Netherlands Organization for Scientific Research (NWO), the Ministry of Health, Welfare and Sport. The Kinder NeuroImaging Centrum Rotterdam (KNICR) has been supported in part by a ZonMw TOP project (No. 91211021, Simons Foundation grant (No. 307280), and the Sophia Children’s Hospital Foundation / Vrienden van de Sophia.

Internal collaborations

• Generation R Study Group
• Department of Radiology and Nuclear Medicine / Population Imaging
• Department of Child and Adolescent Psychiatry
• Department of Neurology
• Department of Pediatrics

External collaborations

• Adolescent Brain Cognitive Development (ABCD Study Group) National Institute of Health (NIH), United States
  www.abcdstudy.org
• Department of Psychology, Chinese Academy of Science

Cavum Septum Pellucidum in the General Pediatric Population and Its Relation to Surrounding Brain Structure Volumes, Cognitive Function, and Emotional or Behavioral Problems. Dremmen et al (2019)
www.ncbi.nlm.nih.gov/pubmed

Paediatric population neuroimaging and the Generation R Study: the second wave. White et al. (2018)
www.ncbi.nlm.nih.gov/pubmed

The Generation R Study: design and cohort update 2017. Kooijman et al. (2016) 
www.ncbi.nlm.nih.gov

• Marjolein Dremmen.
• Tonya White.
• Meike Vernooij.