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  • Review Article
  • Published:

Methodological considerations on diffusion MRI tractography in infants aged 0–2 years: a scoping review

Pediatric Research volume 97, pages 880–897 (2025)Cite this article

Abstract

Diffusion MRI (dMRI) enables studying the complex architectural organization of the brain’s white matter (WM) through virtual reconstruction of WM fiber tracts (tractography). Despite the anticipated clinical importance of applying tractography to study structural connectivity and tract development during the critical period of rapid infant brain maturation, detailed descriptions on how to approach tractography in young infants are limited. Over the past two decades, tractography from infant dMRI has mainly been applied in research settings and focused on diffusion tensor imaging (DTI). Only few studies used techniques superior to DTI in terms of disentangling information on the brain’s organizational complexity, including crossing fibers. While more advanced techniques may enhance our understanding of the intricate processes of normal and abnormal brain development and extensive knowledge has been gained from application on adult scans, their applicability in infants has remained underexplored. This may partially be due to the higher technical requirements versus the need to limit scan time in young infants. We review various previously described methodological practices for tractography in the infant brain (0–2 years-of-age) and provide recommendations to optimize advanced tractography approaches to enable more accurate reconstructions of the brain WM’s complexity.

Impact

  • Diffusion tensor imaging is the technique most frequently used for fiber tracking in the developing infant brain but is limited in capability to disentangle the complex white matter organization.

  • Advanced tractography techniques allow for reconstruction of crossing fiber bundles to better reflect the brain’s complex organization. Yet, they pose practical and technical challenges in the fast developing young infant’s brain. Methods on how to approach advanced tractography in the young infant’s brain have hardly been described.

  • Based on a literature review, recommendations are provided to optimize tractography for the developing infant brain, aiming to advance early diagnosis and neuroprotective strategies.

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Fig. 1: Diffusion patterns.
Fig. 2: Diffusion MRI analysis approaches.
Fig. 3: Diffusion MRI (dMRI) tractography process from acquisition to analysis.
Fig. 4: Common approaches for local diffusion modeling.
Fig. 5: Illustrative visualization of white matter reconstruction differences between tractography methods on neonatal dMRI.
Fig. 6: Deterministic and probabilistic tractography.
Fig. 7: In-/exclusion flowchart of identified and eligible papers on diffusion MRI tractography in the infant (0–2 years of age) brain.
Fig. 8: Progression of methods used for infant brain tractography over time.
Fig. 9: Application of tractography algorithms in the neonatal and young infant brain.
Fig. 10

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Data availability

All data supporting the findings of this study are available within the paper and its Supplementary Information Files.

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Funding

A.S.V. is jointly supported by the Royal Netherlands Academy of Arts and Sciences (KNAW, Amsterdam, The Netherlands) ter Meulen Fund [KNAWWF/1327/TMB202126], Isala Science and Innovation Fund (Zwolle, the Netherlands) and Science Fund Medical Specialist Isala (Zwolle, the Netherlands). L.M.L.’s research program is jointly supported by the Alberta Children’s Hospital Foundation, Alberta Children’s Hospital Research Institute and the Calgary Health Foundation (Calgary, Canada). C.M.W.T. is supported by the Wellcome Trust [215944/Z/19/Z] and a Veni grant (17331) from the Dutch Research Council (NWO). The sponsors had no role in the design and conduct of the study, the collection, management, analysis and interpretation of the data, the preparation, review and approval of the manuscript, or the decision to submit the manuscript for publication. For the purpose of open access, the author has applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission.

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Authors and Affiliations

  1. Department of Radiology, Isala Hospital Zwolle, Zwolle, The Netherlands

    Anouk S. Verschuur & Martijn F. Boomsma

  2. Department of Pediatrics, Section of Newborn Critical Care, University of Calgary, Calgary, Canada

    Anouk S. Verschuur, Regan King & Lara M. Leijser

  3. Image Sciences Institute, University Medical Center Utrecht, Utrecht, The Netherlands

    Anouk S. Verschuur, Chantal M. W. Tax & Alexander Leemans

  4. CUBRIC, School of Physics and Astronomy, Cardiff University, Cardiff, United Kingdom

    Chantal M. W. Tax

  5. Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht, The Netherlands

    Martijn F. Boomsma

  6. Department of Neonatology, Isala Women and Children’s Hospital Zwolle, Zwolle, The Netherlands

    Gerda van Wezel-Meijler

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  1. Anouk S. Verschuur
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Contributions

Anouk Verschuur: Conceptualization, data curation, formal analysis, funding acquisition, investigation, methodology, project administration, validation, visualization, writing – original draft, writing – review & editing. Regan King: Conceptualization, data curation, investigation, methodology, validation, writing – original draft, writing – review & editing. Chantal Tax: Conceptualization, methodology, supervision, validation, writing – review & editing. Martijn Boomsma: Conceptualization, funding acquisition, methodology, supervision, validation, writing – review & editing. Gerda Meijler: Conceptualization, funding acquisition, methodology, supervision, validation, writing – review & editing. Alexander Leemans: Conceptualization, methodology, supervision, validation, writing – review & editing. Lara Leijser: Conceptualization, data curation, funding acquisition, investigation, methodology, supervision, validation, writing – original draft, writing – review & editing.

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Correspondence to Anouk S. Verschuur.

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Verschuur, A.S., King, R., Tax, C.M.W. et al. Methodological considerations on diffusion MRI tractography in infants aged 0–2 years: a scoping review. Pediatr Res 97, 880–897 (2025). https://doi.org/10.1038/s41390-024-03463-2

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