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Updated: Sep 29, 2026

Scanning Dos and Don'ts: Using Magnetic Resonance Imaging in Awake Children Aged 3 to 5 Years to Assess Brain Structure and Function
Published on: March 10, 2026
Assessment of spatial normalization of whole-brain magnetic resonance images in children
Marko Wilke1, Vincent J Schmithorst, Scott K Holland
1Imaging Research Center, Children's Hospital Research Foundation at Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA. wilke@athena.chmcc.org
Insights
Age significantly impacts spatial normalization parameters in pediatric brain imaging. Using a pediatric template minimizes deformation, crucial for accurate developmental neuroimaging studies.
Area of Science:
- Neuroimaging
- Developmental Neuroscience
- Medical Image Analysis
Background:
- Standard spatial normalization frameworks rely on adult brain templates, which may not accurately represent developing pediatric brains.
- Pediatric brains exhibit significant changes in size and shape throughout childhood, necessitating age-appropriate normalization methods.
- Understanding age-related variations in spatial normalization is critical for interpreting neuroimaging data in children.
Purpose of the Study:
- To investigate the influence of age on spatial normalization parameters in healthy children aged 5-18 years.
- To evaluate the impact of using different templates (adult vs. pediatric) and normalization constraints on deformation.
- To provide guidance for optimizing spatial normalization in pediatric neuroimaging research.
Main Methods:
- Analyzed linear scaling parameters and non-linear deformations using SPM99 on 148 healthy children (5-18 years).
- Assessed the effect of brain masking on linear normalization and varying regularization constraints on non-linear normalization.
- Compared normalization results using both a standard adult template and a custom pediatric template.
Main Results:
- Significant age-correlation found in the X-dimension (left-right) linear scaling based on brain tissue; overall scaling showed no age-correlation.
- Whole-head linear scaling demonstrated strong age-effects across all dimensions.
- Non-linear deformations correlated with age, particularly in frontal and parietal regions; using a pediatric template significantly reduced volume change.
Conclusions:
- Age-dependent deformations in specific cortical areas warrant caution when assigning imaging findings to anatomical structures in children.
- Employing a pediatric template is recommended to minimize deformation during non-linear spatial normalization in pediatric neuroimaging.
- Findings have significant implications for the accuracy and interpretation of developmental neuroimaging studies.
Abstract:
Commonly used frameworks for spatial normalization of brain imaging data (e.g., Talairach-space) are based on one or more adult brains. As pediatric brains are different in size and shape from adult brains and continue to develop through childhood, we aimed to assess the influence of age on various spatial normalization parameters. One hundred forty-eight healthy children aged 5-18 years were included in this study. The linear scaling parameters and the deformations from the non-linear spatial normalization to both a standard adult and a custom pediatric template were analyzed within SPM99. The effect of using a brain mask on the linear and of using different levels of constraint on the non-linear spatial normalization was assessed. Of the linear scaling factors, only the X-dimension (left-right) showed a significant age-correlation when based on brain tissue, whereas the overall scaling was not correlated with age. When based on the whole head, a very strong age-effect can be found in all dimensions. Non-linear deformations also show localized correlations with age, most pronounced in parietal and frontal areas. The total amount of volume change is significantly lower when using a pediatric template. It is also substantially influenced by the degree of regularization that is exerted on the spatial normalization parameters. Our results suggest that in the cortical areas showing a strong correlation of deformation with age, caution should be used in assigning imaging results in children to a specific morphological structure. Also, to minimize the amount of deformation during non-linear spatial normalization, a pediatric template should be used. Further implications of our findings on developmental neuroimaging studies are discussed.

