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Methodological limitations of the BrainStructureAges pipeline from the volBrain platform: a brief report of the normative pediatric group
Background
Predicted brain age is a widely used neuroimaging biomarker of brain maturation. However, limited normative pediatric datasets in model training raise concerns about systematic biases when applied to children. This study evaluates the hypothesis of predicted brain age overestimation in typically developing pediatric populations.
Objective
To analyze predicted brain age and brain delta in a large, age- and sex-matched sample of typically developing children and to test whether there is any potential systematic overestimation of predicted brain age in children using the BrainStructureAges pipeline (LaBRI, CNRS/University of Bordeaux, Bordeaux, France).
Materials and methods
We estimated predicted brain age from 105 brain MRI scans of healthy and typically developing children aged 6–9 years with well-documented medical histories. All scans were performed on a Magnetom Amira 1.5-T scanner (Siemens Healthineers, Erlangen, Germany), using T1-weighted MPRAGE sequences. Brain age prediction utilized the BrainStructureAges pipeline on the volBrain (ITACA Institute, Universitat Politècnica de València, Valencia, Spain, and LaBRI, CNRS/University of Bordeaux, Bordeaux, France) platform. The brain delta was defined as the difference between chronological age and predicted brain age. Regional estimates were obtained for 133 brain structures.
Results
The mean predicted brain age was 9.3±1.2 years, compared to a chronological age of 7.7±0.4 years, resulting in a mean brain delta of 1.6±1.2 years. No significant sex differences were observed for chronological age, predicted brain age, or delta (boys, 1.55 years; girls, 1.61 years; t=0.27, P=0.79). Positive brain delta values were seen in 95.2% of participants across all structures, with the largest deviations in the left cerebellar exterior (+3.3 years), left occipital fusiform gyrus (+3.3 years), cerebellar lobules VI–VII (+2.9 years), left inferior occipital gyrus (+2.9 years), and right frontal pole (+2.8 years).
Conclusions
These findings suggest a systematic overestimation of predicted brain age in children, highlighting the need for caution in clinical interpretations to prevent misinterpretations in pediatric populations.