Spatial normalization is an important step for group image processing and evaluation of mean brain perfusion in anatomical regions using arterial spin labeling (ASL) MRI and is typically performed via high-resolution structural brain scans. However, structural segmentation and/or spatial normalization to standard space is complicated when gray-white matter contrast in structural images is low due to ongoing myelination in newborns and infants. This problem is of particularly clinical relevance for imaging infants with inborn or acquired disorders that impair normal brain development. We investigated whether the ASL MRI perfusion contrast is a viable alternative for spatial normalization, using a pseudo-continuous ASL acquired using a 1.5 T MRI unit (GE Healthcare). Four approaches have been compared: (1) using the structural image contrast, or perfusion contrast with (2) rigid, (3) affine, and (4) nonlinear transformations – in 16 healthy controls [median age 0.83 years, inter-quartile range (IQR) ± 0.56] and 36 trigonocephaly patients (median age 0.50 years, IQR ± 0.30) – a non-syndromic type of craniosynostosis. Performance was compared quantitatively using the real-valued Tanimoto coefficient (TC), visually by three blinded readers, and eventually by the impact on regional cerebral blood flow (CBF) values. For both patients and controls, nonlinear registration using perfusion contrast showed the highest TC, at 17.51 (CI 6.66–49.38) times more likely to have a higher rating and 17.45–18.88 ml/100 g/min higher CBF compared with the standard normalization. Using perfusion-based contrast improved spatial normalization compared with the use of structural images, significantly affected the regional CBF, and may open up new possibilities for future large pediatric ASL brain studies.