34 Chapter 2 craniosynostosis patients, regions of interest (ROI) were therefore placed manually, which made spatial normalization escapable.12 However, this practice is time consuming, and it increases the likelihood of error in delineation and decreases the repeatability across subjects. To overcome the issues with spatial normalization of T1w images, we propose to use different contrast than from the structural images for the spatial normalization. In this study, we set to investigate if the ASL CBF image contrast can be directly used for spatial normalization in children with trigonocephaly and healthy controls under the age of 18 months. We combined technical and clinical expertise to compare the standard method that uses structural images for the normalization with three different registrations of ASL directly to MNI using rigid, affine, and nonlinear transformations. We hypothesize that direct ASL spatial normalization to the MNI space is possible, that nonlinear registration can be used in this context to improve the normalization quality in young healthy controls and trigonocephaly patients, and that this normalization will have a significant effect on the measured regional CBF. With this study we aim to facilitate the investigation of frontal lobe perfusion in trigonocephaly patients in a clinical setting to assess the value of vault surgery in these patients. MATERIALS AND METHODS The Ethics Committee approved this prospective imaging study in patients with trigonocephaly (METC-2018-124), which is part of ongoing work at the Erasmus Medical Center involving protocolized care, brain imaging, clinical assessment, data summary, and evaluation.13 To participate in this study, informed research consent has been obtained. Subjects Preoperative MRI brain scans from 36 children with metopic synostosis for whom a surgical correction was considered were included over a period of 2 years (2018– 2020). Surgery was considered only for moderate and severe presentation of metopic synostosis, mainly defined by severe narrowing and a protruding midline ridge of the forehead, hypotelorism (eyes close together), and biparietal widening.14 Children were less than 2 years of age at the time of the MRI brain study. The control group consisted of sixteen subjects undergoing MRI brain studies for clinical reasons, with the following inclusion criteria: (1) no neurological pathology of the head or neck (e.g., children with intracranial masses, prior neurosurgeries, known myelin disorders); (2) no neurological or psychological morbidity on follow-up; and (3) no residual motion artifacts in the subjects’ brain MRI data.
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