85 Microstructures | Trigonocephaly is difficult to assess neuro-cognitive function and (mild) disorders in neurodevelopment at the age of the patients included in the study (<3 years). Future studies should further assess DTI in older patients with trigonocephaly and its relation with neurocognitive function. To our knowledge, only one study has investigated DTI in metopic synostosis in a small sample of patients. Cabrejo et al. used DTI to investigate combined sagittal and metopic synostosis patients (n = 5) and found an increased FA value in the cingulate tract of these patients as compared to isolated sagittal synostosis patients (N = 5).14 However, they did not investigate isolated metopic synostosis, nor did they include normal controls. In contrast to this study, we did not find a significant difference in the cingulate tract or other tracts in patients with metopic synostosis as compared to controls. Our study has several limitations. Currently, large cohort studies and standardized DTI values and thresholds in healthy infants and young children are missing. In addition, DTI depends on many technical variables, such as the type of scanner used and the amount of diffusion encoding directions. This makes it impossible to compare the values in our study to other pediatric DTI studies. In addition, in this study, we have chosen to use tract-based technology rather than a region-of-interest or whole-brain voxel-based approach. A region-of-interest approach could perhaps be valuable to assess specific local differences. In addition, we obtained controls from a historic cohort of subjects who had undergone an MRI brain scan for clinical reasons. Next, we were unable to fully match the age of patients and controls. Myelination development is greatest during the first years of life, and small differences in age affect FA and MD. However, we did not have enough statistical power to subdivide our cohort into groups of 0-1, 1-2, and 2+ years. In line with this, we observed a significant effect of age on the FA and MD values in both patients and controls. Although we did an additional analysis between patients and controls of similar age in the supplemental table, we were still not able to find any statistically significant difference between patients and controls. Finally, the trigonocephaly cohort consists of 81% male patients, whereas the control group consists of 36% males. However, by linear regression, sex has demonstrated no significant impact on the FA or MD values. Future perspectives In this study, we could not identify a significant difference between the main white matter tracts of the frontal lobe in young patients with trigonocephaly and controls. However, one could argue that the potential mechanical restriction of the metopic synostosis and/or intrinsically affected white matter is too subtle to measure/not yet measurable with DTI or arterial spin labelling on this age. We investigated whole tracts as a parameter of white matter microstructure in patients with trigonocephaly. Insight into other brain structures than white matter microstructure, for example, by volumetric 5
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