58 Chapter 3 those of patients with developmental delay disorders.6, 23, 24 Further studies into the microstructure of the brain, using diffusion tension imaging, for example, are required to further clarify brain development in trigonocephaly patients and understand the underlying pathophysiology. Our findings differ from those of previous imaging single-photon emission computed tomography studies in trigonocephaly patients.9, 10 This can be explained by the development of different, more advanced imaging techniques over the last few years. We used a quantitative method instead of the qualitative comparison. Another reason for the different findings could be the difference in age range (1 to 9 years).9 Our findings are roughly similar to those of the largest arterial spin labeling study of healthy children to date.25 Carsin-Vu et al. showed a mean perfusion of 54.6 ml/100 g/min and of 68.4 ml/100 g/min in the frontal lobes of healthy children aged 6 to 11 months (n = 4) and 12 to 23 months (n = 14), respectively.25 It is difficult to compare our findings with those of other arterial spin labeling studies as there are differences in the methodology of brain region definition (e.g., manual or automatic regions of interest), different arterial spin labeling strategies (i.e., pulsed, pseudocontinuous), and different arterial spin labeling acquisition readout parameters.25-28 Because of our limited sample size, we did not conduct additional analyses on age and its correlation with cerebral perfusion. As the age range of patients and control subjects was similar, we expected that age would not have had a significant effect on our results. Using the default statistical parametric mapping– based pipeline in ExploreASL, our initial attempts to register and segment the brain of trigonocephaly patients showed poor performance. Our registration was complicated by the skull malformation and the relatively poor tissue contrast in these young patients. A strength of this study is that we were able to combine our previously developed cerebral blood flow–based registration with a low-degree-of-freedom, nonlinear component to improve the registration for the deformed skulls, thus achieving a better registration.17 Our study has several limitations. First, our study focuses on a limited number of patients. It is difficult, therefore, to establish with certainty that no difference exists in cerebral blood flow between trigonocephaly patients and control subjects. We demonstrated that the range of cerebral blood flow in both trigonocephaly patients and control subjects is similar to the range found in previous studies. In our cohort, there was no evidence of a difference in cerebral blood flow between trigonocephaly patients and control subjects. Nevertheless, large cohort studies and, therefore, standardized cerebral blood flow values in pediatric patients are lacking. Arterial spin labeling studies that focus on clinical relevance of differences in cerebral blood flow range are required for a pediatric setting. Before incorporating this concept into clinical decision-making, this study should be further expanded. Validation of cerebral blood flow values in trigonocephaly patients at different age categories compared to an age-
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