96 Chapter 6 Frontal Occipital Horn Ratio Since ventriculomegaly is an associated abnormality in sCS patients that can affect DTI metrics, the Frontal Occipital Horn Ratio (FOHR) was used as a parameter to correct for ventricular size.19 FOHR is defined as (frontal horn width + occipital horn width)/biparietal diameter*2 and gives a ratio of ventricle size that can be interpreted independent of age. A FOHR ≥ 0.4 was considered ventriculomegaly. Reliability and Reproducibility Inter-observer reliability of tract measurements was determined by comparing the results of two trained raters blinded to subject information. Both performed all structural measurements twice in 10 subjects, 5 patients and 5 control subjects. Interrater reliability was based on 10 repeated ratings and found to be high, as depicted in Rijken et al.14 Partial volume effects due to brain deformity and abnormal ventricular size and shape potentially influenced the DTI fiber tractography data in patients with sCS. The FA threshold was set at 0.1, and the maximum angle threshold, at 45°. This DTI fiber tractography protocol has been used in craniosynostosis patients and controls.14 Of note, even though a FA threshold of 0.2 is commonly used,20 a threshold of 0.1 made it possible to track all structures in the control group and almost all structures in the sCS group. However, the FA threshold of 0.1 meant that more aberrant tracts were generated and additional AND and NOT ROIs were required to exclude aberrant fibers. Additionally, by extracting particular segments from a white matter tract (by using 2 AND operators), we could measure identical white matter structures and make fair comparisons between patients with sCS and control subjects.14 Statistical Analysis Analyses were carried out using R Studio Version 1.1.442 – © 2009-2018 RStudio, Inc. Parametric statistics were used when the distribution of the data did not violate assumptions of normality. To minimize false positives resulting from multiple tests, multivariate analysis of variance (MANOVA) was used to determine whether patients and controls differed in patterns of ʎ1, ʎ2 and ʎ3 in the examined tracts. For ʎ1, ʎ2 and ʎ3 a ƞ2 was calculated, in which Cohen’s guideline for “high” is ƞ2 > 0.14. 21 The significant lambda values gave information from which tract FA or which diffusivity value could be affected in patients versus controls (see above, DTI Metrics). Subsequent analyses used linear regression on corpus callosumgenu and hippocampal segment of the left cingulate bundle with sCS/control, sex, FOHR and tractvolume added to the model as independent variables. ß-Coefficients were calculated (stats package) for each regression. The Bonferroni correction was conducted and a p-value < 0.025 (p-value = 0.05/2) was considered statistically significant. To investigate these tracts syndrome specifically, we undertook an additional linear regression dividing the
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