Head size markedly differs among individuals. To our knowledge, there have been no studies that systematically investigated the effect of head size on diffusion tensor measures of the brain. The purpose of this study was to evaluate the effect of head size or total intracranial volume on diffusion tensor measures (FA and MD). A total of 821 normal subjects (304 females and 517 males) were included in this study. We investigated the effect of total intracranial volume on FA and MD mainly using tract-based spatial statistics (TBSS). There were a number of regions where FA or MD was significantly correlated with total intracranial volume. There was no significant interaction between total intracranial volume and sex. The results indicate that total intracranial volume significantly influences diffusion tensor measures such as FA and MD. The possible explanations of the relationship between diffusion tensor measures and total intracranial volume may be 'partial volume effects' or micro-architectural differences related to head size. When total intracranial volumes are significantly different between groups, it may be necessary to control for total intracranial volume in the statistical analysis, depending on the hypothesis being tested.
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