Controlling for premorbid brain size in imaging studies: T1-derived cranium scaling factor vs. T2-derived intracranial vault volume.

Intracranial vault (ICV) volume, obtained from T2-weighted magnetic resonance imaging (MRI), is generally used to estimate premorbid brain size in imaging studies. T1-weighted sequences lack the signal characteristics for ICV measurements [they have poor contrast at the outer boundary of sulcal cranium scaling factor (CSF)] but are valuable in imaging studies due to their excellent gray vs. white matter contrast. Smith et al. [NeuroImage 17 (2002) 479] suggested a T1-derived cranium scaling factor as an alternative control variable for premorbid brain size in cross-sectional studies. This index, which is computed using the SIENAX software, is a scaling factor comparing an individual's skull to a template skull derived from the Montreal Neurological Institute (MNI) average of 152 T1 studies (the MNI152). SIENAX computes coarsely defined estimates for the individual and MNI skulls rather than well-defined volumes. To test how well this approach would work as a control variable for premorbid brain size in cross-sectional studies, we compared the T1-derived cranium scaling factor to T2-derived ICV measurements in a sample of 92 individuals: 39 white males, 22 white females, and 31 African-American males, with an age range of 26-78 years. The correlation between T1- and T2-derived variables was 0.94 and did not differ across subject groups. The T1-derived cranium scaling factor accounted for a statistically significant portion (87%) of the variance of the T2-derived ICV measure and thus is a good surrogate for ICV measurement of premorbid brain size as a reference measure in MRI atrophy studies. Furthermore, neither race, sex, nor age accounted for any additional variance in ICV, indicating that neither race-, gender-, nor age-associated cranial bone thickness effects were present in this data set.