Many brain aging studies use total intracranial volume (TIV) as a proxy measure of premorbid brain size that is
unaffected by neurodegeneration. T1-weighted Magnetic Resonance Imaging (MRI) sequences are commonly used to
measure TIV, but T2-weighted MRI sequences provide superior contrast between the cerebrospinal fluid (CSF)
bounding the premorbid brain space and surrounding dura mater. In this study, we compared T1-based and T2-based
TIV measurements to assess the practical impact of this superior contrast on studies of brain aging. 810 Alzheimer’s
Disease Neuroimaging Initiative (ADNI) participants, including healthy elders and those with mild cognitive impairment
(MCI) and Alzheimer’s Disease (AD), received T1-weighted and T2-weighted MRI at their baseline evaluation. TIV
was automatically estimated from T1-weighted images using FreeSurfer version 4.3 (T1TIV), and an automated active
contour method was used to estimate TIV from T2-weighted images (T2TIV). The correlation between T1TIV and
T2TIV was high (.93), and disagreement was greater on larger heads. However, correcting a FreeSurfer-based measure
of total parenchymal volume by dividing it by T2TIV led to stronger expected associations with a standardized measure
of cognitive dysfunction (MMSE) in Poisson regression models among individuals with AD (z=1.73 vs. 1.09) and MCI
(z=3.15 vs. 2.79) than a corresponding parenchymal volume measure divided by T1TIV. This effect was enhanced when
the analysis was restricted to the cases where T1TIV and T2TIV disagreed the most. These findings suggest that T2-
based TIV measurements may be higher fidelity than T1-based TIV measurements, thus leading to greater sensitivity to
detect biologically plausible brain-behavior associations.
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