Effects of T2-weighted MRI based cranial volume measurements on studies of the aging brain

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.