Trends in Brain Volume Change with Normal Ageing

In order to measure cerebral atrophy due to neurodegenerative diseases, the major confounding factor of normal age-related atrophy must be taken into account. Furthermore, in order to compare cerebral volume measurements across multiple subjects, normalisation for differences in head size is also required. We describe an investigation of these normalisations based on measurements of cerebro-spinal fluid (CSF) volumes in MR images of 70 normal volunteers. First, we demonstrate that, to within the limits imposed by segmentation errors, normalisation to the total intracranial volume (TIV) (the usual normalisation for head size differences) is statistically identical to normalisation to the volume of the bounding box of the CSF space, a quantity that is considerably easier to compute. Second, we investigate several possible functional dependencies for CSF volumes with age, and conclude, based on a combination of goodness-of-fit probabilities and biological plausibility, that the dependence obeys a Weibull cumulative distribution function. We also investigate the regional dependency of CSF volumes with age at coarse scales, and conclude that CSF volume increase due to normal ageing occurs uniformly throughout the cranium. Finally, we describe a meta-study in which our results are compared to previously published CSF and TIV measurements. This study incorporates measurements from ≈ 1300 subjects, and shows close agreement between the separate studies involved.