More problems for atrophy measurement….the pulsating brain


Nakamura K, Brown RA, Narayanan S, Collins DL, Arnold DL; Diurnal fluctuations in brain volume: Statistical analyses of MRI from large populations. Neuroimage. 2015 Jun 3. pii: S1053-8119(15)00467-X. doi: 10.1016/j.neuroimage.2015.05.077. [Epub ahead of print].

We investigated fluctuations in brain volume throughout the day using statistical modeling of magnetic resonance imaging (MRI) from large populations. We applied fully automated image analysis software to measure the brain parenchymal fraction (BPF), defined as the ratio of the brain parenchymal volume and intracranial volume, thus accounting for variations in head size. The MRI data came from serial scans of multiple sclerosis(MS) patients in clinical trials (n=755, 3269 scans) and from subjects participating in the Alzheimer’s Disease Neuroimaging Initiative (ADNI, n=834, 6114 scans). The percent change in BPF was modeled with a linear mixed effect (LME) model, and the model was applied separately to the MS and ADNI datasets. The LME model for the MS datasets included random subject effects (intercept and slope over time) and fixed effects for the time-of-day, time from the baseline scan, and trial, which accounted for trial-related effects (for example, different inclusion criteria and imaging protocol). There was a statistically significant effect of time-of-day on the BPF change in MS clinical trial datasets (-0.180 per day, that is, 0.180% of intracranial volume, p = 0.019) as well as the ADNI dataset (-0.438 per day, that is, 0.438% of intracranial volume, p < 0.0001), showing that the brain volume is greater in the morning. Linearly correcting the BPF values with the time-of-day reduced the required sample size to detect a 25% treatment effect (80% power and 0.05 significance level) on change in brain volume from 2 time-points over a period of 1 year by 2.6%. Our results have significant implications for future brain volumetric studies, suggesting there is a potential acquisition time bias that should be randomized or statistically controlled to account for the day-to-day brain volume fluctuations.


We recently heard about the glymphatics doing a power flush to clear the brain at night and it can be seen that the size of the brain changes. This current study also comes to this conclusion too. 

So if you are measuring brain atrophy and trying to register one image with another, then the time of day the image was taken could influence the result. 

The brain is larger in the morning so it you compare morning to afternoon you can get apparent shrinkage, so if you are not having your atrophy scans at the same time them this will introduce artefacts. 

We already know that spinal cord atrophy misses all but the tip of the iceberg as it misses a lot of nerve loss as the volume of nerves is replaced be gliosis. One guesses the same may be the case for brain atrophy.  Now it is evident that time of day can influence the scan and needs to be corrected for…..will we see a spate of MRI atrophy papers where they have recalibrated the atrophy levels or interpret old data with more caution?

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