Fast quantification of uncertainty in non-linear diffusion MRI models for artifact detection and more power in group studies

Diffusion MRI (dMRI) allows for non-invasive investigation of brain tissue microstructure. By fitting a model to the dMRI signal, various quantitative measures can be derived from the data, such as fractional anisotropy, neurite density and axonal radii maps. The uncertainty in these dMRI measures is often ignored, while previous work in functional MRI has shown that incorporating uncertainty estimates can lead to group statistics with a higher statistical power. We propose the Fisher Information Matrix (FIM) as a generally applicable method for quantifying the parameter uncertainties in non-linear diffusion MRI models. In direct comparison with Markov Chain Monte Carlo sampling, the FIM produces similar uncertainty estimates at lower computational cost. Using acquired and simulated data, we then list several characteristics that influence the parameter variances, like data complexity and signal-to-noise ratio. In individual subjects, the parameter standard deviations can help in detecting white matter artifacts as patches of relatively large standard deviations. In group statistics, we recommend using the parameter standard deviations by means of variance weighted averaging. Doing so can reduce the overall variance in group statistics and reduce the effect of data artifacts without discarding data from the analysis. Both these effects can lead to a higher statistical power in group studies.