Scalar diffusion-MRI measures invariant to acquisition parameters: A first step towards imaging biomarkers.

An imaging biomarker is a biologic feature in an image that is relevant to a patient's diagnosis or prognosis. In order to qualify as a biomarker, a measure must be robust and reproducible. However, the usual scalar measures derived from diffusion tensor imaging are known to be highly dependent on the variation of the acquisition parameters, which prevents their possible use as biomarkers. In this work, we propose a new set of quantitative measures based on diffusion magnetic resonance imaging from single-shell acquisitions that are designed to be robust to the variations of several acquisition parameters (number of gradient directions, b-value and SNR) while keeping a high discrimination power on differences in the diffusion characteristics of the tissue. These new scalar measures are analytically obtained from a generic diffusion function that does not require the calculation of a diffusion tensor. This way, on one hand, we avoid the use of a specific diffusion model and, on the other hand, we make easier the statistical characterization of the measures. Accordingly, the analysis of the measures bias is carried out and it is used to minimize their dependency with respect to the acquisition noise for different SNRs. The robustness and discrimination power of the measures are tested for different number of gradients, b-values and SNRs using a realistic phantom and three real datasets: (1) 13 control subjects and different acquisition parameters; (2) a public data set from a single subject acquired using multiple shells and (3) 32 schizophrenia patients and 32 age and sex-matched healthy controls with a varying number of gradient directions. The proposed quantitative measures exhibit low variability to the changes of the acquisition parameters, while at the same time they preserve a discrimination power that is able to detect significant changes in the anisotropy of the diffusion.