Diffusional kurtosis imaging (DKI) is a methodology for measuring the extent of non-Gaussian diffusion in biological tissue, which has shown great promise in clinical diagnosis, treatment planning, and monitoring of many neurological diseases and disorders. However, robust, fast, and accurate estimation of kurtosis from clinically feasible data acquisitions remains a challenge. In this study, we first outline a new accurate approach of estimating mean kurtosis via the sub-diffusion mathematical framework. Crucially, this extension of the conventional DKI overcomes the limitation on the maximum b-value of the latter. Kurtosis and diffusivity can now be simply computed as functions of the sub-diffusion model parameters. Second, we propose a new fast and robust fitting procedure to estimate the sub-diffusion model parameters using two diffusion times without increasing acquisition time as for the conventional DKI. Third, our sub-diffusion-based kurtosis mapping method is evaluated using both simulations and the Connectome 1.0 human brain data. Exquisite tissue contrast is achieved even when the diffusion encoded data is collected in only minutes. In summary, our findings suggest robust, fast, and accurate estimation of mean kurtosis can be realised within a clinically feasible diffusion-weighted magnetic resonance imaging data acquisition time.
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