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This work investigates the possibilities of applying high-angular-resolution-diffusion-imaging- (HARDI-) based methods in a clinical setting by investigating the performance of non-Gaussian diffusion probability density function (PDF) estimation for a range of b-values and diffusion gradient direction tables. It does so at realistic SNR levels achievable in limited time on a high-performance 3T system for the whole human brain in vivo. We use both computational simulations and in vivo brain scans to quantify the angular resolution of two selected reconstruction methods: Q-ball imaging and the diffusion orientation transform. We propose a new analytical solution to the ODF derived from the DOT. Both techniques are analytical decomposition approaches that require identical acquisition and modest postprocessing times and, given the proposed modifications of the DOT, can be analyzed in a similar fashion. We find that an optimal HARDI protocol given a stringent time constraint (<10 min) combines a moderate b-value (around 2000 s/mm2) with a relatively low number of acquired directions (>48). Our findings generalize to other methods and additional improvements in MR acquisition techniques. [ABSTRACT FROM AUTHOR]