Copyright © 2015 Mohammad Alipoor et al. The design of an optimal gradient encoding scheme (GES) is a fundamental problem in diffusion MRI. It is well studied for the case of second-order tensor imaging (Gaussian diffusion). However, it has not been investigated for the wide range of non-Gaussian diffusion models. The optimal GES is the one that minimizes the variance of the estimated parameters. Such a GES can be realized by minimizing the condition number of the design matrix (K-optimal design). In this paper, we propose a new approach to solve the K-optimal GES design problem for fourth-order tensor-based diffusion profile imaging. The problem is a nonconvex experiment design problem. Using convex relaxation, we reformulate it as a tractable semidefinite programming problem. Solving this problem leads to several theoretical properties of K-optimal design: (i) the odd moments of the K-optimal design must be zero; (ii) the even moments of the K-optimal design are proportional to the total number of measurements; (iii) the K-optimal design is not unique, in general; and (iv) the proposed method can be used to compute the K-optimal design for an arbitrary number of measurements. Our Monte Carlo simulations support the theoretical results and show that, in comparison with existing designs, the K-optimal design leads to the minimum signal deviation.