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A hybrid topology optimization (HTO) method is adopted to reduce the mutual coupling of a ±45° dual-polarized closely spaced MIMO antenna. In order to shorten the optimization time, only the isolation structure region of the two-element MIMO antenna is selected for optimization. More importantly, by exploiting the symmetry of both the MIMO antenna and the isolation structure, only a quarter of the isolation structure needs to be optimized to achieve good antenna performance. In this way, not only the optimization variables, but also the optimization sub-objectives are greatly reduced, and the optimization time is further diminished. The performance of the dual-polarized MIMO antenna with the optimized isolation structure (OIS) is validated by both simulation and measurement. The OIS resonates in both polarizations, thus lowering the mutual coupling between co-polarization ports (|S₃₁| and |S₄₂|) and between cross-polarization ports (|S₄₁| and |S₃₂|) simultaneously. With the center distance of only 0.35λ₀, the measured mutual coupling between different ports are reduced by 6~11 dB within the 10-dB impedance bandwidth (Reflection coefficients <; -10 dB) by adding the OIS, and the highest mutual coupling between different ports is reduced from -15 to -21 dB. Besides, the antenna maintains a low profile (0.026λ₀), low cross-polarization and excellent radiation pattern performance.