PurposeTo implement a flexible framework, named HydrOptiFrame, for the design and optimization of time-efficient water-excitation (WE) RF pulses using B-spline interpolation, and to characterize their lipid suppression performance. MethodsAn evolutionary optimization algorithm was used to design WE RF pulses. The algorithm minimizes a composite loss function that quantifies the fat-water contrast using Bloch equation simulations. In a first study, B-spline interpolated optimized (BSIO) pulses designed with HydrOptiFrame with durations of 1 and 0.76 ms were generated for 3 T and characterized in healthy volunteers' knees. The femoral bone marrow SNR was compared to that obtained with to 1-1 WE and lipid insensitive binomial off resonant excitation (LIBRE) pulses. In a second study, in the heart at 1.5 T, the water-fat contrast ratio and coronary artery vessel length obtained with a 2.56 ms BSIO pulse was compared to 1-1 WE and LIBRE pulses in free-running cardiovascular MR. ResultsThe 1 ms BSIO pulse resulted in higher fat suppression and lower contrast ratio (CR) in the bone marrow than the state-of-the-art pulses (4.1 +/- 0.2 vs. 4.7 +/- 0.4 and 4.4 +/- 0.3 for the BSIO, the 1-1 WE and LIBRE respectively, p < 0.05 vs. both) at 3 T. At 1.5 T, the BSIO pulse resulted in a higher blood-epicardial fat CR (3.8 +/- 1.3 vs. 1.6 +/- 0.6 and 2.4 +/- 1.1 for the BSIO, 1-1 WE and LIBRE, respectively, p < 0.05 vs. both) and longer traceable left coronary artery vessel length (8.7 +/- 1.4 cm vs. 7.0 +/- 1.0 cm [p = 0.04] and 7.5 +/- 1.2 cm [p = 0.09]). ConclusionThe HydrOptiFrame framework offers a new opportunity to design WE RF pulses that are robust to B0 inhomogeneity at multiple magnetic field strengths and for variable RF pulse durations.