Purpose: To develop a method for MR Fingerprinting (MRF) sequence optimization that takes both the applied undersampling pattern and a realistic reference map into account. Methods: A predictive model for the undersampling error leveraging on perturbation theory was exploited to optimize the MRF flip angle sequence for improved robustness against undersampling artifacts. In this framework parameter maps from a previously acquired MRF scan were used as reference. Sequences were optimized for different sequence lengths, smoothness constraints and undersampling factors. Numerical simulations and in vivo measurements in eight healthy subjects were performed to assess the effect of the performed optimization. The optimized MRF sequences were compared to a conventionally shaped flip angle pattern and an optimized pattern based on the Cramér–Rao lower bound (CRB). Results: Numerical simulations and in vivo results demonstrate that the undersampling errors can be suppressed by flip angle optimization. Analysis of the in vivo results show that a sequence optimized for improved robustness against undersampling with a flip angle train of length 400 yielded significantly lower median absolute errors in (Formula presented.) : (Formula presented.) and (Formula presented.) : (Formula presented.) compared to the conventional ((Formula presented.) : (Formula presented.), (Formula presented.) : (Formula presented.)) and CRB-based ((Formula presented.) : (Formula presented.), (Formula presented.) : (Formula presented.)) sequences. Conclusion: The proposed method is able to optimize the MRF flip angle pattern such that significant mitigation of the artifacts from strong k-space undersampling in MRF is achieved.
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