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Magnetic resonance fingerprinting (MRF) is a method to extract quantitative tissue properties such as [Formula: see text] and [Formula: see text] relaxation rates from arbitrary pulse sequences using conventional MRI hardware. MRF pulse sequences have thousands of tunable parameters, which can be chosen to maximize precision and minimize scan time. Here, we perform de novo automated design of MRF pulse sequences by applying physics-inspired optimization heuristics. Our experimental data suggest that systematic errors dominate over random errors in MRF scans under clinically relevant conditions of high undersampling. Thus, in contrast to prior optimization efforts, which focused on statistical error models, we use a cost function based on explicit first-principles simulation of systematic errors arising from Fourier undersampling and phase variation. The resulting pulse sequences display features qualitatively different from previously used MRF pulse sequences and achieve fourfold shorter scan time than prior human-designed sequences of equivalent precision in [Formula: see text] and [Formula: see text] Furthermore, the optimization algorithm has discovered the existence of MRF pulse sequences with intrinsic robustness against shading artifacts due to phase variation., Competing Interests: Competing interest statement: M.A.G. and D.M. have patents on MRF technology. The other authors declare no competing interests.

Magnetic resonance (MR) fingerprinting is a technique for acquiring and processing MR data that simultaneously provides quantitative maps of different tissue parameters through a pattern recognition algorithm. A predefined dictionary models the possible signal evolutions simulated using the Bloch equations with different combinations of various MR parameters and pattern recognition is completed by computing the inner product between the observed signal and each of the predicted signals within the dictionary. Though this matching algorithm has been shown to accurately predict the MR parameters of interest, one desires a more efficient method to obtain the quantitative images. We propose to compress the dictionary using the singular value decomposition, which will provide a low-rank approximation. By compressing the size of the dictionary in the time domain, we are able to speed up the pattern recognition algorithm, by a factor of between 3.4-4.8, without sacrificing the high signal-to-noise ratio of the original scheme presented previously.