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Purpose: To develop a fast, quantitative 3D magnetization transfer contrast (MTC) framework based on an unsupervised learning scheme, which will provide baseline reference signals for CEST and nuclear Overhauser enhancement imaging. Methods: Pseudo-randomized RF saturation parameters and relaxation delay times were applied in an MR fingerprinting framework to generate transient-state signal evolutions for different MTC parameters. Prospectively compressed sensingaccelerated (four-fold) MR fingerprinting images were acquired from 6 healthy volunteers at 3 T. A convolutional neural network framework in an unsupervised fashion was designed to solve an inverse problem of a two-pool MTC Bloch equation, and was compared with a conventional Bloch equation-based fitting approach. The MTC images synthesized by the convolutional neural network architecture were used for amide proton transfer and nuclear Overhauser enhancement imaging as a reference baseline image. Results: The fully unsupervised learning scheme incorporated with the two-pool exchange model learned a set of unique features that can describe the MTC-MR fingerprinting input, and allowed only small amounts of unlabeled data for training. The MTC parameter values estimated by the unsupervised learning method were in excellent agreement with values estimated by the conventional Bloch fitting approach, but dramatically reduced computation time by ~1000-fold. Conclusion: Given the considerable time efficiency compared to conventional Bloch fitting, unsupervised learning-based MTC-MR fingerprinting could be a powerful tool for quantitative MTC and CEST/nuclear Overhauser enhancement imaging.

Magnetization transfer contrast MR fingerprinting (MTC‐MRF) is a novel quantitative imaging method that simultaneously quantifies free bulk water and semisolid macromolecule parameters using pseudo‐randomized scan parameters. To improve acquisition efficiency and reconstruction accuracy, the optimization of MRF sequence design has been of recent interest in the MRF field, but has been challenging due to the large number of degrees of freedom to be optimized in the sequence. Herein, we propose a framework for learning‐based optimization of the acquisition schedule (LOAS), which optimizes RF saturation‐encoded MRF acquisitions with a minimal number of scan parameters for tissue parameter determination. In a supervised learning framework, scan parameters were subsequently updated to minimize a predefined loss function that can directly represent tissue quantification errors. We evaluated the performance of the proposed approach with a numerical phantom and in in vivo experiments. For validation, MRF images were synthesized using the tissue parameters estimated from a fully connected neural network framework and compared with references. Our results showed that LOAS outperformed existing indirect optimization methods with regard to quantification accuracy and acquisition efficiency. The proposed LOAS method could be a powerful optimization tool in the design of MRF pulse sequences.