Despite being a powerful medical imaging technique which does not emit any ionizing radiation, magnetic resonance imaging (MRI) always had the major problem of long scanning times that can take up to an hour depending on the application. It also requires uncomfortable breath-holds due to the slow acquisition, sedation of children and repeated scans in the cases of degraded image quality due to body motion.

Recent years have seen new image reconstruction techniques that need less amount of acquired data (i.e., accelerated scans) for reconstructing MRI images: parallel imaging and compressed sensing (CS). Although much work has been done on the reconstruction side, there has been relatively less work on experimental design, i.e., which parts of the Fourier domain to acquire during the scan, an essential factor that considerably affects the performance of image reconstructions. The state-of-the-art experimental designs use random subsampling either based on parametric models or heuristical adaptive models. The requirement of extensive parameter tuning and the random nature of the performance render these methods impractical and unreliable for clinical use.

Can we systematically use the data acquired during past MRI scans for the design of accelerated scans with a reliable image quality? This problem is the focus of this thesis which proposes a data-driven scan design approach and training procedures which efficiently and effectively learn the structure inherent in the data, and accordingly, design the scans that directly acquire only the most relevant information during acquisition given an acceleration rate constraint. As a result, this boosts the performance of the existing state-of-the-art compressive sensing techniques on real-world datasets. Moreover, this approach provides strong theoretical guarantees by using tools from statistical learning theory.

The intensive computational training procedures of our approach are made feasible by large-scale implementations on a parallel computing cluster. In return, this approach avoids any dependence on parametric or heuristic models and provides a reliably consistent image reconstruction performance for accelerated scans. Our approach is flexible and capable of giving deterministic scan designs specific to the anatomy, to the acceleration rate in use, to the reconstruction algorithm and the scan settings such as static/dynamic and parallel imaging.

Apart from measurement designs for MRI, this thesis also considers the reconstruction problem. In particular, we focus on the inverse problems that involve a mixture of regularizers in the objective function, exploiting multiple structures at the same time. For these problems, we propose a reliable and systematic optimization framework and illustrate its effectiveness. Finally, in the last part of the thesis, we present a data-driven model and an optimization method for the design of nearly isometric, linear and dimensionality reducing embeddings.