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Introduction First-pass myocardial perfusion cardiovascular magnetic resonance imaging (CMR) has become an established method for the non-invasive diagnosis of ischaemic heart disease (IHD). As complete datasets are acquired every heart beat, first-pass perfusion CMR is challenging, and compromises have to be made between competing demands for spatial resolution, cardiac coverage, and temporal resolution. Accelerating data acquisition with k-t undersampling techniques is a strategy that could overcome some of the remaining limitations of first-pass perfusion CMR, and influence the management of patients with IHD. The use of a k-t Principle Component Analysis (PCA) acceleration method will be investigated for its technical feasibility and clinical merit for acquisition with improved spatial resolution, greater myocardial coverage, and higher heart rates. Supplemented by three additional chapters as appendices, this thesis presents the use of spatiotemporal undersampling for advanced perfusion CMR. The research has the following aims. Aims and Methods 1. To establish the clinical feasibility of 3D perfusion CMR technique in relation to fractional flow reserve (FFR) and the Duke Jeopardy Score. Accuracy in diagnosis and comparison of ischaemic burden with invasive indices of myocardial ischaemia, will be determined. 2. To compare the estimation of ischaemic burden using 3D perfusion CMR against the estimation using the clinical standard single-photon emission computed tomography (SPECT). 3. Optimization and design of a 3D perfusion CMR sequence based on k-t acceleration and PCA reconstruction using a turbo field-echo (TFE) pulse sequence, and development of balanced steady-state free precession (bSSFP) perfusion imaging at 3 Tesla (3T). 4. To use k-t acceleration schemes to establish the feasibility of first-pass stress perfusion CMR in a rodent model, and to validate this against the microspheres method. 5. Multicentre evaluation of 3D perfusion CMR imaging for the detection of IHD defined by fractional flow reserve (FFR)(appendix). 6. To use k-t acceleration schemes for high-resolution quantitative first-pass perfusion imaging, and to determine reproducibility (appendix). 7. To compare advanced perfusion CMR imaging techniques: high-spatial resolution versus 3D whole-heart coverage (appendix). Results This research provides novel experimental evidence and technical advancements on the clinical utility of k-t PCA acceleration methods, and demonstrates the following: 1. That 3D whole-heart myocardial perfusion CMR imaging at 3T accurately detects functionally significant CAD; 2. That 3D whole-heart myocardial perfusion CMR imaging can determine ischaemic burden with accuracy comparable to current imaging techniques that rely on ionising radiation; 3. That the development of a 3D bSSFP myocardial perfusion CMR sequence is feasible using radio frequency (RF) shimming with dual-source parallel RF transmission at 3T. 4. That first-pass myocardial stress perfusion CMR imaging is feasible in a murine model using a 3T clinical scanner. The use of k-t spatio-temporal undersampling also yielded the following findings: 5. 3D whole-heart myocardial perfusion CMR imaging was highly efficient in the detection of functionally significant CAD in a multicentre study (appendix). 6. Quantitative high-resolution myocardial perfusion CMR showed inter-study reproducibility with no significant diurnal variation (appendix). Conclusion These findings have important implications, lending support to the clinical use of 3D whole-heart perfusion imaging for the detection of coronary disease. The use of k-t acceleration schemes is feasible for both clinical and pre-clinical models. When combined with CMR assessment of function and viability, the technique holds promise as a completely non-invasive and radiation-free diagnostic and risk-stratification tool for patients with known or suspected CAD.