Development of whole-heart myocardial perfusion magnetic resonance imaging

Myocardial perfusion imaging is of huge importance for the detection of coronary artery disease (CAD), one of the leading causes of morbidity and mortality worldwide, as it can provide non-invasive detection at the early stages of the disease. Magnetic resonance imaging (MRI) can assess myocardial perfusion by capturing the rst-pass perfusion (FPP) of a gadolinium-based contrast agent (GBCA), which is now a well-established technique and compares well with other modalities. However, current MRI methods are restricted by their limited coverage of the left ventricle. Interest has therefore grown in 3D volumetric \whole-heart" FPP by MRI, although many challenges currently limit this. For this thesis, myocardial perfusion assessment in general, and 3D whole-heart FPP in particular, were reviewed in depth, alongside MRI techniques important for achieving 3D FPP. From this, a 3D `stack-of-stars' (SOS) FPP sequence was developed with the aim of addressing some current limitations. These included the breath-hold requirement during GBCA rst-pass, long 3D shot durations corrupted by cardiac motion, and a propensity for artefacts in FPP. Parallel imaging and compressed sensing were investigated for accelerating whole-heart FPP, with modi cations presented to potentially improve robustness to free-breathing. Novel sequences were developed that were capable of individually improving some current sequence limits, including spatial resolution and signal-to-noise ratio, although with some sacri ces. A nal 3D SOS FPP technique was developed and tested at stress during free-breathing examinations of CAD patients and healthy volunteers. This enabled the rst known detection of an inducible perfusion defect with a free-breathing, compressed sensing, 3D FPP sequence; however, further investigation into the diagnostic performance is required. Simulations were performed to analyse potential artefacts in 3D FPP, as well as to examine ways towards further optimisation of 3D SOS FPP. The nal chapter discusses some limitations of the work and proposes opportunities for further investigation.Open Acces

Cardiovascular Magnetic Resonance Imaging for the Investigation of Ischaemic Heart Disease

Introduction: Coronary artery disease (CAD) remains the number one cause of mortality worldwide; improving diagnosis and treatment is a priority. Multi- parametric cardiovascular magnetic resonance (CMR) offers quantitative assessment of the cardiovascular system with a variety of techniques allowing assessment of anatomy, function, myocardial composition and perfusion during a single scan. Aims: To assess 1.) diagnostic accuracy of visual and quantitative perfusion CMR to single-photon emission computed tomography (MPS-SPECT) in patients with left main stem CAD. 2.) the hypothesis that patients with ischaemic (ICM) and non-ischaemic cardiomyopathy (NICM) have different torsion and strain parameters 3.) development and validation of a contemporary multivariable risk model of CAD from a large population undergoing X-ray angiography. 4.) a rapid 3D mDIXON pulse sequence for image quality and quantitation of MI. 5.) T1 rho prepared (T1ρ) dark blood sequence and compare to blood nulled PSIR (BN) and standard myocardium nulled PSIR (MN) for detection and quantification of scar. Methods: Patients were recruited between 2008 and 2017. Patients in chapters 3,4,6,7 underwent multi-parametric CMR including late gadolinium enhancement (LGE) imaging at 1.5 or 3.0T. Patients in chapter 5 underwent angiography. Results: 1.) CMR demonstrated significantly higher area under the curve for detection of LMS or equivalent disease over MPS-SPECT(P=0.0001). 2.) Despite no difference in LV dimensions, EF and strain between ICM and NICM, NICM patients had significantly lower LV twist(P=0.023) and torsion(P=0.017) compared to ICM. 3.) The developed model discriminated well and was well-calibrated. Diamond and Forrester and Duke scores substantially over-predicted CAD risk, whilst CAD Consortium risk models slightly under-estimated risk. 4.) Image quality was comparable between 3D and 2D LGE(P=0.162). Time for 3D image acquisition was only 5% of the time required for a standard 2D acquisition. 5.) CNRscar-blood was significantly increased for BN and T1ρ compared to MN LGE. BN LGE demonstrated significantly higher reader confidence scores

Doctor of Philosophy

dissertationDynamic contrast enhanced magnetic resonance imaging (DCE-MRI) is a powerful tool to detect cardiac diseases and tumors, and both spatial resolution and temporal resolution are important for disease detection. Sampling less in each time frame and applying sophisticated reconstruction methods to overcome image degradations is a common strategy in the literature. In this thesis, temporal TV constrained reconstruction that was successfully applied to DCE myocardial perfusion imaging by our group was extended to three-dimensional (3D) DCE breast and 3D myocardial perfusion imaging, and the extension includes different forms of constraint terms and various sampling patterns. We also explored some other popular reconstruction algorithms from a theoretical level and showed that they can be included in a unified framework. Current 3D Cartesian DCE breast tumor imaging is limited in spatiotemporal resolution as high temporal resolution is desired to track the contrast enhancement curves, and high spatial resolution is desired to discern tumor morphology. Here temporal TV constrained reconstruction was extended and different forms of temporal TV constraints were compared on 3D Cartesian DCE breast tumor data with simulated undersampling. Kinetic parameters analysis was used to validate the methods

Analysis of first pass myocardial perfusion imaging with magnetic resonance

Early diagnosis and localisation of myocardial perfusion defects is an important step in the treatment of coronary artery disease. Thus far, coronary angiography is the conventional standard investigation for patients with known or suspected coronary artery disease and it provides information about the presence and location of coronary stenoses. In recent years, the development of myocardial perfusion CMR has extended the role of MR in the evaluation of ischaemic heart disease beyond the situations where there have already been gross myocardial changes such as acute infarction or scarring. The ability to non-invasively evaluate cardiac perfusion abnormalities before pathologic effects occur, or as follow-up to therapy, is important to the management of patients with coronary artery disease. Whilst limited multi-slice 2D CMR perfusion studies are gaining increased clinical usage for quantifying gross ischaemic burden, research is now directed towards complete 3D coverage of the myocardium for accurate localisation of the extent of possible defects. In 3D myocardial perfusion imaging, a complete volumetric data set has to be acquired for each cardiac cycle in order to study the first pass of the contrast bolus. This normally requires a relatively large acquisition window within each cardiac cycle to ensure a comprehensive coverage of the myocardium and reasonably high resolution of the images. With multi-slice imaging, long axis cardiac motion during this large acquisition window can cause the myocardium imaged in different cross- sections to be mis-registered, i.e., some part of the myocardium may be imaged more than twice whereas other parts may be missed out completely. This type of mis-registration is difficult to correct for by using post-processing techniques. The purpose of this thesis is to investigate techniques for tracking through plane motion during 3D myocardial perfusion imaging, and a novel technique for extracting intrinsic relationships between 3D cardiac deformation due to respiration and multiple ID real-time measurable surface intensity traces is developed. Despite the fact that these surface intensity traces can be strongly coupled with each other but poorly correlated with respiratory induced cardiac deformation, we demonstrate how they can be used to accurately predict cardiac motion through the extraction of latent variables of both the input and output of the model. The proposed method allows cross-modality reconstruction of patient specific models for dense motion field prediction, which after initial modelling can be use in real-time prospective motion tracking or correction. In CMR, new imaging sequences have significantly reduced the acquisition window whilst maintaining the desired spatial resolution. Further improvements in perfusion imaging will require the application of parallel imaging techniques or making full use of the information content of the ¿-space data. With this thesis, we have proposed RR-UNFOLD and RR-RIGR for significantly reducing the amount of data that is required to reconstruct the perfusion image series. The methods use prospective diaphragmatic navigator echoes to ensure UNFOLD and RIGR are carried out on a series of images that are spatially registered. An adaptive real-time re-binning algorithm is developed for the creation of static image sub-series related to different levels of respiratory motion. Issues concerning temporal smoothing of tracer kinetic signals and residual motion artefact are discussed, and we have provided a critical comparison of the relative merit and potential pitfalls of the two techniques. In addition to the technical and theoretical descriptions of the new methods developed, we have also provided in this thesis a detailed literature review of the current state-of-the-art in myocardial perfusion imaging and some of the key technical challenges involved. Issues concerning the basic background of myocardial ischaemia and its functional significance are discussed. Practical solutions to motion tracking during imaging, predictive motion modelling, tracer kinetic modelling, RR-UNFOLD and RR-RIGR are discussed, all with validation using patient and normal subject data to demonstrate both the strength and potential clinical value of the proposed techniques.Open acces

Myocardial first-pass perfusion cardiovascular magnetic resonance: history, theory, and current state of the art

In less than two decades, first-pass perfusion cardiovascular magnetic resonance (CMR) has undergone a wide range of changes with the development and availability of improved hardware, software, and contrast agents, in concert with a better understanding of the mechanisms of contrast enhancement. The following review provides a perspective of the historical development of first-pass CMR, the developments in pulse sequence design and contrast agents, the relevant animal models used in early preclinical studies, the mechanism of artifacts, the differences between 1.5T and 3T scanning, and the relevant clinical applications and protocols. This comprehensive overview includes a summary of the past clinical performance of first-pass perfusion CMR and current clinical applications using state-of-the-art methodologies

Flow pattern analysis for magnetic resonance velocity imaging

Blood flow in the heart is highly complex. Although blood flow patterns have been investigated by both computational modelling and invasive/non-invasive imaging techniques, their evolution and intrinsic connection with cardiovascular disease has yet to be explored. Magnetic resonance (MR) velocity imaging provides a comprehensive distribution of multi-directional in vivo flow distribution so that detailed quantitative analysis of flow patterns is now possible. However, direct visualisation or quantification of vector fields is of little clinical use, especially for inter-subject or serial comparison of changes in flow patterns due to the progression of the disease or in response to therapeutic measures. In order to achieve a comprehensive and integrated description of flow in health and disease, it is necessary to characterise and model both normal and abnormal flows and their effects. To accommodate the diversity of flow patterns in relation to morphological and functional changes, we have described in this thesis an approach of detecting salient topological features prior to analytical assessment of dynamical indices of the flow patterns. To improve the accuracy of quantitative analysis of the evolution of topological flow features, it is essential to restore the original flow fields so that critical points associated with salient flow features can be more reliably detected. We propose a novel framework for the restoration, abstraction, extraction and tracking of flow features such that their dynamic indices can be accurately tracked and quantified. The restoration method is formulated as a constrained optimisation problem to remove the effects of noise and to improve the consistency of the MR velocity data. A computational scheme is derived from the First Order Lagrangian Method for solving the optimisation problem. After restoration, flow abstraction is applied to partition the entire flow field into clusters, each of which is represented by a local linear expansion of its velocity components. This process not only greatly reduces the amount of data required to encode the velocity distribution but also permits an analytical representation of the flow field from which critical points associated with salient flow features can be accurately extracted. After the critical points are extracted, phase portrait theory can be applied to separate them into attracting/repelling focuses, attracting/repelling nodes, planar vortex, or saddle. In this thesis, we have focused on vortical flow features formed in diastole. To track the movement of the vortices within a cardiac cycle, a tracking algorithm based on relaxation labelling is employed. The constraints and parameters used in the tracking algorithm are designed using the characteristics of the vortices. The proposed framework is validated with both simulated and in vivo data acquired from patients with sequential MR examination following myocardial infarction. The main contribution of the thesis is in the new vector field restoration and flow feature abstraction method proposed. They allow the accurate tracking and quantification of dynamic indices associated with salient features so that inter- and intra-subject comparisons can be more easily made. This provides further insight into the evolution of blood flow patterns and permits the establishment of links between blood flow patterns and localised genesis and progression of cardiovascular disease.Open acces

Relevance of accurate Monte Carlo modeling in nuclear medical imaging

Monte Carlo techniques have become popular in different areas of medical physics with advantage of powerful computing systems. In particular, they have been extensively applied to simulate processes involving random behavior and to quantify physical parameters that are difficult or even impossible to calculate by experimental measurements. Recent nuclear medical imaging innovations such as single-photon emission computed tomography (SPECT), positron emission tomography (PET), and multiple emission tomography (MET) are ideal for Monte Carlo modeling techniques because of the stochastic nature of radiation emission, transport and detection processes. Factors which have contributed to the wider use include improved models of radiation transport processes, the practicality of application with the development of acceleration schemes and the improved speed of computers. This paper presents derivation and methodological basis for this approach and critically reviews their areas of application in nuclear imaging. An overview of existing simulation programs is provided and illustrated with examples of some useful features of such sophisticated tools in connection with common computing facilities and more powerful multiple-processor parallel processing systems. Current and future trends in the field are also discussed