UCLA

Congenital heart disease (CHD) is the most common congenital defect affecting about 1% of live births. Cardiovascular MRI (CMR) is increasingly used in pediatric patients with CHD to complement echocardiography and invasive catheterization for anatomical and functional assessment of the heart and blood vessels. For children, the non-invasiveness, unrestricted field of view, absence of contrast nephrotoxicity and ionizing radiation make CMR an attractive imaging modality.

Current pediatric CMR protocol includes, among others, 2D cardiac cine and 3D first-pass contrast-enhanced MR angiography, both performed with breath-holding. However, reliable breath-holds are usually hard to achieve in these pediatric patients due to their limited cooperation. In addition, prolonged and repeated breath-holds are undesirable for patients with unstable cardiopulmonary status. More importantly, the data acquisitions in current CMR protocols are limited by the breath-hold duration, the need to capture the first-pass of the gadolinium bolus and relatively thick 2D slices in cardiac cine. Consequently, despite its exquisitely detailed definition of extra-cardiac vascular anatomy, conventional CMR methods fall short of providing a comparable definition of dynamic cardiac anatomy, although the status of these structures is often the basis for treatment and surgical planning. Moreover, a conventional pediatric CMR protocol requires a lot of clinical resources, including an average of 1-2 hours of scanner time and the need for physician’s presence to ensure appropriate geometric interrogation of the complex congenital cardiac anatomy. All the aforementioned issues have prevented pediatric CMR from reaching its full potential.

The overall aim of this thesis is to propose an innovative, effective, and reliable CMR approach to address the aforementioned issues of conventional protocol. The proposed pediatric CMR approach includes the use of ferumoxytol as an intravascular contrast agent and the development of the 4D Multi-phase Steady-state Imaging with Contrast (4D MUSIC) pulse sequence using a ROtating Cartesian K-space (ROCK) sampling pattern, cardiac and respiratory motion self-gating and compressed sensing image reconstruction. The proposed approach potentially represents a new paradigm of CMR in pediatric CHD patients whereby comprehensive volumetric information about cardiovascular anatomy and function can be acquired non-invasively in 10 minutes, without ionizing radiation, without exposure to a Gadolinium-based contrast agent and without breath-holding.

Chapter 1 introduces the conventional CMR protocol and discusses its utility in the clinical management of pediatric patients with CHD, which bring out the motivation of the technical development of this thesis. In Chapter 2, a brief technical background of MRI is provided. Chapter 3 introduces the concept of performing CMR with respiratory and cardiac motion compensation during the steady-state distribution of ferumoxytol. The prototype 4D MUSIC pulse sequence and preliminary clinical results from eight pediatric patients with CHD are presented in this chapter. In Chapter 4, several technical developments were made to optimize the 4D MUSIC sequence, including an efficient and flexible ROCK sampling pattern, a robust retrospective motion compensation strategy, and a compressed sensing image reconstruction algorithm. These technical developments further improve the clinical performance of 4D MUSIC in terms of image quality, scan efficiency, and reliability, and potentially eliminate the need for external physiological signal monitoring for motion gating. The optimized 4D MUSIC sequence was validated in a clinical study of ten pediatric patients with CHD. Chapter 5 exploits the potential of 4D MUSIC for cardiac functional evaluation where a motion-weighted image reconstruction strategy was evaluated to improve the temporal resolution of 4D MUSIC images. The results from a retrospective clinical study of sex pediatric patients with CHD showed that 4D MUSIC could offer accurate cardiac functional measurements.

Several techniques developed in Chapters 3-5 can be applied to other MRI applications. In Chapter 6, a segmented golden ratio radial reordering scheme is proposed in order to improve the k-space sampling efficiency in 2D cardiac CINE acquisitions and enable image reconstruction with retrospectively defined temporal resolution. A 4D respiratory resolved MRI technique is proposed in Chapter 7, utilizing the ROCK sampling pattern developed in Chapter 4. The proposed technique can be used to quantitatively evaluate the breathing pattern of individual patients and help to optimize the dose delivery in radiation therapy.