Development of Quantitative Myocardial Tissue Characterization

  • Author / Creator
    Chow, Kelvin
  • Diffuse myocardial fibrosis and other remodeling of the extracellular volume (ECV) in the heart are common pathological features in a variety of cardiac diseases. These microscopic alterations can be imaged non-invasively via changes in the spin-lattice (T1) relaxation time in magnetic resonance imaging (MRI). A growing body of literature supports the hypothesis that myocardial T1 and derived ECV measurements are correlated with fibrosis and disease severity in a variety of cardiomyopathies and that ECV may be an independent predictor of mortality. ECV is a promising biomarker for assessing cardiac disease and could potentially be a therapeutic target for medical interventions aimed at controlling fibrosis progression. The widely used "MOLLI" T1 imaging technique is known to have numerous systematic errors that increase measurement variability and may lead to erroneous interpretations of fibrosis. A thorough understanding of these confounding effects is essential to support translation of ECV measurements to routine clinical practice. The goal of this thesis was to gain analytic insight into factors affecting MOLLI T1 values and the development and optimization of a new T1 imaging technique which is robust against these potential confounders. A simple analytical model of the MOLLI technique was developed, describing the apparent spin-lattice relaxation rate (1/T1*) as the time-weighted average (TWA) of two distinctive relaxation rates. The TWA model was validated through simulations and experimental data and the model characterizes the relationship between the measured MOLLI T1* and the true T1 as a function of several confounding factors. In contrast to existing literature that phenomenologically describes many of these confounders in isolation, the TWA model provides a unified theory for the effect of these factors as well as their interaction. A novel cardiac T1 measurement technique termed SASHA was developed and validated through simulations and experimental data. SASHA T1 measurements were found to be accurate and robust against changes in heart rate, spin-spin relaxation time (T2), flip angle, and off-resonance, which are known sources of error in MOLLI T1 values. Normal ranges for SASHA T1 values were established in a group of healthy controls and altered T1 values consistent with fibrosis were found in small study of patients with heart failure. Precision of SASHA measurements can be significantly improved using a 2-parameter model to calculate T1 values at the expense of greater systematic errors, particularly due to incomplete magnetization saturation. Robust saturation pulses were developed using hard pulse trains with numerically optimized flip angles and experimentally validated to result in less than 1% residual magnetization over the range of B0 and B1 magnetic field inhomogeneities expected at common imaging field strengths. A variable flip angle (VFA) imaging readout was also designed to reduce SASHA T1 errors caused by readout effects when using a 2-parameter model. SASHA-VFA was found to significantly reduce the magnitude of T1 errors in phantom experiments and consistently reduce image artifacts due to off-resonance. Together, robust saturation pulse trains and VFA readouts minimize systematic errors in 2-parameter SASHA T1 values, enabling accurate in-vivo T1 measurements with comparable precision to the existing MOLLI technique. ECV quantification using T1 measurements can be easily added to existing clinical MRI protocols and can potentially provide clinically useful information due to the ubiquitous presence of myocardial fibrosis in cardiac disease. The characterization and development of improved T1 measurement techniques in this thesis directly translate to more reliable ECV measurements that may drive its clinical adoption.

  • Subjects / Keywords
  • Graduation date
  • Type of Item
  • Degree
    Doctor of Philosophy
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
  • Institution
    University of Alberta
  • Degree level
  • Department
    • Medical Sciences-Biomedical Engineering
  • Supervisor / co-supervisor and their department(s)
    • Wilman, Alan (Biomedical Engineering)
    • Thompson, Richard (Biomedical Engineering)
    • Paterson, Ian (Division of Cardiology)
  • Examining committee members and their departments
    • Wright, Graham (Medical Biophysics)
    • Beaulieu, Christian (Biomedical Engineering)
    • Haykowsky, Mark (Rehabilitation Medicine)