UCLA

Heart Disease, including Coronary Artery Disease, Hypertension, and Stroke, is the number one cause of death in the United States. Coronary artery disease (CAD) or ischemic heart disease (IHD) kills over 360,000 people per year, make up for 1 in 7 deaths in the United States. In current clinical diagnosis and management of patients with suspected CAD, various noninvasive methods including personal history, stress electrocardiogram (ECG) tests, and advanced imaging techniques are normally performed in patients with intermediate risk of CAD. If any combination of the noninvasive results suggests high-risk coronary lesion(s), the patient is then suggested to undergo invasive catheterization where invasive coronary angiography (ICA) and/or fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR) are performed as the final steps of a diagnostic work-up.

Studies have shown that over 50% of patients who undergo invasive catheterization were found to have non-obstructive (<50% degree stenosis) or functionally nonsignificant (FFR > 0.80) coronary lesions, resulting in unnecessary invasive procedures. This suggests that better noninvasive methods are needed to help increase the diagnostic yield for invasive catheterization. An emerging noninvasive technique based on coronary computed tomographic angiography (CTA) in combination with computational fluid dynamics simulations to measure the functional significance of a coronary lesion, FFRCT, has shown promise. However, the method requires exposure to ionizing radiation, uses an anatomical model to simulate the hemodynamic behaviors in the coronary arteries, and may be hindered by blooming artifacts caused by densely calcified plaques which could reduce the accuracy of the overall technique.

This dissertation introduces the development of a magnetic resonance (MR) based noninvasive functional assessment for the diagnosis and management of stable CAD. The developed noninvasive technique mimics the invasive FFR and iFR methods to calculate an index using pressure. The proposed noninvasive pressure measurement framework utilizes flow velocity information obtained using phase-contrast magnetic resonance imaging (PC-MRI) in conjunction with the Navier-Stokes (NS) analysis to derive a pressure gradient across the coronary lesion of interest. Validation studies of PC-MRI velocity measurements and NS derived pressure gradient measurements were assessed in a small-caliber stenotic flow phantom at different degrees of narrowing, in healthy coronary arteries, and in a pilot patient study with diseased coronary arteries. In patient studies, noninvasive pressure gradient measurements were compared with invasive FFR and iFR to evaluate the potential of the proposed method for noninvasive functional assessment in patients with stable CAD. In addition, the method was further improved using a stack-of-stars MR acquisition approach with compressed sensing image reconstruction to allow for shorter scan time, compared to Cartesian acquisition. The approach was tested in phantoms and healthy volunteers to assess feasibility.

The success of the proposed noninvasive pressure gradient measurement method discussed in this dissertation may serve as a complementary approach to current clinical diagnostic tools, providing added information to better risk-stratify and manage patients with stable CAD. In addition, the method has the potential to serve as a gatekeeper for patients who are unlikely to benefit from invasive catheterization, hence, decrease the number of unnecessary invasive procedures.