Quantifying hemodynamic conditions in the abdominal aorta of small animals using phase contrast MRI and computational fluid dynamics
Manipulation of the murine genome has made small animal models standard surrogates for better understanding the human cardiovascular system. It has therefore become increasingly important to understand how results scale from mouse to human.
Hemodynamics play a critical role in both health and disease in the cardiovascular system. Quantifying hemodynamic parameters requires measurements of vessel geometry and blood flow, ideally in vivo by non-invasive methods. Accomplishing this in small animals is difficult because of challenges associated with achieving adequate spatial and temporal resolution. The work presented here describes implementation, validation, and application of a phase-contrast MRI (PCMRI) sequence at 4.7T to quantify blood flow velocities in the abdominal aorta of rats and mice in vivo. Derived volumetric flow rates were combined with anatomical MRI and computational fluid dynamics (CFD) methods to study hemodynamic parameters, non-invasively, in small animal models.
The methodology was first applied to empirically derive an allometric scaling law for wall shear stress (WSS) in the non-diseased infrarenal aortas of mice, rats, and humans. Mean WSS was significantly greater in mice and rats compared to humans (87.6, 70.5, 4.8 dynes/cm2, p < 0.01) and a scaling exponent of -0.38 (R2 = 0.92) was determined. The empirical results were consistent with recent theoretical predictions.
Subsequent investigation included serial quantification of geometry and hemodynamics during disease progression in a rat model of abdominal aortic aneurysm (AAA). AAA enlargement was asymmetric and deviation of the direction of the velocity field away from the longitudinal axis of the aorta was a distinguishing factor in the largest AAAs. Histological measurements of inflammation and elastic fiber number were performed along the extent of the aorta (anterior and posterior surfaces). Inflammation was heterogeneously distributed along both walls with maximum inflammation rarely occurring at the largest diameter. Elastic fibers were degraded along the anterior wall while largely retained posteriorly.
Neither PCMRI or CFD, nor the combination, has been broadly applied to study in vivo blood flow in small animals. The work presented here suggests these synergistic methods could be utilized to a greater extent when studying small animal models as surrogates for the human condition.