Copyright © 2017 SPIE. The utility and accuracy of computational modeling often requires direct validation against experimental measurements. The work presented here is motivated by taking a combined experimental and computational approach to determine the ability of large-scale computational fluid dynamics (CFD) simulations to understand and predict the dynamics of circulating tumor cells in clinically relevant environments. We use stroboscopic light sheet fluorescence imaging to track the paths and measure the velocities of fluorescent microspheres throughout a human aorta model. Performed over complex physiologicallyrealistic 3D geometries, large data sets are acquired with microscopic resolution over macroscopic distances.