Non-invasive Assessment of Elastic Modulus of Arterial Constructs during Cell Culture Using Ultrasound Elasticity Imaging

Abstract

Mechanical strength is a key design factor for engineered arteries. Most existing techniques assess the mechanical property of arterial constructs destructively, leading to a large number of animal sacrifices. We propose an ultrasound-based non-invasive mechanical strength assessment technique for engineered arterial constructs. Tubular scaffolds made from a biodegradable elastomer and seeded with vascular fibroblasts and smooth muscle cells were cultured in a pulsatile-flow bioreactor. Scaffold distension was computed from ultrasound radiofrequency signals of the pulsating scaffold via two-dimensional phase-sensitive speckle tracking. The Young's modulus was then calculated by solving inverse problem from the distension and the recorded pulse pressure. Stiffness thus computed from ultrasound correlated well with direct mechanical testing results. As the scaffolds matured in culture, ultrasound measurements showed increased Young's modulus and histology confirmed the growth of cells and collagen fibrils in the constructs. The results show that ultrasound elastography non-invasively assesses and monitors the mechanical properties of arterial constructs.

Inflation and Bi-Axial Tensile Testing of Healthy Porcine Carotid Arteries

“…These data revealed good correspondence with the bi-axial tensile test. Other similar studies determined mainly the Young's modulus and found good agreement between inflation experiments and bi-axial tensile testing (Dutta et al 2013;Kim et al 2008). Although the Young's modulus is also a linear elastic parameter, it is valid only for small strains, whereas the neo-Hookean model can also be used to describe large deformations such as those found in this study.…”

A computationally efficient approach for inverse material characterization combining Gappy POD with direct inversion

“…In all three cases, the partial-field measurements were assumed to be obtained from some type of nondestructive testing in the linear range of the solid behavior. First, two numerical examples were considered in which the "experiment" was simulated through finite element analysis, as described in Section 3.1, then a physical (i.e., "real life") example was considered relating to elastography of an arterial construct [33].…”

“…Successful translation of such technologies, especially with aids of Gappy POD for realistic computational power, can result in significant savings in time and money for both noninvasive preclinical studies and clinical uses. The example followed a nearly identical format as the work shown in [33], with the exception of the inverse solution estimation procedure (the prior work used a computationally expensive non-gradient-based optimization procedure). For simplicity, the behavior of the artery for all analyses was assumed to obey the plane strain condition, and the initial cross-sectional geometry of the artery was estimated from ultrasound imaging, as shown in Fig.…”

“…In addition, to sufficiently support the artery for the analyses, the vertical displacement of an approximately 2 mm long region vertically centered on both the left and right sides of the outer surface and the horizontal displacement of an approximately 3 mm long region centered horizontally on both the top and bottom of the outer surface were assumed to be fixed. As was similarly used in [33], only 15 discrete vertical displacement measurements in the approximately 0.4 mm × 0.6 mm rectangular region shown in Fig. 12 were used as the partial-field measurements for the inverse solution estimation process, as those measurements were considered the most reliable with the largest signal-to-noise ratio.…”

“…The estimated two-layer elastic modulus distribution was consistent with the referenced previous study, with the inner modulus of approximately 330 kPa considerably higher than the outer modulus of approximately 110 kPa. Furthermore, as stated in [33], the artery was tested destructively through a tensile testing method following the imaging experiment, and the bulk (i.e., averaged) elastic modulus of the artery was determined to be approximately 184 kPa. Therefore, the approximate average modulus of the distribution estimated herein of 220 kPa was relatively accurate in comparison to the destructive test (noting that the conditions for the two testing procedure were substantially different).…”