Computational and experimental investigation of particulate matter deposition in cerebral side aneurysms

Abstract

Intracranial aneurysms frequently develop blood clots, plaque and inflammations, which are linked to enhanced particulate mass deposition. In this work, we propose a computational model for particulate deposition, that accounts for the influence of field forces, such as gravity and electrostatics, which produce an additional flux of particles perpendicular to the fluid motion and towards the wall. This field-mediated flux can significantly enhance particle deposition in low-shear environments, such as in aneurysm cavities. Experimental investigation of particle deposition patterns in in vitro models of side aneurysms, demonstrated the ability of the model to predict enhanced particle adhesion at these sites. Our results showed a significant influence of gravity and electrostatic forces (greater than 10%), indicating that the additional terms presented in our models may be necessary for modelling a wide range of physiological flow conditions and not only for ultra-low shear regions. Spatial differences between the computational model and the experimental results suggested that additional transport and fluidic mechanisms affect the deposition pattern within aneurysms. Taken together, the presented findings may enhance our understanding of pathological deposition processes at cardiovascular disease sites, and facilitate rational design and optimization of cardiovascular particulate drug carriers.

Biophysical targeting of high‐risk cerebral aneurysms

“…To study the ability of particles with different physical properties (i.e., size and density) to localize in aneurysm cavities, we performed in vitro experiments in a well‐defined, transparent cerebral side aneurysm models 12 , 24 subjected to physiological pulsatile flow while imaging the deposition pattern in the parent vessel and in the aneurysm cavity (see SM for detailed description of the experimental setup). The WSS in our models is low reaching 0 at the apex and averaging around 1.27 dyne/cm 2 in the cavity while the average in the parent is over 20 dyne/cm 2 .…”

“…While gravity has little effect under normal arterial flow conditions, under the low velocity hemodynamics existing in aneurysms, gravity forces may become dominant and affect the targeted delivery of drug carriers. 24 These forces depend on the relative acceleration of the particle toward the wall. All the particles in this study have very small relaxation time suggesting that most of them reach terminal velocity before hitting the wall in which case F d = F g = 2.9·10 −18 N (see SM for details on calculation), where F d and F g are the drag and gravity forces, respectively.…”

“…The simplified aneurysm models were designed in SolidWorks and 3D printed using a FormLabs clear resin V4 on Form 2 3D printer. The models were based on the same geometry previously used by us 12 , 24 and were similar to other models used in the literature. 2 , 12 , 25 , 26 , 27 Then, silicone (Elastosil by Wecker) was poured into the mold, left to cure overnight, and then placed in acetone for a few hours to remove the mold.…”

“…To study the ability of particles with different physical properties (i.e. ; size and density) to localize in aneurysm cavities we performed in vitro experiments in a well-defined, transparent cerebral side aneurysm models 12,24 However, the PLGA particles settle only on one side of the aneurysm which could be problematic for localized delivery. Moreover, in an unfavorable gravity situation the PLGA particles will drift away from the aneurysm cavity thus reducing their aneurysm targeting.…”