Physical Vein Models to Quantify the Flow Performance of Sclerosing Foams

Abstract

Foam sclerotherapy is clinically employed to treat varicose veins. It involves intravenous injection of foamed surfactant agents causing endothelial wall damage and vessel shrinkage, leading to subsequent neovascularization. Foam production methods used clinically include manual techniques, such as the Double Syringe System (DSS) and Tessari (TSS) methods. Pre-clinical in-vitro studies are conducted to characterize the performance of sclerosing agents; however, the experimental models used often do not replicate physiologically relevant physical and biological conditions. In this study, physical vein models (PVMs) were developed and employed for the first time to characterize the flow behavior of sclerosing foams. PVMs were fabricated in polydimethylsiloxane (PDMS) by replica molding, and were designed to mimic qualitative geometrical characteristics of veins. Foam behavior was investigated as a function of different physical variables, namely (i) geometry of the vein model (i.e., physiological vs. varicose vein), (ii) foam production technique, and (iii) flow rate of a blood surrogate. The experimental set-up consisted of a PVM positioned on an inclined platform, a syringe pump to control the flow rate of a blood substitute, and a pressure transducer. The static pressure of the blood surrogate at the PVM inlet was measured upon foam administration. The recorded pressure-time curves were analyzed to quantify metrics of foam behavior, with a particular focus on foam expansion and degradation dynamics. Results showed that DSS and TSS foams had similar expansion rate in the physiological PVM, whilst DSS foam had lower expansion rate in the varicose PVM compared to TSS foam. The degradation rate of DSS foam was lower than TSS foam, in both model architectures. Moreover, the background flow rate had a significant effect on foam behavior, enhancing foam displacement rate in both types of PVM.

Foam‐in‐vein: A review of rheological properties and characterization methods for optimization of sclerosing foams

“…Furthermore, Bottaro et al showed that DSS foams demonstrate greater dwell times in the varicose PVM, while both Bottaro et al and Carugo et al demonstrate that DSS foams are more stable and exhibit longer dwell times in general. In conclusion, dwell time analysis reveals that foam performance from best to worst is PEM > DSS > Tessari (Bottaro, Paterson, Zhang, et al, 2019).…”

“…Sclerotherapy involves the injection of a surfactant solution—using a needle or a catheter—that damages the inner vessel wall. This process involves the activation of calcium signaling and nitric oxide pathways in response to the sclerosant's injection, causing endothelial cell lysis, vascular fibrosis, and subsequent endovascular occlusion (Figure 3) (Bottaro, Paterson, Zhang, et al, 2019; Carugo et al, 2013; Eckmann, 2009). Upon injection, the efficacy of liquid sclerosants decreases due to dilution and rapid deactivation by blood components, making liquid sclerotherapy ineffective when conducted on larger veins such as saphenous veins (Cameron, Chen, Connor, Behnia, & Parsi, 2013; Carugo et al, 2015).…”

“…An earlier study has experimentally demonstrated the binding of serum albumin to sclerosing agents such as sodium tetradecyl sulfate (STS) and polidocanol, leading to inhibition (Parsi et al, 2008). To overcome dilution and deactivation, the sclerosant is mixed with a gas and is administered in large veins as a foam (Bottaro, Paterson, Zhang, et al, 2019; Cameron et al, 2013; Carugo et al, 2015). The main benefit of administering sclerosing foams lies in their capacity to mimic a piston that displaces intravenous blood, leading to a greater contact surface area with venous endothelium, reduced mixing with blood and subsequent deactivation, and reduced staining of the leg due to trapped blood in the collapsed vessel (Carugo et al, 2015).…”

“…Only a handful of studies have focused on characterizing foam physics in application‐relevant setups that are discussed here. On a general note, reported studies have investigated the effect of foam production technique (Bottaro, Paterson, Zhang, et al, 2019; Carugo et al, 2015; Critello et al, 2017), syringe size and number of pumping cycles (Bai et al, 2018; Nastasa et al, 2015), surfactant concentration (Cameron et al, 2013; Wong et al, 2015) and temperature (Bai et al, 2018), different liquid to gas ratios (Cameron et al, 2013; Carugo et al, 2015; Wong et al, 2015) and various gas types (Carugo et al, 2013, 2015; Hashimoto, Uchida, Horikawa, Mimura, & Farsad, 2018) on characteristics of sclerosing foams such as bubble count, bubble size distribution and static half‐life. The issue taken with these approaches is the relevance of attributes such as drainage time and bubble properties to clinical performance of sclerotherapy.…”

“…Some recent efforts have been made to optimize sclerosing foams in vitro (Bai et al, 2018; Critello, Fiorillo, & Matula, 2017; Wong, Chen, Connor, Behnia, & Parsi, 2015); however, they lack clinically relevant parameters that can correlate physical characteristics of foams with clinical outcomes of sclerotherapy. Other studies have instead defined new parameters that could directly reflect the performance of sclerosing foams (Bottaro et al, 2019; Carugo et al, 2013).…”