Raman Spectroscopic Characterization of Polymerization Kinetics of Cyanoacrylate Embolic Glues for Vascular Embolization

Abstract

Endovascular glue embolization is a minimally invasive technique used to selectively reduce or block the blood supply to specific targeted vessels. Cyanoacrylate glues, mixed with radiopaque iodized oil, have been widely used for vascular embolization owing to their rapid polymerization rate, good penetration ability and low tissue toxicity. Nevertheless, in clinical practice, the selection of the glue-oil proportion and the manual injection process of mixtures are mostly based on empirical knowledge of operators, as the crucial physicochemical effect of polymerization kinetics has rarely been quantitatively investigated. In this study, the Raman spectroscopy is used for studying the polymerization kinetics of n-butyl-cyanoacrylate-based glues mixed with an iodized oil. To simulate the polymerization process during embolization, glue-oil mixtures upon contact with a protein ionic solution mimicking blood plasma are manually constructed and their polymerization kinetics are systematically characterized by Raman spectroscopy. The results demonstrate the feasibility of Raman spectroscopy in the characterization of polymerization kinetics of cyanoacrylate-based embolic glues. The polymerization process of cyanoacrylate-based mixtures consists of a fast polymerization phase followed by a slow phase. The propagation velocity and polymerization time primarily depend on the glue concentrations. The commonly used 50% mixture polymerizes 1 mm over ∼21.8 s, while it takes ∼51 min to extend to 5 mm. The results provide essential information for interventional radiologists to help them understand the polymerization kinetics of embolic glues and thus regulate the polymerization rate for effective embolization.

Keywords: Raman spectroscopy; cyanoacrylate glues; endovascular embolization; polymerization kinetics.

Figure 1

Initiation and propagation steps for alkyl (R) cyanoacrylate polymerization activated by nucleophile (Nu$${}^{-}$$).

Figure 2

Schematic of experiment setup for characterizing the polymerization kinetics of glue–oil mixtures induced by blood substitute.

Figure 3

Time evolution of Raman spectra (a) and C=C intensity change at 1617 cm$${}^{-1}$$ (b) during the fast polymerization phase of GO mixture ($$C_G=50\%$$) in contact with blood substitute BSA8.

Figure 4

Time evolution of Raman spectra (a) and intensity change in chemical bonds (b) during the slow polymerization phase of GO mixture in contact with blood substitute BSA8. The Raman shifts of C=C, C=O, C≡N and C=CH$${}_2$$ are 1617 cm$${}^{-1}$$, 1731 cm$${}^{-1}$$, 2239 cm$${}^{-1}$$ and 3128 cm$${}^{-1}$$, respectively.

Figure 5

Time evolution of intensity change in C=C during the fast (a) and slow (b) polymerization phases of GO mixtures in contact with blood substitute BSA8.

Figure 6

Time evolution of intensity change in C=C during the fast (a) and slow (b) polymerization phases of the GO mixture $$C_G=50\%$$ in contact with BSA4 and BSA8, respectively.