X-ray Microtomography to Assess Determinants of In Vivo N-Butyl Cyanoacrylate Glubran®2 Polymerization: A Rabbit-Model Study

Abstract

Although introduced decades ago, few cyanoacrylate glues have been approved for endovascular use, despite evidence of their usefulness, notably for complex procedures suchas hemostatic embolization. Indications include massive bleeding requiring emergent hemostasis and prevention of severe bleeding during scheduled surgery to remove a hypervascular tumor. Adding radiopaque Lipiodol Ultra Fluid® (LUF) modulates glue polymerization and allows fluoroscopic guidance, but few comparative in vivo studies have assessed the impact of the resulting change in glue concentration or of other factors such as target-vessel blood flow. In a rabbit model, we used ex vivo X-ray microtomography to assess the results of in vivo renal-artery embolization by various mixtures of N-butyl cyanoacrylate (NBCA), metacryloxysulfolane, and LUF. Overall, penetration to the superficial interlobular arteries was achieved in about two-thirds of cases and into the capillaries in nearly half the cases, while cast fragmentation was seen in slightly more than half the cases. Greater NBCA dilution and the blocked-blood-flow technique were independently associated with greater distality of penetration. Blocked-blood-flow injection was independently associated with absence of fragmentation, capillary penetration, a shorter cast-to-capsule distance, and higher cast attenuation. A larger mixture volume was independently associated with higher indexed cast ratio and deeper penetration. Finally, microtomography is an adapted tool to assess ex vivo distribution of glue cast.

Iodixanol as a New Contrast Agent for Cyanoacrylate Embolization: A Preliminary In Vivo Swine Study

“…Swine closely resemble humans regarding blood flow, renal vessel diameters, and hemostasis. The terminal configuration of the renal arterial vasculature allows an assessment of glue-cast properties, including distribution after injection [6,20]. Therefore, we chose the renal arteries of swine for these embolization experiments.…”

“…The embolized kidney areas were segmented, starting at the first renal-artery bifurcation to avoid cast-volume variability linked to trunk length, as previously described [6]. In the first segment, the cast was sub-segmented according to whether attenuation was 1000 to 1300 HU, >1300 to 1600 HU, or >1600 HU.…”

“…These cutoffs were chosen based on the high attenuations of LUF and other ICAs, which create a risk of streak artifacts. We validated this one in a past work for Lipiodol and cyanoacrylate mixture [6]. We assumed that all pixels whose attenuation was greater than that of the renal parenchyma were from embolized vessels.…”

“…In two swine studies, at least a 1/6th proportion of iopamidol was required to prevent adhesion within the microcatheter, and the optimal NBCA-LUF-iopamidol ratio was 2/3/1 [16][17][18]. Although iopamidol is a low-osmolar agent, iodixanol is iso-osmolar and might, therefore, be expected to cause a greater delay in NBCA polymerization and, therefore, greater distality of penetration [6,7,19]. To our knowledge, no in vivo study of NBCA mixed with iodixanol for embolization procedures has been published.…”

“…LUF has been Biomedicines 2023, 11, 3177 2 of 13 reported to provide good visibility during embolization [4]. Moreover, dilution with LUF slows the polymerization rate, and a greater glue dilution, therefore, results in a greater distality of glue penetration along the vascular bed [5,6]. The dilution ratio can thus be chosen according to the specific needs of each patient.…”