Micro-CT and Histological Assessment of Renal Arterial Embolization with Glubran®2 Cyanoacrylate: A Medium-Term Follow-Up Study in a Rabbit Model

Micro-CT and Histological Assessment of Renal Arterial Embolization with Glubran®2 Cyanoacrylate: A Medium-Term Follow-Up Study in a Rabbit Model | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Micro-CT and Histological Assessment of Renal Arterial Embolization with Glubran®2 Cyanoacrylate: A Medium-Term Follow-Up Study in a Rabbit Model Romaric Loffroy, Kévin Guillen, Olivier Chevallier, Mohamed Fouad, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6239046/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 22 Apr, 2025 Read the published version in CVIR Endovascular → Version 1 posted 5 You are reading this latest preprint version Abstract Background Cyanoacrylate glues are widely used in interventional radiology as effective embolic agents due to their rapid polymerization and ability to achieve vessel occlusion. Nonetheless, concern remains regarding cast stability and potential recanalization over time. This study used multiple modalities to evaluate the medium-term outcomes of Glubran ® 2 glue (methacryloxysulfolane and N butyl cyanoacrylate) embolisation in a rabbit renal-artery model. Methods The left renal arteries of six rabbits were embolized with 12.5% or 25% Glubran ® 2. In-vivo micro-CT scans were performed immediately after embolisation (M0) and ex-vivo scans and a histological assessment were done at one month (M1). Magnetic resonance imaging (MRI) was done at M1 to assess arterial occlusion and parenchymal changes. Quantitative and semi-quantitative parameters reflecting glue distribution, cast integrity, and tissue response were analysed. Statistical comparisons used non-parametric tests. Results All six embolisations were completed without complications. Micro-CT at M1 revealed significant cast resorption and fragmentation with both concentrations, but with no evidence of arterial recanalization. MRI and histology confirmed the persistent vascular occlusion with chronic ischemic changes in the renal parenchyma. Compensatory neovascularization from the renal capsule was observed, with no significant differences in histological inflammation between the two concentrations. Glue casts remained within the arterial lumens and were often surrounded by granulomatous inflammation. Conclusions Glubran ® 2 was effective for renal artery embolisation, even at a low concentration of 12.5%: despite partial cast resorption, the arteries remained occluded. Micro-CT proved to be a powerful tool for assessing changes in glue casts. Longer-term studies are warranted to further assess vascular remodelling and occlusion durability. Transcatheter arterial embolisation N-butyl cyanoacrylate glue Animal model Medium-term outcomes. Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Background Cyanoacrylate glues are widely used for transcatheter arterial embolisation because they polymerize promptly upon contact with body fluids, thereby providing prompt vessel occlusion [ 1 ]. This rapid effect is crucial in several indications such as arteriovenous malformations (AVMs) and arterial bleeding [ 2 , 3 ]. The histological effects of cyanoacrylate glues have been extensively documented [ 4 , 5 ]. Acute vascular inflammation is followed by a foreign-body granulomatous reaction with macrophage infiltration and the formation of multinucleated giant cells [ 6 , 7 ]. Although cyanoacrylate glues have been proven effective in achieving vessel occlusion, evidence of partial cast resorption over time after AVM embolisation has raised concern about the durability of the occlusive effect [ 8 ]. Whether this partial cast resorption affects the degree of occlusion or the risk of recanalization remains unclear. Microcomputed tomography (micro-CT) provides accurate three-dimensional images of glue casts within blood vessels [ 9 ]. Cast distribution and changes over time can be assessed. The primary objective of this animal-model study was to perform micro-CT assessments of changes in glue casts over the first post-embolisation month and to compare micro-CT findings with histological findings at one month. The secondary objective was to look for histological evidence of persistent arterial occlusion at one month. Methods Animal model and embolisation procedure The study protocol was approved by the local animal experimentation ethics committee (CEEA n°106, #25592) on 23rd June 2020. We studied six, 3-month-old, female rabbits obtained from Charles River (Écully, France). For the procedure, the animals were sedated with intramuscular buprenorphine (Buprecare ® 0.3 mg/mL, 0.17 mL/kg; Animalcare, York, UK) then anaesthetised with 2% isoflurane (IsoFlow ®, Zoetis, Parsippany-Troy Hills, NJ, USA). Two interventional radiologists (POC and KG) performed the procedures using a monoplane angiographic system (Veradius, Philips, Amsterdam, The Netherlands). A 4-Fr introducer was inserted surgically into the femoral artery. A baseline angiogram of the abdominal aorta was obtained using a 4-Fr vertebral catheter and manual injection of the water-soluble contrast agent iobitridol (Xenetix 350, Guerbet, Villepinte, France) via a 10-mL syringe, at a flow rate of about 4 mL/s. A 2.3-Fr microcatheter (Phenom ™ 21, Medtronic, Dublin, Ireland) was then inserted co-axially into the 4-Fr catheter in the left renal artery. Special care was taken to avoid selecting ventral or dorsal branches and to ensure that the glue was injected under free-flow conditions. To prevent premature glue polymerisation, the microcatheter was first flushed with 5% glucose in a volume of at least 0.43 mL, i.e., at least the volume of the lumen. The glue-LUF mixture was injected under fluoroscopic guidance using a 5-mL syringe (Plastipak ™ , Becton Dickinson Plastic, Franklin Lakes, NJ, USA) and an automated syringe pump (Harvard Apparatus PHD 2000 ™ , Holliston, MA, USA) at a standardised flow rate of 0.03 mL/s, as in previous studies [ 9 , 10 ]. Embolisation was deemed complete when reflux along the microcatheter was detected or the glue ceased to advance within the vascular tree. Either of these signs led to immediate withdrawal of the microcatheter to avoid adhesion to the vessel wall. The injected volume was computed by subtracting the volume of the microcatheter lumen (0.43 mL) from the total injected volume. The duration of the injection was recorded for each procedure. The 4-Fr introducer was removed and the puncture site was closed with sutures. Embolic agent All procedures were done using Glubran ® 2 glue (N-butyl-2-cyanoacrylate [NBCA] plus methacryloxysulfolane, GEM SRL, Viareggio, Italy) mixed manually with Lipiodol ® Ultrafluid (LUF, Guerbet) at room temperature. We studied two glue concentrations, 12.5% (glue/LUF ratio, 1:7) and 25% (1:3). The mixtures at each of the two concentrations were injected under free-flow conditions into the left renal arteries of three animals. Micro-CT evaluation Each rabbit underwent an in-vivo micro-CT scan immediately after embolisation (M0). One month later (M1), the animals were euthanised and the left kidney of each was removed and imaged ex-vivo by micro-CT. In-vivo image acquisition Immediately after embolisation, the rabbit was transported to the micro-CT room for in-vivo imaging while continuously anaesthetised using a 2% isoflurane mask (Zoetis). We used a CosmoScan GX (Rigaku Analytical Devices, Tokyo, Japan) equipped with a dedicated small-animal camera. The settings for each acquisition were as follows: 90 kV, 88 µA, field-of view 72 mm, pixel size 144 µm, and acquisition duration 4 minutes. Image reconstruction was with both soft and hard filters. ViVoquant™ software (Invicro, Needham Heights, MA, USA) was used for post-processing. Figure 1 shows the in-vivo micro-CT images of a rabbit embolized with 12.5% Glubran ® 2. Ex-vivo image acquisition The micro-CT component of the NanoSPECT/CT Plus small-animal camera (Bioscan, Washington DC, USA) was used for imaging. Acquisition parameters were as follows: 55 kV; exposure time, 1000 ms for each of the 240 projections; axial range, 40–50 mm; and step size, 1. The scan acquisition time was 6 to 9 minutes. Bioscan image processing software was used for image reconstruction, with application of a cone-beam filtered-backprojection algorithm to generate image slices with a voxel size of 36 × 36 × 73 µm³. Each reconstructed slice was post-processed using ViVoquant™ software (Invicro). Objective evaluation: quantitative parameters To assess depth of glue penetration, we measured the cast-to-capsule distance (mm) at the upper pole, mid-region, and lower pole of each kidney. Segmentation started at the first bifurcation of the renal artery. This technique minimises variability in cast volume measurement due to differences in the length of the extra-renal artery included in the sample [ 6 ]. Cast segmentation was based on the attenuation level with three categories (1000–1300 HU, > 1300–1600 HU, and > 1600 HU) chosen to account for the high attenuation of LUF, which can create artifacts. To reduce variability due to differences in animal characteristics such as weight and age, we computed the ratio of cast volume over renal parenchyma volume. A cast attenuation ≥ 1300 HU was selected for comparing ratios, based on our previous experience [ 9 ]. Subjective evaluation: semi-quantitative parameters Image quality To assess image quality across the different micro-CTs, we used a 5-point Likert scale to measure noise (1, unacceptable; 2, above-average; 3, average; 4, below-average; and 5, minimal). Disagreements were resolved by consensus. Embolisation assessment We used a semi-quantitative scale to assess depth of glue penetration: 1, main renal artery and its first branches; 2, interlobar artery; 3 corticomedullary junction; 4, deep cortical interlobular arteries; and 5, superficial cortical interlobular arteries. Cast fragmentation was scored 0 (none), 1 (slight), or 2 (marked). Cast heterogeneity, defined as the presence of decreased attenuation within the glue cast, was evaluated in the first three of the five above-described penetration zones using a 0–4 scale (0, homogeneous; and 1, 2, 3, and 4, hypoattenuation in < 25%, 25–50%, 50–75%, and ≥ 75% of the cast, respectively). Cast heterogeneity proved difficult to assess in the small distal arteries and we consequently used only the scores for the first two glue-penetration zones in the statistical analysis. Finally, we assessed overall cast resorption on the micro-CT at one month, as follows: 0, none; 1, moderate; and 2, marked. Magnetic resonance imaging MRI scans were performed immediately after embolisation (M0) and one month later, just before the animal was euthanised, to assess the persistence of arterial occlusion over time and the changes in the parenchyma. A Biospec 4.7 T preclinical MRI (Bruker, Billerica, MA, USA) machine adapted for small animals was used with 2D coronal T1 ultra-fast dynamic sequences acquired at the early arterial phase to visualize progression of the contrast bolus along the vascular tree. The images were reconstructed using 3DSlicer software (V5 slicer.org). Histopathological evaluation One month after the embolisation, the animal was euthanised under general anaesthesia with an intravenous bolus of Euthasol (0.34 mL/kg, Med-Vet International, Mettawa, IL, USA). Each renal artery/kidney unit was harvested and rapidly fixed in 10% neutral buffered formalin solution. Fixed samples were then sectioned and embedded in paraffin. Longitudinal sections of each kidney at two different levels were prepared and stained with haematoxylin-eosin. The 12 resulting histological slides were evaluated by a pathologist blinded to the characteristics of the procedure. For each slide, the pathologist assessed arterial lumen dilation (0, none; 1, mild; 2, moderate; 3, severe). Intimal arteritis was defined as the presence of inflammatory cells, primarily lymphocytes and monocytes, in the subendothelial compartment of one or more arteries and was quantified using the Banff 97 scale (0, no arteritis; 1, mild intimal arteritis; 2, marked intimal arteritis with loss of ≥ 25% of the luminal area; and 3, transmural arteritis and/or fibrinoid arterial changes [ 11 , 12 ]. Intimal necrosis was evaluated as follows: 0, none; 1, focal intimal necrosis with smooth muscle vacuolisation; and 2, multifocal necrosis with expanded and flattened intima. Arterial occlusion by glue was assessed as 0, no occlusion; 1, incomplete occlusion; 2, nearly complete occlusion; and 3, complete occlusion. The percentage of necrotised parenchyma was calculated. Glue penetration was evaluated based on the five above-described penetration zones. For each parameter and each kidney, the highest value was collected. Whether revascularization had occurred from the capsule was documented, and the thickness of the renal parenchyma occupied by newly formed blood capillaries was measured (µm) from the capsule surface. Statistical analysis The Shapiro-Wilk test showed a skewed distribution for some variables. We therefore described all variables as median [interquartile range] (range) [ 13 ]. Semi-quantitative variables (e.g., arterial lumen dilation, intimal arteritis, intimal necrosis, and glue penetration) were handled as ordinal variables. To compare the micro-CT parameters between M0 and M1 in each rabbit, given the small sample size, we chose the non-parametric Wilcoxon test. The Mann-Whitney test was applied to compare histological data at M0 and M1. Values of p ≤ 0.05 were considered statistically significant. Statistical analyses were performed using DATAtab: DATAtab Team (2024) (Graz, Austria, https://datatab.net ) Results Embolisation procedures The renal arteries of six rabbits were embolized using either of the two glue concentrations. No instances of microcatheter adhesion to the vessel walls or other intra-procedural complications occurred. The median weight of the rabbits was 3.05 [2.68–3.67] kg. There were no significant differences between the two glue-concentration groups regarding weight, glue volume injected, or injection duration. Table 1 lists the characteristics of the rabbits and procedures. Table 1 Characteristics of the six rabbits and embolisation procedures. NBCA-MS 12.5% NBCA-MS 25% Total p value Embolised arteries, n (%) 3 (50) 3 (50) 6 (100) > 0.99 Parenchymal histological sections, n (%) 6 (50) 6 (50) 6 (100) > 0.99 Rabbit weight (kg), median [IQR] (range) 3.1 [2.89–3.39] [2.68–3.67] 3 [2.96–3.1] [2.91–3.19] 3.05 [2.93–3.17] [2.68 − 3.67] 0.17 Injected glue-mixture volume (mL), median [IQR] (range) 0.23 [0.22–0.40] (0.22–0.58) 0.25 [0.18–0.25] (0.11–0.26) 0.24 [0.22–0.25] (0.11 − 0.58) 0.42 NBCA-MS, N-butyl cyanoacrylate methacryloxysulfolane Imaging results Comparison of Micro-CT results at M0 and M1 Quantitative parameters The cast-to-kidney ratio ranged from 0.04–30.49%, and the cast-to-capsule distance from 0.08 mm to 4.38 mm. The cast-to-kidney ratios decreased significantly from M0 to M1. The cast-to-capsule distance showed a non-significant decrease between M0 and M1. Results are summarized in Table 2 . Table 2 Micro-CT findings immediately after embolization (M0) and one month later (M1). Total NBCA-MS 12.5% NBCA-MS 25% Findings M0 M1 p values a M0 M1 M0 M1 Semi-quantitative parameters, n (%) Image quality, Likert scale rating 2 1 (17) 0 0.014 1 0 0 0 3 5 (83) 0 2 0 3 0 4 0 (0) 1 (17) 0 1 0 0 5 0 (0) 5 (83) 0 2 0 3 Distality of glue penetration, n (%) Interlobular arteries of the deep cortex 5 (83) 1 (17) 0.046 2 1 3 0 Interlobular arteries of the superficial cortex 1 (17) 5 (83) 1 2 0 3 Cast fragmentation, n (%) Slight 5 (83) 0 (0) 0.025 3 0 2 0 Marked 1 (17) 6 (100) 0 3 1 3 Cast heterogeneity score, n (%) Renal artery and first branches >50% and ≤75% NA 3 (50) NA NA 1 NA 2 75–100% NA 3 (50) NA 2 NA 1 Interlobar artery >25% and ≤50% NA 1 (17) NA NA 1 NA 0 >50% and ≤75% NA 2 (33) NA 0 NA 2 75–100% NA 3 (50) NA 2 NA 1 Overall resorption, n (%) Moderate NA 2 (33) NA NA 1 NA 1 Marked NA 4 (66) NA 2 NA 2 Quantitative parameters, median [IQR] (range) Cast-to-capsule distance (mm) 2.06 [1.6–2.74] (1.49 − 4.38) 0.75 [0.29–1.31] (0.08 − 2.47) 0.116 1.56 [1.53–1.64] (1.49 − 41.71) 0.91 [0.5–1.69] (0.08 − 2.47) 2.85 [2.64–3.62] (2.42 − 4.38) 0.25 [0.39–1.01] (0.59 − 0.18) Indexed cast ratio (%) 10.6 [8.53–12.66] (1.16 − 30.49) 0.08 [0.05–0.53] (0.04 − 1.29) 0.028 12.79 [10.59–21.64] (8.38 − 30.49) 0.06 [0.06–0.08] (0.05 − 0.1) 8.96 [5.06–10.6] (1.16 − 12.24) 0.67 [0.36–0.098] (0.04 − 1.29) a Wilcoxon test NBCA-MS, N-butyl cyanoacrylate methacryloxysulfolane NA, not available Semi-quantitative parameters Image-quality Likert-scale scores for the micro-CTs were 2 or 3 at M0 and 4 or 5 at M1 ( p = 0.014). Given the higher noise levels at M0, probably ascribable to respiratory movements, cast heterogeneity was not evaluated at this time point. At M1, glue was seen in zone 5 (superficial interlobular arteries) in five kidneys and in zone 4 (deep interlobular arteries) in one kidney. Penetration was significantly more distal at M1 than at M0. Cast fragmentation was observed in all six kidneys at both M0 and M1 and was significantly more marked at M1 than at M0 ( p = 0.025). Results are summarized in Table 2 . Figure 3 shows micro-CT images at M0 and M1 of a kidney embolized with 12.5% NBCA-MS. Magnetic resonance imaging The MRIs done immediately after embolisation (M0) showed evidence of sudden parenchymal infarction indicating arterial occlusion: size was normal and the parenchyma showed no enhancement at the arterial or venous phase. Figure 4 shows an example. The findings from the in-vivo MRIs at M1 were markedly different from those at M0, with typical signs of chronic renal ischemia and parenchymal shrinkage. The contrast-enhanced sequences visualised delayed parenchymal enhancement related to neovascularisation from the capsule. Figure 5 shows an example. Histological findings Glue In all 12 samples, glue remnants were visible as amorphous plugs of eosinophilic material confined to the vascular lumen. No glue was detected outside the lumens. Granular aggregates of greyish to bluish material were seen occasionally, probably due to loss of small amounts of glue, consistent with the lack of tissue anchorage and the frequent presence of optically empty areas within the dilated vascular lumens. Alterations in arterial lumen and wall Lumen dilation was observed in all 12 samples and was severe in five. All 12 samples exhibited transmural arteritis, intimal necrosis, and complete or nearly complete occlusion of the arterial lumen. Results are summarized in Table 3 . Figure 6 shows examples of the main histological findings. Table 3 Histological findings in the six embolised kidneys (two slides per kidney). Findings NBCA-MS 12.5% NBCA-MS 25% Total p value a Arterial lumen dilation, n (%) Mild 4 (33) 3 (25) 7 (58) 0.39 Moderate to severe 2 (17) 3 (25) 5 (42) Intimal arteritis, n (%) Transmural 6 (50) 6 (50) 12 (100) > 0.99 Intimal necrosis, n (%) Multifocal 6 (50) 6 (50) 12 (100) > 0.99 Arterial occlusion, n (%) Nearly complete 3 (25) 2 (17) 5 (42) 0.70 Complete 3 (25) 4 (33) 7 (58) Distality of glue penetration Interlobular arteries of the deep cortex: zone 4 2 (17) 4 (23) 6 (50) 0.31 Interlobular arteries of the superficial cortex: zone 5 4 (33) 2 (17) 6 (50) Parenchymal inflammation, n (%) Mild 5 (42) 2 (17) 7 (58) 0.13 Marked 1 (8) 4 (33) 5 (42) Necrotic parenchyma (% of total parenchyma, median [IQR] (range) 90 [90–90] (80–90) 95 [90–100] (90–100) 90 [90–92.5] (80–100) 0.093 Revascularization from the capsule (µm), median [IQR] (range) 985 [792–1072) (350 − 1080) 850 [700–1075] (350 − 1480) 960 [700–1080] (350 − 1480) 0.94 a Mann-Whitney test NBCA-MS, N-butyl cyanoacrylate methacryloxysulfolane Glue penetration In all six kidneys, glue was observed in the interlobular arteries of the deep or superficial cortex. The glue penetrated to the mid or distal parts of the interlobular arteries (score 5) in six samples. In the remaining six samples, the score was 4, with glue present in the arcuate arteries or the proximal part of the interlobular arteries. Inflammation and host tissue reaction For most of the medium and small arteries, no reactive changes were seen in the tissue surrounding the glue casts. In contrast, the glue remnants within large, obstructed arteries (i.e., chiefly the lobar and interlobular arteries) were surrounded by a pronounced granulomatous reaction, with lymphocytes and numerous macrophages, some of which formed multinucleated giant cells, creating a foreign body-type granuloma. Renal parenchymal changes Arterial occlusion by glue was associated with extensive necrosis of the renal parenchyma. The necrosis was sometimes surrounded by small areas of mononuclear inflammatory-cell infiltration and interstitial fibrosis. In the medulla, some of the parietal tubular cells appeared hyperbasophilic with a large euchromatic nucleus, indicating active tubular regeneration. The renal capsule was thickened in some areas, and revascularization from the capsule towards the cortex was observed. The thickness of the renal parenchyma occupied by blood capillaries, measured from the capsule, varied from 350 to 1480 µm. None of the histological parameters showed significant differences between the two glue concentrations (12.5% vs. 25%). Detailed results are provided in Table 3 . Discussion Micro-CT imaging of Glubran ® 2 casts within the renal vascular system of rabbits detected notable changes over the first month following embolisation. Various degrees of partial resorption manifesting chiefly as increased fragmentation compared to baseline were seen in all kidneys. Partial resorption was similar with the 12.5% and 25% Glubran ® 2 concentrations. Importantly, in no instance did this partial resorption result in arterial recanalization: the MRI and histological findings documented the persistence of complete vessel occlusion. Micro-CT scanning provided accurate information on the consequences of Glubran ® 2 embolisation. To our knowledge, our study provides the first data on glue-cast changes over time. As expected, we found signs of renal infarction, with MRI evidence of parenchymal shrinkage predominating in the cortex [ 14 ]. The significant decrease in the cast-to-parenchyma volume ratio between M0 and M1 is consistent with a faster pace of cast resorption than of parenchymal atrophy. Alternatively, residual contrast material not yet excreted via the urinary tract may have resulted in cast-volume overestimation by the in-vivo segmentation calculations. In future studies, micro-CT may provide valuable data on vessel remodelling after glue embolisation. A major strength of our study is the assessment of a low Glubran ® 2 concentration, of 12.5%. Low concentrations are used in emerging clinical applications such as prostatic artery embolisation. In a retrospective cohort study of 103 patients with benign prostatic hyperplasia, a glue/LUF ratio of 1:8 was used, corresponding to an absolute glue concentration of 11.1%, to facilitate greater distality of penetration [ 15 ]. Good 6-month outcomes were documented. In the present study, even the low concentration of 12.5% ensured persistent arterial occlusion without cast recanalisation at M1. The histological evidence of inflammation was not significantly different between the two concentrations, in keeping with a previous study [ 16 ]. Neocapillaries developed from the renal capsule during the 1-month follow-up, as documented histologically and by the late-phase parenchymal enhancement on the MRI at M1. The degree of neovascularisation was not significantly different between the two glue concentrations. The partial resorption of the glue over the 1-month follow-up is consistent with data on the long-term degradation of NBCA after embolisation, which occurs via several mechanisms. First, hydrolysis of the cyanoacrylate ester group partially fragments the polymer. The by-products of this hydrolysis, such as formaldehyde, contribute to the local inflammation and gradual glue resorption [ 17 ]. Second, the prolonged presence of glue within tissues causes an immune response with a foreign-body-type inflammatory process [ 18 ]. A granuloma consisting of macrophages and multinucleated giant cells develops around the glue and releases lysosomal enzymes that contribute to cast resorption. Finally, fibrotic scar tissue builds up gradually, encapsulating the glue and contributing to its resorption [ 19 ]. The combination of these three mechanisms results in gradual disappearance of the glue cast. One major limitation of our study is the small sample size, with only three rabbits in each glue-concentration group, which limits the statistical power of our study and the general applicability of our findings. However, the 3Rs principles for maximising animal welfare include the use of the smallest possible number of animals. Second, the predominantly terminal nature of the renal vasculature may affect the durability of arterial occlusion. Third, we used different micro-CT machines for the in-vivo scanning at M0 and the ex-vivo scanning at M1. Fourth, the resolution of in-vivo scans was slightly lower than that of the ex-vivo scans. As a result, cast heterogeneity was evaluable on the ex-vivo but not the in-vivo images. The lower resolution in vivo is probably ascribable to the respiratory movements. Optimisation of micro-CT acquisition protocols might produce sufficient resolution to assess cast heterogeneity in vivo. Conclusions By combining micro-CT, MRI, and histology, we obtained detailed information about changes in Glubran ® 2 casts over the first month following embolisation. We documented substantial cast resorption over time, with fragmentation and dissolution in the renal parenchyma. Importantly, the histological assessments showed that cast resorption did not affect arterial occlusion, even with the low Glubran ® 2 concentration of 12.5%. Longer-term studies are needed to further characterise the durability of arterial occlusion by Glubran ® 2. Abbreviations AVM, arterio-venous malformation LUF, Lipiodol Ultra Fluid M, month NBCA, N-butyl cyanoacrylate Declarations Ethics approval and consent to participate The study protocol was approved by the local animal experimentation ethics committee (CEEA n°106, #25592) on 23 rd June 2020. The animals were housed and studied in a laboratory accredited by the French Ministry of Health for research on animal models. Requirements set forth in the 2019 updated version of the European Directive 2010/63/EU for the protection of animals used for scientific purposes were followed. Consent does not apply to this study. Consent for publication Not applicable. Availability of data and material The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests The experiments were performed at the R&D Department of the Guerbet Corporation. The rabbits and Lipiodol ® Ultra Fluid were founded by Guerbet (Villepinte, France). Guerbet had no role in data collection, analysis, or interpretation, manuscript drafting or revision. EC, AD, PR, SC are employees of Guerbet. RL serves as a consultant for Guerbet and GEM Srl. The other authors declare no conflict of interest. Funding This study was funded by R&D, Guerbet Research, 95943, Roissy Charles de Gaulle, France. Authors' contributions All authors attest that they meet the current International Committee of Medical Journal Editors (ICMJE) criteria for Authorship. RL, OC, PR, SC, AVS and POC, concepted and designed of the study. KG, EC, AD and POC performed the experiments. KG, OC and POC performed data acquisition. RL, OC, MF, PR, AVS and POC interpreted the results. SAG conducted the statistical analysis. RL and POC drafted the manuscript. All authors edited and revised the manuscript critically for important intellectual content. All authors read and approved the final version of the manuscript. Acknowledgements None. References Ko G, Choi JW, Lee N, Kim D, Hyeon T, Kim HC. Recent progress in liquid embolic agents. Biomaterials. 2022;287:121634. Comby PO, Guillen K, Chevallier O, et al. 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Granuloma formation following cyanoacrylate glue injection in peripheral veins and arteriovenous malformation. Phlebology. 2020;35:115–23. Gupta K, Vasishta RK, Dutta U, Kochhar RK, Singh K. Embolization of cyanoacrylate glue in systemic circulation in a case of hepatocellular carcinoma: An autopsy report. Diagn Pathol. 2009;4:45. Cite Share Download PDF Status: Published Journal Publication published 22 Apr, 2025 Read the published version in CVIR Endovascular → Version 1 posted Editorial decision: Minor revision 03 Apr, 2025 Reviewers agreed at journal 25 Mar, 2025 Reviewers invited by journal 25 Mar, 2025 Editor assigned by journal 19 Mar, 2025 First submitted to journal 17 Mar, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6239046","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":433660355,"identity":"c04a1f52-a509-43d3-a406-031f91797e2a","order_by":0,"name":"Romaric Loffroy","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABHUlEQVRIiWNgGAWjYNACAwYGPgbGBx+ATDkGCSDJY8AGJBkf4NXCxsBsOAPINEbSwmyA1yKYlsQGsBawGHYt5u3diZ8rCuwY2NibGZsrKg6n98/uMWB4U8AnZ87AzPYBixaZM2c3S54xSGZg4znM2HjmzOHcGXfOGDDOMWAztmxgZp6BRYuERO4GyQaDAwxsEvnHHza2Hc7dIJFj/hvol8QNB/gPY3MYUMvmnxAtyYyNQC3pBhI5BswQLczMOLRsk0TWkkBYC8/ZbZYNBsk8YL80nEk3nHEjrQDsF4PDOLSw926+2fDHTo4fGGKNDRXW8vwzkjcwvPlzTM7geDNWLTDAA6WbYQLHgNGCTwMC1MEYNcSpHwWjYBSMgpEAAJJSWGQRjJbBAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-3107-5967","institution":"CHU Dijon: Centre Hospitalier Universitaire Dijon Bourgogne","correspondingAuthor":true,"prefix":"","firstName":"Romaric","middleName":"","lastName":"Loffroy","suffix":""},{"id":433660356,"identity":"0c803e2d-f3d4-40a6-9cbc-bc6840b7d080","order_by":1,"name":"Kévin Guillen","email":"","orcid":"","institution":"CHU Dijon: Centre Hospitalier Universitaire Dijon Bourgogne","correspondingAuthor":false,"prefix":"","firstName":"Kévin","middleName":"","lastName":"Guillen","suffix":""},{"id":433660357,"identity":"647334ea-237c-4307-b229-31e029dba985","order_by":2,"name":"Olivier Chevallier","email":"","orcid":"","institution":"CHU Dijon: Centre Hospitalier Universitaire Dijon Bourgogne","correspondingAuthor":false,"prefix":"","firstName":"Olivier","middleName":"","lastName":"Chevallier","suffix":""},{"id":433660358,"identity":"e85997fa-6514-4a86-aac2-986b4ff3c5c6","order_by":3,"name":"Mohamed Fouad","email":"","orcid":"","institution":"CHU Dijon: Centre Hospitalier Universitaire Dijon Bourgogne","correspondingAuthor":false,"prefix":"","firstName":"Mohamed","middleName":"","lastName":"Fouad","suffix":""},{"id":433660359,"identity":"968ead5e-b02c-4c2f-a56f-8ea735935dc8","order_by":4,"name":"Emilie Couloumy","email":"","orcid":"","institution":"Guerbet France SA","correspondingAuthor":false,"prefix":"","firstName":"Emilie","middleName":"","lastName":"Couloumy","suffix":""},{"id":433660360,"identity":"c7af2c37-62be-4e7c-a533-a87dc3348eb0","order_by":5,"name":"Anne Dencausse","email":"","orcid":"","institution":"Guerbet France SA","correspondingAuthor":false,"prefix":"","firstName":"Anne","middleName":"","lastName":"Dencausse","suffix":""},{"id":433660361,"identity":"b671315d-37b4-4fed-8266-1665bad7fa75","order_by":6,"name":"Philippe Robert","email":"","orcid":"","institution":"Guerbet France SA","correspondingAuthor":false,"prefix":"","firstName":"Philippe","middleName":"","lastName":"Robert","suffix":""},{"id":433660362,"identity":"622c88e3-22c4-44de-b09a-494a93547e65","order_by":7,"name":"Sarah Catoen","email":"","orcid":"","institution":"Guerbet France SA","correspondingAuthor":false,"prefix":"","firstName":"Sarah","middleName":"","lastName":"Catoen","suffix":""},{"id":433660363,"identity":"7effcd43-9305-47cd-b61d-dd5e2577093f","order_by":8,"name":"Anne-Virginie Salsac","email":"","orcid":"","institution":"Compiègne University of Technology Department of Mechanical Engineering: Universite de Technologie de Compiegne departement Ingenierie mecanique","correspondingAuthor":false,"prefix":"","firstName":"Anne-Virginie","middleName":"","lastName":"Salsac","suffix":""},{"id":433660364,"identity":"f9a48ee6-6c2b-434a-95c9-c2151e2d098d","order_by":9,"name":"Serge Ludwig Aho-Glele","email":"","orcid":"","institution":"CHU Dijon: Centre Hospitalier Universitaire Dijon Bourgogne","correspondingAuthor":false,"prefix":"","firstName":"Serge","middleName":"Ludwig","lastName":"Aho-Glele","suffix":""},{"id":433660365,"identity":"12f7fea8-e9de-4021-ad0c-c0d24a0c6490","order_by":10,"name":"Pierre-Olivier Comby","email":"","orcid":"","institution":"CHU Dijon: Centre Hospitalier Universitaire Dijon Bourgogne","correspondingAuthor":false,"prefix":"","firstName":"Pierre-Olivier","middleName":"","lastName":"Comby","suffix":""}],"badges":[],"createdAt":"2025-03-16 18:19:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6239046/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6239046/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s42155-025-00549-8","type":"published","date":"2025-04-22T15:56:58+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":80106534,"identity":"6dc4d9e0-6159-4841-b5bc-04a176689161","added_by":"auto","created_at":"2025-04-08 03:30:56","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":139488,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eIn-vivo micro-CT images obtained immediately after embolization (M0).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAxial \u003cstrong\u003e(A)\u003c/strong\u003e, coronal \u003cstrong\u003e(B)\u003c/strong\u003e, and sagittal \u003cstrong\u003e(C)\u003c/strong\u003e reconstructions.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6239046/v1/5c070b9e4117e83f7b196d4e.jpg"},{"id":80106535,"identity":"d5ba2be8-a979-4eec-aa25-5dcd18ef10e5","added_by":"auto","created_at":"2025-04-08 03:30:56","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":376146,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDiagram of the experimental protocol.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6239046/v1/7598e2e0f9d030de91efb59e.jpg"},{"id":80106544,"identity":"5f48c714-cc72-48ca-98b6-22e3b2cbdcb9","added_by":"auto","created_at":"2025-04-08 03:30:56","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":175439,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMaximum intensity projection reconstructions of micro-CT scans of the same rabbit kidney embolised with 12.5% Glubran\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e®\u003c/strong\u003e\u003c/sup\u003e\u003cstrong\u003e2.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(A)\u003c/strong\u003e immediately after embolization (M0), and \u003cstrong\u003e(B)\u003c/strong\u003e one month later (M1).\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6239046/v1/7e96654b4e34b0f1c4192769.jpg"},{"id":80107088,"identity":"911272be-f834-4327-bf86-0e2d68fe51c1","added_by":"auto","created_at":"2025-04-08 03:38:56","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":160894,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMRI done immediately after embolization (M0) of the left renal artery with 25% Glubran\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e®\u003c/strong\u003e\u003c/sup\u003e\u003cstrong\u003e2.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCoronal T1 view \u003c/strong\u003eafter contrast injection at the arterial phase showing occlusion of the left renal artery with no enhancement of the left renal parenchyma.\u003c/p\u003e","description":"","filename":"Figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6239046/v1/b352bb353d442e4235bacbfa.jpg"},{"id":80106536,"identity":"49058d4e-01ab-4183-a7f0-f589366fac78","added_by":"auto","created_at":"2025-04-08 03:30:56","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":373536,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMRI done one month (M1) after embolization of the left renal artery with 25% Glubran\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e®\u003c/strong\u003e\u003c/sup\u003e\u003cstrong\u003e2.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(A) \u003c/strong\u003ecoronal T1 view after contrast injection at the early arterial phase: persistent occlusion of the left renal artery with no parenchymal enhancement. \u003cstrong\u003e(B)\u003c/strong\u003e coronal T1 view at the late venous phase: parenchymal enhancement due to subcapsular neovascularisation.\u003c/p\u003e","description":"","filename":"Figure5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6239046/v1/06ab3b9701ee36f4bbb51edc.jpg"},{"id":80107089,"identity":"b5fb083c-f340-4004-80f8-2e37d5f7c354","added_by":"auto","created_at":"2025-04-08 03:38:56","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":723039,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMain histological findings in the embolised kidneys (haematoxylin-eosin stain).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe arteries containing glue (*) were obstructed and dilated, and their walls were necrotic and flattened. Coagulative necrosis was visible in most of the renal parenchyma, with preservation of the normal architecture and ghost-like necrotic cells (°) and only a few preserved areas (top left panel). Small neocapillaries (→) were visible focally beneath the renal capsule (∆), indicating revascularisation (top right panel). Glue plugs completely obstructing some of the large vessels were surrounded by inflammatory granulomas (bottom left panel) containing activated macrophages and multinucleated giant cells (▲). A few neocapillaries with large lumens (→) were present focally, again indicating reperfusion (bottom right panel).\u003c/p\u003e","description":"","filename":"Figure6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6239046/v1/b20d33dc99cd242accf216d1.jpg"},{"id":81569625,"identity":"a7b92edc-03c5-41b3-b6c4-e3c9a6ed2f54","added_by":"auto","created_at":"2025-04-28 16:08:14","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3444728,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6239046/v1/7fddfc63-98db-4936-bdf3-3f04d6d6ec84.pdf"}],"financialInterests":"","formattedTitle":"Micro-CT and Histological Assessment of Renal Arterial Embolization with Glubran®2 Cyanoacrylate: A Medium-Term Follow-Up Study in a Rabbit Model","fulltext":[{"header":"Background","content":"\u003cp\u003eCyanoacrylate glues are widely used for transcatheter arterial embolisation because they polymerize promptly upon contact with body fluids, thereby providing prompt vessel occlusion [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. This rapid effect is crucial in several indications such as arteriovenous malformations (AVMs) and arterial bleeding [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The histological effects of cyanoacrylate glues have been extensively documented [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Acute vascular inflammation is followed by a foreign-body granulomatous reaction with macrophage infiltration and the formation of multinucleated giant cells [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAlthough cyanoacrylate glues have been proven effective in achieving vessel occlusion, evidence of partial cast resorption over time after AVM embolisation has raised concern about the durability of the occlusive effect [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Whether this partial cast resorption affects the degree of occlusion or the risk of recanalization remains unclear.\u003c/p\u003e \u003cp\u003eMicrocomputed tomography (micro-CT) provides accurate three-dimensional images of glue casts within blood vessels [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Cast distribution and changes over time can be assessed.\u003c/p\u003e \u003cp\u003eThe primary objective of this animal-model study was to perform micro-CT assessments of changes in glue casts over the first post-embolisation month and to compare micro-CT findings with histological findings at one month. The secondary objective was to look for histological evidence of persistent arterial occlusion at one month.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eAnimal model and embolisation procedure\u003c/h2\u003e \u003cp\u003e The study protocol was approved by the local animal experimentation ethics committee (CEEA n\u0026deg;106, #25592) on 23rd June 2020. We studied six, 3-month-old, female rabbits obtained from Charles River (\u0026Eacute;cully, France). For the procedure, the animals were sedated with intramuscular buprenorphine (Buprecare\u003csup\u003e\u0026reg;\u003c/sup\u003e 0.3 mg/mL, 0.17 mL/kg; Animalcare, York, UK) then anaesthetised with 2% isoflurane (IsoFlow\u003csup\u003e\u0026reg;,\u003c/sup\u003e Zoetis, Parsippany-Troy Hills, NJ, USA).\u003c/p\u003e \u003cp\u003eTwo interventional radiologists (POC and KG) performed the procedures using a monoplane angiographic system (Veradius, Philips, Amsterdam, The Netherlands). A 4-Fr introducer was inserted surgically into the femoral artery. A baseline angiogram of the abdominal aorta was obtained using a 4-Fr vertebral catheter and manual injection of the water-soluble contrast agent iobitridol (Xenetix 350, Guerbet, Villepinte, France) via a 10-mL syringe, at a flow rate of about 4 mL/s. A 2.3-Fr microcatheter (Phenom\u003csup\u003e\u0026trade;\u003c/sup\u003e 21, Medtronic, Dublin, Ireland) was then inserted co-axially into the 4-Fr catheter in the left renal artery. Special care was taken to avoid selecting ventral or dorsal branches and to ensure that the glue was injected under free-flow conditions.\u003c/p\u003e \u003cp\u003eTo prevent premature glue polymerisation, the microcatheter was first flushed with 5% glucose in a volume of at least 0.43 mL, i.e., at least the volume of the lumen. The glue-LUF mixture was injected under fluoroscopic guidance using a 5-mL syringe (Plastipak\u003csup\u003e\u0026trade;\u003c/sup\u003e, Becton Dickinson Plastic, Franklin Lakes, NJ, USA) and an automated syringe pump (Harvard Apparatus PHD 2000\u003csup\u003e\u0026trade;\u003c/sup\u003e, Holliston, MA, USA) at a standardised flow rate of 0.03 mL/s, as in previous studies [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eEmbolisation was deemed complete when reflux along the microcatheter was detected or the glue ceased to advance within the vascular tree. Either of these signs led to immediate withdrawal of the microcatheter to avoid adhesion to the vessel wall. The injected volume was computed by subtracting the volume of the microcatheter lumen (0.43 mL) from the total injected volume. The duration of the injection was recorded for each procedure.\u003c/p\u003e \u003cp\u003eThe 4-Fr introducer was removed and the puncture site was closed with sutures.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eEmbolic agent\u003c/h3\u003e\n\u003cp\u003eAll procedures were done using Glubran\u003csup\u003e\u0026reg;\u003c/sup\u003e2 glue (N-butyl-2-cyanoacrylate [NBCA] plus methacryloxysulfolane, GEM SRL, Viareggio, Italy) mixed manually with Lipiodol\u003csup\u003e\u0026reg;\u003c/sup\u003e Ultrafluid (LUF, Guerbet) at room temperature. We studied two glue concentrations, 12.5% (glue/LUF ratio, 1:7) and 25% (1:3). The mixtures at each of the two concentrations were injected under free-flow conditions into the left renal arteries of three animals.\u003c/p\u003e\n\u003ch3\u003eMicro-CT evaluation\u003c/h3\u003e\n\u003cp\u003eEach rabbit underwent an in-vivo micro-CT scan immediately after embolisation (M0). One month later (M1), the animals were euthanised and the left kidney of each was removed and imaged ex-vivo by micro-CT.\u003c/p\u003e\n\u003ch3\u003eIn-vivo image acquisition\u003c/h3\u003e\n\u003cp\u003eImmediately after embolisation, the rabbit was transported to the micro-CT room for in-vivo imaging while continuously anaesthetised using a 2% isoflurane mask (Zoetis).\u003c/p\u003e \u003cp\u003eWe used a CosmoScan GX (Rigaku Analytical Devices, Tokyo, Japan) equipped with a dedicated small-animal camera. The settings for each acquisition were as follows: 90 kV, 88 \u0026micro;A, field-of view 72 mm, pixel size 144 \u0026micro;m, and acquisition duration 4 minutes. Image reconstruction was with both soft and hard filters. ViVoquant\u0026trade; software (Invicro, Needham Heights, MA, USA) was used for post-processing. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the in-vivo micro-CT images of a rabbit embolized with 12.5% Glubran\u003csup\u003e\u0026reg;\u003c/sup\u003e2.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eEx-vivo image acquisition\u003c/h3\u003e\n\u003cp\u003eThe micro-CT component of the NanoSPECT/CT Plus small-animal camera (Bioscan, Washington DC, USA) was used for imaging. Acquisition parameters were as follows: 55 kV; exposure time, 1000 ms for each of the 240 projections; axial range, 40\u0026ndash;50 mm; and step size, 1. The scan acquisition time was 6 to 9 minutes. Bioscan image processing software was used for image reconstruction, with application of a cone-beam filtered-backprojection algorithm to generate image slices with a voxel size of 36 \u0026times; 36 \u0026times; 73 \u0026micro;m\u0026sup3;. Each reconstructed slice was post-processed using ViVoquant\u0026trade; software (Invicro).\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eObjective evaluation: quantitative parameters\u003c/h2\u003e \u003cp\u003eTo assess depth of glue penetration, we measured the cast-to-capsule distance (mm) at the upper pole, mid-region, and lower pole of each kidney. Segmentation started at the first bifurcation of the renal artery. This technique minimises variability in cast volume measurement due to differences in the length of the extra-renal artery included in the sample [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Cast segmentation was based on the attenuation level with three categories (1000\u0026ndash;1300 HU, \u0026gt;\u0026thinsp;1300\u0026ndash;1600 HU, and \u0026gt;\u0026thinsp;1600 HU) chosen to account for the high attenuation of LUF, which can create artifacts.\u003c/p\u003e \u003cp\u003eTo reduce variability due to differences in animal characteristics such as weight and age, we computed the ratio of cast volume over renal parenchyma volume. A cast attenuation\u0026thinsp;\u0026ge;\u0026thinsp;1300 HU was selected for comparing ratios, based on our previous experience [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSubjective evaluation: semi-quantitative parameters\u003c/h3\u003e\n\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eImage quality\u003c/h2\u003e \u003cp\u003eTo assess image quality across the different micro-CTs, we used a 5-point Likert scale to measure noise (1, unacceptable; 2, above-average; 3, average; 4, below-average; and 5, minimal). Disagreements were resolved by consensus.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eEmbolisation assessment\u003c/h2\u003e \u003cp\u003eWe used a semi-quantitative scale to assess depth of glue penetration: 1, main renal artery and its first branches; 2, interlobar artery; 3 corticomedullary junction; 4, deep cortical interlobular arteries; and 5, superficial cortical interlobular arteries. Cast fragmentation was scored 0 (none), 1 (slight), or 2 (marked). Cast heterogeneity, defined as the presence of decreased attenuation within the glue cast, was evaluated in the first three of the five above-described penetration zones using a 0\u0026ndash;4 scale (0, homogeneous; and 1, 2, 3, and 4, hypoattenuation in \u0026lt;\u0026thinsp;25%, 25\u0026ndash;50%, 50\u0026ndash;75%, and \u0026ge;\u0026thinsp;75% of the cast, respectively). Cast heterogeneity proved difficult to assess in the small distal arteries and we consequently used only the scores for the first two glue-penetration zones in the statistical analysis. Finally, we assessed overall cast resorption on the micro-CT at one month, as follows: 0, none; 1, moderate; and 2, marked.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eMagnetic resonance imaging\u003c/h2\u003e \u003cp\u003eMRI scans were performed immediately after embolisation (M0) and one month later, just before the animal was euthanised, to assess the persistence of arterial occlusion over time and the changes in the parenchyma. A Biospec 4.7 T preclinical MRI (Bruker, Billerica, MA, USA) machine adapted for small animals was used with 2D coronal T1 ultra-fast dynamic sequences acquired at the early arterial phase to visualize progression of the contrast bolus along the vascular tree. The images were reconstructed using 3DSlicer software (V5 slicer.org).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eHistopathological evaluation\u003c/h2\u003e \u003cp\u003eOne month after the embolisation, the animal was euthanised under general anaesthesia with an intravenous bolus of Euthasol (0.34 mL/kg, Med-Vet International, Mettawa, IL, USA). Each renal artery/kidney unit was harvested and rapidly fixed in 10% neutral buffered formalin solution. Fixed samples were then sectioned and embedded in paraffin. Longitudinal sections of each kidney at two different levels were prepared and stained with haematoxylin-eosin. The 12 resulting histological slides were evaluated by a pathologist blinded to the characteristics of the procedure.\u003c/p\u003e \u003cp\u003eFor each slide, the pathologist assessed arterial lumen dilation (0, none; 1, mild; 2, moderate; 3, severe). Intimal arteritis was defined as the presence of inflammatory cells, primarily lymphocytes and monocytes, in the subendothelial compartment of one or more arteries and was quantified using the Banff 97 scale (0, no arteritis; 1, mild intimal arteritis; 2, marked intimal arteritis with loss of \u0026ge;\u0026thinsp;25% of the luminal area; and 3, transmural arteritis and/or fibrinoid arterial changes [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Intimal necrosis was evaluated as follows: 0, none; 1, focal intimal necrosis with smooth muscle vacuolisation; and 2, multifocal necrosis with expanded and flattened intima. Arterial occlusion by glue was assessed as 0, no occlusion; 1, incomplete occlusion; 2, nearly complete occlusion; and 3, complete occlusion. The percentage of necrotised parenchyma was calculated. Glue penetration was evaluated based on the five above-described penetration zones. For each parameter and each kidney, the highest value was collected. Whether revascularization had occurred from the capsule was documented, and the thickness of the renal parenchyma occupied by newly formed blood capillaries was measured (\u0026micro;m) from the capsule surface.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe Shapiro-Wilk test showed a skewed distribution for some variables. We therefore described all variables as median [interquartile range] (range) [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Semi-quantitative variables (e.g., arterial lumen dilation, intimal arteritis, intimal necrosis, and glue penetration) were handled as ordinal variables. To compare the micro-CT parameters between M0 and M1 in each rabbit, given the small sample size, we chose the non-parametric Wilcoxon test. The Mann-Whitney test was applied to compare histological data at M0 and M1. Values of \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026le;\u0026thinsp;0.05 were considered statistically significant. Statistical analyses were performed using DATAtab: DATAtab Team (2024) (Graz, Austria, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://datatab.net\u003c/span\u003e\u003cspan address=\"https://datatab.net\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e)\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eEmbolisation procedures\u003c/h2\u003e \u003cp\u003eThe renal arteries of six rabbits were embolized using either of the two glue concentrations. No instances of microcatheter adhesion to the vessel walls or other intra-procedural complications occurred. The median weight of the rabbits was 3.05 [2.68\u0026ndash;3.67] kg. There were no significant differences between the two glue-concentration groups regarding weight, glue volume injected, or injection duration. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e lists the characteristics of the rabbits and procedures.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of the six rabbits and embolisation procedures.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNBCA-MS 12.5%\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNBCA-MS 25%\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEmbolised arteries, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParenchymal histological sections, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRabbit weight (kg), median [IQR] (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.1 [2.89\u0026ndash;3.39] [2.68\u0026ndash;3.67]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 [2.96\u0026ndash;3.1] [2.91\u0026ndash;3.19]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.05 [2.93\u0026ndash;3.17] [2.68\u0026thinsp;\u0026minus;\u0026thinsp;3.67]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInjected glue-mixture volume (mL), median [IQR] (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.23 [0.22\u0026ndash;0.40] (0.22\u0026ndash;0.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.25 [0.18\u0026ndash;0.25] (0.11\u0026ndash;0.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.24 [0.22\u0026ndash;0.25] (0.11\u0026thinsp;\u0026minus;\u0026thinsp;0.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.42\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eNBCA-MS, N-butyl cyanoacrylate methacryloxysulfolane\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eImaging results\u003c/h2\u003e \u003cdiv id=\"Sec18\" class=\"Section3\"\u003e \u003ch2\u003eComparison of Micro-CT results at M0 and M1\u003c/h2\u003e \u003cdiv id=\"Sec19\" class=\"Section4\"\u003e \u003ch2\u003eQuantitative parameters\u003c/h2\u003e \u003cp\u003eThe cast-to-kidney ratio ranged from 0.04\u0026ndash;30.49%, and the cast-to-capsule distance from 0.08 mm to 4.38 mm. The cast-to-kidney ratios decreased significantly from M0 to M1. The cast-to-capsule distance showed a non-significant decrease between M0 and M1. Results are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMicro-CT findings immediately after embolization (M0) and one month later (M1).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eNBCA-MS 12.5%\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003eNBCA-MS 25%\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFindings\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM0\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e values\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eM0\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eM1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eM0\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eM1\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"8\" nameend=\"c8\" namest=\"c1\"\u003e \u003cp\u003eSemi-quantitative parameters, n (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"8\" nameend=\"c8\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eImage quality, Likert scale rating\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e\u003cb\u003e0.014\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"8\" nameend=\"c8\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDistality of glue penetration, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInterlobular\u003c/p\u003e \u003cp\u003earteries of the\u003c/p\u003e \u003cp\u003edeep cortex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e0.046\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInterlobular\u003c/p\u003e \u003cp\u003earteries of the\u003c/p\u003e \u003cp\u003esuperficial\u003c/p\u003e \u003cp\u003ecortex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"8\" nameend=\"c8\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCast fragmentation, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSlight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e0.025\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMarked\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"8\" nameend=\"c8\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCast heterogeneity score, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"8\" nameend=\"c8\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRenal artery and first branches\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;50% and\u003c/p\u003e \u003cp\u003e\u0026le;75%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e75\u0026ndash;100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"8\" nameend=\"c8\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eInterlobar artery\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;25% and\u003c/p\u003e \u003cp\u003e\u0026le;50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;50% and\u003c/p\u003e \u003cp\u003e\u0026le;75%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e75\u0026ndash;100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"8\" nameend=\"c8\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOverall resorption, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModerate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMarked\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"8\" nameend=\"c8\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eQuantitative parameters, median [IQR] (range)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCast-to-capsule distance (mm)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.06\u003c/p\u003e \u003cp\u003e[1.6\u0026ndash;2.74] (1.49\u0026thinsp;\u0026minus;\u0026thinsp;4.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.75\u003c/p\u003e \u003cp\u003e[0.29\u0026ndash;1.31] (0.08\u0026thinsp;\u0026minus;\u0026thinsp;2.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.116\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.56\u003c/p\u003e \u003cp\u003e[1.53\u0026ndash;1.64] (1.49\u0026thinsp;\u0026minus;\u0026thinsp;41.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.91\u003c/p\u003e \u003cp\u003e[0.5\u0026ndash;1.69] (0.08\u0026thinsp;\u0026minus;\u0026thinsp;2.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.85\u003c/p\u003e \u003cp\u003e[2.64\u0026ndash;3.62] (2.42\u0026thinsp;\u0026minus;\u0026thinsp;4.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003cp\u003e[0.39\u0026ndash;1.01] (0.59\u0026thinsp;\u0026minus;\u0026thinsp;0.18)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIndexed cast ratio (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.6\u003c/p\u003e \u003cp\u003e[8.53\u0026ndash;12.66] (1.16\u0026thinsp;\u0026minus;\u0026thinsp;30.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003cp\u003e[0.05\u0026ndash;0.53]\u003c/p\u003e \u003cp\u003e(0.04\u0026thinsp;\u0026minus;\u0026thinsp;1.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.028\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12.79\u003c/p\u003e \u003cp\u003e[10.59\u0026ndash;21.64] (8.38\u0026thinsp;\u0026minus;\u0026thinsp;30.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003cp\u003e[0.06\u0026ndash;0.08] (0.05\u0026thinsp;\u0026minus;\u0026thinsp;0.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8.96\u003c/p\u003e \u003cp\u003e[5.06\u0026ndash;10.6]\u003c/p\u003e \u003cp\u003e(1.16\u0026thinsp;\u0026minus;\u0026thinsp;12.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.67\u003c/p\u003e \u003cp\u003e[0.36\u0026ndash;0.098] (0.04\u0026thinsp;\u0026minus;\u0026thinsp;1.29)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003e\u003csup\u003ea\u003c/sup\u003eWilcoxon test\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eNBCA-MS, N-butyl cyanoacrylate methacryloxysulfolane\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eNA, not available\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003eSemi-quantitative parameters\u003c/h2\u003e \u003cp\u003eImage-quality Likert-scale scores for the micro-CTs were 2 or 3 at M0 and 4 or 5 at M1 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.014). Given the higher noise levels at M0, probably ascribable to respiratory movements, cast heterogeneity was not evaluated at this time point. At M1, glue was seen in zone 5 (superficial interlobular arteries) in five kidneys and in zone 4 (deep interlobular arteries) in one kidney. Penetration was significantly more distal at M1 than at M0.\u003c/p\u003e \u003cp\u003eCast fragmentation was observed in all six kidneys at both M0 and M1 and was significantly more marked at M1 than at M0 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.025). Results are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows micro-CT images at M0 and M1 of a kidney embolized with 12.5% NBCA-MS.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003eMagnetic resonance imaging\u003c/h2\u003e \u003cp\u003eThe MRIs done immediately after embolisation (M0) showed evidence of sudden parenchymal infarction indicating arterial occlusion: size was normal and the parenchyma showed no enhancement at the arterial or venous phase. Figure\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e shows an example.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe findings from the in-vivo MRIs at M1 were markedly different from those at M0, with typical signs of chronic renal ischemia and parenchymal shrinkage. The contrast-enhanced sequences visualised delayed parenchymal enhancement related to neovascularisation from the capsule. Figure\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e shows an example.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section2\"\u003e \u003ch2\u003eHistological findings\u003c/h2\u003e \u003cdiv id=\"Sec23\" class=\"Section3\"\u003e \u003ch2\u003eGlue\u003c/h2\u003e \u003cp\u003eIn all 12 samples, glue remnants were visible as amorphous plugs of eosinophilic material confined to the vascular lumen. No glue was detected outside the lumens. Granular aggregates of greyish to bluish material were seen occasionally, probably due to loss of small amounts of glue, consistent with the lack of tissue anchorage and the frequent presence of optically empty areas within the dilated vascular lumens.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec24\" class=\"Section2\"\u003e \u003ch2\u003eAlterations in arterial lumen and wall\u003c/h2\u003e \u003cp\u003eLumen dilation was observed in all 12 samples and was severe in five. All 12 samples exhibited transmural arteritis, intimal necrosis, and complete or nearly complete occlusion of the arterial lumen. Results are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Figure\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e shows examples of the main histological findings.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eHistological findings in the six embolised kidneys (two slides per kidney).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFindings\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNBCA-MS 12.5%\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNBCA-MS 25%\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eArterial lumen dilation, n (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMild\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.39\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModerate to severe\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (42)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIntimal arteritis, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTransmural\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIntimal necrosis, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultifocal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eArterial occlusion, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNearly complete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.70\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComplete\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (58)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDistality of glue penetration\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInterlobular arteries of the deep\u003c/p\u003e \u003cp\u003ecortex: zone 4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInterlobular arteries of the superficial\u003c/p\u003e \u003cp\u003ecortex: zone 5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (50)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eParenchymal inflammation, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMild\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMarked\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (42)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNecrotic parenchyma (% of total parenchyma, median [IQR] (range)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e90 [90\u0026ndash;90]\u003c/p\u003e \u003cp\u003e(80\u0026ndash;90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95 [90\u0026ndash;100]\u003c/p\u003e \u003cp\u003e(90\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e90 [90\u0026ndash;92.5]\u003c/p\u003e \u003cp\u003e(80\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.093\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRevascularization from the capsule (\u0026micro;m), median [IQR] (range)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e985 [792\u0026ndash;1072) (350\u0026thinsp;\u0026minus;\u0026thinsp;1080)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e850 [700\u0026ndash;1075] (350\u0026thinsp;\u0026minus;\u0026thinsp;1480)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e960 [700\u0026ndash;1080]\u003c/p\u003e \u003cp\u003e(350\u0026thinsp;\u0026minus;\u0026thinsp;1480)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.94\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003ea\u003c/sup\u003eMann-Whitney test\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eNBCA-MS, N-butyl cyanoacrylate methacryloxysulfolane\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec25\" class=\"Section3\"\u003e \u003ch2\u003eGlue penetration\u003c/h2\u003e \u003cp\u003eIn all six kidneys, glue was observed in the interlobular arteries of the deep or superficial cortex. The glue penetrated to the mid or distal parts of the interlobular arteries (score 5) in six samples. In the remaining six samples, the score was 4, with glue present in the arcuate arteries or the proximal part of the interlobular arteries.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec26\" class=\"Section3\"\u003e \u003ch2\u003eInflammation and host tissue reaction\u003c/h2\u003e \u003cp\u003eFor most of the medium and small arteries, no reactive changes were seen in the tissue surrounding the glue casts. In contrast, the glue remnants within large, obstructed arteries (i.e., chiefly the lobar and interlobular arteries) were surrounded by a pronounced granulomatous reaction, with lymphocytes and numerous macrophages, some of which formed multinucleated giant cells, creating a foreign body-type granuloma.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec27\" class=\"Section3\"\u003e \u003ch2\u003eRenal parenchymal changes\u003c/h2\u003e \u003cp\u003eArterial occlusion by glue was associated with extensive necrosis of the renal parenchyma. The necrosis was sometimes surrounded by small areas of mononuclear inflammatory-cell infiltration and interstitial fibrosis. In the medulla, some of the parietal tubular cells appeared hyperbasophilic with a large euchromatic nucleus, indicating active tubular regeneration. The renal capsule was thickened in some areas, and revascularization from the capsule towards the cortex was observed. The thickness of the renal parenchyma occupied by blood capillaries, measured from the capsule, varied from 350 to 1480 \u0026micro;m.\u003c/p\u003e \u003cp\u003eNone of the histological parameters showed significant differences between the two glue concentrations (12.5% vs. 25%). Detailed results are provided in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eMicro-CT imaging of Glubran\u003csup\u003e\u0026reg;\u003c/sup\u003e2 casts within the renal vascular system of rabbits detected notable changes over the first month following embolisation. Various degrees of partial resorption manifesting chiefly as increased fragmentation compared to baseline were seen in all kidneys. Partial resorption was similar with the 12.5% and 25% Glubran\u003csup\u003e\u0026reg;\u003c/sup\u003e2 concentrations. Importantly, in no instance did this partial resorption result in arterial recanalization: the MRI and histological findings documented the persistence of complete vessel occlusion.\u003c/p\u003e \u003cp\u003eMicro-CT scanning provided accurate information on the consequences of Glubran\u003csup\u003e\u0026reg;\u003c/sup\u003e2 embolisation. To our knowledge, our study provides the first data on glue-cast changes over time. As expected, we found signs of renal infarction, with MRI evidence of parenchymal shrinkage predominating in the cortex [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The significant decrease in the cast-to-parenchyma volume ratio between M0 and M1 is consistent with a faster pace of cast resorption than of parenchymal atrophy. Alternatively, residual contrast material not yet excreted via the urinary tract may have resulted in cast-volume overestimation by the in-vivo segmentation calculations. In future studies, micro-CT may provide valuable data on vessel remodelling after glue embolisation.\u003c/p\u003e \u003cp\u003eA major strength of our study is the assessment of a low Glubran\u003csup\u003e\u0026reg;\u003c/sup\u003e2 concentration, of 12.5%. Low concentrations are used in emerging clinical applications such as prostatic artery embolisation. In a retrospective cohort study of 103 patients with benign prostatic hyperplasia, a glue/LUF ratio of 1:8 was used, corresponding to an absolute glue concentration of 11.1%, to facilitate greater distality of penetration [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Good 6-month outcomes were documented. In the present study, even the low concentration of 12.5% ensured persistent arterial occlusion without cast recanalisation at M1. The histological evidence of inflammation was not significantly different between the two concentrations, in keeping with a previous study [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNeocapillaries developed from the renal capsule during the 1-month follow-up, as documented histologically and by the late-phase parenchymal enhancement on the MRI at M1. The degree of neovascularisation was not significantly different between the two glue concentrations.\u003c/p\u003e \u003cp\u003eThe partial resorption of the glue over the 1-month follow-up is consistent with data on the long-term degradation of NBCA after embolisation, which occurs via several mechanisms. First, hydrolysis of the cyanoacrylate ester group partially fragments the polymer. The by-products of this hydrolysis, such as formaldehyde, contribute to the local inflammation and gradual glue resorption [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Second, the prolonged presence of glue within tissues causes an immune response with a foreign-body-type inflammatory process [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. A granuloma consisting of macrophages and multinucleated giant cells develops around the glue and releases lysosomal enzymes that contribute to cast resorption. Finally, fibrotic scar tissue builds up gradually, encapsulating the glue and contributing to its resorption [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The combination of these three mechanisms results in gradual disappearance of the glue cast.\u003c/p\u003e \u003cp\u003eOne major limitation of our study is the small sample size, with only three rabbits in each glue-concentration group, which limits the statistical power of our study and the general applicability of our findings. However, the 3Rs principles for maximising animal welfare include the use of the smallest possible number of animals. Second, the predominantly terminal nature of the renal vasculature may affect the durability of arterial occlusion. Third, we used different micro-CT machines for the in-vivo scanning at M0 and the ex-vivo scanning at M1. Fourth, the resolution of in-vivo scans was slightly lower than that of the ex-vivo scans. As a result, cast heterogeneity was evaluable on the ex-vivo but not the in-vivo images. The lower resolution in vivo is probably ascribable to the respiratory movements. Optimisation of micro-CT acquisition protocols might produce sufficient resolution to assess cast heterogeneity in vivo.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eBy combining micro-CT, MRI, and histology, we obtained detailed information about changes in Glubran\u003csup\u003e\u0026reg;\u003c/sup\u003e2 casts over the first month following embolisation. We documented substantial cast resorption over time, with fragmentation and dissolution in the renal parenchyma. Importantly, the histological assessments showed that cast resorption did not affect arterial occlusion, even with the low Glubran\u003csup\u003e\u0026reg;\u003c/sup\u003e2 concentration of 12.5%. Longer-term studies are needed to further characterise the durability of arterial occlusion by Glubran\u003csup\u003e\u0026reg;\u003c/sup\u003e2.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAVM, arterio-venous malformation\u003c/p\u003e\n\u003cp\u003eLUF, Lipiodol Ultra Fluid\u003c/p\u003e\n\u003cp\u003eM, month\u003c/p\u003e\n\u003cp\u003eNBCA, N-butyl cyanoacrylate\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEthics approval and consent to participate\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol was approved by the local animal experimentation ethics committee (CEEA n°106, #25592) on 23\u003csup\u003erd\u0026nbsp;\u003c/sup\u003eJune 2020. The animals were housed and studied in a laboratory accredited by the French Ministry of Health for research on animal models. Requirements set forth in the 2019 updated version of the European Directive 2010/63/EU for the protection of animals used for scientific purposes were followed. Consent does not apply to this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eConsent for publication\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAvailability of data and material\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCompeting interests\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe experiments were performed at the R\u0026amp;D Department of the Guerbet Corporation. The rabbits and Lipiodol\u003csup\u003e®\u003c/sup\u003e Ultra Fluid were founded by Guerbet (Villepinte, France). Guerbet had no role in data collection, analysis, or interpretation, manuscript drafting or revision. EC, AD, PR, SC are employees of Guerbet. RL serves as a consultant for Guerbet and GEM Srl. The other authors declare no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was funded by R\u0026amp;D, Guerbet Research, 95943, Roissy Charles de Gaulle, France.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAuthors' contributions\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors attest that they meet the current International Committee of Medical Journal Editors (ICMJE) criteria for Authorship. RL, OC, PR, SC, AVS and POC, concepted and designed of the study. KG, EC, AD and POC performed the experiments. KG, OC and POC performed data acquisition. RL, OC, MF, PR, AVS and POC interpreted the results. SAG conducted the statistical analysis. RL and POC drafted the manuscript. All authors edited and revised the manuscript critically for important intellectual content. All authors read and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAcknowledgements\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKo G, Choi JW, Lee N, Kim D, Hyeon T, Kim HC. Recent progress in liquid embolic agents. Biomaterials. 2022;287:121634. \u003c/li\u003e\n\u003cli\u003eComby PO, Guillen K, Chevallier O, et al. Endovascular use of cyanoacrylate-lipiodol mixture for peripheral embolization: Properties, techniques, pitfalls, and applications. J Clin Med. 2021;10:4320. \u003c/li\u003e\n\u003cli\u003ePollak JS, White RI. The use of cyanoacrylate adhesives in peripheral embolization. J Vasc Interv Radiol. 2001;12:907\u0026ndash;13. \u003c/li\u003e\n\u003cli\u003eWhite RI, Strandberg JV, Gross GS, Barth KH. Therapeutic embolization with long-term occluding agents and their effects on embolized tissues. Radiology. 1977;125:677\u0026ndash;87. \u003c/li\u003e\n\u003cli\u003eVinters HV, Galil KA, Lundie MJ, Kaufmann JC. The histotoxicity of cyanoacrylates. A selective review. Neuroradiology. 1985;27:279\u0026ndash;91. \u003c/li\u003e\n\u003cli\u003eLevrier O, Mekkaoui C, Rolland PH, et al. Efficacy and low vascular toxicity of embolization with radical versus anionic polymerization of n-butyl-2-cyanoacrylate (NBCA). An experimental study in the swine. J Neuroradiol. 2003;30:95\u0026ndash;102. \u003c/li\u003e\n\u003cli\u003eBrothers MF, Kaufmann JC, Fox AJ, Deveikis JP. N-Butyl 2-cyanoacrylate--substitute for IBCA in interventional neuroradiology: Histopathologic and polymerization time studies. AJNR Am J Neuroradiol. 1989;10:777\u0026ndash;86. \u003c/li\u003e\n\u003cli\u003eRao VR, Mandalam KR, Gupta AK, Kumar S, Joseph S. Dissolution of isobutyl 2-cyanoacrylate on long-term follow-up. AJNR Am J Neuroradiol. 1989;10:135\u0026ndash;41. \u003c/li\u003e\n\u003cli\u003eGuillen K, Comby PO, Salsac AV, et al. X-ray microtomography to assess determinants of in vivo n-butyl cyanoacrylate Glubran\u003csup\u003e\u0026reg;\u003c/sup\u003e2 polymerization: A rabbit-model study. Biomedicines. 2022;10:2625. \u003c/li\u003e\n\u003cli\u003eComby PO, Dencausse A, Robert P, et al. Blocked-flow vs. free-flow cyanoacrylate glue embolization: Histological differences in an in vivo rabbit renal artery model. Diagn Interv Imaging. 2024;105:137\u0026ndash;43. \u003c/li\u003e\n\u003cli\u003eRacusen LC, Solez K, Colvin RB, et al. The Banff 97 working classification of renal allograft pathology. Kidney Int. 1999;55:713\u0026ndash;23. \u003c/li\u003e\n\u003cli\u003eRoufosse C, Simmonds N, Clahsen-van Groningen M, et al. A 2018 Reference guide to the Banff classification of renal allograft pathology. Transplantation. 2018;102:1795\u0026ndash;814. \u003c/li\u003e\n\u003cli\u003eBarat M, Jannot AS, Dohan A, Soyer P. How to report and compare quantitative variables in a radiology article. Diagn Interv Imaging. 2022;103:571\u0026ndash;3. \u003c/li\u003e\n\u003cli\u003eCylwik B, Darewicz J, Karasewicz B. Morphometric and histological examinations of dog kidneys after embolization of the renal artery with the cyanoacrylic glue \u0026ldquo;Chirurcoll-Polfa.\u0026rdquo; Int Urol Nephrol. 1985;17:303\u0026ndash;9.\u003c/li\u003e\n\u003cli\u003eLoffroy R, Quirantes A, Guillen K, et al. Prostate artery embolization using n-butyl cyanoacrylate glue for symptomatic benign prostatic hyperplasia: A six-month outcome analysis in 103 patients. Diagn Interv Imaging. 2024;105:129\u0026ndash;36. \u003c/li\u003e\n\u003cli\u003eSadato A, Wakhloo AK, Hopkins LN. Effects of a mixture of a low concentration of n- butylcyanoacrylate and ethiodol on tissue reactions and the permanence of arterial occlusion after embolization. Neurosurgery. 2000;47:1197\u0026ndash;203. \u003c/li\u003e\n\u003cli\u003eMontanaro L, Arciola CR, Cenni E, et al. Cytotoxicity, blood compatibility and antimicrobial activity of two cyanoacrylate glues for surgical use. Biomaterials. 2001;22:59\u0026ndash;66. \u003c/li\u003e\n\u003cli\u003eParsi K, Kang M, Yang A, Kossard S. Granuloma formation following cyanoacrylate glue injection in peripheral veins and arteriovenous malformation. Phlebology. 2020;35:115\u0026ndash;23. \u003c/li\u003e\n\u003cli\u003eGupta K, Vasishta RK, Dutta U, Kochhar RK, Singh K. Embolization of cyanoacrylate glue in systemic circulation in a case of hepatocellular carcinoma: An autopsy report. Diagn Pathol. 2009;4:45. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"cvir-endovascular","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cire","sideBox":"Learn more about [CVIR Endovascular](https://www.springer.com/journal/42155)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/cire/default.aspx","title":"CVIR Endovascular","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Transcatheter arterial embolisation, N-butyl cyanoacrylate glue, Animal model, Medium-term outcomes.","lastPublishedDoi":"10.21203/rs.3.rs-6239046/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6239046/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eCyanoacrylate glues are widely used in interventional radiology as effective embolic agents due to their rapid polymerization and ability to achieve vessel occlusion. Nonetheless, concern remains regarding cast stability and potential recanalization over time. This study used multiple modalities to evaluate the medium-term outcomes of Glubran\u003csup\u003e\u0026reg;\u003c/sup\u003e2 glue (methacryloxysulfolane and N butyl cyanoacrylate) embolisation in a rabbit renal-artery model.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThe left renal arteries of six rabbits were embolized with 12.5% or 25% Glubran\u003csup\u003e\u0026reg;\u003c/sup\u003e2. In-vivo micro-CT scans were performed immediately after embolisation (M0) and ex-vivo scans and a histological assessment were done at one month (M1). Magnetic resonance imaging (MRI) was done at M1 to assess arterial occlusion and parenchymal changes. Quantitative and semi-quantitative parameters reflecting glue distribution, cast integrity, and tissue response were analysed. Statistical comparisons used non-parametric tests.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAll six embolisations were completed without complications. Micro-CT at M1 revealed significant cast resorption and fragmentation with both concentrations, but with no evidence of arterial recanalization. MRI and histology confirmed the persistent vascular occlusion with chronic ischemic changes in the renal parenchyma. Compensatory neovascularization from the renal capsule was observed, with no significant differences in histological inflammation between the two concentrations. Glue casts remained within the arterial lumens and were often surrounded by granulomatous inflammation.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eGlubran\u003csup\u003e\u0026reg;\u003c/sup\u003e2 was effective for renal artery embolisation, even at a low concentration of 12.5%: despite partial cast resorption, the arteries remained occluded. Micro-CT proved to be a powerful tool for assessing changes in glue casts. Longer-term studies are warranted to further assess vascular remodelling and occlusion durability.\u003c/p\u003e","manuscriptTitle":"Micro-CT and Histological Assessment of Renal Arterial Embolization with Glubran®2 Cyanoacrylate: A Medium-Term Follow-Up Study in a Rabbit Model","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-08 03:30:52","doi":"10.21203/rs.3.rs-6239046/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Minor revision","date":"2025-04-03T06:29:46+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2025-03-25T17:34:29+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-03-25T09:49:27+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-03-19T09:05:09+00:00","index":"","fulltext":""},{"type":"submitted","content":"CVIR Endovascular","date":"2025-03-17T10:54:46+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"cvir-endovascular","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cire","sideBox":"Learn more about [CVIR Endovascular](https://www.springer.com/journal/42155)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/cire/default.aspx","title":"CVIR Endovascular","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"500672ca-d7a4-42e6-8786-4135195dd176","owner":[],"postedDate":"April 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-04-28T16:01:13+00:00","versionOfRecord":{"articleIdentity":"rs-6239046","link":"https://doi.org/10.1186/s42155-025-00549-8","journal":{"identity":"cvir-endovascular","isVorOnly":false,"title":"CVIR Endovascular"},"publishedOn":"2025-04-22 15:56:58","publishedOnDateReadable":"April 22nd, 2025"},"versionCreatedAt":"2025-04-08 03:30:52","video":"","vorDoi":"10.1186/s42155-025-00549-8","vorDoiUrl":"https://doi.org/10.1186/s42155-025-00549-8","workflowStages":[]},"version":"v1","identity":"rs-6239046","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6239046","identity":"rs-6239046","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}