WEB shape modifications: angiography-histopathology correlations in rabbits.

BACKGROUND: WEB Shape Modification (WSM) over time is frequent after aneurysm treatment. In this study, we explored the relationship between histopathological changes and angiographic evolution over time in experimental aneurysms in rabbits treated with the Woven EndoBridge (WEB) procedure. METHODS: Quantitative WSM was assessed using flat-panel computed tomography (FPCT) during follow-up by calculating height and width ratio (HR, WR), defined as the ratio between either measurement at an index time point and the measurement immediately after WEB implantation. The index time point varied from 1 day to 6 months. HR and WR were evaluated with angiographic and histopathological assessments of aneurysm healing. RESULTS: Final HR of devices varied from 0.30 to 1.02 and final WR varied from 0.62 to 1.59. Altogether, at least 5% of HR and WR variations were observed in 37/40 (92.5%) and 28/40 (70%) WEB devices, respectively, at the time of final assessment. There was no significant correlation between complete or incomplete occlusion groups and HR or WR (p=0.15 and p=0.43). Histopathological analysis revealed a significant association between WR and aneurysm healing and fibrosis 1 month following aneurysm treatment (both p<0.05). CONCLUSION: Using longitudinal FPCT assessment, we observed that WSM affects both the height and width of the WEB device. No significant association was found between WSM and aneurysm occlusion status. Although presumably a multifactorial phenomenon, the histopathological analysis highlighted a significant association between width variations, aneurysm healing and fibrosis in the first month following aneurysm treatment.

Comparison of arterial wall integration of different flow diverters in rabbits: The CICAFLOW study.

BACKGROUND AND PURPOSE: New coated flow diverters (FDs) claim antithrombotic properties and increased arterial wall integration. The aim of this study is to compare in vivo endothelial coverage of coated and uncoated FD in the context of different antiplatelet regimens. METHODS: Different FDs (Silk Vista - SV, Pipeline with Shield technology - PED shield and Surpass Evolve - SE) were implanted in the aorta of rabbits, all 3 in each animal with 3 different antiplatelet regimens: no antiplatelet therapy, aspirin alone, or aspirin and ticagrelor. Four weeks after FD implantation, angiography, flat-panel CT, and optical coherence tomography (OCT) were performed before harvesting the aorta. Extensive histopathology analyses were performed including environmental scanning electron microscopy (ESEM), multiphoton microscopy (MPM) and histological staining with qualitative and/or quantitative assessment of device coverage. RESULTS: All 23 FDs that were implanted remained patent without hyperplasia. Qualitative stent coverage assessment revealed that there were no statistically significant differences between the FD groups (p = 0.19, p = 0.45, p = 0.40, and p = 0.84 for OCT, ESEM, MPM and histology, respectively). Quantitative neointimal measurement of histological sections also showed similar results in all 3 FD groups (p = 0.70). However, there were significant differences between the 3 groups of antiplatelet regimens (p = 0.07) with a higher rate in the no antiplatelet group (p = 0.05 versus aspirin alone and p = 0.03 versus aspirin and ticagrelor). CONCLUSION: Our study provides evidence that FD integration into the arterial wall is similar with coated (PED shield) and uncoated devices (SV, SE), regardless of the antiplatelet regimen. FD integration with specific surface coverage should be promoted. TRIAL REGISTRATION: APAFIS #2022011215518538.

Fucoidan-coated coils improve healing in a rabbit elastase aneurysm model.

BACKGROUND: Recanalization of coiled aneurysms remains unresolved. To limit aneurysm recanalization after embolization with coils, we propose an innovative approach to optimize aneurysm healing using fucoidan-coated coils. OBJECTIVE: To evaluate the short-term efficacy and long-term safety of the new coil system with conventional angiography, histology, and multiphoton microscopy for follow-up of fibrosis and neointima formation. METHODS: We conducted a feasibility study on rabbit elastase-induced aneurysms. Embolization was carried out with bare platinum coils, fucoidan-coated coils, or dextran-coated coils. Aneurysms were controlled after 1 month by digital subtraction angiography (DSA). Aneurysm samples were collected and processed for histological analysis. Aneurysm healing and fibrosis were measured by quantifying collagen according to the histological healing score by combining standard light microscopy and multiphoton imaging. We divided 27 rabbits into three groups: bare platinum group, fucoidan group, and dextran group as controls. RESULTS: Angiographic grading showed a trend toward less recanalization in the fucoidan group, although there were no significant differences among the three groups (P=0.21). Histological healing was significantly different according to the presence of more collagen in the neck area of aneurysms in the fucoidan group versus the bare platinum group (P=0.011), but not in the dextran group. Histological index was significantly better at the aneurysm neck in the fucoidan group than in the bare platinum group (P=0.004). Collagen organization index was also significantly better in the fucoidan group than in the bare platinum group (P=0.007). CONCLUSION: This proof-of-concept study demonstrated the feasibility and efficacy of treatment with fucoidan-coated coils to improve aneurysm healing. The results in this rabbit in vivo model showed that fucoidan-coated coils have the potential to improve healing following endovascular treatment.

Bioactive refinement for endosaccular treatment of intracranial aneurysms.

Endovascular treatment is the first-line therapy for most intracranial aneurysms; however, recanalisation remains a major limitation. Developments in bioengineering and material science have led to a novel generation of coil technologies for aneurysm embolisation that address clinical challenges of aneurysm recurrence. This review presents an overview of modified surface coil technologies and summarises the state of the art regarding their efficacy and limitations based on experimental and clinical results. We also present potential perspectives to develop biologically optimised devices.

212Pb α-Radioimmunotherapy Targeting CD38 in Multiple Myeloma: A Preclinical Study.

Multiple myeloma (MM) is a plasma cell cancer and represents the second most frequent hematologic malignancy. Despite new treatments and protocols, including high-dose chemotherapy associated with autologous stem cell transplantation, the prognosis of MM patients is still poor. α-radioimmunotherapy (α-RIT) represents an attractive treatment strategy because of the high-linear-energy transfer and short pathlength of α-radiation in tissues, resulting in high tumor cell killing and low toxicity to surrounding tissues. In this study, we investigated the potential of α-RIT with 212Pb-daratumumab (anti-hCD38), in both in vitro and in vivo models, as well as an antimouse CD38 antibody using in vivo models. Methods: Inhibition of cell proliferation after incubation of the RPMI8226 cell line with an increasing activity (0.185-3.7 kBq/mL) of 212Pb-isotypic control or 212Pb-daratumumab was evaluated. Biodistribution was performed in vivo by SPECT/CT imaging and after death. Dose-range-finding and acute toxicity studies were conducted. Because daratumumab does not bind the murine CD38, biodistribution and dose-range finding were also determined using an antimurine CD38 antibody. To evaluate the in vivo efficacy of 212Pb-daratumumab, mice were engrafted subcutaneously with 5 × 106 RPMI8226 cells. Mice were treated 13 d after engraftment with an intravenous injection of 212Pb-daratumumab or control solution. Therapeutic efficacy was monitored by tumor volume measurements and overall survival. Results: Significant inhibition of proliferation of the human myeloma RPMI8226 cell line was observed after 3 d of incubation with 212Pb-daratumumab, compared with 212Pb-isotypic control or cold antibodies. Biodistribution studies showed a specific tumoral accumulation of daratumumab. No toxicity was observed with 212Pb-daratumumab up to 370 kBq because of lack of cross-reactivity. Nevertheless, acute toxicity experiments with 212Pb-anti-mCD38 established a toxic activity of 277.5 kBq. To remain within realistically safe treatment activities for efficacy studies, mice were treated with 185 kBq or 277.5 kBq of 212Pb-daratumumab. Marked tumor growth inhibition compared with controls was observed, with a median survival of 55 d for 277.5 kBq of 212Pb-daratumumab instead of 11 d for phosphate-buffered saline. Conclusion: These results showed 212Pb-daratumumab to have efficacy in xenografted mice, with significant tumor regression and increased survival. This study highlights the potency of α-RIT in MM treatment.