Kadirvel, Ram

Background and purpose New Zealand White Rabbits are a useful preclinical model for neurovascular research. Inducing right common carotid artery aneurysms in New Zealand White Rabbits gives researchers the ability to test neurovascular devices in vivo. This study takes advantage of archived angiograms to obtain vascular measurements of interest for future research in rabbit models. Methods Rabbit angiograms from endovascular studies conducted in-house between 2005 and 2024 were analyzed using ImageJ at points of interest along the thoracic and abdominal aorta. Using scale references, the diameters of various New Zealand White Rabbit (2.5–3.5 kg) arteries were measured for aneurysm models and controls. Anatomic vascular variations were categorized and recorded. Results Measurable artery diameters at 39 points of interest were recorded for 170 female New Zealand White Rabbits. Type 1 vascular anatomy was the most common rabbit aortic arch, characterizing 85% of identifiable rabbit anatomies in this study. Conclusion By making these measurements available, this study simplifies future neurovascular studies, allowing for vasculature to be selected by size depending on the application. Additionally, the study offers insight into the relationship between elastase-induced aneurysms and surrounding vasculature size and draws size comparisons between some key arteries of interest.

Background The first-pass effect (FPE) refers to the complete or near-complete revascularization with a single pass of mechanical thrombectomy devices. While previous claims suggest a link between larger catheters and the effectiveness of contact aspiration (CA) thrombectomy, no extensive research has confirmed if larger distal inner diameter (ID) catheters achieve higher FPE rates. Methods We searched PubMed, Scopus, and Web of Science to assess the impact of aspiration catheter distal ID size on FPE. The primary outcome was FPE rate, defined as thrombolysis in cerebral ischemia (TICI) grades 2c-3 at first pass, and the secondary outcome was modified FPE (TICI 2b-3 in a single pass). Aspiration catheters were categorized based on distal ID: 0.060–0.069 (medium bore), 0.070–0.074 (large bore), and greater than 0.074 inches (super-large bore). Rates of FPE were pooled using random effect models and compared using a Chi-square test. Results Our study included 34 articles with 4831 patients. FPE rates were 27.7% (95% CI, 15.1–45.3) for medium bore, 46.6% (95% CI, 33.7–59.9) for large, and 58.3% (95% CI, 44.8–70.7) for super-large catheters. The FPE rate was significantly higher for super-large bore catheters compared with other groups (χ² = 7.26, p = 0.03). A similar trend was observed for modified FPE rates, which were 51.1% (95% CI, 45.3–56.8) for medium bore, 60.0% (95% CI, 52.8–66.8) for large bore, and 80% (95% CI, 56.3–94.2) for super-large bore catheters (χ² = 8.14, p = 0.03). Conclusion Our analysis indicates that larger CA catheters are correlated with higher FPE rates.

Objective Aneurysm wall enhancement (AWE) is a potential biomarker of inflammation within the aneurysm wall that has been correlated with a higher risk of rupture. Aspirin (ASA) may decrease AWE due to its anti-inflammatory properties. We aimed to assess the effect of ASA on AWE in an animal model and a cohort of patients with unruptured intracranial aneurysms (UIAs). Methods Three rabbits with elastase-induced aneurysms were exposed to ASA for 8 weeks and three rabbits were used as controls. 3 T high-resolution magnetic resonance imaging (HR-MRI) was performed at 7 days and 8 weeks to evaluate changes in AWE through histological and immunohistological analyses. Additionally, we evaluated AWE in patients who underwent imaging with a 3 T HR-MRI protocol. ASA exposure was defined as daily intake of 81 mg for at least six months prior to HR-MRI. AWE was quantified using three-dimensional AWE maps and histograms. Results Among rabbits exposed to ASA, the mean AWE was lower at 8 weeks compared to the controls (2.11 vs 2.15, p = 0.13). Immunostaining of the aneurysm wall in rabbits that received ASA revealed a reduced expression of CD68 + or cyclooxygenase-2 + cells, compared to the controls. A total of 99 patients with 120 UIAs were included in the HR-MRI analysis of UIAs. UIAs exposed to ASA (22/120) had significantly lower median AWE than those that were not exposed (0.60 vs 0.72, p = 0.032). Conclusion ASA therapy is associated with an objective reduction in AWE, suggesting a potential role in lowering the risk of aneurysm rupture.

We have developed a cost-effective method to study the fate of stents, particularly flow diverter stents placed in the abdominal aorta, in a rat model. This technique utilizes (caudal) tail artery access,1–5 thereby avoiding the need for surgical exposure of the femoral or carotid arteries and reducing procedural invasiveness,6 7 aligning with the principles of refinement and reduction in animal research.7 This approach may be particularly beneficial for studies requiring multiple or iterative vascular access. The use of ultrasound guidance further reduces costs and infrastructure requirements by eliminating the need for specialized angiography suites.8 This makes this technique accessible to a broader range of research settings, promoting wider adoption and collaboration in the field of endovascular research. A detailed demonstration of this method is provided in the accompanying educational video (video 1). Video 1 -Technical video describing the tail artery access and flow diverter deployment using ultrasound guidance.

Background Left ventricular assist devices (LVADs) are used as definitive therapy or as a bridge to heart transplant in patients with advanced heart failure. Thromboembolic complications such as acute ischemic stroke (AIS) are common among patients with LVAD support. This study aims to evaluate the current evidence on the efficacy and safety of mechanical thrombectomy (MT) in patients with AIS due to large vessel occlusions (LVO) and LVAD-support. Methods A comprehensive systematic review was conducted in PubMed, Embase, and Scopus to find observational studies with reports of ≥5 MTs in adult patients with LVAD support (PROSPERO registration code CRD42024597541). Rates of successful and complete reperfusion, favorable functional outcomes at 90 days (modified Rankin Scale (mRS) 0–2 or equal to pre-stroke mRS), mortality at 90 days, any intracerebral hemorrhage (ICH) and symptomatic ICH (sICH) were pooled using generalized linear mixed models. Results Eight studies were included with data from 51 patients and 62 MTs. The rate of successful reperfusion was 87.4% (95% CI 62.5% to 96.6%) and complete reperfusion rate was 57.3% (95% CI 35.1% to 76.9%). Rate of favorable functional recovery was 62.5% (95% CI 42.2% to 79.2%). Rate of sICH was 6.4% (95% CI 0.9% to 34.0%). Mortality rate was 16.7% (95% CI 7.1% to 34.7%). Between 25–40% of patients who were waiting for a heart transplant before their stroke received a heart transplant after MT. Conclusions MT for the emergent treatment of AIS in the setting of LVAD is relatively safe and efficacious for achieving successful reperfusion and good functional recovery.

Background Aneurysm treatments are crucial to minimize the rupture risk. The underlying molecular processes mediating cellular remodeling, endothelialization, and aneurysm healing following endovascular treatment are poorly understood. The current study aims to explore circulating miRNA as a treatment and outcome-associated biomarkers in patients undergoing endovascular treatment. Methods Patients undergoing endovascular interventions for unruptured intracranial aneurysms, using either flow diverter placement or coil embolization, were enrolled. Blood samples were collected before the intervention and during a follow-up period between 6 and 18 months. Total mRNA/miRNA was isolated from plasma, followed by RNA-seq analysis. Gene Ontology analysis was used to identify pathways linked to altered miRNA expression. Results Twenty-three patients participated, with 13 (56.5%) undergoing flow diversion and 10 (43.5%) coil embolization. The median follow-up sample collection time was 10.70 months (SEM ± 1.32). No significant differences in angiographic occlusion were noted between intervention groups. Differentially expressed miRNAs were not identified between groups at baseline. However, at follow-up, 39 miRNAs were upregulated and 41 were downregulated, independent of intervention. Notably, three miRNAs (miR-4746-5p, miR-4685-3p, and miR-490-3p) were downregulated in the flow diversion group compared to the coil embolization group. Bioinformatics analysis revealed associations with upregulated fluid shear stress, p53, adherens junction pathways, along with downregulated apoptosis pathways. Conclusions This study suggests that fluid shear stress and apoptosis may influence aneurysm healing or thromboembolic events in flow diverter-treated patients. Further research is warranted to elucidate the functional significance of these findings in treatment outcomes, providing valuable insights for improved patient care in intracranial aneurysm management.

Introduction: Intracranial aneurysms are associated with local degradation of the vessel wall resulting in the formation of a blood-filled sac. Approximately 6 million people are estimated to have intercranial saccular aneurysms in the US alone. Most aneurysms remain undetected until rupture, resulting in hemorrhage which carries a high mortality rate (>50%). Flow diverters are placed across the aneurysm neck to divert blood flow away from the sac, preventing rupture once occluded. However, flow diverters carry significant risk for thromboembolism, which is a major cause of morbidity. The elevated risk of thromboembolism is likely due to endothelial injury of the parent artery at the neck of the aneurysm. We hypothesize that the bionanomatrix can promote faster endothelialization and aneurysm occlusion thereby reducing the risk of thromboembolism after flow diverter treatment. Methods: The bionanomatrix is composed of peptide amphiphiles containing endothelial cell adhesive ligand (YIGSR) and a nitric oxide (NO) donor (KKKKK), both components critical for recruiting and retaining endothelial cells on the device. The NO releasing bionanomatrix was coated onto the flow diverters using ultrasonic spray coating, and the NO effects on endothelial cell (EC) and smooth muscle cell (SMC) proliferation on the coated devices was assessed, in vitro, using calcien-AM staining. For the in vivo study, an elastase-induced rabbit aneurysm model was created. The bionanomatrix coated and uncoated flow diverters were implanted into the rabbit aneurysm model for 4 weeks. The coated and uncoated flow diverters were then analyzed for endothelialization, smooth muscle cell proliferation, and aneurysm occlusion by angiography, gross image, and immunohistochemistry analyses. Results: In vitro , the bionanomatrix coated flow diverters significantly enhanced endothelial cell proliferation as well as reduced smooth muscle cell proliferation on the flow diverters compared to the uncoated device. In vivo, after 4 weeks, the bionanomatrix coated flow diverters demonstrated enhanced neck coverage, more complete endothelialization, and reduced smooth muscle thickness on the coated flow diverters compared to the uncoated devices as seen by gross image analysis and histology. Conclusions: The bionanomatrix coated flow diverters can successfully promote faster endothelialization and brain aneurysm occlusion which is critical for reducing the risk of thromboembolism after neurointervention.

Background The angiographic shape of an occlusion, like the clot meniscus sign and the claw sign, has been reported to potentially impact the recanalization rate and clinical outcome in patients undergoing mechanical thrombectomy for acute ischemic strokes. Method Following PRISMA guidelines, a systematic literature search was conducted across PubMed, Scopus, Embase and Web of Science databases. Patients were grouped into clot meniscus/claw sign positive and negative groups based on the definitions obtained from each study. Primary outcomes included technical success, with a meta-analysis performed using a random-effects model to calculate proportions and odds ratios (OR) with 95% confidence intervals (Cl). Results We included seven studies recruiting 1572 patients. The results indicated that the positive and negative groups had comparable first-pass effect (OR 1.95; 95% CI 0.76 to 5.01; P=0.167) and final recanalization (OR 1.36; 95% CI 0.81 to 2.27; P=0.248) rates. However, the rate of having a favorable functional outcome was significantly higher in the positive group than in the negative sign group (OR 1.91; 95% CI 1.25 to 2.92; P<0.003). Within the sign-positive population, the use of contact aspiration was associated with a significantly higher rate of recanalization compared with using a stent retriever (OR 0.18; 95% CI 0.07 to 0.49; P<0.001). This result did not translate into a clinical impact, as both stent retriever and contact aspiration showed comparable rates of functional independence at 3 months (OR 0.22; 95% CI 0.02 to 2.33; P=0.210). Conclusion The presence of the clot meniscus/claw sign is not associated with recanalization outcomes after thrombectomy. However, it might be a good sign to predict which thrombectomy technique might be associated with better recanalization, although current evidence may need further confirmation.

Background Cerebral sinus venous thrombosis (CSVT) has traditionally been treated medically with systemic anticoagulation. Recent advances in endovascular therapy (EVT) may represent an alternative treatment to medical therapy for CSVT. We conducted a systematic review and meta-analysis to evaluate the use of EVT for CSVT. Methods We conducted a systematic literature review using PubMed, Embase, Scopus, and Web of Science. We included studies that reported outcomes following EVT for CSVT. The primary outcome of interest was rate of modified Rankin Scale (mRS) 0–2. Secondary outcomes of interest were rates of complete, partial, and failed recanalization, mortality, and new or expansion of hematoma. We calculated pooled rates (%) and their corresponding 95% confidence intervals (CIs). Results Thirty-eight studies with 682 patients were included. Rate of mRS 0–2 was 82.6% (95% CI, 75.3%–88.0%). Rate of complete recanalization was 60.9% (95% CI, 49.1%–71.5%), rate of partial recanalization was 34.2% (95% CI, 24.1%–45.9%), and rate of failed recanalization was 5.4% (95% CI, 3.1%–9.2%). Rate of mortality was 6.7% (95% CI, 4.1%–10.8%), and rate of new hematoma or expansion of hematoma was 5.1% (2.9%–8.8%). Conclusions In this systematic review and meta-analysis, EVT for CSVT was associated with favorable rates of mRS 0–2 and recanalization. Furthermore, EVT was associated with a promising safety profile. Future prospective, comparative studies are warranted to assess EVT for CSVT.

Purpose Optimizing the preparation of a 10 ml syringe for manual injection of contrast media can help operators obtain easier and faster injections. This study aims to compare the flow rates of different contrast media injection methods. Methods Different contrast media solutions were compared: 100% contrast (10 ml contrast), mixed contrast solution (8:2 contrast/saline), and layered contrast below saline (“Parfait”) in different volumes. Contrast media were injected at room temperature (20°C) and after heating (37°C). Four operators injected 10 ml syringes filled with different mediums through 5-French angiographic catheters. The average flow rate was used to compare different contrast injection mediums. The Kruskal-Wallis test with post-hoc pairwise comparisons using Bonferroni correction or Mann-Whitney U-tests were employed depending on the type of comparison. Results Compared to the 100% contrast solution, every Parfait media and mixed contrast solution demonstrated significantly higher flow rates (p < 0.001). The 5 ml saline Parfait had the highest flow rate among the Parfait solutions. The 5 ml saline Parfait and the mixed solution had comparable flow rates (p = 0.237). Higher flow rates were observed upon heating both 100% contrast (p < 0.001) and mixed contrast solutions (p < 0.001) in comparison to their flow rates at room temperature. Conclusion This study demonstrates the capability of the Parfait and mixed contrast injections to achieve higher flow rates than the 100% contrast solutions. Heating the contrast media to 37°C also proves to be a viable strategy for further enhancing the flow rates for 100% and mixed contrast solutions.