Citations

AbstractShape memory polymer (SMP) foam‐coated coils (FCCs) are new embolic coils coated with porous SMP designed to expand for increased volume filling and enhanced healing after implantation. The purpose of this study was to compare chronic aneurysm healing after treatment with SMP FCCs to bare platinum coil (BPC) controls in the rabbit elastase aneurysm model. BPCs or SMP FCCs were implanted in rabbit elastase‐induced aneurysms for follow‐up at 30 days (n = 10), 90 days (n = 5), and 180 days (n = 12 for BPCs; n = 14 for SMP FCCs). Aneurysm occlusion and histologic healing, including a qualitative healing score, neointima thickness, collagen deposition, and inflammation were compared between the two groups. The mean neointima thickness was significantly greater in groups treated with SMP FCCs for all three time points. Histologic healing scores and collagen deposition quantification suggested that aneurysms treated with SMP FCCs experience more complete healing of the dome by 90 days, but the differences were not statistically significant. More progressive occlusion and recanalization were observed in aneurysms treated with SMP FCCs, but neither difference was statistically significant. Additionally, the SMP foam used in the FCCs was found to degrade faster in the rabbit elastase model than expected based on previous studies in a porcine sidewall aneurysm model. This study suggests that SMP FCCs can promote neointima formation along the aneurysm neck, and may lead to more complete healing of the dome and neck. These findings indicate potential benefits of this device for aneurysm occlusion procedures. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2466–2475, 2019.

Background: Flow diverters (FD) are increasingly used in the treatment of intracranial aneurysms. The risk of distal thromboembolic complications with FD is high, even in patients treated with dual antiplatelet therapy. The aim of the study was to understand the downstream vascular wall changes, by measuring the pulse wave velocity and vascular contractility following flow diverter treatment in a rabbit model. Methods: FD (Pipeline Embolic Device, Medtronic) were implanted in normal rabbits and sham-operated aorta were used as controls (n=5 for each group). Pulse wave imaging with ultra-fast ultrasound at 1600 frames per second (Vantage, Verasonics, Inc.) was performed in the vessel wall distal to FD, prior to device implantation and at 8 weeks follow up to measure the pulse wave propagation. Force contraction studies were conducted in the aortic rings using organ bath to assess the vascular functions. Results: The difference in pulse wave velocity (PWV) in the follow-up compared to pre-implantation was significantly higher (p=0.03,Fig 1A) in the distal vessels compared to sham controls (mean difference of PWV was 1.18 m/s and -0.37m/s, respectively as shown in Fig 1B). Conversely, the distal aortic segments to FD exhibited 55% increase in the level of vascular contractility compared to that of proximal segments (p=0.002). There is a significant positive correlation between mean PWV and mean vascular contractility. Conclusion: Our study found changes in the PWV after implantation of the FD, which correlated with vascular contractility. These results could explain vascular wall changes downstream following FD implantation.

Introduction: The composition of acute ischemic stroke (AIS) blood clots can impact their successful removal via endovascular therapy. Identification of the clot composition prior to endovascular treatment may influence the optimal treatment strategy. In this study, we aimed to investigate the relationship between the Hounsfield Unit intensity on CT and machine-learned characterization of clot composition. Methods: Prior to endovascular treatment, each patient had a non-contrast CT performed. Histopathological analysis of the clots was performed and clot composition was quantified via standard thresholding techniques using Adobe Photoshop. In addition, following representative cell labeling by an expert pathologist, image segmentation algorithms (Orbital Image Analysis, Actelion Ltd.) were trained on each case to quantify composition by cell type. The clots were categorized into 3 groups: red blood cell (RBC) dominant (>50%), RBC proportion equal to fibrin and fibrin dominant (>50%). Correlations between clot composition and Hounsfield Units (HU) density on CT were assessed. A positive Hyperdense Artery Sign was defined as ≥50 HU. Results: Twenty patients were included in the study. There was a significant correlation between clots quantified using Adobe Photoshop Image-Pro and Orbit image analysis ( ρ = 0.837, p < 0.001). A significant relationship was found between clot composition and the presence of a HAS sign, ( X 2 (2) = 6.496, p = 0.039). There is a significant positive correlation between percentage of RBC in the clot and the presence of a HAS sign ( ρ = 0.632, p = 0.002**). There is also a significant positive correlation between the presence of fibrin-rich and the absence of a HAS sign ( ρ = 0.600, p = 0.004**). Conclusion: Machine learning software can accurately quantify AIS clot composition. The Hounsfield unit density of an AIS clot on a non-contrast CT correlates with the composition of the clot. Measuring the HU of the clot on CT prior to endovascular intervention may inform the clinician of the clot type and help to determine the most appropriate treatment strategy for that clot.

Background and purpose Vertebrobasilar dolichoectatic and fusiform aneurysms (VBDAs) are known to have a poor natural history, with high rates of growth, rupture, and stroke. The purpose of this study was to identify hemodynamic characteristics that differ between VBDAs associated with growth, rupture, and stroke. Materials and methods VBDAs with CT angiography or MR angiography followed longitudinally without treatment were studied. Unstable aneurysms were defined as those that grew or ruptured during follow-up. Aneurysms associated with stroke were defined as those associated with posterior circulation infarct at follow-up. Baseline data, including demographics, comorbidities, and aneurysm morphology and size were collected. Image based computational fluid dynamics models were created and run under pulsatile flow conditions. Relevant hemodynamic and geometric variables were calculated and compared between groups (stable vs unstable and no stroke vs stroke) using the Wilcoxon test. Results A total of 37 VBDAs were included (24 stable, 13 unstable; 30 no stroke, 7 stroke). Unstable aneurysms had lower shear rates (P=0.05), blood flow velocity (P=0.03), and lower vorticity (P=0.049) than stable aneurysms. In addition, unstable aneurysms had higher mean oscillatory shear indices (P=0.001). There were no differences in the hemodynamic characteristics of aneurysms in the stroke group compared with the non-stroke group. Conclusion This small study suggests there may be hemodynamic differences between unstable and stable VBDAs. Unstable VBDAs appear to be under lower flow conditions with lower velocity, vorticity, and shear rates, and have more oscillatory flow. There was no difference in the hemodynamic characteristics of aneurysms in the stroke and no stroke group.

Background Intracranial aneurysms represent a significant health concern and are poorly understood despite decades of research. Our study focused on understanding temporal patterns of endothelial cell distribution in different spatial locations within the aneurysm early after creation in a rabbit model. Methods Elastase induced saccular aneurysms were created in rabbits and harvested on day 1 (n=3) and after 2 (n=5), 4 (n=4), 8 (n=5), and 12 (n=6) weeks. Sham operated controls (n=3) were harvested on the same day. Aneurysm and control tissue samples were subjected to en face whole mount CD31 staining for endothelial cells. Semiquantitative scoring was performed on the basis of endothelial coverage of the vessel wall (proximal, middle, and distal portions of the aneurysm dome). Mixed effects models were used to assess the effect of time and aneurysm section on endothelial coverage. Results Aneurysmal segments were near completely de-endothelialized at 4 and 8 weeks but had re-endothelialized by 12 weeks. Compared with controls, aneurysms at all time points showed decreased endothelialization, but the difference was only significant compared with the 4 and 8 week groups. Both time (P=0.03) and aneurysm section (P=0.07) were significantly associated with the degree of endothelialization. Proximal locations showed increased endothelialization compared with distal locations (P=0.03). Conclusion In experimental aneurysms of rabbits, endothelial cells regress during the first month after creation, followed by ascending re-endothelialization that stays incomplete. These findings suggest that re-population of endothelial cells comes from resident cells in the adjacent parent artery and that deranged hemodynamics may affect full reconstitution of endothelial cells long term.

Shape memory polymers can be programmed into a secondary geometry and recovered to their primary geometry with the application of a controlled stimulus. Porous shape memory polymer foam scaffolds that respond to body temperature show particular promise for embolic medical applications. A limitation for the minimally invasive delivery of these materials is an inherent lack of X-ray contrast. In this work, a triiodobenzene containing a monomer was incorporated into a shape memory polymer foam material system to chemically impart X-ray visibility and increase material toughness. Composition and process changes enabled further control over material density and thermomechanical properties. The proposed material system demonstrates a wide range of tailorable functional properties for the design of embolic medical devices, including X-ray visibility, expansion rate, and porosity. Enhanced visualization of these materials can improve the acute performance of medical devices used to treat vascular malformations, and the material porosity provides a healing scaffold for durable occlusion.

Background and purpose Because computed tomography (CT) is the most commonly used imaging modality for the evaluation of acute ischemic stroke patients, developing CT-based techniques for improving clot characterization could prove useful. The purpose of this in-vitro study was to determine which single-energy or dual-energy CT techniques provided optimum discrimination between red blood cell (RBC) and fibrin-rich clots. Materials and methods Seven clot types with varying fibrin and RBC densities were made (90% RBC, 99% RBC, 63% RBC, 36% RBC, 18% RBC and 0% RBC with high and low fibrin density) and their composition was verified histologically. Ten of each clot type were created and scanned with a second generation dual source scanner using three single (80 kV, 100 kV, 120 kV) and two dual-energy protocols (80/Sn 140 kV and 100/Sn 140 kV). A region of interest (ROI) was placed over each clot and mean attenuation was measured. Receiver operating characteristic curves were calculated at each energy level to determine the accuracy at differentiating RBC-rich clots from fibrin-rich clots. Results Clot attenuation increased with RBC content at all energy levels. Single-energy at 80 kV and 120 kV and dual-energy 80/Sn 140 kV protocols allowed for distinguishing between all clot types, with the exception of 36% RBC and 18% RBC. On receiver operating characteristic curve analysis, the 80/Sn 140 kV dual-energy protocol had the highest area under the curve for distinguishing between fibrin-rich and RBC-rich clots (area under the curve 0.99). Conclusions Dual-energy CT with 80/Sn 140 kV had the highest accuracy for differentiating RBC-rich and fibrin-rich in-vitro thrombi. Further studies are needed to study the utility of non-contrast dual-energy CT in thrombus characterization in acute ischemic stroke.

Purpose Long-term occlusion of coiled aneurysms frequently fails, probably because of poor intrasaccular healing and inadequate endothelialization across the aneurysm neck. The purpose of this study was to determine if attachment of autologous mesenchymal stem cells (MSCs) to platinum coils would improve the healing response in an elastase-induced aneurysm model in rabbits. Materials and methods With approval from the institutional animal care and use committee, aneurysms were created in rabbits and embolized with control platinum coils (Axium; Medtronic) (n=6) or coils seeded ex vivo with autologous adipose-tissue MSCs (n=7). Aneurysmal occlusion after embolization was evaluated at 1 month with angiography. Histological samples were analyzed by gross imaging and graded on the basis of neck and dome healing on H&E staining. Fibrosis was evaluated using a ratio of the total area presenting collagen. Endothelialization of the neck was quantitatively analyzed using CD31 immunohistochemistry. χ2 and Student's t-test were used to compare groups. Results Healing score (11.5 vs 8.0, p=0.019), fibrosis ratio (10.3 vs 0.13, p=0.006) and endothelialization (902 262 μm2 vs 31 810 μm2, p=0.041) were significantly greater in the MSC group. The MSC group showed marked cellular proliferation and thrombus organization, with a continuous membrane bridging the neck of the aneurysm. Angiographic stable or progressive occlusion rate was significantly lower in the MSC group (0.00, 95% CI 0.00 to 0.41) compared with controls (0.67, 95% CI 0.22 to 0.96) (p=0.02). Conclusions Autologous MSCs attached to platinum coils significantly improve histological healing, as they result in improved neck endothelialization and collagen matrix formation within the aneurysm sac.

Objective To assess the feasibility of using MicroFil polymer perfusion to detect concomitant saccular aneurysms in an intracranial arterial dolichoectasia (IADE) model in mice, and to report detailed histomorphometric features of these aneurysms. Materials and methods IADE models were created in C57/BL6 mice via microsurgical injection of 25 mU elastase into the cisterna magna. The cerebral vasculature was perfused with MicroFil polymer and harvested at 1, 3, and 7 days, and 2 and 4 weeks (n=8 for each group). IADE was defined by a tortuosity index >10 combined with a 25% increase in diameter of the A1 segment of the anterior cerebral artery (ACA), internal carotid artery (ICA), or basilar artery compared with the baseline of controls, which received heat-inactivated elastase. Saccular aneurysm occurrence rate, location, and morphological parameters were investigated using macroscopic and microscopic analysis. Results IADE was present in 95% (36/38) of the subjects, with a mortality rate of 5% (2/40). Fifteen concomitant saccular aneurysms were detected in 8 (21%) of the 38 surviving mice, including 6 at the posterior communicating artery, 1 along the ACA, 2 along the anterior communicating artery complex, 3 along the ICA, and 3 along the middle cerebral artery. Rupture was confirmed in two aneurysms. Histological examination indicated that the aneurysms develop via arterial-wall remodelling, which is characterized by internal elastic lamina disruptions and muscular layer discontinuity in the media. Conclusions The proportion of subjects developing saccular aneurysms in addition to IADE in our mouse model is similar to the 15% of patients with IADE who have concomitant saccular aneurysms.