Kadirvel, Ramanathan

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.

The dual-layer Woven EndoBridge (WEB) device (WEB II) is designed to improve the performance of the first-generation WEB device. This study was performed to evaluate the acute and chronic performance of WEB II for aneurysm occlusion in an elastase-induced aneurysm model in rabbits. We implanted WEB II devices in 36 elastase-induced aneurysms and followed up for one, three, six, and 12 months. Degree of aneurysm occlusion at follow-up was graded on the Web Occlusion Scale (WOS): Grade A, complete aneurysm occlusion; Grade B, complete occlusion with recess filling; Grade C, residual neck filling; and Grade D, residual aneurysm filling. Hematoxylin and eosin staining was performed for histological assessment of aneurysm healing. Grades A, B, C, and D aneurysm occlusion at one-month follow-up were noted in three (17%), three (17%), eight (44%), and four (22%) of 18 cases, respectively. At the three-month time point Grades A, B, C, and D were shown in two (33%), two (33%), one (17%), and one (17%) aneurysms. Six months after treatment, one (17%), two (33%), two (33%), and one (17%) cases demonstrated Grades A, B, C, and D occlusion. At the 12-month time point, Grades B, C, and D were shown in three (50%), two (33%), and one (17%) aneurysms. Histologic evaluation showed progressive thrombus organization within aneurysm lumen from one to 12 months. These results indicated that the WEB II device can achieve high rates of aneurysm occlusion over time in experimental aneurysms.

We report histopathological findings from a human cerebral aneurysm following treatment with a flow diverter. A 75-year-old male underwent flow diversion treatment (Pipeline Embolization Device (PED)) and coil embolization for treatment of an aneurysm at the basilar tip. At four months, angiography showed complete aneurysm occlusion; at 12 months angiography demonstrated that the aneurysm had reopened. The patient expired from brainstem compression. The aneurysm cavity was primarily filled with unorganized thrombus. Thick, interrupted neointima crossed the neck interface indicating blood flow into aneurysm through small channels. Along the parent artery the PED was covered by neointima having a measured thickness of 0.19 ± 0.01 mm; the maximal stenosis of the proximal parent artery was 27%. The perforating arteries that were crossed by the PED remained patent. Findings in this human case are similar to those in the elastase-induced aneurysms in rabbits.

Background and Purpose— Vertebrobasilar, nonsaccular, and dolichoectatic aneurysms generally have a poor natural history. We performed a study examining the natural history of vertebrobasilar, nonsaccular, and dolichoectatic aneurysms receiving serial imaging and studied imaging characteristics associated with growth and rupture. Methods— We included all vertebrobasilar dolichoectatic, fusiform, and transitional aneurysms with serial imaging follow-up seen at our institution over a 15-year period. Two radiologists and a neurologist evaluated aneurysms for size, type, mural T1 signal, mural thrombus, daughter sac, mass effect, and tortuosity. Primary outcomes were aneurysm growth or rupture. Univariate analysis was performed with chi-squared tests for categorical variables and Student’s t test or analysis of variance for continuous variables. Multivariate logistic regression analysis was performed to identify variables independently associated with aneurysm growth or rupture. Results— One hundred and fifty-two patients with 542 patient-years (mean 3.6±3.5 years) of imaging follow-up were included. Aneurysms were fusiform in 45 cases (29.6%), dolichoectatic in 75 cases (49.3%), and transitional in 32 cases (21.1%). Thirty-five aneurysms (23.0%) grew (growth rate=6.5%/year). Eight aneurysms (5.3%) ruptured (rupture rate=1.5%/year). Variables associated with growth and rupture on univariate analysis were size >10 mm (57.6% versus 16.0%, P <0.0001), mural T1 signal (39.7% versus 16.3%, P =0.001), daughter sac (56.3% versus 21.3%), and mural thrombus (45.5% versus 13.4%, P <0.0001). 26.7% of fusiform aneurysms, 9.3% of dolichoectatic aneurysms, and 59.4% of transitional aneurysms grew or ruptured ( P <0.0001). The only variable independently associated with rupture was transitional morphology ( P =0.003). Conclusions— Vertebrobasilar, nonsaccular, and dolichoectatic aneurysms are associated with a poor natural history with high growth and rupture rates. Further research is needed to determine the best treatments for this disease.