Kallmes, David F.

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.

Background Predicting recanalization success for patients undergoing endovascular treatment for acute ischemic stroke is of significant interest. Studies have previously correlated the success of recanalization with the density of the clot. We evaluated clot density and its relationship to revascularization success and stroke etiology. Methods We conducted a retrospective review of 118 patients undergoing intra-arterial therapy for acute ischemic stroke. Mean and maximum thrombus density was measured by drawing a circular region of interest on an axial slice of a non-contrast computed tomography scan. T-tests were used to compare clot density to recanalization success or to stroke etiology, namely large artery atherosclerosis and cardioembolism. Recanalization success was compared in four device groups: aspiration, stent retriever, aspiration and stent retriever, and all other. Results There was no significant difference in the mean clot density in patients with successful ( n = 80) versus unsuccessful recanalization ( n = 38, 50.1 ± 7.4 Hounsfield unit (HU) vs. 53 ± 12.7 HU; P = 0.17). Comparing the large artery thromboembolism ( n = 35) to the cardioembolic etiology group ( n = 56), there was no significant difference in mean clot density (51.5 ± 7.7 HU vs. 49.7 ± 8.5 HU; P = 0.31). A subgroup analysis of middle cerebral artery occlusions ( n = 65) showed similar, non-statistically significant differences between groups. There was no difference in the rate of recanalization success in patients with a mean clot density greater than 50 HU or less than 50 HU in each of the four device groups. Conclusions There was no relationship between clot density and revascularization success or stroke etiology in our study. More research is needed to determine if clot density can predict recanalization rates or indicate etiology.

Abstract BACKGROUND: Early and mid-term safety and efficacy of aneurysm treatment with the Pipeline Embolization Device (PED) has been well demonstrated in prior studies. OBJECTIVE: To present 5-yr follow-up for patients treated in the Pipeline for Uncoilable or Failed Aneurysms clinical trial. METHODS: In our prospective, multicenter trial, 109 complex internal carotid artery (ICA) aneurysms in 107 subjects were treated with the PED. Patients were followed per a standardized protocol at 180 d and 1, 3, and 5 yr. Aneurysm occlusion, in-stent stenosis, modified Rankin Scale scores, and complications were recorded. RESULTS: The primary endpoint of complete aneurysm occlusion at 180 d (73.6%) was previously reported. Aneurysm occlusion for those patients with angiographic follow-up progressively increased over time to 86.8% (79/91), 93.4% (71/76), and 95.2% (60/63) at 1, 3, and 5 yr, respectively. Six aneurysms (5.7%) were retreated. New serious device-related events at 1, 3, and 5 yr were noted in 1% (1/96), 3.5% (3/85), and 0% (0/81) of subjects. There were 4 (3.7%) reported deaths in our trial. Seventy-eight (96.3%) of 81 patients with 5-yr clinical follow-up had modified Rankin Scale scores ≤2. No delayed neurological deaths or hemorrhagic or ischemic cerebrovascular events were reported beyond 6 mo. No recanalization of a previously occluded aneurysm was observed. CONCLUSION: Our 5-yr findings demonstrate that PED is a safe and effective treatment for large and giant wide-necked aneurysms of the intracranial ICA, with high rates of complete occlusion and low rates of delayed adverse events.

Background and purpose The HydroSoft coil was developed as a finishing coil, ideally to be placed along the aneurysm neck to enhance intracranial aneurysm healing. The GEL THE NEC (Gaining Efficacy Long Term: Hydrosoft, an Emerging, New, Embolic Coil) multicenter registry was developed to assess the safety and efficacy of HydroSoft coils in treating intracranial aneurysms. We report angiographic and clinical results of this prospective registry. Materials and methods GEL THE NEC was performed at 27 centers in five countries. Patients aged 21–90 years with a ruptured or unruptured aneurysm 3–15 mm in size were eligible for enrollment. The following variables were obtained: demographics/comorbidities, aneurysm geometry, adjunctive devices used, proportion of patients in whom HydroSoft coils were successfully placed, and long-term angiographic outcomes (graded by an independent core laboratory using the Modified Raymond Scale), and procedure-related adverse events. Predictors of good angiographic outcome were studied using χ2 and t-tests. Results A total of 599 patients with 599 aneurysms were included in this study. HydroSoft coils were successfully deployed in 577 (96.4%) patients. Procedure-related major morbidity and mortality were 0.5% (3/599) and 1.3% (8/599), respectively. The most common perioperative complications were iatrogenic vasospasm (30/599, 5.0%), thromboemboli (27/599, 4.5%), and aneurysm perforation (16/599, 2.7%). At last angiographic follow-up (mean 9.0±6.3 months), the complete occlusion rate was 63.2% (280/442) and near complete occlusion rate was 25.2% (107/442). The core laboratory read recanalization rate was 10.8% (46/425) and the retreatment rate was 3.4% (20/599). Conclusions Endovascular treatment of intracranial aneurysms with HydroSoft coils resulted in complete/near complete occlusion rates of 88% and a major complication rate of 1.8%. Trial registration number NCT01000675.

Treatment of symptomatic intracranial atherosclerotic stenosis usually involves maximizing medical therapy. In patients with medically refractory symptoms despite maximum pharmacologic therapy, intracranial angioplasty and/or stenting has become an accepted treatment option. The use of percutaneous transluminal angioplasty (PTA) for idiopathic intracranial stenoses has not been reported to date. We describe a case of idiopathic intracranial stenosis which was refractory to medical therapy and was successfully treated with percutaneous transluminal angioplasty. The presenting symptoms included multiple episodes of aphasia and right-sided weakness as well as a left basal ganglia infarct. The patient underwent treatment with two intracranial angioplasty procedures. There was a recurrence of the stenosis and symptoms following the first procedure. However, after a second treatment with a slightly larger balloon, flow in the MCA normalized. Furthermore, the symptoms attributed to her MCA stenosis had essentially resolved. This case suggests that patients with medically refractory idiopathic intracranial stenosis can be successfully treated with percutaneous transluminal angioplasty.

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.

We studied the use of minor and major recurrence classifications with regard to observer variability, which directly affects validity of these terms as outcome measures. Recurrences at the time of a three to six month follow-up angiogram were assessed independently by two experienced observers in 83 cases. Intra- and interobserver concordance is approximately 90% for assessment of minor and major recurrence.

The proliferation of new endovascular devices and therapeutic strategies calls for a prudent and rational evaluation of their clinical benefit. This evaluation must be done in an effective manner and in collaboration with industry. Such research initiative requires organisational and methodological support to survive and thrive in a competitive environment. We propose the formation of an international consortium, an academic alliance committed to the pursuit of effective neurovascular therapies. Such a consortium would be dedicated to the design and execution of basic science, device development and clinical trials. The Consortium is owned and operated by its members. Members are international leaders in neurointerventional research and clinical practice. The Consortium brings competency, knowledge, and expertise to industry as well as to its membership across a spectrum of research initiatives such as: expedited review of clinical trials, protocol development, surveys and systematic reviews; laboratory expertise and support for research design and grant applications to public agencies. Once objectives and protocols are approved, the Consortium provides a stable network of centers capable of timely realization of clinical trials or preclinical investigations in an optimal environment. The Consortium is a non-profit organization. The potential revenue generated from client-sponsored financial agreements will be re-directed to the academic and research objectives of the organization. The Consortium wishes to work in concert with industry, to support emerging trends in neurovascular therapeutic development. The Consortium is a realistic endeavour optimally structured to promote excellence through scientific appraisal of our treatments, and to accelerate technical progress while maximizing patients' safety and welfare.

Perforation of intracranial aneurysms during endovascular treatment with platinum micro-coils is a well-known and serious complication reported to occur in 2–4% of patients. Inflation of a remodelling balloon across the aneurysm neck or within the proximal parent vessel is an additional technique that theoretically might be useful to reduce flow within the aneurysm and achieve hemostasis. In the case reports that follow, we present our experience using this technique for managing intraprocedural aneurysm rupture.