Ju-Yu Chueh

Reduction in Distal Emboli With Proximal Flow Control During Mechanical Thrombectomy: A Quantitative In Vitro Study

Background and Purpose— To evaluate the impact of proximal flow control on efficacy and safety of mechanical thrombectomy in an in vitro middle cerebral artery occlusion. Methods— Three independent variables, including clot type, device (Merci Retriever, Solitaire FR, and Trevo devices), and use of a balloon guide catheter, were used to ascertain the impact of proximal flow control on the size and number of distal emboli generated during thrombectomy. Secondary end points were the recanalization rate and amount of flow restored. Results— Use of the balloon guide catheter during thrombectomy of the fragile, hard clot significantly reduced the formation of large distal emboli with a diameter >1 mm, regardless of the device used (P<0.01). Applying aspiration via the balloon guide catheter in place of the conventional guide catheter resulted in a significant increase of flow reversal (P<0.0001). Prior to thrombectomy, deployment of the stent-trievers produced immediate flow restoration through the soft and hard clot occlusions, 69.2±27.3 and 45.5±22.8 mL/min, respectively, that was preserved after the balloon inflation because of collateral flow via the posterior communication artery. After deployment but before thrombectomy, no flow was restored when using the Merci Retriever. After thrombectomy, complete flow restoration was achieved in a majority of cases. The Merci Retriever required more thrombectomy attempts to achieve hard clot removal compared with the stent-trievers when the conventional guide catheter was used (1.5 versus 1.1). Conclusions— The risk of distal embolization was significantly reduced with the use of the balloon guide catheter.

Mechanical Characterization of Thromboemboli in Acute Ischemic Stroke and Laboratory Embolus Analogs

BACKGROUND AND PURPOSE: Mechanical behavior of the thromboembolus is one of the key factors that determine the efficacy of thrombectomy devices for revascularization in AIS. We characterized the mechanical properties and composition of thromboemboli from clinical cases and compared them with commonly used EAs. MATERIALS AND METHODS: Thromboemboli were obtained from patients with AIS by using aspiration devices and from carotid atherosclerotic plaques harvested during endarterectomy. In the laboratory, common EAs were created by varying blood donor species (human, porcine, and bovine), thrombin concentration, and presence of barium sulfate. Stiffness and elasticity of the specimens were measured with DMA. Scanning electron microscopy and histology were used to investigate the ultrastructure and composition of all specimens. RESULTS: Red thromboemboli from patients composed mainly of fibrin and erythrocytes were much softer than the calcified and cholesterol-rich material. Of the EAs created in the laboratory, those made from bovine blood presented the highest stiffness that was independent of thrombin concentration. Addition of thrombin increased the stiffness and elasticity of human and porcine EAs (P < .05). The presence of barium sulfate significantly reduced the elasticity of all EAs (P < .05). CONCLUSIONS: Endovascular device testing and development requires realistic EAs. The stiffness and elasticity of the cerebral thromboemboli analyzed in this study were closely matched by recalcified porcine EAs and thrombin-induced human EAs. Stiffness of the thrombus extracted from carotid endarterectomy specimens was similar with that of the thrombin-induced bovine and porcine EAs.

Risk of distal embolization with stent retriever thrombectomy and ADAPT

Background There is a discrepancy in clinical outcomes and the achieved recanalization rates with stent retrievers in the endovascular treatment of ischemic stroke. It is our hypothesis that procedural release of embolic particulate may be one contributor to poor outcomes and is a modifiable risk. The goal of this study is to assess various treatment strategies that reduce the risk of distal emboli. Methods Mechanical thrombectomy was simulated in a vascular phantom with collateral circulation. Hard fragment-prone clots (HFC) and soft elastic clots (SECs) were used to generate middle cerebral artery (MCA) occlusions that were retrieved by the Solitaire FR devices through (1) an 8 Fr balloon guide catheter (BGC), (2) a 5 Fr distal access catheter at the proximal aspect of the clot in the MCA (Solumbra), or (3) a 6 Fr guide catheter with the tip at the cervical internal carotid artery (guide catheter, GC). Results from mechanical thrombectomy were compared with those from direct aspiration using the Penumbra 5MAX catheter. The primary endpoint was the size distribution of emboli to the distribution of the middle and anterior cerebral arteries. Results Solumbra was the most efficient method for reducing HFC fragments (p<0.05) while BGC was the best method for preventing SEC fragmentation (p<0.05). The risk of forming HFC distal emboli (>1000 µm) was significantly increased using GC. A non-statistically significant benefit of direct aspiration was observed in several subgroups of emboli with size 50–1000 µm. However, compared with the stent-retriever mechanical thrombectomy techniques, direct aspiration significantly increased the risk of SEC fragmentation (<50 µm) by at least twofold. Conclusions The risk of distal embolization is affected by the catheterization technique and clot mechanics.

Neurovascular Modeling: Small-Batch Manufacturing of Silicone Vascular Replicas

BACKGROUND AND PURPOSE: Realistic, population based cerebrovascular replicas are required for the development of neuroendovascular devices. The objective of this work was to develop an efficient methodology for manufacturing realistic cerebrovascular replicas. MATERIALS AND METHODS: Brain MR angiography data from 20 patients were acquired. The centerline of the vasculature was calculated, and geometric parameters were measured to describe quantitatively the internal carotid artery (ICA) siphon. A representative model was created on the basis of the quantitative measurements. Using this virtual model, we designed a mold with core-shell structure and converted it into a physical object by fused-deposit manufacturing. Vascular replicas were created by injection molding of different silicones. Mechanical properties, including the stiffness and luminal coefficient of friction, were measured. RESULTS: The average diameter, length, and curvature of the ICA siphon were 4.15 ± 0.09 mm, 22.60 ± 0.79 mm, and 0.34 ± 0.02 mm−1 (average ± standard error of the mean), respectively. From these image datasets, we created a median virtual model, which was transformed into a physical replica by an efficient batch-manufacturing process. The coefficient of friction of the luminal surface of the replica was reduced by up to 55% by using liquid silicone rubber coatings. The modulus ranged from 0.67 to 1.15 MPa compared with 0.42 MPa from human postmortem studies, depending on the material used to make the replica. CONCLUSIONS: Population-representative, smooth, and true-to-scale silicone arterial replicas with uniform wall thickness were successfully built for in vitro neurointerventional device-testing by using a batch-manufacturing process.

Effectiveness of mechanical endovascular thrombectomy in a model system of cerebrovascular occlusion

BACKGROUND AND PURPOSE: A number of thrombectomy devices are currently undergoing clinical evaluation; meanwhile, various novel devices are under investigation. The aims of this study were to quantify flow restoration and the particle size distribution of the effluent pursuant to MET in an in vitro occlusion model. MATERIALS AND METHODS: The model system was composed of 3 elements: an ICA/MCA replica, a clot model with mechanical properties similar to those of thrombi found in patients at risk of stroke, and a pulsatile flow loop. Different thrombectomy mechanisms including mechanical retrieval, aspiration, and waveguide induced cavitation were used. The efficacy end points were recanalization rate and amount of flow restoration. The risk of the embolic shower was assessed to evaluate device safety. RESULTS: The recanalization rates were the following: Merci, 67%; Solitaire, 100%; Penumbra, 83%; Enterprise, 17%; and the waveguide, 0%. In experiments in which recanalization was achieved, the amount of flow restoration for the Merci, Solitaire, and Enterprise devices was 100%, 92%, and 86%, respectively. The mean sizes of generated small and large clot fragments were between 23 and 37 and 215 and 285 μm, respectively, depending on the device used. The Merci device generated the fewest number of large fragments compared with the Penumbra system (P < .05) and Solitaire (not significant). CONCLUSIONS: The risk of embolic shower was influenced by the mechanism of action for the thrombectomy device. Clinically reported recanalization rates for the Solitaire, Penumbra, and Merci devices were nearly identical in this model system, suggesting that this model may provide a predictive tool for preclinical evaluation of MET.

Preclinical acute ischemic stroke modeling

Preclinical ischemic stroke is at the crossroads in search of reliable and robust simulation models as past experiences with their translation from the laboratory to the standard of clinical care have often been disappointing. The efficacy of neuroprotective agents is still elusive, and the use of thrombolytics alone is limited to the narrow time window of presentation from the onset of the deficit. Hence, the focus has shifted to interventional revascularization to salvage the parenchyma at the risk of infarction. As the burden of disease morbidity and mortality is so enormous, neurointerventionalists have adopted a more aggressive approach to mechanical revascularization with the limited approved tools available—the Penumbra and the MERCI retrieval system, and the recently incorporated stent retrievers. In fact, the interventional space is among the fastest growing fields in stroke research today. Assessing treatment efficacy in these scenarios is infinitely complex as the heterogeneity of the cerebrovasculature, physical and mechanical nature of the occlusive embolus and the time of presentation are all confounders in assessing treatment outcomes. As no single thromboembolic model is apt to address all of these questions, an integrated methodology with a combination of both in vitro and in vivo assessment needs to be adopted. This involves clinically relevant thromboembolic analogs in device evaluation in vascular replicas, thromboembolic stroke induction in large animal gyrencephalic ischemic stroke models for thrombolytic, imaging and neuroprotection research and a native cerebrovascular target for evaluation of the safety and efficacy of mechanical thrombectomy devices.

Endovascular treatment of tandem vascular occlusions in acute ischemic stroke.

Background and purpose Tandem vascular occlusions are an important cause of acute ischemic stroke (AIS) and present unique treatment challenges. We report our experience of managing a subset of AIS patients with extracranial vascular stenting/angioplasty and intracranial revascularization. Methods Consecutive patients who presented at three centers with AIS from tandem vascular occlusions confirmed by brain and neck CT imaging were included in the study. We retrospectively analyzed the patient demographics, National Institute of Health Stroke Scale (NIHSS) score and modified Rankin Scale (mRS) score at the time of admission, treatment strategy, angiographic results using the Thrombolysis In Cerebral Infarction (TICI) score, and clinical and imaging follow-up. Results Twenty-eight patients were included. The mean NIHSS score at admission was 18. Extracranial carotid occlusions with a concomitant middle cerebral artery occlusion were seen in 89.3% of patients (n=25) and vertebral artery combined with basilar artery lesions in 10.7% (n=3). An antegrade approach (ie, treatment of the extracranial lesion first) was used in 24 patients (85.7%). Proximal occlusion recanalization was achieved usually with a stent (n=27; 96.4%). Pursuant to intracranial revascularization techniques, ≥TICI 2A recanalization was seen in 96.4% of patients. An mRS score of ≤2 at 90 days was achieved in 56.5% of patients. Conclusions Our study shows preliminary data from three centers on recanalization of tandem occlusions in patients presenting with AIS. There was a preference to revascularize the proximal occlusion using a stent followed by distal recanalization with mechanical thrombectomy, intra-arterial thrombolysis or a combination of these. This approach has low periprocedural complications and can achieve an excellent angiographic and clinical outcome.

Quantitative evaluation of C-arm CT cerebral blood volume in a canine model of ischemic stroke

BACKGROUND AND PURPOSE: Previous studies have shown the feasibility of assessing qualitative CBV measurements in the angiography suite by using FPD-CBCT systems. We have investigated the correlation of FPD-CBCT CBV lesion volumes to the infarct volume. MATERIALS AND METHODS: Unilateral strokes were created in 7 adult dogs. MR imaging and FPD-CBCT data were obtained after MCA occlusion. FPD-CBCT CBV and ADC maps were generated for all subjects. The animals were sacrificed immediately following the last imaging study to measure infarct volume on histology. The reliability of FPD-CBCT-based lesion volume measurements was compared with those measured histologically by using regression and Bland-Altman analysis. RESULTS: The best correlation (R2 = 0.72) between lesion volumes assessed with FPD-CBCT and histology was established with a threshold of mean healthy CBV − 2.5 × SD. These results were inferior to the correlation of lesion volumes measured with ADC and histology (R2 = 0.99). Bland-Altman analysis showed that the agreement of ADC-derived lesion volumes with histology was superior to the agreement of FPD-CBCT-derived lesion volumes with histology. CONCLUSIONS: We correlated FPD-CBCT measurements of CBV and MR ADC lesion volumes with histologically assessed infarct volume. As expected, ADC is a very accurate and precise method for determining the extent of infarction. FPD-CBCT CBV lesion volumes are correlated to the size of the infarct. Improvement of FPD-CBCT image quality provides an opportunity to establish quantitative CBV measurement in the angiography suite.

The Effect of Intracranial Stent Implantation on the Curvature of the Cerebrovasculature

BACKGROUND AND PURPOSE: Recently, the use of stents to assist in the coiling and repair of wide-neck aneurysms has been shown to be highly effective; however, the effect of these stents on the RC of the parent vessel has not been quantified. The purpose of this study was to quantify the effect of intracranial stenting on the RC of the implanted artery using 3D datasets. MATERIALS AND METHODS: Twenty-four patients receiving FDA-approved neurovascular stents to support coil embolization of brain aneurysms were chosen for this study. The stents were located in the ICA, ACA, or MCA. We analyzed C-arm rotational angiography and contrast-enhanced cone beam CT datasets before and after stent implantation, respectively, to ascertain changes in vessel curvature. The images were reconstructed, and the vessel centerline was extracted. From the centerline, the RC was calculated. RESULTS: The average implanted stent length was 25.4 ± 5.8 mm, with a pre-implantation RC of 7.1 ± 2.1 mm and a postimplantation RC of 10.7 ± 3.5 mm. This resulted in a 3.6 ± 2.7 mm change in the RC due to implantation (P < .0001), more than a 50% increase from the pre-implantation value. There was no difference in the change of RC for the different locations studied. The change in RC was not impacted by the extent of coil packing within the aneurysm. CONCLUSIONS: The implantation of neurovascular stents can be shown to have a large impact on the RC of the vessel. This will lead to a change in the local hemodynamics and flow pattern within the aneurysm.

Shear-Activated Nanoparticle Aggregates Combined With Temporary Endovascular Bypass to Treat Large Vessel Occlusion

Background and Purpose— The goal of this study is to combine temporary endovascular bypass (TEB) with a novel shear-activated nanotherapeutic (SA-NT) that releases recombinant tissue-type plasminogen activator (r-tPA) when exposed to high levels of hemodynamic stress and to determine if this approach can be used to concentrate r-tPA at occlusion sites based on high shear stresses created by stent placement. Methods— A rabbit model of carotid vessel occlusion was used to test the hypothesis that SA-NT treatment coupled with TEB provides high recanalization rates while reducing vascular injury. We evaluated angiographic recanalization with TEB alone, intra-arterial delivery of soluble r-tPA alone, or TEB combined with 2 doses of intra-arterial infusion of either the SA-NT or soluble r-tPA. Vascular injury was compared against stent-retriever thrombectomy. Results— Shear-targeted delivery of r-tPA using the SA-NT resulted in the highest rate of complete recanalization when compared with controls (P=0.0011). SA-NT (20 mg) had a higher likelihood of obtaining complete recanalization as compared with TEB alone (odds ratio 65.019, 95% confidence interval 1.77, >1000; P=0.0231), intra-arterial r-tPA alone (odds ratio 65.019, 95% confidence interval 1.77, >1000; P=0.0231), or TEB with soluble r-tPA (2 mg; odds ratio 18.78, 95% confidence interval 1.28, 275.05; P=0.0322). Histological analysis showed circumferential loss of endothelium restricted to the area where the TEB was deployed; however, there was significantly less vascular injury using a TEB as compared with stent-retriever procedure (odds ratio 12.97, 95% confidence interval 8.01, 21.02; P<0.0001). Conclusions— A novel intra-arterial, nanoparticle-based thrombolytic therapy combined with TEB achieves high rates of complete recanalization. Moreover, this approach reduces vascular trauma as compared with stent-retriever thrombectomy.