OBJECTIVE Stroke is a major cause of disability and death in adults. Several large randomized clinical trials have shown the significant benefit of mechanical thrombectomy with modern stent retrievers in the treatment of large-vessel occlusions. However, large clots located at bifurcations remain challenging to treat. An in vivo model of these recalcitrant clots needs to be developed to test future generations of devices. METHODS Autologous blood was drawn from anesthetized swine via a femoral sheath. Blood was then mixed with thrombin, calcium chloride, and saline, and injected into silicone tubing to form cylindrical clots in the standard fashion. Matured clots were then delivered in an unfragmented fashion directly into the distal extracranial vasculature, at branch points where vessel sizes mimic the human middle cerebral artery, by using Penumbra aspiration tubing and the Penumbra ACE68 reperfusion catheter. RESULTS A total of 5 adult swine were used to develop the model. The techniques evolved during experiments in the first 3 animals, and the last 2 were used to establish the final model. In these 2 swine, a total of 8 autologous clots, 15–20 mm, were injected directly into 8 distal extracranial vessels at branch points to mimic a bifurcation occlusion in a human. All clots were delivered directly at a distal bifurcation or trifurcation in an unfragmented fashion to cause an occlusion. Ten revascularization attempts were made, and none of the branch-point occlusions were fully revascularized on the first attempt. CONCLUSIONS Using novel large-bore distal access catheters, large unfragmented clots can be delivered into distal extracranial vessels in a swine occlusion model. The model mimics the clinical situation of a recalcitrant bifurcation occlusion and will be valuable in the study of next-generation stroke devices and in training settings.

OBJECTIVEAppropriately chosen candidates with medically refractory epilepsy may benefit from hemispheric disconnection. Traditionally, this involves a large surgical exposure with significant associated morbidity. Minimally invasive approaches using endoscopic assistance have been described by only a few centers. Here, the authors report on the feasibility of endoscope-assisted functional hemispherotomy in a cadaver model and its first translation into clinical practice in appropriately selected patients.METHODSThree silicone-injected, formalin-fixed cadaver heads were used to establish the steps of the procedure in the laboratory. The steps of disconnection were performed using standard surgical instruments and a straight endoscope. The technique was then applied in two patients who had been referred for hemispherectomy and had favorable anatomy for an endoscope-assisted approach.RESULTSAll disconnections were performed in the cadaver model via a 4 × 2–cm paramedian keyhole craniotomy using endoscopic assistance. An additional temporal burr hole approach was marked in case the authors were unable to completely visualize the frontobasal and insular cuts from the paramedian vertical view. Their protocol was subsequently used successfully in two pediatric patients. Full disconnection was verified with postoperative tractography.CONCLUSIONSFull hemispheric disconnection can be accomplished with minimally invasive endoscope-assisted functional hemispherotomy. The procedure is technically feasible and can be safely applied in patients with favorable anatomy and pathology; it may lead to less surgical morbidity and faster recovery.

BACKGROUND Delta-24-RGD, an oncolytic adenovirus, shows promise against glioblastoma. To enhance virus delivery, we recently demonstrated that human bone marrow-derived mesenchymal stem cells loaded with Delta-24-RGD (hMSC-D24) can eradicate glioblastomas in mouse models. There are no studies examining the safety of endovascular selective intra-arterial (ESIA) infusions of MSC-D24 in large animals simulating human clinical situations. OBJECTIVE To perform canine preclinical studies testing the feasibility and safety of delivering increasing doses of hMSCs-D24 via ESIA infusions. METHODS ESIA infusions of hMSC-D24 were performed in the cerebral circulation of 10 normal canines in the target vessels (internal carotid artery [ICA]/P1) via transfemoral approach using commercially available microcatheters. Increasing concentrations of hMSC-D24 or particles (as a positive control) were injected into 1 hemisphere; saline (negative control) was infused contralaterally. Toxicity (particularly embolic stroke) was assessed on postinfusion angiography, diffusion-weighted magnetic resonance imaging, clinical exam, and necropsy. RESULTS ESIA injections were performed in the ICA (n = 7) or P1 (n = 3). In 2 animals injected with particles (positive control), strokes were detected by all assays. Of 6 canines injected with hMSC-D24 through the anterior circulation, escalating dose from 2 × 106 cells/20 mL to 1 × 108 cells/10 mL resulted in no strokes. Two animals had ischemic and hemorrhagic strokes after posterior cerebral artery catheterization. A survival experiment of 2 subjects resulted in no complications detected for 24-h before euthanization. CONCLUSION This novel study simulating ESIA infusion demonstrates that MSCs-D24 can be infused safely at least up to doses of 1 × 108 cells/10 mL (107 cells/ml) in the canine anterior circulation using commercially available microcatheters. These findings support a clinical trial of ESIA infusion of hMSCs-D24.

Objective Contrast-enhanced cone-beam computed tomography (CBCT) imaging is commonly used for evaluating neurovascular stents and their relationship to the parent artery or vascular pathologies such as arteriovenous malformations (AVMs) and dural arteriovenous fistulas (dAVFs) in the context of surrounding anatomical structures. The purpose of this study was to understand the effects of varying concentrations of contrast medium used in CBCT imaging for optimal visualization of various endovascular devices and anatomical pathologies. Methods Thirty-five patients with various neurovascular pathologies were included in the study. Contrast-enhanced CBCT images (20 s DR, Siemens syngo DynaCT, Siemens AG, Forchheim, Germany) were acquired in all cases, with varying dilutions of contrast medium, from 1% to 30%. The injection rate was kept constant at 3 cc/sec with an X-ray delay of two sec, and a total volume of 66 cc of diluted contrast was administered. Results from visual and quantitative analysis were reported. Results Ten percent dilution of contrast medium resulted in the best image differentiation between flow-diverter devices and the parent artery. Concentrations as low as 2.5% contrast medium also resulted in identifying AVMs in the context of the surrounding brain parenchyma, whereas 20% to 30% dilution provided the best visualization of residual AVMs with prior Onyx embolization and dAVFs in the presence of bony structures. Conclusions Simultaneous visualization of brain parenchyma, bony structures, devices, and pathological anatomy using contrast-enhanced CBCT imaging is feasible with appropriate doses of iodinated contrast, and should be tailored to the individual case based on the goals of CBCT.

CBCT images of neurovascular devices can be obtained successfully using a 10 s acquisition protocol. In addition, the 10 s protocol offers faster acquisition, thus allowing its use in awake patients and with an added advantage of lower radiation and contrast dose.