William D. Bichard

In vivo assessment of calcium alginate gel for endovascular embolization of a cerebral arteriovenous malformation model using the Swine rete mirabile.

OBJECTIVE We sought to assess the stability of calcium alginate as an embolic agent in an animal model of a cerebral arteriovenous malformation (AVM). Swine cerebral AVM models were used to test the injectability, radiographic visualization, mechanical stability, and biocompatibility of calcium alginate as an occlusive agent. METHODS The swine cerebral AVM model included a carotid-to-jugular anastomosis to increase flow to the rete mirabile (RM), thereby simulating the pressure gradient and shunted blood flow of an AVM. Alginate and the reactive component, calcium chloride, were injected from double-lumen microcatheters to form a complete RM occlusion in the “acute swine” AVM model and a partial occlusion in a “survival swine” model. RESULTS Angiographic and histological results verified complete occlusion of the left RM in acute animals when alginate was injected in stages. Partial RM occlusion in the survival animals blocked blood flow to the inferior portion of the RM but left flow open to the superior portion of the RM and the circle of Willis. One-week survival results showed that the alginate remained a stable occlusive material. Histological results showed a minor bioactive response and encapsulation of the alginate polymer, thereby increasing the stability and effective occlusion of the embolization material. CONCLUSION Calcium alginate proved to be an effective endovascular occlusion material that blocked blood flow to the swine RM. The swine AVM models provided assessment of alginate injectability and effective occlusion and provided initial in vivo characteristics of alginate stability and biocompatibility.

Calcium Alginate Gel as a Biocompatible Material for Endovascular Arteriovenous Malformation Embolization: Six-month Results in an Animal Model

OBJECTIVE:We sought to expand our assessment of calcium alginate as an embolic agent in an animal model of a cerebral arteriovenous malformation (AVM). The objective of this study was to assess the long-term biocompatibility and stability of calcium alginate in AVM swine models that survived from 1 to 6 months. METHODS:The swine model included a carotid-jugular anastomosis to redirect flow to the rete mirabile (RM), thereby simulating flow to an AVM. Alginate and the reactive component, calcium chloride, were injected from double-lumen or concentric-tube microcatheters to form an occlusion of the RM feeding vessel and the inferior portion of the RM. RESULTS:Angiography and histology verified complete occlusion of the RM feeding vessel for up to 6 months in eight of nine swine. Blood flow remained open to the superior portion of the RM and the circle of Willis. No evidence of downstream calcium alginate gel was seen in the follow-up angiograms or the histological preparations of the circle of Willis. A minor bioactive response to the alginate gel was noted at 1 month, yet no degenerative or inflammatory response was seen. At 6 months, there was moderate fibrous tissue around the alginate, which further sealed off flow to the embolized areas of the RM. CONCLUSION:Over a period of 6 months, calcium alginate was an effective endovascular occlusion material that blocked blood flow to the inferior portion of the RM. The chronic AVM model verified the long-term stability and biocompatibility of calcium alginate.

Titanium Aneurysm Clips: Part I-Mechanical, Radiological, and Biocompatibility Testing

Most aneurysm clips are made of cobalt-based alloys. Although these clips are nonferromagnetic, they still produce artifact that degrades the quality of magnetic resonance (MR) images. A new aneurysm clip of pure titanium was developed to minimize artifact on postoperative MR images. We evaluated these clips in a series of mechanical tests in vitro, biocompatibility tests in rabbits, and radiological tests in greyhound dogs. The clip sizes and shapes matched those of conventional aneurysm clips. The average closing forces ranged between 151.6 and 181.8 g and were not diminished by repeated sterilization or stress. After > 20 million cycles of high-pressure and high-frequency pulsations, the clips did not open and the closing forces were not reduced. Titanium aneurysm clips implanted in the subarachnoid space of 12 rabbits for 1 or 6 months produced mild gliosis identical to that produced by implantation of cobalt alloy clips in 12 control rabbits. Based on pre- and postoperative weights and electron microscopic scans, the titanium implants did not corrode. The artifact on computed tomographic and MR imaging produced by a titanium clip placed on the internal carotid artery of a greyhound was less than that produced by an identical cobalt-chrome alloy clip by a factor of two to three. This study demonstrated that titanium aneurysm clips are mechanically equivalent to conventional clips, biocompatible, and corrosion resistant. Furthermore, titanium clips have superior imaging characteristics, creating less computed tomographic and MR imaging artifact and permitting better resolution of anatomic structures than cobalt alloy clips.

Application of a hydrogel sealant improves watertight closures of duraplasty onlay grafts in a canine craniotomy model

OBJECT The authors evaluated whether a polyethylene glycol-based hydrogel sealant system improved dural closures with collagen-based duraplasty onlay grafts. METHODS Dural defects 1.5 cm in diameter were created in 12 canines and repaired with one of two commercially available duraplasty onlay products. In six animals, hydrogel was applied onto the dural onlays, and the other six animals underwent duraplasty only. Before bone flap replacement, watertight closure was assessed. Before the animals were killed, the craniotomy was reopened, adhesions were rated by a neurosurgeon blinded to the treatment groups, and dural integrity was assessed using pressure testing. RESULTS The animals that received the hydrogel sealant in addition to the duraplasty withstood intraoperative Valsalva maneuvers up to 20 cm H2O without cerebrospinal fluid (CSF) leakage. The duraplasty-only animals leaked CSF at spontaneous pressures (p = 0.0022). Postoperatively, all six duraplasty-only dogs developed CSF subcutaneous accumulations, compared with only one (16.7%) dog who underwent hydrogel application (p = 0.0152). At the time of harvesting (8 weeks after implantation), duraplasty-only dogs had extensive scarring between the bone flap and the dura mater (median adhesion score 4, range 3-4). The animals receiving hydrogel showed minimal scarring (median adhesion score 0.5, range 0-2). In hydrogel-treated dogs, the mean adhesion score was 82.6% lower than the scores in duraplasty-only animals (p = 0.0043). In animals receiving hydrogel, the mean dural leak pressure was 56.8 +/- 2.5 cm H2O compared with 9.8 +/- 3.8 cm H2O in duraplasty-only dogs (p = 0.0392). Application of the hydrogel was not associated with neurotoxicity, delayed healing, degenerative changes, or increased dura-cortex adhesions. CONCLUSIONS The hydrogel sealant applied to collagen-based dural grafts significantly reduced CSF leakage and functioned as an adhesion barrier. Such technology could be an important tool for cranial surgery.

Preliminary investigation of calcium alginate gel as a biocompatible material for endovascular aneurysm embolization in vivo.

OBJECTIVEWe sought to expand our assessment of calcium alginate as an embolic agent in an aneurysm model in swine that survived from 30 to 90 days. The objective of this study was to assess the biocompatibility and stability of calcium alginate in aneurysms in vivo. METHODSTen models were created from a venous pouch sutured to the carotid artery, simulating flow to a side-wall aneurysm. Eight swine received complete embolizations, and two were less than 50% embolized to be used as controls. Alginate and calcium chloride were injected from concentric-tube microcatheters to form a mass that filled the aneurysm pouch. RESULTSAngiography and histology verified complete aneurysm occlusion and neck healing up to 90 days in eight swine. Both control animal aneurysms ruptured within 8 days. No animals showed evidence of downstream calcium alginate gel propagation. A minor bioactive response to the alginate gel was noted at 30 days, and fibrous tissue grew over the aneurysm orifice, sealing off the defect. No degenerative or inflammatory response was observed. At 90 days, moderate fibrous tissue surrounded the alginate. Tissue growth across the aneurysm neck remained complete and stable with no signs of neointimal growth into the parent vessel. CONCLUSIONCalcium alginate was an effective endovascular occlusion material that filled the aneurysm and provided an effective template for tissue growth across the aneurysm neck after 30 days and up to 90 days. Complete filling of the aneurysm with calcium alginate ensures stability, biocompatibility, and optimal healing for up to 90 days in swine.

Cerebrospinal fluid drainage and induced hypertension improve spinal cord perfusion after acute spinal cord injury in pigs.

BACKGROUND Acute spinal cord injury (SCI) is commonly treated by elevating the mean arterial pressure (MAP). Other potential interventions include cerebrospinal fluid drainage (CSFD). OBJECTIVE To determine the efficacy of aggressive MAP elevation combined with intrathecal pressure (ITP) reduction; our primary objective was to improve spinal cord blood flow (SCBF) after SCI. METHODS All 15 pigs underwent laminectomy. Study groups included control (n = 3); SCI only (n = 3); SCI combined with MAP elevation (SCI + MAP) (n = 3); SCI combined with CSFD (SCI + CSFD) (n = 3); and SCI combined with both MAP elevation and CSFD (SCI + MAP + CSFD) (n = 3). SCBF was measured with laser Doppler flowmetry. RESULTS In the SCI group, SCBF decreased by 56% after SCI. MAP elevation after SCI resulted in a 34% decrease in SCBF, whereas CSFD resulted in a 59% decrease in SCBF. The combination of CSFD and MAP elevation resulted in a 24% increase in SCBF. The SCI + MAP group had an average ITP increase of 5.45 mm Hg after MAP elevation 1 hour after SCI and remained at that level throughout the experiment. CONCLUSION Both MAP elevation alone and CSFD alone led to only short-term improvement of SCBF. The combination of MAP elevation and CSFD significantly and sustainably improved SCBF and spinal cord perfusion pressure. Although laser Doppler flowmetry can provide flow measurements to a tissue depth of only 1.5 mm, these results may represent pattern of blood flow changes in the entire spinal cord after injury.

In Vivo Experimental Aneurysm Embolization in a Swine Model with a Liquid-to-Solid Gelling Polymer System: Initial Biocompatibility and Delivery Strategy Analysis

OBJECTIVE Current treatments for cerebral aneurysms are far from ideal. Platinum coils are prone to compaction, and currently used liquid embolics are delivered with angiotoxic agents. This work presents initial in vivo studies of a novel liquid-to-solid gelling polymer system (PPODA-QT), focusing on biocompatibility and effective delivery strategies. METHODS PPODA-QT was used to embolize surgically created lateral wall carotid artery aneurysms in swine using three delivery strategies. Group 1 aneurysms were completely filled with PPODA-QT (n = 5), group 2 aneurysms were subcompletely (80%-90%) filled (n = 3), and group 3 aneurysms underwent three-dimensional coil placement followed by polymer embolization (n = 3). The study was designed such that three animals per treatment group survived to 1 month. RESULTS The group 1 delivery strategy (100% filling) resulted in survival of 3/5 animals. This strategy led to aneurysm stretching, which resulted model failure in 2/5 animals. Group 2 aneurysms, although initially <100% filled with the polymer, displayed robust neointimal tissue coverage and complete obliteration after 1 month. Group 3 aneurysms showed less prominent neointimal tissue coverage as well as two instances where excess polymer was found in the parent vessel. The PPODA-QT material showed good biocompatibility with vascular tissue in all animals at 1 month. CONCLUSIONS This small-scale pilot study highlighted first-time in vivo use of PPODA-QT as an embolic agent for aneurysm treatment. Filling aneurysms to 80% to 90% capacity proved to be a safe and effective delivery strategy, and PPODA-QT showed excellent biocompatibility. This study indicates that future investigation of PPODA-QT for aneurysm embolization is warranted, as it may prove to be a viable alternative to current embolic materials.

Titanium aneurysm clips: Part II--Seizure and electroencephalographic studies in implanted rabbits.

Because titanium is widely used in neurosurgical procedures, we compared spontaneous and induced epileptiform activity in 12 rabbits with titanium clips implanted in the subarachnoid space with 12 rabbits with cobalt alloy clips and 6 rabbits that were not operated on that served as controls. Beginning 1 week after surgery, 30-minute electroencephalographic recordings were made at monthly intervals for 6 months. Recordings were scored by an electroencephalographer unaware of which treatment group was being recorded. In 48 recordings made during 6 months, no epileptiform activity was observed in any animal. Seizure threshold was evaluated by continuous intravenous injection of the convulsant drug, pentylenetetrazole (2 mg/kg/min), with continuous electroencephalographic recording. Time to spiking for the nonsurgical control group was 327 mean seconds +/- 181 standard deviation (SD), 216 mean seconds +/- 135 SD for the titanium group, and 389 mean seconds +/- 290 SD for the cobalt group. There were no significant differences among the groups (P = 0.17). Latency to behavioral tonicoclonic seizure was 1031 seconds +/- 537 SD for the group not operated on, 875 seconds +/- 334 SD for the titanium group, and 1267 seconds +/- 764 SD for the cobalt group. This study suggests that titanium clips are well tolerated within the brain and will not induce seizures.

Carotid Endarterectomy Surgical Simulation Model Using a Bovine Placenta Vessel.

BACKGROUND Carotid endarterectomy (CEA) is a common, well-developed surgical procedure. Although surgical simulation is gaining in importance for residency training, CEA practice opportunities for surgical residents are limited. OBJECTIVE To describe a new haptic CEA model. METHODS Six bovine placentas were used to create the model. Each placenta provided about 6 large arterial and venous bifurcations. In total, 36 large-vessel bifurcations were dissected and prepared for the CEA simulation. Bovine placenta vessels were arranged to simulate the common carotid artery (CCA), internal carotid artery (ICA), and external carotid artery (ECA). The diameters and wall thicknesses were measured and compared with human CCA, ICA, and ECA parameters. RESULTS All bovine placentas provided vessels suitable for modeling carotid artery bifurcations and CEA training. Mean ± SD diameters of simulated CCAs, ECAs, and ICAs were 11.2 ± 1.8, 4.3 ± 0.5, and 9.8 ± 3.0 mm, respectively, from nondilated veins and 8.7 ± 1.4, 4.4 ± 1.3, and 7.2 ± 1.7 mm, respectively, from nondilated arteries. Mean vessel wall thicknesses were 2.0 ± 0.6 mm for arteries and 1.4 ± 0.5 mm for veins. Placental vessel tissue had dimensions and handling characteristics similar to those of human carotid arteries. The CEA procedure and its subtasks, including vessel-tissue preparation and surgical skills performance, could be reproduced with high fidelity. CONCLUSION A bovine placenta training model for CEA is inexpensive and readily available and closely resembles human carotid arteries. The model can provide a convenient and valuable simulation and practice addition for vascular surgery training.