Neurointerventional Radiology for Skull Base Lesions

Particulate Embolic Materials

Many different particles have been used for tumor embolization, and their further subdivision into polyvinyl alcohol (PVA), tris-acryl gelatin (embospheres), and polyzene F-coated hydrogel (embozenes) is based on the composition of the microsphere polymer matrix. PVA microspheres can be further subdivided into nonspherical PVA, spherical PVA, and acrylamido PVA.

The catheters required to inject these particles must have a larger inner diameter and be stiffer than those used for the delivery of liquid embolic agents. Catheters are wire guided and more difficult and hazardous to navigate through distal friable vessels than flow-guided catheters. All these restrictions make it difficult to optimize the particle size of embolic agents used to penetrate the capillary bed of the tumor without occluding the arterial pedicle or passing through the nidus into the venous system.

The size of the particles is important. Larger particle size (more than 150 μm) is believed to enable the efficient penetration of the tumor’s capillary bed. Meanwhile, particle size more than 150 μm is also safe in cases of dangerous vessel embolization. The same is true for tris-acryl gelatin and polyzene-F hydrogel microspheres.

Tris-acryl gelatin and polyzene-F hydrogel microspheres do not aggregate and tend to lodge in vessels that are close in size to the particle diameter, and blood does not flow beyond the embolized region. They are less likely to clump and clog the microcatheter. By contrast, PVA particles aggregate in vessels larger than the particle’s diameter, preventing blood flow into regions peripheral to the embolized region. However, both methods produce only temporary occlusion. Therefore, no more than 7 days between particle embolization and surgery is critical to ensure sufficient devascularization. Seemingly, tris-acryl gelatin and polyzene-F hydrogel are superior to PVA for tumor penetration to achieve embolization. But one meta-analysis assessing five widely used embolic particles (three types of PVA particles, tris-acryl gelatin, and polyzene-F hydrogel) in uterine fibroid embolization found no evidence of the superiority of any embolic agent.

Liquid Embolic Materials

The two most widely used and most effective agents for embolizing vascular lesions are polymers: n-butyl cyanoacrylate (NBCA [Histoacryl], Braun, Melsungen, Germany, and Trufill, Cordis Neurovascular, Miami, FL) and ethylene-vinyl alcohol (EVA) (Onyx; EV3 Neurovascular, Irvine, CA) dissolved in the solvent base dimethyl sulfoxide (DMSO). Like Onyx, SQUID (Emboflu, Fribourg, Switzerland) is also an EVA dissolved in DMSO but it is available in different concentrations: 4.9% and 6.0%. Micronized tantalum powder is added to both Onyx and SQUID to provide radiopaque contrast. Both Onyx and SQUID must be vortexed (Vortex-Genie, Scientific Industries, Bohemia, NY) at least 20 min to ensure stable mixing of the tantalum with the polymer.

NBCA is a liquid monomer that polymerizes into an adhesive when in contact with an anionic solution (i.e., blood). It is radiolucent but becomes radiopaque when mixed with agents such as Lipiodol (Lipiodol Ultra Fluide, Guerbet, Solingen, France), Ethiodol (Savage Laboratories, Melville, NY), or Tantalum powder (American Elements, Los Angeles, CA). A small, flexible microcatheter is safely and gently navigated into the capillary bed of the tumor for NBCA delivery. A significant level of experience is needed to deliver NBCA appropriately. It is difficult to control the polymerization time of NBCA. In our institution, we usually mix NBCA with Lipiodol in a ratio of 1:2 to 1:3 to slow polymerization. The relationship between the NBCA to Lipiodol ratio and polymerization time is not linear. Gluing the microcatheter to the vessel wall is another risk. Delayed migration of the polymerized glue into the intracranial circulation 12 h after NBCA embolization has also been reported.

The benefits of Onyx over NBCA have been well described. Onyx polymerizes after contact with blood or any aqueous solution and with diffusion of the solvent DMSO. Onyx forms a spongy surface layer but remains liquid at its center. This characteristic causes it to flow like lava within blood vessels and to form a nonadherent plug without fragmentation during injection. During the Onyx injection, the operator can interrupt the procedure several times to allow assessment of the outcome of embolization and early recognition of dangerous intracranial anastomoses. SQUID (another EVA copolymer dissolved in DMSO polymer) has become available in Europe. It is less viscous (which facilitates vascular penetration), less dense, and contains 30% less tantalum, all of which may help visualize structures behind dense embolic casts under X-ray. The micronized tantalum particles in SQUID are smaller than those in Onyx and allegedly are dispersed into a more homogeneous suspension. SQUID has been successfully used for embolization of tumors without any complication.

Particulate embolic agents are usually cheaper than liquid agents, but they have several disadvantages. The particles are radiolucent and require the addition of a contrast agent to indirectly determine the extent of tumor embolization. This adds to the embolic load, which should be a consideration when carrying out the procedure in young patients. The particles (especially PVA) tend to aggregate in and clog the microcatheters, necessitating recatheterization of the feeding arteries; this makes particulate embolization more time consuming than liquid embolization. The devascularization effect of particulate embolization is temporary, and tumor resection should be performed within 7 days.

During surgical or endoscopic procedures, it is often very difficult to distinguish tumor tissue from the surrounding tissue. Onyx provides an additional advantage in that tumor tissue is readily distinguishable both visually and under X-ray examination, making it possible to determine intraoperatively whether residual tumor tissue exists and where it is located. The clear demarcation by Onyx of the tumor from its surroundings allows for complete tumor removal and may account for the much lower recurrence rates associated with Onyx use for embolization.

Onyx and NBCA are associated with similar complications. However, Onyx use is also associated with trigeminocardiac reflex, a rare complication defined as the sudden onset of parasympathetic dysrhythmia, sympathetic hypotension, apnea, or gastric hypermotility during stimulation of any of the sensory branches of the trigeminal nerve. Because Onyx use is more expensive and more time consuming than NBCA use, it should be reserved for selective cases.

Transarterial Embolization

Skull base tumors are often devascularized under general anesthesia. Some institutions monitor neurophysiologic activity (electroencephalography, somatosensory evoked potentials, and brainstem auditory evoked potentials) and maintain activated clotting times between 250 and 300 s during the procedure. At our institution, we maneuver a 6Fr Envoy (Cordis; Miami Lakes, FL) guide catheter or 4Fr diagnostic catheter of 100 cm length (Vertebral, Glide catheter; Terumo, Tokyo, Japan) into the appropriate ECA and selectively catheterize the feeding vessels with either an SL-10 microcatheter (Stryker Neurovascular, Fremont, CA) or a 2.9F microcatheter (Progreat, Terumo) using the coaxial technique. Selective angiograms of those feeder arteries are performed to assess the portion of the tumor supplied by the artery, the degree of tumor pedicle vascularity, and the location of potentially dangerous extracranial/intracranial anastomoses ( Fig. 17.1 ).

Particulate embolization of skull base tumors is performed by placing the microcatheter tip as close to the capillary bed of the tumor as possible under fluoroscopic guidance. The antegrade flow in the feeders carries the particles to the target tumor. We prefer to start with particles about 150–250 μm in diameter to penetrate the capillary bed of the tumor and then introduce particles 250–350 μm in diameter till contrast medium stasis is observed in the feeders ( Fig. 17.2 ). Transarterial particulate embolization is performed under continuous fluoroscopic guidance until nearly complete stasis of the blood flow within each feeding pedicle is achieved. In some centers, nitroglycerine is administered intraarterially to prevent arterial spasm and to promote appropriate forward flow of particles. Many authors prefer to block the main trunk with gelfoam pledgets (Gelfoam, Upjohn, Kalamazoo, MI) or platinum microcoils (Target Therapeutics, Fremont, CA) after obtaining cessation of flow. Sometimes, we use microcoils to occlude the branches supplying normal tissue to decrease the risk of damage to the normal tissue.

During NBCA embolization, the NBCA and Lipiodol are mixed in an appropriate ratio based on the flow dynamics and micro-angio-architecture depicted on the angiogram. The catheter is then prepared by flushing with 5% dextrose water. The NBCA-Lipiodol mixture is then injected slowly under guidance using a single-column method. Injection is stopped immediately if reflux or flow into dangerous vessels is found. After withdrawal under moderate negative pressure, the micro- and guide catheters are rapidly pulled away from the site of injection to prevent them from being glued in place. The technique is repeated as many times as necessary to achieve maximal devascularization of the neoplasm. Before the NBCA-Lipiodol injection for brain arteriovenous malformations, some authors prefer to have the patient under moderate hypotension or ask the anesthesiologist to apply a Valsalva maneuver to the patient during the injection because this increases venous pressure, preventing or reducing the movement of the NBCA-Lipiodol mixture into the draining vein. We do not use this maneuver during devascularization of skull base tumors. The short polymerization time of NBCA limits the amount of embolic injected and always requires multiple injections. The injection of NBCA cannot be halted during the procedure to allow assessment of the degree of embolization and early recognition of dangerous anastomoses ( Fig. 17.3 ).

Onyx polymerizes after contact with blood or any aqueous solution and with diffusion of the solvent DMSO. Compared with NBCA, Onyx is more easily controlled. However, all DMSO-compatible microcatheters are stiffer than the microcatheters used for injection of other agents, and DMSO can cause angionecrosis and vasospasm. Before injection, Onyx must be mixed for at least 20 min. Otherwise, visualization of the Onyx during injection could be suboptimal and sedimentation of the tantalum powder could block the microcatheter hub or shaft.

Onyx is available in two concentrations and viscosities: Onyx-18, with a polymer to solvent ratio of 6% and a viscosity of 18 cP and Onyx-34, with a polymer to solvent ratio of 8% and a viscosity of 34 cP. The impact of viscosity on intraparenchymal penetration is theoretically an important consideration. In devascularization of skull base tumors, Onyx-18 is preferred.

Before embolization, removal of microcatheter redundancy should be done under fluoroscopic guidance. The contrast material in the microcatheter is cleared by flushing with saline. Then, DMSO is injected into the catheter to fill dead space in the microcatheter. Onyx injection is conducted under blank road map fluoroscopy over a 90-s period to replace the DMSO in the dead space, thereby eliminating the angionecrotic potential of DMSO. Onyx infusion is stopped when reflux around the catheter tip is detected. After several minutes, a new blank road map is created and injection is resumed. Ideally, antegrade flow is reestablished, and the Onyx enters other compartments. This procedure (the plug and push technique) is repeated until the desired effect is obtained or a normal branching vessel can be occluded. After multiple rounds of injection, reflux, and waiting, the reflux may extend 1.0–1.5 cm from the tip of the microcatheter. Finally a plug may form around the tip completely blocking blood flow and changing pressure gradients within the tumor’s capillary bed until Onyx penetrates the tumor more deeply. Unlike NBCA, Onyx requires that the microcatheter be pulled straight before retracting it with gradually increased force and then either snapping it out of the Onyx cast or slowly pulling it out. We use postembolization ECA angiograms to assess the degree of devascularization.

Embolization by Direct Puncture

Many centers suggest direct intratumoral puncture as the first-choice devascularization technique for head and neck tumors. In our institution, the rationale for using direct puncture for skull base tumor devascularization is reserved for the following conditions: impossible superselective catheterization of the feeding arteries because of their small size and tortuosity, high possibility of reflux into a dangerous intracranial anastomosis, and persistence of leakage after transarterial embolization. Using the transarterial approach, optimal intraparenchymal tumor penetration with liquid agents is difficult to achieve unless the microcatheter is situated within 2 cm of the tumor.

A single dose of preoperative antibiotics is administered because of the theoretical but low risk of infection from oral or nasal flora. A detailed angiographic evaluation of the degree of lesion is obtained, and the tumor extent is confirmed by CT or MR examination. Depending on the location of the tumor and the important adjacent neurovascular structures, needles can be placed directly into the tumor via the transzygomatic, transnasal, transoral, transbuccal, transpalatal, transorbital, or percutaneous route. Which approach is selected depends on proximity to the tumor and appropriate margins needed to protect vital neurovascular structures. An 18- or 20-gauge needle is used to puncture the tumor under angiographic and fluoroscopic guidance and subsequently advanced to the center of the lesion under fluoroscopic road map guidance. An intratumoral angiogram is performed to confirm the position of the needle within the tumor, assess the microvasculature of the tumor, determine the venous drainage pattern, and identify dangerous intracranial anastomoses. Then the hub of the puncture needle is connected to a 10-cm Luer Lock extension tube. The dead space is slowly filled with DMSO (when Onyx is the embolic agent) or 5% dextrose water (when NBCA is the embolic agent) using a 1-mL Luer Lock syringe as needed. Embolization of the tumor is performed under subtracted road map guidance. In large heavily vascularized tumors, the needle can be redirected under road map guidance to a different compartment of the tumor to allow a more thorough penetration of embolic agents. Intermittent ECA and ICA angiography is needed to assess the degree of devascularization and detect hemodynamic changes such as recruitment of short arterial feeders from the ICA or VA after partial embolization. If this happens, placement of a temporal balloon at the origin of these arteries in the ICA or VA may theoretically be helpful in preventing nontarget embolization during further intratumoral injection of a liquid embolic agent. However, this increases the complexity of the procedure and may subject the patient to the additional risk of dissection or a thromboembolic event. Feeders from the ophthalmic artery are a relative contraindication for direct puncture embolization with a liquid embolic agent. Embolization is continued until the desired degree of tumor penetration is achieved.