Interventional Neuroradiology Practice and Technique

Interventional neuroradiology offers minimally invasive therapies for lesions of the head, neck, spine, brain, and spinal cord. Endovascular therapies include embolotherapy (see images below), the goal of which is occlusion of abnormal blood vessels (eg, vascular malformations, aneurysms, vascular tumors), and cerebral revascularization, performed with the goal of reopening occluded or narrowed normal vessels. Nonvascular interventions include pain management, percutaneous biopsies, percutaneous vertebral augmentation procedures, and percutaneous management of disk disease.[1, 2, 3, 4, 5, 6, 7, 8]

A, Gadolinium-enhanced MRI of a large meningioma. B, External carotid angiogram obtained before embolization. C, Selective catheterization of the feeder branch (ie, the middle meningeal artery). D, Photomicrograph of Bead Block microemboli. E, Image obtained after embolization with polyvinyl alcohol (PVA) particles. The tumor was subsequently surgically resected with minimal blood loss.

Detachable silicone balloons uninflated (A) and inflated (B). Carotid-cavernous sinus fistula before embolization (C) and after embolization (D) with Gold Valve detachable balloons.

Among endovascular therapies, embolization of aneurysms (see image below) is one of the principal procedures. Although all patients with ruptured or unruptured aneurysms should be evaluated for endovascular therapy, not all are best served by this therapy. Conventional surgical clipping is still a consideration. In selecting appropriate therapy, referring and interventional physicians should consider the configuration of the aneurysm and its neck, the location(s) and number of aneurysms, and the patient's preference and overall physical condition (eg, ability to tolerate anesthesia and surgery). They should weigh the risks and benefits of each therapy on a case-by-case basis and should present their conclusions and recommendations to patients who are able to give consent and to their families and the referring physician.

Large ruptured aneurysm before embolization (A) and after embolization (B, C) embolization with Guglielmi detachable coils.

Embolotherapy

Although embolotherapy has been practiced for approximately 40 years, application of this therapy for definitive or preoperative adjunctive management of aneurysms, vascular malformations, and vascular tumors continues to evolve. Progressive improvement in outcomes of endovascular therapy is principally the result of ongoing development and refinement of microcatheter delivery systems and of safer and more varied embolic agents and devices. New microcatheters increase superselectivity; this, in turn, improves target-specific embolization with increased preservation of adjacent normal vascular anatomy. These microcatheters can be used to deliver all currently available embolic agents, including particulate emboli, coils, balloons, tissue adhesives, nonadhesive agents, sclerosing agents, and chemotherapeutic agents.[9, 10]

Particulate embolic agents

Particulate agents are the embolic materials of choice for occluding the microvascular supply of tumors and for managing many hemorrhagic conditions. These agents are divided into 2 general categories: absorbable and nonabsorbable agents.

Absorbable agents

Absorbable agents, as their name implies, do not permanently occlude vessels and therefore provide benefit only within the first few hours of therapy. Absorbable agents are most effective for management of transient bleeding such as that associated with epistaxis, or for preoperative devascularization of vascular lesions such as meningiomas and some hypervascular metastases. Materials in this category include gelatin sponge, available as a powder of 40-60 µm in particulate diameter or in sheets that can be cut into large particles or into pledgets. Microfibrillar collagen is supplied as a powder with a particle size of approximately 50 µm. It is widely used as a topical thrombotic agent in conventional surgery and provides very rapid thrombosis of vessels treated endovascularly.

On occasion, absorbable embolic agents can be used to protect normal vessels. With this technique, a normal vessel is temporarily occluded, allowing redirection of the flow of permanent embolic agents into abnormal vessels. An autologous blood clot may be used for temporary protective occlusion because it rapidly recanalizes. Likewise, a pledget of gelatin sponge can be placed in the origin of a normal arterial branch to ensure that permanent embolic materials or chemotherapeutic agents infused proximally do not enter that vessel, and that they are directed to abnormal vessels.

Vessels occluded with autologous clot and/or Gelfoam pledgets recanalize in a short time, reestablishing flow to normal territory. However, abnormal vessels embolized with nonabsorbable agents remain occluded, and those treated with chemotherapeutic agents remain open for repeat therapy. For large vessels of the cervical arterial anatomy, similar utility is seen with the use of nondetachable, low-pressure balloon catheters. This technique is particularly effective when used to direct the flow of chemotherapeutic agents into vessels of the head and neck that are too small to be selectively catheterized, while temporarily diverting flow away from normal vessels.

Absorbable agents are effective when used as preoperative adjunctive therapy immediately preceding surgery. However, the author's philosophy is that preoperative embolization should be as complete and permanent as possible. The recommended approach requires the use of nonabsorbable agents, given the possibility of delayed surgery or incomplete surgical resection of the lesion. In the event of the latter, permanent embolization of the unresected portion of the tumor may improve the overall outcome. Use of permanent agents at the outset may obviate the need for repeat embolizations.

Nonabsorbable agents

The nonabsorbable particulate agents most commonly used are polyvinyl alcohol (PVA) particles. Prepackaged PVA particles are provided in a range of sizes, varying from one manufacturer to another. Particles are typically 150 to 1000 μm in particulate diameter. Small particles are most frequently used to embolize vascular tumors, whereas larger particles are most useful for occluding large, low-flow vascular malformations. In larger, higher-flow vascular pathology, macroembolic agents, including microcoils and occasionally suture material, can be used to build a framework or mesh against which microparticulate agents may accumulate.

(See image below.)

Arteriovenous malformation before embolization (A) and after embolization (B and C) with polyvinyl alcohol (PVA) particles, ethanol, and coils.

Vessels embolized with PVA alone tend to recanalize after a few weeks. Although the particle itself is nonabsorbable, the extremely irregular surface of each particle creates a high coefficient of friction, which often results in adhesion of particles proximal to the wall of the vessel without complete occlusion of the nidus. Blood flow is usually eliminated initially. However, the thrombus that forms between particles may eventually recanalize. Neoendothelium covers particles remaining on the surface. This limitation can be partially overcome by packing the vessel with high concentrations of small PVA particles, then performing proximal occlusion with large particles or microcoils.

Different combinations of agents may be used to achieve a more permanent occlusion. Absolute ethanol mixed with particles not only will occlude the target vessel, but it will also denature the vascular endothelium, resulting in a fibrotic reaction within the lumen and around the particles. Because it is a nonparticulate and is extremely cytotoxic, the concern is that ethanol is likely to pass through vessels with a diameter approximating the size of the particles, resulting in necrosis of perilesional normal tissue. In addition, the presence of alcohol in the external carotid system tends to be painful. Sodium tetradecyl sulfate injection has been used as an alternative sclerosing agent because it is less painful than ethanol.

Another alternative combination consists of a mixture of PVA particles and microfibrillar collagen. This combination offers several advantages. When mixed in contrast material, microfibrillar collagen forms a colloidal suspension in which PVA particles remain suspended and somewhat evenly dispersed. This suspension, in turn, facilitates delivery of particles through the small lumen of the microcatheter, decreasing the likelihood that particles in the catheter will be impacted, leading to occlusion. This advantage helps to avoid a time-consuming exchange of catheters.

With an average particle size of 50 μm, microfibrillar collagen fills the gaps between PVA particles, helping to provide more complete occlusion. Histologic studies have shown that microfibrillar collagen in occluded vessels will form a collagen matrix that adheres to both endothelium and PVA particles. This combination offers an advantage over the PVA–ethanol mixture in that it produces less patient discomfort and is less likely to pass through small anastomoses and injure adjacent normal tissue. After the PVA–microfibrillar collagen admixture is infused, the residual lumen of the abnormal vessel at the catheter tip may be occluded with the use of a platinum microcoil to reduce arterial pulsations against occlusive particles. This coiling appears to slow the rate of recanalization long enough for luminal fibrosis to occur.

Long-term studies on the evolution of vessels embolized with PVA, microfibrillar collagen, and coils have not been conducted; however, in the author's experience, this combination has proved effective for management of vascular tumors of the head and neck. Microfibrillar collagen is not routinely included in intracerebral and intraspinal embolizations; this serves to minimize inadvertent embolization of the normal cerebral or spinal microvasculature.

Soft, smooth, deformable particles (Embospheres) and compressible microspheres of liquid PVA (Bead Block) tend to ovalize when confined—a trait that makes these agents effective in distal embolotherapy. Because they do not adhere to vascular walls as crystalline PVA particles do, these soft particles are most likely to reach the capillary bed of a tumor or the nidus of a malformation. Both Embospheres and Bead Block can be tagged with chemotherapeutic agents and isotopes.

Liquid embolic agents

Among the most notable liquid embolic agents are N -butyl cyanoacrylate (NBCA) and acrylic tissue adhesive. Acrylic tissue adhesive rapidly polymerizes on contact with any ionic substance such as blood, saline, ionic contrast medium, and vascular epithelium. Polymerization time is prolonged with the mixture of various amounts of glacial acetic acid and/or oil-based contrast agents such as ethiodized oil .

The flow velocity of an arteriovenous shunt may be reduced by other agents prior to NBCA infusion to minimize the risk of errant passage of glue into the venous system. For example, platinum microcoils may be deployed distally with the intent of reducing, not occluding, flow, prolonging the length of time NBCA remains in the lumen of the target vessel for polymerization. The main advantage of this tissue adhesive is its ability to rapidly occlude high-flow arteriovenous malformations (AVMs), achieving a result that is more permanent than that possible with particulate agents. NBCA is more likely than particulate agents to reach and occlude the nidus of an AVM.

Use of NBCA involves several disadvantages. The catheter must be rapidly withdrawn after each injection of NBCA to prevent gluing of the catheter tip to the vessel wall. This results in frequent, time-consuming catheter exchanges. If the lesion was difficult to access initially and additional infusions are required, considerable time may be needed to reposition a new catheter within the vessel a second or third time.

Failure to rapidly withdraw the catheter increases the chance that the catheter may be glued in place. Complications secondary to incorrect polymerization time add to the risk. Polymerization time that is too short may result in proximal vessel occlusion and possible incorporation of the catheter tip. Prolonged polymerization time may result in passage of acrylic through the malformation and solidification within the venous outflow tract, increasing the risk of hemorrhage. Because the resultant glue cast is rigid, patient discomfort may be notable and a foreign-body sensation may occur after embolization of lesions of the face, mouth, tongue, or neck. For these reasons, use of NBCA is limited to occlusion of high-flow AVMs of the brain and spinal canal.

The remarkable increase in demand for interventional procedures has spurred the development of embolic agents and devices that are safer and more permanent. Nonadhesive, flexible polymers offer all the advantages of NBCA without the risk that a catheter may be glued in place and without the need to exchange catheters after each infusion. One nonadhesive liquid embolic agent, Onyx, appears to be safer and more effective than NBCA for treatment of high-flow AVMs. Onyx provides the added advantage of forming soft, pliable casts, which, unlike the more brittle NBCA, facilitate less complicated surgical resection of embolized AVMs.

(See image below.)

Right temporal arteriovenous malformation (AVM) supplied by the right middle cerebral artery (RMCA) (A and B) and left vertebral artery (LVA) (C and D). E and F, Casts of nonadhesive liquid embolic agent (Onyx) in the feeders and nidus. G and H, Postembolization angiograms show no residual flow to the AVM.

Sclerosing agents

Absolute ethanol is the prototypic sclerosing agent. Solutions opacified with metrizamide powder have produced excellent results in the obliteration of large vascular malformations. Sodium tetradecyl sulfate behaves similarly to alcohol, but with less associated pain. As has been discussed, ethanol has been included in particulate admixtures, most notably in the admixture of microfibrillar collagen and PVA particles.

As a cytotoxic agent, ethanol facilitates tissue necrosis during tumor embolization. This effect is especially useful when neoplasms of nonneural origin are treated. Risks associated with the use of ethanol include peritumoral swelling, pain, and necrosis of normal peritumoral tissue via normal microscopic anastomotic branches. Aggressive clinical monitoring by an anesthesiologist during embolotherapy is essential for reducing pain and preserving an airway when lesions of the oropharynx and neck are treated.

In the author's experience, embolotherapy with absolute ethanol, compared with particulate agents alone and with NBCA, has resulted in more permanent occlusion of abnormal vessels without the inherent risks associated with tissue adhesives.

Coils

Historically, fibered stainless steel Gianturco and Hilal coils were used to reduce or redirect blood flow in large arteriovenous malformations (AVMs), arteriovenous fistulas (AVFs), and hemorrhagic traumatic vascular injuries of the extracranial circulation. Magnetic resonance (MR)-compatible platinum coils have largely replaced MR-incompatible stainless steel coils. The older coils are considerably larger in diameter than the microcatheter delivery systems. Catheters of size 4F or larger are required with these 0.035-inch and 0.038-inch coils. Catheters of this size severely limit the distance into which a vessel can be cannulized. Unless the malformation is large, it is unlikely that coils of this size will reach the nidus.

The coil itself often does not produce complete thrombosis of the vessel, and it secondarily inhibits further embolization with other agents. Therefore, use of large coils is limited to occlusions of large vessels in the neck and skull base—usually those occurring after penetrating trauma (see image below). Proximal vessel embolization with larger coils may help retard recanalization of distal vasculature embolized with smaller microcoils and/or particles.

A, Gunshot wound to the right side of the neck transects the right vertebral artery (RVA) and the right internal maxillary artery (RIMAX), with partial transection and pseudoaneurysm formation in the midcervical right internal carotid artery (RICA). B and C, Transected segments of the RVA and RIMAX are coil embolized. The RICA pseudoaneurysm was successfully treated with a 7 x 40-mm Wallgraft covered stent.

A variety of microcoils have been developed for use with microcatheter systems to facilitate distal deployment in small vessels of the head, neck, and spine. Hilal coils, the earliest of the fibered microcoils, were effective but were made of stainless steel and were relatively stiff. These were later replaced by a softer, platinum version that was MR compatible. Platinum microcoils 0.010 and 0.016 inches in diameter, with and without Dacron polyester fibers, are available for use with microcatheter systems and are supplied in a variety of shapes, sizes, and lengths. Most of these are woven with small polyester fibers to increase their thrombogenicity. These small coils can be deployed just proximal to the nidus of a malformation if it is accessible with a microcatheter, or they can be directed by blood flow and floated peripherally if direct access to the nidus cannot be achieved. Microcoils are effective for rapid establishment of hemostasis in patients with traumatic vascular injuries.

Soft Berenstein Liquid coils lack fibers and are intended to flow farther into a vessel than more rigid fibered coils. Because these coils are small, distal occlusion is most effectively achieved. Flow velocity is often reduced to the point where subsequent particulate or liquid embolization provides more thorough occlusion of abnormal vessels. As has been mentioned, these coils are frequently deployed proximally in a vessel after particulate embolization to reduce the likelihood of recanalization. Although it is one of the most useful devices in the armamentarium, this coil is no longer in production. Unless well anchored in place, this coil may pass through fistulas or go more distally than intended in high-flow states. Many coils may be needed to occlude high-flow fistulas without the use of a liquid embolic. Also, vessels occluded only with these coils may still recanalize over time, possibly clogging the microcatheter, especially when longer lengths are used.[11]

If coiling is still the main endovascular technique for treatment of unruptured aneurysms, several other techniques are available, including stent-assisted coiling, flow diversion, and flow disruption.[12]  Aneurysm coiling affords good protection against bleeding (for unruptured aneurysms) and rebleeding (for ruptured aneurysms) at 1 year, with rates of 0.0% and 1.0%, respectively. Aneurysm occlusion and dome-to-neck ratio are factors that appear to play a role in the occurrence of rebleeding.[13]

Interventional management of aneurysms with detachable coils is distinctly different from management with nondetachable coils and is discussed separately in the following paragraphs.

Balloons

Detachable balloon macroemboli are no longer available. For the sake of completeness, a short discussion is included in this section.

Advantages of balloon embolization include the following:

• Ability to occlude a vessel at a precise location

• Ability to navigate attached, partially inflated balloons to distal locations along a tortuous course

• Ability to rapidly occlude vessels larger than the caliber of the catheter

• Ability to repeatedly inflate, deflate, and reposition the balloon until the desired position is achieved

The original latex balloons were manually bound to coaxial microcatheter assemblies with latex ligatures. Although effective, this technique was tedious and time consuming. Latex and silicone elastomer balloons with mitered valves were subsequently developed to facilitate attachment and detachment.

Latex and silicone balloons have different properties with respect to distensibility, time to deflation, and surface-friction characteristics. Latex balloons are more distensible and compliant than silicone balloons and therefore most readily conform to the shape of a vessel while reducing the risk of vascular rupture. Latex also has a far greater coefficient of surface friction when compared to silicone. This feature reduces the likelihood of balloon migration. These properties make latex balloons preferable for occluding large, high-flow vessels, as in trapping procedures, and for treating carotid-cavernous sinus fistulas.

In contrast, silicone balloons are relatively noncompliant and inflate to a preformed shape. Therefore, they are less likely than latex balloons to mold to the vascular contour. Because of their lowered coefficient of friction, they are more likely than latex balloons to migrate after detachment. Silicone is less porous than latex; thus, silicone balloons tend to remain inflated longer, averaging more than 24 weeks to deflation versus 2-4 weeks to deflation for latex balloons.

Although they were effective in their day, detachable balloons have largely been replaced by a wide variety of macrocoils and microcoils, which can be deployed more rapidly through smaller delivery systems and at lower cost to the patient.

Endovascular management of intracranial aneurysms (IAs) has evolved considerably over past decades. Technological advances have been driven by the experience that coils fail to completely exclude all IAs from the blood circulation and by the need to treat the diseased parent vessel segment that led to aneurysm formation; endovascular therapy has been expanded to treat more complex IAs. Stents were initially developed to support placement of coils inside wide-neck aneurysms. However, early work on stent-like tubular braided structures led to a more sophisticated construct that later was coined as a flow diverter (FD) and found its way into clinical application. Although FDs were initially used to treat wide-neck large and giant internal carotid artery aneurysms amenable only to surgical trap with or without a bypass or endovascular vessel sacrifice, their use in other types of IAs and in cerebrovascular pathology promptly followed. We have witnessed an explosion in the application of FDs and subsequently in their modifications, leading to their ubiquitous use in endovascular therapy.[14]

History

The first endosaccular treatments for aneurysms consisted of open surgical techniques, including magnetic direction of ferrous spherical emboli released in the proximal arterial anatomy and deployment of charged copper wires through an aneurysm dome. The work of Drs. Werner and Blakemore in the late 1930s represented an extrapolation of the use of copper wire for treatment of abdominal aortic aneurysms. Although successful, these techniques did not offer outcomes better than those associated with conventional surgical clipping.

Initial endovascular management of aneurysms was based on endosaccular deployment of appropriately sized latex balloons (see image below) via an angiographic rather than an open surgical approach. Developed in Russia by Dr. Fedor Serbinenko in 1962, this technique was associated with a high incidence of aneurysmal rupture. This complication was believed to result from rigid balloons exerting asymmetric pressure on the walls of aneurysms, causing deformity of the aneurysm that frequently led to rupture.

Although the use of endosaccular wires and balloons in aneurysm therapy was fraught with complications and was short lived, this work inspired extensive research into the development of safer, more effective devices for endovascular management of IAs.

(See image below.)

Detachable silicone balloons uninflated (A) and inflated (B). Carotid-cavernous sinus fistula before embolization (C) and after embolization (D) with Gold Valve detachable balloons.

Coils

Guglielmi detachable coil

Although the use of balloons to treat aneurysms quickly fell out of favor, Serbinenko's work provided the momentum that eventually led to the development of the detachable coil technique pioneered by Dr. Guido Guglielmi in 1990. The Guglielmi detachable coil (GDC) has been modified extensively over the years, but the basic design remains, and it is the most widely used device for embolotherapy of intracranial aneurysms to date.

Endovascular management of aneurysms requires a coil with unique properties, including control and recoverability, softness, and maximum packability. GDC coils are long, nonfibered, platinum microcoils fused to a guidewire. These coils—the first to gain FDA approval—can be positioned, withdrawn, and repositioned repeatedly until the desired position is obtained. Detachment is then achieved by passing a low-voltage, low-amperage current through the guidewire to hydrolyze the connection between the guidewire and the coil. This current also initiates platelet and red blood cell (RBC) aggregation, promoting thrombosis. These coils offer a distinct advantage over detachable balloons in that conformable platinum coils exert minimal, more uniformly distributed pressure on the wall of the aneurysm. This feature reduces the risk of periprocedural rupture—a problem inherent to the use of rigid coils and balloons.

Bioactive coils

A GDC variant called the Matrix coil is coated with polyglycolic-polylactic acid (PGLA) copolymer that promotes fibrosis within and around the coil mass, which is intended to improve the permanence of the procedure while promoting shrinkage of the aneurysm. Alternatively, the Cerecyte coil is a platinum coil with a bioactive PGLA copolymer core. Functionally similar to GDCs, Cerecyte coils differ in that they are detached thermally rather than hydrolytically. Another device, the HydroCoil Embolic System, consists of a platinum core with integrated hydrogel and was developed to reduce recurrence by enhancing packing density and healing within the aneurysm.[15]  The HydroCoil expands in a fluid environment after deployment but is not considered bioactive because hydrogel does not promote fibrosis, as does PGLA. A randomized. controlled trial found that coiling of small to medium-sized aneurysms with second-generation HydroCoil resulted in less recurrence when compared to use of a bare platinum coil, without causing increased harm. The study authors concluded that these data support the use of the second-generation HydroCoil for embolization of IAs.[15]

Balloon-assist technique

Until the early 2000s, endovascular therapy could be offered only to patients with aneurysms of a configuration that was amenable to coiling; that is, the aneurysm had to have a relatively small neck that could hold detached coils in place within the lumen of the aneurysm and outside the parent artery. However, this changed with the advent of the balloon-assist technique, which uses extremely soft, compliant, nondetachable balloon catheters made of silicone. With this technique, inflation across the neck of the aneurysm with the balloon catheter increases the degree of coil packing in aneurysms with wide necks that were previously considered untreatable by the endovascular approach.

Stents

Stents were first developed to support the placement of coils inside wide-neck aneurysms. However, early work on stent-like tubular braided structures led to a more sophisticated construct that later was coined a flow diverter (FD) and found its way into clinical application.[14]

The introduction of the Neuroform stent further increased the number of wide-necked aneurysms that would be amenable to embolotherapy. This soft, self-expanding nitinol stent is deployed across the neck of the aneurysm. If the aneurysm is unruptured, the stent is left in place for several weeks to allow assimilation of the ends of the stent into the arterial walls distal and proximal to the aneurysm neck. This assimilation stabilizes the stent, so that subsequent coil embolization through the interstices of the stent can be performed with greater safety.

Covered stents have yet to be developed for use intracranially, although the Jostent covered coronary graft stent and the Wallgraft covered stent have been used to successfully treat patients with pseudoaneurysms in the cervical segments of the carotid and vertebral arteries (see image below). Development of a smaller, more distally deliverable covered stent will offer yet another minimally invasive tool for reconstructing arteries and sequestering aneurysms from arterial flow.

A, Gunshot wound to the right side of the neck transects the right vertebral artery (RVA) and the right internal maxillary artery (RIMAX), with partial transection and pseudoaneurysm formation in the midcervical right internal carotid artery (RICA). B and C, Transected segments of the RVA and RIMAX are coil embolized. The RICA pseudoaneurysm was successfully treated with a 7 x 40-mm Wallgraft covered stent.

Bioresorbable vascular scaffolds (BVSs; resorbable stents) have changed practice patterns in cardiology. The authors of a retrospective review concluded that absorbable stent technology has potential applications in interventional neuroradiology as well and suggested that BVSs should be optimized for cerebral circulation if prospective studies are to be undertaken for cerebrovascular applications.[16]

In a single-center series, Sahnoun and colleagues found that intrasaccular flow disruption with the WEB embolization system is a safe and efficacious technique that has significantly changed endovascular management of wide-neck bifurcation aneurysms (WNBAs). Use of a stent in combination with WEB is occasionally required. The study authors concluded that combining WEB and stent is a therapeutic strategy that can be used to manage WNBAs. In this series, the combination was used in 11.2% of patients treated with WEB, resulting in no morbidity or mortality and high efficacy at 6 and 12 months (complete aneurysm occlusion in 88.2% and 92.9%, respectively).[17]

Flow diversion

Flow diversion is a technique that is used to treat large or giant wide-necked aneurysms that are not amenable to endovascular coil embolization. Rather than directing treatment toward the lumen of the aneurysm, the surgeon places a stent device inside the parent blood vessel across the aneurysm neck. The Pipeline Stent (EV3) is a braided cylindrical mesh, which, when deployed across an aneurysm neck, slows and disorganizes the flow of blood into the aneurysm, which, in turn, promotes thrombosis. Intracranial aneurysms (IAs) treated with the Pipeline Stent remained occluded in up to 94% of patients at 1-year angiographic follow-up.

Flow-diverting stents are increasingly used for minimally invasive treatment of IAs. However, correct positioning of such devices can be challenging because of varying vessel diameters and the complex anatomy of the neurovasculature. As a consequence, unsuccessful treatment outcomes are increasingly reported, requiring improved understanding of stent-induced flow modification. Roloff and Berg examined an experimental framework using stereoscopic particle image velocimetry (PIV) to address this problem. They found that high-resolution in vitro PIV measurements enable accurate quantification of treatment efficacy for flow-diverting devices. Furthermore, insufficient treatment outcomes can be reproduced, allowing for assessment of intra-aneurysmal hemodynamic changes.[18]

Intracranial aneurysms in distal locations are sometimes difficult to treat because of their branching locations and the presence of blister-like or very wide-necked aneurysms. Braided intracranial stents, including flow diverters (FDs) and low-profile braided intracranial stents (LPBSs), may provide additional advantages due to their flow-diverting properties. These devices have shifted the interest from filling of the aneurysm sac to regional remodeling through the effect of flow diversion. After a critical review of the literature, review authors concluded that FDs modify the regional anatomy and that careful preprocedural consideration of the regional hemodynamic equilibrium is mandatory, as is an effective antiplatelet regimen. LPBSs provide a moderate flow-diversion effect, which may offer an advantage, especially for very distal and small aneurysms.[19]

Parent vessel sacrifice

Occasionally, aneurysms occur as the result of a blowout of the parent artery. In these cases, reconstruction of the parent artery or endovascular embolization may not be feasible. The remaining alternative of last resort may be occlusion or sacrifice of the parent vessel from which the aneurysm arises.

Success of this technique is dependent on the integrity of the circle of Willis and the ability of remaining basilar and/or carotid arteries to supply the cerebral arterial distribution of the artery to be sacrificed. This may be readily apparent on diagnostic cerebral angiography if the anterior and/or posterior communicating arteries are identified and are widely patent. If these collateral vessels are not readily apparent, sacrifice may still be an option.

To ensure the adequacy of collateral flow, an intra-arterial balloon test occlusion with concurrent technetium single-photon emission computed tomography (SPECT) imaging may be performed. If the test occlusion fails, the patient should not be deemed a candidate for permanent parent vessel sacrifice. If the patient does not manifest a focal neurologic deficit over a 30-minute test occlusion, parent vessel sacrifice will likely be well tolerated by the patient. If the SPECT study shows decreased uptake in that vascular distribution, even if the patient does not manifest a neurologic deficit, the sacrifice will still likely be successful, but several days of postembolization hypertensive therapy will be required.

Arterial sacrifice was originally achieved via a trapping procedure with the use of detachable balloons, in which parent vessel occlusion would first be performed distal to the aneurysm to prevent retrograde filling, then would be followed by occlusion proximal to the aneurysm to prohibit antegrade flow to the aneurysm. This same result can now be more easily accomplished with deployment of 0.035- or 0.038-inch fibered platinum coils such as the Vortex coil.

Endovascular treatment of aneurysms with flow diverters or coiling is sometimes complicated by intraprocedural or postprocedural thrombosis along or within the devices. Thrombus composition and structure associated with such complications may provide insights into mechanisms of thrombus formation and clinical strategies to remove the thrombus.[20]

The use of robotics in medicine may enable increased technical accuracy, reduced procedural time and radiation exposure, and remote completion of procedures. Researchers have described the first-in-human, robotic-assisted cerebral aneurysm treatment using the CorPath GRX Robotic System. They report early experiences and outcomes when this robotic device was used for endovascular treatment of IAs via stent-assisted coil embolization and flow diversion. The CorPath GRX Robotic System demonstrated precise control over microcatheter, wire, and stent during aneurysm treatment. Investigators concluded that robotic neuroprocedures seem to be safe and effective and produce stable occlusion results at midterm follow-up.[21]

Assessment of 3D T1-SPACE (application-optimized contrast via different flip-angle evolutions) combined with 3D-TOF (3-dimensional time-of-flight) magnetic resonance angiography for follow-up evaluation of stent-assisted coil embolization for intracranial aneurysm revealed that the 3D T1-SPACE sequence provides better image quality and greater accuracy for evaluating stented parent arteries compared to TOF-MRA. Researchers found that 3D-TOF MRA has merit in evaluation of aneurysm occlusion, and that the combination of these modalities can be used as an optional follow-up evaluation after endovascular treatment of IAs.[22]

Thromboembolic events represent the most frequent complications of endovascular treatment for unruptured intracranial aneurysms using stent-assisted coilling or flow-diverter stents. Dual antiplatelet therapy has become the standard for preventing these events but remains unstandardized. A retrospective review of safety and efficacy data from patients treated over 5 years with antiplatelet standardized regimens found no significant difference in safety and efficacy in the context of endovascular treatment of unruptured aneurysm using stent or flow diverters. This study provided data on the use of Cangrelor, an intravenous platelet P2Y12 antagonist, during neuroendovascular intervention. Randomized, controlled studies are warranted to confirm these findings.[23]

Stroke statistics

The Centers for Disease Control and Prevention (CDC) has provided the following stroke statistics.[24]

• Every year, more than 795,000 people in the United States (US) have a stroke. About 610,000 of these are first or new strokes. In 2020, 1 in 6 deaths from cardiovascular disease was due to stroke.
• Every 40 seconds, someone in the US has a stroke. Every 3.5 minutes, someone dies of stroke. About 185,000 strokes—nearly 1 in 4—occur in people who have had a previous stroke.
• About 87% of all strokes are ischemic strokes, in which blood flow to the brain is blocked. Stroke-related costs in the US came to nearly $53 billion between 2017 and 2018. This total includes the cost of health care services, medicines to treat stroke, and missed days of work.
• Stroke is a leading cause of serious long-term disability. Stroke reduces mobility in more than half of stroke survivors 65 years of age and older.
• The lifetime risk of stroke for women between the ages of 55 and 75 in the US is 1 in 5. Stroke kills twice as many women as breast cancer does, making stroke the third leading cause of death for women.
• Stroke is a leading cause of death in the United States, but the risk of having a stroke varies with race and ethnicity. The risk of having a first stroke is nearly twice as high for Blacks as for Whites, and Blacks have the highest rate of death due to stroke. Although stroke death rates have declined for decades among all race/ethnicities, Hispanics have seen an increase in death rates since 2013.
• Stroke risk increases with age, but strokes can—and do—occur at any age. In 2014, 38% of people hospitalized for stroke were younger than 65 years old.

Stroke risk factors

Stroke risk factors are listed below, based on reports by Johns Hopkins University.[25]

Risk factors that can be changed, treated, or medically managed include the following:

• High blood pressure
• Heart disease
• Diabetes
• Smoking
• Use of birth control pills (oral contraceptives)
• History of transient ischemic attacks (TIAs)
• High red blood cell count
• High blood cholesterol and lipids
• Lack of exercise
• Obesity
• Excessive alcohol use
• Use of illegal drugs
• Abnormal heart rhythm
• Cardiac structural abnormalities

Risk factors that cannot be changed include the following:

• Older age
• Race
• Gender
• History of prior stroke
• Heredity or genetics

Other risk factors include the following:

• Where you live: Strokes are more common among people living in the southeastern US than in other areas. This may be because of regional differences in lifestyle, race, smoking habits, and diet.
• Temperature, season, and climate: Stroke deaths occur more often during extreme temperatures.
• Social and economic factors: Evidence suggests that strokes are more common among low-income people.

Stroke therapy summary

The National Institute of Neurological Disorders and Stroke (NINDS) recommends the following for patients presenting with an acute neurologic deficit.

Target times are as follows:

• Door to doctor: 10 minutes

• Door to computed tomography (CT) completion: 25 minutes

• Door to CT reading: 45 minutes

• Door to treatment: 60 minutes

• Access to neurologic expertise: 15 minutes

• Access to neurosurgical expertise: 2 hours

• Admission to a monitored bed: 3 hours

• Acute stroke algorithm (immediate assessment: < 10 min from arrival):

  • Alert stroke team: Neurologist, radiologist, and CT technician

  • Assess airway, breathing, and circulation (ABCs) and vital signs

  • Provide oxygen by nasal cannula

  • Attain intravenous access; obtain blood samples (CBC, electrolytes, coagulation studies)

  • Check blood glucose; treat if indicated

  • Obtain 12-lead electrocardiogram (ECG) to check for arrhythmias

  • Perform general neurologic assessment

• Immediate neurologic assessment (< 25 min from arrival):

  • Review patient history

  • Establish time of onset (< 3 hr for fibrinolytic therapy)

  • Perform general physical examination

  • Perform detailed neurologic examination: Determine level of consciousness (Glasgow Coma Scale) and level of stroke severity (National Institutes of Health [NIH] Stroke Scale or Hunt and Hess Scale score)

  • Order urgent noncontrast CT scan

  • Obtain cervical spine radiograph (if comatose or history of trauma)

• General therapies for stroke patients:

  • Maintain blood pressure (systolic, 160-180 mm Hg)

  • Titrate fluids and vasoactive agents as needed

  • Maintain adequate ventilation (arterial PCO2 30-35 mm Hg)

  • Maintain moderate hypoxia (arterial PO2 >100 mm Hg)

  • Use lowest possible positive end-expiratory pressure 

  • Keep arterial pH at 7.3 to 7.5

  • Immobilize (neuromuscular paralysis) as needed

  • Sedate as needed

  • Provide anticonvulsants as needed

  • Correct blood abnormalities (eg, anemia, electrolytes)

  • Monitor and maintain normal serum glucose level

  • Give thiamine (100 mg) if malnourished or alcoholic

  • Give osmotherapy (mannitol or glycerol) as needed for monitored intracranial pressure elevation or secondary neurologic deterioration

  • Avoid hypotonic fluids; avoid excessive fluids

  • Keep temperature normal (allow low temperature; treat high temperature)

  • Start nutritional support within 48 hours

A critical point is to never “normalize” the blood pressure of a patient experiencing an acute neurologic deficit. The target systolic blood pressure is 160-180 mm Hg.

Fibrinolytic therapy consists of the following:

• Systemic intravenous recombinant tissue plasminogen activator (rt-PA) within 3 hours (only FDA-approved protocol for cerebral thrombolysis)

• Regional intra-arterial tissue plasminogen activator (t-PA)/urokinase/abciximab (ReoPro) within 6 hours

• Local intra-arterial t-PA/urokinase/abciximab within 6 hours

Intravenous tissue plasminogen activator (t-PA) therapy requires the following:

• Inclusion criteria:

  • Age 18 years or older

  • Clinical diagnosis of ischemic stroke causing measurable neurologic deficit

  • Time of symptom onset well established as less than 180 minutes before treatment begins

• Exclusion criteria:

  • Intracranial hemorrhage on noncontrast head CT scan

  • Only minor or rapidly improving stroke symptoms

  • High suspicion of subarachnoid hemorrhage even if CT scan is normal

  • Active internal bleeding (eg, gastrointestinal bleeding or urinary bleeding within last 21 days)

  • Known bleeding diathesis, including but not limited to (1) platelet count less than 100,000/µL, (2) heparin received within last 48 hours and elevated partial thromboplastin time, and (3) recent warfarin therapy with prothrombin time greater than 15 seconds

  • Less than 3 months since intracranial surgery, head trauma, or previous stroke

  • Less than 14 days since major non-neurosurgery or serious trauma

  • Less than 7 days since lumbar puncture

  • Recent arterial puncture at a noncompressible site

  • History of intracranial hemorrhage, arteriovenous malformation (AVM), or aneurysm

  • Witnessed seizure at onset of symptoms

  • Recent acute myocardial infarction

  • Systolic blood pressure greater than 185 mm Hg and/or diastolic blood pressure greater than 110 mm Hg; refractory to medications

Intravenous t-PA dosage is as follows:

• 0.9 mg/kg undefined 10% as a bolus over 2 minutes with the remainder infused over 1 hour

Concurrent therapies can include the following:

• Provide oxygen

• Correct electrolytes

• Maintain vital signs

• Do not treat with anticoagulants (eg, heparin, warfarin, platelet inhibitors [eg, aspirin, clopidogrel])

Intra-arterial fibrinolysis therapy requires the following:

• Inclusion criteria (relative and absolute):

  • Diagnosis of ischemic stroke with neurologic deficit undefined within 6 hours of clinical onset

  • No age restriction

• Exclusion criteria (relative and absolute):

  • Beyond 6 hours of onset (fluctuating)

  • Known bleeding diathesis (platelet count < 100,000/µL)

  • Presence of intracranial aneurysm or AVM

• Absolute exclusion criteria:

  • Identifiable acute infarct or hemorrhage by CT

  • Uncontrolled hypertension

  • Improving neurologic function

Medical care for patients with stroke has historically focused on limiting the extent of the stroke with volume expansion and anticoagulation followed by rehabilitation. No therapy directed at stroke reversal was available to a large segment of the population. Given tremendous strides made in the areas of cardiac and limb salvage and newly available advanced imaging techniques, new modalities are directed at reestablishing cerebral blood flow. If this is accomplished quickly enough, neurologic function may be restored.

Intra-arterial cerebral revascularization incorporates several new technologies and new techniques that have been well established in the field of peripheral revascularization. The focus on acute stroke reversal offers a challenge to those who practice interventional neuroradiology, whereby thrombolytic therapy delivered selectively only to occluded vessel leads to recanalization in a fraction of the time, with a significant reduction in total dosage and with fewer complications than are associated with intravenous thrombolytic therapy.

The most important factors affecting the successful outcome of any reperfusion therapy are early diagnosis of a stroke in progress and patient arrival to a hospital that can offer these therapies as quickly as possible. Public education must be a priority to alert not only high-risk individuals but also their families to the availability of acute care with the potential to reverse a stroke. For this reason, many national stroke organizations have redefined stroke as a "brain attack." The phrase "heart attack" now evokes the idea of angioplasty, coronary bypass, and newer medical therapies. People have come to expect that a heart attack can be reversed. The hope is that using the phrase "brain attack" will evoke similar expectations that stroke is a treatable disorder, and that thrombolytic therapies, as well as mechanical thrombectomy, angioplasty, and stenting, may reverse an acute stroke in progress.

Commonly used agents

Most thrombolytic agents are classified as plasminogen activators. Historically, these have included streptokinase, urokinase, and tissue plasminogen activator (t-PA) (see image below). Streptokinase is no longer used because of its tendency to cause hypersensitivity reactions. Although effective and associated with a lower hemorrhagic conversion rate than t-PA, urokinase is also no longer used. Prourokinase is a genetically engineered variant of urokinase. The Prolyse in Acute Cerebral Thromboembolism (PROACT) trial showed that prourokinase was effective in treating cerebral intra-arterial thrombolysis. Yangiang and associates reported that intracoronary prourokinase during percutaneous coronary intervention (PCI) is more efficient than, and as well tolerated as, PCI alone for treatment of patients with ST-segment elevation myocardial infarction.[26]  However, prourokinase has never been made available for use in the treatment of stroke.[27, 28]

A 47-year-old woman had a sudden onset of left hemiplegia while in the ICU. She was excluded from the intravenous tissue-type plasminogen activator (tPA) protocol because she recently underwent heart-lung transplantation. A, Right internal carotid angiogram demonstrates occlusion of the right middle cerebral artery. B and C, Flow is reestablished at 28 minutes after selective infusion of urokinase into the right middle cerebral artery. The patient recovered neurologic function while she was still on the angiography table.

The only fibrinolytic agent available for intra-arterial thrombolysis is t-PA. Intra-arterial t-PA therapy is often augmented with the use of abciximab. Abciximab is a platelet aggregation inhibitor, which, when applied to an acute thrombus, appears to also have platelet antiaggregate properties. In the author’s program, concurrent administration of up to 10 mg of abciximab directly into the clot within an occluded vessel or proximal to the clot in a recanalizing vessel has contributed to a significant reduction in the amount of intra-arterial t-PA infused, which, in turn, has led to a reduction in the rate of hemorrhagic conversion.

Review of data in a monocentric prospective registry of patients with acute ischemic stroke treated by mechanical thrombectomy revealed that, in contrast to alteplase, abciximab efficiently limits thrombus accretion from flowing blood by blocking platelet aggregation. These results underscore a key role for platelet aggregation and the potential of glycoprotein IIb/IIIa antagonists as rescue therapy in post-mechanical thrombectomy immediate reocclusion.[29]

Thrombolytic protocols

Several protocols are in effect for intravenous (IV) administration of thrombolytic agents, most notably t-PA. These methods establish a systemic lytic state with relatively large doses of thrombolytic agents. Risks include lysis of thrombi anywhere in the body, including the musculature, lungs, and abdominal viscera, as well as in peptic ulcers and recent wounds. Evidence suggests an increased incidence of hemorrhagic conversion of strokes older than 6 hours when IV t-PA is provided. The FDA has approved the use of t-PA for patients with stroke of less than 3 hours' duration.

The American Heart Association/American Stroke Association (AHA/ASA) guidelines for administration of t-PA following acute stroke were revised to expand the window of treatment from 3 hours to 4.5 hours to provide more patients with an opportunity to receive benefit from this effective therapy.[30, 31, 32, 33, 34]

Eligibility criteria for treatment within 4.5 hours after acute stroke are similar to those for treatment at earlier periods, with any of the following additional exclusion criteria:

• Older than 80 years

• Taking oral anticoagulants regardless of international normalized ratio (INR)

• Baseline NIH Stroke Scale score greater than 25

• History of stroke and diabetes

"Drip & ship"

Patients admitted and imaged at hospitals unequipped to provide dedicated stroke care may be given a half-dose of intravenous t-PA and transferred to a stroke center. On arrival, depending on response to the initial half-dose of t-PA, the patient may receive supportive therapy, volume expansion, anticoagulant with or without antiplatelet therapy, the second half-dose of intravenous t-PA, or endovascular therapy.

Delivery of thrombolytic agents

Intra-arterial delivery of thrombolytic agents allows for administration of smaller volumes of more concentrated thrombolytic agent over a shorter period beyond the 3- to 4.5-hour limitation of the intravenous (IV) t-PA protocol. Concurrent anticoagulant therapy and platelet inhibition appear to augment the effects of locally infused lytic agents. Although anticoagulants and platelet inhibitors used with the IV t-PA protocol have not been approved, their use in intra-arterial therapy appears to augment the effectiveness of intra-arterial thrombolytic therapy, recanalizing vessels more rapidly and possibly promoting more complete neurologic recovery with fewer complications.

The arterial route offers the distinct advantage of infusing the drug directly into the clot, accelerating flow restoration. A systemic lytic state is not produced; therefore risks of hemorrhage at other sites, although not eliminated, are markedly reduced. Extensive research is under way to develop agents that are clot specific and that can lyse thrombi even more rapidly with fewer adverse effects.

Selective intra-arterial dissolution of thrombus has been achieved with newer antiplatelet agents. Abciximab, as has been discussed, is an antiplatelet agent that has thrombolytic properties similar to those of plasminogen activators. Lower intra-arterial doses of plasminogen activator may be given concurrently, which may lead to a reduced incidence of hemorrhagic complications. This technique has become the preferred approach to intra-arterial chemothrombolytic management of thromboembolic stroke at the author’s institution.

In the author’s experience, the apparent rate at which a clot lyses with a plasminogen activator appears to decline as flow across the thrombosed vessel improves. This has led to speculation that in vivo activation of plasminogen to plasmin may not be as instantaneous as has been believed. Progressive reduction in clot lysis as flow improves suggests that a portion of the plasminogen activation does not occur until after the clot has passed, making this approach less effective as a local thrombolytic procedure.

Nonthrombolytic techniques

Nonthrombolytic techniques include low-pressure angioplasty of the thrombus and mechanical thrombectomy. A variety of compliant and noncompliant balloon catheters are available in sizes of 2-10 mm to allow access to both cervical and primary branches of the intracranial arterial anatomy. Angioplasty rapidly remodels the thrombus to reestablish flow, but this does not entail extraction or dissolution of the thrombus. Risks include distal embolization by fragmented thrombus and occlusion of small perforator branches of the circle of Willis.

Mechanical thrombectomy devices include AngioJet and Neurojet devices. These tend to be most applicable for use in large vessels of the neck. However, these devices are cumbersome and are poorly navigable, and they have little application in the current management of stroke. The Merci Retriever is capable of attaining significantly greater distal access to the intracranial arterial and venous anatomy. Designed to extract a clot in a state of flow arrest, the Merci device has contributed to a significant reduction in time to recanalization while reducing and often eliminating the need for chemothrombolysis and its associated risk of hemorrhagic complications. The Merci device has inspired the development of newer, more effective, more navigable endovascular thrombectomy devices.

(See image below.)

Penumbra System mechanical thrombectomy device. Used with permission from Penumbra, Inc.

The Penumbra uses a bulbous separator mounted on a guidewire, which is passed through a microcatheter and is repeatedly advanced and withdrawn across an occluded segment of vessel. This process is designed to mechanically disrupt the thrombus and aspirate liberated fragments through the delivery catheter, which is maintained under continuous negative pressure.

Stent retriever devices have also been introduced.[35] The Solitaire stent retriever is designed to grab and extract a thrombus through a technique similar to that used with the Merci device. Delivery guidewires with permanently affixed open-ended Solitaire stents of various sizes facilitate greater distal access and improved rates of successful clot extraction. The Trevo Stentriever is an open-ended stent retriever that is available in a single-stent diameter designed to fit a wider range of vessel diameters—a feature that reduces the amount of inventory needed. The Solitaire and Trevo devices are intended to be used in a state of flow arrest, with clot extraction facilitated by aspiration of a balloon-occlusive guide catheter during withdrawal.

Angioplasty and flow-directing stent placement

An integral part of cerebral revascularization consists of treatment of the source of an embolus, most commonly cardiogenic or carotid-vertebral athero-occlusive disease. Technological advances have made angioplasty and stenting of proximal arterial stenoses in carotid and vertebral vessels as fast and easy a process as possible. Dilation of thromboembolic foci increases cerebral perfusion pressure and cerebral blood volume and reduces risks of reembolization and reocclusion.

Endovascular treatment of intracranial aneurysms (IAs) has evolved considerably. We have witnessed an explosion in the application of FDs and subsequently in their modifications, leading to their ubiquitous use in endovascular therapy.[14]

Treatment techniques and management guidelines for IAs have been continually evolving, and this rapid development has altered treatment decision-making for clinicians. In some cases, as in complex aneurysms, a single approach may be inadequate in completely resolving the IA, and successful treatment may require a combination of microsurgical and endovascular techniques. Treatment options should be considered based on factors such as age; past medical history; comorbidities; patient preference; aneurysm characteristics such as location, morphology, and size; and finally, the operator's experience. This decision-making process is dynamic and will be directed by current best scientific evidence and future technological advances.[36]

Flow diversion is a relatively new treatment technique that is especially useful for large and morphologically unfavorable IAs. Giant IAs remain one of the most daunting clinical problems to treat. Flow-diverter displacement is a rare (0.5-0.75%) and possibly fatal complication. Currently, no clinical guidelines exist for its management. Adjunctive coiling is a possible rescue strategy for stabilizing an FD that foreshortens and prolapses into the aneurysmal sac. Additional studies are needed to discover the best approach for managing this complication.[37]

Cerebral bypass has been an important tool in the treatment of complex IAs. Researchers have investigated the placement of flow-diverting stents for endovascular arterial reconstruction and their impact on outcomes of cerebral bypass in the treatment of IAs. Since FDs were introduced, cerebral bypass has been performed in a lower proportion of patients with aneurysms. Patients selected for bypass in the flow-diverter era had worse preoperative modified Rankin Scale scores, indicating greater patient complexity. Cerebral bypass in well-selected patients and revascularization remain important techniques in vascular neurosurgery and are useful as rescue techniques after FD treatment of aneurysms has failed.[38]

Flow diverters (FDs) have changed the management of brain aneurysms, not only for complex aneurysms (giant, fusiform, and blister) refractory to conventional therapies, but also for unruptured lesions previously managed by traditional surgical or coil-based endovascular methods. Since 2011, when the Pipeline Embolization Device was cleared by the FDA for use in adults with large or giant wide-neck IAs of the internal carotid artery proximal to the posterior communicating segment, the role of flow diversion for aneurysm treatment has been expanded and supported by favorably low complication rates and high cure rates compared to alternative treatments.[39]

Intracranial aneurysms in distal locations are sometimes difficult to treat because of their branching locations and the presence of blister-like or very wide-necked aneurysms. Braided intracranial stents, including FDs and low-profile braided intracranial stents (LPBSs), may provide additional advantages because of their flow-diverting properties. FDs modify the regional anatomy; thus, careful preprocedural consideration of regional hemodynamic equilibrium is mandatory, as is an effective antiplatelet regimen. LPBSs provide a moderate flow-diversion effect, which may be an advantage, especially for very distal and small aneurysms.[19]

Flow models of IAs can be used to test new and existing endovascular treatments with flow modulation devices (FMDs). Additionally, 4-dimensional (4D) flow magnetic resonance imaging (MRI) offers the ability to measure hemodynamics. In this way, the effect of FMDs can be determined noninvasively and patient data can be compared. Praydiytseva and colleagues presented a method that allows the use of neurovascular models in approximately 15-30 hours. These models were found to be geometrically accurate, reproducing main flow patterns, and suitable for implanting FMDs and conducting 4D flow MRI.[40]

Flow diverters have poor radiopacity, challenging visualization of deployment and vessel wall apposition with conventional neuroimaging modalities. Researchers reported on a novel cone beam computed tomography (CT) imaging technique that allows virtual dilution (VD) of contrast media to facilitate workflow and ensure accurate assessment of FD wall apposition. They found that VD imaging with dual cone beam CT enables accurate assessment of FD wall apposition after deployment with greater confidence and improves interreader agreement versus conventional 2-dimensional (2D) digital subtraction angiography (DSA) alone, with comparable X-ray exposure.[41]

Schmalz and coworkers presented a case report on progressive Hunterian ligation of an intracranial aneurysm by flow diversion using the endovascular Selverstone clamp. Researchers found that this approach remains a treatment option for select complex brain aneurysms. They describe that progressive occlusion over time (as accomplished with Selverstone clamping) can enable collateral flow to develop while the aneurysm regresses or occludes. This case report suggests that progressive Hunterian ligation via endovascular flow diversion can be an effective treatment strategy for true PICA aneurysms. However, this strategy should be considered only if no immediate aneurysm occlusion is required, or when all alternative methods are associated with substantial risk.[42]

Pain management

Over the past few decades, interventional neuroradiology (INR) has been a rapidly growing and evolving area of neurosurgery. Both sevoflurane and propofol are suitable anesthetics for INR procedures. Although the depth of anesthesia is widely monitored, few studies have examined the patient state index (PSI) during clinical neuroanesthesia. An investigation by Schmalz examined differences in PSI values and in hemodynamic variables between patients who underwent embolization for a nonruptured intracranial aneurysm who received sevoflurane or propofol. Researchers concluded that the PSI can be used to detect changes in anesthetic concentrations and in the depth of anesthesia during INR procedures. Although extubation was faster under sevoflurane anesthetic, propofol anesthetic led to a smoother recovery.[43]

In a review by Sou et al that was performed to determine the state of the art in anesthetic management of acute ischemic stroke by interventional neuroradiologists, the authors discussed the general anesthetic approach of endovascular stroke therapy and highlighted recent advances and considerations for optimal intraoperative management of acute ischemic stroke. They noted that randomized, controlled trials have shown no differences in clinical outcomes between monitored anesthesia care with sedation versus general anesthesia for endovascular stroke therapy. The COVID-19 pandemic has complicated decision-making in the neurointerventional setting. Advances in imaging techniques have extended the window of treatment for endovascular therapy. They concluded that optimal time to intervention, attainment of hemodynamic stability, use of novel imaging techniques, and careful consideration of the anesthetic plan can impact patient outcomes in reperfusion stroke therapy.[44]

Percutaneous biopsy

Image-guided percutaneous biopsy has become the initial procedure of choice in most cases for obtaining bone samples for histologic and microbiologic assessment. This minimally invasive procedure offers multiple advantages over open surgical biopsy, including preserved bone structure, minimal soft tissue injury, reduced need for general anesthesia, reduced hospital stay, and a low rate of postprocedure complications. In some cases, it can be combined with therapeutic procedures such as cementoplasty and cryoablation via the same access route. For the radiologist, knowledge of the key principles is essential for a safe and effective procedure.[45, 46]

In a retrospective review of an institutionally maintained biopsy registry, Navin and colleagues reviewed procedural techniques, anticoagulation/antiplatelet therapy, and tumor anatomic characteristics in a group of patients who underwent ultrasound-guided percutaneous mediastinal mass core-needle biopsies at a single quaternary referral center. The authors concluded that image-guided percutaneous core-needle biopsy of mediastinal masses is a safe procedure with high diagnostic yield but stated that additional prospective studies are needed to assess the complication profile for higher-risk patients.[47]

Percutaneous vertebral augmentation procedures

Vertebral augmentation includes all percutaneous techniques used to achieve internal vertebral body stabilization. Vertebral augmentation is an established and safe procedure. Vertebral augmentation may be performed under fluoroscopic or computed tomography (CT) guidance. The choice is a matter of operator preference and patient characteristics. Although serious complications of vertebral augmentation are infrequent, there should be prompt access to surgical, interventional, and medical management of complications. When vertebral augmentation is performed, success is defined as achievement of significant pain relief and/or improved mobility as measured by validated measurement tools. Major complications occur in less than 1% of patients treated for compression fractures secondary to osteoporosis and in less than 5% of treated patients with neoplastic involvement.[48]

Vertebroplasty and kyphoplasty

Vertebroplasty and kyphoplasty are FDA-approved techniques for vertebral reconstruction that involve injection of bone cement into abnormal vertebral bodies of the spine. These procedures are most commonly performed to treat painful vertebral compression fractures that have not responded to conventional therapies such as bed rest, bracing, or analgesia. These fractures are typically caused by osteoporosis; however, occasionally, fractures due to trauma and tumor such as metastases, multiple myeloma, and hemangioma can be treated to reduce associated pain. Neither vertebroplasty nor kyphoplasty is intended for treatment of pain due to disk disease.[49, 50, 51, 52, 53, 54, 55]

Inclusion and exclusion criteria are the same for vertebroplasty and kyphoplasty. Inclusion criteria consist of pain localized to fracture or tumor, pain refractory to medical management, and fracture less than 12 months old. Exclusion criteria comprise fracture extending to the posterior vertebral cortex, a retropulsed fragment, cord compression, symptoms limited to radicular pain, infection (fever, sepsis, abscess, diskitis-osteomyelitis), pain that responds to minimal analgesia, coagulopathy, and penetrating trauma.

A study on pain reduction after vertebroplasty and kyphoplasty noted that these are the most effective and safest types of treatment for vertebral compression fractures. Hackbarth et al concluded that pain reduction by means of percutaneous vertebroplasty or percutaneous kyphoplasty in patients with vertebral compression fractures was discernible over the period of observation. Both procedures contribute to desired treatment results. However, the low level of pain may not remain constant. Long-term results are needed for qualitative evaluation.[56]

Vertebroplasty

Vertebroplasty consists of transpedicular or peripedicular placement of an 11-gauge (lumbar) or 13-gauge (thoracic) needle into the anterior third of the affected vertebral body under radiographic guidance (fluoroscopy or CT). Once positioned, bone cement—methylmethacrylate—is injected through the needle into the vertebral body (see image below). Methylmethacrylate is a medical-grade polymer that has been used for more than 30 years in work with artificial joints and cranioplasty. The cement is mixed with a powder containing barium to enhance radiographic visibility. Radiopacity may be further enhanced by the addition of tantalum or tungsten powder.

A and D, Osteoporotic anterior wedge compression fractures. B, Placement of a needle into the collapsed vertebral body. E and R, Result after the injection of methylmethacrylate. This therapy is principally indicated for the management of pain. C, The primary goal is to fuse the fracture fragments to prevent their continued motion. F, Vertebroplasty occasionally elevates the superior endplate of an acute fracture, reducing kyphotic deformity. A, B, and C modified from Netter.

When injected, the material at first has the consistency of toothpaste. After approximately 10 minutes, the cement solidifies, becoming harder than the native bone. Following the procedure, the patient is kept supine for 3 hours and is discharged to home. This procedure is not painful and requires only local and deep anesthesia with mild sedation and analgesia.

In most cases, pain is reduced or eliminated immediately after the procedure. Patients must still exercise caution in subsequent activities because other osteoporotic vertebral bodies may be prone to fracture. Medical management of the underlying medical disorder that weakened the vertebral bodies should be initiated. Risks of the procedure are low but may include infection, worsening of pain, and neurologic sequelae such as weakness or pain.

Kyphoplasty

Kyphoplasty, similar to vertebroplasty, is intended to treat the pain of vertebral compression fractures while providing the hypothetical added advantage of restoring vertebral height and reduction following an exaggerated kyphotic curvature of the spine caused by an anterior wedge compression fracture. This effect is accomplished via placement of 1 or 2 high-pressure balloons into the fractured vertebral bodies. When inflated, these balloons create a cavity within the trabeculae, theoretically resulting in separation of fracture fragments. A preparation of methylmethacrylate that is thicker than that used in vertebroplasty is then injected into the bone via the same technique. This technique is limited to acute compression fractures and is not intended for treatment of neoplastic lesions of the vertebrae.[49, 50, 51, 52, 53]

Percutaneous management of disk disease

Low back pain is an extremely common pathology affecting a great share of the population—in particular, young adults. Degenerative disk changes are usually associated with vascular and nervous fiber infiltration from outer portions of the annulus fibrosus (AF) into deeper structures of the disk, leading to symptoms; on the other hand, a bulging disk may cause compression and, therefore, inflammation of the adjacent nerve root, resulting in neurogenic pain from the affected fiber.[57]

Percutaneous intervertebral disk procedures are practical and reproducible treatments for symptomatic intervertebral disk herniations for which a combination of 4-6 weeks of conservative therapy associated with a session of steroid infiltration has failed. These procedures carry a success rate of 75-80% and involve rare complications (~0.5%), with spondylodiskitis being the most severe (0.24%). Sterile techniques and prophylactic antibiotics are a prerequisite. Imaging guidance allows clinical success with a markedly decreased complication rate. There is no definitive evidence regarding the difference in efficacy between surgical options and the percutaneous decompression technique, although the latter results in only minimal destruction of surrounding structures—in particular, of muscles that support the altered intervertebral disk—and is considerably more cost-effective. In conclusion, percutaneous intervertebral disk therapeutic techniques are viable as valid treatment before surgery for treatment of symptomatic herniation of the cervical and lumbar spine.[57]

Disk herniation is a common health problem with important social and economic consequences. Radiofrequency nucleoplasty and laser decompression are less invasive than open surgery but can be performed only in contained disk herniations. Pain relief has been reported in up to 80% of selected patients treated with percutaneous disk decompression. Minimally invasive techniques, such as radiofrequency nucleoplasty and percutaneous laser disk decompression (PLDD), have challenged open surgical management of diskogenic back pain. However, microdiskectomy is still considered the gold standard treatment.[58]

DeKompressor

The DeKompressor percutaneous diskectomy probe uses a self-contained motorized drill to remove the nucleus pulposus from the annular compartment through a small channel under fluoroscopic guidance. Superficial, deep, peridiskal, and intradiskal anesthesia is provided with lidocaine. First, diskography is performed to define the margins of the nuclear compartment. Then the cannula is advanced via a posterolateral approach into the thoracic or lumbar intervertebral disk space. As the device is activated, the drill bit disrupts nuclear tissue and mechanically draws the material into a collection chamber at the base of the motor assembly. Patients rarely have any discomfort during this procedure. The probe is capable of aspirating disk material from intervertebral disk spaces of the lumbar, thoracic, and cervical spine.[59, 60, 61]

Klessinger et al conducted a long-time retrospective review to examine the frequency of additional surgery after use of the DeKompressor (PLDD). They assessed the correlation between clinical symptoms and outcomes and analyzed the time between PLDD and open surgery. They found that the short-term success rate was worsened by a resurgery rate of 26.0%. Subsequent surgery a short time after PLDD suggests that PLDD is not a replacement for open diskectomy. Because patients with radicular pain had worse outcomes and more frequent resurgeries, study authors concluded that whether radicular pain is an ideal indication for PLDD should be discussed.[62]

Disk nucleoplasty and coblation

Disc nucleoplasty uses a unique plasma technology called coblation to remove tissue from the center of the nucleus pulposus. During the procedure, a probe is introduced through a needle and is placed into the center of the disk, where a series of channels are created to remove tissue from the nucleus. This coblation plasma technology has been used for many years in arthroscopic surgical procedures and in otolaryngologic procedures. Coblation decompresses the disk while preserving adjacent healthy tissue by using plasma energy rather than heat energy to remove tissue.[63, 64]

The disk is accessed through a 17-gauge (cervical or thoracic) or 19-gauge (lumbar) cannula with an obturator stylet via an anterolateral approach in the cervical spine or a posterolateral approach in the thoracolumbar spine. While the patient is monitored, the probe is advanced into the disk. As the probe is advanced, the coblation plasma mode is activated and tissue along the path of the device is removed by means of molecular dissociation.

Tissue is turned into gas, which exits the disk through the introducer cannula. After a predetermined depth is reached, the probe is slowly withdrawn to the starting position. Sufficient thermal energy is generated to denature nerve fibers adjacent to the channel in the nucleus pulposus. After the first channel is created, the probe is rotated clockwise and is readvanced to create another channel. Approximately 6 channels are made, depending on the amount of tissue reduction desired.

Average pain reduction is a clinically significant 55-60%. Patient satisfaction is high—about 90%—largely because of the relative ease of the procedure and lack of a painful rehabilitation period, and because the procedure does not preclude subsequent procedures (eg, open surgery). Early studies have showed that pain relief is sustained for as long as 2 years after surgery.

A study by Yin et al sought to explore and compare the surgical levels (single vs double) of percutaneous disk nucleoplasty (PDN) for patients with lumbar disk herniation (LDH). Researchers compared visual analog scale scores, patient satisfaction, and reoperation occurrence between single-level and double-level groups and concluded that PDN is a safe and minimally invasive approach that effectively treats patients with LDH. They surmised that the number of surgical levels might be an important factor influencing the efficacy of PND. Caution should be exercised in strictly following the clinical indications for nucleoplasty.[65]

Nucleotome

The Nucleotome system involves a percutaneous approach to rapid removal of the nucleus pulposus from a lumbar intervertebral disk. The probe of the system has a rounded tip that reduces the risk of penetrating the anterior annulus. A vacuum draws nucleus material into a cutting port while the reciprocating, enclosed guillotine resects and aspirates portions of the nucleus. This action does not damage the annulus or the endplates. Continuous irrigation removes aspirated material from the probe and allows the physician to collect and examine extracted tissue.

Performed under local anesthesia, this procedure was traditionally surgical; however, its potential as a fluoroscopically guided procedure warrants consideration.

More than 125,000 procedures have been performed worldwide with no treatment-associated deaths reported. Success rates are greater than 75%. Complication rates for this technique have been consistently reported at less than 1%—a considerable reduction from the normal 3-4% reported for open spinal surgery.[66, 67, 68, 69]

Percutaneous diskectomy

Back pain related to a herniated intervertebral disk is one of the most common causes of chronic disability. Although many cases of acute low back pain resolve with conservative therapy, surgical decompression is often considered when pain is unimproved after physical therapy and when pain characteristics clearly suggest a neuropathic origin.

Open surgery was historically used to treat radicular pain with diskectomy (ie, removal of part of the abnormal intervertebral disk) or with decompressive laminectomy (ie, resection of portions of the lamina to relieve pressure on the spinal canal and nerve roots). Initial surgical success rates have been in excess of 90%; however, conventional surgical techniques have been associated with an approximate 17% incidence of failed back syndrome, in which symptoms recur as a consequence of scar formation in the operative bed, compromising adjacent nerves. Decompressive surgical techniques have advanced to the point where procedures using laser or radiofrequency energy are performed through small incisions or with endoscopy. These newer, less invasive surgical techniques have been associated with a lower incidence of failed back syndrome compared with open surgical decompressive therapies.

Percutaneous disk decompression has been used for over 40 years to treat more than 500,000 patients with herniated nuclei. A variety of techniques have been used, including chemical, mechanical, and thermal methods such as radiofrequency and laser ablation. Early procedures conclusively showed that percutaneous disk decompression effectively relieves pain for appropriate patients.

Intradiskal electrothermal annuloplasty (IDET) is another older, minimally invasive approach used to treat low back pain. A heated element is used to treat pain that is thought to arise from sensory nerves in the surrounding annulus. This procedure has had limited clinical success.

The Nucleotome system, the DeKompressor percutaneous diskectomy probe, and the Disc Nucleoplasty device are examples of FDA-approved percutaneous diskectomy devices. The last 2 are used most often. None of the techniques using these devices—surgical or percutaneous—are targeted at the extruding disk fragment; rather, they are designed to reduce the volume of the residual nonherniated nucleus pulposus remaining within the annulus, in an attempt to reduce pressure on the herniated fragment during load bearing.

Percutaneous disk decompression has been used to treat symptomatic patients with contained herniated disks. The ideal patient meets the following common criteria: radicular symptoms (eg, leg pain greater than back pain); computed tomography (CT) or magnetic resonance imaging (MRI) evidence of contained posterolateral disk protrusion and 1 failed selective nerve root block (included to ensure that the patient's condition is given the opportunity to respond to conservative care); failed conservative therapy for 3 months; and diskographic findings positive for concordant pain. Exclusion criteria consist of disk height less than 50%, evidence of severe disk degeneration, spinal stenosis, traumatic spinal fracture, infection, tumor, pregnancy, and severe coexisting medical disease. This procedure is not indicated for treatment of pain originating from structures other than herniated disks. Patients with a free disk fragment or with severe and rapidly progressing neurologic deficits are excluded.

Potential complications include infection, bleeding, nerve damage, worsening of pain, paralysis, idiosyncratic reaction, anaphylaxis, and death.

This procedure should be performed with the patient under local anesthesia or conscious sedation to allow the patient to participate in monitoring for signs of segmental nerve root irritation. After the device has been inserted into the disk space under fluoroscopic guidance, disk decompression is performed within a few minutes. The entire procedure lasts about 30 minutes per level, and the patient can be discharged shortly afterward. Patients typically have little pain after the procedure, and any pain that occurs is usually managed with analgesics. Patients are advised to avoid lifting and strenuous exercise; they may go back to sedentary work after 1 week. Patients with physically demanding occupations may need to wait longer than this to recommence their daily activities. Additional physical therapy during the recovery period may prove beneficial.

Percutaneous diskectomy may decrease procedural time, need for anesthesia, and recovery time; may lower complication and morbidity rates; and may substantially reduce postoperative spinal instability. Percutaneous diskectomy has demonstrated the potential to produce outcomes equivalent to or better than those of conventional decompressive surgery. This procedure is permanent, simple, quick, and relatively atraumatic, with less perineural scarring and postoperative fibrosis and shorter recovery times. Clinical results are promising, and patients generally can expect rapid and sustained pain reduction.