Contents
Maarten Smits, Max Seidensticker
UMC Utrecht and LMU Hospital Munich
Principle of embolization
This article is about therapeutic embolization, in which a part of the blood circulation is impeded by the introduction of embolization agents.
An embolus is defined as “Undissolved material carried by the blood and impacted in some part of the vascular system (…)” (Dictionary.com).
The indications for embolization can be grossly categorized into bleeding control, occlusion of pathologic vasculature, and tissue ablation. See table 1.
Catheterization
Access to the vessel to be embolized can be obtained by direct puncture (superficial varicose veins, fistula or malformation) or indirectly via an endovascular approach. We will focus on the endovascular approach. The target vessel should be catheterized with a catheter that is able to negotiate the vasculature and allow passage of the embolization agent.
Microcatheters are most suitable for this purpose. These catheters usually have a straight tip and a typical outer diameter (OD) of 1.5-3 French (F). They can be advanced coaxially through a larger supporting catheter (OD 4-6 F) in order to reach deep in the vasculature. Guiding sheaths or guiding catheters can be used for support as well.
A stable position of the entire coaxial system is key when administering the embolization agent to minimize the risk of non-target embolization. Exciting developments in this field are the anti-reflux catheters that use either a cone- or umbrella-shaped tip (e.g. Surefire infusion system®, Surefire Medical Inc.), or a balloon (Occlusafe®, Terumo) to prevent reflux of embolization agent and thus non-target embolization. These catheters are mainly used for chemoembolization or radioembolization.
When using agents like histoacryl or ethylene-vinyl alcohol (Onyx®) there is a risk that the microcatheter gets stuck in the embolus. Leaving a microcatheter inside the body (after cutting off the external part) causes surprisingly little symptoms, and the catheter will eventually be integrated in the vessel wall. This is of course not a desirable situation. To overcome this issue, manufacturers have developed catheters with a detachable tip akin to a lizard’s tail (e.g. Apollo® [Medtronic] and Sonic® [Balt]). The tip breaks off when the tip is fixed in an embolus and the rest of the catheter is pulled outwards, leaving only a small part of the catheter in situ.
Embolization agents
There is a large variety of agents available to perform embolization, ranging from autologous blood clot to devices like coils or vascular plugs, see Table 2.
Choosing the embolization agent depends on the indication and the experience at hand. Each agent has its specific advantages and disadvantages. Factors influencing the choice of material comprise the size of the target vessel, flow velocity, and duration of embolization (permanent/temporary).
Thrombin
Thrombin is well known for embolizing false aneurysms (aneurysm spurium), particularly in the groin after femoral arterial puncture. This technique – first described in 1986 – consists of direct, ultrasound guided injection of thrombin in the false aneurysm. The primary success rate is about 90%. Aneurysms should have a small neck to avoid spill of thrombin into the femoral artery which can cause femoral artery thrombosis (0.5-1% risk).
A variety of coil shapes: a. Nester® coil [Cook Medical], b. Complex helical coil [Boston Scientific], c. Straight Hilal® coil [Cook Medical], d. Figure 8 coil [Boston Scientific], e. Vortx coil [Boston Scientific], f. Vortx Diamond coil [Boston Scientific], g. Multi-curled Hilal® coil [Cook Medical], h. AZUR® framing coil [Terumo]
Coils
Coils are probably the most used type of embolic agent. Coils are braided wires generally made of platinum or stainless steel that can be loaded into a catheter and will coil into shape when released out of the catheter or sleeve. Coils come in a large variety of shapes and sizes fit for specific situations. Most coils have protruding fibers to enhance thrombosis.
Common thicknesses of coils are: 0.014”, 0.018”, 0.035” and 0.038”. Microcatheters will generally only accomodate 0.014” and 0.018” coils. Other important dimensions of coils are their length (mostly in the range of 1-10cm) and their diameter when deployed (range of 1-20mm). As a general rule, the diameter of the coil should be oversized about 20% compared to the vessel diameter as measured on DSA.
Indications:
– Traumatic hemorrhage
– Aneurysms
– Varices (in certain cases)
– Arteriovenous fistulas
Case of embolization for acute hemorrhage from a branch of the left hepatic artery (arrow). This was iatrogenic injury after abdominal surgery. A combination of Gelfoam, straight- and figure-8 coils was used. No more extravasate after embolization (B).
Coil delivery
Coils often come packaged in a protective sheath (see figure). The coil is inserted by placing the sheath in the back end of the catheter. Then, the plunger that comes with the coil, is pushed all the way into the back end of the sheath containing the coil. The coil is then loaded into the catheter.
From there on, coils can be pushed through the catheter using a coil pusher. Alternatively, pushing the coil with a saline bolus is a fast way to deliver coils (saline-flush technique).
Coiling techniques
Packing coils in a large calliber vessel can be challenging. Here are a few techniques that can be used.
Detachable coils
Conventional coils are deployed once pushed out of the catheter. Incorrectly placed coils can cause serious complications and can be hard to retrieve. Several types of detachable coils have been developed to enable more controlled coil-embolization. Detachable coils are helpful for embolization in high-flow vessels, embolization close to the origin of a vessel, and for aneurysms when dense coil packing is desired. Detachable coils can be retracted and redeployed a number of times until satisfactory placement is reached and the coil is detached.
There are several types of detachable coils that have their own method of detaching. Some coils are locked onto the pusher and are released when the coil is fully pushed out of the catheter. Most detachable coils work with some kind of detacher that mechanically or electronically activates a release mechanism (see images for examples).
a. Dense coil packing in the gastroduodenal artery prior to yttrium-90 radioembolization. b. The attempt to embolize up to the origin of the gastroduodenal artery led to a coil protruding into the proper hepatic artery (arrow). c. Embolization up to the origin of a vessel is easier controlled using detachable coils (different case then a and b, using Interlock®[Boston Scientific]).
a-c. PCOM aneurysm embolized using detachable coils
Plugs
Vascular plugs are devices made of a nitinol mesh that expand into their original shape when deployed. Plugs can be used as alternatives to coils for controlled embolization of a large vessel, vessel wall defect or pseudoaneurysm. A single plug can be used to embolize a vessel that would otherwise require multiple coils. Vascular plugs are detachable.
Indications:
– High flow vessels
– Large defects
Endoleak repair with a plug post TEVAR. a. DSA from the left subclavian artery shows a small endoleak. An Amplatz plug (14mm x 10mm) was placed in the origin of the subclavian artery (b). c. Volume rendered CTA image shows the position of the plug in relation to the TEVAR stent.
Detachable Balloon
The first use of detachable balloons were described by dr. Serbinenko in 1974. Detachable balloons are an excellent tool for obstructing high-flow vessels or fistulas where coils can easily dislodge. The method of detachment can differ, one system works by pushing a larger catheter over the balloon catheter wheras another systems requires gentle traction on the balloon catheter to detach the balloon.
Indications:
– High flow vessels
– Fistulas
Particles
Embolic particles can be devided into spherical and non-spherical particles.
Spherical particles, sometimes called spheres or microspheres, come in several sizes ranging from app. 40 – 1300μm (micron). Some products are advertised to have a tight size callibration which is favorable for controlled embolization. Examples of spherical particles are: Embozene® [Boston Scientific], Embosphere®/Embogold®/Quadrasphere® [Merit Medical Systems], Contour SE™ [Boston Scientific], Bead Block® [BTG], and LC Bead®/DC Bead® [AngioDynamics], see Table.
Microspheres can be used for embolization of tumors as well, especially when containing drugs or radioactive elements. TransArterial ChemoEmbolization (TACE) and Radioembolization (a.k.a. Selective Internal Radiation Therapy, SIRT) are well known examples of embolization for oncologic purposes. Tumor embolization can also be performed with inactive particles, which is referred to as ‘bland’ embolization.
Poly-vinyl alcohol particles (PVA) are mostly non-spherical, although spherical PVA particles are available as well. PVA particles are irregularly shaped, can aggregate and the embolization is slightly less predictable then with spherical particles.
Non-target embolization is a great risk of particles. Since particles are very small they can shunt into non-target vessels or through arteriovenous shunts and cause severe complications and even death. Most types of particles are not visible under angiography.
Indications:
– Recurring hemorrhages, access for future embolization needs to be preserved (e.g. nasopharyngeal or bronchial hemorrhage)
– Tumors
– Hemoptysis
– Uterine fibroids
Embolization of a uterus myoma. a. DSA pre-embolization b. post-embolization with 700μm Embozene® particles.
Gelfoam®
Gelfoam® [Pfizer] is a sterile compressed sponge created from gelatin granules and purified porcine skin. Gelfoam® comes as a layer of foam that should be cut into small pieces and then mixed with contrast solution to create a very thick mixture (slurry) that can be used for embolization.
Gelfoam® is a fast, cheap and reliable embolic agent. Its key characteristic is non-permanent embolization. Gelfoam® is usually completely resorbed in a few weeks.
Indications:
– Traumatic hemorrhage
– Post-partum fluxus
– Uterine fibroids
Liquid embolics
There is a variety of liquid embolics. Liquid embolics can be applied by direct injection into the target region or transcatheter injection. Liquids can be combined with non-liquid embolic agents such as coils or plugs.
Glue
Cyanoacrylate (Histoacryl®) is similar to glue used for all kinds of purposes in and around the house. It is a monomere that polymerizes when in contact with water or blood. Histoacryl is a blue colored substance that comes in small pipets (see image).
Histoacryl can be diluted with Lipiodol for radiopacity and to prevent immediate solidification. The catheter needs to be primed with 5% glucose water before injection. Then, Histoacryl is slowly injected and a cast will form distal to the catheter tip. After a few seconds the catheter can be retracted with a firm pull. Make sure there is no reflux to prevent non-target embolization or catheter entrapment.
Indications:
– Traumatic or iatrogenic hemorrhage
– Vascular malformations
– Tumor embolization
– Portal vein embolization
Sclerosants
Intravascularly injected sclerosants lead to and inflammatory reaction resulting in endothelial damage and fibrotic obstruction of the vessel or vascular malformation. Sclerosants are indicated to embolize a peripheral vascular bed.
Examples are:
Polidocanol (Aethoxysklerol®), alcohol, detergents, and antibiotics (doxycycline, bleomycine).
Indications:
– Varices
– Vascular malformations
– Tumor embolization
Precipitating agents
There is a category of liquid embolics consisting of ethylene vinyl alcohol copolymers that are dissolved in dimethyl sulfoxide (DMSO) and are mixed with tantalum powder for radiopacity. Examples of available products in this category are: Onyx® [Covidien], SQUID™[Emboflu], and PHIL® [Microvention].
These precipitating agents need to be shaken at least 20 minutes prior to use to obtain a homogeneous mixture of the tantalum powder. Catheters and hubs used need to be compatible with DMSO since standard plastics are dissolved by DMSO. The dead space of the catheter needs to be primed with DMSO before injection.
Once injected into the body, DMSO dissolves and the ethylene vinyl alcohol copolymeres precipitate inside the blood vessels. The embolic agent can be pushed deep into the vascular bed by slow, intermittent injections. Backflow along the catheter can be managed by pausing injection and waiting for a plug to form around the catheter tip. Consequent injections will follow the path of least resistance which is then hopefully away from the catheter and into the target vasculature. Microcatheters with a detachable tip are strongly recommended.
Indications:
– Vascular malformations
– Hemangiomas
– Aneurysms
Choice of material
The choice of embolic agent depends on many factors. Safety is the main factor, therefore experience of the interventionalist with the embolic agent and risk of non-target embolization should always be weighed.
Other factors are the organ or lesion to be embolized, the desired effect of embolization (permanent or temporary), proximal or distal embolization. Availability and costs of the embolic agent are not unimportant either.
Distal embolization (using liquids or small particles) is more likely to cause tissue necrosis since end-arterioles are blocked and collaterals have no way of reaching the vascular bed. Distal embolization carries a high risk of shunting to non-target organs such as the lungs or brain.
Many embolic agents can be combined to increase efficacy.
References
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1. Cope C, Zeit R. Coagulation of aneurysms by direct percutaneous thrombin injection. AJR Am J Roentgenol 1986; 147: 383–387.
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2. Vascular Embolotherapy – Vol 1. General Principles, Chest, Abdomen and Great Vessels-2006. Springer.