2. Introduction
• Factors to consider in selecting embolic materials
• Degree of permanence: temporary or permanent agents
• Location or level of occlusion
• Embolic agent characteristics: size, radiopacity, material composition,
mechanism of occlusion & biologic behavior
3.
4. Indications for embolization
1. Occlusion of vascular abnormalities which have potential to cause adverse
health effects.
2. Treatment of acute or recurrent hemorrhage
3. Devascularization of benign or malignant tumors for palliation or to reduce
operative blood loss
4. Ablation of non-neoplastic tissue causing adverse health effects
5. Flow redistribution to protect normal tissue or to facilitate subsequent
treatment
6. Management of endoleak
7. Targeted delivery of drug or other agents
6. Mechanical
Occlusive Devices
• 1. COILS (permanent):
• stainless steel of platinum
• different sizes
• Action: mechanical obstruction, platelet activation, and
the patient’s own clotting cascade to fully occlude
vessels
• Notes:
• Tight coil packing is important
• Coil stability
7. COIL STABILITY
• Use of a guiding catheter
• Coil oversizing: 15% in arteries &
greater degree in veins
• Use of detachable coils: can test stability of coils
before detaching, released by mechanical or
electrolytic detachment or by degradation of
polymer adhesive.
• Coil anchoring technique or devices:
• AMPLATZ SPIDER
• RETRIEVABLE COIL ANCHORS
8. Vascular Plugs
permanent occlusive devices which
consist of self-expanding nitinol mesh in
a threedimensional (3D) disc geometry.
Amplatzer vascular plug vary by mesh
layers, shape, number of lobes, diameter
range, unconstrained length & length of
time to achieve vessel occlusion.
9. Vascular Plugs
• Oversized by 30-50% as recommended by the manufacturer
• deployed by unscrewing the lock in a counterclockwise direction
• considered when single-step occlusion of a larger vessel or branch is
desired, or when an initial plug is needed to act as a scaffold for
subsequent coil embolization.
12. Particulate Embolic Agents
administered from a selective
position within the arterial supply
deposited in a flow-directed
manner to target area
• used for the embolization of tumor and tumor-related symptoms
• Embolic particles differ in: available size ranges, uniformity of size and
shape, tendency to aggregate, especially nonspherical PVA, and
compressibility.
• Classified as resorbable or nonresorbable.
14. Gelfoam
• Temporary
• Rapidity and degree of resorption
depends on the amount used,
degree of saturation with blood,
and site at which it is used.
• The treated vessel typically
recanalizes within a few weeks.
• Can be shape in numerous ways.
• Gelfoam “Torpedoes”
• Gelfoam slurry
15. Avitene
• Temporary
• Microfibrillar collagen
• Available in powder and sheet form
• Moderate recanalization occurs by 2
weeks and total recanalization by 2
months
• useful agent for tumor necrosis and
organ ablation
16. . Polyvinyl alcohol PVA
• Permanent
• Irregularly shaped shavings from PVA blocks or sheets and are available in
sizes from 50 to 1200 μm.
• PVA is also supplied in the form of microspheres.
particles produce
mechanical occlusion
of the vessel
activate thrombin
induce fibroblast
ingrowth
which leads to
relatively permanent
vessel occlusion
• PVA particles are distributed dry or in solution and are prepared by mixing in a
solution of contrast and saline.
17. Maneuvers to reduce clumping of PVA
• In the mixing vial
• Particles are mixed in a solution containing 40% contrast. This mixture should
maintain suspension of the particles in solution and prevent flocculation.
• Dilute the particles in a 40-mL solution of contrast and saline. After the first syringe
is used, add another 10-mL solution to the bowl to maintain or increase dilution.
Occasionally, this process continues up to a final solution of 70 to 80 mL per vial of
1 mL PVA particles.
18. Maneuvers to reduce clumping of PVA
• In the syringe immediately prior to injection
• A 10-mL or 20-mL syringe is used to aspirate the particles mixed with contrast and
saline from the mixing vial and serves as a reservoir and is connected to the middle
hub of a three-way stopcock. A 3-mL or 5-mL syringe is then connected to the end hub
of the three-way stopcock (in line with the microcatheter), and the syringes are
aspirated back and forth to mix the particles.
• Another method uses a 3-mL non-Luer lock syringe. After aspirating the solution from
the reservoir syringe, the injection syringe is rotated continuously during the slow
injection of the particles to prevent precipitation and clogging.
19. Spherical embolics
(“microspheres”)
• size ranging from 40 to 1,200 μm
• Injection technique for spherical embolic agents
• The syringe containing the particles and a 3- to 5-mL
syringe with contrast material are connected to a
three-way stopcock. The contrast is aspirated into the
particle syringe, and after 3 to 5 minutes, a uniform
suspension is obtained. Once mixed, this solution can
be injected easily and slowly.
20. Spherical embolics
(“microspheres”)
• Flow-directed injection of particles respects
the physiology of the circulation and allows for
deposition of particles preferentially to the
tumor even with a catheter in a non-
superselective location.
21. Drug-eluting particles/ Drug-eluting
microspheres
electric charge of particles can be used to temporarily bind
medications with an opposite charge
DC Beads are produced from biocompatible, nonbiodegradable PVA
hydrogel that has been modified with sulphonate groups to allow for
the controlled loading and delivery of a chemotherapeutic drug.
Doxorubicin-loaded beads (DEBDOX) have been used for the
treatment of hepatocellular carcinoma and Irinotecan-loaded beads
(DEBIRI) for the palliative treatment of metastatic colorectal cancer
22. Drug-eluting
particles
• Theoretical advantages
• higher local concentration of the
therapeutic agent resulting in less
systemic adverse effects,
• longer exposure of the target to the
therapeutic agent,
• potential to use drugs that are
potentially toxic if injected
systemically.
24. GLUE
(cyanoacrylate)
• Liquid monomeric cyanoacrylate is converted to a solid long-chain
polymer immediately on contact with anionic substances such as
plasma, blood cells, endothelium, or saline.
• GLUE is mix with Lipiodol (1:5 or 2:5 ratio)
• The bolus of glue is introduced into the catheter after it has been
flushed with 5% dextrose solution (D5W) and is pushed out of the
catheter with another bolus of D5W.
• Catheter is typically changed after each injection.
25. GLUE (cyanoacrylate)
• treatment of vascular malformations,
particularly intracranial
Most common application
• rapid polymerization and reflux resulting in
gluing the catheter in place or feeding
vessel occlusion without the desired nidal
penetration.
• If the polymerization time is too long, the
cyanoacrylate can pass into the venous
circulation, resulting in pulmonary emboli.
Risks
26. Onyx
• ethylene vinyl alcohol copolymer dissolved in
various concentrations of dimethyl sulfoxide
(DMSO) and opacified with micronized tantalum
powder
• mixture contacts aqueous media such as blood,
the DMSO rapidly diffuses away, resulting in in
situ precipitation and solidification of the
polymer
• Two different preparations which differ in the
concentration of EVOH, Onyx 18 with 6% EVOH
and Onyx 34 with 8% EVOH.
• A DMSO-compatible catheter is required.
27. Alcohol
• It can be injected via an intravascular route or
direct percutaneous puncture
• Upon contact with the vessel wall, ethanol
denudes the endothelium, which leads to
thrombosis and eventual fibrosis
• DISADVANTAGE
• risk of necrosis of neighboring tissues
including nerves or skin
• The risk of systemic toxicity increases with
doses above 1 mL per kg or if the total volume
exceeds 60 mL.
28. Methods to decrease the risk of nontarget
embolization when using ALCOHOL:
Controlling reflux with occlusion balloons
Using in vascular beds without significant collaterals (e.g., kidney)
Precisely defining the anatomy of the vessels to be occluded including assessment of supply to
normal tissues
Placing the catheter in as selective a position as possible
Using the smallest volume likely to achieve the intended effect, usually in small aliquots
Occluding venous outflow to isolate the target vascular bed
Opacifying ethanol with tantalum powder or Ethiodol to improve visualization
29. Ethanolamine oleate
• mixture of 5% ethanolamine oleate and Ethiodol (ratio 5:1 to 5:2)
• Oleic acid causes intimal irritation, which leads to an inflammatory response
which ultimately causes mural necrosis, thrombosis, and fibrosis.
• predominantly for venous sclerosis, including treatment of gastroesophageal
varices and venous malformations, as well as for cyst sclerosis.
• 50% of the oleic acid may combine with serum proteins within 30 minutes
and can cause renal toxicity in association with a marked intravascular
hemolysis, hemoglobinuria, and hepatotoxicity.
30. Sodium tetradecyl sulfate
• anionic surfactant widely used for sclerosis of
esophageal varices, varicose veins, and venous
malformations
• containing 2% benzyl alcohol
• causes intimal inflammation and thrombus formation
and subsequent formation of fibrous tissue resulting in
vessel occlusion
Polidocanol
• nonionic surfactant sclerosant
• Causes vascular injury through endothelial overhydration
Other sclerosing
agents
31. Sodium morrhuate-
• irritant and sclerosing agent composed of a sodium salt
of fatty acids in cod liver oil.
• This agent has been used in the treatment of varicose
veins and venous malformations
Ethibloc
• used effectively for the treatment of venous, lymphatic,
and arteriovenous malformations.
• approximately 10 to 15 minutes to solidify into a viscous
solution,
• allowing it to remain static within the target lesion to
cause intravascular thrombosis, necrosis, and fibrosis
Other sclerosing
agents
32. In Summary
Summary
Different embolizing agents including its duration of action, mechanism of
actions, advantages and disadvantages
Factors to consider in choosing the right embolizing agents depending on the
clinical scenario.
Various techniques, in preparation and administration of different embolizing
agents.
33. References
• 1. Golzarian J, Sun S, Sharafuddin MJ. Vascular Embolotherapy: A Comprehensive Approach.
Volume 1: General Principles, Chest, Abdomen, and Great Vessels. Heidelberg, Germany:
Springer; 2006.
• 2. Greben CR, Setton A, Putterman D, et al. Double microcatheter single vascular access
embolization technique for complex peripheral vascular pathology. Vasc Endovascular Surg.
2010;44:217–222.
• 3. Wilson MW, Gordon RL, LaBerge JM, et al. Intravascular occluding device using a modified
Gianturco stent as a coil cage. J Vasc Interv Radiol. 2000;11:221–224.
• 4. Golzarian J, Patel P, Beasley, R. Clinical techniques utilizing the Ruby embolization coil.
Endovascular Today. 2014;1–4. 5. Laganà D, Carrafiello G, Mangini M, et al. Indications for
the use of the Amplatzer vascular plug in interventional radiology. Radiol Med.
2008;113(5):707–718.
• 6. Laurent A. Microspheres and nonspherical particles for embolization. Tech Vasc Interv
Radiol. 2007;10(4):248–256. 7. Liapi E, Geschwind JF. Intra-arterial therapies for
hepatocellular carcinoma: where do we stand? Ann Surg Oncol. 2010;17:1234–1246. 8.
Howington JU, Kerber CW, Hopkins LN. Liquid embolic agents in the treatment of
intracranial arteriovenous malformations. Neurosurg Clin N Am. 2005;16:355–363.
• 9. Rosen RJ, Nassiri N, Drury JE. Interventional management of high-flow vascular
malformations. Tech Vasc Interv Radiol. 2013;16:22–38.
• 10. Do YS, Yakes WF, Shin SW, et al. Ethanol embolization of arteriovenous malformations:
interim results. Radiology. 2005;235:674–682. 11. Kaji N, Kurita M, Ozaki M, et al.
Experience of sclerotherapy and embolosclerotherapy using ethanolamine oleate for
vascular malformations of the head and neck. Scand J Plast Reconstr Surg Hand Surg.
2009;43:126–136.
• 12. Loffroy R, Guiu B, Cercueil JP, et al. Endovascular therapeutic embolisation: an overview
of occluding agents and their effects on embolised tissues. Curr Vasc Pharmacol.
2009;7:250–263.
Good afternoon everyone.
Today Im going to report about the Different embolizing agents.
Therapeutic embolization is defined as the deliberate introduction of occluding material into a blood vessel in order to reduce or obstruct blood flow.
Several factors determine the selection of an embolic material.
One of the most important factors is the degree of permanence desired; therefore, agents are often classified as temporary or permanent agents (Table e-93.1).
A temporary agent is often used in cases of traumatic injury because it allows healing of an otherwise normal vessel to occur before blood flow is reestablished.
Conversely, in a patient with an arteriovenous fistula, permanent vascular occlusion is required in order to achieve the therapeutic endpoint.
Another consideration is the desired location or level of occlusion.
An example would be when treating an arteriovenous malformation, agents which occlude flow at the level of the nidus are needed.
Finally, there are important characteristics of each embolic agent with which the interventionist should be familiar.
These include size, radiopacity, material composition, mechanism of occlusion, and biologic behavior.
This is a table of various embolizing agents and their characteristics.
First is the duration of action. We have 2 temporary agents the gelfoam and avitene.
The gelfoam occlusive effects only last for several weeks and it usually used to stop traumatic or spontaneous bleeding or to devascularize a lesion prior to surgical removal.
For avitene the vessel recanalizes within 8 weeks and It is a useful agent for tumor necrosis and organ ablation.
The rest of the agents and permanent.
Such as coils, vascular plugs, detachable balloons, PVA, embolic spheres, drugs eluting particles, glue, onyx, alcohol, ethalomine and sclerosants which will be further discussed in the next slides.
Indications for Embolization
1. Occlusion of vascular abnormalities which have potential to cause adverse health effects (e.g., congenital or acquired aneurysm, pseudoaneurysm, vascular malformation)
2. Treatment of acute or recurrent hemorrhage
3. Devascularization of benign or malignant tumors for palliation or to reduce operative blood loss
4. Ablation of non-neoplastic tissue causing adverse health effects (like in cases of hypersplenism and varicocele)
5. Flow redistribution to protect normal tissue or to facilitate subsequent treatment (like in right portal vein embolization to induce left lobe hypertrophy prior to surgical resection)
6. Management of endoleak
7. Targeted delivery of drug or other agents
For the Mechanical Occlusive Devices
we have coils, vascular plugs and balloons
-Coils are made from either stainless steel or platinum and are available in a wide variety of sizes.
They may have fibers placed at right angles to the long axis of the coil, or coatings such as hydrogel, to increase the surface area and thereby increase the speed and permanence of thrombosis.
Coils rely on mechanical obstruction, platelet activation, and the patient’s own clotting cascade to fully occlude vessels.
Therefore, in the setting of thrombocytopenia and coagulopathy, the efficacy of coil embolization is compromised.
Tight coil packing is therefore important to achievement of arterial occlusion and reduction of early recanalization.
All coils are permanent devices and should be used when permanent occlusion is desired.
Coil stability is essential to prevent nontarget embolization.
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When larger nonterminal vessels are occluded with coils, there is relatively rapid formation of collateral arteries. These collateral vessels bypass the point of occlusion and perfuse the distal vascular bed, although at a lower pressure than that prior to embolization.
Stability can be aided by the following:
Use of a guiding catheter
Coil oversizing is essential to minimize the risk of dislodgment.
However, this should be weighed against the negative effect that an elongated and incompletely formed coil has on hemostasis. Oversizing by approximately 15% has been suggested in arteries. A greater degree of oversizing is required in veins.
Certain coils such as the AZUR Peripheral HydroCoil - do not require oversizing.
c. Use of detachable coil designs allow the operator to test the stability of the coil before detaching, which is preferred in high-risk situations or those in which the embolization target is in close proximity to an arterial branch whose patency is desired.
Detachable coils can be released by electrolytic or mechanical detachment, or by degradation of a polymer adhesive.
In a high-flow situation such as arteriovenous fistula, embolization can be performed using detachable coils with the double microcatheter technique.
d. Coil anchoring technique. The use of anchoring techniques using coils or other devices can help achieve the stable deployment of coils into a large vessel with high flow or high wall compliance. In the image at least 2cm of a coil is advance into the side branch. Which is normally sacrifice. The rest of the coil is then deployed just proximal to that side branch and additional coils are packed..
Coil anchoring devices include both purpose-built commercial devices and modifications of existing designs.
Coil anchoring devices are particularly useful for occlusion of large arteriovenous fistulae in the lungs and large portosystemic collaterals. In the image above is an example of TYPE 4 retrievable coil anchor with fibers
(1) Another device is the use of The Amplatz spider which is a stainless-steel, self-expanding metallic device that can be introduced through a guiding catheter or vascular sheath. It prevents the movement of coils and allows rapid occlusion of the vessel. One modification allows the spider to be screwed onto a threaded guidewire before loading into the catheter, which allows it to be retrieved and repositioned to ensure accurate placement.
(2) Retrievable coil anchors offer the advantage of improved safety due to the ability to retrieve and redeploy suboptimally placed devices. They are also intended to enhance occlusive efficacy by allowing a high density of occlusive material without compromising the self-anchoring capability of the nested coils.
Other qualities that can affect coil selection like the amount of fibers, volume of the metal, and radial force can affect tractability, packing, and delivery.
As new coil products become available, each product boasts desirable features compared with
its predecessors. For example, the Ruby coil (Penumbra Inc, Alameda, CA) offers a high volume coil that can be easily delivered through a high flow microcatheter. It can be used in a variety of situations, most notably when aneurysmal packing is needed (4).
Many other coils are available in different sizes and shapes that can be used in smaller microcatheters to reach more distal vessels in cases such as gastrointestinal (GI) bleeding.
(After placing the first microcatheter at the desired level of deployment in the target vessel, a coil can be delivered but not detached. It is used to prevent migration of more proximal coils delivered through the second microcatheter. The distal coil can be detached or retracted at the end of the procedure (2).)
2. Next is the Vascular plugs they are permanent occlusive devices which consist of self-expanding nitinol mesh in a threedimensional (3D) disc geometry.
The Amplatzer Vascular Plug is available in four versions (AVP I, II, III, and IV).
These plugs vary by the number of mesh layers, the shape and number of lobes, diameter range, unconstrained length, and the length of time to achieve vessel occlusion.
Each plug has radiopaque platinum marking bands, is attached to a delivery wire by a microscrew, and must be deployed through either a guide catheter or sheath (5 to 9 Fr.). The maximal length of the delivery system is 100 cm for plugs I and II and 120 cm for plug III.
AVP I has a single mesh layer, single lobe design which is well suited for a short landing zone due to its short unconstrained length (7 to 8 mm).
The AVP IV is available in 4- to 8-mm sizes and can be deployed using a 0.038-in. guidewire-compatible braided diagnostic catheter no longer than 125 cm. Due to the low profile and flexible design of the AVP IV, it is well suited for use in tortuous vessels.
Plugs should be oversized relative to the target vessel diameter by 30% to 50% as recommended by the manufacturer.
The devices are deployed by unscrewing the lock in a counterclockwise direction; therefore, precise positioning and repositioning can be achieved.
In general, due to their compact design, the relatively large surface area, and tight nitinol mesh structure, plugs should be considered when single-step occlusion of a larger vessel or branch is desired, or when an initial plug is needed to act as a scaffold for subsequent coil embolization.
Various applications include occlusion of internal iliac arteries prior to the deployment of aortoiliac stent grafts, exclusion of visceral arterial aneurysms, and treatment of ascending aortic pseudoaneurysms or emergency embolization of active bleeding
The microvascular plug (ev3 Endovascular Inc, Covidien, Plymouth, MN ) has become popular due to its ease of use. This plug can be deployed through a microcatheter into vessels up to 5 to 7 mm in diameter. They are partially covered, allowing immediate occlusion of the target vessels.
Larger devices are becoming available that can be used through 0.038-in. lumen diagnostic catheters. The release technique is electrical or mechanical.
The third one is the Detachable balloons they were on the market in the United States several years ago but were recalled due to manufacturing problems and difficulties with placement. The use of these devices has been replaced by the use of detachable coils or plugs.
Particulate embolic agents are typically used for the embolization of tumor and tumor-related symptoms such as mass effect or tumoral hemorrhage in addition to the treatment of certain hemorrhagic conditions not caused by a mass.
Embolic particles differ in available size ranges, uniformity of size and shape, tendency to aggregate, especially nonspherical PVA, and compressibility.
More compressible particles in theory will result in more distal embolization.
Particulate embolic agents tend to be classified as resorbable or nonresorbable.
In general, these agents are administered from a selective position within the arterial supply of the target organ and are subsequently deposited in a flow-directed manner to the area of desired treatment.
The different types of particulate embolic agents are gelfoam, avitene, PVA, spherical embolics and drug eluting particles.
Gelfoam is a water-insoluble, hemostatic agent prepared from purified pork skin gelatin.
It is used when a temporary effect is desired, such as to stop traumatic bleeding or to devascularize a lesion prior to surgical removal. It is usually resorbed completely with little tissue reaction.
The rapidity and degree of resorption depends on the amount used, degree of saturation with blood, and site at which it is used.
The treated vessel typically recanalizes within a few weeks.
Gelfoam can be prepared and shaped in numerous ways, depending on the indication for embolization.
“Torpedoes” can be created by cutting a section into columns of the preferred size and a column is twisted with the fingers to sharpen its edge.
These torpedoes are then placed in a syringe through its tip, and contrast is aspirated into the syringe as well.
You can injecting them through a catheter placed at, or slightly proximal to, the level of intended embolization.
Gelfoam torpedoes are also useful in the embolization of needle or catheter tracts.
Alternatively, less selective embolization can be performed with Gelfoam slurry. The slurry can be created by cutting a sheet into strips or squares, which can be loaded into a syringe connected via a three-way stopcock to another syringe filled with contrast. The materials are pumped back and forth between the syringes to create a suspension of smaller Gelfoam particles .
-------------
Gelfoam powder is no longer commercially available.
Next is Avitene. Iti s a microfibrillar collagen which was previously more often used in practice.
It is available in powder and sheet form.
In arteries embolized with Avitene, moderate recanalization occurs by 2 weeks and total recanalization by 2 months.
It is a useful agent for tumor necrosis and organ ablation because it can be delivered through a microcatheter.
Thrid one is Polyvinyl alcohol (PVA) it has historically been used in cements, packaging materials, water-resistant adhesives, cosmetics, and household sponges. They are irregularly shaped shavings from PVA blocks or sheets and are available in sizes from 50 to 1200 μm.
PVA is also supplied in the form of microspheres.
PVA particles produce mechanical occlusion of the vessel, activate thrombin, and induce fibroblast ingrowth, all of which leads to relatively permanent vessel occlusion.
PVA particles are distributed dry or in solution and are prepared by mixing in a solution of contrast and
saline.
------------------
Although the permanence of PVA as an embolic agent is well established,
It is also clear that the occlusion caused by PVA particles is not always permanent. Proposed mechanisms for recanalization include angiogenesis and capillary regrowth caused by vascular proliferation inside the organized thrombus. In addition, resorption of the thrombus found among clumps of PVA in the lumen of an embolized vessel can occur after the resolution of inflammation (6).
PVA particles tend to clump, leading to occlusion of vessels that are larger than the diameter of the individual particles.
As a result, these particles can be used to occlude a large range of vessel diameters from arterioles to larger arteries.
The level of occlusion can be controlled to some degree by the dilution of the particles.
There are several maneuvers that can reduce clumping:
In the mixing via (1) Particles are mixed in a solution containing 40% contrast. This mixture should maintain suspension of the particles in solution and prevent flocculation.
(2) The use of highly diluted particles is essential to prevent catheter occlusion or clumping, which may result in proximal embolization. So we can Dilute the particles in a 40-mL solution of contrast and saline.
After the first syringe is used, add another 10-mL solution to the bowl to maintain or increase dilution.
Occasionally, this process continues up to a final solution of 70 to 80 mL per vial of 1 mL PVA particles.
b. In the syringe immediately prior to injection (1) A 10-mL or 20-mL syringe is used to aspirate the particles mixed with contrast and saline from the mixing vial and serves as a reservoir and is connected to the middle hub of a three-way stopcock. A 3-mL or 5-mL syringe is then connected to the end hub of the three-way stopcock (in line with the microcatheter), and the syringes are aspirated back and forth to mix the particles.
(2) Another method uses a 3-mL non-Luer lock syringe. After aspirating the solution from the reservoir syringe, the injection syringe is rotated continuously during the slow injection of the particles to prevent precipitation and clogging.
Next is the Spherical embolics (“microspheres”) Compared to conventional PVA particles, the principal advantages of spherical embolic agents are ease of injection and reduced aggregation.
The end result is a more predictable level of occlusion with less clogging of catheters.
Microspheres are available in size ranging from 40 to 1,200 μm and are supplied in apyrogenic sterile sodium chloride solution.
There are physical and mechanical differences between each of the spherical embolic agents that can significantly influence clinical outcomes.
For Injection technique for spherical embolic agents (1) The syringe containing the particles and a 3- to 5-mL syringe with contrast material are connected to a three-way stopcock.
The contrast is aspirated into the particle syringe, and after 3 to 5 minutes, a uniform suspension is obtained. Once mixed, this solution can be injected easily and slowly. There is no need to perform the back and forth aspiration as for PVA particles because it might damage the spheres.
In cases of clumping you can add a 10mL or 20-mL contrast solution to create greater dilution.
(3) The injection technique of embolic particles is of paramount importance.
Flow-directed injection of particles respects the physiology of the circulation and allows for deposition of particles preferentially to the tumor even with a catheter in a non-superselective location.
Forceful injection can result not only in vessel damage or reflux but in some situations may also provoke the opening of vascular anastomoses with subsequent nontarget embolization.
-------------------------------
Embosphere microspheres (Merit Medical Systems, South Jordan, UT) were the first microspheres to be used in patients and are biocompatible, hydrophilic, nonresorbable, precisely calibrated trisacryl gelatin particles. Embospheres are U.S. Food and Drug Administration (FDA)-approved for use in the embolization of hypervascular tumors and uterine fibroids. EmboGold Microspheres (Merit Medical, South Jordan, UT) are made from trisacryl cross-linked with gelatin impregnated with 2% elemental gold for visibility. Currently, there are additional embolic agents available including Contour SE PVA microsphere (Boston Scientific, Natick, MA); Bead Block PVA-based hydrogel microsphere (Biocompatibles UK Ltd, Surrey, United Kingdom); QuadraSphere (Merit Medical, South Jordan, UT) super absorbing polymer microspheres; and Embozene hydrogel microspheres covered with Polyzene-F coating (CeloNova BioSciences Inc, San Antonio, TX).
the Drug-eluting particles offer the possibility of simultaneous embolization with sustained controlled drug release.
The electric charge of particles can be used to temporarily bind medications with an opposite charge.
After the beads are delivered, the drug elutes over time.
To date, the beads have been most commonly loaded with chemotherapeutic agents although in theory any water-soluble biologically active agent could be delivered.
Currently these beads are provided unloaded and the physician loads by soaking in his or her medication of choice.
Example are DC Beads produced from biocompatible, nonbiodegradable PVA hydrogel that has been modified with sulphonate groups to allow for the controlled loading and delivery of a chemotherapeutic drug. Doxorubicin-loaded beads have been used for the treatment of hepatocellular carcinoma and Irinotecan-loaded beads for the palliative treatment of metastatic colorectal cancer.
They can elute a local, controlled, sustained dose of a drug to the targeted tumor.
----------------------------
b. QuadraSphere microspheres (Merit Medical, South Jordan, UT) are superabsorbent polymer (SAP) microspheres that are biocompatible, hydrophilic, nonresorbable, acrylic copolymer microspheres that can absorb up to 64 times their dry-state volume. SAP microspheres can be loaded with doxorubicin or cisplatin and to date have been largely used for the treatment of hepatocellular carcinoma. These beads are marketed in Europe as HepaSphere.
c. Embozene tandem particles (CeloNova, BioSciences Inc, San Antonio, TX) are spherical, biocompatible, nonresorbable, hydrogel microspheres coated with an inorganic prefluorinated polymer. They are available in a range of sizes suitable for embolic therapy. They may be loaded with drugs such as doxorubicin or irinotecan and subsequently embolized.
The theoretical advantages of drug-loaded particles include a higher local concentration of the therapeutic agent resulting in less systemic adverse effects, longer exposure of the target to the therapeutic agent, and the potential to use drugs that are potentially toxic if injected systemically.
---------------------------
In the field of particulate embolization, the trend is toward the development of resorbable, loadable, and visible microspheres to improve the outcome.
Next are the liquid embolic agents such as Glue, Onyx, Alcohol, Ethanolamine Oleate, and other sclerosing agents such as Sodium tetradecyl sulfate, Polidocanol, Sodium morrhuate and Ethibloc
Glue (cyanoacrylate) is a fast and efficient, nonresorbable, nonradiopaque liquid embolic material.
Liquid monomeric cyanoacrylate is converted to a solid long-chain polymer immediately on contact with anionic substances such as plasma, blood cells, endothelium, or saline.
The reaction proceeds so rapidly that the glue will solidify in a catheter unless a substance is added that extends the polymerization time.
The most commonly used agent is Lipiodol an ethiodized oil typically in cyanoacrylate to oil ratios ranging from 1:5 to 2:5 depending on length of time needed until polymerization.
Some operators also add powdered tantalum to increase radiopacity and facilitate visualization during injection.
It is critical that this preparation takes place in an ion-free environment to prevent premature polymerization, preferably on a separate side table from that used for the remainder of the angiographic procedure.
The bolus of glue is introduced into the catheter after it has been flushed with 5% dextrose solution (D5W) and is pushed out of the catheter with another bolus of D5W. The catheter is typically changed after each injection.
Histopathologic studies of glue demonstrate that cyanoacrylate provokes a more intense inflammatory reaction than that caused by PVA and involves the wall of the vessel and the adjacent interstitial areas.
This inflammatory reaction ultimately leads to vessel necrosis, fibrous ingrowth, and permanent occlusion.
The most common application of glue is the treatment of vascular malformations, particularly intracranial, although it has been applied throughout the body for virtually every embolic indication.
Risks of using cyanoacrylates include rapid polymerization and reflux resulting in gluing the catheter in place or feeding vessel occlusion without the desired nidal penetration. If the polymerization time is too long, the cyanoacrylate can pass into the venous circulation, resulting in pulmonary emboli.
Seconde if the Onyx which is a biocompatible liquid embolic agent.
It is an ethylene vinyl alcohol copolymer dissolved in various concentrations of dimethyl sulfoxide (DMSO) and opacified with micronized tantalum powder.
When this mixture contacts aqueous media such as blood, the DMSO rapidly diffuses away, resulting in in situ precipitation and solidification of the polymer.
It forms a soft elastic embolus without adhesion to the vascular wall or the catheter.
The polymerization process is mainly influenced by the amount of ethylene vinyl alcohol (EVOH) in the mixture.
Onyx comes in two different preparations which differ in the concentration of EVOH, Onyx 18 with 6% EVOH and Onyx 34 with 8% EVOH.
The lower the concentration of EVOH, the less viscous the solution, the longer it will take to precipitate and will penetrate more distally into the treated vessel.
Because the polymer will solidify on contact with aqueous media, the delivery catheter must be preflushed with DMSO.
A DMSO-compatible catheter is also required (e.g., Rebar, Echelon) (ev3 Endovascular Inc, Covidien, Plymouth, MN).
Onyx is nonadhesive, allowing for easy removal of the delivery catheter and of the polymer itself.
As opposed to glue, there is no concern for catheter adherence to the embolic material which can cause difficulty in removing the catheter from the patient. Unfortunately, Onyx is quite expensive. It is primarily used for intracranial aneurysms; however, in peripheral embolization, it has been successfully used for both the treatment of aortic graft endoleak and high flow vascular malformations (9).
Absolute alcohol is a very effective embolization agent; however, it must be used with great care. It can be injected via an intravascular route or direct percutaneous puncture.
Upon contact with the vessel wall, ethanol denudes the endothelium, which leads to thrombosis and eventual fibrosis.
In addition, ethanol induces further thrombosis as it contacts blood.
Both actions lead to complete permanent vascular occlusion. This effective occlusion can be used from an intra-arterial approach for tumor or organ ablation, particularly renal embolization.
In the hands of a very skilled practitioner, it can be used in the treatment of vascular malformations. Despite its efficacy, it is important to consider the risk of toxicity and adverse effects of alcohol.
The principal disadvantage of absolute alcohol is the risk of necrosis of neighboring tissues including nerves or skin.
The risk of systemic toxicity increases with doses above 1 mL per kg or if the total volume exceeds 60 mL. The patient must be monitored closely, including continuous vital sign assessment. Some practitioners advocate the use of pulmonary artery pressure monitoring during procedures involving ethanol.
Methods to decrease the risk of nontarget embolization include:
Controlling reflux with occlusion balloons
Using in vascular beds without significant collaterals (e.g., kidney)
Precisely defining the anatomy of the vessels to be occluded including assessment of supply to normal tissues
Placing the catheter in as selective a position as possible
Using the smallest volume likely to achieve the intended effect, usually in small aliquots
Occluding venous outflow to isolate the target vascular bed
Opacifying ethanol with tantalum powder or Ethiodol to improve visualization
Ethanolamine oleate is a mixture of 5% ethanolamine oleate and Ethiodol (ratio 5:1 to 5:2).
The oleic acid causes intimal irritation, which leads to an inflammatory response which ultimately causes mural necrosis, thrombosis, and fibrosis.
Compared with ethanol, ethanolamine has less penetrative effect, so it may be safer to use in situations where vascular structures are in proximity to nerves.
Ethanolamine has been used predominantly for venous sclerosis, including treatment of gastroesophageal varices and venous malformations, as well as for cyst sclerosis.
Approximately 50% of the oleic acid may combine with serum proteins within 30 minutes and can cause renal toxicity in association with a marked intravascular hemolysis, hemoglobinuria, and hepatotoxicity. Prophylactic haptoglobin may be helpful during and after the injection to reduce nephrotoxicity
Other sclerosing agents such as
Sodium tetradecyl sulfate is an anionic surfactant widely used for sclerosis of esophageal varices, varicose veins, and venous malformations.
It is an anionic detergent containing 2% benzyl alcohol.
It causes intimal inflammation and thrombus formation and subsequent formation of fibrous tissue resulting in vessel occlusion.
It is not as effective as other agents in the treatment of high-flow vascular malformations but can be used in low-flow lesions.
It can be injected in liquid form or can be mixed with room air or carbon dioxide to form a foam consistency.
Although toxicities such as urticaria, anaphylaxis, hemolysis, and hematuria can be seen with larger doses,
NEXT IS Polidocanol IT is a nonionic surfactant sclerosant that was first developed as an anesthetic. It causes vascular injury through endothelial overhydration. The agent’s attractive anesthetic properties make it nearly painless. Its use is primarily restricted to venous disease. -----
5. Other sclerosing agents Technically, all liquid embolic agents can be considered sclerosants; however, the term is usually applied to low-viscosity agents used predominately in venous disease. Each agent has also been used with varying success in other types of embolization and cyst ablation.
the Third one is Sodium morrhuate it is an irritant and sclerosing agent composed of a sodium salt of fatty acids in cod liver oil.
This agent has been used in the treatment of varicose veins and venous malformations; however, it has been reported to be 1.5 to 4 times less effective than sodium tetradecyl sulfate.
The last one is Ethibloc it is composed of a solution of zein, sodium amidotrizoate, oleum papaveris, and propylene glycol.
It is derived from corn gluten and forms hard shells used in coatings of foods and pharmaceutical products.
Ethibloc has been used effectively for the treatment of venous, lymphatic, and arteriovenous malformations.
It requires approximately 10 to 15 minutes to solidify into a viscous solution, allowing it to remain static within the target lesion to cause intravascular thrombosis, necrosis, and fibrosis
-In summary I have reported the Different embolizing agents including its duration of action, mechanism of actions, advantages and disadvantages
- I have also mentioned the differenct Factors to consider in choosing the right embolizing agents depending on the clinical scenario as well as the various techniques, in preparation and administration of different embolizing agents.
