embolizing agent( Interventional Radiology).pptx

embolizing agnet

1. Embolizing Agents Presenter: Swastika Pandit B.Sc.MIT 4th year NAMS,Bir hospital

2. Embolization Embolization  refers to lodging of an embolus within the  bloodstream. It may be of natural origin embolism (Pathology),for example pulmonary embolism. Or Artificially induced. Therapeutic introduction of substances into circulation, to arrest or prevent hemorrhage, to devitalize a structure, tumor or organ by occluding blood supply.

3. Embolization means: “obliteration of a vessel by introducing into the bloodstream an occlusive agent (foreign body, biological tissue, sclerosing fluid, etc.), which produces the deliberate interruption of vascular flow, mechanically or by producing an intense inflammatory reaction of the vessel wall”. Deliberate occlusion of a blood vessel to achieve a therapeutic result.

4. Therapeutic goals of Embolization An adjective goal : preoperative , adjunct to chemotherapy or radiotherapy. A curative goal : definitive treatment in case of aneurysm, AVFs, AVMs and traumatic bleeding. A palliative goal : relieving symptoms such as large AVMs

5. Embolic agents Permanent Temporary Gel Foam Collagen Thrombin Particles PVA Embospheres Coils Pushable Injectable Detectable -Mechanical -Electrolytic -Hydrolytic Others Ampltser Plugs GGVOD Detectable Ballons Glue Liquid agents Alcohol Onyx AL GEL

6. Device selection Vascular territory to be embolized Degree of occlusion—proximal or distal—desired Permanence of occlusion i.e Temporarary or Permanant

7. Permanent Large-Vessel Occlusions Coils- Pulmonary AVM Balloons Amplatz Vascular Plug Guide wires Silk suture material

8. Permanent Small-Vessel Occlusions Particles Liquid sclerosants Liquid adhesive Ethiodol Thrombin Onyx

9. Temporary Large-Vessel Occlusions Gel foam sponge Autologous clot Temporary Small-Vessel Occlusions Gel foam powder Starch microspheres Fibrillated collagen

10. Temporary embolic agents   Gelfoam (Gelatin Foam) It is the most widely used temporary embolic agent, is an absorbable bioprosthetic material available as a block (sponge or sheet) or as a powder. Gel-foam powder particles range from 10 to 100 μ. It provides a temporary occlusion lasting approximately 3 to 6 weeks. It is made up of purified skin gelatin First used for cortico -cavernous fistula(1964) It is available in sterile sheets & powder. Gel foam is cut into 1-2 mm pieces Mixed with dilute contrast Injected as pledgets / prepared as slurry

11. Mechanism of action of gel foam Its aggregates or swells on hydration into larger particles Mechanical obstruction Slowing of blood flow Hastening thrombus formation

12. Advantage As it is temporary in nature advantageous in haemoptysis & trauma Low cost widely available and easily modified to the size of the target artery Disadvantage Can cause infection due to the trapped air bubbles Can lead to ischemia due to small size (< 70 µm ) Used for embolization of pelvic trauma or postpartum hemorrhage, (especially when there are multiple punctuate bleeding sites from various branches of the internal iliac artery.)

13. Setup for particle embolization. Larger syringe is reservoir and smaller is for injection. Open end of the three-way connects to the catheter. This setup is for all particles as well as gelfoam slurry.

14. Embolization material and substance 1 st agent used was Autologous blood clot ( temporary occlusive agent) Method : Aspirate roughly 20 mL of the patient's blood and allow it to clot, then discard the supernatant and reintroduce the clot through the catheter. If desired, the clot can be opacified by adding sterile tantalum powder . Advantage: Easily and quickly obtained Absence of cost. Lack of adverse reaction(biocompatible ). Disadvantage: Recanalization occurs within hours to days due to body’s natural clot lysis mechanism

15. Schematic display of thrombin injection in a false aneurysm. Uses: Autologous blood clot seal (ABCS) after biopsy of lung lesions can reduce or prevent pneumothorax. Epidural blood patch to relieve post Dural puncture headaches caused by lumbar puncture.

16. Permanent embolizing agent Particles: Polyvinyl Alcohol Particles First used in 1974 it is a plastic sponge that is fragmented and filtered to a certain size range. They produce permanent occlusion by adhering to the vessel wall and causing an inflammatory reaction and vessel fibrosis Particles are made from PVA sheets – vacuum dried & rasped into particles Particles are filtered with sieves(filtering devices) and PVA is available in sizes between 50 and 2000 µm, the typical size ranges used clinically are 300 to 500 µm or 500 to 700 µm.

17. Mechanism of action PVA PVA particles are irregular in shape which (oval, oblong, irregular and angulated) promote aggregation . PVA particles : Adherent to vessel wall Stagnation of flow Inflammatory reaction Vessel fibrosis Permanent occlusion

18. Uses Uterine fibroid embolization -either for preoperative devascularization or as definitive treatment. JNA (Juvenile nasopharyngealAngiofibroma ) embolization. Bronchial artery embolization. Portal vein embolization. Etc Disadvantage Occludes vessels from proximally due to irregular size. Can cause catheter occlusion which can lead to non targeted embolization when catheter is flushed. Smaller particles have a significant risk of tissue infarction due to their distal level of occlusion.

19. Microspheres ( embospheres , biosphere medical ) They are perfectly round and slightly deformable embolic agents, they can be compressed approximately 20% of their diameter. They have the advantage of having a uniform size, which decreases the risk that smaller spheres may end up in distal vessels and cause ischemic complications. Its diameter varies between 50 and 1,200 microns. They are not radiopaque, so they must be mixed with contrast medium

20. Embosphere : Tris -acryl Gelatin Microspheres Embospheres are precisely calibrated, spherical, hydrophilic, micro porous beads made of an acrylic co-polymer, which is then cross-linked with porcine gelatin. The hydrophilic surface prevents aggregation, allowing a more predictable, uniform vessel occlusion than PVA, as well as easier delivery through small catheters. Embospheres are available in six size ranges: 40 to 120 μm , 100 to 300 μm , 300 to 500 μm , 500 to 700 μm , 700 to 900 μm , and 900 to 1200 μm . Embospheres are packaged in 20-mL prefilled syringes containing 2 mL of spheres in saline . Embosphere gold particles are colored for visibility.

21. Diagrammatic representation

22. SIR Spheres SIR-Spheres microspheres contain resin based  microspheres  with an average diameter between 20 and 60  micrometre . The microspheres are impregnated with  90 Y , a  beta radiating  isotope of  yttrium Once injected into the hepatic artery via a  catheter   the microspheres will preferably lodge in the  vasculature  of the tumour . The radiation will lead to damage of tumour tissue and, in the best case to a complete elimination of the tumour . Due to the half-life almost all of the radiation is delivered within 2 weeks. After 1 month almost no radioactivity will remain. used to treat patients with unresectable   liver cancer . Provide internal radiation of hepatic malignancies. SIR Spheres microspheres

23. Mechanism of microsphere Same as PVA Particles . That is they: Adherent to vessel wall Stagnation of flow Inflammatory reaction  focal angio -necrosis Vessel fibrosis Permanent occlusion

24. Advantage Particles accumulation in catheter tube is uncommon. Disadvantage Needs intermittent brisk stirring to prevent sedimentation . Embospheres are composed of porcine gelation which has allergic potential Careful attention in sizing is required because same size embosphere will penetrate more deeply compared with PVA which could cause unintended ischemia . Uses In the treatment of fibroid by uterine artery embolization liver embolization in patients with metastatic neuroendocrine tumors In the preoperative embolization of meningiomas Embolization of facial AVM Microspheres in uterine Fibroids treatment

25. Coils Coils are permanent embolic agents that come in a variety of shapes and sizes . First embolic coils consisted of pieces of stainless steel guide wires onto which strands of wool had been woven to add a matrix for thrombus formation. They are typically used for occlusion of larger vessels and cause complete occlusion equivalent to surgical ligation . Stainless-steel coils are best suited for high-flow applications due to their high radial force, which helps prevent dislodging. Coils are generally made of steel or platinum. Although more expensive, platinum coils are more malleable and radiopaque and are easier to see under fluoroscopy compared with similarly sized and shaped steel coils Platinum coils are highly visible under fluoroscopy and are much softer than stainless steel . This facilitates accommodation of the coil to the vessel. Appropriate sizing is important to ensure occlusion of the vessel at the intended location.

26. MECHANISM OF ACTION Coils in blood vessel Vessel wall damage Release of thrombogenic factors Thrombogenesis Clot formation Slowing of blood flow Clot formation Thrombogenesis

27. Coils Size - 0.008 to 0.052 inches Length – 1 to 300 mm Diameter – 1 to 27 mm Shape – J or C shaped, helical, conical, straight and complex 3D shapes. Coils may be bare or fibered with material such as dacrum , nylon fiber, polyster , wool, silk or PVA (to increase thermogenicity ) In general coils should be sized 20 to 30 % larger than what the vessel measures on pre deployment angiogram to prevent distal embolization / migration.

28. Advantage Easy to see, control and display Causes complete occlusion of vessels Disadvantage Occlusion of non target vessels Coil migration Vessel dissection/ perforation Vessels rupture(soft coils are used to reduce incident) Infection Allergic reaction

29. Uses of coil Applications for coil embolization include treatment of hemorrhage – Aneurysm . Occlusion of arteriovenous fistulas . Preoperative or pre-stent graft vessel occlusion. *The main goal is prevention of rupture in unruptured aneurysms, and prevention of rebleeding in ruptured aneurysms by limiting blood circulation to the aneurysm space * Embolization with coils produces a focal occlusion, leaving the vessel distal to the coil patent, similar to surgical ligature. Therefore, coils are utilized in almost any application in which precise vessel occlusion.

30. Coils Methods of delivery Pushable coils Injectable coils Detachable coils Mechanical Electrolytic Hydrolytic

31. Pushable coils Most commonly used Special guide wire with bulbous tip is used to physically push the coil through an end hole catheter into a desired position Advantage Ready availability Relative cost and easy to use Disadvantage Reposition is not possible Can be trapped at sharp curves of vessels. If incompatible with the catheter, can become irretrievably jammed in the catheter

32. Pushable coil. Left to right: package, loaded introducer, initial introducing stylet .

33. Injectable coils(liquid coils) These are the soft, non fibered platinum coils of 0.008 to 0.016 inch in diameter . Injection through a catheter via a small syringe with saline. Quicker method. Liquid coils are deployed by forceful injection of contrast through the catheter after loading the coil . Advantage Tight coil compaction Ability to accommodate to tortuous anatomy Ability to flow to a target distal to the catheter if required Disadvantage Vigorous injection can result in pushing the catheter back substantially and risking non target embolization

34. Detachable coils The first detachable coil was described in 1977 by Professor Cesare Gianturco . Cesare first used these coils to embolize renal tumors These coils are not routinely used . It is non fibered, extremely soft . Uncoated platinum coil fixed to a stainless steel delivery wire . They come in a variety of shapes such as– 3D basket type,2D helical type . Current detachable coils deploy by a variety of mechanisms including mechanically, by electrolysis, and via hydrostatic means . Used in AVM and Aneurysms.

35. Disadvantage expensive, large setup time the coil can rotate or flip at detachment by inadvertent detachment during wire manipulation . The disadvantage of this system is that there is often friction between the microcoil and microcatheter

36. Mechanically detached coil (hinge mechanism).

37. A. Mechanical coils Mechanical detachment includes interlocking mechanical detachment and screw-release mechanisms . The interlocking mechanism uses small metal beads, or hinge, at the proximal coil tip and end of the wire . The coil is fastened by overlapping the beads hinge . Within the catheter the coil is attached, but once out of the catheter the beads separate and the coil is released. D isadvantage : friction between the microcoil and microcatheter

38. B. Electrolytic coils(GDC- Gugliemi detachable coil) Electrolytic detachment coil was designed and first used by Dr. Guido Guglielmi in 1991 . The original GDC is a non-fibered, extremely soft, uncoated platinum coil affixed to a stainless steel delivery wire. Coil is welded to the pusher wire in the desired position.

39. The wire is attached to a battery device. The current melts the welded connection between the coil and the wire and detaches the coil. Currently, the platinum coil is welded to platinum- tungsten alloy and has a highly successful deployment rate A 1-mA current is used to detach the coil at the weld point. A 2-mA current can alternatively be used to detach the coil more quickly Advantage : Minimally invasive Requires less time than surgery Disadvantage : Expensive

40. C.HYDROGEL COILS It is a detachable platinum coils(0.008-to-0.016-inch diameters) coated with an expandable polymer. When detached in the vasculature > polymer expands> coil diameter increases from 0.014 to 0.027 inches . Complete expansion occurs within 20 minutes. These are extremely soft, non fibered platinum coils . Although made of metal, liquid coils can be delivered across tight bends and conform to the space into which they are injected

41. Advantage : greater volume expansion & occlusion than regular coil Do not depend on thrombus formation ability to accommodate to tortuous anatomy, and ability to flow to a target distal to the catheter if desired Disadvantage : coil can get struck in the catheter if the coil is not compatible with the delivery system.

42. Others 1)Detachable balloon It was first used in 1974 Balloon is made up of latex of size 6 to 14 mm and silicon size 6 to 10 mm . Uses cortico - cavernous fistula, pulmonary AVMs, large vessel occlusion. Advantage Ability to occlude large vessel. possible reposition. Disadvantage Rupture of vessels, deflation, migration and premature detachement .

43. 2) Amplatzer vascular plug It is a new device (expandable nitinol mesh occlusion device) Amplatzer I – simple thick disk 4 to 16 mm Amplatzer II – thin disk 3 to 22 mm They have stainless steel screw attachment to delivery wire & radio- opaque marker bands at both ends. Uses Internal iliac artery, mesenteric artery, Renal artery, Portal vein, Splenic Artery.

44. Advantage reduces need for multiple coil hence saves money and time. Disadvantage used in straight segment of vessel which dose not taper. Does not cause immediate thrombosis . They are not fibered & depend on patient’s ability to form thrombus.

45. DETACHABLE SACK VASCULAR OCCLUSION DEVICE First described by Dr. Ronald G. Grifka and Prof. Cesare Gianturco , the detachable sack Grifka-Gianturco vascular occlusion device. (GGVOD) incorporates a flexible nylon sack in varying diameters attached to a 4.5F sack catheter . Coils are advanced into the sack and then the filled sack is released from the catheter by advancing a release catheter up against the neck of the sack. The sack catheter is the withdrawn firmly, which releases the sack. The GGVOD allows repositioning of the device before release; coils can be pulled out of the sack and the sack can be pulled back into the sack catheter

46. Permanent liquid agents 1.Glue  Glue (N-BUTYL- 2 CYNOACRYLATE - NBCA ) Preparation: 1 gm. of tubes of NBCA – free monomer, when expended to anionic environment(blood & water ) polymerization occurs. 10 ml ethiodized oil(Made from iodine and poppyseed oil) – vehicle and acts as a polymerization occurs . 1gm of tantalum powder – provides radiographic opacification and initiates polymerization These are mied immediately before use.

47. N-butyl-cyanoacrylate (NBCA) N -butyl-2-cyanoacrylate (NBCA), also commonly known as “glue,” is a clear free-flowing radiolucent liquid It is one of the main liquid adhesive agents used mainly in the treatment of high-flow arteriovenous malformations, highly vascular tumors and lymphatic malformations. I t polymerizes rapidly on contact with ionic solutions such as blood or normal saline and forms a cast of the vessel. Although in principle it was used without radiopaque agents, it is currently used in combination with oils such as Ethiodol in a ratio of 1: 4 ( Ethiodol : NBCA). Due to the viscosity of this component, it occludes the vessels, and also generates an acute inflammatory process in the wall of these, which subsequently progresses to chronic in approximately four weeks .

48. Mechanism of action Glue adherent to vessel wall Inflammatory reaction Chronic inflammation Polymerization of glue starts immediately on contact with anion

49. Glue   To avoid unintended polymerization by premature contact with anion catheter should be flushed with 5% dextrose in water intermittently. That is why it requires special set up i.e 3 way stopcock (syringe for NBCA and 5% dextrose) Immediately after glue injection, catheter tip is retracted to avoid catheter adhesion . Advantage permanent completely occludes the vessels works instantly Disadvantage Can get entrapped in the occluded vessel . Require expertise, Polymerization can spread distally or reflux proximally to the intended lesion.

50. 2.Onyx (Ethylene Vinyl Alcohol Co-polymer- evoh ) First used as embolic agent by Dr taki in 1990 Co-polymer of ethylene vinyl alcohol, prepared with dimethyl sulfoxide solvent . Tantalum powder is added for opacity . On contact with blood, the DMSO diffuses away allowing polymerization of the EVOH, which forms a cast of blood vessels After Onyx is injected into the target lesion, the dimethyl sulfoxide solvent rapidly diffuses away, causing precipitation of the polymer and formation of a spongy cast . Used mainly in Cerebral and Peripheral AVM emboization

51. Mechanism of action Onyx / EVOH on contact with blood DMSO (dimethyl sulfoxide ) diffuse away Polymerization of EVOH Forms a cast

52. Procedure EVOH comes with separate vail of DMSO and DMSO compatible catheters should be used for procedure . Catheter is placed in place DMSO is injected to fill the catheter dead space Which inhibits in catheter polymerization of EVOH EVOH is injected under fluoroscopy guidance

53. Advantage Non adhesive allows longer injection times and ability to temporally suspend embolization which allows further procedure during angiography. Disadvantage Need DMSO compatible catheter DMSO is toxic and rapid injection causes vasospasm and necrosis . Use in cerebral AVM Injection Rate : < 0.3 ml/ > 40 seconds

54. Sclerosing agents 3.Absolute alcohol ( ethanol) Ethanol is the most commonly used sclerosant and causes protein denaturation, which leads to endothelial damage and permanent vascular occlusion . Inadvertent introduction of alcohol into a normal vascular territory can result in serious complications . Latex occlusion balloon catheters are often used to control the flow of ethanol, prevent reflux of ethanol, and keep ethanol in place for a few minutes, allowing the ethanol to interact with the endothelium. Peripheral indications for ethanol use include renal tumor ablation and portal vein embolization before partial hepatectomy

55. Cause protein denaturation, leading to endothelial destruction and vascular occlusion. Occlusion by sclerosants is usually permanent . Sodium tetradecyl sulfate ( Setrol ) and Polidocanol Uses ablation of tumours , solid organs, veins, or vascular malformations.

56. Absolute Alcohol Absolute Alcohol Denaturation of proteins Thrombosis Fibrosis Infarction Mechanism of action

57. Advantage Less cost, easily available Disadvantage Difficulty to control placement ,Lack of opacity and rapid dilution by vascular inflow

58. 4.Calcium Alginate Gel ( Algel ) It is polymer of alginic acid Procedure: Calcium alginate Liquide alginate (premixed with contrast for visibility) Calcium chloride Forms a non adhesive gel foam

59. Advantage Unlike coils, gel fills the entire structure to be occluded Catheter occlusion is less likely because two components are injected separately Disadvantage Requires expertise.

60. References Diagnostic imaging : Interventional procedures 2 nd edition by Brandt C.Wible . Sandeep Vaidya , M.D ,   Kathleen R. Tozer ,  and  Jarvis Chen .An Overview of Embolic Agents . Semin Intervent Radiol .  2008 Sep; 25(3): 204–215.doi :  10.1055/s-0028-1085930 María A L, Alejandra D V, Luis F A, Jorge R U and Alejandro R. Transcatheter Embolization . Rev. Colomb. Radiol. 2017; 28(4): 4773-81. Avinash M, Albert Z, Philip O et.al .A Case-Based Approach to Common Embolization Agents Used in Vascular Interventional Radiology. American Journal of Roentgenology . 2014;203: 699-708. 10.2214/AJR.14.12480. Slideshare

61. Thank you