Contrast agents

Contrast agents

1. CONTRAST MEDIA Dr. PRITHVIRAJ JADHAV Assisstant Professor Dept . Of Radiodiagnosis

2. Aims of this session Why contrast agents are used What are the desirable features of a contrast agent Types of contrast agents used in clinical settings Methods of administrating contrast agents Examples of examinations utilising contrast agents Problems/issues associated with administrating contrast agents

3. Why contrast agents are used Different tissues within the body attenuate the beam of X-rays to different degrees. The degree of attenuation of an X-ray beam by an element is complex, but one of the major variables is the number of electrons in the path of the beam with which it can interact.

4. The number of electrons in the path of the beam is dependent upon three factors: The thickness of the substance being studied Its density The number of electrons per atom of the element (which is equal to its atomic number)

5. Where there is inherent considerable difference between the densities of two organs

6. However, if the two organs have similar densities and similar average atomic numbers, then it is not possible to distinguish them on a radiograph, because no natural contrast exists. For example, it is not possible to identify blood vessels within an organ, or to demonstrate the internal structure of the kidney, without artificially altering one of the factors mentioned earlier

7. 2)CONTRAST MEDIUM: It is a chemical substance of very high or very low atomic number or weight, therefor it increase or decrease the density of the organ under examination. OR A substance which when introduced into the body will increase the radiographic contrast in an area where it was absent or low before.

8. Two of the factors important in organ contrast can be artificially altered, the density of an organ, and, more usefully, the average atomic number of a structure.

9. What are the desirable features of a contrast agent Easy to administer No toxicity/carcinogenecity Stable compound Concentrates in area of interest Proper demonstration of the organ system Should have rapid elimination Minimal distress to patients (viscosity) Cost effective

10. MODE OF ADMINISTRATION Orally. Rectally. Intravenously – (injection/ infusion). Mechanically – Filling of a body cavity or potential space. Intra-muscularly

11. CLASSIFICATION OF CONTRAST MEDIA Oily/non water soluble IODINATED CM Water soluble IODINATED CM Renal excretion Hepatic excretion Iopanoic acid High osmolar low osmolar Ionic dimers Non-ionic monomers Ionic monomers I O T H ALAM A TE DIATRIZOATE IOXAGLIC ACID IOCAMIC ACID M E T R I Z AMI D E IOHEXOL Non ionic dimers IOTROL I O T R OLAN X-RAY & CT ULTRASOUND MRI Positive CM Negective CM w at e r ,ai r , C O2 Non water soluble BaSO4 IODINATED CM

12. Types of contrast media C O N TRA S T MEDIA POSITIVE C ONT R AST I O D I NE BASED BARIUM SULPH A TE NEGATIVE C ONTRAST

13. POSITIVE CONTRAST Contrast material is radiopaque. high atomic number material white on film Example : 1) Barium sulfate USE: GI Studies. 2) Iodine compounds. USE : angiography, intravenous and retrograde urography hysterosalphingography sialography myelography cholangiography NEGATIVE CONTRAST Contrast material that is not radiopaque Low atomic number material Black on film Example: 1) Water, Air and carbon dioxide CONTRAST MEDIA FOR X-RAY AND CT

14. NEGATIVE CONTRAST AGENTS Air CO2 O2 E.g. PEG Air arthrogram Double contrast barium examinations

15. The density of a hollow organ can be reduced by filling it with gas or air, providing negative contrast NEGATIVE CONTRAST

16. The average atomic number is INCREASED positive contrast

17. POSITIVE CONTRAST AGENTS BARIUM SULPHATE Radiological contrast media are usually water soluble solutions, but there is one commonly used variety that is based on a suspension of large insoluble particles Examinations of the upper and lower gastrointestinal tracts

18. Barium sulphate suspensions have better coating properties than the iodinated contrast media, and tend to form thin layers spread over the lining of the gut WHY BARIUM IN GI SERIES

19. BARIUM SULPHATE Atomic number:56 Highly radiopaque. Non absorbable. Non toxic. Insoluble in water/lipid. Inert to tissues. Can be used for double contrast studies. Route: Orally Or Rectally (aqueous suspension with 0.3 to 1 g dry weight per milliliter) Uses: barium swallow barium meal barium meal follow through Enteroclysis barium enema

20. BARIUM SWALLOW BARIUM MEAL BARIUM MEAL FOLLOW THROUGH

21. ENTEROCLYSIS BARIUM ENEMA

22. CONTRAINDICATION: Integrity of gut wall compromised or GI Perforation. Previous allergic reactions to barium. Suspected fistula between oesophagus and lung. Side effects: Aspiration. Granuloma(Leakage:Mediastinum, tissue around Rectum or Intraperitoneal cavity). Leakage into the vasculature(life threatening). Constipation. worsening ulcerative colitis inflammation. peritonitis through perforation. Fatal Reaction(rare).

23. IODINE: Atomic number 53 Atomic weight 127 1) Radioopacity depends on : iodine concentration of the solution, so dependent on number of iodine atoms in each molecule of the contrast medium. 4) Iodine particle ratio: the ratio of number of iodine atoms per molecule to the number of osmotically active particles per molecule of solute in solution 5) Iodine is preferred because: High contrast density due to high atomic number Allows firm binding to highly variable benzene ring Low toxicity

24. IODINATED CONTRAST MEDIA Oily/non water soluble IODINATED CM Hepatic excretion Iopanoic acid High osmolar Water soluble IODINATED CM Renal excretion low osmolar Ionic monomers Non-ionic monomers Non ionic dimers I O T H ALAM A TE DIATRIZOATE Ionic dimers IOXAGLIC ACID IOCAMIC ACID M E T R I Z AMI D E IOHEXOL IOTROL IOTROLAN

25. WATER VS OIL BASED OIL BASED NEVER INJECTED ONLY DUCTS NOT INGESTED WATER BASED INJECTED VESSELLS/DUCTS INGESTED Organ function/flow

26. OILY/NON WATER SOLUBLE IODINATED CM Fatty Acids Insoluble in water White on the radiograph Examples: Iophendylate (Myodil, Pantopaque)- myelographic agent Lipiodrol Ultrafluide (Ethiodol)- lymphangiographic agent. COMPLICATION: 1) Fat Embolism LYMPHANGIOGRAPHY

27. USE: Sialography Hysterosalpingography Myelography Lymphangiography Dacryocystography Galactography Broncography

28. SIALOGRAPHY HYSTROSALPHINGOGRAPHY MYELOGRAPHY

29. DACROCYSTOGRAPHY GALACTOGRAPHY BRANCHOGRAPHY

30. Renal excretion Hepatic excretion Iopanoic acid High osmolar low osmolar Ionic monomers Non-ionic monomers Non ionic dimers I O T H ALAM A TE DIATRIZOATE Ionic dimers IOXAGLIC ACID IOCAMIC ACID M E T R I Z AMI D E IOHEXOL IOTROL IOTROLAN WATER SOLUBLE IODINATED CM

31. IOPANOIC ACID is an iodine-containing radiocontrast medium . potent inhibitors of thyroid hormone release from thyroid gland, as well as of peripheral conversion of thyroxine (T 4 ) to triiodothyronine (T 3 ) Hepatic excretion Use: Cholecystography Hyperthyroidism:adjunctive therapy with thioamides (propylthiouracil, carbimazole).

32. HIGH OSMOLAR IODINE CONTRAST MEDIA IONIC MONOMER

33. Example: Diatrizoate(urograffin, angiograffin , urovideo, urovision, trazograff) Iothalamate(conray, Triovideo) Ioxithalamate Metrizoate Disadvantage: High osmolality (8 X plasma) because of the non radiopaque cations (Na & meglumine) is responsible for the adverse effects.

34. LOW OSMOLAR IODINE CONTRAST MEDIA IONIC DIMERS. NON IONIC MONOMERS. NON IONIC DIMERS.

35. IONIC MONOMER IONIC DIMER NONIONIC MONOMER NONIONIC DIMER Iodine particle ratio 3:2 6:2 OR 3:1 3:1 6:1 Molecular weight 600-800 1269 600-800 1500-1626 Iodine content at 0.3 osmol/kg H2O ( 300mg I/ml) 70 150 150 300 Osmolality at 280mgI2/ml (osmol/kg H2O) 1500 560 600 300 LD50 (g of I/kg wt of mouse) 7 12 22 >>26

36. Methods of Administration Orally Rectally Intravenous Intra cavitatory

37. Examples of examinations utilising contrast agents Angiography Intravenous urography (IVU), intravenous pyelography (IVP) Computed tomography (CT) Interventional techniques GI series Other examinations

38. ADDITIVES USED IN CONTRAST MEDIA Stabilizer: Ca or Na EDTA Buffers: Stabilizes pH during storage, Na acid phosphates Preservatives: Generally not disclosed by the manufacturers.

39. IDEAL CONTRAST MEDIA High water solubility. Heat & chemical stability(shelf life) ideally- 3 to 5yrs. Biological inertness( non antigenic). Low viscosity. Low or isoosmolar to plasma. Selective excretion, like excretion by kidney is favorable. Safety: LD50 (lethal dose) should be high. Reasonable cost.

40. POINTS TO REMEMBER Contrast media used for myelography- non-ionic CM. CM used for cerebral angiography- only meglumine salt. Least osmolar- Ioxaglate (Hexabrix). Most hyperosmolar- Iohexol. Max nausea & vomiting - Ioxaglate (Hexabrix). Bronchospasm - Meglumine salts. Viscosity : Increase with concentration Higher for dimers(big size) High viscosity interferes with mixing of contrast media with plasma & body fluids. Least viscosity- Omnipaque240 Meticulous heparinization is required during angiography as incidence of thromboembolic phenomenon is high when CM is mixed with blood.

41. Choice of contrast Infants (introduction of hyperosmolar fluid into the bodies of very young children can cause problems of fluid balance) The elderly (for the same reason) Diabetics Patients with cardiac impairment Patients with renal impairment Asthmatics Patients who have previously reacted adversely to a contrast medium Patients with a history of allergy Patients who are unduly anxious

42. Adverse effects VASCULAR TOXICITY --VENOUS --1. pain at injection site –result of perivenous injection --2. pain extending up the arm –due to stasis of contrast in arm – relieved by abduction of arm --3. delayed limb pain –due to thrombophlebitis as a result of toxic effect on endothelium ARTERIAL –arterial endothelial damage & vasodilation –related to hyperosmolarity SOFT TISSUE TOXICITY – pain ,swelling , erythema even sloughing of skin due to extravasated contrast medium --increased risk when pumps are used to inject large amt of contrast media

43. CARDIOVASCULAR TOXICITY -- Intracoronary injection – cardiac rhythm disturbances Increased vagal activity – depression of SA & AV node – bradycardia , asystole Injection of hypertonic contrast medium – significant fluid & ion shift e.g. – hypervolemia – due to diffusion of extracellular fluid through capillary walls HEMATOLOGICAL CHANGES – Erythrocyte damage – injection of HOCM  loss of water from RBC  dehydrated shrunken RBC  Increased internal viscocity with loss of ability of RBC to deform to traverse capillary obstruction of important capillary beds (cerebral , renal, coronary, pulmonary ) 2. Red cell aggregation & coagulation may occur 3. Thrombus formation may occur – commoner with LOCM 4.Sickle cell crisis may be precipitate

44. NEPHROTOXICITY -- CONTRAST INDUCED NEPHROPATHY –sr. creat conc . starts to rise within first 24 hrs , reaches peak by 2-3 days & returns to baseline by 3- 7 days PREDISPOSING FACTORS – preexisting impairment of renal function -- diabetes mellitus --dehydration --large doses of contrast --age --multiple myeloma --concurrent use of nephrotoxic drug NEUROTOXICITY – if BBB is impaired , nerve cells are exposed to toxic effects of contrast media THYROID FUNCTION – thyrotoxicosis may be exacerbated in preexisting thyrotoxic symptoms

45. Idiosyncratic reaction CLASSIFIED AS – MINOR REACTION -- do not interfere with examination but require patient reassurance --e.g. –nausea, vomiting, mild rash , light headache 2. INTERMEDIATE REACTION –interfere with examination --e.g.- urticaria , facial edema, dyspnea, hypotension 3. SEVERE REACTION -- warrant urgent tretment & hospitalisation e.g. –circulatory collapse, pulmonary edema, severe angina convulsions,

46. Mechanism HISTAMINE RELEASE – histamine – primary mediator of anaphylaxis –released by mast cells due to contrast media COMPLEMENT ACTIVATION – contrast media may activate complement system which induce histamine release & other biological mediators PROTEIN BINDING & ENZYME INHIBITION –contrast media are weakly protein bound & thus inhibit enzyme acetylcholinesterase --contrast media side effects are cholinergic effects – e.g.—vasodilation, bradycardia , bronchospasm CHEMOTOXICITY – due to cations - especially Na+, effects are seen in neurons, myocardial cells , capillary endothelium, RBC, kidney ANXIETY – most contrast reaction result of patients fear & apprehension --high autonomic nervous system activity in anxious patient is stimulated further after contrast administration

47. Prophylaxis

48. PROPHYLAXIS OF RENAL ADVERSE REACTION IDENTIFICATION OF PATIENTS AT INCREASED RISK- Referring clinician should identify patients with preexisting renal impairment & inform radiology department sr.creat should be measured within 1 week before administration of contrast PRECAUTIONS FOR PATIENTS WITH SIGNIFICANT RENAL IMPAIRMENT ( sr.creat > 130 micromol / l) 1.Consider alternative imaging method 2. 48 hr before stop any treatment with metformin . It should be withheld for further 48 hrs after procedure & renal function should be reassessed before restarting metformin 3. 24 hr before stop all nephrotoxic drugs, mannitol , & loop diuretics 4. 6 hr before start hydrating patient either orally or intravenously 5. Use smallest possible dose of contrast medium 6. Use low or iso-ismolar contrast media --no definite evidence that hemodialysis protect patients with impaired renal function From contrast medium induced nephrotoxicity

49. PROPHYLAXIS OF NON RENAL ADVERSE EFFECTS IDENTIFICATION OF PATIENTS AT INCREASED RISK OF ANAPHYLACTOID REACTION– patients should be asked for history of— 1. previous contrast reaction 2. asthma 3. previous allergic reaction requiring medical treatment PRECAUTIONS FOR PATIENTS AT INCREASED RISK OF ANAPHYLACTOID CONTRAST REACTION – Consider an alternative test If contrast is necessary – a. use non ionic contrast media b. for previous reactors use a different non ionic contrast than used previously c. maintain close supervision d. leave canula in place & observe for 30 min. e. be ready to treat promptly any adverse reaction & ensure that emergency drugs & equipment are ready 3. Premedication may be used e.g.- prednisolone 30 mg orally given 12 hr & 2hr before contrast administration

50. Treatment

51. OXYGEN – high dose oxygen ( upto 100% ) at rate of of 10- 12 lit /min via face mask EPINEPHRINE – available in 2 dilutions – --1 in 1000 – 1mg in 1 ml – s. c. or i.m . use --1 in 10000 –1mg in 10 ml– for i.v. administration Epinephrine is administered – --sc. In a dose 0.1 – 0.3 ml ( 0.1 – 0.3 mg) can be repeated every 10-15 min until a total dose of 1 mg is administered -- i.v. in same dose of 0.1- 0.3 mg , so due to greater dilution 1-3 ml is injected COMPLICATIONS- hypertensive crisis , myocardial ischemia , infarction Administered carefully in following pts - with cardiac disease , with hypertension on beta blockers CORTICOSTEROIDS – effective in reducing late reactions , which can be observed upto 48 hrs -- i.v. doses of 100- 1000 mg of hydrocortisone recommended --can be followed by continuous infusion of 300-500 mg in 250 ml saline at rate 60 ml/ hr PRINCIPLES OF TREATMENT

52. MILD REACTION -- reassure patient --loosen tight clothing, tell patient to take few deep breath & relax --stay with patient & watch until symptoms subside

53. Moderate-severe reaction SKIN REACTION – usually no treatment is needed -- if pruritus is severe use diphenhydramine ( 50 mg ) --if patient develops severe erythema or angioedema use H1 & H2 blockers ( cimetidine 300 mg in 20 ml ) – if no response use epinephrine 0.1-0.3 ml RESPIRATION REACTION – causes of respiratory decompensation 1. airway & laryngeal edema 2. bronchospasm 3. pulmonary edema LARYNGEAL EDEMA MANAGEMENT – O2 --epinephrine --intubation if necessary

54. 2.BRONCHOSPASM – MILD – O2 --metered dose inhaler albuterol 2-3 inhalation MODERATE –epinephrine -- aminophylline – 5 mg/kg i.v. slowly over 10-20 min SEVERE – epinephrine i.v. 3. PULMONARY EDEMA – elevate head end of bed --O2 10 L/ min --furosemide 40 mg i.v. slowly --morphine 1-3 mg i.v. --hydrocortisone 100 mg i.v. slowly --shift to ICU HYPOTENSION – MILD – 1. release any abdominal compression 2. elevate legs 3. O2 4. isotonic i.v. fluids – administered rapidly SEVERE – BRADYCARDIA – atropine 0.6 mg i.v. slowly , repeat 3- 5 min, max upto 3mg --TACYCARDIA – epinephrine 1- 3ml ( 1: 10000) i.v. upto 10 ml or dopamine

55. SEIZURES OR CONVULSIONS – MILD –1. turn patient to one side to avoid aspiration . Be sure airway is clear & open 2. O2- 10 L/min SEVERE – diazepam 5 mg i.v. slowly HYPERTENSIVE CRISES –1. O2 10 L/ min --nitroglycerine 0.4 mg tablet sublingually -- if no response , nifedipine --10 mg capsule sublingually -- ECG -- if pheochromocytoma , phentolamine 5 mg i . v. -- frusemide 40 mg i.v. slowly EXTRAVASATION OF CONTRAST MATERIAL – 1.eLevation of affected extremity above heart level 2. Ice packs ( 20 min t.i.d . for 2-3 days ) 3. Plastic surgery consultation if – large volume extravasation -- skin ulceration or blistering -- worsening symptoms after 2-4 hrs 4. Close follow up until resolution

56. MRI CONTRAST MEDIA MECHANISM OF ACTION – act indirectly by altering magnetic properties of Hydrogen ions (protons ) in water & lipid . They alter rate of relaxation of protons FERROMAGNETIC – retain magnetism even when applied field is removed . Interfere with cell function – unsafe for clinical use PARAMAGNETIC – e.g. gadolinium . Have magnetic moments which align to applied field , but once gradient field is turned off, thermal energy within overcome alignment. Their maximum effect is on protons – shortening of T1 relaxation time & hence increased signal intensity ( white ) on T1 images . SUPERPARAMAGNETIC – particles of iron oxide ( Fe3O4), small particles of iron Oxide ( SPIO ), ultrasmall particles of iron oxide ( USPIO ) --cause abrupt changes in local magnetic field – results in rapid proton dephasing – Reduction in T2 relaxation – decreased signal intensity ( black ) on T2 images

57. THANK YOU