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

8. 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.

9. 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.

10. 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

11. MODE OF
ADMINISTRATION
1) Orally.
2) Rectally.
3) Intravenously – (injection/
infusion).
4) Mechanically – Filling of a
body cavity or potential
space.
5) Intra-muscularly

12. 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
IOTHALAMA
TE
DIATRIZOAT
E
IOXAGLIC
ACID
IOCAMIC
ACID
METRIZAMI
DE
IOHEXOL
Non ionic dimers
IOTRO
L
IOTROL
AN
X-RAY & CT ULTRASOUND MRI
Positive CM Negective CM
water,air,CO2
Non water soluble BaSO4 IODINATED CM

13. Types of contrast media
CONTRA
ST
MEDIA
POSITIV
E
CONTRA
ST
IODIN
E
BASE
D
BARIU
M
SULPHA
TE
NEGATIV
E
CONTRA
ST

14. 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 carbondioxide
CONTRAST MEDIA FOR X-RAY
AND CT

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

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

18. The average atomic number is
INCREASED positive contrast

19. 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

20. • 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

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

22. BARIUM
SWALLOW
BARIUM
MEAL
BARIUM MEAL FOLLOW
THROUGH

23. ENTEROCL
YSIS
BARIUM
ENEMA

25. 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).

26. IODIN
E:
1) Atomic number 53
2) 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

27. 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
IOTHALAMA
TE
DIATRIZOA
TE
Ionic dimers
IOXAGLIC
ACID
IOCAMIC
ACID
METRIZAMI
DE
IOHEXOL
IOTROL
IOTROL
AN

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

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

30. USE:
1) Sialography
2) Hysterosalpingograp
hy
3) Myelography
4) Lymphangiography
5) Dacryocystography
6) Galactography
7) Broncography

31. SIALOGRAP
HY
HYSTROSALPHINGOGR
APHY
MYELOGRAP
HY

32. DACROCYSTOGR
APHY
GALACTOGRA
PHY
BRANCHOGRA
PHY

33. Renal excretion
Hepatic excretion
Iopanoic acid
High osmolar low osmolar
Ionic monomers Non-ionic monomers Non ionic dimers
IOTHALAMA
TE
DIATRIZOA
TE
Ionic dimers
IOXAGLIC
ACID
IOCAMIC
ACID
METRIZAMI
DE
IOHEXOL
IOTROL
IOTROL
AN
WATER SOLUBLE
IODINATED CM

34. 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 (T4)
to triiodothyronine (T3)
Hepatic excretion
• Use:
1) Cholecystography
2) Hyperthyroidism:adjunctive
therapy with thioamides
(propylthiouracil, carbimazole).

35. HIGH OSMOLAR IODINE
CONTRAST
MEDIA
IONIC
MONOMER

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

37. LOW OSMOLAR IODINE CONTRAST MEDIA
1) IONIC DIMERS.
2) NON IONIC
MONOMERS.
3) NON IONIC DIMERS.

38. 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

39. Methods of
Administration
• Orally
• Rectally
• Intravenous
• Intra
cavitatory

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

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

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

43. 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.

44. 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

45. 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

46. CARDIOVASCULAR TOXICITY --
1. Intracoronary injection – cardiac rhythm disturbances
2. Increased vagal activity – depression of SA & AV node –bradycardia , asystole
3. Injection of hypertonic contrast medium – significant fluid & ion shift
e.g. – hypervolemia – due to diffusion of extracellular fluid through capillary walls
HEMATOLOGICAL CHANGES –
1. 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

47. 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

48. Idiosyncratic reaction
CLASSIFIED AS –
1. 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,

49. 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

50. {
Prophylaxis

51. PROPHYLAXIS OF RENAL ADVERSE REACTION
IDENTIFICATION OF PATIENTS AT INCREASED RISK-
1. Referring clinician should identify patients with preexisting renal impairment
& inform radiology department
2. 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

52. 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 –
1. Consider an alternative test
2. 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

53. {
Treatment

54. 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

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

56. 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
1. LARYNGEAL EDEMA MANAGEMENT – O2
--epinephrine
--intubation if necessary

57. 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

58. 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

59. 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

60. THANK YOU