Contrast media drugs and pathophysiology and management

1. Contrast Media and Drugs
Dr. Pradeep Kumar
MD. Radiodiagnosis

2. 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.

3. CLASSIFICATION OFCONTRASTMEDIA
Oily/non water soluble
IODINATED CM
Water soluble
IODINATED CM
Renal
excretion
Hepatic
excretion
Iopanoic
acidHigh
osmolar
low
osmolar
Ionic
dimers
Non-ionic
monomers
Ionic monomers
IOTHALAMATE
DIATRIZOATE IOXAGLIC ACID
IOCAMIC ACID
METRIZAMIDE
Non ionic
dimers
IOTROL
IOTROLAN
X-RAY & CT ULTRASOUND MRI
Positive CM Negective CM
water,air,CO2
Non water soluble BaSO4
IODINATED CM

4. • Positive
• Water-soluble (Iodinated contrast media) are of two
types- HOCM and LOCM.
• Water-insoluble: Barium sulphate.
• Negative
• CO2
• N2O
• Air
• O2

5. IODINATED CONTRAST MEDIA
• Water-soluble positive contrast media
• Chemically they are the derivatives of 2,4,6
triiodobenzoic ring.
• Clinically classified into two groups
• HOCM
• LOCM

7. HOCM
Name Type I/particle
ratio
Osmolality
• Diatrizoate
(Urograffin
)
• Iothalamat
e
(Conray)
• Metrizoate
(Isopaque)
Ionic
monomer
3/2= 1.5 1500

8. Ionic monomer
Diatrizoate (Urograffin)

9. LOCM
Name Type I/particle
ratio
osmolality
Ioxaglate(
hexabrix)
Ionic dimer 6/3=2 490
Iopamidol
Iohexol
Iopramide
Iopentol
ioversol
Non-ionic
monomer
3/1=3 470
Iotrolan
Iodixanol
Non-ionic dimer 6/1=6 Isoosmolar

10. Non-ionic monomer
IOVERSOL (OPTIRAY)

11. Non-ionic monomer
iobitridol (xenetix)

12. Non-ionic monomer
Iopromide (Ultravist)

13. HOCM Vs LOCM
HOCM LOCM
• High osmolality
• I to particle ratio 1.5
• All are ionic monomers
• Higher incidence of
adverse rxns and toxic
effects.
• Low osmolality
• I to particle ratio 2, 3 or 6.
• Ionic dimers, non-ionic
monomers and non-ionic
dimers
• Lower incidence of
adverse rxns and toxic
effects.

14. HOCM VS LOCM
HOCM LOCM
Adverse rxns for ionic ICM
( from a large study
comprising 6000 pts)
1.Mild 2.5%
2.Moderate 1.2%
3.Severe 0.4%
Adverse rxn for non-ionic
ICM ( from a large study
comprising 7170 pts)
1.Mild 0.58%
2.Moderate 0.11%
3.Severe 0%

15. HOCM VS LOCM
HOCM LOCM
• Low cost
• Use- used due to
their low cost.
• Expensive
• Use- if cost was not
the factor LOCM
would have replaced
all other ICM .
LOCM are used in
high risk groups.

16. Sodium and meglumine salts
Sodium salts Meglumine salts
1. More neuro and
cardiotoxic.
2. Cause less histamine
release and hence less
chance of bronchospasm.
3. Immediate and delayed
pain at injection site is
more common.
4. Use- preferred in
asthmatic and allergic pts
1. Less so.
2. More histamine. 4 fold rise
of incidence of
bronchospasm compared
to Na salts.
3. Less common.
4. Use- preferred in CNS and
cardiac cases as well as in
cases with volume
overload.

17. MRI CONTRAST MEDIA
• Contrast agents are used in MRI to enhance the inherent
contrast bet tissues .
• Mechanism of action:
• Large magnetic field density due their unpaired
electrons.
• Interacts with the magnetic moments of the protons
in the tissues and so shorten their T1 relaxation time–
increase in signal intensity.
• Electron magnetic moments also cause local changes
in magnetic field, which promotes rapid dephasing of
proton and so shortens the T2 relaxation time. This
rapid T2 relaxation produces reduced signal intensity.

18. MRI CONTRAST AGENTS
MRI contrast agents possess unpaired electron spins.
The agents may be classified into two groups:
A. Oral contrast agents
• Positive contrast; Manganese chloride, oil emulsions
• Negative contrast; Barium, blue berry and pineapple
juice
B. Parenteral contrast agents

19. MRI CONTRAST AGENTS
On the basis of Susceptibility:
• Ferromagnetic
• Paramagnetic
• Super-paramagnetic.

20. MRI CONTRAST AGENTS
On the basis of relaxivity
• Positive relaxation agents (T1 agents)
Eg: Gd, Mn-DPDP
• Negative relaxation agents (T2 agents)
Eg: Iron oxide particles, high dose Gd

22. FERROMAGNETIC
• Have magnetic moments which align with
scanner’s applied field– maintain their alignment
even after applied field is removed.
• Retained magnetism may cause particle
aggregation and cell function interference.
• So unsafe for MR contrast agents.
• Eg: Iron, Cobalt, Nickel

23. PARAMAGNETIC
• Example: Gadolinium, Oxygen, Melanin
• Have magnetic moments which align to the applied
field
• Alignment return to normal after gradient field is
turned off.
• May be made soluble by chelation and hence can be
used IV.
• Maximum effect is on protons of water molecule,
shortening the T1 relaxation time– increased signal
intensity on T1 images.

24. SUPERPARAMAGNETIC
• Example: Ferrite
• Are aggregation of paramagnetic ions in a
crystalline lattice.
• Cause abrupt change in local magnetic
field which results in rapid proton
dephasing and reduction of T2 relaxation
time: Produce decreased signal intensity
on T2 images.
• Are less soluble than PM agents- So
available only as colloidal suspensions.

25. GADOLINIUM
• Rare earth element
• Atomic number: 64
• Paramagnetic agent
• Usual dose: 0.1mmol/kg
• Median lethal dose: 6-3o mmol/Kg
• Gadolinium chelates: DTPA, DOTA, BOTA

26. Extracellular Liver Agent Blood pooling
Gd-DTPA Gd-BOPTA Vasovist
Gadopentetatedumeglumine Gadobenate Gadofosvesettrisodium
(Magnevist) (Multihance)
Gd-DTPA-bismethylamide Gd-DTPA
Gadodiamide (omniscan) Gadoxetate disodium
Gd-DO3A (Primovist)
Gadoteridol(ProHance).

28. LINEAR, NON IONIC OMNISCAN
(GADODIAMIDE)

29. LINEAR, IONIC
MAGNEVIST (GADOPENTETATE)

30. MACROCYCLIC, IONIC
DOTAREM (GADOTERATE)

31. INDICATIONS OF GADOLINIUM
• CNS tumours/infections
• Demyelinating disease- acute/ chronic plaques
• More accurate delineation of tumour margins from edema.
• Discrimination of tumour recurrence from post op fibrosis.
• Cardiac and aortic imaging
• Body imaging

32. Safety issues
1.Renal failure
2.History of allergy/asthma
3.Pregnancy
4.Lactation

33. Dose
•Usually 0.1mmol/kg body weight upto 0.2 mmol/kg
when used in low-field magnets.
•Slow iv injection.

34. SIDE EFFECTS
 Warmth
 Pain at inj site
 Seizure
 Strange taste
 Nausea
 Headache
 Dizziness
 Anaphylactoid rxn
 Nephrogenic systemic fibrosis

35. NONENCAPSULATEDMICROBUBBLES ENCAPSULATEDMICROBUBBLES
EncapsulatedAir
Microbubbles
Encapsulated
Perflurocarbon MB
1)Albunex
2)Echovist
galactose
3)Levovist
galactose & palmitic acid
4)Cavisomes –
gas filled cyanoacrylate
microspheres for Liver,
spleen & LN
Optison:
Albumin coated
microspheres that
contain
Octafluropropane
gas
Uses:Cardiac app
1)Formed by hand
agitation
2)Unstable & breech
quickly
3)Large size, small
fraction pass
through pulmonary
circulation
4)Adequate for right
heart visualization
TYPESOFULTRASOUND
AGENTS

36. Contrast Agents in Ultrasound
Requirements:
• Easily introducible in vascular spaces
• Stable for the period of diagnostic examination
• Low toxicity
• Modifying one or more acoustic properties to be detected by
ultrasound beam

37. Contrast Agents in Ultrasound
Requirements:
• Gas microbubbles are used
• Should be less than 7 micron.
• US contrast media depend on interaction between encapsulated microbubbles
and US beam.
• Allow imaging of vascular structures which cannot be evaluated even with
sophisticated doppler techniques.

38. Blood Pool contrast Agents
• Free Gas bubbles
- Agitated normal saline into left ventricle
- Disadvantages;
Large size effectively filtered by lungs
Unstable
• Encapsulated air bubbles

39. US contrast agents
• Levovist
• Most widely used.
• Microbubbles of air enclosed by a thin layer of
palmitic acid in a galactose sol.
• Stable in blood for 1- 4 min.
• Echovist
• Precursor of Levovist
• Bubbles in galactose but no palmitic acid.
• Can’t pass thro pulm beds
• Used for tubal patency.

40. US contrast agents
• Albunex
• Sonicated air microbubbles coated with human serum albumen.
• Used in echocardiography.
• Survives only a short time in left ventricle.
• Little enhancement of arterial tree.
• EchoGen
• An emulsion of dodecafluoropentane which changes its phase converting into
echogenic gas microbubbles by hypobaric activation prior to iv injection.

41. US contrast agents
• SonoVue
• An aqueous suspension of stabilized sulphur hexafluoride microbubbles.
• After reconstitution of the lyophilisate with saline, the suspension is stable
and can be used for upto 4 hrs.

42. GASTROINTESTINAL MRI CONTRAST AGENTS
• Easily miscible with bowel contents
• Palatable
• Two groups:
– Positive agents: Fatty oils and gadolinium. Act by T1 shortening effect.
– Negative agents: Ferrite and barium sulphate; Act by T2 shortening.

43. GASTROINTESTINAL CONTRAST MEDIA
•Water insoluble: BaSO4
•Water soluble: ICM and Gases

44. BARIUM SULPHATE
Barium Mixtures
• Before barium was discovered for use in GI studies,
Bismuth was used with many unwanted effects
because of its solubility.
• Barium, with its high atomic number of 56 and its
insolubility in water is a good contrast agent for GI
examinations because it is very dense and won’t
be absorbed by the GI tract.
• However, suspending agents are required to
counter the insolubility in water.

45. ADDITIVES IN BARIUMS MIXTURES
1. Suspending agents: Keeps barium in solution
2.Vegetable gums Creates viscosity and suspends barium
particles in solution
3.Carboxy Methylcellulose - Avoids clumping of barium and
aids in the dispersion of barium
4.Dispersing agents Keeps barium particles dispersed evenly
throughout the suspension
5.Simethicone - An anti-foam agent prevents air bubble
formation
6.Sorbitol improves the coating qualities of barium. It is
hypertonic and therefore there is a fluid shift into the bowel
lumen, thereby decreasing transit time of barium in the small
bowel.

46. BARIUM SULPHATE
HIGH DENSITY LOW VISCOCITY

47. PARTICLE SIZE OF BARIUM
Particles of barium must be small to make them more stable
in suspension. A non-ionic suspension medium is used
otherwise the barium particles would aggregate into
clumps.
Three different sizes of barium particles:
Micronized 1 μ: Used for upper GI,
colon
Colloidal 1/10 μ: Used for small bowel, colon
Variable 1/2-40 μ: Used for upper GI, colon
PH of the Barium suspension is 5.3 which makes it
stable in gastric acid.

48. DENSITY OF BARIUM SUSPENSION
• Density of the Ba suspension can be expressed in terms of
weight/volume or weight/weight.
• Different densities of Ba preparations available for examinations of
different parts of GI tract.

49. BARIUMSWALLOW
(E-Z HD200% to250% w/v)
BARIUMMEAL
E-Z HD250% w/v
BARIUMMEALFOLLOW
THROUGH
E -Z paque 60–100% w/v

50. ENTEROCLYSIS
E –Z paque 60
% w/v
BARIUMENEMA
Pollibar115% w/v

52. • Barium swallow: E-Z HD 250% W/V 100 ml or
more as required.
• Barium meal: E-Z HD 250% W/V 135 ml.
• BFT: E-Z paque 60- 100 % W/V 300 ml
• SBE: E-Z Paque 60% W/V 1500 ml
• Barium enema: Polibar 115% W/V 500 ml or
more as required.

54. ADVANTAGES OF BARIUM
• Excellent coating of mucosa as compared to water-soluble
contrasts.
• Cost

55. DISADVANTAGES OF BARIUM
• High morbidity when Ba is spilled in peritoneal cavity.
• Subsequent CT and US rendered difficult.

56. COMPLICATIONS OF BARIUM
• Perforation
• Aspiration
• Intravasation
• Impaction
• Constipation

57. WATER-SOLUBLE CONTRAST MEDIA
IN GI TRACT
• They are iodinated contrast media and gases.
• Two commonly used ICM agents are
• Iopamidol (gastromiro)- 61% w/v; 300mg iodine per ml sol. This is LOCM.
• Meglumine diatrizoate 66% and sod diatrizoate 10% ( Gastrografin)- 370 mg I per ml sol.
This is HOCM.

58. INDICATIONS OF WATER-SOLUBLE CM IN GI
TRACT:
• Suspected perforation
• Meconium ileus
• To distinguish bowel from other structures on CT.
• LOCM is used if aspiration is a possibility.

59. Complications
• Pulmonary edema if aspirated ( not for LOCM)
• Hypovolemia in children
• Allergic rxn due to absorbed contrast media
• May precipitate in hyperchlorhydric gastric acid( not for non-
ionics)
• Ileus

60. GASEOUS AGENTS IN GI STUDY
• CO2 and air are used in conjunction with Ba for double contrast
effect.
• Air is used in Ba enema.
• CO2 is used in the form of gas producing granules/ powder to
study the upper GI tract in double contrast study.

61. BILIARY CONTRAST MEDIA
• Like conventional urographic contrast media, biliary
contrast media are also triiodobenzoic acid
dearivative.
• Iopanoic acid ( telepaque) was introduced in 1951
and later compounds were all modifications of it.
Differences occur in prosthetic group and amino
group.
• These agents are excreted via biliary route and not
thro kidneys due to the absence of prosthetic group
in position 5.

62. BILIARY CONTRAST MEDIA
• Oral agents-
• Single benzene ring
• Examples are iopnoic acid( telepaque) and sodium ipodate( biloptin). They
come in capsule forms.
• IV agents
• Meglumine iotroxate( biliscopin) is a dimer with the polymethylene chain
connecting the two rings.
• IV agents are rarely used these days.

63. METABOLIC PATHWAY OF ORAL AGENTS
• Absorption from gut by passive diffusion.
• After absorption albumen bound.
• Carried to liver by portal vein.
• In liver taken up by hepatocytes.
• Conjugation with gluduronic acid to form more water soluble glucuronides.
• Excretion into bile is an active process which can become saturated and is the
rate-limiting step.
• Concentrated in gb by absorption of water. Peak opacification of gb occur
after 12 h of ingestion.
• Oral agents are finally excreted in stool. Reabsorption is limited by the fact
that after conjugation they are no longer lipophilic.

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• A rising serum creatinine level is
usually the first sign of an impending
change in renal function.
• Serum creatinine level often rises
within the first 24 hours. (Elevation
may not occur for 72 hours).
• Peaks in three to five days.
• Returns to baseline by seven to 10
days after the procedure

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