Contrast Media and Its Types
Upakar Paudel
B.Sc.MIT 2nd Year
Roll no-6
UCMS Bhairahawa, Nepal
Introduction
• Contrast agents are the substances which possess an atomic no or
have an e- density which differs significantly from that of surrounding
structures & permits the visualization of the details of internal organs
that would not otherwise be demonstrable.
2
History
• 1896, walter B. Cannon use radiopaque sustances.
• 1904, colloidal silver was used in retrograde urography.
• 1910, Krause use barium sulphate for visualisation of GIT.
• 1923, Osborne reported the opacification of UT after the injection of
10% NaI soln.
3
History
• 1928, compound with no of pyridine rings containing iodine .
• 1952, first tri-iodinated compound (sodium acetrizoate) was
introduced.
• Until the early 1970s all CM were ionic compounds with osmolalities
of 1200-2000 mosmal/kg.
4
History
• Ionic monomer:
1954, diatrizoate (urografin)
1962, iothalamate (conray)
1962 – 1972,
Metrizoate,Iodamide,Ioxithalamate,
Ioglicate
5
History
• Non-ionic monomers
1969 Metrizamide (Amipaque®)
1974 Iopamidol (Isovue®)
1976 Iohexol (Omnipaque®)
1979 Iopromide (Ultravist®)
post 1980 Iopentol
(Imagopaque®),Iomeprol,Ioxilan.
6
History
• Ionic dimers
1978 Ioxaglate(Hexabrix®)
7
• Nonionic dimers
Post 1980
Iodecol
Iotrolan (Isovist®)
Iodixanol (Visipaque®)
Function of contrast media
• CM alters the attenuation of x-ray beam by altering the density of
related structures.
• The atomic no of the related structures also alter & helps in
visualisation of similar density structures within the region of
interest.
8
Classification of CM
On the basis of physical properties:
• Negative Contrast Media.
• Positive Contrast Media
9
Negative CM
• Gaseous substances which has low atomic number and specific weight,
absorb X-rays to a lesser extent than the surrounding body structures.
CO2
N2O
Air
O2
10
Positive CM
• Substances which, because of their higher specific weight and atomic
number, absorb X-rays to a greater extent than the body tissues.
Barium sulphate
Iodinated contrast media
Contrast media for MRI and Ultrasound.
11
Barium sulphate
• Ba Suspension is made up of pure Ba Sulphate.
• Particles of Ba must be small (0.1-3μm),which makes more stable in
suspension.
• Barium, having atomic no 56, is a good contrast agent for GI
examinations because it is very dense and won’t be absorbed by the
GI tract.
• In most situation it is diluted with water to give a lower density.
12
Ba sulphate
• Solution has a pH of 5.3, which makes it stable in gastric acid.
• Examinations of different parts of GI tract require Ba preparation
with differing properties & different concentration.
• A non ionic suspension medium is used, otherwise its particles would
aggregate into clumps.
13
Advantage of Ba
• Excellent coating which can be achieved.
• Allowing the demonstration of normal and abnormal mucosal
patterns.
• Economic because of lower cost.
14
Iodinated CM
• Most of IV CM contain Iodine which has 53 atomic no. & 127 atomic
weight.
• Total iodine content in the body is 50 mg.
• It is Preferred because
 High contrast density due to high atomic
no.
Low toxicity.
•Conc ranges from 140-370mgI/ml.
15
Iodinated CM
• They are water soluble .
• It is classified as:
Ionic
Non-ionic
Ionic monomers CM High-osmolar
Ionic dimer CM Low-osmolar
Monoionic/diionic
non-ionic monomer CM Low-osmolar
Non-ionic dimer CM. Iso-osmolar
16
Ionic CM
• In solution, ionic contrast media ionize into two particles, i.e. the
cation and the anion.
• The anion in an ionic contrast medium is the triiodinated benzoic acid
part while the cation is usually sodium, calcium or meglumine.
17
Ionic monomers
• Iodine to particle ratio is 3:2
• Sodium or meglumine act as cations.
18
Ionic monomers
• Examples:
Iothalamic Acid
Has better neural tolerence but decrease
cardiovascular tolerence.
Eg. Conray
Diatrizoic Acid
Increase solubiliy
Decrease plasma protein binding & increase
glomerulus filtration.
Improves patient tolerence.
Eg. Urografin
19
Ionic dimer
• Monoionic dimers ionize to give two particles but the number of iodine
atoms present is 6. Therefore the iodine atom to particle ratio is 6:2,
i.e.3 .Eg: Hexabrix.
• Diionic dimers ionise to give three particles (two cations and one anion)
with six iodineatoms present so that the iodine atom to particle ratio is
6:3, i.e. 2.
20
Non-ionic monomer
• The molecule does not ionize & do not give two particles.
• Formed by replacing the cation radical portion of benzene ring with a
non-dissociating organic chain.
• It remains as one single molecule when in solution because of an amide
group on the acid part.
21
Non-ionic monomer
• Less toxic effect becoz of removal of acid group & replacement of large
no of OH group which make them more hydrophilic.
22
Non-ionic monomer
• These molecules do not ionize in solution so that the iodine to particle
ratio is 3:1. Therefore these are also ratio-3 molecules.
• Eg: Iohexol (Omnipaque), Ioversol (Optiray) Iopromide (Ultravist).
23
Non-ionic dimer
• These molecules will give six iodine atoms for every molecule so that
their iodine atom to particle ratio is 6:1 which makes them ratio-6
molecules.
• Disadvantage is high viscosity becoz of relatively large size of molecule.
• Eg: Iodecol, Iotrolan (Isovist), Iodixanol (Visipaque®)
24
Osmolality
• Osmolality is measure of no. of particles of solute in solution per kg
of water.
• Osmolality can be described as the property of a liquid to give up its
water to or to take up water from another liquid separated by a semi-
permeable membrane.
• Hypo-osmolar liquid gives up water to the second liquid.
• Hyper-osmolar liquid takes up water from the second liquid.
• Iso-osmolar liquids have the same osmolality and do not exchange
water.
25
Osmolality
26
Low and iso-osmolar compounds are tolerated
better by the body and give rise to fewer side
effects
Osmolality
27
Osmolality
28
Viscosity
• Viscosity is a measure of the flow properties of solutions.
• Iodine conc. determines the injection speed.
29
Characteristics of an ideal IV CM
• provides maximum opacity to X-rays;
• is biologically inert;
• has high water solubility;
• is chemically stable;
• is selectively excreted;
• has a low viscosity;
• exerts minimal osmotic effects;
• is safe; and
• is not expensive
30
Application of CM
•Contrast media may be introduced into the body via
The gastro-intestinal tract (oral or rectal).
Into the circulatory system (usually by the intravenous or intra-arterial
routes)
Into the cerebrospinal fluid (usually by the intrathecal route)
Directly into a duct or tract (e.g. lymph vessels, lacrimal duct, salivary duct,
etc).
31
Contd…
• Barium Sulphate is used in GI tract:
Ba Swallow, 200-250% w/v.
Ba meal, 250% w/v.
Ba follow-through, 60-100% w/v.
Small bowel enema, 60% w/v.
Barium enema, 115% w/v.
CT of GI tract, 1-2% w/v.
32
Contd…
• To achieve double contrast effect:
 for Oesophagus, Stomach & Duodenum-
CO2 & less often, air is used.
CO2 is administered orally in the form of
gas producing granules/ powder.
For large bowel, room air is administered
per rectum via hand pump attached to the
enema tube.
33
34
• Ionic CM
This type of CM can used in:
Fistulography
Sinography
HSG
MCU
RGU
CT GI tract (Oral CM)
35
• Non-ionic CM:
This type of CM we can used widely.
IVU, CT , Angiography
Myelography- specially used Iohexol.
Arthrography of joint with air.
Non-ionic dimer are suitable for
bronchography.
36
CM used in MRI
• 1981, first CM enhanced, ferric chloride in GI tract.
• 1984, gadolinium compound used as diagnostic IV MRI contrast agent.
• Now a days, frequently MRI examinations are performed with CM.
37
Types of MRI CM
• Ferromagnetic
• Paramagnetic
• Super-paramagnetic
38
Ferromagnetic
• Retain magnetism even when the applied field is removed.
• It may cause particle aggregation and cell function interference.
• So unsafe for MR contrast agents.
39
Paramagnetic
• 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.
• Eg: Gadolinium.
40
Gadolinium
• Gadolinium is a rare earth metal “heavy metal”
• Gadolinium is chelated to diethylene triamine penta-acetic acid
(DTPA)
• Generic name is demeglumine gadopentate.(Magnevist)
• By binding DTPA to the Gadolinium sites, only one “free” gadolinium
site is available to attach to water molecules
• Diffuse freely & excreated by kidneys
• Gadolinium chelates are small mole. Wt. substance.
41
Super-paramagnetic
• 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.
• Eg: Particals of iron oxide.
42
USG CM
• Gas micro-bubbles are used
• Should be less than 7 μm.
• The gas molecules are encapsulated in palmitic acid, galactose or
albumen.
• US contrast media depend on interaction bet encapsulated micro-
bubbles and US beam.
• Allow imaging of vascular structures which cannot be evaluated even
with sophisticated doppler techniques.
43
USG CM
•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.
44
USG CM
• Albunex-
Sonicated air micro-bubbles 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 micro-bubbles by hypobaric activation
prior to iv injection.
45
USG CM
• SonoVue
An aqueous suspension of stabilised sulphur
hexafluoride micro-bubbles.
After reconstitution of the lyophilisate with
saline, the suspension is stable and can be
used for upto 4 hrs.
46
Conclusion
• Use of contrast media helps for easy diagnosis of diseases by tissue
differentiation.
• Choice of CM depends on the type of procedure being performed.
• On going development of CM, more safe for patients.
47
References
• A guide to radiological procedures: Stephen Chaman & Richard
Nakielny, 5th edition.
• Contrast media chemistry, pharmacology and pharmaceutical
aspects, John Stephen Forte.
• Clark’s special procedures. Latest edition.
48
???
• What is contrast media?
• Classify contrast media?
• What is negative CM?
• What is positive CM?
• Applications of contrast media?
• Differentiate ionic & non-ionic CM?
• What are the uses of double contrast technique?
• Characteristic of an ideal IV CM.
• Types of MRI contrast media.
49
50

Radiology Contrast media and its Types

  • 1.
    Contrast Media andIts Types Upakar Paudel B.Sc.MIT 2nd Year Roll no-6 UCMS Bhairahawa, Nepal
  • 2.
    Introduction • Contrast agentsare the substances which possess an atomic no or have an e- density which differs significantly from that of surrounding structures & permits the visualization of the details of internal organs that would not otherwise be demonstrable. 2
  • 3.
    History • 1896, walterB. Cannon use radiopaque sustances. • 1904, colloidal silver was used in retrograde urography. • 1910, Krause use barium sulphate for visualisation of GIT. • 1923, Osborne reported the opacification of UT after the injection of 10% NaI soln. 3
  • 4.
    History • 1928, compoundwith no of pyridine rings containing iodine . • 1952, first tri-iodinated compound (sodium acetrizoate) was introduced. • Until the early 1970s all CM were ionic compounds with osmolalities of 1200-2000 mosmal/kg. 4
  • 5.
    History • Ionic monomer: 1954,diatrizoate (urografin) 1962, iothalamate (conray) 1962 – 1972, Metrizoate,Iodamide,Ioxithalamate, Ioglicate 5
  • 6.
    History • Non-ionic monomers 1969Metrizamide (Amipaque®) 1974 Iopamidol (Isovue®) 1976 Iohexol (Omnipaque®) 1979 Iopromide (Ultravist®) post 1980 Iopentol (Imagopaque®),Iomeprol,Ioxilan. 6
  • 7.
    History • Ionic dimers 1978Ioxaglate(Hexabrix®) 7 • Nonionic dimers Post 1980 Iodecol Iotrolan (Isovist®) Iodixanol (Visipaque®)
  • 8.
    Function of contrastmedia • CM alters the attenuation of x-ray beam by altering the density of related structures. • The atomic no of the related structures also alter & helps in visualisation of similar density structures within the region of interest. 8
  • 9.
    Classification of CM Onthe basis of physical properties: • Negative Contrast Media. • Positive Contrast Media 9
  • 10.
    Negative CM • Gaseoussubstances which has low atomic number and specific weight, absorb X-rays to a lesser extent than the surrounding body structures. CO2 N2O Air O2 10
  • 11.
    Positive CM • Substanceswhich, because of their higher specific weight and atomic number, absorb X-rays to a greater extent than the body tissues. Barium sulphate Iodinated contrast media Contrast media for MRI and Ultrasound. 11
  • 12.
    Barium sulphate • BaSuspension is made up of pure Ba Sulphate. • Particles of Ba must be small (0.1-3μm),which makes more stable in suspension. • Barium, having atomic no 56, is a good contrast agent for GI examinations because it is very dense and won’t be absorbed by the GI tract. • In most situation it is diluted with water to give a lower density. 12
  • 13.
    Ba sulphate • Solutionhas a pH of 5.3, which makes it stable in gastric acid. • Examinations of different parts of GI tract require Ba preparation with differing properties & different concentration. • A non ionic suspension medium is used, otherwise its particles would aggregate into clumps. 13
  • 14.
    Advantage of Ba •Excellent coating which can be achieved. • Allowing the demonstration of normal and abnormal mucosal patterns. • Economic because of lower cost. 14
  • 15.
    Iodinated CM • Mostof IV CM contain Iodine which has 53 atomic no. & 127 atomic weight. • Total iodine content in the body is 50 mg. • It is Preferred because  High contrast density due to high atomic no. Low toxicity. •Conc ranges from 140-370mgI/ml. 15
  • 16.
    Iodinated CM • Theyare water soluble . • It is classified as: Ionic Non-ionic Ionic monomers CM High-osmolar Ionic dimer CM Low-osmolar Monoionic/diionic non-ionic monomer CM Low-osmolar Non-ionic dimer CM. Iso-osmolar 16
  • 17.
    Ionic CM • Insolution, ionic contrast media ionize into two particles, i.e. the cation and the anion. • The anion in an ionic contrast medium is the triiodinated benzoic acid part while the cation is usually sodium, calcium or meglumine. 17
  • 18.
    Ionic monomers • Iodineto particle ratio is 3:2 • Sodium or meglumine act as cations. 18
  • 19.
    Ionic monomers • Examples: IothalamicAcid Has better neural tolerence but decrease cardiovascular tolerence. Eg. Conray Diatrizoic Acid Increase solubiliy Decrease plasma protein binding & increase glomerulus filtration. Improves patient tolerence. Eg. Urografin 19
  • 20.
    Ionic dimer • Monoionicdimers ionize to give two particles but the number of iodine atoms present is 6. Therefore the iodine atom to particle ratio is 6:2, i.e.3 .Eg: Hexabrix. • Diionic dimers ionise to give three particles (two cations and one anion) with six iodineatoms present so that the iodine atom to particle ratio is 6:3, i.e. 2. 20
  • 21.
    Non-ionic monomer • Themolecule does not ionize & do not give two particles. • Formed by replacing the cation radical portion of benzene ring with a non-dissociating organic chain. • It remains as one single molecule when in solution because of an amide group on the acid part. 21
  • 22.
    Non-ionic monomer • Lesstoxic effect becoz of removal of acid group & replacement of large no of OH group which make them more hydrophilic. 22
  • 23.
    Non-ionic monomer • Thesemolecules do not ionize in solution so that the iodine to particle ratio is 3:1. Therefore these are also ratio-3 molecules. • Eg: Iohexol (Omnipaque), Ioversol (Optiray) Iopromide (Ultravist). 23
  • 24.
    Non-ionic dimer • Thesemolecules will give six iodine atoms for every molecule so that their iodine atom to particle ratio is 6:1 which makes them ratio-6 molecules. • Disadvantage is high viscosity becoz of relatively large size of molecule. • Eg: Iodecol, Iotrolan (Isovist), Iodixanol (Visipaque®) 24
  • 25.
    Osmolality • Osmolality ismeasure of no. of particles of solute in solution per kg of water. • Osmolality can be described as the property of a liquid to give up its water to or to take up water from another liquid separated by a semi- permeable membrane. • Hypo-osmolar liquid gives up water to the second liquid. • Hyper-osmolar liquid takes up water from the second liquid. • Iso-osmolar liquids have the same osmolality and do not exchange water. 25
  • 26.
    Osmolality 26 Low and iso-osmolarcompounds are tolerated better by the body and give rise to fewer side effects
  • 27.
  • 28.
  • 29.
    Viscosity • Viscosity isa measure of the flow properties of solutions. • Iodine conc. determines the injection speed. 29
  • 30.
    Characteristics of anideal IV CM • provides maximum opacity to X-rays; • is biologically inert; • has high water solubility; • is chemically stable; • is selectively excreted; • has a low viscosity; • exerts minimal osmotic effects; • is safe; and • is not expensive 30
  • 31.
    Application of CM •Contrastmedia may be introduced into the body via The gastro-intestinal tract (oral or rectal). Into the circulatory system (usually by the intravenous or intra-arterial routes) Into the cerebrospinal fluid (usually by the intrathecal route) Directly into a duct or tract (e.g. lymph vessels, lacrimal duct, salivary duct, etc). 31
  • 32.
    Contd… • Barium Sulphateis used in GI tract: Ba Swallow, 200-250% w/v. Ba meal, 250% w/v. Ba follow-through, 60-100% w/v. Small bowel enema, 60% w/v. Barium enema, 115% w/v. CT of GI tract, 1-2% w/v. 32
  • 33.
    Contd… • To achievedouble contrast effect:  for Oesophagus, Stomach & Duodenum- CO2 & less often, air is used. CO2 is administered orally in the form of gas producing granules/ powder. For large bowel, room air is administered per rectum via hand pump attached to the enema tube. 33
  • 34.
  • 35.
    • Ionic CM Thistype of CM can used in: Fistulography Sinography HSG MCU RGU CT GI tract (Oral CM) 35
  • 36.
    • Non-ionic CM: Thistype of CM we can used widely. IVU, CT , Angiography Myelography- specially used Iohexol. Arthrography of joint with air. Non-ionic dimer are suitable for bronchography. 36
  • 37.
    CM used inMRI • 1981, first CM enhanced, ferric chloride in GI tract. • 1984, gadolinium compound used as diagnostic IV MRI contrast agent. • Now a days, frequently MRI examinations are performed with CM. 37
  • 38.
    Types of MRICM • Ferromagnetic • Paramagnetic • Super-paramagnetic 38
  • 39.
    Ferromagnetic • Retain magnetismeven when the applied field is removed. • It may cause particle aggregation and cell function interference. • So unsafe for MR contrast agents. 39
  • 40.
    Paramagnetic • Have magneticmoments 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. • Eg: Gadolinium. 40
  • 41.
    Gadolinium • Gadolinium isa rare earth metal “heavy metal” • Gadolinium is chelated to diethylene triamine penta-acetic acid (DTPA) • Generic name is demeglumine gadopentate.(Magnevist) • By binding DTPA to the Gadolinium sites, only one “free” gadolinium site is available to attach to water molecules • Diffuse freely & excreated by kidneys • Gadolinium chelates are small mole. Wt. substance. 41
  • 42.
    Super-paramagnetic • Are aggregationof 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. • Eg: Particals of iron oxide. 42
  • 43.
    USG CM • Gasmicro-bubbles are used • Should be less than 7 μm. • The gas molecules are encapsulated in palmitic acid, galactose or albumen. • US contrast media depend on interaction bet encapsulated micro- bubbles and US beam. • Allow imaging of vascular structures which cannot be evaluated even with sophisticated doppler techniques. 43
  • 44.
    USG CM •Levovist Most widelyused. 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. 44
  • 45.
    USG CM • Albunex- Sonicatedair micro-bubbles 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 micro-bubbles by hypobaric activation prior to iv injection. 45
  • 46.
    USG CM • SonoVue Anaqueous suspension of stabilised sulphur hexafluoride micro-bubbles. After reconstitution of the lyophilisate with saline, the suspension is stable and can be used for upto 4 hrs. 46
  • 47.
    Conclusion • Use ofcontrast media helps for easy diagnosis of diseases by tissue differentiation. • Choice of CM depends on the type of procedure being performed. • On going development of CM, more safe for patients. 47
  • 48.
    References • A guideto radiological procedures: Stephen Chaman & Richard Nakielny, 5th edition. • Contrast media chemistry, pharmacology and pharmaceutical aspects, John Stephen Forte. • Clark’s special procedures. Latest edition. 48
  • 49.
    ??? • What iscontrast media? • Classify contrast media? • What is negative CM? • What is positive CM? • Applications of contrast media? • Differentiate ionic & non-ionic CM? • What are the uses of double contrast technique? • Characteristic of an ideal IV CM. • Types of MRI contrast media. 49
  • 50.