This document discusses various contrast agents used in medical imaging. It begins by defining contrast agents and describing their classification. It then focuses on water soluble iodinated contrast agents, describing their physiology and classifications including conventional high osmolar agents, low osmolar agents, and iso-osmolar agents. The document also discusses ultrasound contrast agents, their generations and mechanisms of action. It concludes by covering MR contrast agents such as gadolinium chelates and their uses and properties.

1. CONTRAST AGENTS

2. OVERVIEW
• Introduction & Definition
• Classification
• Water soluble iodinated contrast media
• Physiology of contrast media
• Ultrasound contrast media
• MR contrast agents
• Adverse reactions to contrast media
• Contrast induced nephrotoxicity

3. DEFINITION
• Contrast medium-a substance used in radiography which
permits visualization of internal body structures, also called
contrast agent, contrast material.
• Positive contrast-the use of a contrast material that is
radiopaque such as insoluble barium sulfate salt and a variety
of organic iodine compounds. Barium is used for
gastrointestinal studies. Water-soluble, iodinated contrast
media are used for many procedures, including all types of
angiography, intravenous and retrograde urography,
hysterosalphingography, sialography , myelography
,cholangiography etc
• Negative contrast- material that is not radiopaque such as
air or carbon dioxide

5. Barium sulphate
• Has high atomic number 56, highly radiopaque.
• Non absorbable, non toxic.
• Insoluble in water/lipid.
• Inert to tissues.
• Can be used for double contrast studies.
• Uses: barium swallow, barium meal, barium meal
follow through, enteroclysis, barium enema

10. Water soluble iodinated contrast
media
IODINE :
• Atomic number 53 & atomic weight 127
• Radio-opacity is dependent on iodine conc of the solution, so
dependent on number of iodine atoms in each molecule of the
contrast medium.
• 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
• High radio-opacity & low osmolality are required.
• Iodine is preferred because
*High contrast density due to high atomic number
*Allows firm binding to highly variable benzene ring
*Low toxicity

11. Conventional contrast media / High
osmolar contrast media / Ionic
monomers
• These are salts of sodium or meglumine
cation & triiodinated benzoate anion(C2, C4 &
C6). C3 & C5 are connected to amines which
reduce the toxicity & increase the solubility.
*Diatrizoate (urograffin , angiograffin ,
urovedeo, trazograff)
*Iothalamate(conray , triovideo)
*Ioxithalamate
*Metrizoate

12. Conventional contrast media / High
osmolar / Ionic monomers
• Iodine particle ratio is 3:2
• Molecular weight 600-800
• Iodine content at 0.3 osmol/kg H2O- 70mg I/ml
• Osmolality at 280mg I2/ml -1500 osmol/kg H2O
• LD-50 = 7(g of I/kg wt of mouse)
• Disadvantage : high osmolality (8 times that of
plasma), responsible for the adverse effects,
because of the non radiopaque cations( Na &
meg)

14. Low osmolar contrast media
• IONIC DIMERS- Ioxaglate(Hexabrix) Only
compound, mixture of sodium and meglumine
salts
• Two benzene rings (each with 3 iodine atoms)
are linked by a bridge to form a large
compound, carries only one carboxyl group, so
known as monoacid dimers

15. IONIC DIMERS- Ioxaglate(Hexabrix)
• Iodine particle ratio is 6:2 or 3:1
• Molecular weight is 1269
• Iodine content at 0.3 osmol/kg H2O- 150mg
I/ml
• Osmolality at 280mg I2/ml 560 osmol/kg H2O
• LD-50 = 12(g of I/kg wt of mouse)

16. NON IONIC MONOMERS
• First gen- Metrizamide
• Sec gen
*Iopromide (Ultravist)
*Iohexol (Omnipaque)
*Iopamidol (Iopamiro)
*Ioversol (Optiray)
*Ioxilan
*Iomeron
*Xenetix
• Carboxyl group (-COOH) is replaced by non ionising
radical & CONH2

17. NON IONIC MONOMERS
• Iodine particle ratio is 3:1
• Molecular weight 600-800
• Iodine content at 0.3 osmol/kg H2O- 150mg
I/ml
• Osmolality at 280mg I2/ml -600 osmol/kg H2O
• LD-50 = 22(g of I/kg wt of mouse)

18. NONIONIC DIMERS
*Iotrolan(Isovist)
*Iodixanol (Visipaque)
• Each molecule contains 2 non ionosing tri-
iodinated benzene rings linked together

19. NONIONIC DIMERS
• Iodine particle ratio is 6:1
• Molecular weight 1550-1626
• Iodine content at 0.3 osmol/kg H2O- 300mg
I/ml
• Osmolality at 280mgI2/ml -300 osmol/kg H2O
• LD-50 = >>26(g of I/kg wt of mouse)

20. 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.)

21. Ideal contrast media should have:
• High water solubility
• Heat & chemical stability(shelf life) ideally- 3 to
5yrs
• Biological inertness( non antigenic)
• Low viscosity
• Low or iso osmolar to plasma
• Selective excretion, like excretion by kidney is
favorable.
• Safety: LD50 (lethal dose) should be high
• Reasonable cost

22. Physiology
• On intravascular injection , the contrast media
is distributed rapidly by capillary permeability
into extravascular, extra cellular space (except in
CNS).
• They do not enter the interior of blood cells or
tissue cells and they are rapidly excreted, over
90% being eliminated by glomerular filteration
by kidneys within 12 hrs

23. Imp points to remember
• Contrast media used for myelography are non-ionic CM.
• CM used for cerebral angiography, are CM containing only meglumine
cation.
• CM containing only meglumine cation- conray 280, triovideo 280, trazograff
60% and angiograffin.
• CM which cause max nausea & vomiting are – Ioxaglate (Hexabrix). •
Meglumine salts cause bronchospasm, so CI in bronchial asthma.
• Among newer CM, Iohexol is most hyperosmolar
• Viscosity increases as conc increases & tends to be higher for big sized
molecules (dimers). High viscosity interferes with mixing of contrast media
with plasma & body fluids. Omnipaque240 has least viscosity.
• Meticulous heparinization is required during angiography as incidence of
thrombo embolic phenomenon is high when CM is mixed with blood

24. INDICATIONS
• 1.urinary tract imaging: IVU, Cystography,RGU,MCU
• 2.vascular:angiography,venography,lymphangiography
• 3.dacryocystography
• 4.arthrography
• 5.sialography
• 6.fistulography/sinusography
• 7.ERCP/T tube cholangiogram
• 8.myelography
• 9.CT

27. CONTRAINDICATIONS/RELATIVE
CONTRAINDICATIONS
• 1.A previous s/v rxn: carries 30 % r/o similar
rxn on a subsequent study
• 2. CV ds: give non sodium containing LOCM
• 3. h/o atopy/allergy
• 4.hepatic failure
• 5.renal failure
• 6.DM

28. CONTRAINDICATIONS/RELATIVE
CONTRAINDICATIONS
• 7.myeloma
• 8.SCD
• 9.infants & elderly
• 8.pregnancy
• 9.poorly hydrated pts
• 10.thyrotoxicosis: iodine load alters the results
of TFTs; therefore C/I only prior to TFTs.

29. Ultrasound contrast agents
• Also called ECHO ENHANCING AGENTS.
• These agents increase the echogenicity of blood, which heightens
the tissue contrast & allows better delineation of body cavities.
• Consist of microscopic gas filled bubbles whose surface reflect sound
waves.
• Their extremely high reflectivity(backscatter) arises from the fact
that microbubbles easily change their size, contracting in compression
part of the ultrasonic cycle & expanding in the rarefaction part.
• Thus they resonate in the ultrasound beam when there is a
mismatch b/w their diameter and ultrasonic wavelength, which occurs
for microbubbles in 2 to 7um at usg freq of 2-10 MHz

30. Generations of Echo Enhancers
• First gen- unstabilised bubbles in indocyanine
green , cant survive pulmonary passage,
therefore used only for cardiac & large vein
study.
• Second gen- longer lasting bubbles coated
with shells of protein, lipids or synthetic
polymers.
• Third gen- encapsulated emulsions or bubbles,
offer high reflectivity.

32. Ideal ultrasound contrast agent
• Be injectable by a peripheral vein
• Be non toxic
• Small enough to pass through pulmonary, cardiac
& capillary systems
• Stable enough to undergo the shear forces,
hydrostatic pressure changes & diameter changes
• Half life should be sufficient to allow complete
examination
• Should require little preparation

33. Mechanism of action
• Pri mechanism of signal enhancement is microbubble
backscatter, which relates to differences in microbubble
versus blood compressibility.
• Increased echogenicity may be seen as an increased signal in
color or spectral doppler signal strength or gray scale image
intensity.
• The half life or persistence of microbubble depends on –
*size(<7um passes through pul cirltn)
*surface tension & gas diffusion across the bubble shell.
*transducer frequency & power
• Mechanical index (MI) –peak pressure of usg beam
calculated from frequency & power of usg beam. Higher the
MI, more likely the bubble will break

34. Doppler rescue:
• Application of UCA results in enhancement of
colour, power & spectral doppler waveform &
this improves doppler imaging & is termed as
“doppler rescue “

35. Applications
• Evaluating normal, increased or decreased
vascularity.
• Detecting vascular stenosis & occlusions
• Improving neoplasm detection
• Analysing & characterizing tumour neovascularity
• Differentiating normal variants such as renal
column of bertin from neoplasm.
• Echocardiography – cardiac cavities, valves,
coronary artery & myocardial viability

39. Artifacts
• Colour blooming – grey scale pixels are
displayed as colour pixel in areas that lack flow,
occurs when high conc of UCA is delivered by
bolus inj.
• Bubble noise – audible sound accompanied on
visible spectral doppler tracing blips
• An increase (17 to 45 %) in maximum doppler
shift frequency

40. Contrast media used in MRI
• Gadolinium chelates
• Blood pool agents
• Liver contrast agents
• Endoluminal contrast agents
• Targeted contrast agents

41. Gadolinium
• Is the standard exogenous contrast agent used in
clinical MR imaging.
• It is T1 relaxing agent and is paramagnetic.
• It belongs to lanthanide metal group with atomic no.
64.
• It has a high spin contrast number which produces
desirable relaxivity contrast agents
• Three agents have been approved by FDA, they are-
*Gd-HP-DO3A:Gadoteridol/ProHance (non ionic)
*Gd-DTPA :Gadopentetate diglumine/Magnevist(ionic)
*Gd-DTPA-BMA: Gadodiamide/Omniscan (nonionic)

42. Gadolinium
• These function as extracellular contrast agents.
• They are rapidly excreted by glomerular filteration with half
lives b/w 1 – 2hrs.
• As these compounds are excreted by renal excretion,
caution shd be taken in renal impaired patients.
• 3 –5% of adverse reactions, occur in the form of nausea •
Dose- 0.1 to 0.3mmol/kg body weight
• Disadvantages:
*enhancement is non specific neither organ specific nor
pathology specific.
*short window for imaging of blood vessels as it is diluted in
blood stream and excreted rapidly.

43. Blood pool agents
• These agents reversibly bind to plasma albumin
achieving a substantial improvement in magnitude
and duration of blood pool enhancement.
• Eg- SPIO-super paramagnetic iron oxide crystals -
USPIO -Magnetite
• These cause predominant T2 shortening.
• Uses – to image small vessels, vessels with slow
flow (eg pul emb, DVT), arteriovenous
malformation - perfusion studies
• Disadv: overlap b/w arterial and venous
structures and separation is difficult

44. Liver contrast agents
• Gadobenate dimeglumine
(MultiHance,Bracco)
• Small iron particles- Endorem & Resovist
• Manganese containing contrast agents-
Teslascan – absorbed by liver, pancreas and
cortex of kidneys, T1 relaxation

45. Endoluminal contrast agents
• Negative contrast agents, based on iron
particles(Abdoscan, Nycomed-Amersham) for use in
MR enteroclysis & MR imaging of rectal cancer.
• Combination of methyl cellulose solution for
bowel distention & iv gadopentate dimeglumine for
bowel wall enhancement.
• Natural contrast- blueberry juice acts as a
negative contrast in upper abdominal MR imaging,
eg MRCP

46. Targeted contrast agents
• Blood pool agents
• Liver specific agents
• Necrosis specific agents (bis-gadolinium-
mesoporphyrin)
• Lymphographic contrast agents
• Agents targeted at inflammation detection.

47. References
• Grainger & Allison –Diagnostic radiology-5th
edition.
• Radiological procedures- Dr.Bhushan N
Lakhkar.