Radiographic contrast media were developed starting in the late 19th century to increase differences in tissue attenuation and improve organ visualization on radiographs. The first effective contrast agents used barium and iodine compounds. Modern contrast media are tri-iodinated benzene derivatives that are either ionic or non-ionic, and monomeric or dimeric in structure. They carry risks of both idiosyncratic and non-idiosyncratic adverse reactions that depend on their osmolality, viscosity, and other properties. Appropriate use and precautions seek to minimize risks while maximizing diagnostic value.

1. Radiographic
Contrast Media
DR. DEEPESH KALRA
INSTITUTE OF UROLOGY
MMC, CHENNAI

2.  1896 -WALTER BRADFORD discovered contrast media.
 1897 - First reported GI contrast study performed using Bismuth - TOXIC!
 1910 - Barium Sulphate used (safer)
 1920’s - Sodium Iodide used to treat syphilis.
 Iodine was found to be radio opaque to x-rays.
 Basis of all modern contrast agents.
 1927 - First reported IVU with iodised organic salts (Uroselectan)

3.  CONTRAST:
It is the difference in
optical density
between different
parts of image

5.  The degree of attenuation of radiation depends on number of
electrons in the path of the beam .
 Beam attenuation = U*d
1. Thickness of the substance being studied (d)
 U= linear coefficient of radiation, governed by
 2. Physical Density (atomic weight )
 3. The number of electrons per atom of the element ( atomic
number)
 Proportional to at. Wt.
 Proportional to 3’rd power of at. No.

6.  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
 Radiographic contrast media (RCM) were developed to
increase differences in the attenuation (absorption) of radiation
by soft tissues.
 Two of the factors important in organ contrast can be artificially
altered
 Density of an organ
 More usefully, the average atomic number of a structure

8. NEGATIVE CONTRAST
 The density of a hollow organ can be
reduced providing negative contrast
 Contrast material that is not radiopaque
 Low atomic number material
 Radiation penetrates easily

9.  Organ becomes radiolucent
 Black on film
 Air
 O2
 CO2
 N2O

10. Positive contrast
 The average atomic number is
INCREASED
 Contrast material is radiopaque.
 High atomic number material
 White on film

12. Positive
contrast
Iodine based
Non-iodine
based

13. BARIUM SULPHATE
 Atomic number: 56 Highly radiopaque.
 Non toxic. Inert to tissues.
 Insoluble in water/lipid.
 Better coating properties over the lining of the gut

14.  Extremly low solubillity – very less absorbtion – readily
removed
 Examinations of the upper and lower gastrointestinal tracts.
 Route: Orally Or Rectally (aqueous suspension with 0.3 to 1 g
dry weight per milliliter

17. IODINE BASED
 Early 1920s to treat syphilis with high doses of sodium iodide. The
urine in the bladder was observed to become radio-opaque during
this treatment. Sodium iodide was too toxic.
 The first suitable structure was Pyridine, to which a single iodine
atom could be bound in order to render it radio-opaque.
 The first radiological contrast medium for intravenous urograms
was Uroselectan

18.  In the 1950s, contrast media were developed that were based
on the six-carbon benzoic acid ring rather than the five-
carbon pyridine ring. This structure was able to carry three
atoms of iodine, and therefore was even more radio-opaque.
 Had a very high osmolality

19. Mechanism of action
 Why only iodine :
 High atomic no. 53
 Atomic weight 127
 increases the attenuation by increasing the linear coefficient
of radiation .
 Very tight binding to benzene ring
 Special property of attenuation of routinely used X ray beams
called as “K-edge effect”

20.  Tri-iodinated benzene ring is the basic constituent of all contrast media.
 Benzene ring has 6 carbons numbered 1 to 6 clockwise
 Carbon 1 attachment differentiates ionic from non-ionics
 Iodine attached at position 2,4,6 carbons

21.  C3 & C5 have amide attachments to
increase solubility and also to reduce
protein binding.
 At C1 in ionics acidic group with sodium
or meglumine is attached
 At C1 in non ionics amide group is
attached.
contrast
Ionic Non ionic

22. Parameter Na Salts Meglumine Salts
Solubility Less Better
Viscosity Less Better
Tolerance more Less
Blood Brain Barrier Crosses Doesn’t cross
Vascular effect Marked Less
Diuretic effect Less More
Opacification Better Less
Bronchospasm No Yes

23.  Radioopacity depends on:
 iodine concentration 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
per molecule to the number of osmotically active particles
molecule of solute in solution

24.  Iodine to particle ratio for various
media:
 Dimers - Two benzene rings
(each with 3 iodine atoms)
Contrast
Ionic
Monomer
3:2
Dimer.. 3:1
Non-ionic
Monomer
3:1
Dimer... 6:1

25. Properties
Ø Osmolality :
 Depends on no. of particles so always higher for ionic media and
monomers.
 In general, the higher the osmotic pressure the poorer the tolerance.

26.  Osmolality is directly responsible for :
The sensations of heat
Discomfort or even pain
Damage to the blood-brain barrier,
Renal damage
Electrolyte balance in small children.
 Contrast media classified as HOCM and LOCM .
 Ionic monomers called as HOCM and
rest called as LOCM. (Non ionic dimer : IOCM)

27.  Solubility
• Factors increasing solubility:
 Hydroxyl group
 Amide group
 Salt ( Na / Meg )
 Viscosity
• Depends on :
 Particle size (most imp.)
 Temp (inversely related)
 Solvent

28.  Viscosity and Osmolality
are INVERSELY related to
tolerance but directly to
degree of opacification.
Increasing strength
of contrast medium
Opacifying
power increases
Osmolality and
Viscosity increases
Tolerance declines

29.  CHEMOTOXICITY/LD50
 Mechanism responsible for causing the toxic effects of
contrast media that cannot be explained by other means
osmolality, electrical charge).
 There are a number of properties of contrast media that
relate to this term (e.g. hydrophilicity/lipophilicity, protein-
binding, histamine release).

30. Oil based Water based
Not injected (only
ducts )
Injected
(vessels/ducts)
Not ingested ingested

31. 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

32.  USE:
1) Sialography
2) Hysterosalpingography
3) Myelography
4) Lymphangiography
5) Dacryocystography
6) Galactography
7) Bronchography

33. Water based
Hepatic excretion
IOPANOIC ACID
Renal excretion
High Osmolar/ 1st
Gen
Ionic Monomer
IOTHALAMATE DIATRIAZOATE
Low Osmolar/ 2nd
Gen
Ionic Dimer
HEXABRIX ,
IOCAMIC ACID,
IOXAGLIC ACID
Non-ionic
Monomer
IOHEXOL,
IOVERSOL,
IOPAMDOL
Iso-osmolar/
Latest
Non-ionic Dimer
IODIXANOL,
IOTROL

34. Ionic Monomer
HOCM
Ionic Dimer
LOCM
Non-Ionic
Monomer
LOCM
Non-Ionic Dimer
IOCM
Iodine particle ratio 3:2 6:2, 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
5 times
560
2 times
600
2 times
300
Similar
LD50
(g of I/kg wt of mouse)
7 12 22 >>26

35. ADDITIVES USED IN CONTRAST MEDIA
 Stabilizer:
Ca or Na EDTA
 Buffers:
Stabilizes pH during storage, Na acid
phosphates
 Preservatives:

36. 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.

37. Commonly used preparations
 Ionic contrast media :
 Monomers :
 Diatrizoate based
Urograffin
Gastrograffin
Angiograffin
Trazograph
 Iothalamate based :
Conray

38.  Non ionic monomers : Most commonly used media
Omnipaque : Iohexol
Optiray : Ioversol
Ultravist : Iopromide
Lek-Pamidol : Iopamidol
Iopamiro : Iopamidol
 Non ionic dimers :
Isovist : Iotrolan
Visipaque : Iodixanol

39. Physiology
 Concentration and excretion
1) >90%: passive glomerular filtration.
2) 1%: liver and intestine.
 Half life: 30-60 minutes.
 Do not enter the interior of cells.
 Rapidly excreted, over 90% being eliminated by glomerular filteration by
kidneys within 12 hrs.
 Leaves the body within 24 hours(if normal kidney) and weeks( if diseased kidney).

40. Routes
1) Orally.
2) Rectally.
3) Intravenously – (injection/ infusion).
4) Mechanically – Filling of a bod cavity or potential space.
5) Intra-muscularly

41. DOSE
 Standard : 1-2 ml/kg at concentration of 300 mg/ml
 Max. Limit is : 200 ml of contrast with conc. 320 mg/dl (max 64
gm I)
 Maximum allowable contrast dose (MACD):
5mL × body weight (kg)/serum creatinine (mg/dL)

42. Adverse Effects
 ADRs associated with intravenous (IV) contrast media can be
divided into two broad categories:
ü Idiosyncratic anaphylactoid (IA) and
ü Nonidiosyncratic (NI) reactions.
 Approximately 85% of IA reactions occur during or immediately
after injection of IRCM

43.  More common in patients who have :
Prior ADR to contrast media
Impaired renal function
Diminished cardiac function
Are on β-adrenergic blockers
Asthma
Diabetes

44. idiosyncratic anaphylactoid (IA)
 Mechanism : not Ig mediated
(1) Release of vasoactive substances including histamine
(2) Activation of physiologic cascades including complement, kinin,
coagulation, and fibrinolytic systems
(3) Inhibition of enzymes including cholinesterase, which may cause
prolonged vagal stimulation
(4) The patient's own anxiety and fear of the actual procedure.
 Not dose dependent

45. Non-idiosyncratic
 Dose dependent
 and consequently related to the
Osmolality
Concentration
Volume
Injection rate

46. Mild Non-idiosyncratic Reactions
 Nausea Vomiting
 Flushing Warmth (heat)
 Cough Chills,
 Sweats ,Rash Dizziness
 Headache Nasal stuffiness
 Altered taste Swelling: eyes, face
 Itching Anxiety
 Observation and reassurance

47. Moderate Nonidiosyncratic Reactions
 0.5% to 2% of patients and require treatment but are not immediately life
threatening.
 Tachycardia/bradycardia Dyspnea
 Hypertension Pronounced skin reaction
 Pulmonary edema Bronchospasm, wheezing
 Hypotension Laryngeal edema
 Hydrocortisone 100 to 500 mg IM or IV, or β-agonist inhalation for
bronchospasm in addition to bronchiolar dilators

48. Severe Nonidiosyncratic Reactions
 1 in 1000 uses for HOCM and are far less frequent for LOCM
 Both types of agents resulting in mortality rates of 1 in 170,000 uses (Spring
et al, 1997).
 Laryngeal edema (severe) Hypotension
 Convulsions Clinically manifest Unresponsiveness
 Arrhythmias Cardiopulmonary arrest

49.  Epinephrine - 0.01 mg/kg of 1 : 10,000 dilution or 0.1 mL/kg
slowly into a running IV infusion of saline and can be repeated
every 5 to 15 minutes as needed.
 If no IV access is available, the recommended IM dose of
epinephrine is 0.01 mg/kg of 1 :1000 dilution
 Hypotension resulting from an anaphylactic reaction can be
treated with IV iso-osmolar fluids
 The most effective vasopressor is dopamine. Dopamine should
be used at infusion rates between 2 and 10 μg/kg/min.

50. Premedication Strategies
 No known premedication strategy that will eliminate the risk of a severe
adverse reaction to IRCM.
 Patients at high risk should be premedicated with corticosteroids and
possibly antihistamines 12 to 24 hours before and after use of IRCM.
 Prednisone—50 mg PO at 13 hr, 7 hr, and 1 hr before contrast media
injection
 Plus diphenhydramine —50 mg IV, IM, or PO 1 hr before contrast
medium injection

51.  LOCM should be used.
 Nonionic contrast media should be used.
 If the patient is unable to take oral medication, 200 mg of
hydrocortisone IV may be substituted for oral prednisone.
 One consistent finding is that steroids should be given at least 6
hours before the injection of contrast media regardless of the
route

52. Delayed Contrast Reactions
 3 hours to 7 days
 14% to 30% - Ionic monomers
 8% to 10% - Nonionic monomers.
 Cutaneous reactions are the most frequent - incidence of 0.5% to 9%
 cutaneous exanthem or pruritus without urticaria
 Nausea, vomiting, drowsiness, headache and flulike symptoms
 Almost always resolve spontaneously

53. Extravasation of Contrast Material
 Large-volume extravasation can be seen if not monitored with electrical skin
impedance devices that detect extravasation and arrest the injection process.
 Swelling, edema, erythema, pain
 Inflammatory reaction usually reaches a maximum in 24 to 48 hours.
 Hyperosmolality of the contrast agent.
 Mechanical compression caused by a compartment syndrome

54. Special Considerations

55. Contrast-Induced Nephropathy
 While there are no standard criteria for contrast-induced nephropathy (CIN)
 Diagnosis can be made if one of the following occurs within 48 hours after
administration of iodinated contrast
 Increase in serum creatinine of greater than 0.3 mg/dL
 More than a 50% increase in serum creatinine from baseline
 Urine output reduced to less than 0.5 mL/kg/hr for at least 6 hours
 In the absence of other causes of AKI

56.  The precise cause of CIN is still unknown but is believed to be a combination
of :
 Tubular toxicity
 Tubular obstruction
 Renal ischemia by vasoconstriction
 The incidence - 2% to 5%, and up to 25% of those with CIN will have
persistent renal dysfunction.
 CIN in patients with normal kidney function is rare.
 CIN is the third most common cause of acute kidney failure in hospitalized
patients

58.  Patient related Risk factors for CIN :
 CKD(creatinine clearance <60 mL/min)
 DM
 Dehydration
 Diuretic use
 Advanced age
 CHF
 Hypertension
 Low hematocrit
 Ventricular EF <40%
 Concomitant Chemotherapy
 AG/ NSAIDS
 Hyperuricemia
 End-stage liver disease
 Nephrotic syndrome
 Multiple myeloma
 History of a kidney transplant,
renal tumor, renal surgery, or
single kidney

59.  Non patient-related risk factor -
 HOCM
 Ionic contrast
 Increased contrast viscosity
 Multiple contrast-enhanced studies performed within a short
period
 Large contrast volume infused

61. Prevention of CIN
 Hydration -
Periprocedural IV hydration with 0.9% saline @100 mL/hr (1 ml/kg/hr)12 hours
before to 12 hours after has been shown to decrease the incidence of CIN
(in CHF 0.5 ml/kg/hr , max 50 ml/hr)
 Goals -
 Maintainance of sufficient intravascular volume – renal perfusion
 Preproceudre diuresis
 Avoidance of hypotension

62.  The use of sodium bicarbonate has not been definitively shown to prevent
CIN.
 The use of N-acetylcysteine for the prevention of CIN is controversial
 Furosemide was found to increase the risk of developing CIN
 Use of lowest possible dose
 Use of LOCM/ IOCM

64.  The literature does not support an absolute serum creatinine level that
prohibits the use of contrast media.

65. Renal disease + DM
FOR DIABETIC Creatinine eGFR
Iohexol <1.4 >45
Iodixanol 1.4-2 30-45
NO IV contrast >2 <30
NON-DIABETIC Creatinine eGFR
Iohexol <1.8 >30
Iodixanol 1.8-3 15-30
NO IV contrast >3 <15

66. Metformin
 Metformin is eliminated through the kidneys, most likely by
glomerular filtration and tubular excretion.
 It stimulates intestinal production of lactic acid.
 Some conditions can reduce metformin excretion or increase serum
lactate, such as
Renal disease (decreases metformin excretion)
Liver disease (decreases lactic acid metabolism)
Cardiac disease (increases anaerobic metabolism).

67.  Patients receiving metformin may have an accumulation of the drug after
administering IRCM, resulting in
 Biguanide lactic acidosis with symptoms of vomiting, diarrhea, and
somnolence.
 This condition is fatal in approximately 50% of cases
 Rare in patients with normal renal function.
 Consequently in patients with normal renal function and no known
comorbidities there is no need to discontinue metformin before IRCM use
 Nor is there a need to check creatinine following the imaging study.

68.  However, in patients with renal insufficiency metformin should
be discontinued the day of the study and withheld for 48
hours. Postprocedure creatinine should be measured at 48
hours and metformin started once kidney function is normal

69. Dialysis
 Insult to the renal parenchyma occurs during the first pass of contrast.
 Therefore, timing of hemodialysis, with respect to contrast administration,
is irrelevant.
 Adequate hydration
 It is not imperative that dialysis be performed immediately following the
contrast procedure

70. PREGNANCY & LACTATION
 In exceptional circumstances, when radiographic examination is
essential, iodine- based contrast media may be given to the
pregnant female.
 Following administration of iodine-based agents to the mother
during pregnancy, thyroid function should be checked in the
neonate during the first week.
 Breast feeding may be continued normally when iodine-based
agents are given to the mother

71.  Patients undergoing therapy with radioactive iodine should
not have received iodine-based contrast media for at least two
months before treatment.
 Isotope imaging of the thyroid should be avoided for two
months after iodine-based contrast medium injection.

72. ULTRASOUND CONTRAST AGENTS
 A.k.a Echo Enhancing Agents.
 Consist of Microscopic Gas Filled Bubbles.
 Their Extremely High Reflectivity (backscatter)
easily change their size
contracting in compression part of the ultrasonic cycle & expanding in
the rarefaction part.

73. First Gen. Second Gen. Third Gen.
Unstabilised bubbles
in indocyanine green.
Can`t survive
pulmonary passage,
therefore used only
for cardiac & large
vein study.
Longer lasting
coated with shells of
protein, lipids or
synthetic polymers
Encapsulated
emulsions or bubbles,
offer high reflectivity.

74. Non Capsulated
Microbubbles
Unstable Large
Adequate for right
heart visualization
Encapsulated
Microbubbles
Air MB
Albunex Echovist Levovist Cavisomes
Perfluorocarbon MB
Optison

75. Ideal
1) Injectable by a peripheral vein
2) Non toxic
3) Small enough to pass through pulmonary, cardiac & capillary
systems
4) Stable enough to undergo the shear forces, hydrostatic
pressure changes diameter changes
5) Half life should be sufficient to allow complete examination
6) Should require little preparation

76. CONTRAST MEDIA USED IN MRI
1) Gadolinium chelates
2) Blood pool agents
3) Liver contrast agents
4) Endoluminal contrast agents
5) Targeted contrast agents

77. GADOLINIUM
 It is T1 relaxing agent
 Paramagnetic.
 Three agents have been approved by FDA, they are-
1) Gd-HP-DO3A: Gadoteridol/ProHance (non ionic)
2) Gd-DTPA : Gadopentetate diglumine/Magnevist (ionic)
3) Gd-DTPA-BMA: Gadodiamide/Omniscan (nonionic)

78.  Rapidly excreted by glomerular filteration
 half lives: 1 – 2hrs.
 Caution should be taken in renal impaired patients.
 Dose: 0.1 to 0.3mmol/kg body weight
 Disadvantages:
1) Enhancement is non specific neither organ specific or
pathology specific.
2) Short window for imaging of blood vessels as it is diluted in
blood stream and excreted rapidly.

79.  Acute adverse reactions
 0.07% to 2.4%
 mild, including coldness at the injection site, nausea, emesis, headache, warmth
or pain at the injection site, paresthesias, dizziness, and itching
 Reactions resembling an “allergic” response occur with a frequency of 0.004%
to 0.7%.
 life-threatening anaphylactoid or nonallergic anaphylactic reactions are
exceedingly rare (0.0001% to 0.001%).
 Gd agents are considered to have no nephrotoxicity at approved doses for MRI.

80.  Extracellular MRI agents are known to interfere with some
serum chemistry assays.
 Serum calcium tests will often be measured as a false reading
of hypocalcemia
 iron, magnesium, iron-binding capacity, and zinc may also
have spurious results
 Biochemical assessment is more reliable when performed 24
hours after exposure

81. Nephrogenic Systemic Fibrosis
 Fibrosing disease of the skin, subcutaneous tissues, lungs, esophagus, heart,
and skeletal muscles.
 Initial symptoms typically include skin thickening and/or pruritus.
 GBCM exposure is a necessary factor in the development of NSF.
 Onset of NSF varies between 2 days and 3 months, with rare cases appearing
years after exposure .
 Early manifestations include subacute swelling of distal extremities, followed
by severe skin induration and later even organ involvement.

82.  CKD but GFR more than 30 mL/min/1.73 m2 - extremely low
or no risk for developing NSF if a dose of GBCM of 0.1
mmol/kg or less is used.
 GFR more than 60 mL/min/1.73 m2 - NO increased risk of
developing NSF
 The risk of NSF in patients with a GFR of less than 15
mL/min/1.73 m2. - 1% to 7%

83. Group I: Agents a/w the greatest number of NSF cases:
Gadodiamide (Omniscan)
Gadopentetate dimeglumine (Magnevist)
Group II: Agents a/w few cases of NSF:
Gadobenate dimeglumine (MultiHance)
Gadobutrol (Gadavist)
Gadoterate acid (Dotarem)
Gadoteridol

84. BLOOD POOL AGENTS
 Reversibly bind to plasma albumin achieving improvement in blood pool enhancement.
1)SPIO-super paramagnetic iron oxide crystals
2)USPIO
3)Magnetite
 Predominant T2 shortening.
1)To image small vessels (eg:coronary artery).
2)Vessels with slow flow (eg pulmonary embolism, DVT),
3)Arteriovenous malformation
4)Perfusion studies
 DISADVANTAGE: Overlap b/w arterial and venous structures and separation is difficult

85. LIVER CONTRAST AGENTS
 Gadobenate
: MultiHance,Bracco.
 Small iron particles:
Endorem & Resovist.
 Manganese containing :
Teslascan

86. ENDOLUMINAL CONTRAST AGENTS
 Negative contrast agents:
Based on iron particles(Abdoscan, Nycomed-Amersham) for
Use:
1)MR Enteroclysis.
2)MR imaging of rectal cancer.
 Combination of Methyl Cellulose Solution for bowel distention & I.V Gadopentate
Dimeglumine for bowel wall enhancement.
 Natural contrast:
Blueberry juice acts as a negative contrast in upper abdominal MR imaging.
eg MRCP

87. REFERENCES
 Grainger & Allison –Diagnostic radiology.
 Radiological procedures- Dr.Bhushan N Lakhkar.
 Advances in imaging tachnology - Berry
 Campbell walsh urology
 Duke Radiology Contrast Media Guidelines
 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5658629/
 https://pubs.rsna.org/doi/full/10.1148/rg.2015150033
 American College of Radiology Manual On Contrast Media ,Version 10.3,
2018