CONTRAST AGENTS USED

IN RADIODIAGNOSIS AND
CONTRAST REACTIONS
PRESENTERS :DR.NEHA SHETTY
DR.BHAGYASHREE
MODERATORS : DR.S V KASHIKAR
 DEFINITION AND TYPES
• Contrast media enhance the
optical density of the area under
investigation so that the tissue
absorption differentials are
sufficient to produce adequate
contrast with adjacent structures,
thus enabling imaging to take
place.

• Positive

• Negative
 POSITIVE CONTRAST MEDIA
• Radio-opaque(white)

• High atomic number

• Attenuate radiation more than soft tissues of the

body.

• Contrast agent-filled area appears denser than

body tissue.

• Barium sulfate

• Iodine compounds
 NEGATIVE CONTRAST MEDIA
• Radiolucent (black)

• Low atomic number

• Attenuate theradiation beam less effectively than

body tissue

• Appear darker on the image

• Gases such as O2, NO2,air and CO2 are commonly

used.

• Cystography ,Gastrography ,Peritonography and

Pericardiography .
CLASSIFICATION
 BARIUM SULPHATE
• Has high atomic number (56), highly
radiopaque.

• Insoluble in water/lipid.

• Inert to tissues.

• Barium swallow, barium meal, barium

meal follow through, enteroclysis, barium
enema
BARIUM SWALLOW BARIUM MEAL
BARIUM MEAL FOLLOW THROUGH
ENTEROCLYSIS
BARIUM ENEMA
 WATER SOLUBLE IODINATED CONTRAST MEDIA
• Iodine is preferred because
*High contrast density due to high atomic
number/mass

*Allows firm binding to highly variable

benzene ring

*Low toxicity
• Radio-opacity is dependent number of
iodine atoms in each molecule of the
contrast medium.
WATER SOLUBLE IODINATED CONTRAST MEDIA

• Three defining physical characteristic-

Ionicity, Osmolality, and Viscosity.

• Both the viscosity of a contrast medium and

its osmolality are INVERSELY related to
tolerance but directly to degree of
opacification.

• Higher the osmotic pressure the poorer the

tolerance
 WATER SOLUBLE IODINATED CM

Hepatic excretion Renal excretion

Iopanoic acid

High osmolar Low osmolar

Ionic monomers Ionic dimers Non-ionic monomers Non ionic dimers

Diatrizoate Ioxaglic acid Iopromide Iotrol

Iothalamate Iohexol Iotrolon
Iopamidol
Ioversol
 IONIC NON IONIC

Dissociates into cations and Dissolve into water; but do

anions when injected not dissociate

Creates hypertonic condition Lower osmolality (fewer

particles in a solution
compared to ionic)

Increase in blood osmolality Lower incidence of AEs

 HIGH OSMOLAR CONTRAST MEDIA
• Ionic monomers -Salts consisting of a
sodium or meglumine cation and a
triodinated benzoate anion.

• Anions consisting of a benzoic acid

molecule with three atoms of iodine.

• The C3 and C5 are connected to radicals

R3 and R5, which are amines and greatly
reduce toxicity and increase solubility of
the molecules.
• Iodine particle ratio is 3:2.
DIFFERENCES B/W MEGLUMINE & SODIUM SALTS
Meglumine salts Sodium salts

Solubility Better Same, less in some acids

Viscosity High Low
Tolerance Better Less, nausea & vomiting
Blood Brain
Barrier No effect Crosses BBB
Vascular effects Less Marked
Diuretic effect Strong Less
Opacification Poor Better
Bronchospasm causes No
so CI in asthma
DISADVANTAGES OF CONVENTIONAL CONTRAST MEDIA

• Osmolar concentration is extremely high.

• Osmolar challenge to every cell, tissue and fluid in the body is

responsible for their adverse effects.

• Non-radiopaque cations (Na/Meg) exert just as great as an osmolar

load as do the radiopaque anions. The cation is merely a carrier and
serves no radiological function.
 LOW OSMOLAR CONTRAST MEDIA

• Ionic dimers -Ioxaglate (Hexabrix)

• Mixture of sodium and meglumine salts

• Two benzene rings are linked by a

bridge to form a large compound,
carries only one carboxyl group, so
known as monoacid dimers.

• Iodine Particle ratio is 6:2

 LOW OSMOLAR CONTRAST MEDIA
• Non Ionic Monomers

• First generation- Metrizamide

• Second generation
*Iopromide (Ultravist)
*Iohexol (Omnipaque)
*Iopamidol (Iopamiro)

• Iodine:Particle ratio is 3:1

• Carboxyl group (-COOH) is replaced by

non ionising radical & CONH2
 LOW OSMOLAR CONTRAST MEDIA

• Non Ionic Dimers

*Iotrolan(Isovist)
*Iodixanol (Visipaque)

• Each molecule contains 2 non

ionising tri-iodinated benzene rings
linked together
• Iodine: particle ratio is 6:1.
 Additives Used in Contrast Media

1. Stabilizer - Ca or Na EDTA.

2. Buffers(stabilizes pH during storage) -Na acid phosphates.

3. Preservatives
 IDEAL CONTRAST MEDIA
1. High water solubility.
2. Heat and chemical stability (Shelf life). Ideally-3-5 years.
3. Biological inertness (non-antigenic).
4. Low viscosity.
5. Low or iso-osmolar to plasma.
6. Selective excretion, like excretion by kidney is favourable.
7. Safety : LD50 (lethal dose) should be high.
8. Reasonable cost.
 PHYSIOLOGY
EQUILIBRIUM
EXTRAVASCULAR SIMULTANEOUSLY BETWEEN INTRA
IV CONTRAST AND
SPACE EXCRETED EXTRACELLULAR
SPACE IN 10 MINS

• Concentration and excretion are predominantly by passive

glomerular filtration

• Liver and Intestine excrete 1% of these compounds

• Continued excretion and reentry of contrast media from

E.C.F. to I.CF. lead to decrease in plasma level.

• Plasma half life is 30-60 min.

 CONTRAST MEDIA USED IN ULTRASOUND
Generations of Echo Enhancers
• First-Unstabilised bubbles in
indocyanine green

• Second-Longer lasting bubbles

coated with shells of protein, lipids
or synthetic polymers.

• Third-Encapsulated emulsions or
bubbles, offer high reflectivity.
 Ideal Qualities of Ultrasound Contrast Agents
• High echogenicity

• Low attenuation

• Low blood solubility

• Low diffusivity

• Ability to pass through pulmonary capillary bed

• Lack of biological effects with repeated doses.

• The main mechanism for signal enhancement are backscattering, bubble resonance, and bubble
rupture that is highly dependent on the acoustic power of the transmitted ultrasound also known
as MECHANICAL INDEX.
Lumason
 Types of Ultrasound Contrast Agents
 Tissue specific ultrasound
contrast agents
Levovist
Sonovist [Schering]
Sonozoid [Nycomed-Amersham]

 Vascular Ultrasound Contrast

Agent

Contrast Agents For Targeted

Imaging
 Tissue specific ultrasound contrast agents

• Improves the assessment of certain organs like liver, kidney, pancreas,

prostate, and ovary by improving the acoustic differences between normal
& abnormal portions of organs.

• The bubbles rupture produces a transient pressure wave, resulting in

characteristic mosaic pattern from the tissues, which is termed as induced
acoustic emission.
 LEVOVIST
• First generation ultrasound contrast
agent consist of galactose ground into
crystals.
• Used in echocardiography in left
ventricle functional assessment.
• In vascular phase also it can exhibit a
tissue or organ specific action.
• Gets accumulated in liver & spleen &
improves detection of focal liver lesion.
• The shell stabilizer is galactose/palmitic
acid and the gas used is air.
 SONOVIST
• A biodegradable synthetic capsule filled with sulphurhexa fluoride.

• It is a stable contrast media.

• It has an additional hepatosplenic parenchymal phase following the

pool phase

• Microbubbles are stationary in this phase.

• The shell stabilizer is cyanoacrylate and the gas used is sulphur

hexaflouride.
Sulfur Hexafluoride Lipid–type A Microspheres (Lumason/Sonovist)
 Vascular Ultrasound Contrast Agent

• These are gas microbubbles that pass

through lung capillaries and into the
systemic circulation.

• Used in imaging of malignant tumours in

liver, kidney, ovary, pancreas &
prostate,cardiac evaluation.
• Example:-Albunex & infosan.

The shell stabilizer is albumin and the gas

used is air.
 Contrast Agents For Targeted Imaging

• Improve the image contrast resolution

through differential uptake.

• High sensitivity & specificity

• Noninvasive detection of thrombus,

carcinoma, inflammation& other sites
where specific integrins or adhesion
molecules are expanded.

• Possible targets are molecular makers

on thrombus, endothelial cells &
leucocytes.
 CONTRAST MEDIA USED IN M.R.I.
• The parameters determining
signal intensity and contrast are:
1. Spin density : This cannot be
significantly altered by
a contrast agent, hence has
received less attention.

2. Relaxivity.

3. Magnetic susceptibility.

4. Diffusion and perfusion.

 CONTRAST MEDIA USED IN M.R.I.

Ideal Contrast Media

• Image contrast.
• Tissue specific
• Low toxicity and stability in vivo
• Suitable shelf life.
• Rapid clearance from the target tissue and safe excretion through
renal /hepatobiliary routes.
 Relaxivity

The two relaxivity parameters that are unique to

each tissue are T1 and T2.

• Contrast enhancement depends upon relative

change each impart on either T1 and T2.
• (a)  Contrast agent that predominantly affects
Tl relaxation is referred to as a positive
relaxation agent.
• (b)  Contrast agent that predominantly affects
T2 relaxation is referred to as a negative
relaxation agent
 Magnetic Susceptibility
• Susceptibility describes the ability of a substance to become
magnetised in an external magnetic field.

• (a) Diamagnetic-negligible effect.

(b) Paramagnetic
(c) Super paramagnetic-Very large positive susceptibility effect
(d) Ferromagnetic
• Most commonly used T1 relaxation agents are paramagnetic
substances.

• Of these Gadolinium is the most frequently used.

• Gadolinium is complexed with various ligands that act as chelating

agents.
 T1 Relaxation Agents

• Three agents have been approved by FDA.

They are:
• 1. Gd-HP-D03A : (Gadoteridol/ProHance) --
Non ionic

• 2. Gd-DTPA : (Gadopentetate dimeglurnine/

Magnavist) -Ionic
• 3. Gd-DTPA-BMA:
(Gadodiamide/Ornniscan) – Non ionic
 T1 Relaxation Agents

• These function as extracellular contrast agents.

• They are rapidly excreted by glomerular filtration with half lives

between 1-2 hours.

• These agents also cause T2 shortening but only at higher doses.

• As these compounds are excreted by renal excretion, caution should be

exercised in renal impaired patients.
 T2 Relaxation Agents

• SPIO-Ferrite particles incorporated

by super-para magnetic agents.
• Of the Ferrite particles,
Magnetite(Fe304) is used commonly.
• These are crystalline oxides with
particle size ranges from 0.5 to 1
micron .
• They are used in the study of the
liver, spleen and GIT studies.
 Diffusion and Perfusion

• Hepatobiliary chelaters -2 gadolinium chelaters with hepatobiliary

excretion are
--Gd-BOPTA & Gd-EOB-DTPA
-- MnDPDP (Mangafodipir trisodium)

• Blood pool chelaters -eg. AMI-227

• Reversibly binds to plasma albumin achieving a substantial
improvement in magnitude and duration of blood pool enhancement
Mangafodipir
SPOTTER
 ADVERSE EFFECTS OF
CONTRAST AGENTS USED
IN RADIOLOGY
PRESENTATION BY DR.BHAGYASRI

UNDER GUIDANCE OF DR. S V KASHIKAR

• 1. Reactions unrelated to contrast media

• 2. Hyperosmolarity

• 3.Chemotoxic

• 4. Immunological
REACTIONS UNRELATED TO
CONTRAST MEDIA
• Pyrogenicity – due to unsterile needle and the management is to
assure the patient.

• Vasovagal attack - seen in anxious or psychosomatic patient.

• Hypertensive attacks – seen in pheochromocytoma patients .

• Excessive dehydration and hypoglycemia

 HYPEROSMOLARITY
• Erythrocyte damage
• Capillary endothelial damage
• Vasodilatation
• Hypervolaemia
• Disturbance of BBB -
neurotoxicity
• Cardiovascular effects- peripheral vasodilatation, tachycardia,

• Decreased blood pressure,

• Cardiovascular insufficiency,

• Left venticular stress (acute hypervolaemia)

• Negative ionotropic effect.

 CHEMOTOXIC
• It is mostly due to cations(especially sodium).
• Effects are seen in neurons, myocardial cells, capillary endothelial
cells, RBC, kidney.
 IMMUNOLOGICAL TOXICITY
• Deactivation of angiotensin converting enzyme.

• Damage endothelium.

• Inhibition of cholinesterase enzyme

• Release of vasoactivesubstances(histamine,bradykinin,seratonin)
 Nephrotoxicity of contrast media mainly
due to

• Low renal perfusion,

• Glomerular injury,

• Tubular injury,

• Precipitation of tamm horsfall proteins which

block tubules.

• Swelling in the renal tubules.

NEPHROGENIC SYSTEMIC FIBROSIS
• Thickening and hardening of
skin overlying extremities and
trunk.

• Expansion and fibrosis of dermis

with CD34 positive fibrocytes.
• Gadolinium- Non radioactive,paramagnetic,
Hyperosmolar.

It is a specific trigger for nephrogenic

sytemic fibrosis

Mode of excretion- mailnly kidney

Free gadolinium-highly toxic,precipitate with

anion ,disrupt calcium ion passage in nerve
and muscle
 HIGH RISK GROUPS
• Prior reaction to contrast media • Myelomatosis
• H/O allergy • Polycythemia.
• Cardiac disease • SCA
• Asthma • Pheochromocytoma
• Diabetes • Homocystinuria
• Old age
• Neonates
 SEVERITY OF REACTIONS
• MINOR-Nausea,vomiting,rash,headache,dyspnea,

• INTERMEDIATE – Urticaria, facial edema, bronchospasm,laryngeal

edema, dyspnea,chest pain,hypotension.
• SEVERE – collapse, pulmonary edema, angina, MI, convulsions,
coma, cardiac/respiratory arrest
Incidence of reactions with ionic and non
ionic contrast media
IONIC CONTRAST MEDIA NON IONIC CONTRAST MEDIA
• Contrast reactions incidence – • Less compared to ionic contrst
more media
• Mortality-low • High
• Reaction rate in prior reaction • Low
patients-high
• With steroids as premedication • Low
reaction rate- low
 MANAGEMENT
• Make sure before injecting contrast drugs for allergic reactions are
available.

• Dont leave the patient after injecting contrast until examination is

complete.
• OXYGEN- High dose
oxygen (10-12L/min)
via facemask.
• EPINEPHRINE- 1 in
1000 concentration
epinephrine given
(s.c/i.m )
• 1 in 10000
concentration given
(i.v).
• S.c (0.1-0.3 ml) can be
repeated every 10-15
min until dose of
1mg .
• Life threatning
complications of
epinephrine-
hypertensive crisis,
MI, myocardial
ischaemia

• Care should be taken

while giving it in
patients with cardiac
disease ,hypertension,
and on beta blockers.
• CORTICOSTEROIDS- Useful in reducing late reactions

• Recommended dose- i.v 100-1000mg

• Initial dose can be followed by 300-500 mg in 250 ml solution

@60ml/hr
PRECEEDING SYMPTOMS OF SEVERE
REACTIONS
• Nausea • Disorientation
• Vomiting • Anxiety
• Chills
• Sneezing
• Watery eyes
• Nasal congestion
• Confusion
MANAGEMENT BASED ON THE
SEVERITY OF REACTIONS
• MILD- reassure the patient.

• MODERATE- Usually no treatment needed if pruritis is severe use 50

mg diphenhydramine

• In c/o angioedema – cimetidine 300 mg, if not responded epinephrine

0.1-0.3 ml (1 in 1000 dilution)
RESPIRATORY REACTIONS
• Airway and laryngeal edema
• BRONCHOSPASM-
Mild case- Oxygen 10L/min,MDI (albuterol)
Moderate –epinephrine(1 in1000)
0.1-0.3ml(s.c) repeat 10-15 min
aminophylline-5mg/kg i.v slowly over
10- 20 min
Severe- epinephrine(i.v)
• LARYNGEAL EDEMA-Oxygen,epinephrine,intubation if necessary

• PULMONARY EDEMA-
Elevate head end
Oxygen- 10L/min
Furosemide40 mg i.v slowly
Hydrocortisone 100 mg i.v slowly
• HYPOTENSION-
MILD- elevate legs
Oxygen @ 10L/min
Rapid administration of IVF
• SEVERE WITH BRADYCARDIA-
Atropine 0.6-1 mg repeat 3-5 min upto 3 mg
maximum
SEVERE WITH TACHYCARDIA-Epinephrine 1
in 10000(1-3ml) upto 10 ml
• SEIZURES-
MILD- turn to oneside
Clear the airway
Oxygen- 10L/min
SEVERE- Diazepam 5 mg i.v slowly
HYPERTENSIVE
CRISIS-
Oxygen -10L/min
NTG 0.4 mg
sublingual,if not
responding
Nifedipine 10 mg
In c/o
Pheochromocytoma
phentolamine 5 mg
(i.v )
 EXTRAVASATION OF CONTRAST MATERIAL-
• Elevation of affected extremity above heartlevel.
• Ice packs
• Plastic surgery consultation – in c/o large volume extravasation,skin
ulceration and blistering
THANK YOU