CONTRAST MEDIA

Dr Justin jose

Contrast media are agents which permit visualization of details of internal structure or organs that would not otherwise be demonstrable.

Classification

Classification

ORAL CONTRAST MEDIA

• Earliest contrast medium used was iodised oil• At present contrast medium of choice is barium

sulfate• REASONS• Ba has atomic no56 so highly radioopaque• Nonabsorbable&nontoxic• Insoluble in water&lipid• Inert to tissues• Can be used for double contrast studies

MANUFACTURE

• Manufactured from mines• STEPS• Mined basulfate is reduced to basulfide• Basulfide+sod carbnte-barium carbonate• Ba carbonate+sulfuric acid-insoluble basulfate• Basulfate being insoluble in water is used in the

form of suspension .Conc is indicated by wt/volume

• Here a specified wt of ba sulfate is determined&water is added to enough volume

CHARECTERISTICS INFLUENCING COATING

• Additives are added to influence the rate of settling ,viscosity ,charge, mucosalcoating, thickness,&flocculation.if too much additives viscosity will be high

• Stability indicate that suspension will not settle down when allowed to stand.suspending agents are used toprevent settling.gumacasia&carboxy methyl cellulose are used for this purpose .These additives will increse viscosity of suspension

flocculation

• Flocculation is reduction in no of particle by formation of large masses

• To prevent this antacidsare used which neutralises gastric acids &prevent flocculation

• Antacids used are sod citrate,alum hydroxide,mag sulfate

• Preservatives are added to prevent bacterial&fungal growth. Methyl paraben&sod metabisulfite are used

• Antifoaming agents are added to prevent air bubbles .simethicone&polysiloxane are added

• Colouring&sweetening agents are also added

ADVERSE EFFECTS

• Constipation• Barium inspissation incolonic obstn lead to

hard stone• Hypersensitivity rean to additives like cmc has

been described .methyl paraben&similar comp used as preservatives can induce hypersenstivity rean

• Ba crystals in peritonial cavity cause extensive fibrosis&granulomatous reaction

• Intravasclar ba cause embolism • Barium encephalopathy due to abspn from

peritonium in cases of perforation• Prev contrast medium extravasation may

mimic cancer

OTHER ORAL CONTRAST MEDIA

• GASTROGRAFFIN• 20ml urograffin76%+20mlns+2drops sorbitol• INDICATION• Susp perforn• Susp fistula• History of recent biopsy• Susp LI obstn• Corrosive poisoning

ORAL CONTRAST AGENTS USED IN CT

THE IDEAL GUT CONTRAST • Should fill entire bowel lumen• Should be palatable• Non irritating to mucosa• Should pass rapidly through gi tract without

producing artefact• preferably should coat gut mucosa so that

presence of bowel is detectable when lumen is not distended

• A positive contrast medium must increase ct attenuation value of bowel lumen by 40 hu

• Conventional ba sulfte suspnsn are too dense resulting in streak artefact

• Full strength ba preprn shouldn’t be diluted to low conc needed for ct as barium particle settle out after ingesion leading to in homogenous opacification of bowel lumen

• 1%to3%w/vba sulfte susp or2%to5%gastrograffn or iodinated agents are typically used

I.V CONTRAST MEDIA

IODINE• Most of the I V contrast media contain iodine

which has an atomic number. 53 and atomic wt. 127 gm.• Iodine (atomic weight 127) is the only element

that has proved satisfactory for general use as an intravascular radiological contrast medium (RCM).

• Total iodine content in the body is 0.01 gm.

• Iodine is preferred becoz :-

1) high contrast density due to high atomic number. 2) allows firm binding to highly variable benzene ring. 3) low toxicity.

Useful factors to remember• Osmolality:- is dependent on no. of particles of

solute in solution.• Radio opacity:- is dependent on the iodine

concentration of the solution & is therefore dependent on the no. of iodine atoms in each molecule of the contrast medium.

• High radio opacity & low osmolality are of desirable requirements.

• The ratio of the no. of iodine atoms per molecule to the no. of particles per molecule of solute in solution is therefore a fundamental criteria.

CLASSIFICATION OF IODINATED CONTRAST MEDIA

• There are four chemical varieties of iodinated RCM in clinical use.

• All four are tri - iodo benzene ring derivatives with three atoms of iodine at 2,4,6 positions (in monomers) and six atoms of iodine per molecule of the ring anion (in dimers).

CLASSIFICATION OF IODINATED CONTRAST MEDIA

1. IONIC MONOMERS (CONVENTIONAL/HIGH OSMOLAR CONTRAST MEDIA [HOCM]).

11. NON-IONIC MONOMERS .111. IONIC DIMERS.

1v. NON-IONIC DIMERS.

Class 11, 111, 1v are collectively known as Low osmolar contrast medias.

IONIC MONOMERS (HIGH OSMOLAR CONTRAST MEDIA [HOCM])

• All ionic monomers are salts consisting of a sodium or meglumine (N-methyl glucamine) as the non-radio opaque cation and a tri-iodinated benzoate as the radio opaque anion.

Eg:- iothalamate• Anions consisting of a benzoic acid molecule with three atoms of iodine firmly attached at C2, C4 & C6.

• The C3 & C4 are connected to radicals R3 & R5 which are amines E-NH2, and which greatly reduces toxicity & increase solubility of the molecules.

• These anions include – Diatrizoate (Urograffin, angiograffin, Hypaque)– Iothalamate (Conray)– Ioxithalamate, metrizoate– Iodamic acid

• Each molecule completely dissociates in water solution into two ions – one non-radio opaque cation and one tri-iodinated radio opaque anion, giving an iodine: particle ratio of 3:2 .

• They are very hypertonic - 1600 mosmols kg-1 water at 300 mg iodine /ml compared to physiological osmolality of 300 mosmol kg-1 water.

Sodium or meglumine act as cationsDifferences b/w

Disadvantages of ionic monomers

• Osmolar concentration (osmolality) is extremely high upto 5-8 times the physiological level of 300 mosm/kg water.

• Osmolar challenge to every cell, tissue & fluid in the body is responsible for their adverse effects.

NON-IONIC MONOMERS• Include iohexol (omnipaque), iopamidol,

iopromide (ultravist), ioversol, ioxilan.• None of these molecules dissociate in solution.• They are tri-iodinated non-ionizing compounds

and therefore in solution they provide three atoms of iodine to one osmotically active particle (the entire molecule), producing an iodine: particle ratio of 3:1.

• They have an osmolality of about 600 mosmol kg-1 water at a concentration of 300 mg I/ml compared to physiological osmolality of 300 mosmol kg-1 water.

Eg:- iohexol (omnipaque)

IONIC DIMERS • Ioxaglate , Iocarmate

are the compounds in this group.

• It is a mixture of the sodium and meglumine salts of a monoacidic double benzene ring with each benzene ring having three atoms of iodine at C2, 4, 6 positions. The total molecule therefore contains six atoms of iodine.

Eg:-Ioxaglate

• In solution each molecule dissociates into one radio-opaque hexa-iodinated anion and one non-radio opaque cation (sodium and/or meglumine).

• Ioxaglate therefore has an iodine: particle ratio of 6:2 or 3:1.

• They have an osmolality of about 560 mosmol kg-1 water at a

concentration of 300 mg I/ml compared to physiological osmolality of 300 mosmol kg-1 water.

NON-IONIC DIMERS

• Iotrol, iotrolan and iodixanol are examples of non ionic dimers.

• They do not ionize or dissociate in solution.

• Each molecule contains two non-ionizing

tri-iodinated benzene rings linked by a bridge.

Eg:- iotrolan

• Each molecule therefore provides in solution six atoms of iodine for one molecule, i.e. an iodine:particle ratio of 6:1.

• Non-ionic dimers are physiologically isotonic (300 mosmol kg-1 water) in solution at a concentration of 300 mg I/ml.

Pharmacokinetics• After intravascular injection, the contrast

media are distributed rapidly because of high capillary permeability into the extravascular, extracellular space (whole body opacification) (except in the central nervous system)

& is simultaneously excreted. • Then equilibrium is reached b/w intra &

extravascular space in about 10 min. Continued excretion & re entry of contrast media from ECF to ICF leads to decrease in plasma level.

• Plasma half life is 30 – 60 min.

• They do not enter the interior of blood cells or tissue cells and they are rapidly excreted, with over 90 % being eliminated by passive glomerular filtration by the kidneys

within 12h.

ADDITIVES USED IN CONTRAST MEDIA

• 1) Stabilizer – Ca or Na EDTA• 2) Buffers – stabilizes pH during storage – Na acid phosphates.• 3) Preservatives.• 4) Flavouring substances & Emulsifiers for GIT media.

IDEAL CONTRAST MEDIA SHOULD HAVE:- • 1) High water solubility.• 2) Heat & chemical stability (shelf life). Ideally 3-5 yrs.• 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.

ADVERSE REACTIONS

TYPES OF ADVERSE REACTION

• 1 Idiosyncratic anaphylactoid reactions – most dreaded and most serious and fatal .– occur without warning, cannot be reliably predicted and

are not preventable.– are not dose dependent and death has been known to

occur following a 1 ml IV test dose, or after the full dose of RCM has been given after a negative test dose.

• 2 Non-idiosyncratic reactions– these are dose dependent – related to the chemical composition, osmolality and

concentration of contrast medium and the volume, speed and multiplicity of the injection

• 3 Combined 1 and 2 reactions

Idiosyncratic anaphylactoid reactions

• These ADRs are the most dreaded and most serious and fatal complications of RCM injection as they occur without warning, cannot be reliably predicted and are not preventable in the present state of our knowledge.

• These reactions usually (85 per cent) begin either during or immediately after the injection of contrast medium. ADRs are more frequent in patients who have had a previous adverse reaction to contrast medium, asthmatics, allergic and atopic patients, patients with impaired cardiovascular and renal systems, diabetics and patients on beta-adrenergic blockers and possibly on nonsteroidal analgesics.

Non-idiosyncratic reactions • Unlike the idiosyncratic reactions, these non-

idiosyncratic reactions are dose dependent and therefore relate to the chemical composition, osmolality and concentration of contrast medium and the volume, speed and multiplicity of the injection.

• 1 ) Chemotoxic reactions:- Chemotoxic adverse reactions are probably due to toxicity to the contrast medium anion rather than to its iodine content, as the iodine is very firmly bound to the benzene ring.

• Chemotoxic side effects include cardiac, neurological and renal toxicity as well as vascular manifestations.

• 2) Hyperosmolar reactions:- The very high osmolality of high concentrations of HOCM

(ratio 3:2) is 5–8 times the physiological osmolality (300 mosmol kg-1 water) of every cell in the body.

• The degree of hyperosmolality is much reduced if non-ionic ratio 3:1 (LOCM) and (even more) if ratio 6:1 products isotonic non-ionic dimeric LOCM are injected instead of injecting HOCM of ratio 3:2.

The adverse reactions due in part to hyperosmolality of

the contrast medium include:• Erythrocyte damage• Capillary endothelial damage• Vasodilatation• Hypervolemia• Cardiovascular effects• Vascular pain• Disturbance of BBB• Thrombosis & thrombophlebitis

For clinical purposes contrast media reactions are divided into 3 categories:• Minor (1 in 20 cases-5%) : Flushing, nausea, arm

pain, pruritus, mild urticaria, vomiting and headache.

• Intermediate reactions (1 in 100 cases-1%): Severe urtricaria, facial edema, hypotension, bronchospasm.

• Severe (1 in 2000 cases-0.05%): Convulsions, unconsciousness, laryngeal oedema, severe bronchospasm, pulmonary oedema, severe cardiac dysrhythmias and cardiac arrest, cardiovascular and respiratory collapse.

Incidence of reactions with Ionic contrast media & Non-ionic contrast media in general population

CONTRAST MEDIA REACTIONS

ICM NICM

Incidence 3.8 to 12.7% 0.6 to 3.1%

Mortality 1/30 1/207

In high risk groups serious side effects

0.25% 0.045%

Fatality rates 157/100,000 60 to 126/100,000

In pts known to have prior reaction, reaction rate

18-20% 5-6%

With premedication steroids, reaction rate

Higher Lower

Treatment

• Treatment must be urgently and expertly administered according to a pre-arranged well-practised schedule.

• The airway must be secured and oxygen, artificial respiration, external cardiac massage and electrical DC defibrillation must be administered as and when required. IV fluid infusion (normal saline, lactated Ringer's solution) through an indwelling IV catheter is essential to restore blood volume and to administer IV drugs:

• • A powerful diuretic such as frusemide (Lasix) 20–40 mg IV slowly or IM for pulmonary oedema . • • Diazepam and barbiturates for convulsions . • • Adrenaline (epinephrine) (0.3–0.5 ml, 1/1000 solution [children 0.01 ml kg-1 body weight] by deep SC or IM injection repeated at 10–20 min intervals) provides the most rapid and reliable relief for bronchospasm, angioneurotic oedema and other anaphylactoid symptoms .

• • Salbutamol (b2 agonist metered dose

inhaler). • • Hydrocortisone or methyl prednisolone (100–1000 mg) . • • Aminophylline (very slowly, 250–500 mg) intravenously for intense bronchospasm. • • Chlorpheniramine for allergic or anaphylactic symptoms.

• • Vasopressors, e.g. noradrenaline (or metaraminol [Aramine] 0.5–5 mg slow IV infusion). • • Dihydroxyphenylaline (or dopamine) infusion (2.5–5μg kg-1 min-1) for hypotension with monitoring of the blood pressure .• Sodium bicarbonate infusion should be

administered to correct any acidosis, and atropine 0.6–1.0 mg IV or IM repeated if necessary (children 0.02 mg kg-1 repeated if necessary to 2 mg total) is used for vasovagal reactions, bradycardia and cardiac failure.

High risk patients• Patients with a previous ADR to RCM (excluding mild

flushing, nausea) . • Asthmatics . • Allergic and atopic patients. • Cardiac patients with decompensation, unstable

arrhythmia, recent myocardial infarction. • Renal patients in failure, diabetic nephropathy, on

metformin. • Feeble infants and aged patients. • Patients with a severe general debility .• Very nervous, anxious patients. • Patients with various metabolic and hematological

disorders . • Thyrotoxic: goitrous patients.

SafetyMeasures

• Appropriate indication and selection. • Informed consent.• Hydration.• Test dose.• Smallest dose.• Alternative imaging • Premedication.• Adequate resuscitation facilities

CONTRAST AGENTS FOR CHOLANGIOGRAPHY

• ORAL CHOLECYSTOGRAPHY relies on overnight abspn of oral contrast agent such as sod iopodate

• It is absorbed from bowel excreted into bile &conc in bladder

• Non opacity of g.b means absence or pathology of g.b providedc.b.d is opacified

• i.v agents undergo hepatocyte uptake&biliary excrn by active transport

• Iodipamide meglumine(cholograffin)is only agent in u.s

• The principal requirements for an ultrasound contrast agent is that it should be easily introducible into the vascular system, be stable for the duration of the diagnostic examination, have low toxicity, & modify one or more acoustic properties of tissues which determine the ultrasound imaging process.

• Contrast agents might act by their presence in the vascular system, from where they r ultimately metabolized (blood pool agents) or by their selective uptake in tissue after a vascular phase.

• Gas bubbles have a tremendous difference in acoustic impedance as compared to surrounding fluid due to the large differences in density, elasticity and compressibility.

• Free Gas Bubbles The bubbles may pre-exist in the liquid, or they may be

created via cavitation during injection. Solution used r saline, indocyanine green or renograffin.

IV injection of physiological saline has been used as a contrast medium in echocardiography since the late sixties, but the utility of free gas bubbles is highly limited due to:-– low stability– large bubble size to pass the pulmonary vasculature

• For gas bubbles to be used as transpulmonic contrast media, the gas bubbles should be stable and smaller than 5 µm.

• Bubbles larger than 10 µm may transiently obstruct the capillaries and act as gas emboli.

• Several stabilizing coatings have been developed to produce Encapsulated gas microbubble contrast media.

• The coatings include albumin(Albunex), gelatin, galactose microspheres & palmitic acid (Levovist), polyglutaminic acid, lipophilic monolayer surfactants, and lipid bilayers (liposomes).

LOW SOLUBILITY GAS BUBBLES

• Since the effective duration of action of encapsulated air bubble is very short, Newer agents designed both to increase backscatter enhancement further & to last longer in the blood stream, r currently under intense development.

• Instead of air, many of these take advantage of low solublity gases such as perfluorocarbons, having lower diffusion rate & thereby increasing the longevity of the agent in the blood.

• Several types of particles have been reported as ultrasound contrast media– collagen microspheres (solid)– iodipamide ethyl ester (solid)– perfluorochemicals (inert, dense liquids).

• Perfluorocarbons lead to a large tissue impedance mismatch due to their high density and compressibility.

• After IV injection, it can be detected in the intravascular space for several hours. Due to the small particle size, the contrast medium passes all capillary beds and will therefore enhance perfused tissue.

• Perfluorochemicals are eliminated either by phagocytosis of the reticuloendothelial system or by evaporation in the lungs.

• Due to the selective phagocytosis, liver and spleen show late phase enhancement.

• Particle suspensions are generally less effective than gas bubbles, and much larger doses are needed for enhancement. Perfluorocarbons may furthermore be less safe than the gas bubbles; a relatively high percentage of mild allergic reactions have been shown in humans.

Microbubble Gas Stabilizing shell

First generation, non-transpulmonary vascular Free microbubbles Air None

Echovist (SHU 454) Air None

Second generation, transpulmonary vascular, short half-life (< 5 min)

Albunex Air Albumin Levovist (SHU 508 A) Air Palmitic acid

Third generation, transpulmonary vascular, longer half-life (> 5 min) Aerosomes (Definity, MRX115, DMP115) Perfluoropropane Phospholipids

Echogen (QW3600) Dodecafluoropentane Surfactant

Optison (FSO 69) Octafluoropropane Albumin

PESDA Perfluorobutane Albumin Quantison Air Albumin

QW7437 Perfluorocarbon Surfactant Imavist (Imagent, AFO150) Perfluorohexane Surfactant

Sonovue (BR1) Sulphur hexafluoride Phospholipids

CONTRAST AGENTS USED IN MRI

USES OF CONTRAST AGENTS IN MRI

– Increase the sensitivity of MR to detect pathological process.

– To characterize pathology.– To depict normal & abnormal vasculature or flow

related abnormalities.

• 1 st MR contrast agent introduced in 1988.

• Today 40 – 50 % of all MR examinations use contrast agents.

CLASSIFICATION

• NON TISSUE SPECIFIC ( extra cellular) – initial short intra vascular distribution --> extra cellular

space throughout body.

• TISSUE SPECIFIC– RE cell specific– Hepatocyte specific– Blood pool agents– Enteral – bowel

• BASED ON MECHANISM OF ACTION– T1 relaxation agents– T2 relaxation agents

NON SPECIFIC EXTRACELLULAR AGENTS

• GADOLINIUM– is a rare earth metal.– a paramagnetic substance with 7 unpaired electrons.– tend to accumulate in tissues with a natural affinity to

metals ( membranes, transport proteins, enzymes, osseous matrix , lung, liver, spleen, bone).

– Paramagnetic agents are mainly positive enhancers that reduce the T1 and T2 relaxation times and increase tissue signal intensity on T1-weighted MR images and have almost no effect on T2-weighted images.

– Gd ion is toxic and therefore it is necessary to encapsulate it by a chelate.

– chelating substances like DTPA is used to bind with Gd – Gd DTPA.

• Gd CHELATES

– Gadopentate Dimeglumine -Magnevist– Gadoterate Meglumine- Dotarem– Gadoteridol- Prohance– Gadodiamide- Omniscan– Gadobutrol- Gadovist– Gadoversatamide- Optimark

PHARMACOKINETICS • The pharmacokinetics of all extracellular MRI contrast

agents with the exception of Gd-BOPTA are similar to iodinated water-soluble contrast media.

• After IV injection they are rapidly diffused into the interstitial extravascular space.

• Gd chelates are eliminated unchanged from the intravascular compartment by passive glomerular filtration.

• By 24 hours >95 per cent of the injected dose is excreted in urine with normal renal function.

• A very small amount (<0.1 per cent) is eliminated via faeces. The biological half-life is approximately 1.5h.

• Extracellular MRI contrast agents do not cross the intact specialized vascular blood–brain barrier .

CLINICAL USE OF EXTRACELLULAR MRI CONTRAST AGENTS

• These agents accumulate in tissues with abnormal vascularity (malignant, infective and inflammatory lesions) and in regions where the blood–brain barrier is disrupted.

• DOSAGE– 0.1 millimol/kg or 0.2 ml/kg– max dose – 20 ml– lethal dose– 10 mmol/kg

SAFETY OF EXTRACELLULAR MRI CONTRAST AGENTS

• Extracellular MRI contrast agents are well tolerated with a low incidence of adverse effects.

• In blood, the osmotic load of all Gd-based

contrast media is very low, compared to iodinated contrast media, because only a small amount of the contrast agent is required to produce a diagnostic MRI examination.

• SIDE EFFECTS

– Minimal with standard dose.– Slight transitory increase in bilirubin & blood

iron.– Mild transitory head ache (9.8%).– Nausea (4 %).– Vomiting ( 2%).– Hypotension, rash ( 1%). – Life-threatening reactions are very rare.

CONTRAINDICATIONS

• No known contraindication.• Although , caution in

– hematological disorders- hemolytic anemia.– pregnancy, lactation.– respiratory disorders- asthma.– previous allergy.

HEPATOCYTE SPECIFIC CM• Gadolinium based compounds:• These agents have a capacity for weak and transient protein

binding and is eliminated through both the renal and hepatobiliary pathways.

• The hepatic uptake represents 2–4 per cent of the injected dose. • It behaves as a conventional extracellular contrast agent in the

first minutes following IV administration and as a liver-specific agent in a later delayed phase (40–120 min after administration) when it is taken up specifically by normal functioning hepatocytes.

– Gadobenate dimeglumine (gd- bopta)- multihance– Gadoxetic acid ( gd-eob-dtpa)- eovist

• Mangafodipir trisodium – teslascan– is strongly paramagnetic due to unpaired electrons.– Mn usually toxic , but made tolerable by complexing to a

molecule which facilitates binding to plasma protein.– primarily excreted by liver -70% (as similar chemical

structure to vit b6).– also taken by tissues with active aerobic metabolism-

pancreas, renal cortex, gi mucosa, myocardium, adrenals.

• so far approved by fda only for diagnosing liver lesions.

• acts by shortening T1 relaxation time.

RETICULO ENDOTHELIAL CELL SPECIFIC

• FERUMOXIDES – – are SPIO ( polysaccharide coated super

paramagnetic iron oxide) particles.– contain a central core of iron oxide particle

surrounded by a thin incomplete dextran coating, that causes individual particles to form polycrystalline aggregates.

– they have a size of approx 50- 200 nm.

• RES in liver, spleen, bone marrow take up the agent & has a low signal in TI or T2*.

• Lesions not containing REcells do not take up the agent & remain unaffected, so have a high signal.

• Immediately following IV administration, the contrast agent also causes T1 relaxation and early T1-weighted imaging may be performed.

• USES– differentiate b/w hepatic origin tumor that contain

RES & tumors that do not.

• DOSE

– IV slow infusion over 30 min.– 0.56 mg of iron ( 0.05 ml feridex) /kg.– Should be diluted in 100 ml of 50% dextran. – Further delay of 30 min prior to imaging allow for

maximum uptake by RE cells.– Contrast enhancement observed from 30 min to

4 hrs following infusion.

• SIDE EFFECTS

– Has a good safety profile.– But in <3 % pts- Low back ache during infusion,

usually self limiting, disappear after stopping/ slowing, also leg, groin pain, head, neck pain.

– Rarely -Gi- nausea, vomiting, diarrhea, anaphylaxis, hypotension.

– C/I - pts with allergy, hypersensitive to iron, parenteral dextran.

– USPIO: Ultra Small Super Paramagnetic iron Oxide agents.

– Contains a thicker, more complete coating which causes these particles to remain as small monocrystals in solution.

– So remain in circulation longer & are phagocytosed at a slower rate.

– Increase signal intensity on T1w, decrease signal intensity on T2w.

BLOOD POOL AGENTS

• Circulate in intravascular space for a longer time, cause significant reduction in T1 relaxation time of circulating blood.

• So best for MRA.• Several agents are under development, none

is currently approved for clinical use.

• Gadofosveset (ms-325)• Gadocoletic acid (gd-dtpa coupled with

deoxycholic acid)

OTHER TISSUE SPECIFIC MR CONTRAST MEDIA

• Atherosclerotic plaques (asp)– USPIO s accumulate in monocyte -macrophages of asp.– Gadofluorines accumulate in foam cells & cellular debris

deep to intima at sites of asp.• Necrosis- gadophorins –used to assess myocardial

necrosis.• Tumor specific MR CM -

– eg: monoclonal antibody labeled paramagnetic & super paramagnetic nanoparticles.

• Perfluorinated gases, Gd based aerosols , hyperpolarized He & O2 gas – imaging lungs .

ORAL CONTRAST MEDIA

• Non specific.• Used in abdomen & pelvis studies to provide

reliable differentiation of bowel from adjacent structures & to provide better delineation of bowel wall.

• Positive CM.• Negative CM.

POSITIVE CONTRAST MEDIA• Increase the overall signal intensity within the

image, by shortening T1 times of tissue water.• Generally solution of paramagnetic metal

ions.• Mostly present in natural products ( mn in

tea).• Specifically formulated agents-

– Mn chloride ( lumenhance)- T1 relaxing– Gd dtpa (magnevist enteral)- ,,

NEGATIVE CONTRAST MEDIA

• Eliminate tissue signal from the area of interest by:- – reducing the T2 relaxation time – by using

suspension of furomoxide particles.– or by using an agent that contains no

protons, & therefore produce no visible MR signal.• barium sulphate, used for intra luminal

studies.

CONTRAST MEDIA RELATED TO SPECIFIC CLINICAL AREAS

• RENAL TRACT

There is no doubt that high doses of contrast media impair renal function, usually peaking at 3–5d, causing a decrease in urine output and an increase in serum creatinine and urea levels, decreased creatinine clearance and reduced glomerular filtration rate (GFR). In some patients this may proceed to renal failure with anuria, uraemia and death. Renal dialysis (either intravascular or peritoneal) is very effective and may be life-saving as an alternative method of excreting RCM and uraemic metabolic products.

• These severe adverse reactions are very unlikely to occur if the patient is well hydrated and has normal renal function before the RCM injection. Particularly important adverse factors are pre-existing renal failure and oliguria, diabetic nephropathy, nephrotoxic drugs, patients who are not well hydrated and patients who are liable to be injected with very high doses of RCM for multiple sequential examinations repeated within a few days. Alternative imaging procedures must always be considered.

• The usual recommended dose for IV urography in the normally well-hydrated adult with normal renal function is 15–25 g iodine; this dose may be increased provided the patients are well hydrated (by IV normal saline if necessary before, during and after RCM injection). A maximum of about 70 g of iodine (1 g iodine kg-1 body weight in adults) is generally advisable even in patients with good renal function, but considerably larger quantities (up to 200 g or even 300 g of iodine, i.e. up to 600 g of RCM) may be required, particularly in difficult angiographic and interventional procedures.

• After early uncertainty, it is now established that HOCMs are more nephrotoxic, and LOCMs are preferred for all patients considered to be at increased risk, especially with diabetic nephropathy. There is increasing evidence that RCM (particularly HOCM and large doses) may induce damage to the tubules in the renal medulla and reduce intra-medullary blood flow in patients with acute calculus renal colic.

NERVOUS SYSTEM

• LOCMs are much more comfortable for cerebral arteriography in the conscious patient and are always preferred. Cerebral RCM photographic arteriography is being strongly challenged and partially displaced by CT and MR angiography (MRA).

Cerebral angiography • Adverse reactions to RCM include dilatation of the

external carotid arterial territory causing facial pain and heat. Damage to the blood–brain barrier may cause dangerous cerebral oedema, bradycardia and hypotension.

CARDIOVASCULAR SYSTEM

• Peripheral Arteriography The usual iodine concentration required for conventional

film-screen angiography is about 300 mg I ml-1 contrast medium. Conventional HOCM (1500 mosmol kg-1 water) has been completely displaced for peripheral arteriography by LOCM (600–700 mosmol kg-1 water), because the latter causes much less warmth, discomfort, pain and movement. LOCM permits almost painless angiography in all territories, usually eliminating discomfort, movement and the need for general anaesthesia.

Peripheral Venography

• Venography of the leg for possible deep vein thrombosis (DVT) is the most frequent venographic study. The procedure is performed by injecting RCM into a small vein of the foot, with the leg dependent and tourniquets restricting peripheral venous return. If the deep veins are already compromised and partly thrombosed, peripheral venography of the leg is a potentially dangerous procedure, as both deep and superficial venous return from the leg are compromised, and some cases of venous gangrene due to venous endothelial damage and thrombosis have been induced by attempted venography.

• LOCM is strongly advised because of its lower osmolality and its less irritant effect on the venous endothelium. Endothelial contact time should be reduced to the minimum by washing out with saline, massaging and exercising the leg immediately after satisfactory radiographs have been obtained. Termination of the injection of contrast medium must be seriously considered if the injection causes pain or if the deep veins are seen to be extensively thrombosed, for all RCM may induce thrombophlebitis.

Cardiac and Coronary Angiography

• Intracardiac injections LOCM injections are much preferred as they cause less disturbance of cardiac function, depression of myocardial contractility, peripheral vasodilatation, hypervolaemia, systemic hypotension and ECG changes. They are also much better tolerated subjectively than HOCM.

• Pulmonary angiography LOCM injections should be used for pulmonary angiography as they cause less elevation of the pulmonary artery pressure, coughing, movement and discomfort. Separate unilateral pulmonary artery injections should replace main stem pulmonary artery injection.

• Aortography Injections of LOCM at the 300–400 mg ml-1 iodine concentration are greatly preferred as they cause much less discomfort and vasodilatation.

• Coronary angiography HOCMs (e.g. Urografin 76 per cent) with physiological levels of sodium and which do not bind avidly to serum calcium (related to buffer agents) had a good reputation for selective coronary angiography, but LOCMs are even safer for they cause less marked haemodynamic, myocardial and physiological changes and depression

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