CONTRAST AGENTS- RADIOLOGICAL,CT, US & MRI.

Contrast media is a substance used to enhance the contrast of structures or fluids within the body.  It is commonly used to enhance the visibility of blood vessels and the gastrointestinal tract.

WHY CONTRAST MEDIAS ARE REQUIRED?

Different tissues within the body attenuate the beam of X-rays to different degrees.The degree of attenuation of an X-ray beam by an element is complex, but one of the major variables is the number of electrons in the path of the beam with which it can interact. The number of electrons in the path of the beam is dependent upon three factors:

• The thickness of the substance being studied• Its density• its atomic number

There is a difference between the average atomic numbers of two tissues, such as between soft tissues, which are composed of elements of low atomic number, and bone, which is partly composed of the element calcium, with a rather higher atomic number, then the outlines of the different structures can be seen by natural contrast.

However, 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.

Two of the factors important in organ contrast can be artificially altered, the density of an organ, and, more usefully, the average atomic number of a structure. The density of a hollow organ can be reduced by filling it with gas or air, providing negative contrast.

The average atomic number of hollow structure such as a blood vessel can be increased by filling the cavity with a liquid of much higher average atomic number (such as iodine containing contrast medium) than that of blood. In fact this is the principle by which contrast media consist of solutions or suspensions of non-toxic substances that contain a significant proportion of elements of high atomic number, usually iodine.

History 1. Opacification of urinary tract by excretion in 1923 by

osborn et. al. using sodium Iodide solution.

2. To detoxify the Iodine, Benz K Rath synthesized a number of pyridine rings containing Iodine, e.g. selectan neutral.

3. 1928-29: First proper IVU done with uroselectan (mono-iodinated compound) by Moses Swick . Di-iodinated compounds uroselectan B and Diodone were developed

4. 1948: CM with biliary excretion ( cholegraphic CM) found; devised by Bang & George.

5. 1952 : First triiodinated compound sodium acetrizoate ( urokon) was introduced. Precursor of all modern CM.

6. 1955: Diatrizoate synthesized ( urograffin, Hypaque)

7. 1962: Iothalamate synthesized ( conray)

8. 1972: Iocarmate ( First dimeric CM)

Iodine is the only element which has proved satisfactory for general use as an intravascular contrast media.

Benzene ring derivatives with 3 atoms of Iodine and 6 atoms of carbon per molecule of ring anion

Highly hydrophilic

Low lipid solubility

↓ toxicity

low binding affinities for protein receptors or membranes

molecular weight less than 2000.

Low antigenecity

Ideal Characteristics of Water Soluble CM

Relatively safeK edge(sudden increase in attenuation coefficient of photon occuring at a photon energy just above the binding energy of the K shell elecgtron) 32 keV. i.e. close to mean energy of diagnostic x-ray. Disadvantages:-

Hydrophilic Some of it may split as free iodide leading

to thyroid problems

IODINE

Composition: CM solution (in the vial ) contains:

Iodine : Provides radioopacity Others : ▪ Carriers of I

▪ ↑solubility ▪ ↓toxicity

Additives: Buffers stabilizes the solution Chelating agents e.g .EDTA

PHARMACOLOGY OF CONTRAST AGENTS

All intravascular iodinated contrast agents are based on a tri-iodinated benzene ring. Three primary forms exist:

1) High-osmolar contrast media (HOCM) are the oldest agents. They are relatively

inexpensive, but their utility is limited. They are monomers (single benzene ring) or dimers that ionize in solution with a valence of -1. Their cation is either sodium or meglumine.

IONIC MONOMER:

In CM molecule for 3 Iodine particles there are two particles ( cation and anion) in the solution.Iodine particle ratio: 3:2.

Examples : Meglumine IothalamateSodium IothalamateMeglumine ditrizoateSodium ditrizoate

LAI BHARI FIG 1

Advantages: - Iodine: Particles :: 6:2 - ↓ Osmolality for desired Iodine concentration

Disadvantages:- - ↑ molecule size ↑ viscosity - CM is still ionic Examples:- Ioxaglate

IONIC DIMER

Monomers that dissolve in water but do not dissociate. Iodine: Particle ratio is 3:1 To reduce lipophilicity, amide (-CONH) groups are incorporated in1, 3, 5 positions

Advantages:- No ionisation,

Examples:- - Iomeprol ( Iomeron) (350mgI/ml)- Iohexol ( Omnipaque)- Iopamidol ( Niopam)- Iopromide ( Ultravist)

2) low-osmolar contrast media (LOCM).

LAI BHARI FIG 2

3) Iso-osmolar contrast media (IOCM)

Dimers that consist of a molecule with two benzene rings (again, each with 3 iodine atoms) that does not dissociate in water (nonionic).

LAI BHARI FIG 3

NON IONIC DIMERExamples: Iodixanol 30 (visipaque) Iotrolan ( Isovist)Advantages: Iodine: particle:: 6:1.

Now the best tolerated CM.Disadvantages : Cost Viscosity (larger molecules at room temp.)

Additional modifications that have reduced toxicity include the following:

Adding calcium ions (reduces cardiac toxicity), Establishing a neutral pH (low pH predisposes to vasodilatation), and Altering number and distribution of –OH ions (decreases neural toxicity).

PROPERTIES OF CONTRAST MEDIA:

Viscosity:The viscosity of a liquid is assessed by measuring its rate of flow through a standard thin capilliary tube.The practical importance of viscosity of a contrast medium relates chiefly to the force that is required to inject it through a needle into a patient.

Osmolality:The osmotic pressure of a solution being simply a function of the concentration of particles within it, can be expressed in terms of its concentration of particles (osmoles) per unit weight (kilograms) of solvent. Clinically significant effects that can be attributed to the osmolality problem include damage to the blood-brain barrier, renal damage and disturbance or electrolyte balance.

Chemotoxicity

1. Hydrophilicity.2. Lipophilicity: correlates with the toxicity.3. Protein binding: causes nephrotoxicity.4. Histamine release: produces allergic reactions.

CATEGORIZING CONTRAST REACTIONS

A. According to severity:Mild ModerateSevereDelayed reactions

B. MECHANISM 1)Anaphylactoid. 2)Nonanaphylactoid Chemotoxic – organ-specific Vasovagal Nephrotoxicity Cardiovascular toxicity Neurotoxicity

Mild

Signs and symptoms appear self-limited without evidence of progression

Nausea, vomiting Altered taste, Sweating Cough Itching, Rash, hives Warmth (heat), Pallor, Nasal stuffiness Headache, Flushing, Swelling of eyes and face Dizziness Chills Anxiety Shaking

Treatment: Observation and reassurance. Usually no intervention or medication is required

Moderate

Reactions which require treatment but are not immediately life-threatening:

Tachycardia/bradycardia Hypotension Bronchospasm, wheezing Hypertension Dyspnea Laryngeal edema Pronounced cutaneous Reaction.Pulmonary edema Treatment: Prompt treatment with close observation

Severe

Life-threatening with more severe signs or symptoms including:

Laryngeal edema Profound hypotension Unresponsiveness (severe or progressive) Convulsions Cardiopulmonary arrest arrhythmias

Treatment: Immediate treatment. Usually requires hospitalization.

Delayed Contrast Reactions

Delayed contrast reactions can occur anywhere from 3 hours to 7 days following the administration of contrast.

With the exception of contrast-induced nephropathy, the more common reactions include a cutaneous xanthem, pruritis without urticaria, nausea, vomiting, drowsiness, and headache.

These delayed reactions are T-cell mediated. As such, prophylaxis with oral corticosteroids may not be useful.

Anaphylactoid reactions

are identical to anaphylactic reactions in their manifestations, but they are not initiated by an allergen-IgE complex. Acute contrast reactions are included in this group.

The distinction between anaphylactic and anaphylactoid reactions is subtle, but it has certain important implications for the use of iodinated contrast:

1.A reaction can occur even the first time contrast is administered.

2.The severity of a reaction is not dose-related; therefore a test dose is of no value.

3. The occurrence of a contrast reaction does not necessarily mean that it will occur again (although the risk is greater that it may).

4. Even though the circulating contrast is systemic, the nature of the response is variable. More than one type of reaction may occur simultaneously.

Certain risk factors

Allergic asthma

Drug allergies

Food allergies

Prior reactions to contrast

Patients who are at increased risk for an anaphylactoid reaction benefit from premedication.

Methylprednisolone:

32 mg by mouth 12 and 2 hours before contrast.

Diphenhydramine

50 mg IM or PO 1 hour before contrast.

NON ANAPHYLACTOID CHEMOTOXIC EFFECTS:

NEPHROTOXICITY

Mechanisms:

---Vascular effect: increase in intrarenal pressure due to hyperosmotic effect.

---Tubular injury.

And ---Tubular obstruction due to precipitation of Bence-Jones proteins

risk factors : 1. Age > 65 years 2. Diabetes3. Receiving chemotherapy 4. Diagnosis of a collagen vascular disease 5. Multiple myeloma6. History of a kidney transplant, renal tumor, renal surgery, or single kidney 7. History of endstage liver disease 8. History of severe congestive heart failure

Contrast induced renal failure:

Definition: Unexplained ↑creatinine level>25% within 3 days of contrast

In diabetics on metformin:

Metformin should be withheld at the time iodinated contrast is used.

It may be resumed in 48 hours only if renal function is shown to be normal.

CARDIOVASCULAR TOXICITY

Mechanism

Conducting system:Ionic agents causes electrical changes producing – arrhythmia

Pumping action: - ↓availability of Ca+2 for contraction-

↓cardiac contractility

- Volume over load by HOCM agents- heart failure

- Deformed RBC by HOCM - ↑ pressure overload

- viscous sticky CM- ↑ pressure overload

NEUROTOXICITY

Iodinated contrast agents cause a change in the blood-brain barrier due to their hypertonicity. These risks are reduced when low or iso-osmolar agents are used.

Potential reactions include headache, confusion, seizures, altered consciousness, visual disturbances, and dizziness. VASOVAGAL REACTIONS

Vasovagal reactions are characterized by bradycardia and hypotension.

Simple guidelines for first line treatment of acute reactions to contrast media

Urticaria: H1 antihistaminic intramuscularly.

Bronchospasm: 1. Oxygen by mask (6-10 l/min)2. β-2-agonist metered dose inhaler (2-3 deep inhalations)3. AdrenalineIntramuscular: 1:1,000, 0.1-0.3 ml (0.1-0.3 mg)In pediatric patients: 0.01 mg/kg up to 0.3 mg max.

Laryngeal edema1. Oxygen by mask (6 – 10 l/min)2. Intramuscular adrenaline (1:1,000), 0.5 ml

Hypotension

1. Elevate patient’s legs2. Oxygen by mask (6-10 l/min)3. Intravenous fluid: rapidly, normal saline or Ringer lactate solution.

add 4. Atrophine 0.6-1.0 mg intravenously in vasovagal hypotension.

Generalized anaphylactoid reaction

1. Call for resuscitation team2. Suction airway as required3. Elevate patient’s legs if hypotensive4. Oxygen by mask (6 – 10 l/min)

5. Intramuscular adrenaline (1:1,000), 0.5 ml (0.5 mg) in adults. In pediatric patients 0.01 mg/kg to 0.3 mg (max. dose)6. Intravenous fluids (e.g. normal saline, lactated Ringer’s)7. H1-blocker e.g. diphenhydramine 25-50 mg intravenously

1. Angiography2. Intravenous urography (IVU), 3. Myelography4. Computed tomography (CT)

Radiological examinations that involve the use of contrast media.

Angiography

The term angiography is strictly defined as based on projectional radiography ; however, the term has been applied to newer vascular imaging techniques such as CT and MR angiography.

 For all structures except the heart, the images are usually taken using a technique called digital subtraction angiography (DSA). Images in this case are usually taken at 2 - 3 frames per second. This technique "subtracts" the bones and other organs so only the vessels filled with contrast agent can be seen. The heart images are taken at 15-30 frames per second, not using a subtraction technique. Because DSA requires the patient to remain motionless, it cannot be used on the heart.

Localised narrowing or obstruction of an artery or a pathological circulation in a tumour can then be identified.

Arteriography

In arteriography a contrast medium is introduced via a catheter into an artery, which makes the lumen of that vessel opaque to X-rays. The natural flow of blood carries the contrast medium peripherally, and by taking a series of radiographs a road map of the blood supply to an organ, or a limb can be made.

LOCM are preferred over HOCM ( meglumine salts are preferred )In DSA 200mg/ml for internal carotid & vertebral arteries 300mg/ml for common carotid & AVM.

6-8 ml of CM at a rate of 3-4ml/s.

Adverse reactionsDilatation of external carotid artery causes pain & heatBradycardiaHypotensionDamage to the BBB may cause cerebral edema

CEREBRAL ANGIOGRAPHY

 X-ray images of the transient radiocontrast distribution within the blood flowing within the coronary arteries allows visualization of the size of the artery openings.

Non ionic LOCM is used: dose 3-5ml

LOCM cases less disturbances of: ▪ cardiac function

▪ myocardial contractility

▪ peripheral vasodilatation

▪ systemic hypotension

▪ conductive ECG changes than HOCM

CORONARY ANGIOGRAPHY

300mgI/ml required for conventional film screen angiography

Non ionic LOCM causes less warmth, discomfort pain & undesirable movements

For DSA- 200mgI/ml i.e. 6-8 ml CM.

PERIPHERAL ARTERIOGRAPHY:

It is the Gold standard for diagnosing acute deep venous thrombosis.Venography can also be used to distinguish blood clots from obstructions in the veins, to evaluate congenital vein problems, to see how the deep leg vein valves are working, or to identify a vein for arterial bypass grafting.

Only non Ionic LOCM is used

60-100ml of CM used approx . 250mgI/ml

Complications:-Extravasations of CM-chemical cellulitis ulceration, gangrene.

Post venography thrombosis:Prevented by flushing of CM from vein bysaline bolus after the procedure.

PERIPHERAL VENOGRAPHY

The main indication is to assess the morphology of the kidneys.Further indications are: detection of kidney stones and calcifications in the ureter or bladder, assessment of obstructed urinary flow and investigation of patients with haematuria and congenital abnormalities of the urinary tract.

More than 95% CM is excreted by the kidneys, 30% in first 1 hr ,75% in 6 hrs, totally from body within 2 days.

CM is excreted by glomerular filtration, easily filtered by glomerulous and not bound to protein.

Concentrated in the tubules reaches about 100 times.

No tubular reabsorption.

Choice of CM: Non ionic LOCMDose:: 300mgI/kg BW (1ml/kg BW).

INTRAVENOUS UROGRAPHY

The majority ofmyelograms were performed to examine the lumbar region to confirm the clinicalsuspicion of a prolapsed intervertebral disc.

MYELOGRAPHY

Until late 1970s – ▪ Iophendylate oil ( Myodil/ pantopaque) ▪ Air/ carbondioxide

HOCM were used but toxic to subarachnoid space

Now Non ionic LOCM -Iohexol, Iopamidol, Iotrolan are contrast agents of choice.

Max dose 300mgI/ml upto 3 gm of I.

Adverse effect: ▪ Ch. Arachnoiditis ▪ Pain, disability ▪ Compression of lumbosacral nerve roots.

a. Water solubleb. Relatively safec. Particle size-

- Upto several millimeters- 50% size between- 5-15 µm- Rate of sedimentation directly proportional to

particle sized. Ph – 5.3 ↓ pH- ↑ sedimentation in stomache. Palatability- Chalky tastef. Viscosity- 15-20 pacs

CONTRAST FOR GI STUDIES

BARIUM SULPHATE

Indication:- Upper & lower GI studiesBa swallow- 100% W/V ( thin Ba)Ba meal- 120ml 250% W/V ( high density Ba) For DC 400ml of CO2Ba- enema - 500ml 100% W/V

Contraindication:-Chance of aspirationPerforation:

PeritonitisFibrosisGranuloma formation

Water soluble Iodinated contrast media (Diatrizoate)

Indication:- Perforation/leakage of anastomosis

Advantage:- Easily absorbed by lung, peritoneal cavity

Disadvantages:-

Low radioopacity ↑ osmolality- ↑ hygroscopic effect- ↑ dilutionChance of aspiration

GASTROGRAFFIN

ULTRASOUND CONTRAST MEDIA

INTRODUCTION

• Development of USCA has resulted in significant extension of clinical application of ultrasound in both vascular and parenchymal imaging

• USCA are exogenous substances which when injected into the blood pool or a cavity enhance contrast between normal and abnormal tissue and augment the doppler signal

• Gramiak and Shah first used agitated saline for echocardiography in 1969

MECHANISM OF ACTION

• Increase in back scatter intensity increases the level of signal upto 25-30dB (300 times)

• At high acoustic power (> 100kpa), complex non-linear

interactions occur due to unequality of the compressibility of microbubbles generating harmonic signals.

Mechanical index (MI)Defined as peak negative ultrasound pressure. Reflect the normalized energy to which a target (bubble) is exposed.Varies with the depth in image (i.e. lessen with increase in depth)

Enhancement of signal occurs due to :Reflection / asymmetric vibration – Low mechanical index is used, avoids bubble disruption, used for vascular imaging.

Disruption of microbubbles – High MI is used for parenchymal imaging.

IDEAL USCA

• Should enhance B Mode and all Doppler modes.

• High stability in vascular bed to withstand shear forces and pressure changes.

• Useful half-life to allow complete examination without need for a second injection.

• Injectable I/V , non-toxic with no adverse effects

• Capable of crossing pulmonary bed after peripheral injection.

Microbubbles Gas Stabilization shell

First generationAgitated salineEchovist

AirAir

NoneNone

Second GenerationLevovist (SHU 508A)(Schering)Albunex

Air

Air

Microcrystalline galactose+Palmitic acidSonicated albumin

CLASSIFICATION OF ULTRASOUND MICROBUBBLES

Third generation Optison (FSO69) TycoEchogen (QW3600)QW 7437Sonovue (BRI) BraccoDefinity (DMP115)PESDAQuantisonImagent (AFO 150)

GasPerfluoropropaneDodecafluoropenatanePerfluorocarbonSulphur hexafluoridePerfluorobutanePerfluorobutaneAirPerflurohexane

StabilizationSonicated albuminLiquid droplet, surfactantLiquid droplet, surfactantPhospholipidsPhospholipidsSonicated albuminDried albuminSurfactants

Liver specific agentsLevovist (SHU508A)Sonavist(SHU563A)Sonazoid (NC100100)BR14

AirAirPerfluorocarbonPerfluorobutane

Palmitic acidCyanoacrylateNot public informationPhospholipids

UTILITY OF USCA

• Increases the diagnostic confidence.

•Superior to duplex doppler for detection and quantification of vascular stenosis.

• Improves neoplasm detection and characterization by studying tumor vascularity.

•Differentiate normal variants from a neoplasm.

APPLICATIONS OF USCA• Vascular imaging-carotid artery stenosis, renal

artery stenosis, PVD, echocardiography, graft

vessels.

• Parenchymal- liver, kidneys, myocardium,

prostate, breast, lymph nodes.

• Cavities- VUR, uterus and fallopian tubes

CAROTID ARTERY IMAGING

• The area stenosis on ultrasound angiography strongly correlated with that of conventional angiography (r=0.988)

• Ulcerations, dissection and wall irregularities were more clearly depicted on ultrasound angiography than on duplex ultrasound

• Contrast enhanced B mode images are more reproducible than Doppler images as they are not dependent on the angle of incidence and technical parameters for optimal filling of vessels.

RENAL ARTERY STENOSIS• Incidence - 1-5% of all hypertensives, 16-32% in

selected high risk group• Renal doppler scanning with USCA can be the

method of choice for scanning as well as follow up after PTA

ECHOCARDIOGRAPHY

• Ventricular Wall motion abnormalities are better depicted due to better delineation of endocardial borders.

• Assessment of LV volume, LVEF, thrombus detection.

• Assessing viability and diagnosis of infarction.

• Coronary artery stenosis.

PERIPHERAL VASCULAR DISEASE USCA improve imaging of lower limb occlusive

disease.

USCA IN HEPATIC IMAGING

Applications

•Neoplasm detection (metastasis) and characterization (Benign vs. malignant lesions) - HCC, FNH, HA, hemangioma

•Vessel evaluation ▫Portal hypertension ▫Budd Chiari Syndrome▫Liver transplant evaluation▫Evaluation of flow pattern and transit time to

diagnose cirrhosis

HEPATIC IMAGING

Arterial Portal Late vascular phase

Parenchymal phase

Fatty changes, skip areas of steatosis

Isoechoic Isoechoic Isoechoic Isoechoic

Hemangiomas Hyperechoic (peripheral nodular enhancement)

Centripetal filling Isoechoic if filling is complete (intralesional hypoechoic areas in 50%)

Isoechoic (intralesional hypoechoic areas in 50%)

Focal nodular hyperplasia

Hyperechoic Hyper-or isoechoic nonenhancing central scar in 45%

Hyper-or isoechoic noneenhancing central scar in 45%

Hyper-or isoechoic

Hepatocellular adenoma

Hyperechoic Isoechoic Isoechoic Isoechoic

Regenerating nodules

Iso-or hypoechoic Isoechoic Isoechoic Isoechoic

Metastases Hypo-or hyperechoic (hypervascular)

Hypoechoic with or without rim enhnacement

Hypoechoic Hypoechoic

Hepatocellular carcinoma

Hyperechoic Isoechoic Hypo-orisoechoic (30%)

Hypoechoic

Pulse inversion with contrast

spleen

RENAL IMAGING

• Small RCC (<3cm): USCA increased tumour

conspicuity and detection of concurrent lesions.

• Visualisation of intra tumoral vessles

• Pseudo mass – Focal mass vs column of Bertin

• Role in problematic cystic lesions.

• Renal transplant evaluation.

•Breast – Limited role to differentiate

benign vs

malignant tumours

_ May help differentiate scar from

recurrence

•Prostate – contrast enhanced 3D power

doppler may increase sensitivity for

detecting malignancies from 38 to 85%

BREAST AND PROSTATE IMAGING

VESICOURETERIC REFLUX

• Echoenhanced Ultrasound reduce the number of patients exposed to ionizing radiation

• Disadvantage being assessment of urethra is not possible

CONTRAST MEDIA IN MRI

• In cases where it is difficult to differentiate two types of tissue, because of similar signal intensities, contrast agents are used to differentiate them.

• Types:• According to chemical natures :• 1.

Paramagnetic agents 2. Magnetic iron

oxide

nanoparticles (MION)

Paramagnetic agents

• The basic action lies in the modification of local magnetic environment and shortening of proton relaxation times.

• Have at least one unpaired electron in the outer shell with a magnetic moment 1000 times greater than proton.

• The combination of motion & strong magnetic moment leads to rapid fluctuation of local magnetic fields and local shortening of relaxation times.

• Agents are: ▫ Gadolinium chelates, which are formed by the

chelation of gadolinium to organic ligands such as diethylene triamine penta acetic acid (DTPA).

Gadolinium• Lanthanide group of element• Molecular wt- 592.• Atomic no. -64• K- EDGE (KeV)- 50.2• Half life- 90 mins• Water soluble – highly hydrophilic• Non-radioactive• Low partition co-efficient

• Have seven unpaired electrons

• Forms a stable compound with DTPA

• Paramagnetic effect is highest of all elements

• Low dose causes much shortening of relaxation times & increases signal intensity

Pharmacokinetics After I.V. injection they circulate within the vascular

system and diffuse in the interstitial space ( except Blood Brain Barrier).

• Crosses abnormal blood brain barrier

• Activately taken up by hepatocytes

• Excreted unchanged in the urine

Mechanism• Due to paramagnetic action effectively reduces

both T1 & T2.

• T1 is always greater then T2 in all biological tissues.

• Absolute effect of T1 shortening is greater than T2.

• ↓ T1 causes increase in signal intensity.• ↓ T2 causes decrease in signal intensity

• At low concentration predominant effect is T1 shortening – increased signal intensity

• At high dose: Predominantly T2 shortening – reduces signal intensity

IN HEPATOBILIARY SYSTEM:

• Actively taken up by hepatocytes

• Remains prolonged time in the liver

• Provides image windows for delayed scans

• Increased flexibility in sequence selection

• Increased lesion to liver contrast.

• Dose:- 0.1 -0.3 mmol/kgBW eg: Gd-EOB DTPA Mn-DPDP SPIO

• Cautious use in:

-Allergy,Atopy,Asthma

-Severe anaemia,hypotension

-Cardiac arrythmia

-Severe Renal disease

-Pregnancy

-Lactation

MAGNETIC IRON OXIDE NANOPARTICLES (MIONS)

• Iron oxide based particles with covering of polysaccharides specifically targets RE cell & blood pool.

• Types SPIO (Superparamagnetic iron oxide)[Endorem] USPIO [Ferumoxtan]

Principles: - Actively taken up by RE cells - Has magnetic susceptibility - Magnetic field inhomogeneity -dephasing

of proton - ↓ T2 signal - Metastasis do not have RE cells- no

change in signal

intensity.

BLOOD POOL AGENTS

▫Stays intravascularly for prolonged times.▫Do not diffuse quickly in the interstitial space▫Attain steady state concentration within blood.▫Molecular wt ↑ 70,000.

Examples▫Gd labelled albumin▫Gd labelled dextran

NEPHROGENIC SYSTEMIC FIBROSIS

is a rare and serious syndrome that involves fibrosis of skin, joints, eyes, and internal organs. Its cause is not fully understood. However, there is much evidence to suggest that it is associated with exposure to gadolinium in patients with severe kidney failure.

Proinflammatory condition or event to include a broad group of entities in which the body has sustained major tissue injury through vascular complications (thromboembolic events), surgery, or systemic infection increases the incidence of NSF.

Patients develop large areas of hardened skin with fibrotic nodules and plaques. NSF may also cause joint contractures resulting in joint pain and limitation in range of motion. In its most severe form, NSF may cause severe systemic fibrosis affecting internal organs including the lungs, heart and liver.

At the microscopic level, NSF resembles scleromyxedema. Both conditions show a proliferation of dermal fibroblasts and dendritic cells, thickened collagen bundles, increased elastic fibers, and deposits of mucin . More recent case reports have described the presence of sclerotic bodies (also known as elastocollagenous balls) in skin biopsies from NSF patients.

Most patients with NSF have undergone hemodialysis for renal failure, some have never undergone dialysis and others have received only peritoneal dialysis. Four of the seven gadolinium contrast agents approved by the U.S. Food and Drug Administration have been principally implicated in NSF, including Omniscan, Multihance, Magnevist, and OptiMARK.

While skin involvement is on the foreground, the process may involve any organ and resembles diffuse scleroderma or systemic sclerosis. In 2006, the link between NSF and gadolinium-containing contrast agents was made. As a result, gadolinium-containing contrast is now considered contraindicated in patients with an estimated glomerular filtration rate (a measure of renal function) under 60 and especially under 30 ml/mn.

The European Medicines Agency has classified the gadolinium-containing contrast agents in three groups:

Least likely (safest) to release free gadolinium ions Gd3+ in the body have a cyclical structure: Dotarem (Gadoterate meglumine), Gadovist (Gadobutrol) and ProHance (Gadoteridol).

Intermediate have an ionic linear structure: Magnevist (Gadopentetate Dimeglumine), MultiHance, Primovist and Vasovist

Most likely to release Gd3+ have a linear non-ionic structure: Omniscan (Gadodiamide) and OptiMARK (Gadoversetamide).

Suggested Diagnostic Criteria to Make a Diagnosis of Nephrogenic Systemic Fibrosis (NSF)

Advanced Renal Failure• Chronic kidney disease and glomerular filtration rate<30mL/min• Acute renal insufficiency of any severity due to the hepatorenal syndrome or in the perioperative liver transplantation period.

Skin Lesions• Lesion distribution: mostly upper and lower extremities with involvement of trunk in a minority of cases.

• Lesion morphology: fixed plaques, induration; papules, nodules, erythema, and swelling may be also present

Other Signs and Symptoms

• Joint contractures (with reduced range of motion of fingers, wrists,elbows, ankles, and knees) • Pain• Itching • Burning sensation• Paresthesia • White-yellow scleral plaques with dilated capillary loops (patients <45 years old)

How to Minimize the Risk of NSF

Step 1: Identify patients at risk: ---those patients who have a GFR below 30 mL/min. --- patients with hepatorenal syndrome and those with reduced renal function who have had or are awaiting liver transplantation should be considered at risk of NSF if they have a GFR below 60 mL/min/1.

Step 2: Assess risk–benefit of contrast-enhanced MRI in the patient at risk.

Step 3: Perform any unenhanced MRI sequence that may be helpful before injecting the contrast agent.

Step 4: Do not expose at-risk patients to high doses of GBCA.

CONCLUSION

With advent of organic chemistry newer low & isoosmolar ionic contrast media there is reduction in incidence of contrast reactions. However knowledge and anticipation of anaphylactoid reactions and their management should be completely understood.

Contrast enhanced ultrasound have made possible to study and differentiate hepatic tumors and characterise vascular diseases. In future there will be role in chemotherapy, thrombolysis, liposomal drug and gene therapy.