X-Ray and CT contrast agents

X-Ray and CT contrast agents

1. XRAY AND CT CONTRAST AGENTS BY DRNISHANT RAJ POST GRADUATE RESIDENT DMIMS, WARDHA

2. DEFINITION Contrast media are substances used to highlight areas of the body in radiographic contrast to their surrounding tissues. 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.

3. TYPES OF CONTRAST Contrast media are divided into two main categories. The first is negative contrast media, Radiolucent Low atomic number, causing the part in which they are placed to be more readily penetrated by X-rays than the surrounding tissue; as they attenuate the X-ray beam less effectively than body tissue. Appear darker on the X-ray image. Gases are commonly used to produce negative contrast on radiographic images. The second type is positive contrast media Radio-opaque High atomic number, causing the part in which they are placed to be less readily penetrated by X-rays than the surrounding tissue. Consequently, this contrast agent-filled area appears denser than body tissue. Example: 1) Barium sulfate USE: GI Studies. 2) Iodine compounds: USE: angiography, intravenous and retrograde urography , hysterosalphingography , sialography myelography , cholangiography .

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

5. CLASSIFICATION

6. BARIUM SULPHATE Atomic number:56 Highly radiopaque Non absorbable. Non toxic. Insoluble in water/lipid. Inert to tissues. Can be used for double contrast studies. Route: Orally Or Rectally (aqueous suspension with 0.3 to 1 g dry weight per milliliter ) Uses: Barium swallow Barium meal Barium meal follow through Enteroclysis Barium enema

7. CONTRAINDICATION Integrity of gut wall compromised or GI Perforation. Previous allergic reactions to barium. Suspected fistula between oesophagus and lung.

8. WATER SOLUBLE IODINATED CONTRAST MEDIA Majority of I.V contrast media used in CT contain Iodine, It is preferred because: High contrast density due to high atomic number.(53) Low toxicity Allows firm binging to highly variable benzene ring. Radio-opacity 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 molecule to the number of osmotically active particles per molecule of solute in solution. Not used in MRI

9. WATER SOLUBLE IODINATED CONTRAST MEDIA Routes of Administration: Oral Rectal Intravenously Intravertebral Intrathecal ( iohexol ) & Intravesical

10. WATER SOLUBLE IODINATED CONTRAST MEDIA Basic building block is benzene ring with three iodine molecules attached at positions 2, 4, and 6. Side chains (at positions 3 and 5) are modified with hydroxyl groups or other molecules that further define an agent’s properties. Exist as monomers (one benzene ring) or dimers (two benzene rings). Three defining physical characteristics of iodinated contrast agents: ionicity, osmolality, and viscosity—play a distinct role in the tolerance and adverse reaction profiles.

11. IONICITY: IONIC VS NON-IONIC Ionic Dissolve into solution into anion and cation Usually have high osmolality Associated with more Adverse Effects Non-Ionic Dissolve into water; but do not dissociate Lower osmolality (fewer particles in a solution compared to ionic) Lower incidence of AEs – hydrophilic, reduced protein binding, low tendency to cross cell membranes

12. Osmolality In general, the higher the osmotic pressure the poorer the tolerance. Ionic contrast media undergo this dissociation, whilst newer, non-ionic contrast media do not. Osmolality is directly responsible for a number of clinically important effects Both the viscosity of a contrast medium and its osmolality are INVERSELY related to tolerance but directly to degree of opacification. With increasing strength of contrast medium, the opacifying power of the solution increases, but so, of course, do the osmolality and viscosity, while tolerance tends to decline.

13. VISCOSITY The practical importance of viscosity of a contrast medium relates chiefly to the force that is required to inject . Viscosity increases as concentration increases and tends to be higher for big size molecules. ( Dimers ). High viscosity interferes with mixing of contrast media with plasma and body fluids.

14. IODINATED CONTRAST MEDIA

15. IONIC MONOMER/CONVENTIONAL CONTRAST MEDIA Salts with sodium or meglumine (N- methylglucamine ) as the non- radiopaque cation and a radiopaque tri-iodinated fully substituted benzoic acid ring as the anion. Triiodinated at C2, C4 & C6 of benzene ring. Completely dissociates in water solution therefore provides 3 iodine atoms for two ions, giving iodine : particle ratio of 3:2 Hypertonic, 6-8 times higherosmolality (>1400mosm/kg) than human plasma. Examples: Diatrizoic Acid: Urograffin , Trazograff etc Iothalamic acid( Conray , Triovideo ) Replaced by non-ionic low osmolar contrast media

16. DISADVANTAGES OF HIGH OSMOLAR CONTRAST MEDIA Osmolar concentration is very high i.e upto 8 times of the physiological level. Osmolar challenge to every cell, tissue and fluid in the body is responsible for their adverse effects.

17. Low OSMOLAR CONTRAST MEDIA Ionic Dimer Non-Ionic Monomer Non-Ionic Dimer

18. Ionic DIMER Ioxaglate ( Hexabrix ) Only compound, mixture of sodium and meglumine salts . Two benzene rings (each with 3 iodine atoms) are linked by a bridge to form a large compound, carries only one carboxyl group, so known as monoacid dimers . Molecular weight is= 1269 Osmolality : 560 osmol/kg H2O Iodine Particle ratio is 6:2

19. Non-Ionic MONOMER Carboxyl group (-COOH) at C-1 is replaced by non ionising radical & CONH2 Iodine:Particle ratio is 3:1 Metrizamide ( Amipaque ) was the earliest non-ionic monomer and proved as an excellent contrast media but was very expensive, impossible to autoclave and unstable in solution. Osmolality is around 600 mosmols /kg Second Generation NIM are: Iohexol ( omnipaque ) Iopamidol ( Iopamiro ) Ioversol ( optiray ) Iopromide ( Ultravist )

20. Non-IONIC DIMER Each molecule contains 2 non ionising triiodinated benzene rings linked together Iodine:Particle ratio is 6:1 Molecular weight= 1550-1626 Osmolality is around 300 mosmols /kg Eg : Iotrol , Iotrolan ( Isovist )

21. ADDITIVES USED IN CONTRAST MEDIA Stabilizer: Ca or Na EDTA Buffers: Stabilizes pH during storage- Na Acid Phosphatases Preservatives.

22. PHYSIOLOGY of Water soluble iodinated contrast media Concentration and Excretion mainly via passive glomerular filtration. Net Tubular Excretion and protein binding is negligible in the dose used. Liver and Intestine excrete 1% of these compounds. Plasma life is 30-60 mins

23. IMPORTANT POINTS Contrast media used for myelography - non-ionic CM. CM used for cerebral angiography- only meglumine salt. Least osmolar - Ioxaglate ( Hexabrix ). Most hyperosmolar - Iohexol . Max nausea & vomiting- Ioxaglate ( Hexabrix ). Bronchospasm - Meglumine salts. Least viscosity- Omnipaque240 Meticulous heparinization is required during angiography as incidence of thromboembolic phenomenon is high when contrast is mixed with blood.

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