Part 1: L2, Angiographic Contrast Agents

Question 1

Why are imaging agents necessary? How do they typically interact with the body?

Answer 1

• Trying to image areas of interest that do not have good contrast i.e. differential tissue density or elemental composition
• ‘Drug’ enhances image to elucidate disease or abnormal pathology -> interacts with spectroscopic technique being used
• Usually, these agents are not target specific, but affect the entire body (thus the high dosage)

Question 2

Contrast agent requirements:

Answer 2

• Must enhance the contrast of the imaging tecnhique
• Must be essentially non-toxic, with minimal side effects
• Must be readily removed from body following injection (renal/hepatic/lymphatic systems)
• Must not soluble in aqueous solution if it is to be injected intravenously - also, ionic in nature and of appropriate viscosity
• Must not leach into cells (reduced lipophilicity) to avoid prolonged retention and reducing the contrast enhancement of various tissues

Question 3

Early barium contrast agents:

Answer 3

• Used to image gastrointestinal system
• Insoluble so used as a milled suspension in water
• Often there is a thickening agent that coats the intestine (such as carboxymethyl cellulose)
• pH adjusted to 5.3 to ensure the stomach pH does not affect it too much
• Barium can also be used to coat the colon in a barium enema -> technique replaced by endoscopy

Question 4

Modern contrast agents:

Answer 4

• Iondinated e.g. iodixanol, iohexol, iopamidol
• Extremely high volumes (~300 mg iodine / mL)
• Iodinated can be….Water insoluble, oily contrast media or water-soluble

Question 5

Oily contrast media:

Answer 5

• Historically, lipiodol
• A stable compound of 40% iodine in poppy seed oil, introduced in 1920s
• These oils are still to some extent used for lymphography, and also for hysterosalpingography
• Myelography -> imaging spinal nerves by injecting spinal canal

Question 6

Water soluble iodinated contrast agents:

Answer 6

• Largest group
• Early: monoiodinated pyridine derivatives
• Soon followed by di-iodinated pyridones with higher solubility
• By 1950s, tri-iodinated agents were in use -> monomeric agents for oral and cholegraphic media, uro/angiographic media
• The cations of the salt are usually either sodium, meglumine or both (sodium can upset the balance existing in the body -> mixture has lower cardiotoxicity than either alone
• Dissociate in aqueous solution -> ratio 1.5 agents (3 iodine atoms per 2 parts) -> osmolality issue

Question 7

Osmolality description:

Answer 7

• biological membranes are semi permeable and allow water and small molecules to pass freely; osmosis
• The force exerted is called osmotic pressure; determined solely by concentration of dissolved particles

Question 8

Definition of osmolality vs osmolarity:

Answer 8

• Osmolality: Concentration of particles per unit mass of solvent
• Osmolarity: Concentration of particles per unit volume of solvent

Question 9

Biological implications of osmolality? Give the possible clinically significant effects:

Answer 9

• Closer the osmolality of the radiological contrast media is to that of body fluids, the better to general tolerance
• Osmolality of blood and cerebrospinal fluid is 290 mOsm/kg (most agents in use are well in excess of this by 7-8x)
• Responsible for sensations of heat/discomfort/pain
• Clinically significant effects: damage to BBB, renal damage, electrolyte balance in small children, thrombosis and thrombophlebitis

Question 10

Monomeric non-ionic contrast:

Answer 10

• Low osmolality contrast media has substantially reduced side effects
• Early example: metrizamide (Analogue of sugar)
• Used for uro/angiography