Iodinated contrast media

Last revised by Russell Hutson on 22 Jun 2023

Iodinated contrast media are contrast agents that contain iodine atoms used for x-ray-based imaging modalities such as computed tomography (CT). They can also be used in fluoroscopy, angiography and venography, and even occasionally, plain radiography. Although the intravenous route of administration is most common, they are also administered by many other routes, including gastrointestinal (oral, rectal), cystourethral, vaginal, intraosseous, etc.

The ability to distinguish between tissues of different x-ray attenuation (image contrast) depends upon two types of interactions between photons and matter: Compton scattering and photoelectric absorption. Both these interactions depend upon physical density, but the latter also depends upon atomic number of the matter. As iodine has a high atomic number, 53, compared to most tissues in the body, the administration of iodinated material produces image contrast due to differential photoelectric absorption.

Iodine has a particular advantage as a contrast agent because the k-shell binding energy (k-edge) is 33.2 keV, similar to the average energy of x-rays used in diagnostic radiography 1. When the incident x-ray energy is closer to the k-edge of the atom it encounters, photoelectric absorption is more likely to occur.

Differences in photoelectric absorption across different x-ray energies is harnessed in dual-energy CT, in which patients are scanned with two different x-ray spectra. Material decomposition techniques allows the creation of virtual images in which iodine is preferentially increased in intensity (iodine map) or removed altogether (virtual non-contrast), which can hold additional diagnostic value.

Water-soluble iodinated contrast media is usefully classified by osmolality:

High osmolality contrast media (HOCM) are approximately five to eight times the osmolality of serum. In general, HOCM are ionic compounds that include a benzene ring with three iodine atoms and a side chain containing a carboxylic acid (-COOH) group. As the first generation of iodinated contrast agents, HOCM were associated with high rates of adverse events and fell out of favor in the 1990s for intravascular and intrathecal purposes. HOCM remain used for gastrointestinal and cystourethral administration, including the following agents:

  • diatrizoate sodium/meglumine (Gastrografin, MD-Gastroview, Cystografin)

  • iothalamate sodium/meglumine (Conray, Cysto-Conray)

Low osmolality contrast media (LOCM) are less than three times the osmolality of human serum and preferred for intravascular and intrathecal administration. Modern LOCM are generally, but not always, nonionic monomers composed of tri-iodinated benzene rings with various side chains that contain polar alcohol (-OH) groups that make them water-soluble 3. LOCM in current use include the following:

  • iopamidol (Isovue)

  • iohexol (Omnipaque)

  • iopromide (Ultravist)

  • ioversol (Optiray)

  • ioxilan (Oxilan)

The LOCM category also includes iso-osmolality contrast media (IOCM), which are approximately the same osmolality as serum. The only IOCM in current use is a non-ionic dimer, which is composed of two covalently bound tri-iodinated benzene rings:

  • iodixanol (Visipaque)

The dimer structure of iodixanol fits a higher concentration of iodine atoms per osmole, permitting diagnostic levels of contrast opacification at less toxic osmolality.

Non-ionic LOCM are available in varying concentrations ranging from 240 to 400 mg iodine/mL. Higher concentration formulations produce a greater peak of enhancement (measured in Hounsfield units) but are also more viscous.

Water-insoluble iodinated contrast media have limited uses.
The only currently approved agent is:

A historically-popular but now discontinued water-insoluble iodinated agent was iophendylate (Pantopaque/Myodil), which was used for myelography.

Contrast injected intravenously is often mechanical via a computerized pressure injector. The American College of Radiology recommends a cannula of 20-gauge or larger for the mechanical injection of intravenous contrast for any injections that require a flow rate higher than 3 mL/s 6.

The prewarming of contrast agents, particular ones of higher concentration (370 mg/mL) has been found to lower the chances of contrast extravasation 5.

In the context of the critically ill patient where intravenous access is not possible, iodinated contrast can be administered via an intraosseous injection. Pressure rates must be high due to the intramedullary pressure within the bone. According to the ACR Committee on Drugs and Contrast Media, there are no reported complications of intraosseous injections at 5 mL/s 6. The humerus is the most commonly accepted site of injection 7,8.

Allergic-like reactions to iodinated contrast agents are rare, accounting for 0.6% of cases with only 0.04% considered severe 9. Patients who suffer from allergic reactions to shellfish or topical iodine are not at any higher risk of contrast allergy than patients with any other allergy or asthma, which is only slightly elevated 10-12.

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Cases and figures

  • Figure 1: iodinated contrast
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