Contrast Media

CHAPTER 6


Contrast Media



CHAPTER OBJECTIVES


After completing this chapter, the reader will be able to perform the following:


image Identify the necessity for the use of contrast agents


image List the types of contrast agents that are currently available


image Describe the classes of contrast agents


image Describe the evolution of the organic iodine contrast media


image Define the characteristics of a good contrast agent


image Describe the excretory pathways of the various contrast agents


image Define informed consent as it applies to contrast media studies


image List and describe the general precautions that should be applied to every contrast medium study


image Identify the reactions and complications resulting from the use of contrast agents


image List the specialty contrast agents


All of the examinations designated as special or advanced procedures require the introduction of some type of material into the area of interest to provide contrast. This is necessary because the differences in density among the various tissues in the body are too small to provide adequate contrast for visualization of anatomic details. To compensate for this, it is necessary to increase or decrease the density of the organ to provide the desired contrast. Most of the studies in this text depend on the use of intravascular contrast agents to yield diagnostic information. The use of contrast media has increased with the increase in the use of computed tomography (CT), magnetic resonance imaging (MRI), and digital subtraction angiography (DSA).


Some of the familiar, so-called routine special procedures (e.g., barium enemas, excretory urograms) as well as the advanced procedures increase the subject density by the addition of a radiopaque substance that renders the organ radiopaque. In some cases, however, it may be undesirable to increase the density of an organ. In these situations, the density of the organ can be decreased by the addition of a radiolucent substance.


Unlike the pharmaceuticals discussed in Chapter 5, the amounts used are much greater than those used for therapeutic drugs. They are designed to remain in the organ of interest for a very short period of time and are not designed to cause any changes either biologically or chemically in the body.


Contrast agents can be classified into two broad groups, depending on their interaction with x-radiation—positive contrast agents (radiopaque) and negative contrast agents (radiolucent).



TYPES


Negative Contrast Agents


The absorption of x-rays by a substance is dependent upon several factors, one of which is the atomic weight of the substance. Those materials that have lower atomic weights will attenuate less radiation. The resultant remnant radiation will produce a greater radiographic density (darker image) on the image receptor. This characteristic is useful when the objective is to demonstrate an anatomic structure against the dark background or to provide a silhouette image of the structure.


Examples of radiolucent, or negative, contrast agents are air, oxygen, carbon dioxide, and nitrous oxide. Most of the available gasses have been used as negative contrast agents with varying results; however, the four gases listed here are the most commonly used negative (radiolucent) contrast agents. The negative contrast agents can also be used in conjunction with a positive contrast agent. One common procedure that uses this combination of contrast agents is the double contrast barium enema.


Air and oxygen may be dangerous during certain procedures because they can cause gas emboli, but carbon dioxide and nitrogen do not pose the risk of gas emboli and can be used with relative safety. They are also able to be absorbed rapidly by the body. This factor can be advantageous when rapid absorption is desired, but in cases in which many radiographs are taken, it is a definite disadvantage.



Positive Contrast Agents


Because of their high atomic numbers, positive contrast agents cause an increase in the attenuation of x-rays and are considered to be radiopaque. They produce an area of decreased radiographic density on the image receptor. Contrast agents that are radiopaque contain elements with high atomic numbers such as iodine, bromine, and barium. When these substances are used to fill organs, they essentially make the organ radiopaque, and the image appears clear or white on the radiograph. They can take the form of tablets, powders, and liquids and can be introduced into the body through a variety of routes. They are relatively nontoxic in most cases, but certain patients may exhibit reactions of varying severity, especially to agents containing iodine. In some cases, small doses of these agents may cause death.


The positive contrast agents used during the advanced procedures discussed in this text will be organic iodine compounds.



CLASSES OF RADIOPAQUE CONTRAST MEDIA


Contrast agents used for intravenous injections fall into one of two major classes: ionic and nonionic. The ionic compounds are further subdivided into high osmolality ionic compounds (HOCA) and low osmolality ionic compounds (LOCA). All of the positive contrast agents used for intravenous injection are organic iodine compounds that use iodine as the substance that provides the contrast.


Osmolarity and osmolality were discussed in Chapter 5. The blood-brain barrier separates the parenchyma (organ tissue) of the central nervous system from the blood, preventing or slowing the passage of potentially harmful substances from the blood into the tissue of the central nervous system. The hyperosmolality of the ionic organic iodine contrast agents is at the root of many of the major reactions that occur during radiographic procedures. One example of such a reaction is the degradation of the ionic contrast agents into electrically charged particles that can potentially disrupt the heart’s electrical activity, thereby increasing the risks for arrhythmia.


It has been demonstrated that the nonionic contrast agents produce fewer adverse drug reactions. This has been attributed to the osmolality of the material. The ionic compounds have a greater tendency to pass the blood-brain barrier owing to their hyperosmolality. The following list provides the osmolalities of the various types of organic iodine contrast agents and both plasma and cerebrospinal fluid:

























Agent Osmolality
High osmolality ionic compounds 1800–2100 mOsm/kg water
Low osmolality ionic compounds 600–850 mOsm/kg water
Nonionic compounds 300–484 mOsm/kg water
Plasma 280–295 mOsm/kg water
Cerebrospinal fluid 301 mOsm/kg water


As evidenced from the list of osmolalities, the ionic compounds have two to seven times the osmolality of the cerebrospinal fluid and the blood, creating an increased potential for reactions to these agents.


The nonionic compounds have demonstrated clinically a marked reduction in adverse drug reactions relating to their use in special procedures. Another feature of this type of contrast agent is that patients are much more comfortable during the study. Also, there are fewer subjective side effects. This has the combined effect of producing less anxiety in the patient, and psychogenic responses are less likely to occur. Because the nonionic contrast media are less apt to damage the blood-brain barrier, they demonstrate a very low neurotoxicity. The nonionic agents also exhibit a high compatibility with other intravascular medications used during angiography and the treatment of allergic reactions.


This would lead one to think that it would be advantageous to use nonionic contrast agents exclusively in radiography. Adopting a policy of this nature would be easy from a medical standpoint, but there are economic considerations that make the decision difficult. The cost of the nonionic contrast agents is somewhat greater than that of ionic agents. At the present time, the ionic contrast agents are still used; however, the nonionic or low osmolality contrast media have become the primary type of agent used in the diagnostic and interventional arena. Most institutions screen their patients for a variety of risk factors, and based on this information the radiologist will select the dose and type of contrast media to be used. Depending upon the results of the screening process, it is possible to reduce the use of the low osmolality contrast media. In some institutions the use of nonionic contrast media is restricted to high-risk patients or individuals in which the history identifies a high potential for reaction. This type of protocol can result in a substantial economic saving without a corresponding increase in moderate or severe reactions. Almost all of the institutions performing angiographic studies are using the nonionic contrast agents exclusively despite the drawbacks of cost and lack of adequate reimbursement. The American College of Radiology has developed guidelines for the use of the low osmolality and nonionic contrast media.1



Evolution of the Organic Iodine Class of Contrast Media


Ionic Organic Iodine Compounds


The ionic contrast agents used for vascular studies are salts of organic iodine compounds such as benzene. The basic configuration can be drawn as a six-sided ring structure (Fig. 6-1, A). The locations marked 1 through 6 on the illustration represent places where chemical structures can be attached. Figure 6-1, B, shows the placement of the iodine atoms on the molecule. The addition of iodine atoms in the 2, 4, and 6 positions and the conversion of the acid molecule (COOH) to a salt (Fig. 6-1, C) are the basis for the organic iodine compounds used today. The locations marked with the letter “R” are the sites used to place various side chains. The side chains initially were amino groups that helped to decrease the toxicity of the compound.


image
FIGURE 6-1 Basic foundation structure of the organic iodine compounds. A, Basic ring structure with the positions 1 through 6 marked. B, Basic structure with iodine atoms added to the 2, 4, and 6 positions. The COOH structure designates this as an acid. R indicates positions where side chain molecules are attached. C, Schematic illustration of the material as a salt, showing the cation and anion.

The anions of the common angiographic contrast media begin as organic benzoic acid compounds. The different angiographic contrast agents have the same basic ring structure but can differ in the side chains located at the 3 and 5 position (Fig. 6-2). Different side chains are used to improve solubility and tolerance to the material. The anions are combined with a cation to form a salt (Fig. 6-3). The major cations used to form the compound can be either sodium or meglumine (n-methylglucamine). Each of these salts has different characteristics and will affect the patient differently.


image
FIGURE 6-2 Basic structure of the anions of the organic iodine compounds used during angiography. The three side chains, diatrizoate (a), iothalamate (b), and metrizoate (c), can be substituted in the block marked X on the basic structure to form the different compounds.

image
FIGURE 6-3 Basic structure combined with the anionic side chains and cations to form an organic iodine compound.

When injected into the patient, the ionic organic iodine compounds disassociate to form two particles: an anion (negatively charged) and a cation (positively charged). These conventional contrast agents are considered to be 3:2 compounds; that is, they deliver three atoms of iodine for contrast to two particles to provide osmolality.


Experimental results have shown that the meglumine salts are less toxic than the sodium salts of the organic iodine contrast agents. However, the sodium salts are less viscous than solutions of the meglumine salts with the same iodine content.


The ionic contrast agents currently available for angiographic use are either meglumine salts or combinations of meglumine and sodium salts. The toxicity of the low-viscosity, sodium salt contrast agents can be reduced somewhat by the addition of calcium and magnesium to the solution.



Nonionic Contrast Agents


These substances were developed because the high osmolality of the ionic contrast agents was thought to be responsible for the majority of the undesirable side effects. The basic structure of the nonionic compounds is the same as that of the conventional agents. However, the various side chains added to the basic building block create a substance that does not disassociate (i.e., separate into an anion and a cation) (Fig. 6-4). They are considered to be 3:1 compounds—they contribute three iodine particles in solution to provide contrast and only one particle to provide osmolality. The ionic compounds are 3:2 in that they also contribute three iodine particles for contrast and two particles for osmolality.


image
FIGURE 6-4 Chemical structure of iohexol (Omnipaque), an example of a nonionic contrast agent from Nycomed.

Osmolality depends on the number of particles in solution. The nonionic compounds exhibit less osmolality than conventional ionic contrast agents because they provide fewer osmotically active particles. This results in fewer patient reactions.


Although their chemical structure differs, nonionic contrast agents are as effective as ionic agents in providing the necessary contrast during special procedure radiography. Their main advantage is in the reduction of both subjective and objective side effects in the patient.



Low Osmolality Ionic Contrast Agents


This type of contrast agent overlaps characteristics of the two previously mentioned types of substances; the compound uses the same basic building block but forms what is called a monoacid dimer. This compound is an ionic contrast agent, but it has the same type of compound ratio as the nonionic substances. The contrast agent illustrated in Figure 6-5 is a 6:2 compound; that is, it provides six iodine particles for contrast and two particles for osmolality. This type of contrast agent lies between ionic and nonionic agents in the mediation of side effects. Its advantages are that it more closely mimics the nonionic compounds and is not as costly.


image
FIGURE 6-5 Sodium ioxaglate, a monoacid dimer, is a low osmolality compound with a 6:2 ratio of iodine atoms to particles in solution.


Characteristics of Radiopaque Contrast Media


In the selection of a radiopaque contrast agent, certain characteristics such as viscosity, toxicity, iodine content, miscibility, and persistence must be considered. The ultimate choice of the contrast agent is usually left to the physician performing the procedure, but the radiographer should understand the characteristics of contrast agents to be able to use them intelligently and efficiently during special procedures.



Iodine Concentration


The iodine atoms attached to the basic contrast agent structure are responsible for providing the radiopacity of the substance. As the iodine concentration of the contrast agent increases, the viscosity also increases. Compounds of the meglumine salts have a greater increase in viscosity than those of sodium salts. In considering the use of contrast agents during vascular procedures, viscosity becomes an important factor when long, small-bore catheters are used. More viscous contrast agents require greater injection pressures to deliver the same amount of material, increasing the possibility of patient trauma and catheter damage.


The iodine concentration itself is an important physical characteristic; it can be determined easily if the iodine content of the substance and the amount dissolved in its solvent are known. The iodine content is usually expressed in milligrams per milliliter or per cubic centimeter. Information relating to the physical characteristics of the contrast agents can be found in the product data sheet that is packaged with the contrast agent.


In comparing contrast agents, the amount of iodine delivered per second to the patient should be considered because contrast agents with a greater amount of meglumine salt usually have a lower iodine content as a result of the increased weight of the meglumine ion. Therefore, the amount of iodine delivered per second will be smaller. To illustrate this, if we compare the iodine content of Hypaque (sodium 50%) with that of both Conray (meglumine 60%) and Renografin 60% (meglumine 52%, sodium 8%) (Table 6-1), it can be seen that the Hypaque has a greater iodine content. It should be noted that Hypaque 50% contains 100% sodium salt, whereas Renografin 60% is a mixture of sodium and meglumine salts, and Conray 60% contains 100% meglumine salt. Table 6-2 illustrates the characteristics of some of the low osmolality and nonionic contrast agents.



TABLE 6-1


Characteristics of Some Ionic Intravascular Contrast Media













































































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Feb 27, 2016 | Posted by in GENERAL RADIOLOGY | Comments Off on Contrast Media

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    Iodine Content Chemical Components Viscosity (cP) Sodium Content
Agent Iodine Concentration % mg/ml % Anion Cation* 25° C 37.5° C mEq/ml mg/ml
Hypaque 60% 28 – 31% 282 28 Diatrizoate Mg (60%) 6.22 4.18 0.001 0.02
Conray 60%   282 28 Iothalamate Mg (60)% 6.10 4.0 0.0014 0.03
Renografin 60   288 29 Diatrizoate Mg (52%) 6.0 3.9 0.16 3.76
Hypaque 50%   300 30 Diatrizoate Na (8%) 3.25 2.5 0.8 18.1
          Na (50%)