By: Assoc. Prof Dr. Mohammed Ahmed Ali Ph. D. in Applied Radiation in Medical and Industrial Fields UPM- Malaysia M. Sc. in Oncology and Radiation Therapy B. Sc. in Radiologic Instrumentation Engineering SUST-Sudan B. Sc. in Radiation Therapy and Nuclear Medicine SUST-Sudan

Objectives:  To know the types of contrast media  To know the mechanism of tissue differentiation  To know their toxicity  To know the suitable application References: - ACR Manual on Contrast Media, 2010, American College of radiology. - Contrast Media Safety Issues and ESUR Guidelines 2006, By H. S. Thomsen

Definition of Contrast Media Contrast media is a chemical substances used in radiography that allow visualization of certain tissues with high difference in color or signal. It used with most of imaging techniques to enhance the differences seen between the body tissues on the images. Contrast media alter the response of the tissues to the applied electromagnetic or ultrasound energy by a variety of mechanisms.

The ideal contrast medium would achieve a very high concentration in the tissues without producing any adverse effects. Unfortunately, so far this has not been possible and all contrast media have adverse effects.

Radiographic Contrast Media Radiographic contrast media are divided to the following types: Positive contrast agents: ( The positive contrast media attenuate X-rays more than do the body soft tissues and can be divided into water soluble iodine agents and non water soluble barium agents.) Negative contrast agents: Negative contrast media attenuate X-rays less than the body soft tissues do. No negative contrast media are commercially available.

Iodinated Agents: Water soluble iodinated contrast agents capable to diffuse throughout the extracellular space and are principally used for Angiography, During computed tomography (CT) and Conventional radiography. They can also be administered directly into the body cavities, for example the gastrointestinal tract and urinary tract.

All of these contrast media are based on a benzene ring to which three iodine atoms are attached. A monomer contains one tri- iodinated benzene ring and a dimer contains two tri-iodinated benzene rings.

Iodinated contrast media can be divided into two groups, ionic and nonionic based on their water solubility. The water in the body is polarised unevenly with positive poles around the hydrogen atoms and negative poles around oxygen atoms. Ionic contrast media are water soluble because they dissociate into negative and positive ions which attract the negative and positive poles of the water molecules.

Nonionic contrast media do not dissociate and are rendered water soluble by their polar OH groups Electrical poles in the contrast medium OH groups are attracted to the electrical poles in the water molecules.

The osmolality of contrast media affects the incidence of side- effects. The early contrast media had very high osmolalities in the range of (1500–2000 mosm\kg) and subsequently agents of lower osmolality have been developed.

Contrast media divided into high-, low- and iso-osmolar agents. An indication of the osmolality of an agent is given by the contrast medium ratio which is derived by dividing the number of iodine atoms in solution by the number of particles in solution:

The higher osmolality agents have more particles per iodine atom and therefore have lower ratios. Thus the ionic monomers have a ratio of 1.5 ( three iodine atoms per two particles in solution ), the nonionic monomers and the ionic dimers have a ratio of 3 ( three iodine atoms per particle in solution ) and the nonionic dimers have a ratio of 6 ( six iodine atoms per particle in solution ) (Fig. 1).

The nonionic dimers are iso-osmolar with blood (300 mosm per kg) at all concentrations.

Classification of iodinated contrast media

Example and properties of four different classes of iodinated contrast: 1. Ionic monomeric contrast media (high-osmolar contrast media, HOCM), e.g. amidotrizoate, iothalamate, ioxithalamate 2. Ionic dimeric contrast media (low-osmolar contrast media, LOCM), e.g. ioxaglate 3. Nonionic monomeric contrast media (low- osmolar contrast media, LOCM), e.g. iohexol, iopentol, ioxitol, iomeprol, ioversol, iopromide, iobitridol, iopamidol 4. Nonionic dimeric contrast media (iso-osmolar contrast media, IOCM), e.g. iotrolan, iodixanol

MR Contrast Media MRI contrast agents contain paramagnetic or super paramagnetic metal ions which affect the MR signal properties of the surrounding tissues. They are used to enhance contrast, to characterize lesions and to evaluate perfusion and flow-related abnormalities. They can also provide functional and morphological information.

Paramagnetic Contrast Agents Paramagnetic contrast agents are mainly positive enhancers which reduce T1 and T2 relaxation times and increase tissue signal intensity on T1-weighted MR images.

The most widely used paramagnetic contrast agents are non-specific extracellular gadolinium chelates. Their active constituent is gadolinium, a paramagnetic metal in the lanthanide series, which is characterized by a high magnetic moment and a relatively slow electronic relaxation time.

Non-specific extracellular gadolinium chelates: can be classified by their chemical structure, macrocyclic or Linear, and by whether they are ionic or nonionic form (Fig. 2) and they are excreted via the kidneys.

Paramagnetic contrast agents also include liver specific gadolinium based agents (gadobenate dimeglumine, Gd-BOPTA and gadoxetate, Gd-EOBDTPA) and manganese-based preparations [manganese chelate (mangafodipir trisodium)

These hepatobiliary contrast agents are taken up by hepatocytes and then there is variable biliary excretion. The gadolinium based liver specific contrast media are also excreted by the kidneys.

Advantage and Disadvantages of Contrast Media Both types of I.V contrasts i.e. ionic and non ionic; contain iodine and most of these agents are derivatives of tri-iodobenzoic acid. The idea of using iodine dyes is the simple fact that iodine molecule absorbs x-rays effectively in the energy range at which most clinical imaging systems operate.

There are many types of contrast dyes available in the market like the "Optison - is an ultrasound contrast agent used with an echocardiogram. The "omnipaque" used in the angiocardiography, CT enhanced studies of the head and neck, as well as many other uses. There is also the non- ionic "Vasipaque" which is used in peripheral arteriography, cerebral arteriography, as well as the angiocardiographic studies.

The complications of contrast dyes include both allergic reactions to the dye material, and the common serious complication as nephropathy, which is a variant of acute renal failure (due to the high-osmolality contrast agents).

The allergic, due to direct effect of the iodinated dye material that acts directly on mast cells releasing histamine and other biochemical mediators causing the clinical picture of an allergic reaction, and that is why the possibility of development of allergic reaction and its severity is directly proportional to the concentration of iodine in the specific dye used, as well as on the dose of the intravenous dye that is injected.

The allergic reactions range from mild allergic symptoms to severe life threatening anaphylaxis, and affects about 5-8 % of patients exposed to radiocontrastagents. The mild symptoms of allergic reactions include a feeling of warmth, nausea, and vomiting that develops shortly after injecting the dye, and requires no treatment other than observing the patient

The moderate reaction as (severe vomiting, hives and swelling) requires Treatment & close observation: The treatment involves I.V. anti-emetic agents as well as the H1 antagonist agent Diphenhydramine in a dose of 50 mgs I.V. or I.M., and sometimes a short acting steroid (hydrocortisone) in a dose of 100 mgs I.V may be used. The severe reaction include the life threatening anaphylactic shock, presenting as severe bronchospasm with cyanosis and a circulatory shock, and sometimes a cardiovascular arrest.

The risk for developing severe reaction appear to be higher in patients with conditions like food allergies, iodine skin allergy, bronchial asthma, kidney and thyroid diseases, as well as patients on metformin or beta blocker therapy, so special attention should be given to this patient population prior to applying a radiocontrast dye.

In case of severe shock: immediate infusion of intravenous fluids to support the circulation, I.M injection of 0.5 mgs of epinephrine, to be repeated every 2-5 minutes if there is no response (I.V injection would be more appropriate in a setting of severe shock with compromised perfusion for a more optimum effect ), 200 mgs I.V injection of hydrocortisone, 50 mgs of diphenhydramine as well as respiratory support with oxygen therapy

Case of nephropathy: or impairment of the renal functions: It measured as a 25% increase in serum creatinine level, or 0.5 mgs absolute increase in serum creatinine level within hours of administration of radiocontrast dye. Contrast-induced nephropathy is associated with a higher morbidity and mortality

The iodine compounds are toxic to the kidneys, but an important etiological factor is the hyperosmolarity of the dye material injected, and that is why the development of this complication is more common with the ionic hyperosmolar dye preparations