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Contrast Media T. Murakami, DVM Contrast media: definition • Any substance used to change the imaging characteristics of the patient, thereby providing additional information including: – Anatomy/morphology: tissue versus fluid, location – Physiology: vasculature, vascular integrity, qualitative assessment of function Important Points • Category: is the agent used for photon-based imaging, magnetic resonance imaging, or ultrasound? • Use: what are the special procedures for which a contrast agent is used? Procedures will be discussed in subsequent lectures. • Routes of administration: or more importantly, how should a contrast medium NOT be given? • Indications and Contraindications: what could go wrong? 1 Imaging Modality Photon-based imaging: radiography Imaging Modality Photon-based imaging: fluoroscopy Imaging Modality Photon-based imaging: computed tomography 2 Contrast agents for photonbased imaging • These contrast media work by changing the photon-attenuating characteristics of the patient. – Positive contrast agents: increase the attenuation of tissue, blood, urine, or outline spaces such as the gastrointestinal lumen or subarachnoid space. – Negative contrast agents: normally decrease attenuation by occupying a space such as the bladder, GI tract, or (if you’re unlucky) blood vessels. Positive contrast agents • The two major types of positive contrast agents are barium sulfate agents and various iodinated compounds. – Barium sulfate agents include bariumimpregnated spheres (BIPS) – The iodinated contrast agents are based on benzene rings, and there are many different compounds. Barium sulfate • Barium sulfate is a white, crystalline compound. • Barium has a high atomic number (56). • Barium sulfate is inert and not absorbed by the gastrointestinal tract. It may have soothing qualities. • This compound causes severe reactions within the body. Its ONLY indications are for use outside the body (e.g., GI, marking external structures). 3 Barium sulfate • Sterile iodinated contrast media should be used if gastrointestinal perforation is suspected. • If barium sulfate gets within the body (e.g. peritoneal or pleural surfaces), be prepared to surgically flush out. • Rarely, barium sulfate can embolize via mucosal defects, causing severe reactions. Barium sulfate • Barium sulfate is very effective at outlining mucosal surfaces. • Most special procedures using barium involve the GI tract: – Esophagram – Upper GI series – Colonogram (barium enema) • Barium sulfate is available in different concentrations Barium sulfate • Commercial preparations contain additives to improve shelf-life, prevent flocculation, and prevent settling. • Different special procedures call for differing concentrations of barium sulfate. Barium sulfate is generally sold as a suspension with concentrations expressed as weight-to-volume % or weight-to-weight %. 4 Barium sulfate:% weight-to volume • A certain amount of barium is added to enough water to create a predetermined volume of suspension. For example, 20 grams of barium sulfate in enough water to create 100 ml of suspension would yield a 20% weight to volume suspension. Wallack, ST. The Handbook of Veterinary Contrast Agents. San Diego, San Diego Veterinary Imaging, Inc., 2003. Barium sulfate:% weight-to weight • A certain weight of barium sulfate is added to enough water to obtain a predetermined weight of suspension. For instance, 20 grams of barium sulfate added to 80 grams of water would create 100 grams of suspension. Therefore, barium sulfate is 20% of the weight of the total suspension. Wallack, ST. The Handbook of Veterinary Contrast Agents. San Diego, San Diego Veterinary Imaging, Inc., 2003. Barium sulfate • Recommended concentrations for GI studies vary with references (more in subsequent lectures). • Charts are available for comparison of % weight-to-volume and % weight-to-weight. • Preparations are available in liquid form, as well as pastes/creams. Pick appropriate formulation based on procedure. 5 Barium sulfate: BIPS • Barium-impregnated polyethylene spheres. • Spheres available in a variety of sizes. • Can be given with food, and generally less messy than barium sulfate suspensions. • No mucosal information, unpredictable gastric emptying times, little information about the nature of an obstruction. • Could be considered to search for obstruction. Iodinated contrast agents • Water-soluble agents based on iodinated benzene rings. • Can be classified according to whether the agent dissociates in solution (ionic versus nonionic) and structure (monomer versus dimer) • In general, the potential for adverse reactions increases with the osmolality of the contrast agent. Iodinated contrast agents • Solutions containing ionic agents have higher osmolality due to an increased number of particles in solution when compared with non-ionic agents. • Solutions containing dimeric agents have more iodine atoms per molecule, and therefore have lower osmolalities relative to their monomeric counterparts. 6 Iodinated contrast agents • Plasma is approximately 290 mOsm/kg. • The ionic monomeric agents range from 1970 to 2400 mOsm/kg. • An ionic dimeric agent can have an osmolality around 577 mOsm/kg (ioxaglate). • Non-ionic monomers range from 610 to 915 mOsm/kg. • Non-ionic dimers can be iso-osmolar with plasma (290 mOsm/kg). Iodinated contrast agents • Unfortunately, the ionic monomeric agents are usually far cheaper than the non-ionic monomeric agents. • Dimeric agents are also expensive. Additionally, the large molecular size of the contrast agent leads to increased viscosity of the solution. www.emedicine.com www.invitrogen.co.jp Iodinated contrast agents • High-osmolar agents – Monomeric ionic agents, including diatrizoate, iothalamate, ioxithalamate, and metrizoate. • Low-osmolar agents – Non-ionic monomers, including iohexol, iopamidol, iopentol, ioproimide, and ioversol. – Ionic dimer (ioxaglate) • Iso-osmolar agents – Non-ionic dimers (iodixanol, iotrolan) 7 Iodinated contrast agents • Remember that different preparations of the same contrast agent may have different indications. – Some concentrations of a particular agent may not be labeled for intrathecal use. – Non-sterile preparations may be available for gastrointestinal use. For example, Gastrograffin (sodium and meglumine diatrizoate) for gastrointestinal use. • Always read the label. Iodinated contrast agents • Both the ionic and nonionic contrast agents can be used for: – Physiologic organ enhancement. – Blood flow detection or tracing (angiography or venography. – Detection of vascular leakage. – Urinary tract studies. – Gastrointestinal studies. – Morphologic studies. Iodinated contrast agents • Ionic contrast agents, because of their hypertonicity, draw water into whatever space they occupy. Some effects of this property include: – Severe pulmonary edema if aspirated. – Potential hypovolemic effect as water is pulled into the GI tract if used for an upper GI series. 8 Iodinated contrast agents • Some preparations of nonionic agents are labeled for intrathecal use. • Nonionic agents can be used for procedures involving injection into other “sensitive” areas, e.g. joints. Negative contrast agents • Gas added to a space, with or without positive contrast media, to aid in visualization of organ (s) of interest. Negative contrast agents • More commonly used in studies of the urinary bladder, stomach and colon (negative and double-contrast studies). • Less common studies described in the literature including pnuemoperitoneograms. 9 Negative contrast agents • The complication of greatest concern is the occurrence of gas embolization. • Highly soluble gases are less likely to cause problems. • Gases which are highly soluble in blood include CO2 and N20. Room air contains nitrogen, which is not very soluble. Oxygen diffuses too rapidly to be useful. Negative contrast agents • Infusion of negative contrast agents, as with positive contrast agents, should be infused carefully to prevent over-inflation. • Never attach a gas source directly to the catheter used for infusion. Always load a syringe with the gas, then attach the syringe to the catheter. Imaging Modality Magnetic Resonance Imaging www.canineepilepsy.co.uk 10 MRI contrast agents • Paramagnetic contrast agents: hyperintense on T1 sequences. – Low incidence of adverse reactions. – Ionic or nonionic agents available. – Uses include detection of physiologic organ enhancement, vascular leakage, and disruption of the blood-brain barrier. • Supraparamagnetic agents based on iron oxides, many of which are taken up by the reticuloendothelial system (liver, spleen, bone marrow). Imaging Modality Ultrasound http://radiographics.rsna jnls.org Sonographic contrast agents • Composed of gas bubbles (air or perfluor gases) stabilized by a shell of phospholipids, surfactants, albumin, or polymers. – Blood pool agents. – Generally low risk of adverse reactions. – Currently investigational in veterinary medicine. • Physiologic organ enhancement, blood flow detection, vessel tracing, and vascular leakage. 11 Complications • Complications due to inappropriate use or delivery: – Barium aspiration – Barium within the body – Barium embolization – Aspiration of an ionic iodinated contrast agent – Hypovolemia due to hyperosmolar contrast within the GI tract Complications • Complications due to inappropriate use or delivery (continued): – Gas embolization due to use of low solubility gas in negative or double-contrast study • These complications (and others) are somewhat predictable and can be avoided with care. Adverse reactions • Adverse reactions, on the other hand, usually cannot be predicted. • Occur more commonly with hypertonic contrast agents. Due to the decreased incidence of adverse events, nonionic agents should be used in high-risk patients. • Worsened if the patient is dehydrated (always correct dehydration prior to procedure). • Be prepared to intervene (fluids, drugs). 12 Adverse reactions • Mild reactions may consist of agitation, vomiting, urination, defecation, erythema, urticaria, or coughing. • More severe reactions include mild hypotension, arrythmias, tachycardia or bradycardia. • Severe reactions include severe hypotension, cardiac or respiratory arrest, and vetricular fibrillation. Adverse reactions • Reactions may also be specific to a particular organ system, including: – Contrast-induced renal failure – Neurologic effects such as seizures or cortical blindness • Have the means to intervene (intravenous catheter, fluids, drugs for resuscitation). • Discuss the procedure with the owner. Recommended reading • Wallack ST. The Handbook of Veterinary Contrast Radiography. San Diego, San Diego Veterinary Imaging, Inc. 2003. • Walter P, Feeney D, Johnston G, Diagnosis and Treatment of Adverse Reactions to Radiopaque Contrast Agents. In: Kirk RW, ed. Current Veterinary Therapy. Small Animal Practice IX. Philadelphia: WB Saunders Co., 1986; pp 47-52. • Thrall DE. Textbook of Veterinary Diagnostic Radiology, 4th ed. Philadelphia: Saunders, 2002. 13