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Figure 11.9 • Schematic diagram of an MRI system demonstrating radiofrequency pulses and the strong magnetic field.
zero in comparison with water. Many nonmetallic materials are diamagnetic; they have negative susceptibility and induce weaker magnetic fields in the local environment. Such substances generally have fully paired electrons. Materials with unpaired orbiting electrons are said to be paramagnetic, because when placed in an applied magnetic field, they strengthen the magnetic fields within their vicinity. The magnitude of paramagnetic influence is proportional to the strength of the applied field. A substance with many unpaired electrons will be superparamagnetic, because it produces a stronger supplementary magnetic field. Ferromagnetic materials have very large numbers of unpaired electrons and produce a large, supplementary magnetization to the applied field that remains once the magnetic field has been removed.
Gadolinium-containing contrast agents rely on unpaired electrons to produce magnetic changes in nearby water molecules. These paramagnetic agents predominantly decrease tissue T1 relaxation time, which increases tissue intensity on Tl-weighted images. Such agents are known as positive contrast agents because they brighten tissues associated with the nearby paramagnetic substance.
Many contrast agents used for MRI are extracellular paramagnetic agents. The primary paramagnetic metal ion used is gadolinium, a rare earth element. Gadolinium ions (Gd+3) form when prepared in 0.05 M hydrochloric acid and are extremely effective for enhancing water proton relaxation rates. The ion itself, however, is toxic for human use. The ion quickly binds to ferric (Fe+3) protein-binding sites, most notably plasma transferrin, and has a long biological half-life of several weeks. In addition, the ion readily forms insoluble compounds by interacting with endogenous ions including phosphate, carbonate, and hydroxide.46
Consequently, the development of gadolinium MRI contrast agents has mainly focused on chelated compounds that clear rapidly from the body through the kidneys and exhibit minimal toxicity. These include gadobenate dimeglumine (MultiHance), gadodiamide (Omniscan), gadopentetate dimeglumine (Magnevist), gadoteridol (ProHance), and gadoversetamide (Optimark).47
All intravenous gadolinium complexes are hypertonic when compared with plasma. The most common side effects are headache, nausea, dizziness, taste perversions, and va-sodilation. A rare adverse event, nephrogenic systemic fibro-sis, is more likely to occur in patients with severe acute or chronic renal insufficiency (<30 mL/min). Postmarketing reports identified such an event following single and multiple administrations of gadolinium-based contrast agents. These reports have not always identified a specific agent, and repetitive administration of the same or different agents carries similar risk if the time interval between the administrations precludes clearance of the contrast agent from the body.48,49
Manganese (Mn2+) is strongly paramagnetic and can be used to form complexes used as MRI contrast agents. At this time, the only parenteral manganese compound used in humans is mangafodipir trisodium. This compound is delivered to tissues with active metabolism, such as the pancreas, renal cortex, GI tract, heart, and adrenal glands. The effect of mangafodipir trisodium is to decrease T1 relaxation time, which enhances signal intensity on Tl-weighted images.
Superparamagnetic iron oxide colloids (SPIO) contain a crystalline core composed of iron oxide complexes. The core may be coated with dextran, siloxanes, or another large polysaccharide. The particles vary in size from 1 and 10 /m, and their biological characteristics can be altered by changing their coating. Large particles accumulate in the liver and spleen, whereas smaller particles remain in the circulation longer and tend to aggregate in lymph nodes. Ferumoxides and ferumoxsil are examples of such agents.
Because the main MRI effect of the iron oxide particles is on T2-weighted images, they decrease the signal intensity of the tissue in which they accumulate. Such iron oxide agents are known as negative contrast agents, because they darken tissues associated with the accumulation of ferromagnetic particles. Enhancement of Tl-weighted images is less dramatic, but can be obtained. SPIO contrast agents provide enhancement of the liver and/or spleen when injected intravenously or the bowel when administered orally.50
Ferumoxides (Feridex). Ferumoxides is a black to reddish brown aqueous colloid of SPIO particles associated
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