STATE OF THE ART

Safety Issues in Magnetic Resonance Imaging

Sophia M. Chung, MD

Although generally considered safe, magnetic resonance imaging (MRI) has a number of safety issues, including the effects of high magnetic fields and radiofrequency pulses on the body, and on implanted devices, the side effects of contrast agents, toxicity during pregnancy, claustrophobia, and hearing loss. (J Neuro-Ophthalmol 2002;22: 3539)

MAGNETIC FIELDS, RADIOFREQUENCY PULSES, IMPLANTS, AND DEVICES

Three types of MRI emissions could interact with implants: the powerful static magnetic field, weaker timevarying gradient magnetic fields, and radiofrequency pulses. The static magnetic field of the MRI is always present even when the scanner is not imaging and varies in most institutions from 0.5 to 2.0 tesla (T), although up to 4.0 and 5.0 T are being used in research protocols. This compares with the earths magnetic field of 70 microtesla. Schenck (1) has shown that patients experience vertigo, nausea, and metallic taste more often with 4.0 T than with 1.5 T, although Robitaille (2) reports no adverse effects of 8.0 Tesla. Reversible elevation of the T wave on electrocardiograms is known to occur without ill effects (3,4). This change is not a biologic effect but rather a change in the electrocardiogram-detected voltage. Strong magnetic fields create a torque of magnetic materials, causing alignment of the object with the magnetic field, whereas the associated spatial gradient creates a translational (attractive) force resulting in tearing of tissues. These phenomena pose risks with respect to implanted or foreign metallic objects. Clips, implants, and devices are not designated as ferromagnetic or nonferromagnetic simply based on composition of the metal. The geometry of the object, its location and orientation, the duration
Departments of Ophthalmology and Neurology, Saint Louis University School of Medicine, Saint Louis, Missouri, USA. Correspondence to Sophia M. Chung, MD, 1755 South Grand Boulevard, Saint Louis, MO 63104, USA; E-mail: chungsm@slucare1.sluh.edu Modified from a platform presentation given at the 27th Annual North American Neuro-Ophthalmology Society Meeting, Rancho Mirage, CA, February 1922, 2001.

of implantation, the mechanism by which the device is secured, and the strength of the static and gradient magnetic fields are also important parameters in determining clip or implant motion in MRI (5). Pacemakers are a strict contraindication for MRI. Dislodgement, disruption of the electrical system of the pacemaker, and asynchronous pulsing may result from the magnetic and gradient fields imposed on the pacer (6). Complications include rapid cardiac stimulation, arrhythmias, fibrillation, and burns (7,8). Much anxiety and controversy surrounds the safety of MRI in patients with aneurysm clips. Although no metal is entirely nonferromagnetic, clips may be classified nonferromagnetic for clinical purposes if they pass the widely accepted deflection test (9). On the basis of these studies, New et al. (9) recommended that new implants be made of alloys of titanium, stellite, and Elgiloy. Stellite and Elgiloy are cobaltnickel alloys. Clips made of titanium and its alloys are nonferromagnetic; alloys containing at least 10% to 14% nickel are weakly ferromagnetic but safe for MRI because nickel is able to stabilize the iron into a form that renders it less magnetic. Nearly all aneurysm clips made today are nonferromagnetic and have been deemed safe in the MRI environment (5,1016). In vitro studies of titanium alloy, titanium, austenitic stainless steel, Elgiloy, and Phynox aneurysm clips undergoing long-term or multiple exposures to the strong magnetic fields of a 1.5 Tesla magnetic resonance system have shown less than 2 degrees of deflection, rendering them safe for MRI environments (11, 12,14,17,18). Human studies confirm the safety of these clips (12,13,15,17). However, after the fatality of a patient with a misidentified ferromagnetic clip in 1993, MRI centers are highly sensitized to the appropriate identification of aneurysm clips (19). There are numerous tables identifying aneurysm clips and their MRI compatibility. To insure the patients safety, the written operative note describing the implant specifications should be verified before the MRI procedure. Many other implantable devices must be reviewed for safety before MRI. Vascular implants are both nonferromagnetic and ferromagnetic. However, these implants are

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believed to have become firmly incorporated into the vessel wall within 6 weeks of implantation. Therefore, intravascular coils, filters, and stents are MRI safe (7,20). Intraocular metallic foreign bodies create potentially serious risks for visual loss and are therefore considered a relative contraindication to MRI (21). Prosthetic valves have been shown to be safe (22). Although many such valves do show deflection forces (2.53 degrees in a 1.5 T magnet), these forces are far less than those exerted by the beating heart itself (7,22). Orthopedic implants are nonferromagnetic and therefore compatible with safe MRI scanning. However, the Perfix (Instrument Makar, Okemos, MI) interference screw used in repair of the anterior cruciate ligament is ferromagnetic. The force keeping this screw in place prevents dislodgement and pain but creates artifactual changes precluding interpretation (7). Pellets, bullets, and shrapnel may be ferromagnetic, depending on the country of origin and their intended use. Because of the uncertainty, these objects are considered relative contraindications to MRI scanning. A number of magnetically activated implants, such as magnetic stoma plugs, magnetic sphincters, ocular implants, and certain cochlear implants, are hazardous in the MRI environment and should be removed before imaging (7,23,24). Time-varying gradient magnetic fields create voltages and electrical currents. The currents created in MRI systems are considered insufficient to cause biologic effects except for peripheral nerve stimulation and flashes of light (magnetophosphenes), the latter believed to be generated by rotation and alignment of retinal photoreceptors. Such currents are generated particularly with 4 T MRI units (25,26). Therefore, the Food and Drug Administration (FDA) limits the switching rates (necessary to generate a time-varying gradient magnetic fields) to a factor of three below the mean threshold for peripheral nerve stimulation (4,8). Pulsed radiofrequency fields are used to create MRI signals from tissue. These magnetic fields can cause skin burns when closed conducting loops are created by skin-toskin contact between extremities (27), as by pulse oximeters (28) or electrocardiogram leads (8). Patients may also receive burns at the site of tattoos (29). Metallic prostheses such as artificial hips can absorb heat but do not appear to cause injury (16,30). Gold weight lid implants used to treat impaired eyelid closure after seventh nerve palsies have been shown to be safe for MRI (31). The electromagnetic fields created for MRI render scanning unsafe in patients with neurostimulators, bone growth stimulators, and drug infusion pumps. Local pain and malfunction of the units have been described (24,32 34). Cochlear implants are dangerous because some are controlled electronically, and some have magnets within the implants (35). Dental brace wires cause significant imaging artifacts but are not hazardous.

MAGNETIC RESONANCE IMAGING CONTRAST AGENTS

Six MRI contrast agents are used worldwide for intravenous administration. Four are gadolinium chelates and the other two are mangafodipir trisodium and ferumoxide. All four of the gadolinium chelates are approved by the FDA for use in the United States: Magnevist (gadopentetate dimeglumine, Gd-DTPA, Berlex Laboratories, Wayne, NJ), Omniscan (gadodiamide Gd-DTPA-BMA, Nycomed, Oslo, Norway), ProHance (gadoteridol Gd-HP-DO3A, Bracco Diagnostics, Princeton, NJ), and Dotarem (gadoterate meglumine, Guerbet Laboratories, Aulnay-sous-Bois, France). Mangafodipir trisodium and ferumoxide are used outside the United States. Each gadolinium-based contrast agent is chelated with different agents, thereby altering its ionicity and configuration. Despite their differences, all agents have similar mechanisms of action, biodistribution, and half-lives, and are considered remarkably safe for MRI use. They are administered in the typical diagnostic dose of 0.1mmol/kg. The median lethal dose (LD 50 ) is > 30 mmol/kg for Omniscan, 12 mmol/kg for ProHance, and 6 to 7 mmol/kg for Magnevist (36). Minor adverse side effects of MRI contrast agents are nausea (1%2% for all agents), vomiting, hives (0.3% 0.7%), headache (3.6%), and injection site symptoms (pain, warmth, and a local burning sensation) (3.6%) (37,38). Adverse reactions involving the cardiovascular, respiratory, gastrointestinal, and neurologic systems are rarely reported (< 1%). Although there are safety concerns in those patients with renal dysfunction, primarily with respect to the release of free gadolinium, the contrast media are well tolerated (39). In fact, a recent study demonstrated that 0.3 mmol/kg ProHance was safely administered in end-stage renal disease requiring dialysis (40). Furthermore, the agents are dialyzable, with more than 95% of the dose removed by the third dialysis treatment (41). Anaphylaxis has been reported after administration of Magnevist and ProHance. There have been 13 anaphylactoid reactions to Magnevist, a rate estimated to be 1 in 350,000 to 450,000 injections (7,42). The risk may be higher in patients with a history of atopy, asthma, or previous adverse reactions to iodinated contrast agents (43,44). Therefore, the package insert includes the statement: The possibility of a reaction, including serious, fatal, life-threatening, anaphylactoid, or cardiovascular reactions or other idiosyncratic reactions should always be considered especially in those patients with a known clinical hypersensitivity or history of asthma or other allergic respiratory disorders. There are some adverse reactions unique to Magnevist and ProHance, the agents most studied. Unique to Magnevist is its relatively high osmolality, which is three times that of ProHance and Omniscan. The higher viscosity can
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be readily appreciated on manual injection. Furthermore, pain and tissue necrosis from extravasation are important adverse effects demonstrated both clinically and experimentally (4547). Magnevist was originally shown to cause a transient rise in bilirubin and serum iron. However, after the reformulation of Magnevist, no changes in levels of bilirubin and iron were detected (37). ProHance also causes nausea (1%1.5%), and headache (0.6%), and can rarely cause altered taste sensation (0.9%1.4%) (37). Ten anaphylactoid reactions have occurred in an estimated 150,000 administrations (48). Omniscan and Dotarem have similar profiles to the other gadolinium agents with respect to side effects. There are no known contraindications to use of any of the MRI contrast agents. In vitro studies of sickle erythrocytes demonstrated alignment of deoxygenated cells perpendicular to the external magnetic field (49,50). However, there have been no reports of sickle crisis precipitated by MRI contrast agents.

pregnant patients unless the benefits clearly outweigh the risks (37,38). As a matter of interest, pregnant health care personnel exposed to chronic low levels of static magnetic fields (but not to active gradient or radiofrequency electromagnetic fields, which are found in MRI) do not appear to have a higher rate of spontaneous abortion, preterm delivery, low birth weight, or infertility (54).

CLAUSTROPHOBIA
Claustrophobia, anxiety, and panic attacks are the most disabling psychologic phenomena experienced by patients. The proximity of the patients face to the inner wall of the gantry, the duration of the study, loud noises, restricted body movements, and the temperature and humidity contribute to the patients distress (55). Comforting measures include educating the patient about the specifics related to the procedure, maintaining physical and auditory communication with the patient, and providing ample flow of air and lights to minimize the feeling of close surroundings (56,57). Sedation is many times necessary for adequate relaxation. With the development of wider gantries, these problems are expected to diminish.

MAGNETIC RESONANCE IMAGING AND PREGNANCY

There are numerous experimental studies of pregnant animals exposed to electromagnetic fields (51). Unfortunately, these reports conflict with one another and firm conclusions cannot be made about the safety of MRI in pregnant patients. A recent controlled study compared a group of 20 9-month-old children in whom echo planar imaging (EPI) was performed antenatally to a control group not exposed to EPI (52). There were no demonstrable differences between the two groups with respect to numerous developmental categories, although gross motor function was slightly higher in the EPI-exposed group. Furthermore, there were no ill effects on hearing. The current recommendations are to inform pregnant women that although there have been no data to demonstrate deleterious effects of MRI, there are no data to support its safety. Magnevist crosses the placenta and appears within the fetal bladder soon after intravenous administration. It is excreted into the amniotic fluid, only to be swallowed and go through the same cycle. However, the absorption of any form of gadolinium from the gastrointestinal tract is less than 1.0% (53). Studies have shown that contrast media can cause adverse effects on the fetus of animal models, however. Magnevist has been shown experimentally to cause fetal developmental delay without congenital anomalies when given in 2.5 times the human dose to rats and in 7.5 times the human dose to rabbits (37). ProHance can have adverse effects on the animal fetus at 5 times the human dose. Furthermore, fetal loss is enhanced with increasing doses of ProHance. There are no studies of the safety of MRI contrast agents in pregnant women. The recommendations, therefore, are to defer contrast agents in

HEARING LOSS
The noise created during MRI can be a risk to the patient. As many as 43% of patients without appropriate ear protection report temporary hearing loss (58). Cases of permanent hearing loss have also been reported (59). Duration of exposure, frequency of exposure, and intensity of noise are the most important factors inducing hearing loss. The noise arises primarily from the rapid alterations in currents within the gradient coils. The force causes motion or vibration of the coils which impact against the mountings. The banging that results is typically between 65 and 96 dB (60). As the section thickness and field of view decreases and as the repetition time and echo time become shorter, the noise becomes louder. But as acquisition time is reduced, hearing loss is less likely. Earplugs are the safest and least costly means to prevent hearing loss. They reduce noise by 10 to 20 dB (58). Other options include MRI-compatible headphones and antinoise techniques (61). Fourier analysis of the MRI noise can also be used to create a signal of opposite phase to create a 50% to 70% reduction in perceived noise. REFERENCES
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