STATE OF THE ART

Safety Issues in Magnetic Resonance ImagingSophia M. Chung, MD

Although generally considered safe, magnetic resonanceimaging (MRI) has a number of safety issues, including theeffects of high magnetic fields and radiofrequency pulseson the body, and on implanted devices, the side effects ofcontrast agents, toxicity during pregnancy, claustrophobia,and hearing loss.

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MAGNETIC FIELDS, RADIOFREQUENCYPULSES, IMPLANTS, AND DEVICESThree types of MRI emissions could interact with im-

plants: the powerful static magnetic field, weaker time-varying gradient magnetic fields, and radiofrequencypulses. The static magnetic field of the MRI is alwayspresent even when the scanner is not imaging and varies inmost institutions from 0.5 to 2.0 tesla (T), although up to 4.0and 5.0 T are being used in research protocols. This com-pares with the earth’s magnetic field of 70 microtesla.Schenck (1) has shown that patients experience vertigo,nausea, and metallic taste more often with 4.0 T than with1.5 T, although Robitaille (2) reports no adverse effects of8.0 Tesla. Reversible elevation of the T wave on electrocar-diograms is known to occur without ill effects (3,4). Thischange is not a biologic effect but rather a change in theelectrocardiogram-detected voltage.

Strong magnetic fields create a torque of magneticmaterials, causing alignment of the object with the mag-netic field, whereas the associated spatial gradient createsa translational (attractive) force resulting in tearing oftissues. These phenomena pose risks with respect to im-planted or foreign metallic objects. Clips, implants, and de-vices are not designated as ferromagnetic or nonferromag-netic simply based on composition of the metal. The geom-etry of the object, its location and orientation, the duration

of implantation, the mechanism by which the device is se-cured, and the strength of the static and gradient magneticfields are also important parameters in determining clip orimplant motion in MRI (5).

Pacemakers are a strict contraindication for MRI.Dislodgement, disruption of the electrical system of thepacemaker, and asynchronous pulsing may result from themagnetic and gradient fields imposed on the pacer (6).Complications include rapid cardiac stimulation, arrhyth-mias, fibrillation, and burns (7,8).

Much anxiety and controversy surrounds the safety ofMRI in patients with aneurysm clips. Although no metal isentirely nonferromagnetic, clips may be classified nonfer-romagnetic for clinical purposes if they pass the widely ac-cepted deflection test (9). On the basis of these studies, Newet al. (9) recommended that new implants be made of alloysof titanium, stellite, and Elgiloy. Stellite and Elgiloy arecobalt–nickel alloys. Clips made of titanium and its alloysare nonferromagnetic; alloys containing at least 10% to14% nickel are weakly ferromagnetic but safe for MRI be-cause nickel is able to stabilize the iron into a form thatrenders it less magnetic. Nearly all aneurysm clips madetoday are nonferromagnetic and have been deemed safe inthe MRI environment (5,10–16). In vitro studies of tita-nium alloy, titanium, austenitic stainless steel, Elgiloy, andPhynox aneurysm clips undergoing long-term or multipleexposures to the strong magnetic fields of a 1.5 Tesla mag-netic resonance system have shown less than 2 degrees ofdeflection, rendering them safe for MRI environments (11,12,14,17,18). Human studies confirm the safety of theseclips (12,13,15,17). However, after the fatality of a patientwith a misidentified ferromagnetic clip in 1993, MRI cen-ters are highly sensitized to the appropriate identificationof aneurysm clips (19). There are numerous tables identify-ing aneurysm clips and their MRI compatibility. To insurethe patient’s safety, the written operative note describingthe implant specifications should be verified before theMRI procedure.

Many other implantable devices must be reviewed forsafety before MRI. Vascular implants are both nonferro-magnetic and ferromagnetic. However, these implants are

Departments of Ophthalmology and Neurology, Saint Louis Univer-sity School of Medicine, Saint Louis, Missouri, USA.

Correspondence to Sophia M. Chung, MD, 1755 South Grand Boule-vard, Saint Louis, MO 63104, USA; E-mail: chungsm@slucare1.sluh.edu

Modified from a platform presentation given at the 27th Annual NorthAmerican Neuro-Ophthalmology Society Meeting, Rancho Mirage, CA,February 19–22, 2001.

J Neuro-Ophthalmol, Vol. 22, No. 1, 2002 35

believed to have become firmly incorporated into the vesselwall within 6 weeks of implantation. Therefore, intravascu-lar coils, filters, and stents are MRI safe (7,20). Intraocularmetallic foreign bodies create potentially serious risks forvisual loss and are therefore considered a relative contrain-dication to MRI (21). Prosthetic valves have been shown tobe safe (22). Although many such valves do show deflec-tion forces (2.5–3 degrees in a 1.5 T magnet), these forcesare far less than those exerted by the beating heart itself(7,22). Orthopedic implants are nonferromagnetic andtherefore compatible with safe MRI scanning. However,the Perfix (Instrument Makar, Okemos, MI) interferencescrew used in repair of the anterior cruciate ligament is fer-romagnetic. The force keeping this screw in place preventsdislodgement and pain but creates artifactual changes pre-cluding interpretation (7). Pellets, bullets, and shrapnel maybe ferromagnetic, depending on the country of origin andtheir intended use. Because of the uncertainty, these objectsare considered relative contraindications to MRI scanning.A number of magnetically activated implants, such as mag-netic stoma plugs, magnetic sphincters, ocular implants,and certain cochlear implants, are hazardous in the MRI envi-ronment and should be removed before imaging (7,23,24).

Time-varying gradient magnetic fields create volt-ages and electrical currents. The currents created in MRIsystems are considered insufficient to cause biologic effectsexcept for peripheral nerve stimulation and flashes oflight (magnetophosphenes), the latter believed to be gener-ated by rotation and alignment of retinal photoreceptors.Such currents are generated particularly with 4 T MRIunits (25,26). Therefore, the Food and Drug Administration(FDA) limits the switching rates (necessary to generate atime-varying gradient magnetic fields) to a factor ofthree below the mean threshold for peripheral nerve stimu-lation (4,8).

Pulsed radiofrequency fields are used to create MRIsignals from tissue. These magnetic fields can cause skinburns when closed conducting loops are created by skin-to-skin contact between extremities (27), as by pulse oxime-ters (28) or electrocardiogram leads (8). Patients may alsoreceive burns at the site of tattoos (29). Metallic prosthesessuch as artificial hips can absorb heat but do not appear tocause injury (16,30). Gold weight lid implants used to treatimpaired eyelid closure after seventh nerve palsies havebeen shown to be safe for MRI (31).

The electromagnetic fields created for MRI renderscanning unsafe in patients with neurostimulators, bonegrowth stimulators, and drug infusion pumps. Local painand malfunction of the units have been described (24,32–34). Cochlear implants are dangerous because some arecontrolled electronically, and some have magnets withinthe implants (35). Dental brace wires cause significant im-aging artifacts but are not hazardous.

MAGNETIC RESONANCE IMAGINGCONTRAST AGENTS

Six MRI contrast agents are used worldwide for in-travenous administration. Four are gadolinium chelates andthe other two are mangafodipir trisodium and ferumoxide.All four of the gadolinium chelates are approved by theFDA for use in the United States: Magnevist (gadopentetatedimeglumine, 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 (gadoter-ate meglumine, Guerbet Laboratories, Aulnay-sous-Bois,France). Mangafodipir trisodium and ferumoxide are usedoutside the United States. Each gadolinium-based contrastagent is chelated with different agents, thereby altering itsionicity and configuration. Despite their differences, allagents have similar mechanisms of action, biodistribution,and half-lives, and are considered remarkably safe for MRIuse. They are administered in the typical diagnostic dose of0.1mmol/kg. The median lethal dose (LD50) is > 30mmol/kg for Omniscan, 12 mmol/kg for ProHance, and 6 to7 mmol/kg for Magnevist (36).

Minor adverse side effects of MRI contrast agents arenausea (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). Ad-verse reactions involving the cardiovascular, respiratory,gastrointestinal, and neurologic systems are rarely reported(< 1%). Although there are safety concerns in those patientswith renal dysfunction, primarily with respect to the releaseof free gadolinium, the contrast media are well tolerated(39). In fact, a recent study demonstrated that 0.3 mmol/kgProHance was safely administered in end-stage renal dis-ease requiring dialysis (40). Furthermore, the agents aredialyzable, with more than 95% of the dose removed by thethird dialysis treatment (41). Anaphylaxis has been reportedafter administration of Magnevist and ProHance. Therehave been 13 anaphylactoid reactions to Magnevist, a rateestimated 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 contrastagents (43,44). Therefore, the package insert includes thestatement: “The possibility of a reaction, including serious,fatal, life-threatening, anaphylactoid, or cardiovascular re-actions or other idiosyncratic reactions should always beconsidered especially in those patients with a known clini-cal hypersensitivity or history of asthma or other allergicrespiratory disorders.”

There are some adverse reactions unique to Magnev-ist and ProHance, the agents most studied. Unique to Mag-nevist is its relatively high osmolality, which is three timesthat 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 importantadverse effects demonstrated both clinically and experi-mentally (45–47). Magnevist was originally shown to causea transient rise in bilirubin and serum iron. However, afterthe reformulation of Magnevist, no changes in levels of bil-irubin and iron were detected (37). ProHance also causesnausea (1%–1.5%), and headache (0.6%), and can rarelycause altered taste sensation (0.9%–1.4%) (37). Tenanaphylactoid reactions have occurred in an estimated150,000 administrations (48). Omniscan and Dotarem havesimilar profiles to the other gadolinium agents with respectto side effects.

There are no known contraindications to use of any ofthe MRI contrast agents. In vitro studies of sickle erythro-cytes demonstrated alignment of deoxygenated cells per-pendicular to the external magnetic field (49,50). However,there have been no reports of sickle crisis precipitated byMRI contrast agents.

MAGNETIC RESONANCE IMAGINGAND PREGNANCY

There are numerous experimental studies of pregnantanimals exposed to electromagnetic fields (51). Unfortu-nately, these reports conflict with one another and firm con-clusions cannot be made about the safety of MRI in preg-nant patients. A recent controlled study compared a groupof 20 9-month-old children in whom echo planar imaging(EPI) was performed antenatally to a control group not ex-posed to EPI (52). There were no demonstrable differencesbetween the two groups with respect to numerous develop-mental categories, although gross motor function wasslightly higher in the EPI-exposed group. Furthermore,there were no ill effects on hearing. The current recommen-dations are to inform pregnant women that although therehave been no data to demonstrate deleterious effects ofMRI, there are no data to support its safety.

Magnevist crosses the placenta and appears withinthe fetal bladder soon after intravenous administration. Itis excreted into the amniotic fluid, only to be swallowedand go through the same cycle. However, the absorption ofany form of gadolinium from the gastrointestinal tractis less than 1.0% (53). Studies have shown that contrastmedia can cause adverse effects on the fetus of animal mod-els, however. Magnevist has been shown experimentallyto cause fetal developmental delay without congenitalanomalies when given in 2.5 times the human dose to ratsand in 7.5 times the human dose to rabbits (37). ProHancecan have adverse effects on the animal fetus at 5 times thehuman dose. Furthermore, fetal loss is enhanced with in-creasing doses of ProHance. There are no studies of thesafety of MRI contrast agents in pregnant women. The rec-ommendations, therefore, are to defer contrast agents in

pregnant patients unless the benefits clearly outweigh therisks (37,38).

As a matter of interest, pregnant health care personnelexposed to chronic low levels of static magnetic fields (butnot to active gradient or radiofrequency electromagneticfields, which are found in MRI) do not appear to have ahigher rate of spontaneous abortion, preterm delivery, lowbirth weight, or infertility (54).

CLAUSTROPHOBIAClaustrophobia, anxiety, and panic attacks are the

most disabling psychologic phenomena experienced by pa-tients. The proximity of the patient’s face to the inner wallof the gantry, the duration of the study, loud noises, re-stricted body movements, and the temperature and humid-ity contribute to the patient’s distress (55). Comfortingmeasures include educating the patient about the specificsrelated to the procedure, maintaining physical and auditorycommunication with the patient, and providing ample flowof air and lights to minimize the feeling of close surround-ings (56,57). Sedation is many times necessary for adequaterelaxation. With the development of wider gantries, theseproblems are expected to diminish.

HEARING LOSSThe noise created during MRI can be a risk to the

patient. As many as 43% of patients without appropriate earprotection report temporary hearing loss (58). Cases of per-manent hearing loss have also been reported (59). Durationof exposure, frequency of exposure, and intensity of noiseare the most important factors inducing hearing loss.

The noise arises primarily from the rapid alterationsin currents within the gradient coils. The force causes mo-tion or vibration of the coils which impact against themountings. The banging that results is typically between 65and 96 dB (60). As the section thickness and field of viewdecreases and as the repetition time and echo time becomeshorter, the noise becomes louder. But as acquisition time isreduced, hearing loss is less likely.

Earplugs are the safest and least costly means to pre-vent 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 MRInoise can also be used to create a signal of opposite phase tocreate a 50% to 70% reduction in perceived noise.

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