Neurologic Complications of Imaging Procedures

Iodinated Contrast Media

Iodinated contrast medium is used extensively for intravenous and intra-arterial x-ray imaging examinations. The risk of adverse reactions is low, especially as usage has changed from ionic to nonionic, low-osmolality agents. The latter has largely replaced ionic high-osmolality agents and is associated with an incidence of acute adverse reactions (allergic-like plus physiologic) of less than 1 percent. Another advantage of nonionic agents is their isotonicity, which markedly reduces the sensation of heat and flushing.

Contrast reactions are sporadic and largely unpredictable. A prior allergic reaction to contrast material is a substantial risk factor for a recurrent allergic-like adverse event. Atopic individuals and asthmatics are also at increased risk for allergic-like contrast reactions. In addition, hemodynamic changes may occur during or shortly after injections in patients with various cardiovascular diseases.

Idiosyncratic allergic reactions may occur on first or subsequent contrast administration and range from hives to more severe reactions such as pulmonary or cerebral edema, laryngospasm, bronchospasm, and cardiovascular collapse. Dose-related effects of tonicity and chemical toxicity mainly affect the heart, lungs, and kidneys and include cardiovascular depression and renal failure. Life-threatening reactions occur in approximately 0.05 to 0.16 percent with ionic contrast media injections and 0.03 percent with nonionic contrast materials; the death rate, however, is similar with both types of agents, occurring in approximately 1 to 3 per 100,000 injections.

Regardless of the type of contrast medium used, extravasation into the soft tissues of the arm at the time of injection may lead to local tissue injury, including skin necrosis. Swelling, which attends severe extravasation injuries, may also lead to compartment syndromes and therefore to injury of peripheral nerves. This is a rare complication, but the risk increases with the use of automated power injectors, and the administration of contrast to infants, young children, and unconscious or debilitated patients (such as diabetics or patients receiving chemotherapy).

Contrast Media for Magnetic Resonance Imaging

Most contrast agents for magnetic resonance imaging (MRI) are variations of chelates of gadolinium, a lanthanide metal. Gadolinium is toxic in its free form, but through chelation with diethylenetriamine penta-acetic acid (DTPA) or other moieties is typically eliminated from the body by renal clearance. Gadolinium-based contrast media are considered safe and well tolerated by the vast majority of patients; the incidence of complications is less than 0.5 percent. Minor side effects including headache, nausea, and vomiting, are sometimes noted, but the risk of immediate hypersensitivity reactions is extremely low, on the order of 1 per several 100,000 injections. Nonetheless, severe immediate hypersensitivity reactions and death secondary to gadolinium administration do occur. Clement and co-workers have shown that, while rare, allergic hypersensitivity reactions are identified in up to 20 percent of patients experiencing a reaction to intravenous contrast material, including gadolinium, and there is a high incidence of cross reactivity with other agents in the same family, especially for gadolinium agents.

Gadolinium agents cross the placenta, with undetermined effects on developing fetuses, and are seen in small amounts in the breast milk of lactating mothers; therefore, they are not recommended for use in pregnant women unless absolutely necessary. It is unlikely that the small amount of gadolinium absorbed by a nursing infant’s gastrointestinal tract is harmful but, if concern exists, the nursing mother can be advised to discard her breast milk for 24 hours after gadolinium administration.

Based on the structures of the chelating ligands, gadolinium contrast agents can be divided into two categories: linear and macrocyclic. According to their charges, gadolinium can also be subclassified into ionic or nonionic agents. Macrocyclic and ionic agents are more stable than linear agents, as the free gadolinium is completely isolated within the preformed cage of the macrocyclic chelate whereas, in linear molecules, free gadolinium is wrapped around with elongated ligands. Gadolinium may become disassociated from its chelated agent and is then deposited in the tissues, including the brain. This occurs primarily in the dentate nucleus of the cerebellum, but in other areas as well. No known deleterious effects have been identified from this deposition seen on T1-weighted MR scans as high signal, particularly with repeated injections of linear gadolinium agents.

Nephrogenic systemic fibrosis, characterized by fibrosis of skin and other organs, is a rare disorder caused by deposition of free gadolinium following administration to patients with acute renal failure. For this reason, the use of linear gadolinium agents is not advised in patients with a glomerular filtration rate of less than 30 mL/min per 1.73 m ² . Macrocyclic gadolinium contrast agents are much less likely to cause this complication and can be safely administered to patients with glomerular filtration rates between 15 and 30 mL/min per 1.73 m ² .

Other novel MRI contrast agents are now available for limited clinical applications. The superparamagnetic iron chelates work on the basis of reducing signal within normal tissues such as lymph nodes and liver and thus provide contrast for nonenhancing abnormal tissues. Chelates of manganese are also approved for liver imaging. Free manganese has a theoretical risk of parkinsonian complications, but the chelated compound caused no serious side effects during phase 2 clinical trials. Intravascular contrast agents are being evaluated and promise to improve magnetic resonance angiography and perfusion of brain tumors.

Deleterious effects of MRI exposure on pregnant women or the developing fetus have not been shown. Nevertheless, it is recommended that women of reproductive age be screened for pregnancy before entering the MR environment. The clinician should confer with the radiologist and document that the information cannot be acquired by other nonionizing means (e.g., ultrasonography), that the information is needed to care for the patient or fetus during the pregnancy, and that it is not prudent to wait until the patient delivers to obtain the scan.

Miscellaneous Complications of Contrast Media

Rare complications of contrast administration include retrograde reflux of contrast material via the abdominal port of a ventriculoperitoneal shunt after bladder rupture sustained during voiding cystourethrography. The extravasated contrast medium then tracked up the ventriculoperitoneal shunt, causing seizures and ventriculitis. Venous air embolism has been documented during infusion of contrast medium, due to either scalp vein malposition or inadvertent trapping of air within power injectors or tubing. Venous air embolism can cause a stroke, especially in infants with patent cardiac foramen ovale or other right-to-left shunts.

Acetazolamide, a vasodilator of the cerebral circulation, is now occasionally administered for perfusion MR or computed tomography (CT) studies. Comparison of studies before and after acetazolamide allows determination of the cerebral vascular reserve. Acetazolamide, although well tolerated, has minor side effects such as nausea and headache. It is a diuretic, so adequate hydration and satisfactory serum potassium levels must be ensured, particularly in those already receiving diuretics for medical reasons. Acetazolamide is probably not indicated in the setting of acute stroke because its diuretic effect may reduce cerebral perfusion.

Computed Tomography

Neurologic complications of x-ray CT are related to complications of sedation, contrast administration, or other mishaps that incidentally attend the procedure. There is a small risk of radiation-induced cataracts, leukemia, and other tumors following multiple CT studies, especially in children. This concern has increased with recent technologic advances: helical-mode scanners are now used routinely in CT angiography and CT perfusion studies to scan rapidly large regions of the body. Multiple scans during infusions of contrast material may result in additional radiation exposure. For this reason, MRI and ultrasound are better methods for following patients who require repeated imaging procedures, as long as their diagnostic benefit is equivalent to or better than that of CT.

Magnetic Resonance Imaging

MRI has rapidly gained wide acceptance in the imaging of the CNS as well as for musculoskeletal and many cardiac and general body applications. Images are produced by placing a patient in an extremely strong static magnetic field (on the order of 15,000 to 30,000 times the Earth’s magnetic field) and then probing the magnetic relaxation properties of water protons in the body using radiofrequency pulses; computer mathematical manipulation allows the production of images.

Because of the need for a very strong, continuous magnetic field, the presence of metal objects near the imaging environment can be hazardous, since they can accelerate toward the magnet, acting as missiles with resultant harm to patients and staff. Anyone coming into proximity of an MRI machine is therefore routinely screened for ferromagnetic objects prior to entering the magnet room. The major contraindications to MRI examinations include the prior placement of ferromagnetic aneurysm clips or cardiac pacemakers, intraocular metallic foreign bodies, certain types of prosthetic cardiac valves, electronic or magnetically activated medical devices, and any other large, potentially ferromagnetic foreign body. Pacemakers have long been considered an absolute contraindication to MRI, but recent literature suggests that these studies can be safely performed in some patients as long as precautions are taken before, during, and after the study and the benefit of MRI outweighs the risk of pacemaker malfunction or harm to the patient. Implanted cardiac defibrillators likewise have led to no adverse events from repetitive MRI at 1.5 T in patients with implanted defibrillators.

The hazard of aneurysm clips deserves special attention. Most currently manufactured aneurysm clips have few if any ferromagnetic properties, as judged by lack of deflection within a magnetic field when tested in vitro. At least one instance of fatal clip movement in a patient has, however, been reported, and in that case was due to inaccurate information supplied during the screening process. Newer nonferromagnetic clips, such as titanium alloys, are safe at 1.5 T, but discretion is always advised. At higher field strengths, such as 3 T, titanium alloy clips are preferred if MRI is necessary, but care must be taken while moving patients through the opening of the bore toward the center of the magnet, as the largest torque forces occur during this maneuver. The potential information to be gained from the procedure must be carefully balanced against the potential danger of clip movement. Although the metal from the clip may cause significant artifact on the examination, useful information can often still be gleaned by appropriately tailoring the examination.

The potential risks of metallic stents and endovascular detachable coils also merit consideration. A new generation of MRI scanners, including at 3.0 T, with shorter lengths and wider apertures (e.g., 70 cm diameter and about 160 cm length), results in much larger gradients. Larger magnetic susceptibility of the employed material, larger mass, higher magnetic field, and larger gradient will increase the magnetic force on the metallic implant upon entering the MRI magnet. These devices produce ferromagnetic artifacts, and thus the local anatomy is distorted on MRI. MRI is safe at 1.5 T for patients who have recently had placement of a coronary stent.

Some monitoring devices are potentially dangerous because looped metallic wires may acquire induced currents, resulting in burns to the skin attachment sites. The US Food and Drug Administration (FDA) received 1,568 adverse event reports for MR systems between January 1, 2008 and December 31, 2017. Thermal events were the most commonly reported serious injury (59%). In addition, mechanical events—defined as slips, falls, crush injuries, broken bones, and cuts; and musculoskeletal injuries from lifting or movement of the device—were observed in 11 percent, projectile events in 9 percent, and acoustic events in 6 percent. For this reason, all physiologic monitoring equipment and other devices must be carefully screened and approved specifically for use during MRI. Exposure of electrically conductive leads or wires to the RF transmitted power during MR scanning should be performed with caution and appropriate steps taken to ensure that lead or tissue heating does not result. Patients who require EKG monitoring and who are unconscious, sedated, or anesthetized should be examined after each MR imaging sequence and repositioning of the EKG leads and any other electrically conductive material with which the patient is in contact should be considered. Extensive testing and safety information about specific devices is available from MRIsafety.com as well as from Shellock and associates.

Screening of patients referred for MRI is essential prior to the examination. If patients are unable to fill out a questionnaire or are unconscious and their family is not present or unable to provide the required information, they should be thoroughly examined by medical personnel with attention to surgical scars. If these are present, a radiograph is suggested prior to MRI. When in doubt, the presence of a specific medical device must be documented precisely and in writing before entry of the patient into the magnet. This information can be checked against the known magnetic deflection properties of the device, as appropriate. In patients with a history of possible metallic ocular foreign body, plain radiography of the orbit or low-dose orbital CT can be used to exclude the presence of significant metal fragments, as these can move in the magnetic field and result in ocular injury and blindness.

Another potential hazard related to the static magnetic field required for MRI is that of missile injury, mentioned earlier. The missile effect is perhaps the most serious potential hazard because many clinicians entering the MR environment are not aware that the magnet is always “on.” Paper clips, scissors, vacuum cleaners, chairs, floor buffers, oxygen tanks, anesthetic equipment, and other ferromagnetic metallic items have been pulled rapidly into the bore of a magnet when inappropriately brought close to it, sometimes with fatal results. Proper introduction to safety precautions for visitors is important. The American College of Radiology recommends that zones of access be created and labeled to inform the public as they get closer to the magnet room itself.

The rapid switching of the gradient coils used in MRI may result in induced voltage and current in implanted wires, such as cardiac leads or brain-implanted electrodes, as well as thermal injuries. MRI gradients may cause a loud vibration or banging noise that can result in hyperacusis or tinnitus. Both temporary and permanent instances of hearing loss have also been reported; for these reasons, the use of earplugs is mandatory during MR examination for all patients as well as accompanying parents or visitors within the magnet room. These are especially recommended in cases requiring very rapid switching of gradient coils, as with most MR angiography sequences and ultrafast techniques such as fast spin-echo and echo-planar techniques (e.g., diffusion and perfusion imaging and functional MRI). Tissue heating is also a potential but relatively insignificant complication of MRI. The FDA limits the specific absorption rate, which is the radiofrequency energy deposition, to 0.4 W/kg averaged over the body. In animal studies, levels at 10 times this rate over a 75-minute period raise the skin and eye temperature of a sheep by only 1.5°C, with no observed side effects. Nonetheless, the FDA has determined limits, particularly for small infants and children.

Myelography and Intrathecal Injections of Contrast Media

The number of myelographic procedures has diminished dramatically since the introduction of MRI and CT. MRI is superior to myelography in the evaluation of lumbar disc disease, discitis and vertebral osteomyelitis, myelopathy, and extradural and intradural spinal mass lesions.

When myelography is recommended, it usually is performed in conjunction with CT. CT myelography is preferred to plain-film myelography for evaluating the thecal sac in those patients who cannot tolerate MRI because of severe claustrophobia or because of other contraindications to the magnetic environment, discussed previously. Many patients with severe spondylitic disease of the spine or failed-back syndrome may benefit from CT myelography. In such instances, a lumbar puncture is performed for instillation of 5 to 8 ml of iodinated nonionic contrast before thin-section CT scanning is performed. In many patients, CT myelography may complement MRI, especially in patients who have bony osteophytes that may be difficult to distinguish on MR or in those with metal implants that obscure MR images.

Few indications remain for traditional plain-film (high-dose) myelography. Those with suspected cerebrospinal fluid (CSF) loculations or arachnoid cysts may still benefit from myelography because the septations separating these CSF-filled structures can be difficult to detect on MRI and the dynamic nature of myelography can be useful. In addition, myelography in combination with CT is required occasionally to locate precisely the site of a spinal CSF leak. Conventional myelography is also indicated occasionally for the evaluation of patients with back pain after orthopedic instrumentation because CT and MRI are often compromised by metallic artifacts.

The reduction in myelograms performed at teaching institutions has reduced the exposure of trainees in radiology to this procedure. As with any procedure, the incidence of complications associated with a procedure relates to the experience of the practitioner. In the case of myelography, it is our impression that the rate of complications is on the rise because of the decrease in experience of recent trainees. It is therefore appropriate to review the neurologic complications of myelography and intrathecal injections of contrast material despite their decline in use.