Iodinated Contrast Media

Iodinated contrast medium is currently available in ionic and nonionic, water-soluble formulations. Ionic contrast media are less expensive but are associated with a higher incidence of adverse reactions than nonionic contrast agents; approximately 4 to 12 percent of patients receiving ionic media experience some hypersensitivity reaction within minutes or after several hours compared with 1 to 3 percent of patients receiving nonionic contrast media. Nonionic contrast agents have largely replaced ionic contrast media for intravascular use throughout the body and should be used exclusively in children younger than 2 years, patients at risk of allergic reactions, and those with renal failure, diabetes, cardiopulmonary disease, or serious illnesses. Another advantage of nonionic agents is their isotonicity, which markedly reduces the sensation of heat and flushing.

Prior allergic-like reaction to intravenous contrast material is the most substantial risk factor for a recurrent allergic-like adverse event. Although such a history is not an absolute predictor, the reported incidence of recurrent reactions ranges up to 35 percent. Atopic individuals (particularly those with multiple severe allergies) and asthmatics are also at increased risk of allergic-like contrast reactions.

The toxicity of ionic contrast media is well documented and is related to the tonicity, ionic charge, and chemical toxicity of the agents, as well as allergic/anaphylactic phenomena. 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. Secondary neurologic symptoms and signs may result when significant cardiorenal dysfunction occurs. Life-threatening reactions occur in approximately 0.05 to 0.16 percent of 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.

The most common major neurologic complication ascribed to ionic contrast media is a seizure, which occurs primarily in patients with primary or metastatic tumors. Seizures and parkinsonian symptoms as well as cortical blindness have also been reported after the use of ionic media during cardiac or vertebral angiographic procedures. The cortical blindness is usually transient and has been associated with abnormal retention of contrast medium within the occipital cortex. It has been postulated that a time- and dose-related breakdown of the blood–brain barrier leads to subsequent direct neuronal toxicity. Aggravation of myasthenia gravis is a potential risk of intravenous ionic contrast administration but appears to be somewhat less frequent with the nonionic formulations. These complications are now rarely seen because low osmolality, nonionic contrast media have largely replaced ionic media for intravascular use.

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. The risk of severe soft-tissue injury is greatest with extravasation of ionic contrast agents that have been injected by power injectors. Swelling, which attends severe extravasation injuries, can also lead to compartment syndromes and therefore to injury of the peripheral nervous system. Automated power injectors, which are used in daily practice, may result in the extravasation of large volumes of contrast material, leading to severe tissue damage. Infants, young children, and unconscious and debilitated patients (e.g., diabetics, patients receiving chemotherapy) are particularly at risk of extravasation.

Contrast Media for Magnetic Resonance Imaging

Contrast media for magnetic resonance imaging (MRI) have a lower toxicity profile and much higher patient tolerance than iodinated contrast media. Most magnetic resonance contrast agents are variations of chelates of gadolinium, a lanthanide metal. Gadolinium is toxic in its free form, but through chelation with DTPA or other moieties is safely distributed and then eliminated from the body by renal clearance. Both ionic and nonionic formulations of gadolinium are available. Gadolinium-based contrast media are 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 anaphylaxis is extremely low, on the order of 1 per several 100,000 injections. Nonetheless, severe reactions and death secondary to gadolinium administration have been reported. Li and associates showed that among 45 patients who developed reactions to gadolinium, only 3 (6.7%) had prior adverse reactions to iodinated contrast, 3 had prior reactions to a different gadolinium-based compound, and 10 had prior food or drug allergies (9) or asthma (1).

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 will be harmful but, if concern exists, the nursing mother can be advised to discard her breast milk for 24 hours after gadolinium administration.

Nephrogenic systemic fibrosis, characterized by fibrosis of skin and other organs, has been documented following gadolinium administration in patients with renal failure. For this reason, gadolinium administration is not advised in patients with glomerular filtration rate of less than 30 ml/min per 1.73 m ² . Macrocyclic gadolinium contrast agents appear to decrease the availability of free gadolinium and thus of nephrogenic systemic fibrosis in those with renal failure. Dialysis immediately following gadolinium administration is recommended to minimize this possible complication.

Other novel MRI contrast agents are also 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 MR imaging 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 data are needed to effect the care of the patient or fetus during the pregnancy, and that it is not prudent to wait until the patient is no longer pregnant to obtain these data.

Miscellaneous Complications of Contrast Media

Reflux of ionic x-ray contrast medium has been reported into the abdominal port of a ventriculoperitoneal shunt after bladder rupture sustained during voiding cystourethrography. This 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 stroke, especially in infants with patent cardiac foramen ovale or other right-to-left shunts. The presence of iatrogenic air in the venous sinuses is important to recognize and distinguish from infectious causes.

Acetazolamide, a vasodilator of the cerebral circulation, is now occasionally administered before perfusion MR and 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 usually 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 in or around the imaging environment can be hazardous, since they can accelerate as missiles, harming patients and staff. Patients, staff, and others coming into proximity of the magnet are therefore routinely screened for ferromagnetic objects. 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 MR study and the benefit of MR outweighs the risk of pacemaker malfunction or harm to the patient. Implanted cardiac defibrillators likewise have long been considered an absolute contraindication to MRI, but Junttila and colleagues showed no adverse events from repetitive MRI at 1.5 T in 10 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. The performance of MRI in patients with aneurysm clips is therefore a matter of controversy; newer non- ferromagnetic clips, such as titanium alloys, appear to be safe at 1.5 T, but discretion is always advised. At higher field strengths, such as 3 T, titanium alloy clips are preferred if MR 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. 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, oxygen tanks, anesthetic equipment and other ferromagnetic metallic items have been rapidly pulled 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. These gradients may also 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 gradients coils, as with most magnetic resonance 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 to date insignificant complication of MRI. The US Food and Drug Administration (FDA) limits the specific absorption rate (SAR), 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 has clearly been established as superior to myelography in the evaluation of lumbar disc disease, discitis and vertebral osteomyelitis, myelopathy, and extradural and intradural spinal mass lesions. Compared with CT and MRI, myelography is limited as a single investigation of lumbar disc disease because of its insensitivity to extraforaminal, paraspinous, and lateral disc disease.

When myelography is recommended, it is almost invariably 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 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.

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. Myelography is also indicated for the evaluation of patients with back pain after orthopedic instrumentation because CT and MRI are 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.

Discography

The value of discography is primarily as a provocative test that attempts to recreate the patient’s back pain syndrome, with the goal of isolating the generator of pain. A needle is placed in the nucleus pulposus of a lumbar or cervical disc and water-soluble contrast agent is injected while observing the patient’s response. CT can be performed after discography for added spatial resolution. Horton and Daftari found that although MRI and discography correlated in many instances, MRI could not reliably predict which disc was the cause of a patient’s pain.

Discography is a controversial procedure. Johnson found no evidence that diagnostic discography injured normal discs, but two reports have demonstrated exacerbation of preexisting herniated disc material by discography. Carragee and associates found that discography resulted in accelerated disc degeneration, disc herniation, loss of disc height and signal and the development of reactive endplate changes compared to match-controls.

Complications with discography are mainly related to either septic or aseptic discitis. Antibiotics are often added to the contrast media used for discography, but evidence of benefit for their routine use is lacking. Care must be taken to prevent intrathecal instillation of antibiotic-contrast solutions. The incidence of discitis may be related to the length of the procedure, the use of a single needle rather than coaxial technique, and breaks in sterile technique.

Epidural and Transforaminal Anesthetic Neural Block

Patients with back or neck pain often benefit from local anesthetic blockade either to confirm the location of the pain generator or to reduce pain, or both. Diagnostic and therapeutic nerve root blocks involve the local injection of anesthetics such as 0.75 percent bupivacaine with or without steroid compounds around exiting nerves or into the epidural space of patients suffering from local or radicular back or neck pain. Injections are administered via a 22- to 25-gauge needle placed into the area of interest using fluoroscopic or CT guidance. Direct injections are made into the epidural compartment of the spine, facet joints, or focally around an exiting nerve near the neural foramen. Complications of these procedures include spinal cord or cerebellar infarction secondary to injection into or spasm of the vertebral or radiculomedullary arteries, inadvertent injection into the spinal cord or nerve root itself, infection, and rare allergic or other side effects related to the injected agents. Botwin and co-workers reviewed the incidence of complications of fluoroscopically guided lumbar epidural injections in 207 patients and found a 9.6 percent incidence of minor complications ranging from transient headache, back pain, leg pain, facial flushing, vasovagal reaction, and increased blood sugar levels, most likely induced by systemic absorption of corticosteroid. Serious complications such as epidural hematoma, spinal cord injection, and paraplegia or quadriplegia secondary to inadvertent injection into the spinal or vertebral artery have been reported following transforaminal epidural nerve block. An outbreak of fungal meningitis caused by contaminated steroid mixtures occurred in 2012.