In the "olden days" radiologists thought nothing of administering double or triple the standard dose of gadolinium based contrast agents during MRI studies. "The more, the better" was the general rule of thumb. This was especially true in brain oncology cases, cardiac MRI, and vascular MRA studies in which patients were often given doses far above the vendor recommendations.
Unfortunately, recent studies have shown that up to 1% of the gadolinium intravenously injected remains in the patients brain indefinitely. When you consider over 20 million people receive gadolinium enhanced MRI studies each year, this becomes an issue that affects more than a handful of patients.
Multiple oversight agencies have expressed views on this subject, but there isn't total agreement on what to do moving forward. PRAC (Pharmacovigilance Risk Assessment Committee) was the first to weigh in on gadolinium retention in early 2017.
EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) has recommended the suspension of the marketing authorisations for four linear gadolinium contrast agents because of evidence that small amounts of the gadolinium they contain are deposited in the brain.
The agents concerned are intravenous injections of gadobenic acid, gadodiamide, gadopentetic acid and gadoversetamide, which are given to patients to enhance images from magnetic resonance imaging (MRI) body scans.
Shortly after, the ACR stepped into the ring with a strong rebuff of the PRAC recommendations.
On March 10, 2017, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) formally submitted its recommendation to suspend use of some linear gadolinium-based contrast agents (GBCAs) due to the potential risk of gadolinium accumulation within humans. As an organization committed to the highest standards in patient care and safety, the American College of Radiology (ACR) closely follows this evolving and controversial topic. After extensive review of the PRAC position and voluminous other materials, the ACR Committee on Drugs and Contrast Media disagrees with the PRAC recommendation.
Although intracranial gadolinium retention following intravenous GBCA administration has only recently been reported, it has been known for over 10 years that some gadolinium chelates are not completely stable in vivo. Fortunately, there is indisputable evidence that the amount of gadolinium deposited in tissues after a single GBCA dose is incredibly small and is detectable using only the most sensitive of medical and scientific instrumentation. Further, although gadolinium accumulation appears to be dose-dependent, there remains no evidence of cellular toxicity, nor is there credible evidence of neurologic sequelae after over 300 million worldwide human doses.
Within the same month, the good old FDA published its two cents:
A U.S. Food and Drug Administration (FDA) review to date has not identified adverse health effects from gadolinium retained in the brain after the use of gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging (MRI). All GBCAs may be associated with some gadolinium retention in the brain and other body tissues. However, because we identified no evidence to date that gadolinium retention in the brain from any of the GBCAs, including GBCAs associated with higher retention of gadolinium, is harmful, restricting GBCA use is not warranted at this time. We will continue to assess the safety of GBCAs and plan to have a public meeting to discuss this issue in the future.
So where do we go from here???? No one seems to know! With contradicting statements and a lack of evidence to make a strong conclusion, we have no idea what this retention means for the future of MRI studies. What I do know is that we should put forth our greatest effort to reduce the amount of medication we take in general; this includes gadolinium.
Fortunately, MRI has come leaps and bounds in technology that reduces or eliminates the need for contrast.
MRI angiography is a study that traditionally has used at least a single dose of contrast for each body part imaged. The development of multi-chanel phased array coils and 3T magnets have been able to generate arterial signal that has all but eliminated the need for contrast in MRA studies of the head and neck. If you look at the images below, you will see that both studies clearly demonstrate the carotid arteries. The Contrast enhanced study is a little sharper, but for a general patency evaluation, the non contrast study is more than satisfactory. MRA studies of the chest, abdomen, and extremities have come a long way as well. Although still not on par with a contrast enhanced study, the non contrast options are still fair.
The advent of 3T magnets has been another win for the contrast reduction movement. Since 3T magnets prolong the T1 relaxation about 40% more than 1.5T magnets, studies can be performed with approximately half a standard contrast dose and produce the same enhancement quality as a full dose on a 1.5T scanner. Most centers see this as a win- win: the patient gets less contrast, and the center saves money on the amount of contrast being used.
As a patient, what if you absolutely have to have a contrast enhanced study? In this case, it's best to know the safest gadolinium agents to choose from when you have the exam.
Gadolinium contrast agents are classified into two categories: linear and macrocyclic. Both are bound to chelating molecules during manufacturing. Unlike the binding process of linear contrasts, macrocyclic agents are engineered in a "cage like" manner around the molecule. This makes them much less likely to disassociate (come apart) and turn into free gadolinium in the body. Linear agents are less stable and are the primary target of the continued investigation into the safety of gadolinium contrasts.
The following table shows a list of gadolinium agents currently approved by the FDA. The ones highlighted in Blue are macrocyclic:
It would also be helpful to speak with your referring doctor or the radiologist at your chosen imaging site regarding non contrast options. In some cases, physicians leave it up to the radiologist to determine whether contrast is really needed at the time of the exam.
Like all medicine, nothing is 100% safe. Our goal as healthcare providers is to deliver service with as little collateral damage as possible for our patients. Considering alternative measures is always prudent in a patient- care centered institution.
Gadolinium will continue to be evaluated for its safety, as it should be. Until more research is done, gadolinium should be treated like any medicine and only used when needed. It's important to remember that there is no documented evidence that even retained gadolinium is harmful.