Use of MRI/MRA With or Without Gadolinium-Based Contrast Agent (GBCA) for Research
Instructions for Protocol
For research-related MRIs, the protocol should specify the type of MRI being performed [e.g., functional, structural] and whether a contrast agent is used. The protocol should also include the procedures and risks associated with MRIs.
If Gadolinium Based Contrast Agent (GBCA) is used for research purposes:
- Include the GBCA name, intravenous (IV) dosage being administered, the number of times the GBCA will be given for research purposes during the study, and the timing of the GBCA doses.
- The GBCA dosage should not exceed the amount specified in the latest GBCA product label available on the NIH DailyMed website. If the GBCA dosage exceeds the FDA-approved dose, please provide an FDA IND Exemption letter OR provide a claim of IND Exemption in your protocol using criteria from HRP-306 worksheet.
- The research protocol should clearly describe the renal testing procedures being followed.
Below is key safety information from the product insert regarding Gadavist:
- Gadolinium-based contrast agents (GBCAs), including Gadavist, increase the risk of nephrogenic systemic fibrosis (NSF) in patients with impaired drug elimination. Gadavist should only be used in these patients if the diagnostic information is essential and not obtainable through non-contrast MRI or other imaging methods.
The risk of NSF is highest in patients with:
- Chronic, severe kidney disease (GFR < 30 mL/min/1.73 m²), or
- Acute kidney injury.
Patients should be screened for acute kidney injury and other conditions that may impair renal function. For those at risk of chronically reduced renal function (e.g., individuals over 60 years old, or with hypertension or diabetes), renal function should be assessed through laboratory testing to estimate glomerular filtration rate (GFR).
- All studies using IV GBCA for research purposes are determined to be greater than minimal risk by the IRB.
- A copy of the current (most recent) product insert for the specific GBCA intended for research use, as found on the NIH DailyMed website, must be uploaded into the eIRB+ application.
IND Applicability:
- Refer to FDA guidelines on IND Exemption for protocol-specific details: INDs — Determining Whether Human Research Studies Can Be Conducted Without an IND
Participant Information:
The protocol should indicate whether participants will receive MRI results. If they don't, specify if they can request the results and the method to do so. Also, clarify if participants are notified about unusual findings.
Suggested Language for Consent Form
Procedure Section
For all MRIs (with or without contrast), include the following language:
- This study uses MRI to look at [insert the name of the organ(s) to be imaged] using magnetic fields and radio waves to create images, without using any radiation like X-rays.
- For fMRI: Functional MRI, known as fMRI will be used, for example, to measure changes in brain blood flow while performing tasks. No IV contrast agent is used for fMRI.
- For MRA: A magnetic resonance angiogram (MRA) with IV contrast dye will be done to take detailed pictures of the blood vessels in [insert organ name]. A magnetic resonance angiogram (MRA) with an IV contrast agent will be performed, using a substance like a dye that makes certain parts in the body show up more clearly on the scan to create images of blood vessels in the [insert the name of the organ(s) to be imaged e.g., neck, chest, brain].
- MRIs use strong magnets when creating images, so metal in your body that’s attracted to magnets can alter the images or even cause metal objects to move. To ensure the MRI is safe, you’ll need to fill out a form about any metal in your body and questions about your medical history that impact or could lead to harm if you have an MRI. Be sure to tell the researchers if you have:
- Metal fragments in your eyes or face
- Implants like pacemakers, defibrillators, cochlear implants, or nerve stimulators
- Had surgery on your brain's blood vessels or heart valves
- Claustrophobia (fear of small spaces)
- Body piercings or tattoos
- If you have metal in your body, you may not be able to have the research MRI unless the metal is determined to be MRI-safe.
- A urine or blood test will be done to check if you are pregnant. This test is not needed if you are postmenopausal. [The details of this test should be included in the protocol].
- Before the MRI, you’ll be given instructions. You’ll lie still on a table, and your head will be positioned in a special holder with a foam cushion. The table will slide into the MRI scanner, and the scan will take [insert the estimated duration in minutes]. [If multiple MRI sessions are required by the protocol, include the minimum and maximum time intervals between sessions].
- To get the best images, it’s important to stay very still. Let the researchers or MRI technicians know if you feel uncomfortable or if you need to stop the MRI procedure.
- The MRI scanner makes very loud noises, so you’ll be given earplugs or headphones to protect your hearing. You’ll be able to communicate with the MRI technologist through an intercom during the MRI scan for any reason.
For MRIs with a Gadolinium Based Contrast Agent (GBCA):
During the MRI, we will inject a contrast dye [insert specific GBCA product name] into your vein through an IV in your arm. You may feel a small pinprick when the needle is inserted. You might also experience a warm, flushed feeling and a metallic taste in your mouth that lasts a few minutes. In rare cases, itching or hives may occur, [insert any possible serious allergic reactions] but these can be treated with medication. If you feel light-headed or have trouble breathing, tell the technologist or nurse immediately, as this could be a sign of a more serious allergic reaction.
The contrast dye used in this study is called [insert specific GBCA product name]. The dose of GBCA you will receive in this study is [choose: approved/not approved] by the FDA . The dose is [insert dose] and is [choose: within/greater than] FDA-approved guidelines. [If outside FDA-approved guidelines please explain the purpose to the participant and why investigators feel this is still safe].
Before we give you the contrast dye, we’ll ask about any kidney or liver problems, including transplants. We will also take a blood sample, [insert in mLs and teaspoons] within 24 hours before the MRI to check your kidney health. If the blood test shows any significant kidney issues, you won’t be able to participate in the part of the study using a GBCA, and we recommend that you see your primary care doctor.
You should avoid getting additional Gadolinium contrast within 24 hours before or after this MRI.
Risk Section
Risks of MRI (or fMRI):
Some people cannot have an MRI because they have metal in their body. This includes things like pacemakers, artificial heart valves, metal implants (e.g., ear implants, bullet fragments), and devices like chemotherapy or insulin pumps. If you are aware that you have any type of metal in your body, tell the research team so that they can assess whether it is safe for you to have an MRI.
During the MRI, you'll lie in a small, enclosed space inside a large magnetic tube. Some people feel anxious or claustrophobic in this small space. The scan doesn't hurt, but it can be uncomfortable to lie still for a long time. Let the researcher know if you're concerned about claustrophobia or staying still during the test.
The MRI makes very loud banging noises, so earplugs or special headphones will be used to reduce the noise.
Some people experience localized tingling, twitching, or muscle contractions during MRI scans. This is expected, but if it is uncomfortable, please notify the MRI technician or the researcher.
If the MRI is for research, the images may not be readable by you or your doctor. If we notice anything unusual in your images, we’ll inform you and your doctor.
Most studies of MRI during pregnancy show no evidence of risk to the fetus. However, given the limited data and the vulnerability of the fetus, persons who are pregnant should not participate in MRI studies. A urine pregnancy test will be offered prior to the MRI to rule out the possibility of pregnancy. You can withdraw from the study at any time, if you have any concerns, without penalty.
Risks with IV GBCA:
The contrast dye we will administer to you during the MRI session is a GBCA named [insert specific GBCA product name]. It will be injected into your vein (usually in your arm). You will feel a pinprick when the needle is inserted into your vein, and you might experience a warm, flushed feeling or you may notice a metallic taste for a few minutes. Some people may also have side effects like headaches, nausea, or dizziness. These side effects are usually considered temporary, mild, and usually resolve without any treatment.
Nephrogenic Systemic Fibrosis (NSF):
In rare cases, a person can develop NSF after receiving a GBCA, a condition where skin and internal organs become thickened and unable to function normally. NSF is very unlikely to occur if your kidney function is normal and is more likely to occur if you have abnormal kidney function. We will check your kidney function before giving you a GBCA and if your kidney function is too poor, you will not be able to continue participation in a research procedure that requires GBCA administration.
Allergic Reactions:
GBCAs can rarely cause allergic reactions, like hives or itching. Rarely, more serious allergic reactions such as anaphylaxis can occur, which may include difficulty breathing or swelling of the face, the eyes, the tongue, the lips or the throat, which can be serious and/or life-threatening. Let the research team know if you've had allergic reactions to any IV contrast dye in the past, before any MRI is scheduled. While at the MRI, tell the researchers or MRI technician immediately if you start having any allergic symptoms after receiving a GBCA, so that the appropriate treatment can be started immediately. If you experience severe symptoms, such as difficulty breathing or swelling in the facial region or throat, after the MRI or after you leave the hospital, call 911 right away.
Gadolinium Retention:
Regardless of which GBCA you receive, some of the gadolinium can stay in your body, including in the brain, bones, and other organs, for months or years. While it is not yet known how this prolonged retention of gadolinium in the body may affect a person, studies so far have not shown harm related to prolonged retention in body tissues. Those persons at higher risk for having gadolinium retained in the body include people who have received multiple doses of GBCAs, pregnant women and young children.
Respiratory Problems:
Rarely, a serious lung problem called acute respiratory distress syndrome
(ARDS) may occur following injection of the GBCA. Call your healthcare provider right away if you have shortness of breath with or without a fever, trouble breathing, or a fast rate of breathing after receiving the IV contrast agent.
Other Possible Reactions:
Rarely, patients have reported pains, tiredness, and skin, muscle or bone ailments for a long time, but these symptoms have not been directly linked to gadolinium.
For healthy individuals with normal kidney function, about 90% of the GBCA is removed within 24 hours, but this varies among GBCAs. For most people, the remaining GBCA takes much longer to be eliminated from the body, which increases the risk of gadolinium accumulation. Although all the factors that contribute to how much gadolinium is retained by the body are not known at this time, avoiding another GBCA MRI study within the first 24 hours may help reduce risk for accumulation of the GBCA.