- Level of Risk
In general, an MRI procedure is considered to be minimal risk according to federal definitions. However, MRI studies in vulnerable populations, repeated MRI scanning procedures, MRIs requiring contrast or sedation, and MRI done in conjunction with other research interventions may not qualify as minimal risk or for expedited review.
- Risks of MRI
The long-term effects of being placed in a magnet of this strength (3 Tesla) are unknown, but you should be aware that there have been no reports of any ill long-term effects caused by magnets of the same or even higher strength, either here or elsewhere. Also, although there are no known risks associated with pregnancy, we will not scan someone who is pregnant. Therefore, you should understand that if you are a woman in your child-bearing years, pregnancy testing will be used to assure that you are not pregnant.
Some people have reported sensations during the MRI scan, such as "tingling" or "twitching" (or, very rarely, a painful sensation), which are caused by changes in the magnetic field that can stimulate nerves in your body. If you experience sensations and feel that these are uncomfortable, you can tell the MR technologist, and he or she will stop the scan immediately. Occasionally, some people experience nervousness or claustrophobic feelings due to the scanner's small space. If you encounter any discomfort, you can tell the MR technologist, and he or she will stop the scan immediately. Despite these experiences, no one has ever had sensations from the scanning that did not stop as soon as the scanning stopped.
Except for pacemakers and some types of metallic implants, we know of no health hazard from the MRI scan. The MRI scan is not painful, but lying still on the scanning table may be slightly uncomfortable
- Additional Risks of Gadolinium (Current Policy Requirements)
FDA has requested a boxed warning with additional warnings about the risk of nephrogenic systemic fibrosis (NSF) resulting from exposure to gadolinium-based contrast agents (Magnevist, MultiHance, Omniscan, OptiMARK, ProHance) in individuals with acute or chronic severe renal insufficiency. Severe renal insufficiency is defined as a glomerular filtration rate <30mL/min/1.73m2. Investigators who will be using gadolinium as part of MRI studies should ensure that they are appropriately screening participants for potential kidney problems. A properly obtained medical history is generally an adequate screening, but in elderly subjects or those who are cognitively impaired, where a history may be difficult to obtain, it may be necessary to include lab work to test kidney function.
At the 8/3/15 and 8/17/15 meetings and again at the 12/21/15 meeting, the Full Board discussed the FDA's safety announcement released July 27, 2015 stating they are investigating the risk of brain deposits of gadolinium following repeated use of gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging (MRI), and whether these gadolinium deposits are harmful or can lead to adverse health effects (see: http://www.fda.gov/Drugs/DrugSafety/ucm455386.htm). The announcement states the concern relates to patients who have undergone 4 or more scans. Though it is only under investigation at this time, the Full Board felt that participants in protocols using gadolinium should be informed. To address this issue, the Full Board requested the following:
1. Since the advisory relates the potential risk to individuals who have had 4 or more gadolinium MRI scans, protocols should contain the following exclusion criterion so that likelihood of the total number of lifetime gadolinium MRI scans will remain below 4. For a protocol involving:
a. One gadolinium scan, a history of more than 2 scans with gadolinium should be excluded.
b. Two gadolinium scans, a history of more than 1 scan with gadolinium should be excluded.
c. Three gadolinium scans, a history of any scan with gadolinium should be excluded.
d. Four or more gadolinium scans, the PI would need to justify the risk in light of the evidence prompting the FDA investigation and adjust the eligibility criteria accordingly. However, by implication the Board may not be able to approve it.
2. The Board agreed that the advisory was significant new information which may relate to the subject's willingness to continue participation and therefore must be provided to the subject according to 45CFR46: Requirements for Informed Consent. Therefore, the IRB is requiring that investigators provide currently enrolled participants with additional information (orally or in writing) regarding the FDA announcement and document this in the participant's chart.
- Additional Risks of Gadolinium (Current Policy Requirements) continued
3. The CF should explain the issue, with language such as The Food and Drug Administration (FDA) has issued an announcement stating they are investigating a possible risk of adverse health effects from repeated use of gadolinium for MRI. Though the FDA has not reached a conclusion at this time, you should not participate in this study if you have previously had more than (insert # consistent with item (a) above) MRI scan with gadolinium.
4. A discussion template should be prepared conveying similar information to be the basis for discussion with currently enrolled participants.
5. In order to ensure that individuals are systematically queried about previous gadolinium scans, please operationalize questions to determine whether an individual has had a previous gadolinium scan and add this information to the PSF. For example, individuals should be asked whether they had an MRI with an i.v. injection (i.e., Did they give you an injection?) in case people do not know the term gadolinium.
6. The Board also considered known risks of gadolinium, namely vomiting and allergic reactions, and determined updated guidelines for the conduct of gadolinium MRI in the NYSPI MRI suite. Allergic reactions are rare, but can be severe. Vomiting is less rare and occurs in about 1% of cases, and provision should be made to promptly remove participants from the scanner to avoid risks of aspiration.
a. The PSF should clearly state who is responsible for safety procedures during the MRI scans, either the MRI unit staff or the study staff. The MRI Center has safety procedures, including management of nausea/vomiting, and management of allergic reactions including assessment of the participant, administration of epinephrine if indicated, and calling emergency response teams if indicated. If the study staff are responsible for overseeing the MRI scan and MRI-related safety procedures, the PSF must indicate that they will be trained by the Medical Director of the MRI Center and his designees and confirm that the study team will abide by the MRI Center Safety Protocol.
b. The MRI CF should state that if a participant feels nauseous during the MRI, he/she should alert the staff immediately. Because vomiting does occasionally occur as an adverse event of gadolinium contrast agents, it is important for a participant to alert staff so that he/she can be promptly removed from the scanner.
c. The MRI CF should also inform participants of the type of symptoms to be aware of if they were to have an allergic reaction to gadolinium. The Hatch MRI center in its guidelines provides such a list to subjects/patients.
- Minimizing Risk
Each proposal must minimize risks and discomforts to participants, including:
1. Screening for metallic devices, implants and other contraindications to scanning. Use of a screening questionnaire is recommended.
2. Exclusion for pregnancy using a pregnancy test prior to scanning.
3. Exclusion of those unlikely to tolerate the sense of confinement during scanning.
4. Providing adequate medical, safety monitoring and observation during scanning, as appropriate.
5. Reducing scanning time to that necessary to accomplish the scientific aims of the study.
6. Enhancing the subjectâs physical and emotional comfort during the scan.
- Clinical Reading of Research MRIs for Studies Reviewed by the NYSPI IRB
Investigators, in collaboration with a neuroradiogist, must determine whether the proposed scanning procedures will produce images requiring reading according to this policy. In studies that more than one type of scan, and determinations regarding reading requirements must be made for each scan. The proposed scanning method, the determination regarding readability, and the procedures for reading and communication of results to the subject must be detailed in the PSF, CF and supporting documents. All MRIs: All scans must be examined for gross structural abnormalities such as the presence of mass effects or hydrocephalus. T1-weighted images and fMRI studies in which T2-weighted or T2*-weighted echo planar images are acquired: Regardless of resolution or other image characteristics, these scans do not, in general, yield adequate information for a clinical-quality read, and a clinical reading is not required, except as per (3), above. T-2 weighted or T2-FLAIR images: These scans may provide information that is clinically relevant. The quality of clinical information available from these images can vary widely, based on resolution, degree of motion artifact, and numerous aspects of the pulse sequences used to acquire them. All such scans must be read by a clinical neuroradiologist. As with any imaging procedure, if the radiologist determines that the quality of the scan does not lend itself to a clinical reading, he or she will provide written documentation to this effect. Only the radiologist may make this determination. Please note: fMRI studies in which T2-weighted or T2*-weighted echo planar images are acquired require reading only as described in (3), above. Readings of other images: Individual investigators who wish to have other images read clinically may choose to do. Clinical readings, as described above (1, 3-6), must be performed and documented by an appropriately qualified, privileged, and indemnified board-certified or board-eligible radiologist.
- Clinical Reading of Research MRIs for Studies Reviewed by the NYSPI IRB cont.
Timing of Interpretation and Communication of results:
1. Should an MRI technician or other member of the research team suspect that an MRI scan suggests evidence of a significant lesion, the PI of the study should be notified immediately.
2. When the readings yield findings that are of urgent clinical concern, the radiologist should immediately provide an oral report followed by a handwritten or typed note to the PI and the Director of the MRI Unit. A final written transcript of the clinical reading should be provided within two weeks of the oral report.
3. The radiologist must provide routine written reports to the investigator within one month of image acquisition.
4. All results should be shared with research subjects in a manner that is consistent with the acuity and certainty of the finding, and should be communicated by an appropriately qualified member of the research team.
5. Subjects scanned using imaging techniques (T-2 weighted or T2-FLAIR images, as per A.5.) above and all other readings that suggest evidence of mass effects or hydrocephalus or other significant abnormalities (at the discretion of the radiologist) must receive feedback about their scan(s). For other scans, subjects may opt to receive feedback about their MRIs (see consent language).
6. The PSF must detail all procedures for communicating results and incidental findings to subjects as per this policy, and the consent form must indicate that the scan will be read, under what circumstances results will be made available, and a statement about the clinical value or limitations of the reading.
The PSF confidentiality section should describe where scans, associated clinical and identifying data, and clinical readings will be stored and how confidentiality will be maintained. If results are to be maintained on a widely available database (e.g. Webcis) this information should be noted and described in the consent form.
Overview: consent must be discussed and documented by a qualified member of the research team. The individual must certify that he or she has completed human subjects training and has been trained, and observed discussing consent. He or she must be supervised, as needed, during the consent procedure.
Sample Consent Form Language (please adapt as necessary for specific studies):
1. Alternatives to participation (same for all MRIs)
This is not a treatment study. Information being collected is for research purposes only and is to learn more about __________, not about you. It is not necessary to participate in this research study to have an MRI, and the MRI done as part of this study is not the same as one done for medical purposes.
2. Study Procedures (same for all MRIs)
MRI (Magnetic Resonance Imaging). The MRI uses strong magnetic fields and radio waves to take pictures of your brain. MRI involves lying on a table that slides into a large magnet shaped like a cylinder. Before beginning the imaging procedure, we will determine that you do not have a pacemaker or any unsafe metallic implants such as an aneurysm clip or heart valve and certain tattoos, and you will be asked to remove any metal or magnetized objects (such as keys, chains, jewelry, retainers, medication patches, hairpins or credit cards). You will be asked to lie flat on your back in the MRI scanner for ______ minutes and to remain as still as possible. You will not feel anything, but you will hear a knocking, noise. This is a normal sound produced by the MRI scanner and does not indicate that anything is wrong.
3. Study Risks
Study risks must be described in relation to specific scanner and scanning procedures, for example, for 1.5T and 3T magnets.
While there have been no reports of any harmful long-term effects caused by 3T magnets or magnets of even higher strength, the long-term effects of being placed in a magnet of this strength are unknown. Also, although there are no known risks associated with pregnancy, we will not scan someone who is pregnant. If you are a female in your childbearing years, you will be asked to take a pregnancy test to ensure that you are not pregnant.
Some people have reported sensations during MRI scans with the 3T magnet, such as "tingling" or "twitching" (or, very rarely, a painful sensation), which are caused by changes in the magnetic field that can stimulate nerves in your body. With any MRI scan, on occasion, some people experience nervousness or discomfort due to the scanner's small space and the need to lie still. Except for pacemakers, some types of metallic implants, and medication patches, we are not aware of any other potentially dangerous interactions or hazards associated with the MRI scan. The MRI scanner also produces a loud noise; earplugs will be provided to reduce this discomfort. If you experience any discomfort and wish to stop the scan, you can tell the MRI technologist, and he or she will stop the scan immediately. In our experience, no one has had sensations from the MRI that did not stop when the scanning stopped.
4. Benefits regarding MRI
You are not expected to benefit from participation in this study.
5. Results of your MRI
While MRI scans are sometimes done for clinical purposes, the kind of MRI scan you will have as part of this study is for research purposes only. This means that the scans are not designed to provide clinical information that might be helpful to you or your doctor and they may not show problems that would normally be found in an MRI ordered to evaluate a specific medical problem. It is likely that the MRI scan will not have the quality of those done for clinical purposes.
For T1 weighted images:
However, within a month of the MRI, the scan will be read by a neuroradiologist for evidence of any obvious irregularities requiring your follow-up. You, or a physician whom you may designate, will be informed only when significant abnormalities are detected. If you wish, we can also inform you if there were no obvious findings. Given the nature of the scan, the absence of a finding does not mean that one is not present.
For T2 and T2-FLAIR images:
However, within a month of the MRI, your scan will be read by a neuroradiologist and information about the scan will be shared with you or a physician whom you may designate.
6. Confidentiality (re: MRI)
Depending on the location of scanning and interpretation, one of the following statements should be included:
"The results of your MRI scan will be maintained in an electronically secure database at NYSPI or CUMC and accessible only to the members of the research team" or,
"The results of your MRI scan will be maintained on the clinical information system at Columbia University Medical Center and will be accessible to hospital clinicians."
- Guidelines for informing subjects about findings
A. For TI weighted images
The investigator should have the participant indicate, in the consent form, if they wish to be contacted with the results from the reading of their research MRI. If so, subjects should be informed by letter (the template must be approved by the NYSPI-IRB). The letter can indicate that there were no findings detected, but must emphasize the limitations of the scan. When there is evidence of a mass lesion, hydrocephalus or other significant abnormality, a qualified clinician should call the subject and then a letter should be sent, depending on the urgency, and at the discretion of the investigator and radiologist.
B. T2 and T2-FLAIR weighted images
When the approved protocol specifies that the scan will be interpreted, the consent form will indicate that the research will contact the subject or their individual physician by letter with information about their MRI research scan. Form letters, which must be approved by the NYSPI-IRB, can reflect different levels of concern or urgency. Like the decision to have the scan interpreted, the information conveyed to subjects must carefully consider the interpretably of the scan and the significance of the findings. The study PI and neuro-radiologist will confer on the method and content of information to be provided to the subject. The first sample letter (below) indicates that there are no findings (no clinically significant abnormality), the second level indicates findings of uncertain clinical significance, and the last level indicates evidence of an abnormality that requires clinical follow-up. Calling participants with evidence of an abnormality is required.
Sample language for informing participants of findings by letter
A. For T1 weighted images:
1. No findings
The review of your scan was done by a doctor trained in brain MRI interpretation (a neuroradiologist) who found no obvious irregularities during the reading of the MRI. If you would like to request that a copy of the report be sent to your physician please call _________ at ___(phone number)__.
We remind you that the MRI scan of the brain that we performed was for research purposes only. It would not show problems that would be picked up by a more specialized medical MRI scan ordered by your doctor for a specific medical problem. The scan provides little clinical information other than the presence or absence of certain irregularities. In fact, the absence of a finding does not mean that one is not present.
Please contact us if you have any questions.
2. Apparent irregularity
As we mentioned in our recent telephone conversation, the review of your scan by a doctor trained in brain MRI interpretation (a neuroradiologist) showed an irregularity, and we recommend that you follow up with your physician as soon as possible to determine if any further action is necessary. If you would like to request that a copy of the report be sent to your physician, please call ________ at ___________.
B. For T2 and T2-FLAIR weighted images
Thank you for participating in our study. We remind you that the MRI scan of the brain that we performed was for research purposes only. It may not show problems that would be picked up by a more specialized medical MRI scan ordered by your doctor for a specific medical problem.
1. No findings:
"The review of your scan was done by a doctor trained in brain MRI interpretation (a neuroradiologist) who found no significant findings as a result of the MRI. If you would like to request that a copy of this information be sent to your physician please call _________ at ___(phone number)__."
2. Findings of uncertain significance, which may or may not require follow-up, call with questions:
"The review of your scan was done by a doctor trained in brain MRI interpretation (a neuroradiologist). Please call the (the PI) ________ at ___________ so that your MRI findings can be discussed with you. If you would like to request that a copy of this information be sent to your physician please call ___________ at ____________. "
3. Significant (follow-up letter to phone call):
"As we mentioned in our recent telephone conversation, the review of your scan by a doctor trained in brain MRI interpretation (a neuroradiologist) showed an irregularity, and we recommend that you follow up with your physician as soon as possible to determine if any further action is necessary. If you would like to request that a copy of the report be sent to your physician, please call ________ at ___________."