Responsibility: faculty and student investigators. 1.0 Screening participants

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1 UNIVERSITY OF WATERLOO Department of Psychology STANDARD OPERATING PROCEDURES UWHSOP 605: Protocol for functional MRI scanning at Grand River Hospital Purpose: This document is intended to act as a standard operating procedure for University of Waterloo researchers intending to conduct studies involving functional magnetic resonance imaging (fmri) that will use Grand River Hospital(GRH) s 1.5 Tesla Philips MRI scanner to which UW researchers are expected to adhere as part of access to and use of the GRH s MRI. Currently, 16 hours of scan time have been allocated to UW researchers per month. Responsibility: faculty and student investigators 1.0 Screening participants Participants must be screened at two stages during a study to determine their suitability for scanning. First, at recruitment, participants must be asked a set of questions (Appendix A) to determine whether or not they have any metal present in their body that would preclude them from entering the scanner. Second, at the actual time of scanning, participants must complete the same checklist of questions completed at initial recruitment (Appendix A) in the presence of one of GRH s MRI technicians to ensure that they: i. have met the criteria for entering the scanner and ii. do not have any incidental metal items on their person or clothing (see final section of Appendix A). For participants waiting to be scanned, GRH will make available nearby consulting rooms that UW researchers can use to brief participants, obtain consent and screen for suitability to be scanned. Participants will be assigned a lockable locker within which they can place all personal items that would not be allowed in the scanner (e.g., watches, jewellery, wallets, etc.). 2.0 Participant and Researcher Safety Participants safety: Participants will be given a full description of the risks associated with MRI scanning as part of the informed consent process (see Appendix B for an example). The MRI technician will also answer any questions the participant has regarding risks and safety prior to giving informed consent and entering the scanner. Researchers safety: Researchers conducting fmri studies at GRH must also complete the screening questionnaire outlined in Appendix A. This will ensure that it is safe for researchers to enter the scanning room. While researchers only need to complete this form once, they will need to ensure at each study session that they have removed all items (as indicated in Appendix A) from their person or clothing that would preclude them from entering the scanning room. At each session, GRH s MRI technicians will question researchers regarding metal objects on their body or clothing at each scanning session.

2 3.0 Ethics clearance and informed consent It is incumbent upon UW researchers to obtain full ethics clearance for their respective studies from both the University of Waterloo s Office of Research Ethics (contact Dr. Maureen Nummelin ext for details) and the Tri-Hospital Research Ethics Board (contact Dr. Michael Coghlin ext. 5367). See Appendix B for an example of informed consent. 4.0 Data processing and storage Functional MRI data for each study will be immediately transferred to an external hard drive housed at GRH but property of the University of Waterloo. Data will be stored on this hard drive for a period of two weeks at which time it will be erased. During this two week period the hard drive will be securely stored in the locked anteroom adjacent to the MRI control room accessible only by Hilda Pope (GRH MR technician). The reason for this two week storage time is twofold: first, if data that is transferred to UW researchers is somehow corrupted this storage acts as a short term back-up of the data. Second, this period of storage time (2 weeks) allows UW researchers ample time to copy the data top their own storage device so that the data can be checked for quality before continuing on with a study. For example, if the anatomical images are not of sufficient quality, or the functional images do not capture the intended brain region appropriately, this can be verified within two weeks and changes can be made to the scan protocols of that study to correct for any issues. This is standard practice in most functional imaging centres. For each individual research study, UW researchers will need to transfer the data from the external hard drive to their own electronic storage device (i.e., a second external hard drive: ftp protocols will not be enabled from GRH to external sites) to transfer the data to their own labs. All recorded data will be void of identifying material. That is, the electronic imaging data will not have participant s names but will instead have numbers and the investigator s initials assigned to them. For example, if Dr. James Danckert is collecting his 5 th subject for a given study that electronic data will be given the identifier JD5.xxx where xxx refers to the particular file extension. How the data is securely stored once it is taken off site is to be determined by each individual researcher and should have approval from the relevant ethics boards. Normally, we would expect that any data with identifying information will be encrypted to ensure privacy. The functional MRI data collected at GRH is recorded in an Enhanced DICOM format and can be read into MRIconvert ( in order to change it into a variety of other formats (ANALYZE, SPM, NifTI, etc.). In order to download data from the patient administrator tool (Philip s software user interface used for MRI scanning at GRH) it is important that the raw data of each scan is saved. This option is currently part of the default scan parameters adopted in consultation with GRH and UW researchers. Should it fail, the data can still be recorded and can be exported to a second PC in an office next to the MRI control room. These data will be in an older DICOM format (non-enhanced) and will thus require different preprocessing steps before being ready for analysis. In the informed consent form, UW researchers will need to indicate how data will be stored (after it has been removed from the external HD housed at GRH), how long it will be kept and how participants will be identified (see example informed consent form attached as Appendix B). 2

3 5.0 Scheduling and cancelling scan time Scan times will normally be allocated in hourly slots although half hour slots can also be booked. Users will contact Nadine Quehl, Research Assistant, (University of Waterloo; ext ) to book time on the scanner. In general, booking large chunks of scan time months in advance will be discouraged to ensure that no one user monopolises scan time. Booked slots will be posted on a password protected Google Calendar (contact Nadine Quehl for details regarding the site). To avoid the problem of mass booking by a single researcher, research slots will only become available for booking on the calendar 1 month ahead of time. Individual researchers are wholly responsible for booking their own participants. If a booked scan time is no longer needed it must be cancelled a minimum of 24 hours in advance to enable other users (including GRH) to plan to use the slot. Failure to cancel in that time frame will incur full fees for the time booked. Users will need to contact Nadine Quehl to cancel scan time. 5.1 Clinical priority Grand River Hospital reserves the right at any time to cancel an fmri time slot booked by a UW researcher in favour of a medical emergency. Any UW researcher who has had their time cancelled for this reason will not be charged for the time slot. Participants who have their time slot cancelled will be reimbursed for their travel costs and a pro-rated amount based on how long they have been in the scanner will be paid in appreciation of their time commitment. 5.2 Fee schedule UW researchers (i.e., the Principal Investigator on a study) will be charged $265 per hour of scanning. This includes any setup time. It is the responsibility of users to ensure that their participants arrive on time and have completed any pre-scanning requirements (e.g., pre-screening questionnaire, training on the task being used, consent signed). UW researchers will be billed at the end of each month for the scan time used. 6.0 Scan parameters Researchers will be expected to provide technicians with the following information before beginning a scan. Number of slices, orientation of slices, volume collection time (as it relates to stimulus presentation times, this is an important factor (i.e., volume times should be divisible by critical stimulus durations in most instances), number of volumes. We have already established a standard anatomical scan with the following parameters: ANATOMICAL SCAN Number of slices: 150 FOV: 240 x 240 TR: 7.8 msec TE: 3.5 msec Flip angle: 8 Collection time: 6 min: 07 sec 3

4 Any changes to the above parameters need to be specified by the researcher prior to scanning. A standard functional scan for echo-planar images (EPI) has also been saved although this will obviously be modified on a study-by-study basis. The parameters for that scan are as follows: FUNCTIONAL SCAN Number of slices: 26 FOV: 220 x 220 TR: 2000 msec TE: 40 msec Flip angle: 90 Collection time: 3 min: 34 sec (for 100 volumes) 7.0 Incidental findings Occasionally, incidental findings defined as observations of potential clinical significance unexpectedly discovered in healthy research participants or in patients recruited to brain imaging research studies and unrelated to the purpose or variables of the study may appear on an anatomical scan. Recent published data suggests that clinically significant and identifiable neuropathologies occur in 0.5 to 2% of the general population. One must consider the potential for false positives in MRI findings particularly in the context of the fact that there is no research to suggest how useful brain imaging is as a screening tool in asymptomatic individuals. This is particularly important when considering the resolution anatomical images normally collected for research. This resolution is commonly below that used for clinical purposes (in addition, clinical scans often make use of contrast agents in order to fully visualise various pathologies a practice not used in research scans). While some research centres routinely have scans read by a neuroradiologist (approximately 47% of centres engage in this routine) this will not be possible at GRH for several reasons. First, there is no specialised neuroradiologist at Grand River Hospital, brain scans are read by radiologists on a rotational basis. Second, the cost both in terms of time and money of engaging in routine readings of all scanned research participants would be prohibitive. Finally, all scans related to fmri research will be conducted and viewed by non-physicians (i.e., GRH s own MR technicians, UW Ph.D. researchers and their graduates). Thus, any observations of potential interest have an even higher risk of false positive. For these reasons, participants will be informed that the scans that were collected are research scans and do not have the resolution normally needed to detect abnormalities. They will be informed that those viewing the scans are non-physicians who are not trained or qualified to detect clinically significant abnormalities. They will be encouraged to see their family physician and scans will be released to their physician only after explicit consent of the participant. Given the factors outlined above it is unlikely that subtle neurological changes will be detectable given the scan parameters we have set as default in these studies, and the fact that all research users are untrained in detecting such abnormalities. However, larger abnormalities will be easily detectable by both the GRH MR technician and by UW researchers. In these cases, the participant will be told that some atypical findings were detected on their scan and that they should see their family physician. If the GRH technician or UW researcher suspects that there is a more subtle or minor abnormality on the anatomical scan, this scan will be referred to GRH radiologists for a full report at a cost to the UW researcher. Should any abnormalities be detected by the radiologist, the participant will be informed immediately. 4

5 The above procedures relate only to anatomical images as the functional MRI scans do not routinely contain information that has any clinical relevance. All researchers intending to conduct fmri at GRH should read the following article to familiarise themselves with the issues involved with incidental findings. Illes, J., Kirschen, M.P., Edwards, E., Stanford, L.R., Bandettini, P., Cho, M.K., Ford, P.J., Glover, G.H., Kulynych, J., Macklin, R., Michael, D.B., & Wolf, S. M. (2006). Incidental Findings in Brain Imaging Research: What should happen when a researcher sees a potential health problem in a brain scan from a research subject? Science, 311,

6 APPENDIX A MRI PARTICIPANT SCREENING FORM Name: Age: D.O.B. Handedness: right / left / mixed Please answer yes or no to the following questions: YES NO 1. Have you previously had an MRI? 2. Have you ever been a soldier, grinder, welder, metalworker or hobbyist? 3. Have you EVER had a metallic foreign body in your eye? 4. Have you ever experienced claustrophobia? 5. Have you ever had an epileptic seizure? 6. Have you ever had a head injury? 7. Have you had any visual disorders? 8. Can you see clearly at arms length without glasses (contacts are OK)? 9. Do you have: A cardiac pacemaker or defibrillator? Aneurysm clip Cochlear implant Neurostimulator Artificial cardiac valve Caval filter/stent Port cath IUD/Penile implant Tattoos/body piercing(s) Dentures/ retainers/braces Other implanted device(s) or prosthesis 10. Have you had surgery on: Head/ear Neck Spine Chest Abdomen Extremities Other 11. Are you taking any medications which could make you drowsy? 12. Can you stand without assistance? 13. Are you able to lie on your back for one hour without moving? For women only: YES NO 14. Do you have an IUD? 15. Are you pregnant or trying to conceive? 16. Are you breast feeding? 17. Are you wearing an underwire bra? 6

7 Additional comments: Before entering the magnet room, please: remove all jewellery remove your wristwatch remove everything from your pockets keep your credit cards in the control room DONE Participant s signature: Screening individual signature: Date: Date: 7

8 APPENDIX B INFORMATION LETTER Project Title: Functional MRI of. Principal Investigator: UW Researcher s name Contact Details: Office location, Phone (ext.) and Nature and purpose of the study: (give a brief description in lay language of the purpose of the study) Procedures: If you agree to participate, you will have images collected of your brain while you perform various tasks: (outline the tasks in the sequence in which they will be done). You will have the task(s) explained to you by the Principle Investigator and the scans will be collected by a Grand River Hospital (GRH_ MRI technician. The entire session should take approximately 1 hour. Participation includes the following steps: a) You will begin by filling out a checklist to ensure you are an eligible participant. b) The procedure for the scanning session will be explained to you. c) You will be given ear plugs to protect your ears from the noise of the magnet. d) You will then be asked to lie on your back on the well-padded bed of the magnet. A cylindrical coil will be slid into place. This coil does not touch any part of your head but will surround your head. Above this coil are goggles that you can look into (they are not worn like a pair of glasses would be but sit above your eyes without touching you at all). The goggles have LCD screens in them and this is how we present visual stimuli to you in the magnet. You will be asked if you are comfortable at which point the GRH MRI technician will move you and the magnet bed into the long tube of the magnet bore. e) You will have multiple scans (that we call runs ) each lasting approximately 5 to 7 minutes long. Between scanning runs you are not required to do anything and will be able to relax. The time between scans is usually around 1 to 2 minutes long. During each scanning run you will be asked to keep your head still. To help you do this, we will pack foam or deformable material around your head. Each scanning run will have between 100 and 200 trials. f) During the scan you will be asked to (describe whatever task/procedure participants will be requested to do during the study e.g., pressing a button in response to some visual stimulus). g) At the end of the runs described above (i.e., the scanning runs during which you perform the experimental tasks), an additional scan will be taken of the anatomy of your brain. This scan is needed so that we can overlap your brain activity from the functional scans onto an image of your own unique brain anatomy. The whole procedure, including setup time, should take approximately (insert time here). Approximately (provide a number) participants will be included in this study. MRI details: You will be placed in an MRI machine which uses the same hardware and software that is used in MRI for patients. The MRI scans being collected here are designed to address research questions, and not to 8

9 examine your brain for any medical reasons. MRI is a non-invasive technique which does not involve x-rays or radiation. This magnet has a field strength of 1.5 Tesla, which is the standard field strength used in most hospital settings. It is also the lowest field strength used for fmri (i.e., many magnets now use 3 Tesla or higher). There are no known side-effects or complications that have occurred during or following functional MRI examinations over the past 15 years. The most important safety concern with MRI is to avoid having any metal in your body or near the scanner. Any metal on your body will be attracted to the bore of the magnet and could cause damage to the equipment. Thus, it is very important that you carefully complete the checklist included with this form and alert the investigators if you have any concerns. Risks and discomforts of an MRI scan: The MRI scan is not associated with any known risks to your health and there is no evidence that there will be either short-term or long-term side effects. However, if you are a woman of child-bearing age, it is important that you not be pregnant at the time of the MRI scan. Prior to the MRI you will complete a questionnaire designed to identify any reasons why you cannot participate in the study. You may not participate if you have: 1) an implanted cardiac pacemaker. 2) any metal implants, pieces of shrapnel, aneurysm clips, or wires in your head. 3) a history of seizures. 4) known claustrophobia. You will hear moderately loud knocking or beeping sounds during the scan when the MRI machine is in operation. You will be provided with earplugs to dull the noise and to protect your hearing. Although you may find this noise to be unsettling, the machine cannot hurt you in any way. If you wish to stop the study at any time, or feel you need a break, please advise the researcher (who will be able to hear you through a microphone) or by pressing the experimenter call button provided for you. If you have any questions about participation, please feel free to ask the researchers and MRI technicians at any time. During the scanning session you will be in voice contact with the operator of the MRI. You may ask the MRI technician to terminate the experiment at any time. You will also be given a button press device that you can use to communicate your desire to terminate the experiment to the operator in the control room. You may do this at any time. You should terminate the experiment if you feel tired, claustrophobic or for any reason, prefer not to continue. Incidental findings: Use of the MRI scan in this research is designed to answer research questions, not to examine your brain medically. This MRI scan collected in this research project is not a substitute for one that a doctor would order, and it may not show problems that would normally be detected by a medical MRI scan. In addition, the researchers conducting this study are not qualified in the same way a radiologist is, to detect abnormalities on MRI scans. However, in the unlikely event that we do note an atypical finding on your anatomical MRI scan, we will be certain to inform you of our findings and suggest that you arrange a medical follow-up to interpret the significance of the findings, if any. We will also ask a radiologist, or other health professional, to look at your scan, and by signing this consent form, you 9

10 agree to release the scan for this type of review. Since we are not trained to read MRI scans for clinical purposes, we might occasionally think something is abnormal that is, in fact, perfectly normal. We do not want to worry you with such false alarms. Therefore, if anything is seen on your scan that we are unsure of, we may, without informing you at the time, ask a radiologist, or other health professional, to look at your scan. By signing this consent you are giving us permission to do so. If no problem is found by the radiologist, you will not be told that this review step has occurred. If the radiologist cannot confirm that your scan is normal, then we will contact you and suggest that you arrange a follow-up with your general physician. Voluntary participation: Your participation is entirely voluntary. There are no other known or anticipated risks associated with participation in this study. However, if you wish to stop the study at any time, or feel you need a break, please advise the researcher. If you have any questions about participation, please feel free to ask the researchers. Confidentiality and security of data: Each individual s results are confidential. Neither your identity nor any personal information will be available to anyone other than the investigators. All information you provide is considered completely confidential; indeed, your name will not be included or in any other way associated with the data collected in the study. Furthermore, because the interest of this study is in the average neural responses (i.e., the changes in brain activity from one task to the next) of the entire group of participants, you will not be identified individually in any way in any written reports from this research. Paper data collected for this study are kept in a locked filing cabinet (indicate location and who is responsible), and converted to electronic format at the end of each participant s involvement in the study. All computer data are kept on a computer that is password protected in an office in (give researcher s name) lab in the (give on campus location) building at the University of Waterloo, to which only researchers associated with this study have access. Data will be kept for a maximum period of seven years at which time it will be erased (electronic data) or destroyed (paper data) with attention to confidentiality. Benefits: Participation in this study will not provide any personal benefits, but it will provide you with an opportunity to learn about research in psychology in general and the topic of this particular study. The information obtained from the study may benefit society in general by providing a better understanding of (give a brief description of the benefits relative to the study at hand). If you are interested, we would be happy to provide you with the final results of the study when it has been completed, which may take some years. Contact (give researcher s name) directly via should you wish to receive a copy of the final report on the study when it eventually becomes available. Remuneration: You will receive (give a value - $25 is considered the base level) monetary remuneration in appreciation of your time commitment and to cover any travel costs for participation. You will also receive a detailed feedback sheet about the study. If you withdraw from the study the amount of remuneration will be prorated based on the time you spent in the study (i.e., if you spend half an hour in an hour long study you will receive half of the remuneration payment). 10

11 Questions about the study: If you have any further questions about this, please feel free to call (give researcher s name and contact details including ). Ethics clearance: As with all University of Waterloo projects involving human participants, this project was reviewed by, and received ethics clearance through, the Office of Research Ethics (ORE) at the University of Waterloo. Furthermore, as the study is being carried out at Grand River Hospital it has also been reviewed by and received clearance from the Tri-Hospital Research Ethics Board (THREB). Should you have any comments or concerns resulting from your participation in this study, please contact Dr. Maureen Nummelin, Director, ORE, at UW at (519) , Ext., You may also contact Dr. Michael Coughlin at the THREB office on (519) Ext Thank you for your participation in this study. 11

12 CONSENT FORM Project: Functional MRI of. I agree to participate in this study being conducted by (give researcher s name, position, department affiliation), at the University of Waterloo. I have made this decision based on the information I have read in the Information Letter and have had the opportunity to receive any additional details I wanted about the study. I understand that I may withdraw this consent at any time by informing the researcher or the MRI technician, without penalty. I have read the attached information form, and I have been advised of the purpose of my participation, the procedures involved and the potential risks and discomforts to myself, as stated in the attached information sheet. All my questions have been answered to my satisfaction. I understand that I can ask further questions during any stage of the study. I am aware that my participation in the study is voluntary. I may withdraw from the study at any point in time. I am aware that while the study will not benefit me personally, but knowledge will be gained that may benefit others. It has been explained to me that the results of the study are confidential. Neither my identity nor any personal information will be available to anyone other than the investigators. No personal information will be disclosed in any resulting publication or presentation. I will receive (give amount) in appreciation of my time and to cover any travel expenses. If I am a woman of child-bearing age, I confirm that I am not or could not be pregnant at the time of the MRI scan. If I have any further questions I may call (give researcher s name and full contact details including address). I am aware that this study has been reviewed and received ethics clearance through the Office of Research Ethics at the University of Waterloo and by the Tri-Hospital Research Ethics Board (THREB) at Grand River Hospital. I am also aware that the final decision about participation is mine and that if I have any comments or concerns resulting from my participation in this study, I can contact Dr. Maureen Nummelin at this office at (519) Ext or Dr. Michael Coughlin at THREB at (519) Ext Participant: Name: Signature: Witness: Name: Signature: Date: Investigator Name: Signature: Date: 12