1. Human Subjects Issues Specific to Functional MRIA. Health Effects of MRI StudiesElectrical BurnsB. Safety in the High Field EnvironmentB. Distress in the MR environmentLet the Neuroscientist Beware!C. Critical Elements to Informed ConsentC. Risk/Benefit ConsiderationsIntraoperative Registration of Medical Images by Temporarily Implanted Fiducial MarkersREFERENCESHST-583Human Subjects in fMRI ResearchRandy L. Gollub, M.D., Ph.D.Sept. 15, 2004Contents1. Risks to Human Subjects associated with Functional MRI- Health Effects of fMRI Studies- Static B0 fields- RF B1 fields- Tissue heating- Switched gradient fields- peripheral nerve stimulation- Acoustic Noise- Safety in the High Field Environment- 1.5T, 3T, beyond- Screening- Pre-imaging preparation- Distress in the MR environment1. Incidence of distress2. Factors that contribute to distress3. Techniques to minimize subjective distress2. Ethical Conduct of fMRI Research involving Human SubjectsA. Investigator TrainingB. Informed ConsentC. Risk/Benefit Considerations 11. Human Subjects Issues Specific to Functional MRIFunctional neuroimaging poses some significant risks. Entry into the magnet environment alone is one of those risks. Experiments involving injection of drugs or contrast agents, invasive physiological monitoring, emotionally stressful experimental paradigms, and or use of clinical populations each add additional risks. All aspects of a research career in functional neuroimaging require competence in the area of human subjects protections including clear knowledge of the foreseeable risks, obtaining IRB approval to conduct a study, and informed consent from subjects. A. Health Effects of MRI StudiesMagnetic Resonance Imaging (including spectroscopy, conventional, and fast imaging techniques) for medical procedures is associated with acceptable and well controlled risks. However, technological advances in MRI (higher static fields, faster gradients, stronger RF transmitters) have occurred rapidly and many questions regarding the safety of these developments remain unanswered. The standard reference on MR safety is the book by Shellock cited in the references.Informal market research studies indicate that more than 150 million diagnostic MRI examinations were performed worldwide between the onset of clinical MRI in the early 1980s and the end of 1999; the vast majority of these were conducted without any sign of patient injury. MRI related deaths and injuries are attributable to the high field environment required for scanning, which can result in projectile accidents (AKA “missile effect”). Inadequate screening procedures for metallic objects are the other major factor responsible for subject morbidity and mortality. Examples include the death of a 6 year old boy last year by the projectile path of a metal oxygen tank, and the deaths of patients with cardiac pacemakers who were inadvertently scanned. Concerns for patient safety have been raised in regard to each of the three distinct fields used in MRI; the static B0 fields; the radiofrequency (RF) transmission field, B1 and the time dependent magnetic field gradients. - Static B0 fields- no established adverse health effects.Static magnetic fields are measured in Gauss (G) or Tesla (T), with 10,000 G being equal to 1 T. To put things in perspective, the earth's magnetic field varies from approximately 0.3 to 0.7 G between the equator and the poles, respectively. A small refrigerator door magnet may be as strong as 150 G to 250 G. The strengths of the static magnetic fields used in research MR systems for imaging and/or spectroscopy range 0.012 T to over 10 T (100,000 G). According to the most recent recommendations and guidelines provided by the United States Food and Drug Administration (FDA), clinical MR systems inthe US are permitted to function on a routine clinical basis at static magnetic field strengths of up to 4.0 T.Extensive research studies have been conducted in isolated tissues, animals and humans to identify ill effects of exposure to high magnetic fields. While there have been some positive findings, none of these has been replicated. The workperformed to date has yet to prove a single example of a scientifically sound and rigorously verified pathological effect of high magnetic fields 2. The absence of ferromagnetic components in human tissues and the extremely small value of the magnetic susceptibility of these tissues are believed to be responsible for the absence of harmful effects of the high magnetic fields.Magnetohydrodynamic effects on most body tissues are sufficiently small as to be physiologically insignificant. One hypothesized exception is the endolymphatic tissues of the inner ear that may be the source of sensations of nausea and vertigo reported by some human subjects in the presence of higher (e.g. 4 to 7T) static magnetic fields. The comfort of subjects will be enhanced by moving them SLOWLY in and out of the magnet and by minimizing their motion while in the magnet.Note: magnetohydrodynamic forces can induce distortion in recorded ECG signals. It is important to recognize that these distortions do not reflect any change in cardiac conduction, rather they are artifacts in the recording. The safety aspect of the static field is hard to quantify because there is no clear physical phenomena associated with exposure that can be used to establish upper limits for safe subject exposure. The upper limit on the strength of the static magnetic field that can be used for human imaging studies is set by technical, regulatory and cost factors. Current research 2efforts to develop ultra high field imaging systems are of high priority. Future work at these higher fields may establish healtheffects that have not yet been detected.- RF B1 fields- Limiting physiological effect is tissue heating A RF pulse (a short burst of an electromagnetic radiation) is used in MRI to "excite" tissue protons by an exchange of energy. The RF spectrum typically used in MRI covers the same frequencies that are used by radio stations (around 100 MHz). Such high frequency oscillations do not elicit peripheral nerve stimulation (see next section).During MR procedures, the majority of the RF power transmitted for imaging is transformed into heat within the patient's tissue as a result of resistive losses from the induced electric field. This ohmic heating of tissue during MR procedures is greatest at the surface or periphery and minimal at the center