Functional brain-imaging technology includes the following five techniques: functional magnetic resonance imaging (fMRI), positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetoencephalography (MEG), magnetic resonance spectroscopy (MRS), and topographic electroencephalography (TEEG).
These imaging techniques measure the following:
- Glucose metabolism during PET scans, conducted with a form of glucose detectable by the PET scanner
- Regional cerebral blood flow (rCBF) during PET scans, conducted with a detectable form of water or during SPECT with various
- The blood-oxygen-level-dependent (BOLD) signal that relates both regional cerebral blood flow and regional cerebral blood volume during fMRI scans. (See sidebar on page 7 for more information about the risks of MRI for cochlear implant users.)
When designing studies using these techniques, clinicians and researchers consider the spatial and temporal resolutions associated with the images. Spatial resolutions may be as small as 1–2 mm when using fMRI scans or as great as 8–12 mm when using PET scans conducted with labeled water.
Temporal resolution refers to the length of time a stimulus presentation is needed to sample cortical responses to a task. Image acquisition may be very quick as in the case of fMRI (less than 100 milliseconds), or long—30 minutes—for PET scans of glucose metabolism.
The test environment also is an important factor. PET and fMRI scans typically are run in scanners, and fMRI scans produce very loud noises and require heavy acoustic shielding. SPECT scans, on the other hand, may be run in a quiet, acoustically controlled environment.
For studies with individuals who use cochlear implants, fMRI is not an option. Therefore, the spatial and temporal resolution of SPECT or PET most influence study-design issues. SPECT provides the greatest control of the study environment but limits investigators to only one study (experimental condition) per day. PET scans with labeled water provide the greatest experimental flexibility in that six or more study conditions (cognitive conditions) can be examined in one session in the scanner. The temporal resolution is similar for both techniques, about 60 sec for rCBF with PET, and about 30 sec for rCBF with SPECT. Also, the spatial resolution is similar, though generally a little better for SPECT—about 6–8 mm for SPECT and 8–12 mm for PET.
Functional brain-imaging studies require a contrast between cortical function measured under at least two test conditions. The conditions may be simple—eyes opened or eyes closed—or may be more complex manipulations that tease apart the subtleties of auditory perceptions. For example, many of our studies require a contrast between watching and listening to a recording of a person reading a story versus only watching a person reading a story. The listening portion of the test may be varied to present signals to two ears, one ear, or to present manipulated (filtered, etc.) sounds in some fashion.
The colored blobs typically observed in functional brain images may represent simple mathematical operations (e.g., subtracting images acquired in two conditions to obtain a difference score) or more sophisticated statistical constructs regulating the power or reliability of the observations by setting the probability levels and size of the effects.
PET and SPECT studies also involve the injection of a radioisotope that is taken up by the brain fairly rapidly, such as SPECT scans integrating activities over 20 seconds in length, or more slowly, such as PET scans with labeled water integrating activities over two minutes. The physical half-life of the radioisotopes also varies from fairly long (>6 hours) or relatively short (<1 minute). Thus, the temporal and spatial resolution of neuroimaging studies is based on the careful control of the stimulus to be studied, how an individual responds to the stimulus, the statistical manipulation of the data, and the test environment.
Many people believe radiation is harmful at any level and believe any medical imaging procedure using exposure to radiation will increase risk. Medical practice and research expend great efforts (and costs) to minimize radiation exposure for patients, research volunteers, and workers. Some individuals argue fMRI imaging sequences should be used instead of Nuclear Medicine techniques, such as SPECT or PET, in order to avoid the perceived radiation risk of the radioactive tracer techniques. Many times this fear of radiation is fostered by the widespread regulatory use of the "Linear No-Threshold Theory" (described below, in lay language) regarding the assessment of radiation risk. In fact, SPECT and PET brain imaging procedures have no more known risk than MRI-based techniques. Below, we briefly review the data regarding low-level radiation and risk.
The "Linear No-Threshold Theory" is a working hypothesis originated in the 1950s to serve as a prudent operational guideline to describe radiation effects. Unfortunately, many people think it is a fact, even though there is no scientific evidence to support it. The theory makes a big assumption: that is, measures of mortality, introduction of disease or tissue injury caused by very high radiation exposure levels associated with nuclear accidents, atomic bomb exposures, or high levels of intentional radiation therapy treatments may be extrapolated down by many orders of magnitude to much lower levels of radiation exposure incurred in diagnostic imaging. For example, the hypothesis assumes an injury caused by a high level of radiation is lowered in direct proportion to an assumption that "zero-risk" is equal only to "zero exposure."
This interpretation is equivalent to assuming that if a car hitting a wall 10,000 times in a row at 200 miles per hour kills the driver 100% of the time (and, thus, produces 10,000 deaths), then a car hitting the wall 10,000 times in a row at 2 miles per hour (1/100th original velocity) will kill 100 drivers (1/100th the original number of deaths). The "Linear No-Threshold Theory" assumes a single gamma ray stopping in the human body should be associated with some risk. However, most published, peer-reviewed data suggests risk goes to "zero" at radiation exposure levels well above those incurred in diagnostic procedures for both adults and children.
In 1996, the Health Physics Society issued a policy statement indicating "health risks are either too small to be observed or are nonexistent" for radiation exposures below 10 Roentgen Equivalent Man (rem), although there is substantial and convincing scientific evident for health risks at high doses. The whole body dose of a typical SPECT brain imaging procedure is about 0.01 (rem)—a thousand times lower than the dose discussed by the Health Physics Society. The Office of the Clinical Director of the National Institutes of Health (NIH) states, "The risk of increased rates of cancer after low-level radiation exposure is not supported by population studies of health hazards from exposure to background radiation, radon in homes, radiation in the workplace or radiotherapy. Compared to the frequency of daily spontaneous genetic mutations, the biologic effect of low-level radiation at the cellular level seems extremely low. Furthermore, the potentiation of cellular repair mechanisms by low-level radiation may result in a protective effect from subsequent high-level radiation."[italics are our emphasis of the statement]. The NIH concludes their risk review by saying: "Health risks from low-level radiation could not be detected above the "noise" of adverse events of everyday life. In addition, no data were found that demonstrated higher risks with younger ages at low-level radiation exposure." Indeed, there is no data that demonstrate harm to humans by the radiation exposures used for diagnostic imaging.
We italicize a portion of the statement above from the NIH that refers to a potential protective effect from low levels of radiation. The potential protective effect from low levels of radiation is based on a concept known as radiation hormesis. In contrast to the "all radiation is bad" perspective associated with the "Linear No-Threshold Theory," current data on the effects of low-level radiation exposure support the presence of "radiation hormesis" which suggests that low levels of radiation exposure in humans appears to induce beneficial effects of cellular repair and immune system enhancement. This concept builds on the evolution of humans living in a background radiation environment historically many times higher than is currently present. Current background radiation levels vary by an order of magnitude across geographic regions without any indication that individuals living in lower background radiation regions have less cancer prevalence than individuals in higher background radiation areas. Data from the United States, China, India, Austria and the United Kingdom show that populations living in background areas with higher levels of radiation have increased longevity and decreased cancer death rates.
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