Functional magnetic resonance imaging
From Freepedia
Functional Magnetic Resonance Imaging (or fMRI) describes the use of MRI to measure the hemodynamic response related to neural activity in the brain or spinal cord of humans or other animals. It is one of the most recently developed forms of brain imaging.
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Background
It has been known for over 100 years that hemodynamic activity is closely linked to neural activity. When nerve cells are active they consume oxygen supplied by local capillaries. Approximately 4-6 seconds after a burst of neural activity, a hemodynamic response occurs. This means that an active region of the brain is infused with oxygen-rich blood.
Hemoglobin is diamagnetic when oxygenated but paramagnetic when deoxygenated. The magnetic resonance (MR) signal of blood is therefore slightly different depending on the level of oxygenation, a phenomenon called the Blood Oxygenation Level Dependent (BOLD) signal. An MRI scanner can be used to detect the BOLD contrast. Higher BOLD signal intensities are the result of the alleviation of oxygenated hemoglobin, rather than the prescence of deoxgenated hemoglobin per se. That is, oxygenated hemoglobin suppresses the BOLD signal; the locally low frequency of deoxygenated hemoglobin is a mere capitulation to the colocation of a high frequency of oxygenated hemoglobin. Thus we unmask the BOLD signal and obtain a greater profile change from baseline. It is confusing to think of higher intensities as mapping onto lower levels of the thing affecting the instrument and effecting a measurement, but the distinction is arbitrary (i.e., "cold" is a phenomological state, not something measured by a thermometer [see Stroop task]).
Neural correlates of BOLD
The precise relationship between neural signals and BOLD is under active research. In general, changes in BOLD signal are well correlated with changes in blood flow. Numerous studies during the past several decades have identified a coupling between blood flow and metabolic rate; that is, the blood supply is tightly regulated in space and time to provide the nutrients for brain metabolism. However, neuroscientists have been seeking a more direct relationship between the blood supply and the neural inputs/outputs that can be related to observable electrical activity and circuit models of brain function.
While current data indicate that local field potentials, an index of integrated electrical activity, form a better correlation with blood flow than the spiking action potentials that are most directly associated with neural communication, no simple measure of electrical activity to date has provided an adequate correlation with metabolism and the blood supply across a wide dynamic range. Presumably, this reflects the complex nature of metabolic processes, which form a superset with regards to electrical activity. Some recent results have suggested that the increase in cerebral blood flow (CBF) following neural activity is not causally related to the metabolic demands of the brain region, but rather is driven by the presence of neurotransmitter, especially glutamate.
Technique
BOLD effects are measured using a T2-related imaging process (actually T2*), which is different from T1 scan taken in ordinary structural MRI images. A T2 measures the rate of change of spin phase, while T1 detects the half-life of inverted spins. In the brain, this means that in a T2 contrast, water gives a stronger signal than fat; therefore white matter appears dark and grey matter and cerebrospinal fluid appears white. T1 on the other hand contrasts fat more strongly than water so white matter is white and grey matter is grey.
T2* images can be acquired with moderately good spatial and temporal resolution; images are usually taken every 2-5 seconds, and the voxels in the resulting image represent cubes of tissue approximately 3 millimeters on each side. Recent technical advancements, such as multichannel imaging, have improved the spatial resolution (to 1.6 mm) while still retaining a good temporal resolution (2 sec) (Nature Neurosci., 7:1190-2, 2004[1]). Some researchers proposed that both spatial and temporal resolutions can be significantly improved by analyzing the so-called "initial dips" of BOLD responses, but this idea has mostly been studied with animals (using invasive methods), not humans.
The science of applying fMRI is quite complicated and multi-disciplinary. It involves:
- Physics: The physics are complex, but it is beneficial for a researcher to have a moderate understanding of the mechanism they are using in their study.
- Statistics: Because the signals are very subtle, correct application of statistics is essential in the statistical analysis of results to "tease out" observations and avoid false-positive results.
- Psychology: When conducting fMRI on humans it is essential to employ carefully designed psychophysical experiments which allow the precise measurement of the neural effect under consideration.
- Neuroscience: For a non-invasive scan, MRI has moderately good spatial resolution, but relatively poor temporal resolution. Increasingly, it is being combined with other data collection techniques such as electroencephalography (EEG) or magnetoencephalography (MEG), which have much higher recording frequencies.
- Neuroanatomy: Anatomy is critical in understanding the location (and role) of the signals which fMRI is able to detect.
MRI-related techniques
Aside from BOLD fMRI, there are other ways to probe the brain activity using MRI:
Contrast MR
An injected contrast agent such as an iron oxide that has been coated by a sugar or starch (to hide from the body's defense system), causes a local disturbance in the magnetic field that is measurable by the MRI scanner. The signals associated with these kinds of contrast agents are proportional to the cerebral blood volume. While this semi-invasive method presents a considerable disadvantage in terms of studying brain function in normal subjects, it enables far greater detection sensitivity than BOLD signal, which may increase the viability of fMRI in clinical populations. Other methods of investigating blood volume that do not require an injection are a subject of current research, although no alternative technique in theory can match the high sensitivity provided by injection of contrast agent.
Arterial spin labeling
By magnetic labeling the proximal blood supply using "arterial spin labeling" ASL, the associated signal is proportional to the cerebral blood flow, or perfusion. This method provides more quantitative physiological information than BOLD signal, but has less sensitivity for detecting task-induced changes in local brain function.
Magnetic resonance spectroscopic imaging
Magnetic resonance spectroscopic imaging (MRS) is another, NMR-based process for assessing function within the living brain. MRS takes advantage of the fact that protons (hydrogen atoms) residing in differing chemical environments depending upon the molecule they inhabit (H2O vs. protein, for example) possess slightly different resonant properties. For a given volume of brain (typically > 1 cubic cm), the distribution of these H resonances can be displayed as a spectrum.
The area under the peak for each resonance provides a quantitative measure of the relative abundance of that compound. The largest peak is composed of H2O. However, there are also discernible peaks for choline, creatine, n-acetylaspartate (NAA) and lactate. Fortuitously, NAA is mostly inactive within the neuron, serving as a precursor to glutamate and as storage for acetyl groups (to be used in fatty acid synthesis)—but its relative levels are a reasonable approximation of neuronal integrity and functional status. Brain diseases (schizophrenia, stroke, certain tumors, multiple sclerosis) can be characterized by the regional alteration in NAA levels when compared to healthy subjects. Creatine is used a relative control value since its levels remain fairly constant, while choline and lactate levels have been used to evaluate brain tumors.
Diffusion tensor imaging
Diffusion tensor imaging (DTI) is a related use of MR to measure anatomical connectivity between areas. Although it is not strictly a functional imaging technique because it does not measure dynamic changes in brain function, the measures of inter-area connectivity it provides are complementary to images of cortical function provided by BOLD fMRI. As protons are directed along certain axes in the brain (e.g., water flowing down a neuronal axon within a bundle of nerve fibers in cerebral white matter), this directionality can be measured. Connectivity between brain regions may be inferable from diffusion images. Illnesses that disrupt the normal organization or integrity of cerebral white matter (such as multiple sclerosis) have a quantitative impact on DTI measures.
Scanning in practice
Subjects participating in a fMRI experiment are asked to lie still and are usually restrained with soft pads to prevent small motions from disturbing measurements. Some labs also employ bite bars to reduce motion, although these are unpopular as they can cause some discomfort to subjects. It is possible to correct for some amount of head movement with post-processing of the data, but significant motion can easily render these attempts futile. The amount of acceptable motion varies depending on the post-processing package being used, but generally motion in excess of 3 millimeters will result in unusable data. The issue of motion is present for all populations, but most notably within populations that are not physically or emotionally equipped for even short MRI sessions (e.g., those with Alzheimer's Disease or schizophrenia, or young children). In these populations, various positive and negative reinforcement strategies can be employed in an attempt to attenuate motion artifacts, but in general the solution lies in designing a compatible paradigm with these populations.
An fMRI experiment usually lasts 1-2 hours. Depending on the purpose of study, subjects may view movies, hear sounds, smell odors, do cognitive tasks such as memorizing or imagination, or press a few buttons. Researchers are required to give detailed instructions and descriptions of the experiment plan to each subject, who must sign a consent form before the experiment.
Safety is a very important issue in all experiments involving MRI. Potential subjects must ensure that they are able to enter the fMRI environment. Due to the nature of the fMRI scanner, there is an extremely strong magnetic field surrounding the fMRI scanner (at least 1.5 teslas, usually stronger). Potential subjects must be thoroughly examined for any ferromagnetic objects (e.g. watches, glasses, hair pins, pacemakers, bone plates and screws, etc.) before entering the scanning environment.
To this date, fMRI has neither proven therapeutic value nor known damage to the human body. Because fMRI brings no direct benefits to the human subject, cash payment is often used as incentives for researchers to recruit a group of subjects. The payment rate varies anywhere from $20 to $40 per hour, often higher than the payment rate used in other non-invasive human studies.
See also
External links
- About fMRI from Functional MRI Research Center, Columbia University
- Introduction to FMRI from the Oxford Centre for Functional Magnetic Resonance Imaging of the Brain, Oxford University
