Functional magnetic resonance imaging

Functional magnetic resonance imaging or functional MRI (fMRI) measures brain activity by detecting changes associated with blood flow. This technique relies on the fact that cerebral blood flow and neuronal activation are coupled. When an area of the brain is in use, blood flow to that region also increases. Functional magnetic resonance imaging or functional MRI (fMRI) measures brain activity by detecting changes associated with blood flow. This technique relies on the fact that cerebral blood flow and neuronal activation are coupled. When an area of the brain is in use, blood flow to that region also increases. The primary form of fMRI uses the blood-oxygen-level dependent (BOLD) contrast, discovered by Seiji Ogawa. This is a type of specialized brain and body scan used to map neural activity in the brain or spinal cord of humans or other animals by imaging the change in blood flow (hemodynamic response) related to energy use by brain cells. Since the early 1990s, fMRI has come to dominate brain mapping research because it does not require people to undergo shots or surgery, to ingest substances, or to be exposed to ionising radiation. This measure is frequently corrupted by noise from various sources; hence, statistical procedures are used to extract the underlying signal. The resulting brain activation can be graphically represented by color-coding the strength of activation across the brain or the specific region studied. The technique can localize activity to within millimeters but, using standard techniques, no better than within a window of a few seconds. Other methods of obtaining contrast are arterial spin labeling and diffusion MRI. The latter procedure is similar to BOLD fMRI but provides contrast based on the magnitude of diffusion of water molecules in the brain. In addition to detecting BOLD responses from activity due to tasks/stimuli, the fMRI paradigm includes also resting state fMRI, or taskless fMRI, which measures the subjects' baseline BOLD variance. Since roughly 1998, this line of studies has revealed the existence and properties of the default mode network (DMN), aka 'Resting State Network' (RSN), a functionally connected neural network of apparent 'brain states'. fMRI is used both in the research world, and to a lesser extent, in the clinical world. It can also be combined and complemented with other measures of brain physiology such as EEG and NIRS. Newer methods which improve both spatial and time resolution are being researched, and these largely use biomarkers other than the BOLD signal. Some companies have developed commercial products such as lie detectors based on fMRI techniques, but the research is not believed to be ripe enough for widespread commercialization. The fMRI concept builds on the earlier MRI scanning technology and the discovery of properties of oxygen-rich blood. MRI brain scans use a strong, permanent, static magnetic field to align nuclei in the brain region being studied. Another magnetic field, the gradient field, is then applied to spatially locate different nuclei. Finally, a radiofrequency (RF) pulse is played to kick the nuclei to higher magnetization levels, with the effect now depending on where they are located. When the RF field is removed, the nuclei go back to their original states, and the energy they emit is measured with a coil to recreate the positions of the nuclei. MRI thus provides a static structural view of brain matter. The central thrust behind fMRI was to extend MRI to capture functional changes in the brain caused by neuronal activity. Differences in magnetic properties between arterial (oxygen-rich) and venous (oxygen-poor) blood provided this link. Since the 1890s it has been known that changes in blood flow and blood oxygenation in the brain (collectively known as hemodynamics) are closely linked to neural activity. When neurons become active, local blood flow to those brain regions increases, and oxygen-rich (oxygenated) blood displaces oxygen-depleted (deoxygenated) blood around 2 seconds later. This rises to a peak over 4–6 seconds, before falling back to the original level (and typically undershooting slightly). Oxygen is carried by the hemoglobin molecule in red blood cells. Deoxygenated hemoglobin (dHb) is more magnetic (paramagnetic) than oxygenated hemoglobin (Hb), which is virtually resistant to magnetism (diamagnetic). This difference leads to an improved MR signal since the diamagnetic blood interferes with the magnetic MR signal less. This improvement can be mapped to show which neurons are active at a time. During the late 19th century, Angelo Mosso invented the 'human circulation balance', which could non-invasively measure the redistribution of blood during emotional and intellectual activity. However, although briefly mentioned by William James in 1890, the details and precise workings of this balance and the experiments Mosso performed with it remained largely unknown until the recent discovery of the original instrument as well as Mosso’s reports by Stefano Sandrone and colleagues. Angelo Mosso investigated several critical variables that are still relevant in modern neuroimaging such as the ‘signal-to-noise ratio', the appropriate choice of the experimental paradigm and the need for the simultaneous recording of differing physiological parameters. Mosso's manuscripts do not provide direct evidence that the balance was really able to measure changes in cerebral blood flow due to cognition, however a modern replication performed by David T Field has now demonstrated using modern signal processing techniques unavailable to Mosso that a balance apparatus of this type is able to detect changes in cerebral blood volume related to cognition. In 1890, Charles Roy and Charles Sherrington first experimentally linked brain function to its blood flow, at Cambridge University. The next step to resolving how to measure blood flow to the brain was Linus Pauling's and Charles Coryell's discovery in 1936 that oxygen-rich blood with Hb was weakly repelled by magnetic fields, while oxygen-depleted blood with dHb was attracted to a magnetic field, though less so than ferromagnetic elements such as iron. Seiji Ogawa at AT&T Bell labs recognized that this could be used to augment MRI, which could study just the static structure of the brain, since the differing magnetic properties of dHb and Hb caused by blood flow to activated brain regions would cause measurable changes in the MRI signal. BOLD is the MRI contrast of dHb, discovered in 1990 by Ogawa. In a seminal 1990 study based on earlier work by Thulborn et al., Ogawa and colleagues scanned rodents in a strong magnetic field (7.0 T) MRI. To manipulate blood oxygen level, they changed the proportion of oxygen the animals breathed. As this proportion fell, a map of blood flow in the brain was seen in the MRI. They verified this by placing test tubes with oxygenated or deoxygenated blood and creating separate images. They also showed that gradient-echo images, which depend on a form of loss of magnetization called T2* decay, produced the best images. To show these blood flow changes were related to functional brain activity, they changed the composition of the air breathed by rats, and scanned them while monitoring brain activity with EEG. The first attempt to detect the regional brain activity using MRI was performed by Belliveau and colleagues at Harvard University using the contrast agent Magnevist, a ferromagnetic substance remaining in the bloodstream after intravenous injection. However, this method is not popular in human fMRI, because of the inconvenience of the contrast agent injection, and because the agent stays in the blood only for a short time. Three studies in 1992 were the first to explore using the BOLD contrast in humans. Kenneth Kwong and colleagues, using both gradient-echo and inversion recovery Echo Planar Imaging (EPI) sequence at a magnetic field strength of 1.5 T published studies showing clear activation of the human visual cortex. The Harvard team thereby showed that both blood flow and blood volume increased locally in activity neural tissue. Ogawa and others conducted a similar study using a higher field (4.0 T) and showed that the BOLD signal depended on T2* loss of magnetization. T2* decay is caused by magnetized nuclei in a volume of space losing magnetic coherence (transverse magnetization) from both bumping into one another and from intentional differences in applied magnetic field strength across locations (field inhomogeneity from a spatial gradient). Bandettini and colleagues used EPI at 1.5 T to show activation in the primary motor cortex, a brain area at the last stage of the circuitry controlling voluntary movements. The magnetic fields, pulse sequences and procedures and techniques used by these early studies are still used in current-day fMRI studies. But today researchers typically collect data from more slices (using stronger magnetic gradients), and preprocess and analyze data using statistical techniques.