Functional magnetic resonance imaging (fMRI) is an MRI procedure that measures brain activity by detecting associated changes in blood flow.
BOLD: Blood-oxygen-level dependent (BOLD) is the MRI contrast of blood deoxyhaemoglobin first discovered in 1990 by Dr. Seiji Ogawa who also recognized the potential importance of BOLD for functional brain imaging with MRI.
Blood Oxygen Level Dependent functional magnetic resonance imaging (fMRI) depicts changes in deoxyhaemoglobin concentration consequent to task-induced or spontaneous modulation of neural metabolism. Since its inception in 1990, this method has been widely employed in thousands of studies of cognition for clinical applications such as surgical planning, for monitoring treatment outcomes, and as a biomarker in pharmacologic and training programs. Technical developments have solved most of the challenges of applying fMRI in practice. These challenges include low contrast to noise ratio of BOLD signals, image distortion, and signal dropout. More recently, attention is turning to the use of pattern classification and other statistical methods to draw increasingly complex inferences about cognitive brain states from fMRI data.
This is a type of specialized brain and body scan used to map neural activity in the brain or spinal cord of humans or 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, surgery, or to ingest substances, or be exposed to radiation.
The procedure is like MRI but uses the change in magnetization between oxygen-rich and oxygen-poor blood as its basic measure. This measure is frequently corrupted by noise from various sources and hence statistical procedures are used to extract the underlying signal. The resulting brain activation can be presented graphically by color-coding the strength of activation across the brain or the specific region studied. The technique can localize activity to within millimetres but, using standard techniques, no better than within a window of a few seconds.
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 commercialisation.
Functional MRI measures the haemodynamic response (change in blood flow) related to neural activity in the brain or spinal cord.. It is one of the most recently developed forms of neuro-imaging. Since the early 1990s, fMRI has come to dominate the brain mapping field due to its relatively low invasiveness, absence of radiation exposure, and relatively wide availability.
Since the 1890s it has been known that changes in blood flow and blood oxygenation in the brain (collectively known as Haemodynamics) are closely linked to neural activity. When nerve cells are active they increase their consumption of oxygen, switching to less energetically effective, but more rapid anaerobic glycolysis. The local response to this oxygen utilization is to increase blood flow to regions of increased neural activity, which occurs after a delay of approximately 1-5 seconds. This haemodynamic response rises to a peak over 4-5 seconds, before falling back to baseline (and typically undershooting slightly). This leads to local changes in the relative concentration of oxyhaemoglobin and deoxyhaemoglobin and changes in local cerebral blood volume in addition to this change in local cerebral blood flow.
This patient underwent an fMRI to localize language preoperatively.
A motor paradigm was also performed (shown here) BOLD (Blood Oxygenation Level Dependent) Imaging is a functional MRI (fMRI) technique to delineate regional activity.
BOLD: The Science
As neurons do not have internal energy reserves in the form of glucose and oxygen, their firing requires more energy to be delivered quickly. Through a process called the haemodynamic response, blood releases oxygen to them at a greater rate than to inactive neurons. Haemoglobin 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. Higher BOLD signal intensities arise from increases in the concentration of oxygenated haemoglobin since the blood magnetic susceptibility now more closely matches the tissue magnetic susceptibility. By collecting data in an MRI scanner with sequence parameters sensitive to changes in magnetic susceptibility one can assess changes in BOLD contrast. These changes can be either positive or negative depending upon the relative changes in both cerebral blood flow (CBF) and oxygen consumption. Increases in CBF that outstrip changes in oxygen consumption will lead to increased BOLD signal, conversely decreases in CBF that outstrip changes in oxygen consumption will cause decreased BOLD signal intensity. The signal difference is very small, but given many repetitions of a thought, action or experience, statistical methods can be used to determine the areas of the brain which reliably show more of this difference as a result, and therefore which areas of the brain are active during that thought, action or experience.
Almost all current fMRI research uses BOLD as the method for determining where activity occurs in the brain as the result of various experiences, but because the signals are relative and not individually quantitative, some question its rigor. Other methods which propose to measure neural activity more directly have been attempted, but because the electromagnetic fields created by an active or firing neuron are so weak, the signal-to-noise ratio is extremely low and statistical methods used to extract quantitative data have been largely unsuccessful.
Functional magnetic resonance imaging (fMRI) relies on the paramagnetic properties of oxygenated and deoxygenated haemoglobin to see images of changing blood flow in the brain associated with neural activity. This allows images to be generated that reflect which brain structures are activated (and how) during performance of different tasks. Most fMRI scanners allow subjects to be presented with different visual images, sounds and touch stimuli, and to make different actions such as pressing a button or moving a joystick. Consequently, fMRI can be used to reveal brain structures and processes associated with perception, thought and action. The resolution of fMRI is about 2-3 millimetres at present, limited by the spatial spread of the haemodynamic response to neural activity. It has largely superseded PET for the study of brain activation patterns. PET, however, retains the significant advantage of being able to identify specific brain receptors (or transporters) associated with particular neurotransmitters through its ability to image radio-labelled receptor "ligands" (receptor ligands are any chemicals that stick to receptors).
(left) Axial MRI slice at the level of the basal ganglia, showing fMRI BOLD signal changes overlaid in red (increase) and blue (decrease) tones.
As well as research on healthy subjects, fMRI is increasingly used for the medical diagnosis of disease. Because fMRI is exquisitely sensitive to blood flow, it is extremely sensitive to early changes in the brain resulting from ischemia (abnormally low blood flow), such as the changes which follow stroke.
Early diagnosis of certain types of stroke is increasingly important in neurology, since substances which dissolve blood clots may be used in the first few hours after certain types of stroke occur, but are dangerous to use afterwards. Brain changes seen on fMRI may help to make the decision to treat with these agents.
With between 72% and 90% accuracy where chance would achieve 0.8%, fMRI techniques can decide which of a set of known images the subject is viewing.
What are some common uses of the procedure?
fMRI is becoming the diagnostic method of choice for learning how a normal, diseased or injured brain is working, as well as for assessing the potential risks of surgery or other invasive treatments of the brain.
Physicians perform fMRI to:
- Examine the anatomy of the brain.
- Determine precisely which part of the brain is handling critical functions such as thought, speech, movement and sensation, which is called brain mapping.
- Help assess the effects of stroke, trauma or degenerative disease (such as Alzheimer's) on brain function.
- Monitor the growth and function of brain tumours.
- Guide the planning of surgery, radiation therapy, or other surgical treatments for the brain.
A new brain scanner has been developed to help people who are completely paralysed speak by enabling them to spell words using their thoughts. It uses functional magnetic resonance imaging (fMRI) to help patients choose between 27 characters - the alphabet and a blank space. Each character produces a different pattern of blood flow in the brain, and the device interprets these patterns. The British Neurological Association called the research "exciting".
The new technology is based on earlier applications of the technique, which used free-letter spelling to allow people to answer the equivalent of multiple-choice questions, but the new fMRI scanner uses the entire English alphabet and the blank space to allow spelling of words.
Future of fMRI
For the most part, the MRI physics and technology development behind BOLD fMRI acquisitions are mature, and the trade-offs between acquisition speed, resolution, SNR, signal dropout and contrast are well understood. Over the years, a number of investigators have attempted to develop alternatives to BOLD contrast using direct neural current detection, although by now it is understood that the weak size of the neural current signal relative to physiological noise makes a breakthrough unlikely. Another alternative is the use of diffusion weighted imaging to demonstrate activation-related changes in populations of bound vs. free water distributions. A potential advantage is that such diffusion related changes may have more rapid responses than BOLD methods. However, again the signals are weaker than BOLD contrast and their biophysical origin is still unclear.
While a modest research effort will continue in improving acquisition technology, the bulk of research in the development of fMRI has shifted to its application to answering more complex questions in cognitive neuroscience. One promising area is that of using activation maps as input to classification and state change algorithms to predict or classify cognitive behaviour, such as predicting brain states. Other emerging uses of fMRI include the development of quantitative measures, i.e. biomarkers for disease or monitoring behavioural modification such as reading disorders. A cautionary note, however, is that because of the small BOLD responses typical of cognitive processes, most studies are limited to employing group statistics to make inferences about populations rather than about individuals. Thus fMRI’s use in quantifying individual characteristics may continue to be limited to those tasks for which relatively strong BOLD responses are observed, such as primary sensory systems. Resting state networks and their modification by disease conditions such as Alzheimer’s, depression and other psychiatric disorders are gaining attention. However, there is growing awareness that these networks may be much more complex in their spatio-temporal dynamics than previously thought, and much more work is indicated to understand their role and utility in predicting individual behaviour/physiology.
Finally, feedback derived from real-time fMRI has been shown to allow subjects to learn pain-reduction strategies, enhance sensorimotor control and to control relevant brain regions in mood disorder experiments.
Functional MRI has enjoyed an exciting development course with an exponential growth in published studies since its inception in the early 90’s, and it has become commonplace for clinical uses such as presurgical planning, fundamental cognitive neuroscience investigations, behaviour modification and training. Informed by fMRI, more sophisticated modelling of brain networks is certain to lead to new levels of understanding of the human brain.