Blood-oxygen-level dependent contrast imaging, or BOLD-contrast imaging, is a method used in functional magnetic resonance imaging (fMRI) to observe different areas of the brain or other organs, which are found to be active at any given time. Its proof of concept was provided by Seiji Ogawa and colleagues in 1990, following an experiment which demonstrated that an in vivo change of blood oxygenation could be detected with MRI. Other notable pioneers of BOLD fMRI include Kenneth Kwong and colleagues, who first used the technique in human participants in 1992.
Neurons do not have internal reserves of energy in the form of sugar and oxygen, so their firing causes a need for more energy to be brought in quickly. Through a process called the hemodynamic response, blood releases oxygen to them at a greater rate than to inactive neurons. This causes a change of the relative levels of oxyhemoglobin and deoxyhemoglobin (oxygenated or deoxygenated blood) that can be detected on the basis of their differential magnetic susceptibility.
In 1990, three papers published by Seiji Ogawa and colleagues showed that hemoglobin has different magnetic properties in its oxygenated and deoxygenated forms, both of which could be detected using MRI. This leads to magnetic signal variation which can be detected using an MRI scanner. Given many repetitions of a thought, action or experience, statistical methods can be used to determine the areas of the brain which reliably have more of this difference as a result, and therefore which areas of the brain are active during that thought, action or experience.
Criticism and limitations
Although most fMRI research uses BOLD contrast imaging as a method to determine which parts of the brain are most active, because the signals are relative, and not individually quantitative, some question its rigor. Other methods which propose to measure neural activity directly have been attempted (for example, measurement of the Oxygen Extraction Fraction, or OEF, in regions of the brain, which measures how much of the oxyhemoglobin in the blood has been converted to deoxyhemoglobin), 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 so far.
The typical discarding the low-frequency signals in BOLD-contrast imaging came into question in 1995, when it was observed that the “noise” in the area of the brain that controls right-hand movement fluctuated in unison with similar activity in the area on the opposite side of the brain associated with left-hand movement. BOLD-contrast imaging is only sensitive to differences between two brain states, so a new method was needed to analyse these correlated fluctuations called Resting state fMRI.
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The fMRI signal is usually referred to as the blood oxygen level–dependent, or BOLD, signal because the imaging method relies on changes in the level of oxygen in the human brain induced by alterations in blood flow.
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Ogawa et al. were able to demonstrate that in vivo changes blood oxygenation could be detected with MRI.
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