Blood-oxygen-level-dependent imaging

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Blood-oxygen-level-dependent 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. [1]

Contents

Theory

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 haemodynamic response, blood releases oxygen to active neurons 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 (deoxygenated hemoglobin is paramagnetic and oxygenated hemoglobin is diamagnetic), both of which could be detected using MRI. [2] 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 most 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 [3] ), 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 of 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. [1] BOLD-contrast imaging is only sensitive to differences between two brain states, [4] so a new method was needed to analyse these correlated fluctuations called resting state fMRI.

History

Its proof of concept of blood-oxygen-level-dependent contrast imaging 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. [5] In Ogawa's experiments, blood-oxygen-level-dependent imaging of rodent brain slice contrast in different components of the air. At high magnetic fields, water proton magnetic resonance images of brains of live mice and rats under anesthetization have been measured by a gradient echo pulse sequence. Experiments shown that when the content of oxygen in the breathing gas changed gradually, the contrast of these images changed gradually. Ogawa proposed and proved that the oxyhemoglobin and deoxyhemoglobin is the major contribution of this difference. [6]

Other notable pioneers of BOLD fMRI include Kenneth Kwong and colleagues, who first used the technique in human participants in 1992. [7]

See also

Related Research Articles

Hemoglobin Oxygen-transport metalloprotein in red blood cells of most vertebrates

Hemoglobin, abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein in red blood cells (erythrocytes) of almost all vertebrates as well as the tissues of some invertebrates. Hemoglobin in blood carries oxygen from the respiratory organs to the rest of the body. There it releases the oxygen to permit aerobic respiration to provide energy to power functions of an organism in the process called metabolism. A healthy individual human has 12 to 20 grams of hemoglobin in every 100 mL of blood.

Functional magnetic resonance imaging MRI procedure that measures brain activity by detecting associated changes in blood flow

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.

Haemodynamic response

In haemodynamics, the body must respond to physical activities, external temperature, and other factors by homeostatically adjusting its blood flow to deliver nutrients such as oxygen and glucose to stressed tissues and allow them to function. Haemodynamic response (HR) allows the rapid delivery of blood to active neuronal tissues. The brain consumes large amounts of energy but does not have a reservoir of stored energy substrates. Since higher processes in the brain occur almost constantly, cerebral blood flow is essential for the maintenance of neurons, astrocytes, and other cells of the brain. This coupling between neuronal activity and blood flow is also referred to as neurovascular coupling.

Magnetic resonance angiography Group of techniques based on magnetic resonance imaging (MRI) to image blood vessels.

Magnetic resonance angiography (MRA) is a group of techniques based on magnetic resonance imaging (MRI) to image blood vessels. Magnetic resonance angiography is used to generate images of arteries in order to evaluate them for stenosis, occlusions, aneurysms or other abnormalities. MRA is often used to evaluate the arteries of the neck and brain, the thoracic and abdominal aorta, the renal arteries, and the legs.

CO-oximeter

A CO-oximeter is a device that measures the oxygen carrying state of hemoglobin in a blood specimen, including oxygen-carrying hemoglobin (O2Hb), non-oxygen-carrying but normal hemoglobin (HHb), as well as the dyshemoglobins such as carboxyhemoglobin (COHb) and methemoglobin (MetHb). The use of 'CO' rather than 'Co' or 'co' is more appropriate since this designation represents a device that measures carbon monoxide (CO) bound to hemoglobin, as distinguished from simple oximetry which measures hemoglobin bound to molecular oxygen—O2Hb—or hemoglobin capable of binding to molecular oxygen—HHb. Simpler oximeters may report oxygen saturation alone, i.e. the ratio of oxyhemoglobin to total 'bindable' hemoglobin. CO-oximetry is useful in defining the causes for hypoxemia, or hypoxia,.

Neuroimaging Set of techniques to measure and visualize aspects of the nervous system

Neuroimaging is the use of quantitative (computational) techniques to study the structure and function of the central nervous system, developed as an objective way of scientifically studying the healthy human brain in a non-invasive manner. Increasingly it is also being used for quantitative studies of brain disease and psychiatric illness. Neuroimaging is a highly multidisciplinary research field and is not a medical specialty.

The Haldane effect is a property of hemoglobin first described by John Scott Haldane, within which oxygenation of blood in the lungs displaces carbon dioxide from hemoglobin, increasing the removal of carbon dioxide. Consequently, oxygenated blood has a reduced affinity for carbon dioxide. Thus, the Haldane effect describes the ability of hemoglobin to carry increased amounts of carbon dioxide (CO2) in the deoxygenated state as opposed to the oxygenated state. A high concentration of CO2 facilitates dissociation of oxyhemoglobin.

Seiji Ogawa Japanese researcher (born 1934)

Seiji Ogawa is a Japanese biophysicist and neuroscientist known for discovering the technique that underlies Functional Magnetic Resonance Imaging (fMRI). He is regarded as the father of modern functional brain imaging. He determined that the changes in blood oxygen levels cause its magnetic resonance imaging properties to change, allowing a map of blood, and hence, functional, activity in the brain to be created. This map reflected which neurons of the brain responded with electrochemical signals to mental processes. He was the first scientist who demonstrated that the functional brain imaging is dependent on the oxygenation status of the blood, the BOLD effect. The technique was therefore called Blood oxygenation level-dependent or BOLD contrast. Functional MRI (fMRI) has been used to map the visual, auditory, and sensory regions and moving toward higher brain functions such as cognitive functions in the brain.

Kenneth Kin Man Kwong is a Hong Kong-born American nuclear physicist. He is a pioneer in human brain imaging. He received his bachelor's degree in Political Science in 1972 from the University of California, Berkeley. He went on to receive his Ph.D. in physics from the University of California, Riverside studying photon-photon collision interactions.

Event-related functional magnetic resonance imaging (efMRI) is a technique used in magnetic resonance imaging of medical patients.

Neurophysics is the branch of biophysics dealing with the development and use of physical methods to gain information about the nervous system. Neurophysics is an interdisciplinary science using physics and combining it with other neurosciences to better understand neural processes. The methods used include the techniques of experimental biophysics and other physical measurements such as EEG mostly to study electrical, mechanical or fluidic properties, as well as theoretical and computational approaches. The term "neurophysics" is a portmanteau of "neuron" and "physics".

Signal enhancement by extravascular water protons, or SEEP, is a contrast mechanism for functional magnetic resonance imaging (fMRI), which is an alternative to the more commonly employed BOLD contrast. This mechanism for image contrast changes corresponding to changes in neuronal activity was first proposed by Dr. Patrick Stroman in 2001. SEEP contrast is based on changes in tissue water content which arise from the increased production of extracellular fluid and swelling of neurons and glial cells at sites of neuronal activity. Because the dominant sources of MRI signal in biological tissues are water and lipids, an increase in tissue water content is reflected by a local increase in MR signal intensity. A correspondence between BOLD and SEEP signal changes, and sites of activity, has been observed in the brain and appears to arise from the common dependence on changes in local blood flow to cause a change in blood oxygenation or to produce extracellular fluid. The advantage of SEEP contrast is that it can be detected with MR imaging methods which are relatively insensitive to magnetic susceptibility differences between air, tissues, blood, and bone. Such susceptibility differences can give rise to spatial image distortions and areas of low signal, and magnetic susceptibility changes in blood give rise to the BOLD contrast for fMRI. The primary application of SEEP to date has been fMRI of the spinal cord because the bone/tissue interfaces around the spinal cord cause poor image quality with conventional fMRI methods. The disadvantages of SEEP compared to BOLD contrast are that it reveals more localized areas of activity, and in the brain the signal intensity changes are typically lower, and it can therefore be more difficult to detect.

Functional magnetic resonance imaging (fMRI) of the spinal cord is an adaptation of the fMRI method that has been developed for use in the brain (1). Although the basic principles underlying the methods are the same, spinal fMRI requires a number of specific adaptations to accommodate the periodic motion of the spinal cord, the small cross-sectional dimensions, the length, and the fact that the magnetic field that is used for MRI varies with position in the spinal cord because of magnetic susceptibility differences between bone and tissues. Spinal fMRI has been used to produce maps of neuronal activity at most levels of the spinal cord in response to various stimuli, such as touch, vibration, and thermal changes, and with motor tasks. Research applications of spinal fMRI to date include studies of normal sensory and motor function, and studies of the effects of trauma to the spinal cord (1-3) and multiple sclerosis (4). Two different data acquisition methods have been applied, one based on the established BOLD fMRI methods used in the brain, and the other based on SEEP contrast with essentially proton-density weighted spin-echo imaging. The majority of the studies published to date are based on the SEEP contrast method. Methods demonstrated to overcome the challenges listed above include using a recording of the heart-beat to account for the related time course of spinal cord motion, acquiring image data with relatively high spatial resolution to detect fine structural details, and acquiring images in thin contiguous sagittal slices to span a large extent of the spinal cord. Methods based on BOLD contrast have employed parallel imaging techniques to accelerate data acquisition, and imaging slices transverse to the spinal cord, in order to reduce the effects of spatial magnetic field distortions (5). Methods based on SEEP contrast have been developed specifically because they have low sensitivity to magnetic field distortions while maintaining sensitivity to changes in neuronal activity.

Susceptibility weighted imaging

Susceptibility weighted imaging (SWI), originally called BOLD venographic imaging, is an MRI sequence that is exquisitely sensitive to venous blood, hemorrhage and iron storage. SWI uses a fully flow compensated, long echo, gradient recalled echo (GRE) pulse sequence to acquire images. This method exploits the susceptibility differences between tissues and uses the phase image to detect these differences. The magnitude and phase data are combined to produce an enhanced contrast magnitude image. The imaging of venous blood with SWI is a blood-oxygen-level dependent (BOLD) technique which is why it was referred to as BOLD venography. Due to its sensitivity to venous blood SWI is commonly used in traumatic brain injuries (TBI) and for high resolution brain venographies but has many other clinical applications. SWI is offered as a clinical package by Philips and Siemens but can be run on any manufacturer’s machine at field strengths of 1.0 T, 1.5 T, 3.0 T and higher.

Oxygen saturation (medicine) Medical measurement

Oxygen saturation is the fraction of oxygen-saturated hemoglobin relative to total hemoglobin in the blood. The human body requires and regulates a very precise and specific balance of oxygen in the blood. Normal arterial blood oxygen saturation levels in humans are 97–100 percent. If the level is below 90 percent, it is considered low and called hypoxemia. Arterial blood oxygen levels below 80 percent may compromise organ function, such as the brain and heart, and should be promptly addressed. Continued low oxygen levels may lead to respiratory or cardiac arrest. Oxygen therapy may be used to assist in raising blood oxygen levels. Oxygenation occurs when oxygen molecules enter the tissues of the body. For example, blood is oxygenated in the lungs, where oxygen molecules travel from the air and into the blood. Oxygenation is commonly used to refer to medical oxygen saturation.

Robert Turner is a British neuroscientist, physicist, and social anthropologist. He has been a director and professor at the Max Planck Institute for Human Cognitive and Brain Sciences in Leipzig, Germany, and is an internationally recognized expert in brain physics and magnetic resonance imaging (MRI). Coils inside every MRI scanner owe their shape to his ideas.

Magnetic resonance imaging of the brain

Magnetic resonance imaging of the brain uses magnetic resonance imaging (MRI) to produce high quality two-dimensional or three-dimensional images of the brain and brainstem as well as the cerebellum without the use of ionizing radiation (X-rays) or radioactive tracers.

Resting state fMRI Type of functional magnetic resonance imaging

Resting state fMRI is a method of functional magnetic resonance imaging (fMRI) that is used in brain mapping to evaluate regional interactions that occur in a resting or task-negative state, when an explicit task is not being performed. A number of resting-state brain networks have been identified, one of which is the default mode network. These brain networks are observed through changes in blood flow in the brain which creates what is referred to as a blood-oxygen-level dependent (BOLD) signal that can be measured using fMRI.

The following outline is provided as an overview of and topical guide to brain mapping:

MRI sequence

An MRI sequence in magnetic resonance imaging (MRI) is a particular setting of pulse sequences and pulsed field gradients, resulting in a particular image appearance.

References

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