Signal enhancement by extravascular water protons
Encyclopedia
Signal enhancement by extravascular water protons, or SEEP, is a contrast mechanism for functional magnetic resonance imaging
Functional magnetic resonance imaging
Functional magnetic resonance imaging or functional MRI is a type of specialized MRI scan used 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 neuroimaging...

 (fMRI), which is an alternative to the more commonly employed BOLD (blood-oxygen-level dependent) contrast. This mechanism for image contrast changes corresponding to changes in neuronal activity was first proposed by Dr. Patrick Stroman in 2001 (1, 2). SEEP contrast is based on changes in tissue water content which arise from the increased production of extracellular fluid
Extracellular fluid
Extracellular fluid usually denotes all body fluid outside of cells. The remainder is called intracellular fluid.In some animals, including mammals, the extracellular fluid can be divided into two major subcompartments, interstitial fluid and blood plasma...

 (3, 4) and swelling of neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...

s and glial cell
Glial cell
Glial cells, sometimes called neuroglia or simply glia , are non-neuronal cells that maintain homeostasis, form myelin, and provide support and protection for neurons in the brain, and for neurons in other parts of the nervous system such as in the autonomous nervous system...

s at sites of neuronal activity (5, 6). Because the dominant sources of MRI
Magnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...

 signal in biological tissues are water and lipids, an increase in tissue water content is reflected by a local increase in MR
Magnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...

 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 (7, 8). The advantage of SEEP contrast is that it can be detected with MR imaging methods which are relatively insensitive to magnetic susceptibility
Magnetic susceptibility
In electromagnetism, the magnetic susceptibility \chi_m is a dimensionless proportionality constant that indicates the degree of magnetization of a material in response to an applied magnetic field...

 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 (spinal fMRI
Spinal fMRI
Functional magnetic resonance imaging of the spinal cord is an adaptation of the fMRI method that has been developed for use in the brain...

) 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 (7-10).
It is also controversial because it is not universally agreed to exist as a contrast mechanism for fMRI.
However, more recent studies have demonstrated changes in MRI signal corresponding with changes in neuronal activity in rat cortical tissue slices, in the absence of blood flow or changes in oxygenation, and neuronal activity and cellular swelling were corroborated by light-transmittance microscopy.
This demonstrated SEEP contrast in the absence of confounding factors which can occur in-vivo, such as physiological motion and the possibility of concurrent BOLD contrast.
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