BOLD fMRI paradigms generally have several periods of rest alternating with several periods of activation. Images are then compared over the entire activation to the rest periods. Images obtained over the first 3 to 6 seconds of each period are generally discarded due to the delay in hemodynamic response. Alternating paradigms are used because the signal intensity generated by the MRI scanner drifts with time.
fMRI BOLD is best used for studying processes that can be rapidly turned on and off like language, vision, movement, hearing and memory. The study of emotion is hampered by its slow and variable onset and its inability to be quickly reversed. Some have, however, succeeded in using this technique to study emotional processes.
BOLD fMRI is very sensitive to movement so that tasks are limited to those without head movement, including speaking. BOLD fMRI is also limited in that artifacts are often present in brain regions that are close to air (ie. sinuses). Thus there are some problems in observing important emotional regions at the base of the brain like the orbitofrontal and medial temporal cortices. Another problem is that sometimes observed areas of activation may be located more in areas near large draining veins rather than directly at a capillary bed near the site of neuronal activation. Neurologists and neurosurgeons are beginning to use this technique clinically to noninvasively map language, motor and memory function in patients undergoing neurosurgery.
Two fMRI methods have been developed for measuring cerebral blood flow. The first method, called intravenous bolus tracking, relies on the intravenous (iv) injection of a magnetic compound such as a gadolinium-containing contrast agent and measuring its T2 weighted signal as it perfuses through the brain over a short time period of time.
Areas perfused with the magnetic compound show less signal intensity as the compound creates a magnetic inhomogeneity that decreases the T2 signal. The magnetic compound may be injected once during the control and once during the activation task and relative differences in blood flow between the two states may be determined to develop a perfusion image. Alternatively one can measure changes in blood few over time over time after a single injection to generate a perfusion map.
Although gadolinium-based contrasts are not radioactive, the number of boluses that can be given to an individual is limited by the potential for kidney toxicity with repeated tracer administration. This technique also only generates a map of relative cerebral blood flow, not absolute flow as in the text technique. Arterial spin labeling is a T1 weighted noninvasive technique where intrinsic hydrogen atoms in arterial water outside of the slice of interest are magnetically tagged (“flipped”) as they course through the blood and are then imaged as they enter the slice of interest.
Arterial spin labelling is noninvasive, does not involve an IV bolus injection, and can, thus, be repeatedly performed in individual subjects. Also, absolute regional blood flow can be measured which cannot be easily measured with SPECT or BOLD fMRI and requires an arterial line with PET. As absolute information is obtained, cerebral blood flow can be serially measured over separate imaging sessions such as measuring blood flow in bipolar subjects as they course through different disease states. Absolute blood flow information may be important in imaging such processes as anxiety which may be hard to turn on and off. For instance, in social phobics, a relaxation task may be imaged on one day and anticipating making a speech may be imaged on the next day. Comparing these separate tasks in different imaging sessions would not be possible with BOLD fMRI. Arterial spin labelling has some limitations in that it takes several minutes to acquire information on a single slice of interest. Therefore, one must have a specific brain region that one is interested in examining. Also, as it currently takes several minutes to acquire a single slice, it would be tedious obtaining enough images on this slice within a single session to make a statistical statement on a given subject.Brain scanning technology is quickly approaching levels of detail that will have serious implications (Photo credit: Wikipedia)
2. Diffusion-Weighted Imaging (DWI)
Diffusion-weighted imaging is very sensitive to the random movement of 1 H in water molecules (Brownian movement). The amount of water diffusion for a given pixel can be calculated and is called the apparent diffusion coefficient (ADC). Areas with low ADC value (ie. low diffusion) appear more intense. ADC values are direction sensitive. For instance, if images are taken perpendicular to myelin fiber tracts like the optic chiasm, arcuate fasciculus, or corpus callosum, ADC values will be lower than if the images are taken along the length of these fibers. This is thought to because there is little diffusion across myelin sheaths. Thus, ADC direction sensitivity permits detection of Myelination and may allow researchers to understand in greater detail myelin development in infants. On the other hand, this direction sensitivity hampers the study of diffusion in other processes as ADC values differ, depending on the imaging plane (axial, coronal or sagittal). There are now ways to calculate average ADC values incorporating all planes for each pixel, removing “artifacts” due to the direction of acquisition. Removing the directional diffusion sensitivity has been helpful in studying stroke.
While it is currently unclear now diffusion-weighted imaging will be useful in studying psychiatric disorders, it hold great promise for changing the clinical management of acute ischaemic stroke by potentially refining the criteria for patients most likely to benefit from thrombolytic therapy.
3. MRI Spectroscopy (MRS):
MRI spectroscopy (MRS) offers the capability of using MRI to noninvasively study tissue biochemistry. In the conventional and functional MRI techniques listed. The hydrogen atom in water is the main one that is flipped (resonated). In MRS, either 1H atoms in other molecules or other atoms such as 31P, 23Na, K, 19F or Li are flipped. Within a given brain region called a voxel, information on these molecules is usually presented as a spectrograph with precession frequency on the x-axis revealing the identity of a compound and intensity on the y-axis, which helps quantify the amount of a substance. The quantity of a substance is related is related to the area under its spectrographic peak; the larger the area, the more of a substance that is present.
The reason why several molecules can be identified and quantified within a single scan is that the resonant magnetic pulse has a bandwidth over a narrow precession frequency range os that it can flip several molecules at once. The signal intensity at each of these precession frequencies can then be identified using a complicated mathematical procedure called a Fourier transform. For a given precession frequency (or spectrographic peak of a given molecule), information can also be presented spatially as metabolic maps which are created with similar principles to the 1H atom in water spatial map in conventional MRI. The spatial resolution of these maps is generally less than that of conventional MRI as the substance concentration is much less than that of water. Consequently, the minimum area needed to obtain a visible signal is greater.
The two most widely used MRS techniques involve either viewing 1H atoms in molecules other than water or 31P-containing molecules. In 1H MRS, the water signal must first be suppressed as it is much greater than the signal from other 1H-containing compounds and has overlapping spectroscopic peaks with compounds.
Compounds that can be resolved with 1H-MRS include:
a) N-acetylaspartate (NAA) which is though to be a neuronal marker that decreases in processes where neurons die;
b) Lactate which is a product of anaerobic metabolism and may indicate hypoxia;
c) Excitatory neurotransmitters glutamate and aspartate;
d) The inhibitory neurotransmitter gamma-amino butyric acid (GABA);
e) Cytosolic choline which includes primarily mobile molecules involved in phospholipid membrane metabolism but also small amounts of the neurotransmitter acetylcholine and its precursor choline;
1. Myolinositol which is important in phospholipoid metabolism and intracellular second messenger systems; and
2. Creatine molecules such as creatine and phosphocreatine which usually have relatively constant concentrations throughout the brain and are often used as relative reference molecules (ie. one may see NAA concentration reported as the ratio NAA/creatine in the literature).
Phosphorus (31P) MRS allows the quantification of ATP metabolism, intracellular pH, and phospholipid metabolism. Mobile phospholipid, including phosphomonoesters (PME – putative cell membrane building blocks) and phosphodiesters (PDE – putative cell membrane breakdown products) can also be measured, supplying information on phospholipid membrane metabolism.
MRS is an useful tool to be used in the characterization of tumor, stroke and epileptogenic tissue and in presurgical planning.
MRS is restricted to studying mobile magnetic compounds. As neurochemical receptors are noted usually mobile, they cannot be measured with MRS. Thus, receptor-ligand studies in psychiatry are still the domain of SPECT and PET. Another problem with MRS is that due to the low concentrations of many of the imaged substances, larger areas than with water are needed to obtain detectable signals. Larger volume units imaged over longer periods are thus used with this technique, limiting both temporal and spatial resolution compared with conventional MRI and BOLD-fMRI. However, stronger magnetic fields which can spread out precession frequencies over a wider range may improve this resolution.
While there are currently no clinical indications for ordering any of these fMRI techniques, they hold considerable promise for unraveling the neurocircuitry and metabolic pathways of numerous disorders in the immediate future and in further helping in diagnosis and treatment planning.
- “Using Brain Imaging for Lie Detection: Where Science, Law, and Policy Collide” (kolber.typepad.com)
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