Functional Magnetic Resonance Imaging (fMRI) in Neuroradiology:
Dr Himadri S.Das
First, the most commonly used fMRI technique called BOLD-fMRI (Blood-Oxygen-Level-dependent fMRI) potentially offers imaging with a temporal resolution on the order of 100 milliseconds and a spatial resolution of 1-2 millimeters, which is much greater than that of PET and SPECT scanning. This means that transient cognitive events can potentially be imaged and small structures like the amygdala can be more readily resolved. Most fMRI techniques are noninvasive and do not involve the injection of radioactive materials so that a person can be imaged repeatedly. This allows imaging of a patient repeatedly through different disease states or developmental changes Third, with fMRI, one can easily make statistical statements in comparing different functional states within an individual in a single session. Thus, fMRI may be of important use in understanding how a given individual’s brain functions and perhaps, in the future, making psychiatric diagnoses and treatment recommendations. It is in fact already starting to being used in presurgical planning to map vital areas like languages, motor function, and memory.
The four main applications of MRI for functional information can be categorized as :-
1. BOLD-fMRI which measures regional differences in oxygenated blood.
2. Perfusion fMRI which measures regional cerebral blood flow.
3. Diffusion-weighted fMRI which measures random movement of water molecules and
4. MRI spectroscopy, which can measure certain cerebral metabolites noninvasively.
1. BOLD-fMRI (Blood-Oxygen-Level-Dependent fMRI)
BOLD-fMRI is currently the most common fMRI technique
With this technique, it is assumed that an area is relatively more active when it has more oxygenated blood compared to another point in time. This is based on the principle that when a brain region is being used, arterial oxygenated blood will redistribute and increase to this area. This principle has one limitation: there is a time lag of 3-6 seconds between when brain region is activated and blood flow increases to it . During this time lag of 3-6 second, in fact, the activated areas experience relative decrease in oxygenated blood as oxygen is extracted by the active regional neurons. Afterward, the amount of blood flowing to the area far out weighs the amount of oxygen that is extracted so that oxygenated blood is now higher. Although images can be acquired every 100 msecs with echoplanar (a type of rapid acquisition) BOLD fMRI, this predictable but time varied delayed onset of the BOLD response limits the immediate temporal resolution to several seconds instead of the 100 msec potential. In the future, researchers may be able to improve the temporal resolution of fMRI by measuring the initial decrease in oxygenated blood with activation.
BOLD fMRI is a relative technique in that it must compare images taken during one mental state to another to create a meaningful picture. As images are acquired very rapidly (ie. a set of 15 coronal brain slices every 3 seconds is commonly) one can acquire enough images to measure the relative differences between two states to perform a statistical analysis within a single individual. Ideally, these states would differ in only one aspect so that everything is controlled for except the behavior in question.
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.
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.