Functional Magnetic Resonance Imaging (fMRI) inNeuroradiology:First, the most commonly used fMRI technique called BOLD-fMRI (Blood-Oxygen-Level-dependent fMRI) potentially offers imaging with a temporalresolution on the order of 100 milliseconds and a spatial resolution of 1-2millimeters, which is much greater than that of PET and SPECT scanning. Thismeans that transient cognitive events can potentially be imaged and smallstructures like the amygdala can be more readily resolved. Most fMRItechniques are noninvasive and do not involve the injection of radioactivematerials so that a person can be imaged repeatedly. This allows imaging of apatient repeatedly through different disease states or developmental changesThird, with fMRI, one can easily make statistical statements in comparingdifferent functional states within an individual in a single session. Thus, fMRImay be of important use in understanding how a given individual’s brainfunctions and perhaps, in the future, making psychiatric diagnoses andtreatment recommendations. It is in fact already starting to being used inpresurgical planning to map vital areas like languages, motor function, andmemory.The four main applications of MRI for functional information can becategorized 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 techniqueWith this technique, it is assumed that an area is relatively more active when ithas more oxygenated blood compared to another point in time. This is based onthe principle that when a brain region is being used, arterial oxygenated bloodwill 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 andblood flow increases to it . During this time lag of 3-6 second, in fact, theactivated areas experience relative decrease in oxygenated blood as oxygen is
extracted by the active regional neurons. Afterward, the amount of bloodflowing to the area far out weighs the amount of oxygen that is extracted sothat oxygenated blood is now higher. Although images can be acquired every100 msecs with echoplanar (a type of rapid acquisition) BOLD fMRI, thispredictable but time varied delayed onset of the BOLD response limits theimmediate temporal resolution to several seconds instead of the 100 msecpotential. In the future, researchers may be able to improve the temporalresolution of fMRI by measuring the initial decrease in oxygenated blood withactivation.BOLD fMRI is a relative technique in that it must compare images taken duringone mental state to another to create a meaningful picture. As images areacquired very rapidly (ie. a set of 15 coronal brain slices every 3 seconds iscommonly) one can acquire enough images to measure the relative differencesbetween two states to perform a statistical analysis within a single individual.Ideally, these states would differ in only one aspect so that everything iscontrolled for except the behavior in question.BOLD fMRI paradigms generally have several periods of rest alternating withseveral periods of activation. Images are then compared over the entireactivation to the rest periods. Images obtained over the first 3 to 6 seconds ofeach period are generally discarded due to the delay in hemodynamicresponse. Alternating paradigms are used because the signal intensitygenerated by the MRI scanner drifts with time.fMRI BOLD is best used for studying processes that can be rapidly turned onand off like language, vision, movement, hearing and memory. The study ofemotion is hampered by its slow and variable onset and its inability to bequickly reversed. Some have, however, succeeded in using this technique tostudy emotional processes.BOLD fMRI is very sensitive to movement so that tasks are limited to thosewithout head movement, including speaking. BOLD fMRI is also limited in thatartifacts are often present in brain regions that are close to air (ie. sinuses). Thusthere are some problems in observing important emotional regions at the baseof the brain like the orbitofrontal and medial temporal cortices. Anotherproblem is that sometimes observed areas of activation may be located more inareas near large draining veins rather than directly at a capillary bed near thesite of neuronal activation. Neurologists and neurosurgeons are beginning touse this technique clinically to noninvasively map language, motor andmemory 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 contrastagent and measuring its T2 weighted signal as it perfuses through the brainover a short time period of time.Areas perfused with the magnetic compound show less signal intensity as thecompound creates a magnetic inhomogeneity that decreases the T2 signal. Themagnetic compound may be injected once during the control and once duringthe activation task and relative differences in blood flow between the two statesmay be determined to develop a perfusion image. Alternatively one canmeasure changes in blood few over time over time after a single injection togenerate a perfusion map.Although gadolinium-based contrasts are not radioactive, the number ofboluses that can be given to an individual is limited by the potential for kidneytoxicity with repeated tracer administration. This technique also only generatesa map of relative cerebral blood flow, not absolute flow as in the text technique.Arterial spin labeling is a T1 weighted noninvasive technique where intrinsichydrogen atoms in arterial water outside of the slice of interest are magneticallytagged (“flipped”) as they course through the blood and are then imaged asthey 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, absoluteregional blood flow can be measured which cannot be easily measured withSPECT or BOLD fMRI and requires an arterial line with PET. As absoluteinformation is obtained, cerebral blood flow can be serially measured overseparate imaging sessions such as measuring blood flow in bipolar subjects asthey course through different disease states. Absolute blood flow informationmay be important in imaging such processes as anxiety which may be hard toturn on and off. For instance, in social phobics, a relaxation task may be imagedon one day and anticipating making a speech may be imaged on the next day.Comparing these separate tasks in different imaging sessions would not bepossible with BOLD fMRI. Arterial spin labelling has some limitations in that ittakes several minutes to acquire information on a single slice of interest.Therefore, one must have a specific brain region that one is interested inexamining. Also, as it currently takes several minutes to acquire a single slice, itwould be tedious obtaining enough images on this slice within a single sessionto 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 Hin water molecules (Brownian movement). The amount of water diffusion for agiven 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 takenperpendicular to myelin fiber tracts like the optic chiasm, arcuate fasciculus, orcorpus callosum, ADC values will be lower than if the images are taken alongthe length of these fibers. This is thought to because there is little diffusionacross myelin sheaths. Thus, ADC direction sensitivity permits detection ofMyelination and may allow researchers to understand in greater detail myelindevelopment in infants. On the other hand, this direction sensitivity hampersthe study of diffusion in other processes as ADC values differ, depending onthe imaging plane (axial, coronal or sagittal). There are now ways to calculateaverage ADC values incorporating all planes for each pixel, removing“artifacts” due to the direction of acquisition. Removing the directionaldiffusion sensitivity has been helpful in studying stroke.While it is currently unclear now diffusion-weighted imaging will be useful instudying psychiatric disorders, it hold great promise for changing the clinicalmanagement of acute ischaemic stroke by potentially refining the criteria forpatients most likely to benefit from thrombolytic therapy.3. MRI Spectroscopy (MRS):MRI spectroscopy (MRS) offers the capability of using MRI to noninvasivelystudy tissue biochemistry. In the conventional and functional MRI techniqueslisted. 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, informationon these molecules is usually presented as a spectrograph with precessionfrequency on the x-axis revealing the identity of a compound and intensity onthe y-axis, which helps quantify the amount of a substance. The quantity of asubstance is related is related to the area under its spectrographic peak; thelarger the area, the more of a substance that is present.The reason why several molecules can be identified and quantified within asingle scan is that the resonant magnetic pulse has a bandwidth over a narrowprecession frequency range os that it can flip several molecules at once. Thesignal intensity at each of these precession frequencies can then be identifiedusing a complicated mathematical procedure called a Fourier transform. For agiven precession frequency (or spectrographic peak of a given molecule),
information can also be presented spatially as metabolic maps which arecreated with similar principles to the 1H atom in water spatial map inconventional MRI. The spatial resolution of these maps is generally less thanthat of conventional MRI as the substance concentration is much less than thatof water. Consequently, the minimum area needed to obtain a visible signal isgreater.The two most widely used MRS techniques involve either viewing 1H atoms inmolecules other than water or 31P-containing molecules. In 1H MRS, the watersignal must first be suppressed as it is much greater than the signal from other1H-containing compounds and has overlapping spectroscopic peaks withcompounds.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.
LimitationsMRS is restricted to studying mobile magnetic compounds. Asneurochemical receptors are noted usually mobile, they cannot be measuredwith MRS. Thus, receptor-ligand studies in psychiatry are still the domain ofSPECT and PET. Another problem with MRS is that due to the lowconcentrations of many of the imaged substances, larger areas than withwater are needed to obtain detectable signals. Larger volume units imagedover longer periods are thus used with this technique, limiting bothtemporal and spatial resolution compared with conventional MRI andBOLD-fMRI. However, stronger magnetic fields which can spread outprecession frequencies over a wider range may improve this resolution.ConclusionsWhile there are currently no clinical indications for ordering any of thesefMRI techniques, they hold considerable promise for unraveling theneurocircuitry and metabolic pathways of numerous disorders in theimmediate future and in further helping in diagnosis and treatmentplanning.