Imaging through functional MRI is a complex medical technique, a new application in neurology which connects the cerebral structure with its function. This technique uses well established physical principles and has as results mapping of different functional cerebral areas. The article presents the clinical indications of fMRI in pediatric neurology.
WHAT IS MRI?
Magnetic resonance imaging is a medical technique which helps the physician in diagnosis and proper treatment of different medical pathologies.
Imaging through magnetic resonance uses a very powerful magnetic field with radio frequency pulses and a computer for detailed image analysis of dif-ferent organs (soft tissues, bones, internal organs). Images can then be examined on a computer screen, printed and copied to CD. This investigation does not use ionizing radiation (X rays).(8)
Detailed magnetic resonance images can improve the quality of the evaluation of different parts of the body and different tissues that can not be adequately assessed by other imaging methods that use X-rays (radiography, CT) or ultrasound.(l)
HOW IS IT DONE?
To make MRI, the patient is asked to wear a gown or clothing that contains no metal. Recommenda-tions on what can be given as food and drink before the examination varies depending on the specific ex-amination and its facilities. In general, if the patient is not recommended to follow special treatment he may have his usual nutrition and medication.
Some magnetic resonance examinations require the patient to swallow a contrast agent or an intra-venous contrast agent is administered. Radiologists and technicians should ask patients about tolerance to various substances, if the patient has some known allergies to iodinated substances and also to contrast X-rays substances, different medical drugs, food, sur-rounding substances, or if they are suffering from asthma. It should be noted that substances used for contrast in magnetic resonance are called gadolinium and do not contain iodine, so are unlikely to produce an allergic reaction.
Radiologists should be informed if the patient has major medical problems and what surgical interven-tions they had. Some pathology, such as severe renal ones represent a contraindication in using the contrast substances.
Women should inform the doctor or technician about the possibility of being pregnant. Nuclear mag-
netic resonance imagery has been used for scanning patients since 1980 without any pathological effects on pregnant women or their fetuses. However, because the fetus will be placed in a high magnetic field, pregnant women should not carry out this investiga-tion unless its therapeutic potential exceeds its risk.
If the patient suffers from claustrophobia (fear of enclosed spaces) or anxiety, mild sedative may be given.
Jewelry and other accessories, other metal objects or electronics should not be worn during the examination. In this category are included: earrings, watch-es, credit cards, hearing aids, hairpins, metal zippers, mobile prostheses, glasses, pens, etc.
Examination through nuclear magnetic resonance has no harmful effect on people with different metal implants with few exceptions. Thus, people who have the following implants can be scanned and should not enter the magnetic field until they have been carefully trained by radiologists or technicians: internal defi-brillators or a pacemaker, cochlear implants, certain types of clips used on brain aneurysms. If the patient is known to have any medical or electronic device in his body he must inform the technician, because it can interfere with the examination or it can represent a potential life threat. In this category are the following devices: artificial valves, cardiac pacemaker, artificial limb prostheses, peripheral nerve stimulator, metal-lic needles, screwdrivers, plates or surgical staples etc.
In general, metal objects used in orthopedic surgery pose no risk during MRI examination. However, an artificial prosthesis recently introduced requires a dif-ferent imaging procedure. If there is the question of the existence of a metal object the X-ray examination is useful for its detection.
Patients who have different tattoos that contain iodine, during magnetic resonance examination these can overheat, but these events are rarely a problem. Dental fillings and braces usually are not affected by the magnetic field, but may distort images of the facial area or brain, so that the radiologist should be aware of their existence.
HOW THE EQUIPMENT LOOKS LIKE?
The traditional unit of nuclear magnetic resonance imagery is represented by a cylinder-shaped tube sur-rounded by a circular magnet. The patient lies on an examination table that slides up and move into the magnet center.
Some magnetic resonance imaging examination units are designed in a way that the magnet does not completely surround the patient and others are fully open. These types of devices are specially designed for patients who have fear of enclosed spaces or are obese, but some types of examinations can not be made. New magnetic resonance imaging units can provide image quality for different types of examinations.
The computer that processes the images is in a separate room from the scanning device.
What is the principle of this investigation?
Unlike conventional X-ray examination and computer tomography, nuclear magnetic resonance imag-ery does not rely on radiation. Instead, once inserted into the magnet, the radio radiations redirect the pro-tons on the axis of rotation, which are actually nuclei of hydrogen atoms.(9)
In most magnetic resonance units, the magnetic field is produced by passing an electric current through different circuits. Other circuits located in the device or as otherwise looked around the body, send and re-ceive radio waves, producing signals that are detected by other circuits.For each organ separately, including the brain, the images are made from several angles and using multiple sequences. Thus, morphological brain MRI in-cludes axial, coronal or sagittal sections, with images in T1, T2 or Flair sequences (see Figure 1).
The computer processes these signals and gene-rates a series of images, each representing a section of a human body part. Images can be studied from different angles by the doctor.
After analyzing the images, complete differentiation between normal tissue and the abnormal one is more easily done on images acquired by magnetic resonance than on those by computer tomography, X-ray or ultrasound. (1)
HOW TO PERFORM THIS TECHNIQUE?
Examination by magnetic resonance imaging can be performed to hospitalized patients and also to out-patients or discharged ones. The patient will be po-sitioned on an examination table and different belts and sponges are used to restrain him and to maintain proper position during the examination.
Small devices that contain different circuits capable of transmitting or receiving radio waves will be placed around or adjacent to the examined area.
For brain MRI, the head will be placed in a box specially thought to help maintain position.
If it is necessary to administer a contrast agent during MRI examination, a nurse will provide a venous line and will first administrate a saline solution to prevent blockage of the venous line by the contrast substance.
The patient will be introduced in the magnet of the MRI unit and the radiologist or technician will leave the examination room during the examina-tion. When finished, the patient is asked to wait until the technician check all the images and, along with the radiologist, decides if there are more examina-tions needed. Then the intravenous line is removed. Examination by MRI generally includes several sequences of acquisition, some of them for a period lon-ger than a few minutes. The entire examination of the brain is complete after about 45 minutes.
WHAT THE PATIENT EXPERIENCES DURING THE TECHNIQUE?
Most nuclear magnetic resonance examinations are painless. However, some patients find uncomfort-able the “keep still” position during the examination. Others experience the feeling of being closed. Thus, sedation may be useful in patients with anxiety, but less than 1 in 20 patients find it necessary. When sedation is necessary for brain imaging, fMRI cannot be performed because it requires collaboration between the patient and technician or physician. (2)
It is normal that the part which is examined to be felt as slightly warm, but if this feeling is disturb-ing, technician or radiologist should be announced. It is important that the patient maintain still position during image acquisition, over a few seconds up to minutes. For certain types of examinations, the pa-tient may be asked to hold their breath. It is heard when images are acquired as high-frequency sounds are heard when the circuits that generate radio fre-quency waves are activated. The patient can relax be-tween acquisition sequences, but generally is asked to maintain position. To increase comfort earplugs may be used. Examination room is equipped with air con-ditioning and is well lightened, and some patients can listen to music during the test.
Although the patient will be alone in the examina-tion room, the technician can see, hear and talk to him during the examination using an intercom. Multiple magnetic resonance imaging investigation centers allow a relative or friend to sit in the examination room.
For morphological investigation by MRI, some-times, in case of an injury, it is necessary to administer
a contrast agent for assessing reaction to it. When given a contrast substance it is normal for the patient to feel a sense of cool and to see redness for 1-2 minutes. Intra-venous cannula may generate a little discomfort when it is inserted or when it is removed, and small hematomas can occur. There is also little chance of developing a skin irritation at the site of insertion of venous access.
WHAT ARE THE LIMITS OF THE MRI’S USE?
High quality images can be obtained only if the patient is able to maintain position and to maintain their breathing during the process of acquisition. If the patient is anxious, confused or have pain is diffi-cult to maintain position during the examination. An obese person cannot enter the closed magnetic field.
Metallic objects or implants lead to inability to obtain clear images; these artifacts are similar to the motion of the patient.
MRI is not recommended for patients who have acute pathology because it takes a longer period of time to acquire images as well as their interpretation, not men-tioning the failure to perform the technique if the patient needs the equipment to maintain vital functions.
MRI has a higher cost and requires a longer time than other diagnostic evaluation possibilities.
WHAT IS FUNCTIONAL NUCLEAR MAGNETIC RESONANCE IMAGERY?
Neuroscience is a discipline dedicated to study the structure and function of the normal central nervous system and integrating the results in the field of pa-thology with the aim of understanding the complex mechanisms underlying brain activity and thought. Because brain anatomical studies have been conduct-ed post-mortem without any particular problems as in the case of any part of the body, it remained the brain function problem, which can be evaluated only in vivo. Thus, different methods were designed to as-sess the brain areas, initially invasive and with the ad-vent of magnetic resonance imagery it has been tried to create a non-invasive evaluation methods. fMRI is one of the newest areas of medical imaging that uses data taken from images acquired by magnetic resonance and measures the metabolic changes that occur in different brain areas activated by different methods. (2)
WHAT IS THE PRINCIPLE OF FMRI?
While performing functional nuclear magnetic resonance imagery, different methods of activation that increase metabolic activity in brain areas re-sponsible for specific functions, are performed for 30 seconds, and then followed by pause for 30 seconds (these are actually images of control). (2)
In order to see different area of activation, the pa-tient will be asked to perform different activities, the union of thumb with the fingers of the same hand, breaking a piece of paper or to answer some simple questions. All these activities will be followed by a rest period in which the patient is asked to sit still. (1)
Thus, to perform functional MRI is neces-sary a good collaboration with the technician or doctor because you cannot use even the mild se-dation. These details are lowering the address-ability of the method which can be performed only for children over a certain age and for all cooperative patients, generally with normal intellect.
BOLD Technique (blood oxygen level-dependent functional magnetic resonance) is based on detecting rapid variations in oxygenation and cerebral perfu-sion during neural activation. (2) Since hemoglobin has different magnetic signal depending on the state of oxygenation, during fMRI, activation of brain ar-eas occurs and are seen as different ration between oxygenated and deoxygenated hemoglobin. Activa-tion map is determined by the statistical differences between the two states, so that it will be validated as genuine only the positive and eliminate the false posi-tive and negative (see Figure 2). (2)The investigation is performed with a magnetic resonance imaging unit of 1.5-3 T, but can be made with 1T but with a high magnetic field. The scanner needs to be equipped with software that allows rapid acquisition of images but at the expense of lower morphological quality. Thus, for a high resolution scan of the entire brain is needed eight minutes while is performed by fMRI in 2-4 seconds. Devices that perform fMRI may allow acquisition of images at 5 mm thickness in 4 seconds (20-24 slices) or 3 mm in 2-3 seconds or even the entire brain at 1 mm thick-ness in 2 seconds. (8).
In functional magnetic resonance examination, the patient is asked to perform different actions during the image acquisition process, the activation results in an increase in metabolic activity in brain areas responsible for the activity. (2) This technique includes analyzing vasodilatation, chemical changes and increased oxy-genation in activated areas through images acquired by magnetic resonance. (2). The patient will be positioned with the cephalic extremity in a box special thought to help maintain position. The patient may receive special glasses or helmets, so that different auditory or visual stimulation can be transmitted during the test (eg different sounds or images recorded).
When the examination is over, the patient is asked to wait until the technician check all the images and the radiologist decides whether it is longer needed or not. Then intravenous line is removed. fMRI is an indirect method, a non-invasive one, measuring the neuronal activity and helps us to perform a “brain mapping” to determine the brain areas involved in different functions such as thought, speech, movement or sensitivity. (6)
With its help it has been studied: the visual system (identifying primary visual cortex and visual association areas, the optic organization, oculomotric-ity, mental images), the motor system and sensory -sensitive system (primary and association motor and sensory areas, basal nuclei activation during motor gestures), the auditory, vestibular systems, the corti-cal localization and activation of cognitive areas (lan-guage, long-term memory, reasoning, etc.). (3) fMRI allows the noninvasive and dynamic study of the child with the aim of understanding of neural plasticity and the ability of functional recovery of the brain at this age, especially after extensive irreversible damage. (6)
Thus, once understood this, you can assess the effect of brain damage secondary to strokes, brain in-juries or degenerative diseases or predict the effects of interventional therapeutic methods, helping us to plan surgery or radiotherapy or even the recovery. (4)
There are risks of false negative or false positive re-sults because of the “time factor” of activated zones, if the areas will not be acquired or statistically processed in parallel with the moment of activation, resulting an area not primary activated, but one adjacent to it. (5)
We can say that this method is new, experimental, and often needs additional tests or preoperative evaluation of brain areas described as active during fMRI. (4)
The use of fMRI is validated to evaluate the lan-guage and motor areas, so that can replace invasive tests like WADA (intracarotidian injection of amo-barbital sodium and evaluation of the function of each cerebral hemisphere separately in order to determine the dominant hemisphere). (5.7) The evaluation of language area is crucial in epilepsy surgery in patients with epileptogenic focus in the area of speech. (4) Data acquired from fMRI is collected and con-verted into images that can be processed by a special statistical program which includes non parametric, parametric (t-test) measurements, linear regression, cross correlation, etc. (8) A threshold of stimulation is determined to create a level of separation and distinc-tion between experimental signals and the ones of the control images. The acquired activated voxels can have a color code – orange, red, yellow, white and can create a statistical map. It is possible to have a condition with a decrease in the signal between these activations, these voxels representing in this case a state of deacti-vation and codes are – green, red and violet. Areas of deactivation are less understood than those of activa-tion and it means they are activated at a lower level with decreased blood flow or increased extraction of oxyhemoglobin with no vascular response. (8) The ra-diologist or physician trained in this field can acquire these images, and the radiologist examines the images and their results and prepares a report addressed to the clinician who recommended this investigation.
What are the benefits versus the risks of the investi-gation? fMRI’s benefits: 1. fMRI is a non-invasive in-vestigation that does not involve exposure to radiation; 2. fMRI helps the doctor to assess both brain structure and function; 3. MRI helps to detect abnormalities that may be obscured by bone tissue and can not be revealed by other diagnostic procedures; 4. fMRI detects brain abnormalities, as well as evaluates normal functional anatomy of the brain, this cannot be acquired by other imaging techniques; MRI’s risks: 1. MRI has almost zero risk for patients when the recommendations are followed; 2. Although the strong magnetic field is not harmful in itself, medical devices that contain metal may function abnormally and cause problems during the test; 3. It is a very small risk of developing an al-lergic reaction if given a contrast substance, these re-actions are usually mild and are easily controlled by medication; 4. nephrogenic systemic fibrosis is known today as a possible, rare, complication of contrast agents used for MRI examination, especially in patients with decreased renal function.
Functional MRI is a developing investigation, which improves from day to day. Although considered to be as accurate in locating functional brain areas as any other method, has less experience than other MRI techniques. Thus, doctors may recommend additional tests to confirm the results of functional MRI’s if these results help in making critical decisions (as with neurosurgical intervention planning stages). (4)
- Arndt S., Cizadio T., Andreasen N.C., Heckel D., Gold S. and O’Leary D.S. 1996: Tests for comparing images based on randomization and permutation methods, J Cereb Blood Flow Metab, 16:1271-1279 ;
- Arndt S., Gold S., Cizadlo T., Zheng J, Ehrahardt J.C. and Flaum M, 1997: A method to determine activation thresholds în fMRI paradigms , Psychiatry Res. Neuroimaging, 75:15-22 ;
- Baciu M.V., Rubin C., Decorps M. and Segerbarth C.M., 1999: fMRI assessment of hemispheric language domi-nance using a simple inner speech paradigm, NMR Biomed 12:293-298 ;
- Benson R., Belliveau J., Kwong K., Buchbinder B., Jiang H., Cosgrove R. and Rosen B., 1995: Preoperative map-ing of language cortex with funcţional MRI, Hum Brain Mapp, 351 ;
- Benson R.R., Kwong K.K., Buchbinder B.R., Jiang H.J., Belliveau I.W., Cohen M.S., Bookheimer S., Rosen R. and Brady T., 1994: Noninvasive evaluation of language domi-nance using funcţional MRI, JMRI ;
- Benson R.R., FitzGerald D.B., LeSueur L.L., Kennedy D.N., Kwong K.K., Buchbinder B.R., Davis T.L., Weisskoff R.M., Talavage T.M., Logan W.J., Cosgrove G.R., Belli-veau J.W., and Rosen B.R., 1999: Language dominance de-termined by whole brain funcţional MRI în patients with brain lesions, Neurology 52:798-809 ;
- Shaywithz S.E., Shaywitz B.A., Pugh K.R., Fulbright R.K., Constable R.T., Mencl W.E., Shankweiler D.P., Liberman A.M., Skudalrski P., Fletcher J.M., Katz L., Marchlone K.E., Lacadie C., Gatenby C. and Core J.C. 1998: Funcţional disruption în the organization of the brain for reading în dyslexia ;
- Ugurbil K., Garwood M., Ellermann J., Hendrich K., Hinke P., Hu X., Kim S.G., Menon R., Merkle H., Ogawa S. and Salmi R., 1993: Imaging at high Magnetic Fields: Iniţial Experience at 4T, Magn. Res
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