fMRI

Functional MRI (fMRI), also called BOLD imaging, is a magnetic resonance imaging-based neuroimaging technique that makes it possible to detect the brain areas that are involved in a task, a process or an emotion.

Let's start with an representative clinical case, processed in our neuroimaging software suite, BrainMagix. The patient has a brain tumor at the junction of the left temporal, parietal, and occipital lobes. The tumor is close to Wernicke's area of language. Therefore, an fMRI examination was carried out, in order to localize the language network (yellow and blue blobs), and thereby help the neurosurgeon to maximize the tumor resection while minimizing the post-operative deficit.

Now that we understand its clinical interest, let's try to understand how fMRI works! Like for any other MRI examination, the patient is lying in the MRI scanner.

Echo planar imaging (EPI), a fast MR image acquisition technique, is used to sequentially acquire brain images, every few seconds, during several minutes. These images are of average quality and prone to various kinds of artifacts, but their short acquisition time makes them ideal for fMRI acquisitions. In our example, 44 slices were acquired, every 3 seconds, 96 times in a row, leading to a total number of 4,224 images acquired in 4 minutes and 48 seconds.

Functional MRI cannot detect absolute activity in the brain. It can only detect differences in brain activity between several conditions. During the fMRI image acquisition, the patient is therefore asked to alternatively perform several tasks or is stimulated to trigger several processes or emotions. The combination of these conditions is called an fMRI paradigm. The stimuli can be grouped in blocks (e.g. 30s-long) or presented as events. Each of the conditions is repeated several times and can be separated by rest periods. The stimuli are usually presented through an audio-visual fMRI stimulation system, but can involve more complex systems (odors, tastes,etc.). MR-compatible response pads are often used to get a feedback from the patient. ParadigmMagix and our clinical fMRI paradigms are easy-to-use in clinical practice.

The detection of brain areas which are used during a condition is based on the Blood Oxygenation Level Dependent (BOLD) effect. When neurons are activated, the resulting increased need for oxygen is overcompensated by a larger increase in perfusion. As a result, the venous oxyhemoglobin concentration increases and the deoxyhemoglobin concentration decreases. As the latter has paramagnetic properties, the intensity of the fMRI images increases in the activated areas. As the conditions are alternated, the signal in the activated voxels increases and decreases according to the paradigm.

The variation of the BOLD signal induced by the paradigm is very low ( < 2%) and cannot be detected visually. Therefore, advanced statistical methods must be used to identify the voxels in which the signal varies according to the paradigm. In a first step, the images are pre-processed: (slice-timing correction), realignment of fMRI series to correct patient movements, registration with an anatomical scan, (spatial normalization to a brain atlas), (segmentation), and spatial filtering. In a second step, the pre-processed images are statistically analyzed, with a model describing the experiment (e.g. the general linear model). Thresholded fMRI activation maps can be overlaid in color on a high resolution anatomical MR image or displayed on a 3D reconstruction of the brain. BrainMagix's fMRI Module performs a user-friendly analysis of clinical fMRI images.

The main clinical application of functional MRI (fMRI) is the pre-operative detection of eloquent brain areas. Most neurosurgical interventions entail the removal of brain tissue. The challenge in tumor resection is to remove the tumor as extensively as possible (clear margin) while preserving the function of the adjacent areas. Whereas some cognitive deficit might be the price to pay to have the tumor removed, primary functions (motor, language, etc.) must be preserved as much as possible. Clinical fMRI paradigms have therefore been designed to map these areas before the resection.

Another clinical application of fMRI is the assessment of patients with disorders of consciousness (coma, vegetative state, minimally conscious state, locked-in syndrome).

Functional MRI is used in fundamental and clinical research to map more complex functions (e.g. emotions, face recognition, complex motor control, specialized language functions, etc.) in normal and pathological conditions. fMRI studies recruit one or several groups of subjects, requiring group analysis and normalization to a brain template. The paradigms for research are more complex than for clinic. They are usually made of several conditions spread over several runs.

Resting-State fMRI is an fMRI technique, in which the patient is not stimulated with a paradigm, making it possible to study the functional connectivity of the brain.

The main non-medical applications of fMRI are neuromarketing, which can map the brain's reaction to advertisements, and lie detector.

• Matthews et al. Applications of fMRI in translational medicine and clinical practice. Nature Reviews Neuroscience 2006, 7:732-744.
• Amaro and Barker. Study design in fMRI: basic principles. Brain Cogn. 2006, 60:220-2