Functional Magnetic Resonance Imaging

Functional Magnetic Resonance Imaging (or fMRI) is the use of MRI to learn which regions of the brain are active in a specific cognitive task, as in speech or in the conjugation of a verb.

As nerve cells "fire" impulses, they metabolyse oxygen from the surrounding blood. Approximately 6 seconds after a burst of neural activity, a haemodynamic response occurs and that region of the brain is infused with oxygen-rich blood.

Because oxygenated haemoglobin is diamagnetic, while deoxygenated blood is paramagnetic, MRI is able to detect a small difference (a signal of the order of 3%) between the two. This is called a blood-oxygen level dependent, or "BOLD" signal. The precise nature of the relationship between neural activity and the BOLD signal is a subject of current research.

BOLD effects are measured using a T2 imaging process, which is different from the T1 scan taken in ordinary structural MRI images (the former measures the rate of change of spin phases, while the later detects the half-life of inverted spins). T2 images can be acquired with moderately good spatial and temporal resolution; scans are usually repeated every 2-5 seconds, and the voxels in the resulting image tend to be around 0.25 cubic centimeters. Other non-invasive functional medical imaging techniques can improve on one of these figures, but not both.

The science of applying fMRI is quite complicated and multi-disciplinary. It involves:

• A good understanding of the physics of MRI scanners.
• Statistical analysis of results. Because the signals are very subtle, correct application of statistics is essential to both "tease out" observations and avoid false-positive results.
• Psychological study design. When conducting fMRI on humans, for example, it is essential to employ carefully designed experiments which allow the precise neural effect under consideration to be separated.
• For a non-invasive scan, MRI has moderately good spatial resolution, but relatively poor temporal resolution. Increasingly, it is being combined with other data collection techniques such as EEG or MEG, which have much higher recording frequencies.
• Integration with other areas of neuroscience in order to better understand the location (and role) of the signals which fMRI is able to detect. This includes a great deal of neuroanatomy but also other sub-fields such as neurochemistry and neuropathology.

Aside from BOLD fMRI there are other ways to probe the brain activity with MRI:

• By using a injected contrast agent, e.g., MION, causing a local disturbance in the magnetic field that is measurable by the MRI scanner.

The signal associated with these kind of contrast agents are proportional to the cerebral blood volume.

• By using what is called perfusion MRI (pMRI). The associated signal is proportional to the cerebral blood flow.

Magnetic resonance spectroscopic imaging (MRS) is another, NMR-based process for assessing function within the living brain. MRS takes advantage of the fact that protons (H) residing in differing chemical environments depending upon the molecule they inhabit (H₂O vs. protein, for example) possess slightly different resonant properties. For a given volume of brain (typically > 1 cubic cm), the distribution of these H resonances can be displayed as a spectrum. The area under the peak for each resonance provides a quantitative measure of the relative abundance of that compound. The largest peak is composed of H₂O. However, there are also discernable peaks for choline, creatine, n-acetylaspartate (NAA) and lactate. Fortuitously, NAA is mostly inactive compound within the neuron, serving as a precursor to glutamate and as storage for acetyl groups (to be used in fatty acid synthesis) -- but its relative levels are a reasonable approximation of neuronal intergrity and functional status. Brain diseases (schizophrenia, strokes, certain tumors, multiple sclerosis) can be characterized by the regional alteration in NAA levels when compared to healthy subjects. Creatine is used a relative control value since its levels remain fairly constant, while choline and lactate levels have been used to evaluate brain tumors.

Another recently developed functional MRI technique is diffusion tensor imaging (DTI). As protons are directed along certain axes in the brain (for example, as water flowing down a neuronal axon within a bundle of nerve fibers in cerebral white matter), this directionality can be measured. Connectivity between brain regions may be inferable from diffusion images, and illnesses that disrupt the normal organization or integrity of cerebral white matter (such as multiple sclerosis) have a quantitative impact on DTI measures.