Magnetic resonance imaging (MRI) is a noninvasive tool that uses a magnetic field along with radio waves to produce detailed images of the brain, spinal cord, or other body areas. Preliminary studies suggest that MRI may help identify signs of amyotrophic lateral sclerosis (ALS) earlier, but larger studies conducted over a longer time are needed.
ALS is a rapidly progressing neurodegenerative disease that causes muscle wasting and eventual death. It is typically diagnosed within 12 to 14 months from when the symptoms first appear. Disease-specific changes observed in MRI represent potential biomarkers, or characteristic features, for ALS. In addition to potentially aiding early diagnosis, these biomarkers can act as a monitoring tool to follow disease progression and help doctors design better clinical trials.
According to the revised El Escorial criteria for the diagnosis of ALS, the disease must be progressive with affected areas in both upper motor neurons (UMN) in the brain area involved in motor function known as the primary motor cortex, as well as lower motor neurons (LMN) in the brain stem, or posterior part of the brain, and spinal cord.
Many different MRI techniques and sequences — including voxel-based morphometry (VBM), diffusion tensor imaging (DTI), magnetic resonance spectroscopy, iron-sensitive sequences, and functional MRI (fMRI) — are available to study ALS-related changes in the brain or spinal cord.
Recent studies suggest that combining structural and functional MRI methods may help diagnose ALS. Other MRI techniques are also currently being developed to serve as biomarkers for an earlier and more accurate diagnosis of the disease.
Structural MRI detects physical changes in gray matter (a region in the central nervous system, or CNS, composed of nerve cell bodies, synapses, and neuronal fibers) and white matter (a region in the CNS composed of axons).
At present, structural MRI mainly serves as a tool to rule out other diseases mimicking ALS (such as spinal cord tumors and cervical spondylosis). It is also useful in finding cortical atrophy in ALS. VBM and DTI are two different types of structural MRI.
Voxel-based morphometry is an automated technique that uses statistics to identify differences in brain anatomy between groups of subjects to analyze changes in brain volume. It allows detection of differences in the neuronal structure with much greater sensitivity.
Diffusion tensor imaging is sensitive to the movement of protons and detects changes in the degree and directionality of water movement, which is restricted by barriers such as cell membranes. This allows DTI to detect the causes and effects of disease, or pathology, within white matter tracts composed of nerve fibers known as neuronal axons.
According to the consensus guidelines on MRI protocols for studies in ALS patients, DTI is the most promising structural MRI method to detect ALS-related changes not only in the primary motor cortex and the pyramidal tracts (upper motor neurons), but also in brain regions beyond the motor system. The DTI method can also be used for tractography, or imaging of pyramidal tracts, or to study the connection between different cortical gray matter areas.
Functional MRI (fMRI)
Brain fMRI is a recent technique based on blood flow and blood-oxygen-level-dependent (BOLD) contrast, which in turn are based on the activation of neurons.
fMRI can detect activity within the cerebral cortex corresponding to a task (such as a motor task) performed by the patient during scanning. The resting-state technique detects fluctuations in different cortical areas during rest and visualizes different functional networks, such as the sensory-motor network, visual network, and others. fMRI methods are capable of detecting ALS-related differences in brain activation, compensation, and reorganization.
Magnetic resonance spectroscopy
Magnetic resonance spectroscopy (MRS) is an MRI-based technique that neurologists use to quantify chemical changes that occur in specific tissues due to injury or disease. MRS-based quantification of certain neuronal metabolites, such as n-acetyl aspartate (NAA), choline, creatine, and glutamate, may identify people with inherited forms of ALS before the appearance of first signs. These techniques may help clinicians to accurately diagnose ALS, enabling better management. Neurologists are currently evaluating this non-invasive technique as a means to diagnose and monitor ALS.
How MRI is done
MRI is done in a hospital or radiology center. The patient lies on a table that slides into a large tunnel-shaped scanner. Sometimes a contrast dye is given through a vein prior to the test to allow the radiologist to see some areas with more clarity. The test usually lasts for about an hour. The patient may be asked to avoid eating or drinking for four to six hours before the scan. Since MRI uses strong magnets, patients must remove metal objects before the procedure. There are no known side effects associated with the use of magnetic fields or radio waves.
The low average number of participants in MRI studies represents the main limitation of MRI as a biomarker for ALS. Very few published studies have featured more than 30 participants in each of the ALS and control groups. Further studies in larger patient samples over a longer period of time are required before MRI techniques can be used as a screening method to identify people ‘at risk’ of developing ALS.
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