Non-invasive Structural and Physiological Imaging: MRI Technologies

October, 2011

Magnetic Resonance Imaging (MRI) is based on the principle of nuclear magnetic resonance and uses radiofrequency waves to probe tissue structure and function without requiring exposure to ionizing radiation. The two researchers who made MRI clinically feasible in the 1980s by building on initial discoveries of the 1930s won the Nobel Prize in Physiology or Medicine in 2003.

Clinically, MRI has become the most important diagnostic imaging modality in neuroscience.  One of the many benefits of MRI in the central nervous system is that the radiofrequency signals readily penetrate the skull and spinal column, allowing the tissue within it to be images with no interference.  MRI provides the best visualization of parenchymal abnormalities in the brain and spinal cord including tumors, demyelinating lesions, infections, vascular lesions such as stroke, developmental abnormalities, and traumatic injuries. 

There are numerous variations on MRI that are also in wide clinical use.  These include flow-sensitive approaches termed magnetic resonance angiography and magnetic resonance venography that are used to detect stenosis (narrowing) or clotting of arteries and veins, diffusion sensitized MRI that can be used to detect acute strokes just minutes after their onset, and perfusion sensitized MRI that can demonstrate regional cerebral blood flow and blood volume.  In addition to MRI’s uses in clinical care, functional MRI (fMRI) is used to identify specific brain areas involved in activation of motor and cognitive tasks, and to detect reorganization in the brain following injury to a localized area.  

Most MRI techniques use signals from water, which constitutes about two-thirds of human body weight, to develop information on brain structures and functions. Protons (positively charged particles) in hydrogen molecules in water produce the signal when exposed to a strong magnetic field. The MRI machine contains the magnet. Structural MRI measures the nuclear magnetic resonance of water protons to create a computerized three-dimensional image of tissues.

More specifically, protons in the nuclei of hydrogen atoms in water move (oscillate) between two points and vibrate when they are exposed to a strong magnetic field. They absorb energy in the frequency of radio waves; and then they remit this energy in the same radiofrequency (a process called resonance) when they return to their original state. MRI uses the body’s own molecules, while PET and SPECT require introduction of a radioactive label into the body with a drawback of exposure to low levels of ionizing radiation.

Small differences in the protons’ oscillations are mathematically analyzed by computer to build a three-dimensional image of tissues. Variations that occur in the molecular environment of water located in different brain structures and compartments provide contrast, and the ability to see the spatial orientation of various brain structures. The molecular environment of water is also affected by disease processes.

 The contrast differentiates the brain’s gray matter (primarily nerve cell bodies) from white matter (primarily axons and their myelin sheaths) which are the nerve cell communication cables that connect brain regions. Structural MRI undertaken serially over a two-year period, for instance, shows that the brain’s hippocampus (primarily gray matter) becomes progressively smaller (degenerates) in adults with Alzheimer’s compared to adults who are cognitively healthy.

Functional MRI (fMRI) shows the brain in action; scientists use it extensively to elucidate processes involved in higher cognitive functioning. It is highly sensitive so it can detect small changes, and is relatively inexpensive compared to PET, so it is the method of choice for identifying areas of the brain that are activated when a person undertakes a specific cognitive or motor task. It is an indirect measure, however, because the time it takes for dynamic changes to occur in blood flow is much longer than that for neurons to fire off their electrochemical messages. Functional MRI can be used to study the reorganization of function following injury to a single brain area.

Like functional imaging with PET, functional MRI is based on the principle that changes in regional cerebral blood flow and metabolism are coupled to changes in regional neural activity involved in brain functioning, such as memorizing a phrase or remembering a name.  Almost all fMRI techniques use the contrast mechanism called BOLD (blood oxygenation level dependent) MRI. BOLD contrast reflects a complex interaction between the volume of blood, its flow, and its transport of oxygen by an iron-containing protein in red blood cells. Functional contrast is produced only when the oxygen is released from iron and taken up by brain cells. Loss of the oxygen enables iron to become highly magnetized when exposed to the MRI magnetic field.

In addition to using BOLD contrast with fMRI to measure task activation, a perfusion contrast used with fMRI—called arterial spin labeling (ASL)—can be used to quantify regional cerebral blood flow noninvasively.  Whereas BOLD fMRI is primarily sensitive to changes in regional brain function, ASL MRI provides absolute quantification of cerebral blood flow, which renders it sensitive to both static function and changes occurring over longer intervals.  For example, ASL MRI can detect differences in brain function between individuals with different genotypes (genetic make-up) or the effects of chronically administered drugs on regional brain function.  However, these capabilities still rely on a coupling between changes in regional neural activity and changes in cerebral blood flow, so unlike PET performed with molecular tracers, ASL-fMRI will not show what the drug is doing at a molecular level once it gets to its target.

In addition to fMRI, there are several other major MRI techniques. Each technique has a highly specialized function.  

Diffusion-tensor MRI (DTMRI) measures microscopic water motion in any tissue, and in the brain this motion is facilitated along white matter tracts (the brain’s communication cables that connect brain regions). Computerized mathematical models then construct the images of the white matter tracts. DTMRI, therefore, is used to visualize white matter tracts connecting different parts of neural networks in the brain. It is used extensively in pre-surgical planning, such as for removal of a brain tumor, to ensure that these tracts are spared during surgery. Additionally, DTMRI has been applied to the study of neurological conditions, such ADHD and other developmental disorders, that are thought to arise from problems in white matter connections. Related studies use PET imaging to explore possible alterations in specific neurotransmitters in these disorders.

Diffusion-weighted MRI shows whether brain tissue has been damaged due to insufficient blood flow to the tissue. DWMRI can visualize tissue within minutes after it is damaged by an “ischemic” injury (such as a stroke-producing blood clot), to allow early identification of the damage.

Perfusion-weighted MRI can show areas of the brain in which blood flow has been altered based on the time course of regional signal changes induced by an exogenously administered MRI contrast agent.

Diffusion-Perfusion-weighted MRI can be used together to estimate the “ischemic penumbra,” the tissue that has suffered from reduced blood flow but has not yet died. This tissue is the target of intensive therapy for patients who have suffered an ischemic stroke. 

 Magnetic Resonance Spectroscopy (MRS) focuses on magnetic resonance signals from molecules other than water.  Several molecules of interest can be measured using MRS from 1H or 31P.  In general, MRS has much poorer spatial resolution than MRI, but it has greater specificity.  It is a tool that helps to characterize brain diseases according to the natural history of the chemical changes that they produce over time. MRS is conducted in an MRI scanner and like MRI it uses magnetization and radio waves. Instead of creating an image, however, MRS produces a spectrum that reflects the concentrations of various molecules—identified according to their chemical composition—in a specific area. Each type of molecule has a unique radio wave frequency (“radiofrequency’). The strength of a molecule’s radiofrequency depends on how much of the molecule is concentrated in a specific area. While MRS has much less resolution and sensitivity than PET or SPECT in measuring biochemical changes, its non-invasive nature makes it highly preferable to use in studies that contrast biochemical changes in healthy study volunteers from those in patients with specific brain diseases.

MRS can be used to identify the size and stage of specific kinds of brain tumors that are known to contain high levels of certain chemicals. Additionally, beginning in about 2005, MRS has been found able to detect immature (“progenitor”) cells in the brain that develop into neurons and other cells in the brain (a process called “neurogenesis”). The ability to track these cells could lead to important advances in understanding healthy and disordered brain development in children. This ability to track progenitor cells also may provide information on whether neurogenesis slows in adulthood and, if so, whether this lowered rate of brain cell production has serious consequences for adults with degenerative diseases who cannot replace substantial numbers of dying brain cells.