Arches. Photo by Daniel Chia
Apr
09
2012

Neuroimaging

Neuroimaging refers to techniques that produce images of the brain without requiring surgery, incision of the skin, or any direct contact with the inside of the body.  Because these technologies enable noninvasive visualization of the structure and functionality of the brain, neuroimaging has become a powerful tool for both research and medical diagnosis.  Although still relatively young, the field of neuroimaging has rapidly advanced over the years due to breakthroughs in technology and computational methods.  Applications of neuroimaging techniques have likewise become far-reaching.

This article will cover three of the most common techniques in neuroimaging: computerized tomography (CT), functional magnetic resonance imaging (fMRI), and positron emission tomography (PET).  You will likely come across at least one of these techniques while reading about Huntington’s disease (HD) news and research.  For each technique, the article will discuss its working mechanism, its pros and cons, and its relevance to HD.

Computerized tomography (CT)^

Computerized tomography (CT) is a medical imaging procedure that uses x-rays to generate detailed pictures of structures inside the body.  It has become a valuable tool for medical diagnosis and for planning, guiding, and monitoring therapy.

Attribution: Aaron G. Filler, MD, PhDA CT scan of a human brain. (Source: Aaron G. Filler, MD, PhD)

How CT works^

A CT scan uses X-rays positioned at different angles to create cross-sectional images of the brain.  During a CT scan, a movable X-ray source is rotated around the patient’s head.  Detectors record information about the intensity of the rays transmitted through the head at each angle, which is sort of like taking a series of two-dimensional snapshots.  The computer then uses an algorithm to combine all the individual snapshots from different axes of rotation of the source together and to reconstruct them into a 3-D, cross-sectional image.  By allowing doctors and researchers to view the full volume of the head, CT scans can provide much more information about the brain than traditional X-ray scans, which only offer a two-dimensional representation of the brain.

Advantages and Disadvantages of CT^

CT scans are painless, fast, and cost-effective.  CT can image bone, blood vessels, and soft tissue simultaneously and provides very detailed images of many types of tissue.  There are, however, several risks associated with the use of CT.  The main risks, according to the US Food and Drug Administration, are:

  • An increased lifetime risk of cancer due to x-ray radiation exposure
  • Possible allergic reactions or kidney failure due to contrast agent, or “dye” that may be used in some cases to improve visualization
  • The need for additional follow-up tests after receiving abnormal test results or to monitor the effect of a treatment on disease

You and your physician should decide whether or not the benefits of getting the added information from a CT scan outweigh the possible risks.

CT and Huntington’s disease^

CT cannot by itself be used to diagnose HD, since other disorders or conditions can result in similar anatomical change in the brain; often it is used along with family history and medical records in order to provide a more detailed diagnosis.  (The same is true of MRI scans, which will be discussed in the upcoming section.) Doctors use CT (or MRI) to evaluate a patient with HD by checking for characteristic degeneration in the brain and ruling out other possible disorders.  A CT scan for a patient in the early stages of HD may appear normal, but a CT scan for a patient in advanced stages of the disease can often reveal significant degeneration – specifically, reduction in volume of certain regions of the basal ganglia.

Functional Magnetic Resonance Imaging (fMRI)^

Functional magnetic resonance imaging (fMRI) is a specialized form of MRI that indirectly provides information on brain activity by measuring changes in blood flow in the brain.

Public domain, NASA

An fMRI scan of a human brain. (Public domain)

How MRI works^

A traditional MRI scanner contains a very strong electromagnet, which generates a strong magnetic field inside the scanner.  When turned on, this causes randomly spinning protons, or positively charged particles, in the brain (in this case hydrogen protons from water molecules) to align themselves with the direction of the field.  (Think of how a compass needle at rest is aligned with the Earth’s magnetic field, which is why it always points north.) However, the protons still spin while in alignment in the field, and the axis of their spin isn’t perfectly parallel to the direction of the field – rather, the protons behave like wobbling tops. The rate at which the protons wobble is called resonance.

We can also think of resonance as the ability of a system to absorb energy delivered at a particular frequency.  To illustrate this concept, imagine that you are pushing a small child on a playground swing.  If you push the child too quickly or too slowly, the child won’t rise very high.  But if you give the child enough pushes at just the right frequency, the child will rise to the maximum height attainable due to the energy you have provided by pushing.  This frequency is called the resonant frequency of the swing, which is the rate at which the swing will naturally oscillate.  The swing absorbs the most energy when it is pushed at exactly this frequency.  Similarly, protons placed in a strong magnetic field will efficiently absorb energy when the energy is delivered at a particular resonant frequency, namely the rate of “wobbling.”  In the case of MRI, radio waves provide the “push” necessary to move the protons.

During a process called excitation, the MRI scanner emits energy in the form of radio waves at precisely the resonant frequency of protons.  These radio waves knock the protons out of alignment, causing them to flip and spin on their opposite ends.  In order to flip over, the protons have to absorb some energy from the radio waves.  When the radio signal is turned off, the protons flip back around to their original alignment, and in the process release the energy they have absorbed.  This released energy is called the MR (magnetic resonance) signal and can be measured by electromagnetic detectors around the subject.  A computer receives the MR signals as mathematical data and compiles them into an image.

Although fMRI uses the same principles as MRI, there is one important distinction.  MRI (often called structural MRI) reveals brain anatomy, while fMRI reveals brain function, often in the form of neural activity.  For this reason, fMRI is very useful for neuroscience and clinical research, while MRI is traditionally used for clinical characterization in the same manner as CT scans.

However, fMRI doesn’t reveal neural activity directly.  Recall that when neurons are active, they fire action potentials and send messages in the form of neurotransmitters to other neurons. (To read more about this, click here.) While other imaging methods such as EEG (electroencephalography) can measure this activity directly, they often come with severe limitations such as poor spatial resolution.  Instead, fMRI studies neural activity indirectly by measuring the BOLD (Blood Oxygenation Level Dependent) signal.  This method is based on the fact that hemoglobin carrying a bound oxygen molecule (oxyhemoglobin) in the bloodstream emits a different MR signal than oxygen-depleted hemoglobin (deoxyhemoglobin).  When parts of the brain become active, such as when a person is carrying out a cognitive task, they use up more oxygen than relatively inactive parts of the brain.  You might think that this would result in a relative decrease in the level of oxygen in the active areas compared to the inactive areas, but actually the reverse happens!  Because oxygen is being depleted, the brain compensates for the loss by increasing the flow of oxygenated blood to the active area.  There is a slight overcompensation, which causes an increased oxyhemoglobin to deoxyhemoglobin ratio.  As this ratio increases, the BOLD signal gets stronger.  Essentially the BOLD signal measures the ratio of oxyhemoglobin to deoxyhemoglobin in the brain, which enables researches to indirectly gauge neural activity: higher neural activity = higher oxyhemoglobin to deoxyhemoglobin ratio = stronger BOLD signal.

Advantages and Disadvantages of fMRI and MRI^

MRI and fMRI both involve no radiation, and there are no known side effects caused by the magnetic fields and radio waves.  The main risk with MRI is that the presence of metal in the body (such as pacemakers or other implants) can be a safety hazard.  fMRI is also relatively inexpensive, non-invasive, widely available, and provides excellent spatial resolution and good temporal resolution.  Largely because of these factors, fMRI has come to predominate in the field of neuroimaging research.

fMRI and Huntington’s Disease^

Use of fMRI or MRI scans in HD patients sometimes requires sedation since both techniques require remaining extremely still and the results can be ruined by small movements.  It is thought that fMRI can potentially be used as an indicator, or imaging biomarker, of early neuronal dysfunction in individuals before the onset of HD (a stage called pre-HD).  A 2004 study conducted with pre-HD patients demonstrated that fMRI could detect abnormalities in brain activity more than 12 years before the estimated onset of motor systems (Paulsen et al).  fMRI was also able to distinguish differences between patients closer to estimated onset and patients further away from estimated onset.  These results suggest that fMRI may be useful for tracking changes in neural function during the early stages of pre-HD, and could improve the prediction of when HD manifests in an individual.  The study also suggests that fMRI can be helpful in determining the optimal time frame of treatments aimed at slowing down the progression of HD.  However, further research is required to determine whether the potential of fMRI technology will be realized.

Positron Emission Tomography (PET)^

Positron emission tomography is a technique that uses radioactively labeled molecules (called tracers) that are injected into the bloodstream and taken up by active neurons.  PET studies blood flow and metabolic activity in the brain and helps visualize biochemical changes that take place.  Essentially, PET indicates how well the brain is functioning.

Public domain, Jens LangnerA PET scan of a human brain. (Public domain)

How PET works^

The scanner consists of a ring of detectors that surround that subject.  Detectors contain crystals that scintillate (give off light) in response to gamma rays, which are extremely high-energy rays of light.  Each time a crystal in a detector absorbs a gamma ray is called an event.  When two detectors exactly opposite from each other on the ring simultaneously detect a gamma ray, a computer hooked up to the scanner records this as a coincidence event.  A coincidence event represents a line in space connecting those two detectors, and it is assumed that the source of the two gamma rays lies somewhere along that line.  The computer records all of the coincidence events that occur during the imaging period and then reconstructs this data to produce cross-sectional images.

The tracer is usually a substance, such as a type of sugar like glucose, that can be broken down (metabolized) by cells in the body, and it is labeled with a radioactive isotope.  There is minimal risk involved since the dose of radiation is low and the isotope is quickly eliminated from the body through urination.  After it has been injected into the bloodstream, the isotope, which is very unstable, starts to decay, becoming less radioactive over time.  In the process it emits a positron (a positively charged electron).  When a positron collides with an electron, the two particles annihilate each other, producing two gamma rays with the same energy but traveling in opposite directions.  These gamma rays leave the subject’s body and are sensed by two detectors positioned 180 degrees from each other on the scanner, which gets recorded as a coincidence event.  A computer can determine where the gamma rays came from in the brain and generate a three-dimensional image.

As blood is more concentrated in activated brain areas than in inactivated ones, the scanner will detect more gamma rays coming from parts of the brain that are working harder.  On a PET scan regions of the brain show up as different colors depending on the degree of activity in those regions.  Yellow and red regions are “hot” and indicate high brain activity, while blue and black regions indicate little to no brain activity.

The brain function measured by a PET scan varies according to the type of radioisotope that is used.  For instance, oxygen-15 is used to study oxygen metabolism in the brain.  FDG, which is fluorine-18 attached to a glucose molecule, is used to study sugar metabolism in the brain.  Many more radioisotopes exist, and which one is chosen for a specific PET scan depends on what type of brain function a researcher desires to study.

Advantages and Disadvantages of PET^

PET, unlike other imaging tests, is able to detect irregularities in body function caused by disease, which often occur before anatomical changes become observable.  The quality of a PET scan is not affected by small movements, so the subject does not have to remain as still for a PET scan as they would for a fMRI or MRI scan, both of which can be ruined by small movements.

A main setback to PET is that it affords relatively poor spatial resolution, so the images may not be very clear.  Due to this, it is common for PET to be used together with CT or fMRI.  In addition, the use of radiation, even in a small dose, always involves a slight risk.

PET and Huntington’s disease^

PET scans are sometimes ordered by physicians as a follow-up to a CT or MRI scan in order to reveal any irregularities in brain processes.  They can be used as part of a more detailed diagnosis for HD, as well as in research related to abnormalities in metabolism and progression of the disease.   Nowadays PET scans are often combined with CT scans to provide images that pinpoint the location of abnormal activity within the brain; combined, these scans provide more accurate diagnoses than either performed alone.

Conclusion^

CT, fMRI/MRI, and PET are three of the most popular techniques currently used for neuroimaging.  Each method comes with its own advantages as well as its own risks and disadvantages.  While neuroimaging is still a fairly new development in medicine and neuroscience, the discipline will likely continue expanding in the future, and will continue to provide valuable clinical applications and scientific insights about the brain.

Works Cited^

Paulsen JS, Zimbelman JL, Hinton SC, Langbehn DR, Leveroni CL, Benjamin ML, Reynolds NC, Rao SM. fMRI biomarker of early neuronal dysfunction in presymptomatic Huntington’s Disease. AJNR Am J Neuroradiol. 2004 Nov-Dec;25(10):1715-21.

Further Reading^

CT
FAQ about getting CT scans

MRI/fMRI
A more detailed explanation of how MRI works
Additional information about fMRI

PET
FAQ about getting PET/CT scans

J. Nguyen 4.9.12