The Brain:  What's Going On in There?

Imaging The Brain

Scientists increasingly use newer technologies to learn more about how the brain works and how drugs of abuse change how the brain works. Historically, scientists could examine brains only after death, but new imaging procedures enable scientists to study the brain in living animals, including humans.

One of the most extensively used techniques to study brain activity and the effects of drugs on the brain is positron emission tomography (PET). PET measures the spatial distribution and movement of radioisotopes in tissues of living subjects. Because the patient is awake, the technique can be used to investigate the relationship between behavioral and physiological effects and changes in brain activity. PET scans can detect nanomolar concentrations of tracer molecules and achieve spatial resolution of about 4 millimeters.  In addition, computers can reconstruct images obtained from a PET scan in two or three dimensions.

PET requires the use of compounds that are labeled with positron-emitting isotopes. A cyclotron accelerates protons into the nucleus of nitrogen, carbon, oxygen, or fluorine to generate these isotopes. The additional proton makes the isotope unstable. To become stable again, the proton must break down into a neutron and a positron. The unstable positron travels away from the site of generation and dissipates energy along the way. Eventually, the positron collides with an electron leading to the emission of two gamma rays at 180 degrees from one another.

The gamma rays reach a pair of detectors that record the event. Because the detectors respond only to simultaneous emissions, scientists can precisely map the location where the gamma rays were generated. The labeled isotopes are very short-lived. The half-life (the time for half of the radioactive label to disintegrate) of the commonly used radioisotopes ranges from approximately two minutes to less than two hours, depending on the specific compound. Because a PET scan requires only small amounts (a few micrograms) of short-lived radioisotopes, negative pharmacological effects are imperceptible.

PET scans can answer a variety of questions about brain function, including the activity of neurons. Scientists use different radio-labeled compounds to investigate different biological questions. For example, radiolabeled glucose can identify parts of the brain that become more active in response to a specific stimulus. Active neurons metabolize more glucose than inactive neurons. Active neurons will emit more positrons. This will show as red or yellow on PET scans compared to blue or purple in areas where the neurons are not highly active. PET also helps scientists investigate how drugs affect the brain by enabling them to:

• determine the distribution of a drug in the body,

• measure the local concentration of a drug at binding sites,

• estimate receptor occupancy based on competitive binding assays,

• evaluate the effects of drugs on other neurotransmitter systems, and

• investigate the activity of enzymes that metabolize the drug.

In addition to its uses in research, PET also is a powerful tool for for diagnosing and monitoring certain diseases. For example,  PET scans may be used to locate tumors in cancer patients, monitor the spread of cancer, and evaluate the effectiveness of cancer treatment. PET scans are able to reveal the presence of tumors because of the rapid metabolism characteristic of cancerous cells.

Figure 1.6: Photograp of PET imaging equipment. Courtesy of UCLA School of Medicine

PET images reveal this increased glucose utilization by cells that have high metabolic rates. PET is an accurate test for coronary heart disease because it can detect areas of diminished blood flow to the heart. Doctors also employ PET to reveal changes in the brain that occur with Alzheimer’s disease, Parkinson’s disease, or seizure disorders. PET is a valuable tool because it:

• is safe,

• replaces multiple testing procedures with a single exam,

• can detect diseases before they show up on other tests,

• can show the progress of disease, and

• reduces or eliminates the need for invasive procedures such as surgery.

PET scanning is a major neuroimaging technique used in drug abuse research. However, researchers also use other techniques when they better answer a scientific question. Similar to PET, single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), and electroencephalography (EEG) are noninvasive procedures that can measure biological activity through the skull and reveal the living brain at work. Each technique  has its own advantages and each provides different information about brain structure and function. Scientists often use more than one technique when conducting their research studies.

 MRI image of human brain.  Photo courtesy of Penrad Imaging .  Colorado Springs, CO.

Similar to PET, SPECT imaging uses radioactive tracers and a scanner to record data that a computer constructs into two- or three-dimensional images of active brain regions. Because the tracers used in SPECT take longer to deteriorate than those for PET, longer periods of time between tests are required for SPECT. While PET is more versatile than SPECT and produces more detailed images with a higher degree of resolution, SPECT is much less expensive than PET and can address many of the same drug abuse research questions.

MRI uses magnetic fields and radio waves to produce high-quality two- or three-dimensional images of brain structures without injecting radioactive tracers. In this procedure, a large cylindrical magnet creates a magnetic field around the research volunteer’s head, and radio waves are sent through the magnetic field. Sensors read the signals and a computer uses the information to construct an image. Using MRI, scientists can image both surface and deep brain structures with a high degree of anatomical detail, and they can detect minute changes in these structures over time.

 A modification of this technique, called functional MRI (fMRI), enables scientists to see images of blood flow in the brain as it occurs. fMRI provides superior image clarity along with the ability to assess blood flow and brain functions in just a few seconds. However, PET retains the advantage of being able to identify which brain receptors are being activated by neurotransmitters, abused drugs, and potential treatment compounds.

EEG uses electrodes placed on the scalp to detect and measure patterns of electrical activity in the brain. The greatest advantage of EEG is speed: it can record complex patterns of neural activity occurring within fractions of a second after a stimulus has been administered. The drawback to EEG is that it does not provide the spatial resolution of fMRI or PET. Researchers often combine EEG images of brain electrical activity with MRI scans to localize brain activity more precisely.

Reference: The Brain:  Understanding Neurobiology Through the Study of Addiction; Lesson 1~ The Brain:  What's Going On In There? (NIDA) 2004

Compiled and edited by: Deborah Shrira        Dated: January 25, 2001

Asst. Editor: Dee Black                                           Updated: March 16, 2012