Before we can fix or cure drug addiction, it would help to know what's broken. We can get some information by looking at the chemistry of brain schematics after they've died, at a postmortem autopsy. When we do that, it's clear that the brains of addicts are changed. Understanding these chemical changes, what they mean, and what we can do about them is a current frontier. It will not be easy because there are many changes that occur in the brain, and we may have to take into account a large number of them simultaneously to really understand the nature of drug addiction. But this analysis is ongoing. While postmortem analysis is very informative, there are other powerful ways to get information. Brain imaging allows brain measurements in a living human being. Brain imaging is routine now, but 30 years ago it looked as if it was magical, and it really still is. Brain imaging has been very successful in providing important information not only in addiction, but in every field involving the brain. There are different kinds of brain imaging. There are different technologies that tell us different things. There is PET, which stands for positron emission tomography. PET, P-E-T, is useful for a number of things. It can measure metabolism in various brain regions, the levels of specific proteins, such as receptors, in various brain regions, and it can do more. MRI, or magnetic resonance imaging, measures the structure, volume and shape of the brain. FMR, or functional magnetic resonance, is used to measure the relative activity of various brain regions. And there are yet other kinds of brain imaging. I'm going to focus on PET scanning as an example. It'll help you understand the kind of effort that goes into brain imaging and what we can learn. The diagram shows all of the basic features and instrumentation of PET scanning. Let's look at them one by one. PET imaging requires the injection of specific radioactive compounds. These specially prepared compounds contain positron-emitting atoms. When a positron is emitted by an atomic nucleus, it eventually combines with an electron, which is its antimatter particle, and two gamma rays result from this combination that we call an annihilation. The gamma rays shoot off in opposite directions and the image portrays this. This is the basic mechanism, and why it is called positron emission tomography. The subject to be studied is given an injection of a positron-emitting compound. The exact compound that's given depends on the kind of measurement you're making, or on the kind of brain pro, protein that you want to detect and measure. The two gamma rays resulting from the annihilation are detected by a circular array of detectors, shown in the image. The data from the detectors are analyzed by computers and then in images reconstructed and displayed. The data and the image can be processed and analyzed in many useful ways. PET data are usually viewed as slices through the brain, which is what tomography is. The slices can be in different orientations depending on the structure of interest, as is shown in the image. Slicing in the coronal or horizontal planes is most common. Here's an assignment. Do an Internet search on brain atlases. Look through them and try to get comfortable with different views of brain slices. If you have difficulty with this, please do not worry because the meaning of the images that I'll be showing to you will be easy to understand. Now, just an interesting caution, the images we see in PET scanning do not directly show the structure of the brain. The PET images show the distribution of radioactivity in the brain, which can suggest the shape of the brain slice. In this image on the left, you see what a slice through the head, at the level of the eyeballs, would look like by the normal eye. No radioactivity shown. But on the right is a PET image of the distribution of D2 dopamine receptors. The receptors have a positron-emitting substance selectively bound to them, thus measuring the radioactivity reflects the presence of receptors. The intensity of the color parallels the level of the dopamine receptors. Brighter color equals more receptors. But the structure of the brain, its tissue, is not shown as it is on the left. The receptors are shown within the structure, and the structure can sort of be seen even though it's not being explicitly shown. Now, let's visit an actual PET imaging facility. Here we are at a PET center with all of the instrumentation that's need to carry out these measurements. Here is the PET scanner. You can see the platform that the subjects lie down on. It's motorized and can be moved in and out of the detector apparatus. The detector apparatus is this large panel part that the heads of the subjects fit into. Behind these panels is the circular array of detectors that I talked about earlier. So, this is how it works. A subject compatible with an important experiment is chosen. The subject receives an injection of a radiolabeled substance that travels to the brain and that emits a positron. The nature of the substance, as you know, will depend on what we're measuring in the brain. The material that's injected is made in a very special area that we call the hot cell area. Because we're dealing with radioactivity, the synthesis of these compounds and substances is done very, very carefully and according to very strict regulations. It's done remotely by radiochemists who control the synthesis of these substances from a remote station. The total amount of radioactivity that a subject receives is very low, however. It will not do any damage to the subject. While a subject can go through this procedure more than once, there's a limit on the amount of radioactivity that a single subject can be exposed to in a given amount of time. In any case, this is all worked out very nicely and very safely, and great deal of useful information has been obtained from this procedure. After there's, the injection, the subject is moved into the scanner, and here's an example, and the radioactivity coming from the brain is recorded by this apparatus. Then the computers take all of the image data and reconstruct three-dimensionally in space, where the radioactivity's coming from. Basically, this will show what part of the brain contains the radioactive emitter, and how much radioactivity is there. Overall, this is an amazing instrumentation. In the early 1980s, I was lucky enough to be a senior member of the team at the Johns Hopkins University's School of Medicine, that developed this approach for measuring drug receptors in the human brain. I was also fortunate enough to play a role in identifying the dopamine transporter as the cocaine receptor, which has also been imaged using PET. Those discoveries have had a significant impact in understanding what happens when people become addicted. In the following lectures, we will review some of the discoveries around drug addition that came from PET studies.
