Professor Wayne Drevets explains how positron emission tomography (PET) is used to examine biochemicals in the brain such as serotonin.

This is a PET scanner. PET stands for Positron Emission Tomography. We will use this kind of device to measure a range of chemicals in the brain that in general can’t be measured in a non-invasive way using any other imaging modality. For example, we can image a variety of different receptors for serotonin or dopamine or other neurotransmitter systems using PET. We can also measure glucose metabolism. We can measure proteins like beta-amyloid. PET gives us a wide variety of measurements that can’t be obtained using other modalities, such as MRI technology for example. The way that we obtain these various measures is we use different types of radio[active] tracers, which are injected into the bloodstream through an intravenous catheter. The tracer will travel throughout the body. We are specifically imaging the portion of the tracer that is being taken up by the brain. The reason we are interested in these kinds of measurements in psychiatry is that this gives us a way to study the neurochemistry of systems that we know are important to stress responses, emotional behavior, and antidepressant or antipsychotic drug mechanisms in a way that we can’t obtain non-invasively any other way. With PET, we hope to really advance our knowledge about the pathophysiology of illnesses like major depressive disorder and schizophrenia. We expect that the kind of knowledge w e gain from PET will ultimately guide us toward more effective treatments, both in terms of understanding how our current drugs work, but also in terms of discovering new drugs and new drug targets that could ameliorate the symptoms from these severe illnesses. So this is the PET scanner. The PET scanner contains a ring of crystals inside that will detect the radioactive emissions that are coming from the subject’s body, especially the head. We will end up moving this bed into the scanner gantry so that the brain will be positioned right in the center of that crystal detector ring, which is about 15cm wide. The other apparatus that we rely on is this computer monitor, which the subject will view during scanning. In that way we can actually measure blood flow as the subject is performing some kind of a cognitive task. It is important that the individual we are scanning not move and so there are lying on this bed. In addition we use a thermoplastic mask that we place on the face that will at least remind the person that if they do move, they can feel that brushing against their face. It does restrict movement somewhat. We will place this on each subject before each scan in order to prevent movement. This is a panel that is provided with the scanner that will just allow us to move the scanner bed in toward the gantry and then we can position the head up or down or further in or further out in order to center the brain right in the center of the crystal detector. John, we’re all finished and we’re ready to get you out of the scanner. Steve is going to now slide the scanner bed out and then we’ll get you out of the mask and off the table. Today we are going to be using PET imaging to study serotonin type 1A receptors in the brain of an individual who has bipolar disorder. We’ll compare this young man’s scan to a similar scan from a young healthy control subject who will be similar in age and sex with our patient. The hypothesis we plan to test is that the serotonin 1A receptors in the mesial temporal cortex, which includes the amygdala and hippocampus (areas that we know are playing important roles in the pathophysiology of mood disorders from other types of information), the serotonin 1A receptor concentration there is going be to lower in the bipolar individual than in his matched control. We’ll test this hypothesis using a group of similar bipolar individuals versus a group of similarly matched controls over the next few months. Because serotonin 1A receptors play an important role in modulating the neuronal activity in both the amygdala and the hippocampus, we expect that this down-regulation of serotonin 1A may be playing roles in why the neuronal responses of structures like the amygdala are exaggerated in response to some types of emotional stimuli in individuals who have mood disorders. We recruit patients, like the one we will study today, from a research clinic where they undergo a variety of different diagnostic evaluations and we also obtain neuropsychological testing and laboratory testing. The image that we obtain will take about 90 minutes to acquire. We’ll then take that data from the PET scan and then we’ll download it to our computers and model the data so that we generate images that are considered to be an image of binding potential, which is basically the density of the serotonin 1A receptor multiplied by the affinity of that receptor – that’s the chief outcome measure for these kinds of receptor-imaging measures. We’ll then model that binding potential and compare the binding potentials from a group of bipolar individuals to a group of control individuals. One of the capabilities of PET imaging is that you can look at a variety of different chemicals in the brain with very high sensitivity. We look at different types of chemicals by using a different type of radio-ligand, or what we call radio-tracer. What that means is that we will use a molecule that binds to whatever we trying to study and then attach a radioactive nucleotide (or radio nucleotide) to that ligand that is going to bind to what we are trying to study. And then, by using different types of ligands we can look at different types of proteins or receptors in the brain. In this picture you have an image of an MRI scan on the left and a PET scan of serotonin 1A receptors on the right from the very same individual. Some of the brain structures you can see, this would temporal lobe and the frontal lobe and this structure back here is the cerebellum. You can see that the cerebellum doesn’t take up much serotonin 1A radio-ligand and that’s because there are hardly any serotonin 1A receptors expressed in the cerebellum. In contrast, you can see a lot of serotonin receptors, a high concentration of serotonin 1A receptors in the hippocampus. It is know that the hippocampus has one of the highest densities of serotonin 1A receptors in the brain. This is an example of the serotonin 1A receptor in a healthy individual on the left as compared to an individual with bipolar disorder on the right. In group studies, we have been able to show that the average serotonin 1A receptor binding in areas like the hippocampus and amygdala (which we abbreviate here as MTC for mesial-temporal cortex), that you have a lower binding in bipolar disorder individuals or in individuals with major depressive disorder than you have in healthy controls. In some cases you can see this difference so dramatically that you can pick it up in individual cases. Unfortunately this difference hasn’t been so consistent that we can you use this as a diagnostic tool to decide who has bipolar disorder versus who doesn’t. But nevertheless, we have been able to use this type of PET image to show that serotonin 1A receptors are decreased in at least many individuals bipolar depression or unipolar depression.

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