PET represents a new step forward in the way scientists and doctors look at the brain and how it functions. An X-ray or a CT scan shows only structural details within the brain. The PET scanner gives us a picture of the brain at work. - What is PET?
The epigraph above is reflective of the enthusiasm being generated among clinicians concerning the advent of positron emission tomography and its potential for imaging the human brain. The introduction of sophisticated neuroimaging techniques such as computerized tomography and magnetic resonance imaging has shifted the emphasis of neuropsychology from lesion localization to diagnosing the etiology of diseases (Maruish & Moses, 1997).
Behavioral neurology also benefited from innovations in neuroimaging techniques. The advent of improvements in the imaging of brain anatomy through computed tomography (CT) and magnetic resonance imaging (MRI), as well as functional imaging with single photon emission computed tomography (SPECT), positron emission tomography (PET), and activation MRI, have enabled behavioral neurologists to make anatomic correlations of behavior while patients are still alive (Maruish & Moses, 1997).
The introduction of cyclotron-produced, positron-emitting pharmaceuticals for the measurement of brain metabolism and blood flow in the end of the 1960s and in the early 1970s therefore represented a major step forward (N t nen, 1992). Further, new imaging techniques based on innovative radiopharmaceuticals were developed for the three-dimensional measurement of regional blood flow as well as glucose and oxygen utilization; however, these methods received only limited application since they required intracarotid injection of radiopharmaceuticals as well as an immediate access to a cyclotron. In addition, the assessment of cerebral blood flow made possible by these techniques has been only quasi-regional, and the metabolic information yielded to date has been relatively limited (N t nen, 1992). These early efforts were subsequently followed by a number of further developments on the path to an adequate three-dimensional regional measurement of blood flow and metabolism (Raichle, 1983).
This evolution proceeded along some clearly definable points; first, cyclotrons and accelerators, devices for producing positrons by nuclear bombardment, became available for use in brain research, together with innovative techniques that enabled the rapid synthesis of radiopharmaceuticals that were suitable for regional metabolic and hemodynamic studies in humans. The second milestone identified by N. t nen was that of the concomitant development of appropriate mathematical models that provided practical algorithms that enabled physiological parameters to be estimated from the data. Finally, the positron emission tomography was introduced that facilitated the detection of these radiopharmaceuticals in a truly regional and quantitative manner from everywhere in the living human brain (N t nen, 1992).
Statement of the Problem
The introduction of x-ray computed tomography (CT) in 1973 provided a new way of looking at the human brain in vivo had immense clinical significance; however, this innovation also served to stimulate the development of positron emission tomography (PET) and magnetic resonance imaging, which facilitated the imaging of function as well as anatomical investigations. Further complementing the development of these imaging techniques, and absolutely critical to their success in imaging the function of the human brain, was the introduction of various strategies for the measurement of brain blood flow and metabolism, beginning in the late 1940s with the pioneering work of Kety, Sokoloff, Lassen, Ingvar, and their numerous colleagues (in Raichle, 1994).
As a direct consequence of these developments, modem imaging devices now allow clinicians to safely localize and monitor accurately the activity of areas in the normal human brain during specific mental tasks. By virtue of these innovations, the clinical understanding of the neurobiological basis of human behavior should proceed at an unprecedented rate; however, success in this endeavor is highly dependent on a close working relationship between cognitive scientists who understand how to characterize and study the elements of human behavior and neuroscientists who understand how to study brain function at a system level. "This partnership relies on a mutual understanding of brain imaging techniques and how they can be most successfully applied to the study of the human brain" (Raichle, 1994, p. 333).
Purpose of Study
The purpose of this study is two-fold:
1) To determine the current and potential clinical applications for positron emission tomography; and 2) To develop a "best practices" approach to developing a partnership between cognitive scientists and neuroscientists to maximize the returns on investment in PET technology and its applications to the human condition.
Importance of Study
With the introduction of PET in the late 1970s, it became possible to perform direct, quantitative measurements of blood flow and metabolism everywhere in the human brain. According to Roland and Widen (1988), the measurements can be performed regionally from everywhere in the brain simultaneously and with a spatial resolution that permits distinction of most of the anatomical substructures of the cerebrum and even a few major brainstem structures. As these authors point out, "Obviously this is a breakthrough in brain research" (Roland & Widen, 1988, p. 213).
Chapter 2: Review of Related Literature
Background and Overview. Positron emission tomography (PET) is an imaging technique that is currently used in diagnosis and biomedical research. The technique has been shown to be especially useful in studying brain and heart functions, as well as certain biochemical processes involving these organs such as glucose metabolism and oxygen uptake. In PET applications, a chemical compound that is "labeled" with a short-lived, positron-emitting radionuclide (either carbon, oxygen, nitrogen, or fluorine) is injected into the body. The activity of such a radiopharmaceutical is then measured quantitatively throughout the target organs through the use of photomultiplier-scintillator detectors.
To date, the regional brain mechanisms that have been associated with opiate dependence and withdrawal have not been investigated using single photon emission computerized tomography (SPECT) in humans; however, the regional effects of acute morphine administration have been studied using positron emission tomography (PET).
PET study by London et al. (1990) employing fluorodeoxyglucose (FDG) reported that morphine administration reduced glucose metabolism in the whole brain and a large number of cortical and subcortical regions. A preliminary study that used FDG-PET identified evidence of regional alterations in brain function in two heroin-dependent subjects when compared with three subjects who had histories of opiate abuse, but not current physical dependence upon opiates (Charney et al., 1995).
Furthermore, PET studies employing carfentanil have been able to identify regional variations in human [mu] opiate receptor binding (Charney et al., 1995). However, alterations in opiate receptor number of affinity have not yet been described in humans who have experienced opiate dependence or withdrawal using PET opiate receptor binding techniques (Charney et al., 1995).
According to Science News' "Imaging Parkinson's" (2002), positron emission tomography can detect the loss of dopamine neurons, a key suspect in Parkinson's disease. According to research by David J. Tuite and his colleagues of the Adelaide and Meade Hospital in Dublin, "In the next few years, you'll see a change," Tuite predicts. Scans can potentially provide clinicians with "a much more objective test," he says, so doctors will begin to use them more frequently (Imaging Parkinson's, 2002, p. 382).
The PET device itself has become familiar to most American by virtue of its being increasingly featured in the mainstream media; the graphic provided in Figure 1 below is representative of such devices.
Figure 1. Typical Positron Emission Tomography Device, Clinician and Patient [Source: What is PET?, 2004].
During the decay of the radionuclide, positrons are annihilated by electrons, thereby producing gamma rays that are then detected simultaneously by the photomultiplier-scintillator combinations positioned on opposite sides of the patient. The data from the detectors is analyzed, integrated, and reconstructed with the use of a computer to produce images of the organs being scanned (Positron emission tomography, 2004).
Radionuclides Used in PET. There are only a few radionuclides, especially oxygen-15 (15O), nitrogen-13 (13N), carbon-11 (11C), and fluorine-18 (18F) that possess the physical and chemical properties that make them uniquely suitable for PET studies:
1. These nuclides decay by positron emission. Positrons are emitted from the nucleus of these radionuclides which have too few neutrons to be stable. Emitted positrons lose their kinetic energy in the tissue after traveling a short distance (1-6 mm) and then they interact with an electron. The positron and electron annihilate, giving rise to two photons travelling in opposite directions.... It is these annihilation photons that are detected by radiation detectors in the PET. The high energy of the photons gives them excellent tissue penetration and thus good detectability with radiation detectors. The fact that the two photons travel in opposite directions allows tomography algorithms to be applied.
2. The chemical nature of several radionuclides resembles the normal constituents of molecules of living matter so closely that these radionuclides can be incorporated in substances (such as glucose, water, carbon monoxide and dioxide, various amino acids, nitrous oxide) which are involved in most metabolic processes.
3. The short half-life of these radionuclides significantly reduces the dose of radiation received by the subject or patient, as well as by those handling the radionuclides.