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Positron Emission Tomography (PET)
Positron Emission Tomography (PET) WJ Powers, University of North Carolina School of Medicine, Chapel Hill, NC, USA r 2014 Elsevier Inc. All rights reserved.
Positron emission tomography (PET) is a technique for physiological imaging of the brain. It employs the physical properties of radioactive atoms that decay by emission of positrons, negatively charged electrons. Molecules labeled with radioactive atoms have been utilized extensively for many years to investigate physiology and pathology. These radiotracers are administered to an organism in such small quantities that they do not affect the physiological process under study and yet the radioactivity is sufficient that it can be measured by an appropriate detection system. Utilization of radiotracer technology for biological investigation requires three components – a radiotracer, a radiation detection system, and a mathematical model that relates the physiological process under study to the radiation detected. Of the three, the radiation detection system has been the major barrier to the application of radiotracer methods to quantitative regional physiological measurements of the human brain in vivo. In experimental animal studies, radiotracers in the brain are most often measured ex vivo after sacrificing the animal. This is done either by counting the radioactivity in individual samples or by autoradiography of tissue slices. Ex vivo counting of radioactivity relies on a scintillator (solid crystal or liquid) that absorbs the radioactivity and emits a pulse of light, which can be measured and recorded by a photoelectric system. Autoradiography requires exposure of the slice to a special film, which produces a photographic image with intensity proportional to the radioactivity in each region. Extension of these techniques to imaging of the human brain in vivo is not easy. Those radionuclides most commonly used in animal experiments, such as 3H and 14C, decay by electron emission and cannot be detected externally because the electrons are all absorbed by a few millimeters of surrounding tissue. Radionuclides that decay by photon (gamma) emission can be detected externally but present several problems. A variable fraction of the emitted photons is absorbed by the surrounding tissue depending on the photon energy, tissue composition, and path length. Furthermore, the radioactivity from overlapping superficial and deep structures is superimposed and cannot be distinguished by a single external scintillation detector. In the early 1970s, the development of X-ray computed tomography (CT) demonstrated the basic method for accurate reconstruction of three-dimensional structures from a series of two-dimensional X-ray profiles taken at different angles around an object. In X-ray CT, the profiles used in the image reconstruction represent the absorption of X-rays by the object being studied. Application of CT technology to the external detection of radiotracers is not straightforward. For external detection of the radiation emitted by internal radiotracers (or emission CT), the desired data in the reconstructed image are the quantitative spatial distribution of the radioactivity. Unfortunately, the externally recorded profiles will represent the desired information on spatial distribution of radioactivity altered by the variable absorption (attenuation) of this
Encyclopedia of the Neurological Sciences, Volume 3
radiation by the surrounding tissue. Furthermore, the reconstruction process in CT assumes that the spatial resolution of the radiation detectors does not vary with the distance from the detector. Although this is very close to be true for X-ray CT, it is simply not the case for conventional single-photon (gamma) detectors. The resolution of these detectors decreases as the distance from the detector increases. Nevertheless, a variety of single-photon emission computed tomography (SPECT) systems have been built incorporating empiric or other corrections for attenuation and mathematical adjustments for distance-dependent resolution. PET employs the physical properties of positrons to overcome the inherent problems with SPECT and makes possible accurate quantitation of regional radioactivity in vivo. Certain radionuclides decay by emission of a positron, a small particle with the same mass as an electron but the opposite charge. After traveling a few millimeters through tissue, the positron interacts with an electron, resulting in the destruction of both. This annihilation creates two photons (g-rays) that travel away from the annihilation site at 1801 in opposite directions. A pair of external radiation detectors positioned on either side of a positron-emitting source will register these photons at almost the same time. (The difference in time is equivalent to the difference in the distance the two photons travel divided by the speed of light.) If this detector pair is connected by an electronic circuit that records a signal only when two photons arrive within this short-time interval, then only photons arising from positron annihilations occurring between the detector pair will be recorded. Annihilation coincidence detection presents the solution to the problems encountered with SPECT. The spatial resolution of a pair of annihilation coincidence detectors is nearly uniform for most of the regions located between the two detectors. The fraction of radioactivity lost due to absorption by surrounding tissue can be measured accurately and then corrected for in the following way. For an individual photon, this attention fraction depends on the tissue composition and distance the photon travels through the tissue. For a pair of annihilation photons, the tissue composition and total distance traveled by both gamma photons will be the same regardless of where between the detector pair the annihilation occurs. The attenuation fraction for a given path through an object will, therefore, be the same whether the annihilation occurs internally or externally to the object. The attenuation fraction for any pair of coincidence detectors relative to a specific object can be measured accurately before the internal administration of any radiotracers. First, a positron-emitting source is placed between the detector pair and the total number of coincidences per unit time is recorded. The head (or other part of the body to be studied) is then also placed between the detector pair and number of coincidences per unit time is again measured. The fractional reduction in the initial radioactivity represents the annihilation photons absorbed by the head for the tissue path between the detector pair. When a radiotracer is administered,
doi:10.1016/B978-0-12-385157-4.00203-7
949
950
Positron Emission Tomography (PET)
this individually measured attenuation fraction is used to correct the number of coincidence events recorded by the detector pair from inside the body to yield the actual number of positron annihilations that took place with its field of view (Figure 1). A PET scanner consists of multiple rings, each with a large number of detectors. Each detector is connected by coincidence circuits to other detectors in the same or different rings. After corrections for attenuation, the information obtained from each of these detector pairs is used to construct a series of projections, each representing the distribution of regional radioactivity as viewed from a different angle. These projections
are then reconstructed to produce two-dimensional slices representing regional radioactivity within the field of view of the scanner. These individual slices can be combined into a true three-dimensional image. The accuracy of the reconstructed PET image as a quantitative measure of regional radioactivity depends on a variety of technical factors beyond the scope of this article. There is one technical concept, however, that is crucial for the proper interpretation of any PET measurement. This is the effect of image resolution on the accuracy of the measurement of regional radioactivity. In the PET image, radioactivity from a given region in the object is redistributed or smeared over a
Coincidence circuit
A A
A′
1
1 B
2
B′
2
B
3
3
Coincidence circuit
(b)
(a)
Coincidence circuit
A′
B′
A
1 2
B
3 Coincidence circuit
(c)
Figure 1 Measurement of regional radioactivity with external detectors. (a) Conventional single detector systems such as Anger cameras used in clinical nuclear medicine or SPECT employ an array of single external detectors (A, B) to determine the location and amount of radioactivity emitted from a source (1–3) inside the head or elsewhere in the body. Although the entire source is within the field of detector B, only a fraction of the photons (g-rays) emitted from the source ever reach the detector (3). Some are totally absorbed by the surrounding tissues (2), whereas others interact within the tissue and are scattered out of the detector field (1). These scattered photons may be recorded by an adjacent detector (A) and be falsely localized. (b) PET employs pairs of detectors (A-A0 , B-B0 ) connected by electronic coincidence circuits that only record an event when both annihilation photons from a positron decay are detected almost simultaneously (3). When one annihilation photon is absorbed (2) or scattered out of the field of view of the detector pair (1), no event is recorded. (c) With PET, a correction for the fraction of radiation lost due to absorption and scatter can be performed. Before the administration of any radiotracers, an external positron-emitting source (1–3) is placed within the detector field and number of coincidence events for each detector pair is recorded. The head or other part of the body to be imaged is then placed within the detector field, and the fraction of the initial coincidences still recorded by each detector pair (1/1 þ 2 þ 3) is determined. This fraction is then used to correct the data obtained from each detector pair when measuring radioactivity from internally administrated positron-emitting radiotracers. Illustrations by Lydia Counts.
Positron Emission Tomography (PET)
larger area. For a point source of radioactivity, this redistribution approximates the form of a Gaussian (bell-shaped) curve with the maximum value occurring at the original point. As a consequence of this redistribution of radioactivity, a given region in the reconstructed image, regardless of its size, contains only a portion of the radioactivity actually within that region in the original structure. The remainder has been redistributed into surrounding regions of the image. Similarly, some radioactivity originally in these surrounding regions has
0 mm
8 mm
15 mm
Figure 2 Partial volume effect. The effect of differences in image resolution on the measurement of regional radioactivity from (top row) a hexagonal array of 8-mm spheres with no radioactivity surrounded by radioactivity and (bottom row) a hexagonal array of 8-mm spheres with radioactivity surrounded by no radioactivity. Simulated PET images with perfect resolution (0 mm) and with resolution of 8 and 15 mm are shown. The resolution of an image is measured as the width of the intensity curve obtained for a point source of radioactivity at one-half of the maximum value of the curve. Simulated images courtesy of Tom O. Videen, PhD.
Normal
951
been redistributed into the region of interest. Thus, the regional radioactivity measurement made with PET represents some portion of the radioactivity actually within that region as well as a contribution from radioactivity in surrounding regions. This is known as the partial volume effect (Figure 2). Thus, PET will always demonstrate a gradual transition of values between two structures even when there is an abrupt change, such as at the edge of a cerebral infarct or hemorrhage. Furthermore, in areas of brain adjacent to cerebrospinal fluid (CSF), there will be a reduction in the radioactivity measured in the brain due to the usually low or absent radiotracer accumulation in CSF. As a result of the partial volume effect, it is difficult to obtain values that truly represent either pure gray matter or pure white matter. This is especially true for cortical regions that will always contain a contribution from cortical gray matter and contiguous subcortical white matter and CSF. The partial volume effect due to CSF is particularly a problem in patients with cerebral atrophy or hydrocephalus. Various techniques have been developed to provide corrections for partial volume effect. These use X-ray CT or magnetic resonance image to provide structural information about the brain. Positron-emitting radionuclides such as 15O, 11C, and 18F can be used to label a wide variety of molecules thus providing PET with the capability to measure a wide variety of biological processes in vivo in the human brain. PET can be used with highly specific positron-labeled radioligands to study the neuropharmacology of disease in vivo. The most common applications of this approach has been the study of alterations in dopamine and serotonin receptors but, within the constraints of practical consideration of chemical synthesis (see final paragraph), the possibilities are almost limitless (Figure 3). Imaging of specific radioligands can be used for other purposes as well, such as assessment of cortical neuronal density with the central benzodiazepine receptor ligand 11Cflumazenil.
Parkinson’s disease
Figure 3 PET image of Parkinson’s disease. PET images of 18F-fluorodopa radioactivity in a normal subject and in a patient with Parkinson’s disease. In the normal subject, there is high radioactivity bilaterally in the caudate and putamen reflecting uptake and metabolism of the radioactive fluorodopa by dopaminergic neurons. In the patient with Parkinson’s disease, there is minimal uptake of radioactive fluorodopa because of degeneration and death of dopaminergic neurons. Image courtesy of Joel Perlmutter, MD.
952
Positron Emission Tomography (PET)
AD
Control
2.0
FDG
0
2.5 PIB
0
Figure 4 PET images using the 11C amyloid imaging agent Pittsburgh compound B (PIB) and 18F-fluorodeoxyglucose (FDG) from a 67-year-old man who met National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA) criteria for Alzheimer’s disease (AD) and a 62-year-old female control. Modified from Boxer AL, Rabinovici GD, Kepe V, et al. (2007) Amyloid imaging in distinguishing atypical prion disease from Alzheimer disease. Neurology 69: 283–290, with permission from LWW.
Other applications of PET are measurement of cerebral blood flow (CBF) and cerebral metabolism (oxygen and glucose utilization). Measurements of CBF rely on radiotracers that freely diffuse from the blood into brain tissue, primarily 15Owater. The PET CBF measurements are particularly well suited for studying cerebrovascular diseases because of the primary importance of CBF changes in these disorders. PET CBF measurements can be used for physiological brain mapping of normal human cognitive processes because CBF increases when local neuronal activity increases. Although other neuroimaging methods can be used to measure CBF, quantitative measurements of regional cerebral metabolism are a unique capability of PET. Oxygen metabolism can be measured with O15O, and glucose metabolism can be measured with 11C-glucose or with the glucose analog 18F-fluorodeoxyglucose. The combination of
hemodynamic and metabolic measurements has proven especially valuable for understanding the changes that take place during physiological brain activation and during cerebral ischemia. Recently, PET radiotracers that bind to amyloid plaques in the brain have been developed. They permit the detection of one of the pathological signatures of Alzheimer’s disease (AD) before death. These radiotracers have been of great value in research studies that have helped to define the cause and natural history of different dementing illnesses (Figure 4). Currently, PET remains primarily a research tool. Generation of quantitative physiological data often requires rapid, sequential arterial blood sampling and complex computer processing of PET images. Production of the more commonly used positron emitters (11C, 15O, and 18F) requires a cyclotron or linear accelerator; their availability depends on proximity to one of these facilities. Synthesis of molecules incorporating short-lived radionuclides is a specialized field requiring great expertize. The synthesis must be performed rapidly and, at the same time, yield substances that are of sufficient purity to be safe for administration to human subjects. Most positronemitting radionuclides have half-lives of minutes to a few hours. 11C and 15O labeled PET radiotracers must be prepared on site. Those labeled with 18F, which has a half-life of 110 min, can be shipped short distances. Clinically, PET measurements of cerebral glucose metabolism are used to delineate areas of damaged brain that are epileptic foci and are amenable to surgical resection. New PET radiotracers that identify amyloid deposition in the brain hold promise for the diagnostic evaluation of dementia.
See also: Brain Imaging, Physiological. Cerebral Blood Flow, Measurement of. Cerebral Metabolism and Blood Flow. SinglePhoton Emission Computed Tomography (SPECT)
Further Reading Herholz K, Herscovitch P, and Heiss W-D (2004) NeuroPET: Positron Emission Tomography in Neuroscience and Clinical Neurology. Berlin: Springer. Mittra E and Quon A (2009) Positron emission tomography/computed tomography: The current technology and applications. Radiologic Clinics of North America 47: 147–160. PET Clin North Am 2010; 5(1) and (2). Valk PE (2003) Positron Emission Tomography: Basic Science and Clinical Practice. London: Springer.
Positron emission tomography (PET) is a technique for physiological imaging of the brain. It employs the physical properties of radioactive atoms that decay by emission of positrons, negatively charged electrons. Molecules labeled with radioactive atoms have been utilized extensively for many years to investigate physiology and pathology. These radiotracers are administered to an organism in such small quantities that they do not affect the physiological process under study and yet the radioactivity is sufficient that it can be measured by an appropriate detection system. Utilization of radiotracer technology for biological investigation requires three components – a radiotracer, a radiation detection system, and a mathematical model that relates the physiological process under study to the radiation detected. Of the three, the radiation detection system has been the major barrier to the application of radiotracer methods to quantitative regional physiological measurements of the human brain in vivo. In experimental animal studies, radiotracers in the brain are most often measured ex vivo after sacrificing the animal. This is done either by counting the radioactivity in individual samples or by autoradiography of tissue slices. Ex vivo counting of radioactivity relies on a scintillator (solid crystal or liquid) that absorbs the radioactivity and emits a pulse of light, which can be measured and recorded by a photoelectric system. Autoradiography requires exposure of the slice to a special film, which produces a photographic image with intensity proportional to the radioactivity in each region. Extension of these techniques to imaging of the human brain in vivo is not easy. Those radionuclides most commonly used in animal experiments, such as 3H and 14C, decay by electron emission and cannot be detected externally because the electrons are all absorbed by a few millimeters of surrounding tissue. Radionuclides that decay by photon (gamma) emission can be detected externally but present several problems. A variable fraction of the emitted photons is absorbed by the surrounding tissue depending on the photon energy, tissue composition, and path length. Furthermore, the radioactivity from overlapping superficial and deep structures is superimposed and cannot be distinguished by a single external scintillation detector. In the early 1970s, the development of X-ray computed tomography (CT) demonstrated the basic method for accurate reconstruction of three-dimensional structures from a series of two-dimensional X-ray profiles taken at different angles around an object. In X-ray CT, the profiles used in the image reconstruction represent the absorption of X-rays by the object being studied. Application of CT technology to the external detection of radiotracers is not straightforward. For external detection of the radiation emitted by internal radiotracers (or emission CT), the desired data in the reconstructed image are the quantitative spatial distribution of the radioactivity. Unfortunately, the externally recorded profiles will represent the desired information on spatial distribution of radioactivity altered by the variable absorption (attenuation) of this
Encyclopedia of the Neurological Sciences, Volume 3
radiation by the surrounding tissue. Furthermore, the reconstruction process in CT assumes that the spatial resolution of the radiation detectors does not vary with the distance from the detector. Although this is very close to be true for X-ray CT, it is simply not the case for conventional single-photon (gamma) detectors. The resolution of these detectors decreases as the distance from the detector increases. Nevertheless, a variety of single-photon emission computed tomography (SPECT) systems have been built incorporating empiric or other corrections for attenuation and mathematical adjustments for distance-dependent resolution. PET employs the physical properties of positrons to overcome the inherent problems with SPECT and makes possible accurate quantitation of regional radioactivity in vivo. Certain radionuclides decay by emission of a positron, a small particle with the same mass as an electron but the opposite charge. After traveling a few millimeters through tissue, the positron interacts with an electron, resulting in the destruction of both. This annihilation creates two photons (g-rays) that travel away from the annihilation site at 1801 in opposite directions. A pair of external radiation detectors positioned on either side of a positron-emitting source will register these photons at almost the same time. (The difference in time is equivalent to the difference in the distance the two photons travel divided by the speed of light.) If this detector pair is connected by an electronic circuit that records a signal only when two photons arrive within this short-time interval, then only photons arising from positron annihilations occurring between the detector pair will be recorded. Annihilation coincidence detection presents the solution to the problems encountered with SPECT. The spatial resolution of a pair of annihilation coincidence detectors is nearly uniform for most of the regions located between the two detectors. The fraction of radioactivity lost due to absorption by surrounding tissue can be measured accurately and then corrected for in the following way. For an individual photon, this attention fraction depends on the tissue composition and distance the photon travels through the tissue. For a pair of annihilation photons, the tissue composition and total distance traveled by both gamma photons will be the same regardless of where between the detector pair the annihilation occurs. The attenuation fraction for a given path through an object will, therefore, be the same whether the annihilation occurs internally or externally to the object. The attenuation fraction for any pair of coincidence detectors relative to a specific object can be measured accurately before the internal administration of any radiotracers. First, a positron-emitting source is placed between the detector pair and the total number of coincidences per unit time is recorded. The head (or other part of the body to be studied) is then also placed between the detector pair and number of coincidences per unit time is again measured. The fractional reduction in the initial radioactivity represents the annihilation photons absorbed by the head for the tissue path between the detector pair. When a radiotracer is administered,
doi:10.1016/B978-0-12-385157-4.00203-7
949
950
Positron Emission Tomography (PET)
this individually measured attenuation fraction is used to correct the number of coincidence events recorded by the detector pair from inside the body to yield the actual number of positron annihilations that took place with its field of view (Figure 1). A PET scanner consists of multiple rings, each with a large number of detectors. Each detector is connected by coincidence circuits to other detectors in the same or different rings. After corrections for attenuation, the information obtained from each of these detector pairs is used to construct a series of projections, each representing the distribution of regional radioactivity as viewed from a different angle. These projections
are then reconstructed to produce two-dimensional slices representing regional radioactivity within the field of view of the scanner. These individual slices can be combined into a true three-dimensional image. The accuracy of the reconstructed PET image as a quantitative measure of regional radioactivity depends on a variety of technical factors beyond the scope of this article. There is one technical concept, however, that is crucial for the proper interpretation of any PET measurement. This is the effect of image resolution on the accuracy of the measurement of regional radioactivity. In the PET image, radioactivity from a given region in the object is redistributed or smeared over a
Coincidence circuit
A A
A′
1
1 B
2
B′
2
B
3
3
Coincidence circuit
(b)
(a)
Coincidence circuit
A′
B′
A
1 2
B
3 Coincidence circuit
(c)
Figure 1 Measurement of regional radioactivity with external detectors. (a) Conventional single detector systems such as Anger cameras used in clinical nuclear medicine or SPECT employ an array of single external detectors (A, B) to determine the location and amount of radioactivity emitted from a source (1–3) inside the head or elsewhere in the body. Although the entire source is within the field of detector B, only a fraction of the photons (g-rays) emitted from the source ever reach the detector (3). Some are totally absorbed by the surrounding tissues (2), whereas others interact within the tissue and are scattered out of the detector field (1). These scattered photons may be recorded by an adjacent detector (A) and be falsely localized. (b) PET employs pairs of detectors (A-A0 , B-B0 ) connected by electronic coincidence circuits that only record an event when both annihilation photons from a positron decay are detected almost simultaneously (3). When one annihilation photon is absorbed (2) or scattered out of the field of view of the detector pair (1), no event is recorded. (c) With PET, a correction for the fraction of radiation lost due to absorption and scatter can be performed. Before the administration of any radiotracers, an external positron-emitting source (1–3) is placed within the detector field and number of coincidence events for each detector pair is recorded. The head or other part of the body to be imaged is then placed within the detector field, and the fraction of the initial coincidences still recorded by each detector pair (1/1 þ 2 þ 3) is determined. This fraction is then used to correct the data obtained from each detector pair when measuring radioactivity from internally administrated positron-emitting radiotracers. Illustrations by Lydia Counts.
Positron Emission Tomography (PET)
larger area. For a point source of radioactivity, this redistribution approximates the form of a Gaussian (bell-shaped) curve with the maximum value occurring at the original point. As a consequence of this redistribution of radioactivity, a given region in the reconstructed image, regardless of its size, contains only a portion of the radioactivity actually within that region in the original structure. The remainder has been redistributed into surrounding regions of the image. Similarly, some radioactivity originally in these surrounding regions has
0 mm
8 mm
15 mm
Figure 2 Partial volume effect. The effect of differences in image resolution on the measurement of regional radioactivity from (top row) a hexagonal array of 8-mm spheres with no radioactivity surrounded by radioactivity and (bottom row) a hexagonal array of 8-mm spheres with radioactivity surrounded by no radioactivity. Simulated PET images with perfect resolution (0 mm) and with resolution of 8 and 15 mm are shown. The resolution of an image is measured as the width of the intensity curve obtained for a point source of radioactivity at one-half of the maximum value of the curve. Simulated images courtesy of Tom O. Videen, PhD.
Normal
951
been redistributed into the region of interest. Thus, the regional radioactivity measurement made with PET represents some portion of the radioactivity actually within that region as well as a contribution from radioactivity in surrounding regions. This is known as the partial volume effect (Figure 2). Thus, PET will always demonstrate a gradual transition of values between two structures even when there is an abrupt change, such as at the edge of a cerebral infarct or hemorrhage. Furthermore, in areas of brain adjacent to cerebrospinal fluid (CSF), there will be a reduction in the radioactivity measured in the brain due to the usually low or absent radiotracer accumulation in CSF. As a result of the partial volume effect, it is difficult to obtain values that truly represent either pure gray matter or pure white matter. This is especially true for cortical regions that will always contain a contribution from cortical gray matter and contiguous subcortical white matter and CSF. The partial volume effect due to CSF is particularly a problem in patients with cerebral atrophy or hydrocephalus. Various techniques have been developed to provide corrections for partial volume effect. These use X-ray CT or magnetic resonance image to provide structural information about the brain. Positron-emitting radionuclides such as 15O, 11C, and 18F can be used to label a wide variety of molecules thus providing PET with the capability to measure a wide variety of biological processes in vivo in the human brain. PET can be used with highly specific positron-labeled radioligands to study the neuropharmacology of disease in vivo. The most common applications of this approach has been the study of alterations in dopamine and serotonin receptors but, within the constraints of practical consideration of chemical synthesis (see final paragraph), the possibilities are almost limitless (Figure 3). Imaging of specific radioligands can be used for other purposes as well, such as assessment of cortical neuronal density with the central benzodiazepine receptor ligand 11Cflumazenil.
Parkinson’s disease
Figure 3 PET image of Parkinson’s disease. PET images of 18F-fluorodopa radioactivity in a normal subject and in a patient with Parkinson’s disease. In the normal subject, there is high radioactivity bilaterally in the caudate and putamen reflecting uptake and metabolism of the radioactive fluorodopa by dopaminergic neurons. In the patient with Parkinson’s disease, there is minimal uptake of radioactive fluorodopa because of degeneration and death of dopaminergic neurons. Image courtesy of Joel Perlmutter, MD.
952
Positron Emission Tomography (PET)
AD
Control
2.0
FDG
0
2.5 PIB
0
Figure 4 PET images using the 11C amyloid imaging agent Pittsburgh compound B (PIB) and 18F-fluorodeoxyglucose (FDG) from a 67-year-old man who met National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA) criteria for Alzheimer’s disease (AD) and a 62-year-old female control. Modified from Boxer AL, Rabinovici GD, Kepe V, et al. (2007) Amyloid imaging in distinguishing atypical prion disease from Alzheimer disease. Neurology 69: 283–290, with permission from LWW.
Other applications of PET are measurement of cerebral blood flow (CBF) and cerebral metabolism (oxygen and glucose utilization). Measurements of CBF rely on radiotracers that freely diffuse from the blood into brain tissue, primarily 15Owater. The PET CBF measurements are particularly well suited for studying cerebrovascular diseases because of the primary importance of CBF changes in these disorders. PET CBF measurements can be used for physiological brain mapping of normal human cognitive processes because CBF increases when local neuronal activity increases. Although other neuroimaging methods can be used to measure CBF, quantitative measurements of regional cerebral metabolism are a unique capability of PET. Oxygen metabolism can be measured with O15O, and glucose metabolism can be measured with 11C-glucose or with the glucose analog 18F-fluorodeoxyglucose. The combination of
hemodynamic and metabolic measurements has proven especially valuable for understanding the changes that take place during physiological brain activation and during cerebral ischemia. Recently, PET radiotracers that bind to amyloid plaques in the brain have been developed. They permit the detection of one of the pathological signatures of Alzheimer’s disease (AD) before death. These radiotracers have been of great value in research studies that have helped to define the cause and natural history of different dementing illnesses (Figure 4). Currently, PET remains primarily a research tool. Generation of quantitative physiological data often requires rapid, sequential arterial blood sampling and complex computer processing of PET images. Production of the more commonly used positron emitters (11C, 15O, and 18F) requires a cyclotron or linear accelerator; their availability depends on proximity to one of these facilities. Synthesis of molecules incorporating short-lived radionuclides is a specialized field requiring great expertize. The synthesis must be performed rapidly and, at the same time, yield substances that are of sufficient purity to be safe for administration to human subjects. Most positronemitting radionuclides have half-lives of minutes to a few hours. 11C and 15O labeled PET radiotracers must be prepared on site. Those labeled with 18F, which has a half-life of 110 min, can be shipped short distances. Clinically, PET measurements of cerebral glucose metabolism are used to delineate areas of damaged brain that are epileptic foci and are amenable to surgical resection. New PET radiotracers that identify amyloid deposition in the brain hold promise for the diagnostic evaluation of dementia.
See also: Brain Imaging, Physiological. Cerebral Blood Flow, Measurement of. Cerebral Metabolism and Blood Flow. SinglePhoton Emission Computed Tomography (SPECT)
Further Reading Herholz K, Herscovitch P, and Heiss W-D (2004) NeuroPET: Positron Emission Tomography in Neuroscience and Clinical Neurology. Berlin: Springer. Mittra E and Quon A (2009) Positron emission tomography/computed tomography: The current technology and applications. Radiologic Clinics of North America 47: 147–160. PET Clin North Am 2010; 5(1) and (2). Valk PE (2003) Positron Emission Tomography: Basic Science and Clinical Practice. London: Springer.