Functional Imaging in Movement Disorders

W. R. Wayne Martin

• Publisher: CRC Press
• Year: 2019
• ISBN:
  9781000696844
• Edition: 1
• Topic: Medicine
• Subtopic: Neurology

First published in 1990, this indispensable volume brings together authoritative, up-to-date, critical accounts of the present status of positron emission tomography (PET) in the study of movement disorders both in terms of the basic science relevant to PET and the clinical science related to the study of specific disease processes. For better understanding, it includes a review of the basic principles of PET and tracer kinetics. It also reviews clinical studies concerning Parkinson's and Huntington's disease, as well as some of the less common movement disorders such as progressive supranuclear palsy, olivopontocerebellar atrophy, and dystonia. Throughout the text, it emphasizes PET as a tool for the quantitative measurement of meaningful biochemical and physiological processes. This state-of-the-art work provides a perspective concerning the degree to which PET studies have advanced knowledge and the future role anticipated for PET. All clinical and basic researchers interested in functional imaging with PET and movement disorders will find this book an absolute must.

Chapter 1

PRINCIPLES OF POSITRON EMISSION TOMOGRAPHY

Peter Herscovitch

TABLE OF CONTENTS

I.	Introduction
II.	PET Instrumentation A. Formation of the PET Image B. Performance Characteristics of PET Scanners
III.	Radiotracers for PET
IV.	Radiotracer Techniques A. General Principles B. Cerebral Blood Volume C. Cerebral Blood Flow 1. Background 2. Steady-State Method 3. PET/Autoradiographic Method 4. Other Methods for Measuring rCBF D. Cerebral Oxygen Metabolism 1. Background 2. Steady-State Method 3. Brief Inhalation Method E. Cerebral Glucose Metabolism 1. Deoxyglucose Method 2. Adaptation of DG Method to PET 3. Use of ^11Glucose
V.	Analysis and Interpretation of PET Data A. Image Display B. Anatomic Localization in PET Images C. Analysis of Regional PET Data D. Subject Selection and Characterization E. Interpretation of Changes in Cerebral Blood Flow and Metabolism
References

I. INTRODUCTION

The past three decades have seen considerable advances in the methods available for measuring brain blood flow, metabolism, and biochemistry. These advances have culminated in the development of positron emission tomography (PET). To help put the advantages of PET into perspective, the methods that were previously available will be briefly described. The pioneering work of Kety and Schmidt in the 1940s resulted in the development of the nitrous oxide method for measuring hemispheric cerebral blood flow (CBF).¹ These CBF measurements, when combined with measurements of brain arterial-venous differences for glucose and oxygen, permitted the determination of cerebral metabolism as well. The Kety-Schmidt technique, however, did not provide measurements on a regional basis. The desire to obtain regional rather than global data led to the development of methods to measure CBF with radioactive tracers and external probe systems incorporating multiple radiation detectors placed over the head. They were used to measure the clearance from different brain regions of freely diffusible radioactive gases, such as xenon-133, that were administered either by injection into the internal carotid artery or by inhalation.^2,3 Subsequently, external probe techniques using intracarotid injection of tracers labeled with positron-emitting radionuclides were developed for the measurement not only of CBF, but also of cerebral blood volume and metabolism.⁴

These techniques, however, have several drawbacks. The variety of measurements that can be made is quite restricted. Only global measurements of cerebral metabolism can be obtained unless invasive intracarotid artery injections are used. The external detectors employed to obtain regional measurements of CBF have limitations. They record radioactivity from a volume of brain tissue extending a variable depth beneath the probe. Their field of view and sensitivity varies with depth. Radioactivity measurements from heterogeneous tissue elements are superimposed, and the presence of underperfused tissue in the field of view may not be detected. Also, measurements cannot be made from deeper structures such as the basal ganglia.

These limitations provided the impetus for the development of PET, a technique for measuring the absolute concentration of radioactive tracers in the body. From these measurements, the values of physiologic parameters such as blood flow can be calculated on a regional basis. There are three components necessary for the application of PET: (1) tracer compounds of physiologic interest that are labeled with positron-emitting radionuclides; (2) a positron emission tomograph to provide images from which one can accurately measure the amount of positron-emitting radioactivity and thus the amount of tracer compound throughout the brain; and (3) a mathematical model that describes the in vivo behavior of the specific radiotracer used, so that the physiologic process under study can be quantitated from the tomographic measurements of regional radioactivity. The first tomograph to be used in this manner was developed at Washington University in St. Louis by Ter-Pogossian and colleagues in the mid 1970s.⁵ Subsequently, there has been considerable growth in the field. The design of tomographs has become more sophisticated and radiotracer techniques to perform a wide variety of measurements have been developed. These have been applied to the study of both the normal brain and neuropsychiatric disease.^6,7 In addition, PET has been used in other organ systems, including the heart and lung.^{8, 9, 10}

The capabilities of PET are particularly relevant to the study of movement disorders. PET permits quantitative measurements to be made from structures such as basal ganglia and cerebellum that were inaccessible by earlier methods. In addition, several radiotracer methods have been developed to study neurotransmitter-neuroreceptor systems. Previously, it was possible to study these systems only by using post-mortem tissue or indirect approaches, such as monitoring the clinical response to pharmacologic interventions.

By reviewing the principles of PET, this chapter provides a basis for the subsequent sections of this volume. The basic components of PET — instrumentation, radiotracer synthesis, and mathematical modeling — will be discussed. Methods for measuring regional cerebral blood flow, blood volume, and metabolism of oxygen and glucose will be described in detail, and issues related to the analysis and interpretation of PET data will be reviewed. Techniques for studying pre- and postsynaptic dopaminergic neurotransmission are dealt with in later chapters.

II. PET INSTRUMENTATION

A. FORMATION OF THE PET IMAGE

PET is a technique for measuring the regional concentration of positron-emitting radionuclides in the body. It permits absolute quantitation of the in vivo distribution of positronemitting radioactivity by means of radiation detectors arrayed around the body. The measurements are presented in the form of a gray scale image of a cross-section through the body. The intensity of each point or pixel in the image is proportional to the amount of radioactivity at the corresponding position in the body.

PET depends upon the special nature of a type of radioactive decay. Certain radionuclides decay by the emission of a positron, which is a subatomic particle with the same mass as an electron, but a positive charge. After its emission from the nucleus, the positron travels a few millimeters in tissue, losing its kinetic energy. When almost at rest, it interacts with an electron, resulting in the annihilation of both positron and electron. Their combined mass is converted into energy in the form of electromagnetic radiation. This consists of two high-energy (511 keV) photons that travel in opposite directions away from the annihilation site at the speed of light. Detection of these annihilation photon pairs (one pair per radioactive decay event) is used to measure both the amount and the location of radioactivity. The two annihilation photons can be detected by two radiation detectors that are connected by an electronic coincidence circuit (Figure 1A). The circuit records a decay event only when both detectors sense the arrival of the photons almost simultaneously. A very short time window for photon arrival, typically 5 to 20 ns, called the coincidence resolving time, is allowed for registration of a coincidence event. This coincidence requirement for photon detection localizes the site of the decay event to the volume of space between the pair of detectors.

In practice, a ring of radiation detectors connected in pairs by coincidence circuits is used to surround the distribution of positron-emitting radioactivity in the body. With each decay event, the two annihilation photons are detected as a coincidence line, so that the number of coincidence lines recorded by any pair of detectors is proportional to the amount of radioactivity between them. An image of the distribution of radioactivity is then reconstructed from the coincidence lines (Figure 2). These lines are sorted into parallel groups, each group representing a profile or projection of the radioactivity distribution viewed from a different angle. The profiles are then combined by application of the same mathematical principles used in X-ray computed tomography¹¹ to obtain the PET image.

The reconstruction process requires a correction for the absorption or attenuation of annihilation photons that occurs within the tissue. This correction is substantial, as much as a factor of 5 to 6 in the center of the head. Estimates of the amount of radiation attenuated by the tissue between detector pairs can be calculated from outlines of t...

Table of contents

• Cover
• Title Page
• Copyright Page
• Preface
• The Editor
• Contributors
• Table of Contents
• Chapter 1 Principles of Positron Emission Tomography
• Chapter 2 Neurotransmitters and Receptors in the Basal Ganglia
• Chapter 3 Tracer Studies of Neuro-Receptor Kinetics In Vivo
• Chapter 4 Dopamine Receptor Studies with Positron Emission Tomography
• Commentary to Chapter 4 Different Methods of Measuring Binding to the Effector Ligand Binding Sites of Neurotransmitter Receptors: A Note of Caution
• Chapter 5 Parkinson’s Disease and Aging: Presynaptic Nigrostriatal Function
• Chapter 6 Cerebral Energy Metabolism and Blood Flow in Parkinson’s Disease
• Chapter 7 MPTP-Induced Parkinsonism
• Chapter 8 Positron Emission Tomograph in Progressive Supranuclear Palsy
• Chapter 9 Olivopontocerebellar Atrophy
• Chapter 10 Positron Emission Tomography and Huntington’s Disease
• Chapter 11 Clinical Management of Huntington’s Disease: The Role of PET and DNA Linkage Studies
• Chapter 12 Dystonia
• Chapter 13 Dementia in Movement Disorders
• Chapter 14 Future Directions for PET in Neurology
• Index