1 Introduction
Christian Schiepers
C. Schiepers, MD, PhD
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, AR-144 CHS, Los Angeles, CA 90095-6942
went major revisions. A few were updated and had only minor revisions (Chaps. 4, 7 and 15,) and two were left unchanged and re-printed from the first edition. Our selection is aimed at elucidating key processes in cellular mechanisms of the human body, under normal conditions as well as in disease.
1.1
Perspective
NM started as a field where radioactive products were put to use for the benefit of mankind, e.g. thy- roid scintigraphy and therapy. The performed stud- ies in the field have fluctuated tremendously since those early years. Flow imaging of the brain was a frequent procedure in the NM clinic until CT was introduced. Later on, sophisticated triggering tech- niques were developed and true functional imag- ing of cardiac function became a reality. At present, we take the results of these pioneering efforts for granted. The next major step was introduction of tomography and multi-head camera systems in NM facilities. The ever increasing speed of computers allowed for reconstruction within minutes, and permitted standardization of imaging protocols for acquisition, processing and review. Image interpre- tation and reporting, as well as database manage- ment, PACS and teleradiology became easy tasks with the help of computers.
The equipment was tuned for Tc-99m as the radi- onuclide of choice, and radiochemistry was geared toward the Tc-99m pharmaceuticals. Kits that could easily be labeled at room temperature replaced many of the older products.
The main achievement, in my view, is the shift that occurred at the end of the last century, when NM changed from functional to biological imag- ing, with a major change of focus to the cellular and molecular level. The enormous strides of molecular biology, and awareness that defective genes cause disease, have revived mechanistic models of study-
CONTENTS
1.1 Perspective 1 1.2 Objectives 2 1.3 Clinical Overview 2
1.4 Basics of Diagnostic Nuclear Medicine 4 1.5 Future Perspective 4
In the present revised volume of Diagnostic Nuclear Medicine, the advancements in the field of nuclear medicine (NM) are presented with an emphasis on progress in the beginning of this millennium. The name ‘molecular imaging’ is used more frequently for diagnostic NM imaging, but is not commonplace.
We will use the traditional term NM. The various contributions in this imaging field such as new trac- ers and equipment, modifications of existing tests, diagnostic algorithms, and general applications for whole body imaging are discussed. Major achieve- ments during the last decade of the 20th century were the contribution of FDG in positron imaging, receptor and peptide imaging, pharmacological aug- mentation to enhance the accuracy of neuro-, car- diac, renal and hepatobiliary imaging. This progress has broadened the field and strengthened NM as a functional and molecular imaging modality.
The re-focusing of NM on imaging of biological processes had its effects on the selection of topics in this revised edition. Dual modality imaging with combined PET/CT is featured in Chap. 12 from the Zurich group in Switzerland and Chap. 13 from the UCLA group in California. Topics selected were con- sidered representative of the mainstream events. In addition to the new chapters on PET/CT, hepatobil- iary imaging was introduced as a separate chapter.
Other chapters were completely re-written or under-
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ing nature, a trend similar to the one that propelled modern physics at the turn of the 19th century. Two factors played an important part: the advancements in immunology, and the glucose analogue FDG as tracer for metabolic imaging.
In the present volume the interdisciplinary nature of NM imaging is emphasized: the view of clinicians, radiologists, nuclear medicine specialists, engineers and molecular biologists, will be put forward to highlight their view on development and implemen- tation of tests to study organ function in vivo.
1.2
Objectives
This volume is meant for the general NM practi- tioner, who wants to keep abreast of the latest clini- cal developments as well as the interested student and professional. This volume was not meant as a textbook, but as an addition to these readily avail- able texts. There are three different sections, the first of which deals with clinical applications. Con- trary to other volumes, the clinical point of view is central and comes first, and the state of the art in the major fields is presented. In the second section, the principles upon which these scintigraphic imag- ing techniques are based will be discussed and new trends outlined. The progress in radiopharmaceuti- cals, image acquisition and processing is the main subject of this second section of the book. In the last section, the horizon of genetic imaging is explored and early results in the clinical arena are presented.
Selection of topics in the preparation of this volume is one of the prerogatives of an editor. The emphasis has been put on clinical progress in the field as well as on new modalities that are likely to stay. The typi- cal radiological format was chosen, i.e. review by topology, and mixed with the classic internal medi- cine approach of organ system description.
In the clinical section, standard tests in neuro- logical, cardiac, pulmonary, gastrointestinal, renal, and skeletal scintigraphy are being dealt with. In addition, typical multi-organ fields such as oncol- ogy, infection and inflammation are subjects of detailed review. As in any volume, choices have to be made. In this volume, monoclonal antibodies are not presented in a separate chapter. Although there are some very effective therapy protocols with anti- bodies, just a few diagnostic imaging applications are in use, such as granulocyte imaging, tumor anti- gen imaging, and thrombosis detection. The switch
to smaller molecules such as peptides looks far more promising (see Chaps. 10 and 15).
Positron imaging will be discussed interspersed with single photon imaging for neurologic, cardiac and oncologic applications (Chaps. 2, 3, 6 ,7). Three chapters deal exclusively with positron imaging (Chaps. 11–13).
1.3
Clinical Overview
In the first section, the main organ systems are presented. In Chap. 2 brain imaging is reviewed for clinical entities such as stroke, epilepsy, and degenerative disorders. Neuro-receptors and their potential in neuro-degenerative disease as well as applications in psychiatric illness will be discussed.
The use of emission tomography allows assessment of cerebral blood flow, glucose utilization, oxygen metabolism, rate of incorporation of amino acids into proteins, and rate of transport of substrates into the brain. Measurement of the rate of neuro- transmitter storage, release, and binding to specific receptors is possible, but is not used in clinical prac- tice yet. This possibility has raised high expecta- tions among clinical neurologists and psychiatrists for future developments.
Dysfunctional myocardium in patients with poor left ventricular function can be caused by several mechanisms. The concepts of ”hibernation” and
”stunning”, both representing viable myocardium, are discussed in Chap. 3. Distinction of viable myo- cardium from scar tissue is crucial to determine whether revascularization is a therapeutic option.
The available clinical evidence to assess myocardial viability prior to coronary revascularization is pre- sented. Various techniques are highlighted indicat- ing that viability assessment will lead to the correct use of resources, with the potential of decreasing health care costs.
Pulmonary embolism is a common clinical entity,
and the imaging diagnosis remains a topic of fierce
debate. The emphasis on evidence-based medicine
and outcome significantly affects our thinking
about diagnosis and treatment. ”Do we need to treat
all pulmonary emboli?” and ”How do we identify
the patient in whom the risk of treatment is less
than the risk of no treatment?” are questions posed
in Chap. 4. It is the authors’ firm belief that only new
reasoning will allow us to make progress with diag-
nosis and management of pulmonary embolism.
Studies of the urinary tract are directed to quan- tification of renal flow and function. Various trac- ers are discussed and compared, a detailed analysis is given of how they affect the measured param- eters. The addition of pharmacological augmenta- tion became popular for several existing tests of the GI and the GU tract. These topics are dealt with in Chap. 5 and 8. Hepatobiliary imaging and aug- mentation are now incorporated in a new Chap. 9.
Specific applications for pediatric NM are given in Chap. 14.
Bone scintigraphy has been around for a long time.
It remains an exclusively sensitive procedure for eval- uating a variety of skeletal disorders. Main referrals are detection of metastases, trauma, and orthopedic problems. Sports injuries also appear a major indi- cation for performing bone scans. Some 40 years ago
18
F-fluoride was introduced as a bone imaging agent.
This radiopharmaceutical has been revived since PET systems have become commonplace in the NM clinic.
The PET technique allows for true regional quantifi- cation of bone blood flow (Chap. 6).
Wolfgang Becker, who wrote the previous chapter on infection and inflammation, passed away unex- pectedly. The group of Nijmegen, Netherlands has prepared the text of Chap. 7 for the current edition.
In order to localize an infectious process, we need procedures with high sensitivity for all body regions.
The studies available and their clinical effectiveness are discussed. A typical diagnostic dilemma, posed daily, is the differential diagnosis of inflammation versus infection, e.g. after a surgical procedure. A variety of tracers and clinical conditions are pre- sented, as well as interpretation and reporting of the image findings.
The field of receptor imaging came back in vogue in the 1990s with the introduction of new peptides.
Receptors are proteins, which bind specific ligands, and subsequently respond with a well-defined event.
Historically, these radioligands have evolved from monoclonal antibodies, which are large proteins, via
”molecular recognition units” to small peptides. Rec- ognition of tumor-specific properties can be used to detect cancers, and peptide receptors appear highly expressed on tumor cells. Chapter 10 illustrates that peptides have proven effective in clinical practice.
In the field of oncology, the 1990s showed an emerging role for the glucose analog FDG (2-
18F- fluoro-2-deoxy-D-glucose), which is the most fre- quently used PET radiopharmaceutical. High rates of glycolysis are found in many malignant tumor cells with increased membrane transporters. The uptake of FDG varies greatly for different tumor
types. High uptake is usually associated with a high number of viable tumor cells and/or rapidly prolif- erating cells. Increased FDG uptake is not specific for neoplasms and many inflammatory processes have increased uptake. An overview for the common cancers in the Western world is given in Chap. 11.
The main addition in the current volume is dual modality imaging with PET/CT. The pioneering work of the Zurich group is well known and they present their experience in lung, and head and neck cancer in Chap. 12. The PET/CT experience in lym- phoma, breast, GI, and GYN cancers is discussed in Chap. 13.
Pediatric nuclear medicine has special needs, because of the size and age of the patients. A selec- tion of topics is presented in Chap. 14.
1.4
Basics of Diagnostic Nuclear Medicine
The second section of the book deals with the basics in radiopharmaceuticals, instrumentation and image processing. The potential variety of radiop- harmaceuticals which may be developed is unlim- ited, keeping nuclear medicine in the forefront of clinical imaging. Chapter 15 provides an overview of the developments and trends for the near future.
The technological improvements of the standard gamma camera include higher spatial resolution, better uniformity, higher count rate performance, and multi-detector geometry. New hybrid devices were manufactured for both single photon and coin- cidence imaging, bringing the advantages of PET to the general nuclear medicine clinic. These hybrid devices have been discontinued, and the new trend is merging of standard imaging equipment, e.g.
PET with CT, and SPECT with CT. Combining both imaging modalities in one system, which appeared promising in the previous version of the book, has become reality. CT not only provides images of diag- nostic quality, but is also used for attenuation cor- rection, greatly reducing acquisition time. Clinical applications of dual modality imaging are discussed in Chaps. 12 and 13. Chapter 16 provides a text on instrumentation and data acquisition.
Computer speed tends to double per year, an expo-
nential growth curve that will continue up to the limit
set by physics. New reconstruction techniques will be
discussed and compared, leading to improved image
quality. Iterative reconstruction techniques, and cor-
rection for attenuation and scatter are the standard
4 C. Schiepers
