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Integrated PET/CT is a new anatomo-metabolic imaging modality combining two different techniques: Computed Tomography (CT) that provides very detailed anatomic information and Positron Emission Tomography (PET) that provides metabolic information. Integrated PET/CT has several advantages. One of the advantages is the use of CT data for attenuation correction that is significantly faster compared to that in conventional PET systems. Due to the use of CT data for attenuation correction, artefacts can be generated on PET images related to the use of intravenous or oral CT contrast agents, CT beam-hardening artefacts due to metallic implants and motion artefacts (respiratory motion, physical bowel motion, cardiac motion). The purpose of this review is to discuss some technical considerations concerning the CT protocol that can be used for PET/CT in lung cancer imaging and to give a short overview of the initial results of staging of non-small cell lung cancer (NSCLC).

The rapid expansion of modern molecular imaging methods since the time of their initial conception in the 1970s has given rise to numerous discoveries of molecular mechanisms that underlie brain function in health and disease. Uses in clinical diagnosis and therapy monitoring are still evolving. Future clinical trials, in which molecular imaging is imbedded and correlated with clinical outcomes, will be critical to advancing new uses for patient management. Receptor occupancy studies are already well integrated into many drug development studies and clinical trials; such studies will provide a basis for new studies that will further advance clinical uses of brain molecular imaging.

This article traces the evolution of medical imaging, from the crude images of the thyroid gland obtained using Geiger and scintillation counters, to the automatic scanners built to image brain tumors and organs, to gamma cameras, to digital imaging. A computed tomography scanner built in Aberdeen in the late 1960s led to the present-day gamma-camera tomographs, the main workhorse of nuclear medicine. The gradual evolution of the steps needed for clinical magnetic resonance imaging (MRI) are described, along with the rapid development of this novel form of body imaging. A brief account is also given of the present-day use of MRI in clinical medicine worldwide, with some modern cutting-edge applications, and its possible future.

After middle cerebral artery occlusion (MCAO) in the laboratory animal, the ischemic penumbra has been documented as a severely hypoperfused, functionally impaired, but still viable cortex which can regain its function and escape infarction if it is reperfused before a certain time has elapsed. The penumbra surrounds the ischemic core of already irreversibly damaged tissue, and is progressively recruited into the core with increasing MCAO duration. In the animal, the threshold of cerebral blood flow (CBF) below which neuronal function is impaired and the tissue is at risk of infarction is around 22 ml/100 g/min (approximately 40% of normal) in the awake or lightly anesthetized monkey, and around 30--35 ml/100 g/min in the cat and the rat. The threshold of CBF below which the tissue becomes irreversibly damaged and will progress to infarction depends on the duration of ischemia, and is around 10 ml/100 g/min for 1--2 h (approximately 20% of normal) and around 18 ml/100 g/min for permanent ischemia in the monkey. Mildly reduced CBF down to the 40% threshold (termed 'oligemia') is normally well tolerated, and the affected tissue is not at risk of infarction under uncomplicated conditions (in the animal, however, selective neuronal death may occur even with only mildly reduced CBF values, but this sequela of stroke seems an exceptional encounter in man). Classic studies with carotid artery clamping in man have provided estimates for the penumbra threshold at around 20 ml/ 100 g/min for the whole brain, but only recently have imaging studies allowed to document the existence of the penumbra in acute stroke and given estimates of local CBF thresholds. With PET, the penumbra is characterized by a reduced CBF, an increased oxygen extraction fraction, and a relatively preserved oxygen consumption (CMRO(2)). In a series of PET studies performed 5--18 h after stroke onset, we have determined the threshold for penumbra to be around 20 ml/100 g/min, and documented that the extent of neurological recovery is proportional to the volume of penumbra that eventually escaped infarction. Within this time interval, the thresholds for irreversible damage were around 8 ml/ 100 g/min for CBF and around 0.9 ml/100 g/min for CMRO(2). Recent studies with diffusion-weighted and perfusion MR have reported similar relative thresholds for CBF of about 50 and 18% for penumbra and core, respectively. Although it is likely that the threshold for irreversibility will be lower with shorter duration since clinical onset, this has not been documented thus far. Because saving the penumbra will improve clinical outcome, it should constitute the main target of acute stroke therapy. We found evidence of penumbra in about one third of the cases studied between 5 and 18 h after onset, and as late as 16 h after symptom onset in occasional patients, suggesting the therapeutic window may be protracted in at least a fraction of the cases; similar experience has recently accrued from diffusion-weighted MR and perfusion MR. In the remaining patients, there was evidence of early extensive damage or early spontaneous reperfusion, which would make them inappropriate candidates for neuroprotective therapy. Recent evidence from PET studies of relative perfusion performed within 3 h of onset suggests that early thrombolysis indeed saves the tissue with CBF below a critical threshold of 12 ml/ 100 g/min, with a correlation between the volume of such tissue escaping infarction and subsequent neurological recovery. Thus, mapping the penumbra in the individual patient with physiologic imaging should allow to formulate a pathophysiological diagnosis, and in turn to design a rational management of the stroke patient and to increase the sensitivity of drug trials by appropriate patient selection., (Copyright 2001 S. Karger AG, Basel)

The origins of positron emission tomography (PET) date back 70 years. Since the 1970s, however, its use has increased exponentially in the fields of neurology, cardiology and oncology. [18F]-Fluorodeoxyglucose (FDG) whole-body scanning is by far the most widely utilised and recognised application of PET in oncology. However, PET is a very versatile and powerful imaging modality capable of helping bridge the gap between the laboratory and the clinic. This article reviews the history and current applications of PET in oncology and then explores some of the newer applications and potential future uses of this versatile technology particularly in the area of cancer research.

The historical background at the University of Michigan laid a foundation for the innovative development of radionuclides in diagnosis and treatment of endocrine diseases. From that background, Dr. William Beierwaltes, the chief of Nuclear Medicine, inspired two talented young chemists to synthesize unique radiopharmaceuticals that transformed diagnostic approaches to certain endocrine disorders. Dr. Raymond Counsell's 131-I-radiocholesterol, enabled imaging that defined function in the adrenal cortex, and thereby distinguished the different forms of Cushing's syndrome and of primary aldosteronism; in addition, this new technique differentiated benign adrenal cortical adenomas from other adrenal cortical tumors. Dr. Donald Wieland created metaiodobenzlylguanidine (MIBG), a compound that can be tagged with either 131-I or 123-I, and led to the scintigraphic depiction of adrenergic tumors, particularly pheochromocytomas and neuroblastoma, anywhere in the body of a patient. Treatments with large doses of MIBG have reduced the malignant forms of pheochromocytomas and brought remissions to children with neuroblastomas. MIBG also concentrated in the autonomic neurons and so the nerves of the heart were also portrayed. Subsequent novel syntheses included positron-emitting nuclides that, through positron emission tomography, have revealed the physiology and altered physiology of the human heart. These men and their discoveries exemplify the creative endeavors that compel us to seek further the wonders of nuclear science.

The historical role of the French Neurology in the development of anatomo-clinical method is likely to explain why the first communications on electrophysiology were presented in Paris with some delay, as compared with other european societies where the neurophysiological tradition had been more lively. Though clinical neurophysiology, by essence, addresses the pathophysiology of neurological disorders, it has sometimes missed this target at its very beginning, when it aimed at providing data supposed to have some aetiological specificity, causing distrust among neurologists used to accept aetiological diagnosis only when based on post-mortem anatomical evidence. Thanks to the discovery of computerized tomography this time has been over for 25 years, and no one would question anymore the role of clinical neurophysiology and neuroimaging in Neurology, the former giving access to the timing of sensori-motor and cognitive pocesses and the latter to the localization of brain functions. This article reviews the neurophysiological literature published in the Revue Neurologique from 1948 to 1998.

At the forefront of cognitive neuroscience research in normal humans are the new techniques of functional brain imaging: positron emission tomography (PET) and, more recently, magnetic resonance imaging (MRI). The signal used by PET is based on the fact that changes in the cellular activity of the brain of normal, awake humans and laboratory animals are accompanied almost invariably by changes in local blood flow. This robust, empirical relationship has fascinated scientists for well over a hundred years. PET provided a level of precision in the measurement of blood flow that opened up the modern era of functional human brain mapping. Further, the discovery with PET that these changes in blood flow are unaccompanied by quantitatively similar changes in oxygen consumption has paved the way for the explosive rise in the use of MRI in functional brain imaging. The remarkable success of this enterprise is a fitting tribute to men like Michel Ter-Pogossian. He pioneered the use of positron emitting radionuclides in biology and medicine when most had abandoned them in favor of more conventional nuclear medicine radionuclides. Importantly, also, he welcomed into his laboratory young scientists with a broad range of talents, many of whom subsequently became leaders in imaging the mind in research centers throughout the world.

The development of positron emission tomography (PET) illustrates how advances in basic science translates into benefits for human beings. In 1930 Ernest Lawrence and co-workers conceived of the cyclotron. By 1938 Lawrence, Livingston, et al had designed a "medical cyclotron." The subsequent production of C-11, N-13, O-15, and F-18 found many uses in medical and physiologic research. The introduction of F-18 deoxyglucose represents another major step toward practical clinical use of positron-emitting tracers. We have now achieved the transition from the postulation of the existence of positrons to their use in a wide variety of diseases.

Positron Emission Tomography (PET) is a method for determining biochemical and physiological processes in vivo in a quantitative way. This includes the measurement of the pharmacokinetics of labeled drugs and the measurement of the effects of drugs and/or therapy on metabolism. Also deviations of normal metabolism can be measured and insight in biological processes responsible for diseases can be obtained. To accomplish these measurements a multi-disciplinary team is necessary for the expertise in the fields of radionuclide production, radiochemistry, pharmacy, medicine, nuclear imaging and data analysis.

Shortly before the time of this writing, Michael Ter-Pogossian, PhD, passed away at the age of 71. He was considered by many to be the father of PET and is best known for experiments beginning in the 1950s, which led to the development of PET as a practical diagnostic tool (Fig. 1). In my research of the literature for this article, Dr. Ter-Pogossian's name appeared frequently on many of the landmark publications and I have drawn heavily from his work as a historian and scientist. His death is a great loss to the nuclear medicine community. It is with his achievements in mind, as well as the achievements of many other outstanding scientists, that I have written this article. I have tried to be as accurate as possible in my documentation of events as well as in my interpretation of their significance. I trust that the reader will gain as much as I have from this endeavor.

Nuclear Medicine is the application of radioactive materials to the diagnosis and treatment of patients and the study of human disease. The field had its beginning with the discovery of radioactivity by H. Becquerel in 1896 and the tracer principle proposed in 1913 by G. de Hevesy who used a naturally occurring radioactive isotope of lead to obtain information regarding certain aspects of calcium metabolism in plants. The actual development is more recent. F. and I. Joliot-Curie just after the discovery of the artificial radioactivity predicted in their visionary Nobel conference in 1935 the future applications of radioisotopes in biology and medicine. The development of Nuclear Medicine was made possible by the possibility of producing routinely the radioisotopes after World War II and by the development of suitable detectors: moving detector devices (scanners) then gamma cameras after 1957. Nuclear Imaging is today a unique tool for the in vivo investigation of the biochemical functioning of an organ. Two techniques are in rapid development, SPECT (single photon emission computed tomography) and PET (positron emission tomography).

Imaging technology for medical diagnostic purposes had its beginning with the discovery of x rays in 1895. Over the past 100 years, the technological advances of x-ray tubes, power generation, imaging detectors, imaging techniques, nuclear medicine, magnetic resonance, and ultrasound have been astounding. A look back at where we have been, where we are, and in some instances where we are going with respect to a range of imaging technologies is the focus of this paper.

The purpose of this paper is to follow the course of historical development in the use of radiopharmaceuticals as a diagnostic tool in nuclear medicine. This course has been a series of plateaus and growth spurts throughout its history. This article is designed to identify the different phases of the development of nuclear medicine, pointing out the events which most shaped its history along the way. Those events included such things as the discovery of radioactivity, the development of the cyclotron and nuclear reactor as a method of producing high specific activity radioactive material, the development of imaging equipment such as the rectilinear scanner, scintillation camera, PET and SPECT, the application of computers, and the discovery of 99mTc and the development of associated kits designed to image many organs and processes in the human body.

Nuclear medicine translates advances in molecular biology into the care of patients. In the future, diseases will be characterized at the molecular rather than the cellular level, often before detectable structural changes have occurred. Position emission tomography (PET) will play a major role in the study of intercellular communication by making it possible to characterize the actions of "molecules with messages." Diseases will be characterized by defects in intercellular communication. Treatment will be planned based on molecular abnormalities, and the response to treatment will be monitored with molecular probes. PET studies of the brain, heart, and cancer will be extended to all organs of the body. Pharmacology will be strongly influenced by PET because most drugs act by stimulating or blocking "recognition sites" on the surface of cells. In the next century, will single photon emission computed tomography (SPECT) makes PET unnecessary? The answer is no, because both PET and SPECT will have achieved a permanent role in medical practice; both make it possible to examine regional in vivo chemistry in human beings. Carbon-11 and fluorine-18 will continue to lead the way, but many drugs, and some body constituents such as proteins, can be radiolabeled with iodine-123 and technetium-99m. Today, PET is limited by the need to make one's own radiotracers. This is likely to change when regional radiopharmacies become widespread.(ABSTRACT TRUNCATED AT 250 WORDS)

Computed tomography (CT) was a revolution in radiology. Commercially available CT scanners appeared in 1972, a joint effort between the EMI Company, Atkinson Morley's Hospital, London and the Department of Health and Social Security (DHSS). The name of Sir Godfrey Hounsfield will always be associated with these developments. Like most developments in science the breakthrough came by standing on the shoulders of giants and many experiments can, with the curious wisdom of hindsight, be considered precursors to CT. Gabriel Frank's patent in 1940 showed apparatus for back-projection CT and Takahashi developed equipment in the 1940s for reconstructing from a sinogram; in both cases using an optical "computer". A medical CT scanner was reportedly constructed in 1957 in Kiev. Transmission CT was performed by Kuhl in 1965. Cormack built an experimental scanner in 1963. Oldendorf identified what was needed for successful CT as early as 1960. Throughout the 1960s a host of independent workers were busy on the mathematical problems of reconstructing from projections with both medical scanning and non-medical applications in mind. Experiments in early emission tomography influenced the development of CT. With imagination one can even see how close "classical" tomography, as started even before 1920, came to the realization of CT. The pioneering British radiographer Watson stands out from a galaxy of inventors. The lecture at Radiology and Oncology '91 in Brighton was a thumbnail sketch of the origins of radiological CT. A fuller story is told elsewhere (Webb, 1990).

The development of positron emission tomography (PET) took place through the combination of the following recognitions: (1) a handful of short-lived, positron-emitting radionuclides, carbon-11, nitrogen-13, and oxygen-15, exhibit chemical properties that render them particularly suitable for the tracing of important physiological pathways, and (2) the radiation emitted as a result of the annihilation of positrons in matter exhibited physical properties that made it well-suited for nuclear medicine imaging, particularly for tomographic reconstruction. The scientific building blocks that were necessary for the structure of PET were contributed over a period of several decades by many investigators in physics, mathematics, chemistry, and fundamental biology.

The invention of the Anger scintillation camera and the development of 99mTc tracers brought about a tenfold increase in nuclear brain scanning between 1963 and 1973, an increase that plateaued with the introduction of x-ray computed tomography. A second growth curve began in 1976 at which time there were four PET centers in the United States, a number that grew to 60 worldwide over the next decade. PET, SPECT, MRI, and MRS are leading us into a new era of in vivo brain chemistry, based on regional bioenergetics and neurotransmission. The immediate impact is in epilepsy, stroke, brain tumors and the dementias, with psychiatric diseases becoming a major focus of research. Receptivity has become a biochemical as well as a psychological approach to mental functions. The finding of elevated D2 dopamine receptors in schizophrenia in living patients may be the forerunner of a new biochemical approach to psychiatry.