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Genomic research is expected to generate new types of complex observational data, changing the types of experiments as well as our understanding of biological processes. The investigation and definition of relationships among proteins is essential for understanding the function of each gene and the mechanisms of biological processes that specific genes are involved in. Recently, a study by Paulmurugan et al. demonstrated a tool for in vivo noninvasive imaging of protein-protein interactions and intracellular networks.

Positron emission tomography (PET) has now gained a place in the management of patients with cancer, including those with Hodgkin's disease and non-Hodgkin's lymphoma. Restaging studies and those addressing the monitoring of response to treatment are especially in focus. Most of the knowledge gained has been achieved with dedicated BGO-based PET technology, but there are a number of developments that will impact on the use of this metabolic imaging technique in the investigation of patients with lymphoma. The challenges ahead are determined by the need for high-quality whole-body imaging associated with increased patient throughput and the need to investigate the role of new labelled ligands. The latter are likely to yield new insights into tumour cell characterisation, tumour behaviour and tumour outcome assessment. The study of new radiolabelled ligands will impose further demands for rapid dynamic data acquisition and accurate tracer quantification. Current and future developments in PET technology range from the use of new detector materials to different detector geometries and data acquisition modes. The search for alternatives to BGO scintillation materials for PET has led to the development of PET instruments utilising new crystals such as LSO and GSO. The use of these new detectors and the increased sensitivity achieved with 3D data acquisitions represent the most significant current developments in the field. With the increasing demands imposed on the clinical utilisation of PET, issues such as study cost and patient throughput will emerge as significant future factors. As a consequence, low-cost units are being offered by the manufacturers through the utilisation of gamma camera-based SPET systems for PET coincidence imaging. Unfortunately, clinical studies in lymphoma and other cancers have already demonstrated the limitations of this technology, with 20% of lesions <15 mm in size escaping detection. On the other hand, the recent development of combined PET/CT devices attempts to address the lack of anatomical information inherent with PET images, taking advantage of further improvement in patient throughput and hence cost-effectiveness. Preliminary studies using this multimodality imaging approach have already demonstrated the potential of the technique. Although the potential exists, certain technical issues with PET/CT require refinement of the methodology. Such issues include organ movement (such as respiratory motion), which strongly influences the image fusion of a rapidly acquired CT scan with the slower acquisition of a PET dataset, and the derivation of CT-based attenuation coefficients in the presence of contrast agents or metallic implants. The application of the technology for radiotherapy planning also poses a number of associated challenges. Finally, the development of dedicated PET systems based on planar detector arrangements with new detector components has the potential to improve clinical throughput by over 100%, but clinical trials using such systems have still to be carried out in order to establish the associated whole-body image quality.

Despite the advances made in medical imaging over the past 3 decades and the central role that magnetic resonance imaging and other sophisticated technologies now play in routine clinical practice, patients with rheumatoid arthritis have benefited relatively little from these advances thus far. Over the past few years, however, evidence has accumulated to show that magnetic resonance imaging and ultrasonography can identify joint damage in patients with rheumatoid arthritis earlier and more sensitively than other techniques can, and that these techniques can directly visualize and monitor changes in synovium and bone that precede actual bone erosion. Much of this development is being driven by the pharmaceutical and biotechnology industries as they search for novel therapies to combat this disease. Accordingly, the imaging tools that ultimately will be used to direct patients to specific therapies and then to monitor treatment effectiveness and safety are currently being refined and validated in rigorous multicenter and multinational clinical trials aimed at gaining regulatory approval of these new therapies. As these therapies become available for clinical use, we can anticipate increased demand for expertise and experience in evaluating disease progression and treatment response, and to the emergence of magnetic resonance imaging systems specifically adapted for this application. The following discussion reviews the current status of this development, and notable advances that have been reported in the literature in the past year.

Reliable attenuation correction methods for quantitative emission CT (ECT) require accurate delineation of the body contour and often necessitate knowledge of internal anatomic structure. Two broad classes of methods have been used to calculate the attenuation map: transmission-less and transmission-based attenuation correction techniques. Whereas calculated attenuation correction belonging to the first class of methods is appropriate for brain studies, more adequate methods must be performed in clinical applications, where the attenuation coefficient distribution is not known a priori, and for areas of inhomogeneous attenuation such as the chest. Measured attenuation correction overcomes this problem and uses different approaches to determine this map, including transmission scanning, segmented magnetic resonance images, or appropriately scaled CT scans acquired either independently on separate or simultaneously on multimodality imaging systems. Combination of data acquired from different imagers suffers from the usual problems of working with multimodality images--namely, accurate co-registration from the different modalities and assignment of attenuation coefficients. A current trend in ECT is to use transmission scanning to reconstruct the attenuation map. Combined ECT/CT imaging is an interesting approach; however, it considerably complicates both the scanner design and the data acquisition and processing protocols. Moreover, the cost of such systems may be prohibitive for small nuclear medicine departments. A dramatic simplification could be made if the attenuation map could be obtained directly from the emission projections, without the use of a transmission scan. This is being investigated either using a statistical model of emission data or applying the consistency conditions that allow one to identify the operator of the problem and, thus, to reconstruct the attenuation map. This article presents the physical and methodologic basis of attenuation correction and summarizes recent developments in algorithms used to compute the attenuation map in ECT. Other potential applications are also discussed.

Radionuclide myocardial perfusion imaging (MPI) has been on the rise in Europe and the USA. Details on nuclear cardiology in the Czech Republic are not available as yet, as it is impossible to obtain comprehensive data from official registers owing to different methods of reporting and data evaluation. A questionnaire concerning nuclear cardiology activity and practice in 2001 was sent to all nuclear medicine departments in the Czech Republic. All 48 departments completed the questionnaire. In 2001, 50 planar and 54 tomographic (SPET) scintillation cameras were used. The average age of the SPET cameras was 5 years (13% of SPET cameras were >8 years old). Out of the 48 centres, 39 (81%) provided a nuclear cardiology service; the total number of cardiological studies was 15,740 in 2001 (1.5 studies/1,000 population/year). The most frequently employed method was MPI (81.7%), the frequency of which had increased by 10% compared with 2000; 26 of the 39 (67%) departments reported that MPI activity was increasing. Nevertheless, the Czech Republic nuclear cardiology activity remained below the European average (2.2/1,000 population in 1994) and, particularly, below activity in the USA (15/1,000 in 1997). The activity was rather unevenly spread. Whereas two centres with >1,000 studies/year accounted for 20% of the total MPI studies, 16 of 39 (41%) departments exhibited low activity (<200 studies/year) and accounted for only 15% of the total MPI studies. The use of SPET increased from 91% in 2000 to 94% in 2001 (only three institutes performed planar examinations). The most widely used tracer was (99m)Tc-MIBI (60% of total MPI), followed by (201)Tl (21%) and (99m)Tc-tetrofosmin (19%). ECG-gated SPET was employed by 20/39 (51%) centres, of which 11 (28%) performed it as a standard examination; 39% of the total MPI studies included this technique. Thirteen percent (5/39) of the departments used attenuation correction, and 69% (27/39) of the departments used a prone projection. Equilibrium radionuclide ventriculography, with 2,317 examinations (14.7%), ranked second among all nuclear cardiology methods, followed by first-pass angiocardiography (406 studies, 2.6%) and (18)F-FDG (163 studies, 1%).

Instrumentation for emission computed tomography continues to evolve, taking advantage of developments in detector technology, data processing and correction methods, and reconstruction algorithms. This article reviews the basic principles and latest developments in emission computed tomography instrumentation, for both positron emission tomography and single-photon emission computed tomography applications.

Direct visualization of the composition of the atherosclerotic plaque during its natural history and after therapeutic intervention may be helpful in detecting lesions with high risk of acute events and in understanding progression and regression of the disease. A wide variety of invasive and non-invasive imaging techniques is available to detect clue aspects of atherosclerosis from the early stage to the clinical evidence appearance. We will firstly review the ongoing technological and clinical research on both invasive and non-invasive techniques. Afterward, we will discuss in detail the use of high-resolution, multi-contrast magnetic resonance imaging for non-invasive imaging of the plaque and its characterization in terms of its various components (i.e., thickness, lipid, fibrous, calcium, or thrombus). Finally, we will describe the potential of quantitative analysis in describing of plaque constituents with improved reproducibility.

Positron emission tomography (PET) represents a dramatic advance in the imaging of lung cancer. It is valuable for the diagnosis, staging, prognosis, and restaging of disease, and is most useful in patients considered for potentially curative therapy for non-small-cell lung cancer (NSCLC). In this work the current status and potential future applications of PET scanning in lung cancer are discussed. The relevant literature is also discussed, with an emphasis on studies with clinical applicability. Most of these studies involved the use of 18F-fluorodeoxyglucose (FDG). Numerous studies of the use of PET to assess undiagnosed pulmonary nodules have reported significant improvements in accurate diagnosis or exclusion of malignancy compared to conventional structural imaging alone. All of these studies, including metaanalysis, have shown that PET is more accurate than CT-based structural imaging in staging the mediastinum in surgical candidates. PET may have value in radiotherapy planning, and PET-based staging more accurately predicts survival in radiotherapy-treated patients than conventional staging. The rate of unsuspected distant metastasis detection in stage III disease exceeds 20%. PET also facilitates an accurate assessment of response in patients treated with radical chemoradiation or neoadjuvant therapy prior to surgery. PET has rapidly become an indispensable part of the evaluation of patients with potentially curable lung cancer; however, more work is required to define its role., (Copyright 2003 Wiley-Liss, Inc.)

Software-based image fusion is used routinely for the alignment of functional and anatomical images of the brain. For other parts of the body, image registration is more problematic owing to differences in patient positioning, scanner bed profiles and the involuntary movement of internal organs. An alternative to the software approach is a scanner that acquires both function and anatomy during a single imaging session: a fusion of the technologies rather than a fusion of the images post hoc. Consequently, we designed and built a prototype combined PET and CT scanner comprising a clinical CT and a clinical PET scanner mounted together in a single gantry. Over 300 cancer patients have been imaged in the scanner to establish the clinical value of the combined PET/CT approach. The CT images were used to provide essentially noiseless attenuation correction factors for the PET data. The widespread interest created by the patient studies acquired with the prototype PET/CT stimulated commercial activity and several major vendors of medical imaging equipment now offer combined PET/CT designs. This paper reviews the development of the combined PET/CT scanner, and illustrates the clinical aspects with some typical studies in cancer patients. The potential impact on medical practice of the commercial availability of PET/CT scanner technology at affordable cost is assessed.

Up to a few years ago, positron emission tomography (PET) was known as a very expensive research tool using positron emitting radiopharmaceuticals to study metabolic processes in vivo. Recent developments in detector technology enabled the detection of the distribution of positron emitting radionuclides inside the human body through dual-headed gamma camera systems. These much cheaper cameras did move the focus of PET from research to clinical applications. The improved availability of [(18)F]fluorodeoxyglucose has promoted clinical PET. Ongoing developments in detector and image reconstruction technology may lead to even more accurate imaging in the clinical setting. New applications in diagnosing and staging of cancer patients came across and more will arise. In this paper, we present a short historical overview and a technical introduction of PET.

The imaging of specific molecular targets that are associated with cancer should allow earlier diagnosis and better management of oncology patients. Positron emission tomography (PET) is a highly sensitive non-invasive technology that is ideally suited for pre-clinical and clinical imaging of cancer biology, in contrast to anatomical approaches. By using radiolabelled tracers, which are injected in non-pharmacological doses, three-dimensional images can be reconstructed by a computer to show the concentration and location(s) of the tracer of interest. PET should become increasingly important in cancer imaging in the next decade.

Positron emission tomography (PET) is the most powerful molecular imaging technique currently available for clinical use. The aim of this study was to provide public health information on PET procedures carried out in Germany - a country with a very high number of PET installations. To this end, all facilities that in 1999 were running at least one dedicated PET system were contacted and requested to provide information in a questionnaire on the radiopharmaceuticals applied, the total number and age distribution of patients and volunteers examined, the main diagnostic applications and the range of administered activities. Based on the information provided by 48 of the 60 PET facilities in Germany, an annual frequency of about 0.34 PET procedures per 1,000 inhabitants was estimated, associated with an annual per capita effective dose of about 1.9 micro Sv. Averaged over all PET procedures, the mean effective dose to patients was 5.6 mSv. The age distribution of patients and volunteers was skewed markedly towards higher ages; only a very small fraction (<3%) of patients were children younger than 15 years while older patients, and especially those in the age group between 41 and 65 years, were overrepresented relative to the general population. In total, 28 different PET radiopharmaceuticals were used, with only half of these having been administered to more than 20 patients each. The most frequently applied radiotracer was the glucose analogue 2-[(18)F]fluoro-2-deoxy- D-glucose (FDG), which was utilised in more than 84% of all PET procedures. For this tracer, the median value for activities applied for examinations in the three-dimensional (3D) acquisition mode was only half of that used for two-dimensional (2D) measurements. Based on a statistical analysis of the distribution of mean FDG activities administered to patients in the 48 PET facilities who responded to our inquiry, diagnostic reference levels of 370 and 200 MBq are proposed for the 2D and the 3D mode, respectively.

Background: Positron emission tomography (PET) is an emerging imaging modality that is being investigated for use in urologic oncology. PET scanning using the radioactive glucose analog FDG has proven to be a highly accurate imaging test for diagnosing and staging a variety of non-urologic cancer types. This review was performed to determine the role of PET imaging in genitourinary malignancies., Methods: A review of the literature focusing on PET and urologic oncology was performed. The role of PET imaging was reviewed in prostate, bladder, renal, and testicular cancer., Results: In testicular cancer, PET has a higher diagnostic accuracy than computed tomography (CT) for both staging and re-staging and should be the test of choice for the assessment of a CT-visualized residual mass following chemotherapy. In prostate, renal, and bladder cancer, the current role of PET is still being defined, but it has a high positive predictive value and can be used for problem solving in patients with indeterminate findings on conventional imaging. Its role in the diagnosis and staging of prostate cancer is hampered by the generally low glycolytic rate of most prostate tumors and their metastases. It has shown promise for staging and re-staging patients with advanced-stage disease and aggressive tumors suspected by a high tumor grade and high prostate-specific antigen velocity. PET has also demonstrated success when applied to renal cell carcinoma in classifying indeterminate renal masses as well as residual renal fossa masses following nephrectomy, gauging response to therapy, and staging and re-staging patients with a known diagnosis of renal cell carcinoma., Conclusions: PET imaging has demonstrated great potential in certain applications, but further investigations are necessary to determine its eventual place as an imaging modality in genitourinary malignancies.

Recent advances in the technology of non-invasive neuroimaging techniques, include X-ray CT, magnetic resonance imaging, positron CT, etc. The trend of neuroimaging is from the diagnosis of the brain structural change to the functional localization of the brain function with accurate topographical data. Brain activation studies disclosed the responsible regions in the brain for various kinds of paradigms, including motor, sensory, cognitive functions. Another aspect of brain imaging shows the pathophysiological changes of the neurological disorders, such as Alzheimer's disease by abnormal CBF or metabolism changes. It is very important to note that the neurotransmitter receptor imaging is now available for various kinds of transmitters. We recently developed a new tracer for nicotinic type acetylcholine receptor, which might be involved in the pathophysiology of Alzheimer's disease and its treatment. In the near future, we will be able to visualize the proteins in the brain such as amyloid protein, which will make us to diagnose Alzheimer's patients accurately, and with respect to neuroscience research, not only neuronal functional localizations but also relationship between them will become important to disclose the functional aspects of the brain.

For the past years, substantial amount of experimental data has been published on the use of positron emission tomography in different psychiatric disorders. The different PET methods, which evaluate the whole-brain or regional metabolism, tissue perfusion or receptor density may help to identify the disorder specific changes in brain function and also better understand the underlying pathophysiology. In the clinical practice, PET plays an important role in the diagnosis and differential diagnosis of dementias and, presumably, in the near future the PET technique will be also extensively used in the clinical examination of other psychiatric disorders.

Nowadays, a growing number of research groups shows a great interest for the application of PET and SPECT techniques to the development of new drugs. Preliminary studies on small animals require high performance dedicated scanners with a higher spatial resolution and sensitivity than those of clinical systems. In this paper the potential applications of such innovative instruments are shown together with a brief review of the dedicated PET and SPECT tomographs developed worldwide. Most of the scanners have been built as research prototypes. Only two are commercially available: micro-PET(R), designed and developed at UCLA, Los Angeles as a research prototype, and now produced and distributed by Concorde Microsystems Inc. (USA) and HIDAC PET produced by Oxford Positron Systems Ltd. (UK). Also in Italy, a high performance tomograph, YAP-(S) PET able to perform both PET and SPECT studies, has been developed at the University of Ferrara. The technical characteristics and performance of this scanner are described. Tomographs with combined imaging techniques, such as PET/CT or SPECT/CT, are now under study in various international research centers. The advantages of this new generation of animal scanners will be briefly outlined.

Diagnosis and follow-up in clinical oncology are traditionally based on computed tomography (CT). In recent years, however, functional imaging using positron emission tomography (PET) has been recognized as an important imaging modality and adjunct to CT that provides complementary metabolic information in many oncology applications. To overcome the challenges of aligning independently acquired PET and CT image sets several ad hoc concepts of integrating PET and CT imaging in a single device have been proposed. This article comments on the development of the first combined dual-modality PET/CT prototype at the University of Pittsburgh, and illustrates commercial advances to dual-modality PET/CT tomography. The current PET/CT designs from the major manufacturers comprise a commercial CT scanner in tandem with a commercial PET scanner. While the level of physical integration is actually less than that of the original prototype it is fair to assume that current PET/CT models may serve as intermediate solutions towards near-future design concepts that aim at greatly reduced costs of the dual-modality tomographs and offer a greater level of physical integration. The goal of the next generation of PET/CT systems is to design and build a device specifically for imaging the function and anatomy of cancer in the most informative and effective way without necessarily conceptualizing it as combined PET and CT scanners. Such a concept of a diagnostic imaging device relates more to a disease management approach rather than the usual division into medical specialities such as radiology and nuclear medicine.

In oncology drug development there is an increasing need for the in vivo physiological measurement of changes in tumour blood flow in response to therapy. Positron Emission Tomography (PET) is being increasingly used in oncology patients to measure blood flow. Here we review the clinical use of PET to measure vascular parameters in man.

The tumor-seeking agent most widely used in positron emission tomography (PET) is 2-(18)F-fluorodeoxy-D-glucose (FDG). The clinical usefulness of FDG PET has already been proved in detecting, staging and restaging various kinds of malignant tumors, but nuclear medicine physicians suffer from a "diagnostic dilemma," in which a relatively high false positive ratio of FDG PET in diagnosing malignant tumors prevails. To increase more specific tumor uptake or more specific tumor characterization, numerous PET radiopharmaceuticals have been developed, and some of them are being tested in clinical trials. This review will briefly survey the tumor uptake mechanism and clinical significance of representative non-FDG PET radiopharmaceuticals used in clinical trials for patients with cancers.

The glucose analogue 18F-deoxyglucose allowed for the first time the ability to noninvasively probe and characterize the regional metabolism of glucose as a major fuel substrate of the human heart. Used with positron emission tomography, it became the tool for demonstrating the operation of metabolic processes, long before established in invasive or destructive experiments in animals, directly in the human myocardium. Clinical investigations with 18F-deoxy-glucose, combined with other radiotracers of the myocardium's substrate metabolism, showed the dependency of the heart's substrate selection on circulating levels of glucose, free fatty acid and insulin, and the operation of Randle's cycle in the human myocardium. Regional responses in substrate metabolism to the myocardial ischemia were now visualized entirely noninvasively as, for example, decreases in fatty acid usage and oxidation and oxygen consumption, but foremost as an increase in glucose use. Regional 18F-deoxyglucose uptake markedly in excess of myocardial blood flow in dysfunctional myocardium of patients after a myocardial infarction, with chronic coronary artery disease or with ischemic cardiomyopathy, soon became recognized as a hallmark of myocardial viability or potentially reversible contractile dysfunction. Defined as blood flow metabolism mismatch, this particular regional glucose uptake pattern identifies patients to be at high risk for cardiac events and, at the same time, to benefit most from surgical revascularization. The patterns predict a postrevascularization improvement in global left ventricular function and, even more important, in symptoms related to congestive heart failure and in long-term survival. 18F-deoxyglucose is now widely used with positron emission tomography and, more recently, with single photon emission computed tomography and radiotracers of myocardial perfursion for stratifying ischemic cardiomyopathy patients to the most efficacious treatment.

Positron emission tomography (PET) is an intrinsically quantitative method that provides an approach for the clinical cardiologist and cardiovascular researchers to evaluate the heart noninvasively. The ability to label biomolecules with positron-emiting radioisotopes, without disturbing their physiological properties, offers the opportunity to prove and quantify coronary blood flow, myocardial metabolism, and the alterations that occur with disease states. However, the major drawback prohibiting implementation of PET imaging in clinical routine is the limited availability of PET equipment and its greater cost per study. In order to enhance cost savings and resource efficiency in clinical practice, PET studies should be limited to those patients with equivocal studies by other imaging modalities or to define areas of potential viability and improve decisions for recommending coronary bypass grafting or cardiac transplantation. The combined data of multiple investigators suggest that 18-FDG-SPECT imaging may become the protocol of choice for determining myocardial viability because of its increased availability and cost-effectiveness as compared to PET.

Whole-body positron emission tomography (PET) imaging with (18)F deoxyglucose (FDG) is a molecular imaging modality that detects metabolic alterations in tumor cells that are common to neoplastic cells. FDG-PET has recently been approved by the Health Care Finance Administration for Medicare reimbursement for diagnosing, staging, and restaging lung cancer, colorectal cancer, lymphoma, melanoma, head and neck cancer, and esophageal cancer. This review discusses the scientific evidence that led to the emergence of PET imaging as an accepted clinical tool in patients with solitary pulmonary nodules, lung cancer, colorectal cancer, melanoma, lymphoma, breast cancer, and other cancers. When possible, we compare the performance of PET to that of anatomical imaging. We discuss future clinical applications of this imaging modality.

During the past ten years, positron emission tomography (PET) has been increasingly developed for imaging and quantifying molecular mechanisms in oncology. The technique uses radionuclides to label molecules, which can then be imaged in man. The inherent sensitivity and specificity of PET is unrivalled because it can image molecular interactions and pathways, providing quantitative kinetic information down to the subpicomolar level. This technology has the potential to answer a large number of important clinical questions in translational research in oncology. However, the challenges in the methodology are substantial. Molecular imaging has the potential to assist in the optimization of molecular-based targeted therapies in cancer and to investigate the function of the genome.