Melanoma patients evaluated by four different positron emission tomography reconstruction techniques

One hundred and nineteen patients with malignant melanoma were studied using 2-[ F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET). The images were reconstructed using ordered subset expectation maximization with and without attenuation correction and filtered backprojection with and without attenuation correction. The most probable draining lymph node chains were surgically explored and the tumour volume was quantified at histology. The four different reconstructions of the PET images were retrospectively graded on a five-point scale by two blind readers and compared with the tumour volume. The readers agreed within +/-1 grade 93% (529/568) of the time. Comparing the areas under the receiver operating characteristic (ROC) curves gave 0.698, 0.668, 0.694 and 0.684 for the four reconstruction techniques. The lowest value comparing any pair of the four reconstruction techniques was P=0.371. Thus, none of the reconstruction techniques gave significantly better results than any of the others. The sensitivity of detection was 85% for tumour volumes of 113 m or more (about 6 mm in diameter), but only 4% for tumours less than this size. It can be concluded that the use of attenuation correction gives aesthetically more pleasing images, but the sensitivity and specificity are not significantly improved.     

Radiation-induced meningioma evaluated with positron emission tomography with fludeoxyglucose F 18.

We describe a patient with radiation-induced meningioma 12 years after cranial irradiation for ectopic germinoma. PET scans with fludeoxyglucose F 18 showed a high glucose metabolic rate in the meningioma despite a benign histologic appearance.     

18F-Fluoride positron emission tomography and positron emission tomography/computed tomography

(18)F-Fluoride is a positron-emitting bone-seeking agent, the uptake of which reflects blood flow and remodeling of bone. Assessment of (18)F-fluoride kinetics using quantitative positron emission tomography (PET) methods allows the regional characterization of lesions of metabolic bone diseases and the monitoring of their response to therapy. It also enables the assessment of bone viability and discrimination of uneventful and impaired healing processes of fractures, bone grafts and osteonecrosis. Taking advantage of the favorable pharmacokinetic properties of the tracer combined with the high performance of PET technology, static (18)F-fluoride PET is a highly sensitive imaging modality for detection of benign and malignant osseous abnormalities. Although (18)F-fluoride uptake mechanism corresponds to osteoblastic activity, it is also sensitive for detection of lytic and early marrow-based metastases, by identifying their accompanying reactive osteoblastic changes, even when minimal. The instant fusion of increased (18)F-fluoride uptake with morphological data of computed tomography (CT) using hybrid PET/CT systems improves the specificity of (18)F-fluoride PET in cancer patients by accurately differentiating between benign and malignant sites of uptake. The results of a few recent publications suggest that (18)F-fluoride PET/CT is a valuable modality in the diagnosis of pathological osseous conditions in patients also referred for nononcologic indications. (18)F-fluoride PET and PET/CT are, however, not widely used in clinical practice. The limited availability of (18)F-fluoride and of PET and PET/CT systems is a major factor. At present, there are not enough data on the cost-effectiveness of (18)F-fluoride PET/CT. However, it has been stated by some experts that (18)F-fluoride PET/CT is expected to replace (99m)Tc-MDP bone scintigraphy in the future.     

The origins of positron emission tomography.

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.     

Kinetic modeling in positron emission tomography.

Most PET kinetic modeling approaches have at their basis a compartmental model that has first-order, constant coefficients. The present article outlines the one-, two-, and three-compartment models used to measure cerebral blood flow, cerebral glucose metabolism, and receptor binding, respectively. The number of compartments of each model is based on specific knowledge of the physiological and/or biochemical compartments into which the tracer distributes. Additional physical and biochemical properties of the tracer distribution are considered in specifying the use of first-order rate constants. For example, in cerebral blood flow and receptor binding studies transport across the blood-brain barrier by diffusion can be modeled as a first-order process. A saturable carrier-mediated process or saturable enzyme catalyzed reaction, when tracer doses of the labeled substrate are used and the natural substrate is in steady-state, also results in first-order rate constants, as in glucose metabolism studies. The rate of ligand binding, on the other hand, depends on the concentrations of both substrate and available receptors. In order to appropriately model the reaction as pseudo first-order during a specified experimental interval, protocols are carefully designed to assure that the number of available binding sites remains approximately constant throughout the given interval. A broad array of scanning protocols is employed for kinetic analyses. These include single-scan approaches, which function like their autoradiographic counterparts in animal studies and are often called "autoradiographic" methods, which allow estimation of a single parameter. Dynamic scanning to obtain the time course of tissue activity allows simultaneous estimation of multiple parameters. Scanning may be conducted during a period of tracer uptake or after attainment of steady-state conditions. All quantitative modeling approaches share the common requirement that an arterial input function be measured or an appropriate surrogate be found. A vast array of methods is available for estimation of model parameters, both micro and macro. In the final analysis, it is the interaction among all elements of the PET study, including careful tracer selection, model specification, experimental protocol design, and sound parameter estimation methods, that determines the quantitative accuracy of the estimates of the physiological or biochemical process under study.     

Performance standards in positron emission tomography.

A standard set of performance measurements is proposed for use with positron emission tomographs. This set of measurements has been developed jointly by the Computer and Instrumentation Council of the Society of Nuclear Medicine and the National Electrical Manufacturers Association. The measurements include tests of spatial resolution, scatter fraction, sensitivity, count rate losses and randoms, uniformity, scatter correction, attenuation correction, and count rate linearity correction.     

Improved positron emission tomography quantification by Fourier-based restoration filtering.

Positron emission tomography (PET) images are characterized by both poor spatial resolution and high statistical noise. Conventional methods to reduce noise, such as local weighted averaging, produce further deteriorations in spatial resolution, while the use of deconvolution to recover resolution typically amplifies noise to unacceptable levels. We studied the use of two-dimensional Fourier filtering to simultaneously increase quantitative recovery and reduce noise. The filter was based on inversion of the scanner's measured transfer function, coupled with high frequency roll-off. In phantom studies, we found improvements in both "hot" and "cold" sphere quantification. Compared with ramp-only filtering, improvements in hot spot recovery for the highest accuracy filter averaged 13.6% +/- 6.6% for spheres larger than 15 mm; improvements in cold spot recovery averaged 30.7% +/- 4.7%. At the same time, the noise was reduced by a factor of 3 compared with randomly filtering. Fourier-based image restoration filtering is thus capable of improving both accuracy and precision in PET.     

Fundamentals of positron emission tomography

Positron emission tomography is a modern radionuclide method of measuring physiological quantities or metabolic parameters in vivo. The method is based on: (1) radioactive labelling with positron emitters; (2) the coincidence technique for the measurement of the annihilation radiation following positron decay; (3) analysis of the data measured using biological models. The basic aspects and problems of the method are discussed. The main fields of future research are the synthesis of new labelled compounds and the development of mathematical models of the biological processes to be investigated.     

Cardiac positron emission tomography imaging

Cardiac positron emission tomography (PET) imaging has advanced from primarily a research tool to a practical, high-performance clinical imaging modality. The widespread availability of state-of-the-art PET gamma cameras, the commercial availability of perfusion and viability PET imaging tracers, reimbursement for PET perfusion and viability procedures by government and private health insurance plans, and the availability of computer software for image display of perfusion, wall motion, and viability images have all been a key to cardiac PET imaging becoming a routine clinical tool. Although myocardial perfusion PET imaging is an option for all patients requiring stress perfusion imaging, there are identifiable patient groups difficult to image with conventional single-photon emission computed tomography imaging that are particularly likely to benefit from PET imaging, such as obese patients, women, patients with previous nondiagnostic tests, and patients with poor left ventricular function attributable to coronary artery disease considered for revascularization. Myocardial PET perfusion imaging with rubidium-82 is noteworthy for high efficiency, rapid throughput, and in a high-volume setting, low operational costs. PET metabolic viability imaging continues to be a noninvasive standard for diagnosis of viability imaging. Cardiac PET imaging has been shown to be cost-effective. The potential of routine quantification of resting and stress blood flow and coronary flow reserve in response to pharmacologic and cold-pressor stress offers tantalizing possibilities of enhancing the power of PET myocardial perfusion imaging. This can be achieved by providing assurance of stress quality control, in enhancing diagnosis and risk stratification in patients with coronary artery disease, and expanding diagnostic imaging into the realm of detection of early coronary artery disease and endothelial dysfunction subject to risk factor modification. Combined PET and x-ray computed tomography imaging (PET-CT) results in enhanced patient throughput and efficiency. The combination of multislice computed tomography scanners with PET opens possibilities of adding coronary calcium scoring and noninvasive coronary angiography to myocardial perfusion imaging and quantification. Evaluation of the clinical role of these creative new possibilities warrants investigation.     

Imaging the islet graft by positron emission tomography

Clinical islet transplantation is being investigated as a permanent cure for type 1 diabetes mellitus (T1DM). Currently, intraportal infusion of islets is the favoured procedure, but several novel implantation sites have been suggested. Noninvasive longitudinal methodologies are an increasingly important tool for assessing the fate of transplanted islets, their mass, function and early signs of rejection. This article reviews the approaches available for islet graft imaging by positron emission tomography and progress in the field, as well as future challenges and opportunities.     

Assessment of myocardial viability by positron emission tomography

Accurate assessment of myocardial viability is critical for identifying patients likely to benefit from coronary revascularization. Positron emission tomography (PET) has several advantages over single photon emission computed tomography (SPECT), including higher sensitivity and specificity, as well as the ability to measure myocardial blood flow and myocardial metabolism in absolute terms, which is important in understanding the pathophysiology of ischemic cardiomyopathy. The most commonly used PET tracer is [18F]2-fluoro-2deoxy-D-glucose (FDG). The dependence of ischemic myocardium on glucose metabolism makes FDG an ideal tracer in this setting. Studies have shown positive and negative predictive values for the detection of viable myocardium in the range of 48-94%, and 73-96%, respectively. FDG is superior to SPECT using thallium or technetium myocardial perfusion agents, as well as echocardiography with dobutamine infusion. FDG PET also provides important prognostic information. Patients with evidence of myocardial viability by FDG PET have fewer cardiac events and survive longer if revascularized compared to patients who are treated medically. This article will review myocardial metabolism, PET procedures and interpretive criteria, as well as problems and limitations. Data from the literature regarding diagnostic and prognostic information will also be summarized.     

Imaging pancreatic islet cells by positron emission tomography

It was estimated that every year more than 30000 persons in the United States - approximately 80 people per day - are diagnosed with type 1 diabetes (T1D). T1D is caused by autoimmune destruction of the pancreatic islet (β cells) cells. Islet transplantation has become a promising therapy option for T1D patients, while the lack of suitable tools is difficult to directly evaluate of the viability of the grafted islet over time. Positron emission tomography (PET) as an important non-invasive methodology providing high sensitivity and good resolution, is able to accurate detection of the disturbed biochemical processes and physiological abnormality in living organism. The successful PET imaging of islets would be able to localize the specific site where transplanted islets engraft in the liver, and to quantify the level of islets remain alive and functional over time. This information would be vital to establishing and evaluating the efficiency of pancreatic islet transplantation. Many novel imaging agents have been developed to improve the sensitivity and specificity of PET islet imaging. In this article, we summarize the latest developments in carbon-11, fluorine-18, copper-64, and gallium-68 labeled radioligands for the PET imaging of pancreatic islet cells.     

Coronary vasomotor function assessed by positron emission tomography

Cardiac PET has the unique ability to assess coronary flow reserve and coronary endothelial function on the basis of response of blood flow to pharmacological stress and the cold pressor test. Quantitative analysis of coronary vasomotor function is valuable for precise assessment of function and treatment monitoring in the presence of various coronary risk factors. In addition, recent data have shown prognostic value of PET assessment of coronary vasomotor imaging in patients with suspected coronary artery disease. Thus, quantitative analysis of PET has a great potential for wide application in identifying microcirculatory dysfunction and “individualized” monitoring of the effects of primary or preventive medical intervention to optimize cardiovascular outcome.     

A cost analysis of positron emission tomography.

OBJECTIVE: Changes in regulations and improvements in reimbursement have propelled positron emission tomography (PET) into clinical use, making it increasingly important to understand the costs of this emerging service. Cost analyses are important tools to do this. Data published previously on these topics reflect assumptions that are no longer valid. The aim of this study was to determine the cost of developing and operating a PET facility and to evaluate whether a regional cyclotron serving several scanners reduces costs. MATERIALS AND METHODS: Financial data were collected on capital expense and global operating costs through interviews with industry experts, evaluation of prior studies, and review of expenses incurred at the University of Southern California PET center. A data model and cost templates were developed. Expenses were allocated either to the production or purchase of radiopharmaceuticals or to the provision of the PET scan, and the cost per procedure was determined. A sensitivity analysis was performed on the net present value for key parameters. RESULTS: A cyclotron serving a single scanner is not financially viable. The radiopharmaceutical distribution configurations were financially sound. In these cases, the cost of the radiopharmaceutical was approximately $700 per dose with modest levels of production (12 doses per day). In addition, the average cost of PET scans (technical scan and professional charges) ranged from approximately $900 to $1400. The critical factor for profitability was shown to be throughput. CONCLUSION: This analysis provides significant insight into the cost of PET and the comparative costs of offering PET through four operating configurations. Reductions in equipment prices, increased availability of radiopharmaceuticals, growth in demand, and improvements in reimbursement have all contributed to the financial viability of this imaging technique.     

Electrocardiographic gating in positron emission computed tomography.

Electrocardiographic (ECG) synchronized multiple gated data acquisition was employed with positron emission computed tomography (ECT) to obtain images of myocardial blood pool and myocardium. The feasibility and requirements of multiple gated data acquisition in positron ECT were investigated for 13NH3, (18F)-2-fluoro-2-D-deoxyglucose, and (11C)-carboxyhemoglobin. Examples are shown in which image detail is enhanced and image interpretation is facilitated when ECG gating is employed in the data collection. Analysis of count rate data from a series of volunteers indicates that multiple, statistically adequate images can be obtained under a multiple gated data collection format without an increase in administered dose.