Advances In Positron Emission Tomography Research Articles

Lung cancer staging

The staging of lung cancer is a continuously progressing field, with advances in technology not only improving prognostic accuracy, but fundamentally changing pre-operative investigation algorithms. Noninvasive staging is currently undergoing revolutionary developments with the advent of Positron Emission Tomography, whereas Video-Assisted Thoracic Surgery has already been established as an essential, minimally invasive diagnostic tool for invasive histological staging. Molecular staging may transform future lung cancer staging, promising extremely accurate substaging, and potentially prompting a revision of our anatomically based conceptualization of lung cancer spread. This review presents an appraisal of current lung cancer staging modalities, and presents an overview of recent developments in molecular staging.

Whole-body positron emission tomography and positron emission tomography/computed tomography in gynecologic oncology

The advent of positron emission tomography (PET) and PET/computed tomography (CT) now enables us to detect metabolically active gynecologic cancers with greater accuracy than was possible with anatomic imagings. Fluorine-18 fluorodeoxyglucose PET has been useful in differentiation of malignant from benign lymph nodes, and residual or recurrent cancers from post-treatment changes. PET/CT produces additional information for the diagnosis and tissue biopsy as well as radiotherapy planning. This paper reviews the principle and clinical utility of PET and PET/CT in the diagnosis, staging, recurrence, therapeutic response as well as prognosis of gynecologic cancers.

PET for drug development.

The development of new drugs involves an extensive pre-clinical characterization and safety documentation followed by a time-consuming search for appropriate clinical dose levels. Drug development is a time-consuming and costly procedure: The molecule-todrug-time is about 15 years, whereas an investment of about 500 million to 1 billion euro is required to reach registration of a new drug (Campbell 1995; Halldin et al. 2001 a) (Fig. 1). The advent of positron emission tomography (PET) with allied techniques has resulted in a revolutionary change in this respect, as the application of PET in drug development and testing can significantly reduce both molecule-to-drug time and costs (Maziere et al. 1991; Maziere and Delforge 1994; Campbell 1995; Halldin et al. 1995, 2001 a; Farde 1996; Burns et al. 1999; Fowler et al. 1999; Gibson et al. 2000; Eckelman 2002).

Whole-body positron emission tomography and positron emission tomography/computed tomography in gynecologic oncology

The advent of positron emission tomography (PET) and PET/computed tomography (CT) now enables us to detect metabolically active gynecologic cancers with greater accuracy than was possible with anatomic imagings. Fluorine-18 fluorodeoxyglucose PET has been useful in differentiation of malignant from benign lymph nodes, and residual or recurrent cancers from post-treatment changes. PET/CT produces additional information for the diagnosis and tissue biopsy as well as radiotherapy planning. This paper reviews the principle and clinical utility of PET and PET/CT in the diagnosis, staging, recurrence, therapeutic response as well as prognosis of gynecologic cancers.

Parameterization of a model-based 3-D PET scatter correction

Parameterization of a fast implementation of the Ollinger (1996) model-based 3-D scatter correction method for positron emission tomography (PET) has been evaluated using measured phantom data acquired on a GE Advance PET imaging system. The Ollinger method explicitly estimates the 3-D single-scatter distribution using measured emission and transmission data and then estimates the multiple-scatter as a convolution of the single scatter. The main algorithm difference from that implemented by Ollinger is that the scatter correction does not explicitly compute scatter for azimuthal angles; rather, it determines 2-D scatter estimates for data within 2-D "super-slices" using as input data from the 3-D direct-plane (nonoblique) slices. These axial super-slice data are composed of data within a parameterized distance from the center of the super-slice. A model-based scatter correction method can be parameterized, and choice parameters may significantly change the behavior of the algorithm. Parameters studied in this work included transaxial image downsampling, the number of detectors to calculate scatter to, multiples kernel width and magnitude, the number and thickness of super-slices, and the number of scatter estimation iterations. Measured phantom data included imaging of the NEMA NU-2001 image quality (IQ) phantom, the IQ phantom with 2 cm extra water-equivalent tissue strapped around its circumference, and an attenuation phantom (20 cm uniform cylinder with Teflon, water and air inserts) with two 8 cm diameter water-filled nonradioactive arms placed by its side. For the IQ phantom data, a subset of NEMA NU-2001 measures were used to determine the contrast-to-noise ratio (CNR), lung residual bias, and background variability. For the attenuation phantom, region of interests (ROIs) were drawn on the nonradioactive compartments and on the background. These ROIs were analyzed for inter and intra-slice variation, background bias, and compartment-to-background ratio. In most cases, the algorithm was most sensitive to multiple-scatter parameterization and least sensitive to transaxial downsampling. The algorithm showed convergence by the second iteration for the metrics used in this study. Also, the range of the magnitude of change in the metrics analyzed was small over all changes in parameterization. Further work to extend these results to more realistic phantom and clinical datasets is warranted.

Pharmacokinetic imaging: a noninvasive method for determining drug distribution and action.

Advances in positron emission tomography (PET), single photon emission computed tomography (SPECT) and magnetic resonance spectroscopy (MRS), and the ability to label a wide variety of compounds for in vivo use in humans, have created a new technology for making precise physiological and pharmacological measurements. Due to the noninvasive nature of these approaches, repetitive and/or continuous measurements have become possible. Thus far, these techniques have been primarily used for one-time assessments of individuals. However, experience suggests that a major use of this technology will be in the evaluation of new drug therapies. Already, these techniques have been used to measure precisely and noninvasively the pharmacokinetics of a variety of antimicrobial, antineoplastic and CNS agents. In the case of CNS drugs, imaging techniques (particularly PET) have been used to define the classes of neuroreceptors with which the drug interacts. The physiological, pharmacological and biochemical measurements that can be performed noninvasively using modern imaging techniques can greatly facilitate the evaluation of new therapies. These measurements are most likely to be useful during drug development in preclinical studies and in phase I/II human studies. Preclinically, new drugs can be precisely compared with standard therapies, or a series of analogues can be screened for further development on the basis of performance in animal models. In Phase I/II, imaging measurements can be combined with classical pharmacokinetic data to establish optimal administration schedules, evaluate the utility of interventions in specific clinical situations, and aid in the design of Phase III trials.

CNS Assessment Using Functional Neuro-PET Imaging

Disorders of the brain manifest in a variety of manners ranging from feeling or thought abnormalities to total paralysis. Until recently, most imaging methods of the brain have been limited to anatomic considerations, with little information about actual function of the brain except that deduced from clinical examination and physical and cognitive assessment testing. With the advent of positron emission tomography (PET) and enhanced computer and scintigraphic image detection systems, there is keen interest in applying this imaging technique to better understand brain physiology and pathophysiology. Potential applications of PET in CNS assessment is expanding avenues for improved diagnosis and staging of disease, as well as monitoring therapeutic interventions. A general review of the radiopharmaceuticals used for neuro-PET imaging, as well as their application in situations such as cerebrovascular disease, brain activation studies, various movement disorders and dementias, depression, epilepsy, obsessive-compulsive disorder, schizophrenia, and neuropharmacology (including cerebral receptor studies) will be presented.

Influence of OSEM and segmented attenuation correction in the calculation of standardised uptake values for [18F]FDG PET

Standardised Uptake Values (SUVs) are widely used in positron emission tomography (PET) as a semi-quantitative index of fluorine-18 labelled fluorodeoxyglucose uptake. The objective of this study was to investigate any bias introduced in the calculation of SUVs as a result of employing ordered subsets-expectation maximisation (OSEM) image reconstruction and segmented attenuation correction (SAC). Variable emission and transmission time durations were investigated. Both a phantom and a clinical evaluation of the bias were carried out. The software implemented in the GE Advance PET scanner was used. Phantom studies simulating tumour imaging conditions were performed. Since a variable count rate may influence the results obtained using OSEM, similar acquisitions were performed at total count rates of 34kcps and 12kcps. Clinical data consisted of 100 patient studies. Emission datasets of 5 and 15min duration were combined with 15-, 3-, 2- and 1-min transmission datasets for the reconstruction of both phantom and patient studies. Two SUVs were estimated using the average (SUVavg) and the maximum (SUVmax) count density from regions of interest placed well inside structures of interest. The percentage bias of these SUVs compared with the values obtained using a reference image was calculated. The reference image was considered to be the one produced by filtered backprojection (FBP) image reconstruction with measured attenuation correction using the 15-min emission and transmission datasets for each phantom and patient study. A bias of 5%-20% was found for the SUVavg and SUVmax in the case of FBP with SAC using variable transmission times. In the case of OSEM with SAC, the bias increased to 10%-30%. An overall increase of 5%-10% was observed with the use of SUVmax. The 5-min emission dataset led to an increase in the bias of 25%-100%, with the larger increase recorded for the SUVmax. The results suggest that OSEM and SAC with 3 and 2min transmission may be reliably used to reduce the overall data acquisition time without compromising the accuracy of SUVs.

METHODOLOGICAL ISSUES CONFRONTING PET AND fMRI STUDIES OF COGNITIVE FUNCTION

(2000). METHODOLOGICAL ISSUES CONFRONTING PET AND fMRI STUDIES OF COGNITIVE FUNCTION. Cognitive Neuropsychology: Vol. 17, No. 5, pp. 467-484.

Positron Emission Tomography in Lymphoma: Comparison with Computed Tomography and Gallium-67 Single Photon Emission Computed Tomography

With the advent of positron emission tomography (PET), metabolic imaging has become a reality for tumor staging and monitoring response to therapy in lymphoma. Increased Fluorine-18 fluorodeoxyglucose ([18F]FDG) uptake in lymphomas has been well documented in the literature; it is based upon elevated glycolysis and longer residence time of FDG in malignant cells compared to most normal tissues. This suggests that in tumor staging, FDG-PET may be more sensitive and specific than the anatomic imaging modalities. Computed tomography (CT) is the standard imaging modality for the staging and restaging of lymphoma, and Gallium-67 (67Ga) scintigraphy has played an important role in monitoring response to therapy and follow-up of patients. Published results suggest that FDG-PET is superior to 67Ga imaging and may be equal or superior to CT for the detection of nodal as well as extranodal involvement in lymphoma.

Commentary on “Lung Cancer: Value of Various Imaging Modalities”

Lung cancer continues to be a leading cause of death, and non–small-cell lung cancer accounts for nearly 75% of all lung cancers. Potential for cure is maximized if lung cancer is detected when it is resectable. Garcia et al provide an organized review of various useful imaging modalities; however, in the past decade significant advances in positron emission tomography (PET) imaging appear to be changing the traditional practice of radiology in the work up of suspected or proven lung cancer patients. Of the nearly 130,000 new solitary pulmonary nodules (SPNs) found each year in the US, about 50%-60% are benign and can be spared the surgical resection. Plain film and computed tomography (CT) may not be able to differentiate malignant from benign lesions in two thirds of nodules based on pattern of calcification or even CT densitometry.

Early postischemic hyperperfusion: pathophysiologic insights from positron emission tomography.

Early postischemic hyperperfusion (EPIH) has long been documented in animal stroke models and is the hallmark of efficient recanalization of the occluded artery with subsequent reperfusion of the tissue (although occasionally it may be seen in areas bordering the hypoperfused area during arterial occlusion). In experimental stroke, early reperfusion has been reported to both prevent infarct growth and aggravate edema formation and hemorrhage, depending on the severity and duration of prior ischemia and the efficiency of reperfusion, whereas neuronal damage with or without enlarged infarction also may result from reperfusion (so-called "reperfusion injury"). In humans, focal hyperperfusion in the subacute stage (i.e., more than 48 hours after onset) has been associated with tissue necrosis in most instances, but regarding the acute stage, its occurrence, its relations with tissue metabolism and viability, and its clinical prognostic value were poorly understood before the advent of positron emission tomography (PET), in part because of methodologic issues. By measuring both CBF and metabolism, PET is an ideal imaging modality to study the pathophysiologic mechanism of EPIH. Although only a few PET studies have been performed in the acute stage that have systematically assessed tissue and clinical outcome in relation to EPIH, they have provided important insights. In one study, about one third of the patients with first-ever middle cerebral artery (MCA) territory stroke studied within 5 to 18 hours after symptom onset exhibited EPIH. In most cases, EPIH affected large parts of the cortical MCA territory in a patchy fashion, together with abnormal vasodilation (increased cerebral blood volume), "luxury perfusion" (decreased oxygen extraction fraction), and mildly increased CMRO2, which was interpreted as postischemic rebound of cellular metabolism in structurally preserved tissue. In that study, the spontaneous outcome of the tissue exhibiting EPIH was good, with late structural imaging not showing infarction. This observation was supported by another PET study, which showed, in a few patients, that previously hypoperfused tissue that later exhibited hyperperfusion after thrombolysis did not undergo frank infarction at follow-up. In both studies, clinical outcome was excellent in all patients showing EPIH except one, but in this case the hyperperfused area coexisted with an extensive area of severe hypoperfusion and hypometabolism. These findings from human studies therefore suggest that EPIH is not detrimental for the tissue, which contradicts the experimental concept of "reperfusion injury" but is consistent with the apparent clinical benefit from thrombolysis. However, PET studies performed in the cat have shown that although hyperperfusion was associated with prolonged survival and lack of histologic infarction when following brief (30-minute) MCA occlusion, it often was associated with poor outcome and extensive infarction when associated with longer (60-minute) MCA occlusion. It is unclear whether this discrepancy with human studies reflects a shorter window for tissue survival after stroke in cats, points to the cat being more prone to reperfusion injury, or indicates that EPIH tends not to develop in humans after severe or prolonged ischemia because of a greater tendency for the no-reflow phenomenon, for example. Nevertheless, the fact that the degree of hyperperfusion in these cat studies was related to the severity of prior flow reduction suggests that hyperperfusion is not detrimental per se. Preliminary observations in temporary MCA occlusion in baboons suggest that hyperperfusion developing even after 6 hours of occlusion is mainly cortical and associated with no frank infarction, as in humans. Overall, therefore, PET studies in both humans and the experimental animal, including the baboon, suggest that hyperperfusion is not a key factor in the development of tissue infarction and that it may be a harmless phenomenon

Positron emission tomography in the study of hepatic encephalopathy.

Positron-emission tomography (PET) is a quantitative technique that produces images of biological or physiological processes. The nature of the image depends on the tracer used: common tracers used to study HE include 18F-fluordeoxyglucose, a marker of glucose metabolism; 15O-water, a marker of cerebral blood flow; and 13N-ammonia, a marker of ammonia metabolism. Combined blood flow and ammonia metabolism studies can be used to calculate the permeability surface area product for ammonia at the blood brain barrier. To take full advantage of PET, the data should be analyzed using one of the several sophisticated image processing and analysis techniques that are available. Thus, PET is an ideal technique to evaluate ammonia metabolism and, because of a close linkage of blood flow and glucose metabolism with neural activity, to investigate the neural response to drugs and other treatments and to examine neural systems that mediate specific tasks that are impaired in patients with HE.

13 Baroreflex Regulation of Blood Pressure during Dynamic Exercise

From the work of Potts et al. Papelier et al. and Shi et al. it is readily apparent that the arterial (aortic and carotid) baroreflexes are reset to function at the prevailing ABP of exercise. The blood pressure of exercise is the result of the hemodynamic (cardiac output and TPR) responses, which appear to be regulated by two redundant neural control systems, "Central Command" and the "exercise pressor reflex". Central Command is a feed-forward neural control system that operates in parallel with the neural regulation of the locomotor system and appears to establish the hemodynamic response to exercise. Within the central nervous system it appears that the HLR may be the operational site for Central Command. Specific neural sites within the HLR have been demonstrated in animals to be active during exercise. With the advent of positron emission tomography (PET) and single-photon emission computed tomography (SPECT), the anatomical areas of the human brain related to Central Command are being mapped. It also appears that the Nucleus Tractus Solitarius and the ventrolateral medulla may serve as an integrating site as they receive neural information from the working muscles via the group III/IV muscle afferents as well as from higher brain centers. This anatomical site within the CNS is now the focus of many investigations in which arterial baroreflex function, Central Command and the "exercise pressor reflex" appear to demonstrate inhibitory or facilitatory interaction. The concept of whether Central Command is the prime mover in the resetting of the arterial baroreceptors to function at the exercising ABP or whether the resetting is an integration of the "exercise pressor reflex" information with that of Central Command is now under intense investigation. However, it would be justified to conclude, from the data of Bevegard and Shepherd, Dicarlo and Bishop, Potts et al., and Papelier et al. that the act of exercise results in the resetting of the arterial baroreflex. In addition, if, as we have proposed, the cardiopulmonary baroreceptors primarily monitors and reflexly regulates cardiac filling volume, it would seem from the data of Mack et al. and Potts et al. that the cardiopulmonary baroreceptor is also reset at the beginning of exercise. Therefore, investigations of the neural mechanisms of regulation involving Central Command and cardiopulmonary afferents, similar to those being undertaken for the arterial baroreflex, need to be established.

Activation PET scanning in pretreatment evaluation of patients with cerebral tumours or vascular lesions in or close to the sensorimotor cortex.

Treatment of tumours and vascular lesions in or close to eloquent cortex may inflict neurological deficits. Intra-operative mapping procedures have been used for many decades in efforts to minimize neurological sequelae. The possibility for non-invasive pre-operative brain mapping has emerged with the advent of positron emission tomography (PET). In this paper we report on 11 patients with a tumour or vascular lesion in or close to the sensorimotor (10 patients) or visual cortex (one patient). The patients were subjected to activation PET scanning by means of vibrotactile or visual stimulation. The results show that in most of the patients the important relation between the lesion and the sensorimotor cortex could be determined. The patient with a lesion in the occipital lobe had involvement of the entire visual cortex as judged by comparison with activated areas on the nonlesion side.

A study on statistically reliable and computationally efficient algorithms for generating local cerebral blood flow parametric images with positron emission tomography

With the advent of positron emission tomography (PET), a variety of techniques have been developed to measure local cerebral blood flow (LCBF) noninvasively in humans. A potential class of techniques, which includes linear least squares (LS), linear weighted least squares (WLS), linear generalized least squares (GLS), and linear generalized weighted least squares (GWLS), is proposed. The statistical characteristics of these methods are examined by computer simulation. The authors present a comparison of these four methods with two other rapid estimation techniques developed by Huang et al. (1982) and Alpert (1984), and two classical methods, the unweighted and weighted nonlinear least squares regression. The results show that these methods can take full advantage of the contribution from the fine temporal sampling data of modern tomographs, and thus provide statistically reliable estimates that are comparable to those obtained from nonlinear LS regression. These methods also have high computational efficiency, and the parameters can be estimated directly from operational equations in one single step. Therefore, they can potentially be used in image-wide estimation of local cerebral blood flow and distribution volume with PET.

Quantitative analysis of a reconstruction method for fully three-dimensional PET

The major advantage of positron emission tomography (PET) using large area planar detectors over scintillator-based commercial ring systems is the potentially larger (by a factor of two or three) axial field-of-view (FOV). However, to achieve the space invariance of the point spread function necessary for Fourier filtering a polar angle rejection criterion is applied to the data during backprojection resulting in a trade-off between FOV size and sensitivity. A new algorithm by Defrise et al. (ibid., vol.33, p.43-51, 1988) developed for list-mode data overcomes this problem with a solution involving the division of the image into several subregions. A comparison between the existing backprojection-then-filter algorithm and the new method (with three subregions) has been made using both simulated and real data collected from the MUP-PET positron camera. Signal-to-noise analysis reveals that improvements of up to a factor of 1.4 are possible resulting from an increased data usage of up to a factor of 2.5 depending on the axial extent of the imaged object. Quantitation is also improved.

Positron emission tomography and in vivo measurements of tumour perfusion and oxygen utilisation.

The advent of positron emission tomography has provided the clinical investigator with a tool for performing noninvasive (patho)-physiological measurements in humans. The method has been used extensively in the study of cerebral and cardiovascular disease. Oncological applications have been described by a more limited number of centres and have mainly concentrated on cerebral tumours. The first part of this review discusses principles of positron emission tomography and requirements for performing quantitative studies. The second part describes results of one of the most important quantitative techniques: the measurement of tumour blood flow and oxygen metabolism.