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Although any patient with a suspected brain tumor, either primary or metastatic, should be studied with anatomic imaging modalities such as angiography, computerized tomagraphy (CT) or magnetic resonance imaging (MRI), nuclear medicine techniques are available to further characterize some biological features of brain lesions and help in diagnosis and therapy planning. Bloob-brain-barrier disruption can be easily assessed with single-photon emission tomography (SPET), whereas focal metabolic changes can be better demonstrated by positron emission tomography (PET) as specific radiopharmaceuticals are available to detect changes in glucose utilization and aminoacid uptake with this technique. Expression of specific tumoral antigens is the basis of imaging with radioimmunoscintigraphy, a promising technique that can be applied to brain tumor therapy. The major clinical applications of nuclear medicine in the study of brain tumors -- evaluation of the extension of a tumoral mass, differential diagnosis and evaluation of therapy and prognosis -- are discussed.

Aim: Increasing ageing of the population and tumor incidence, along with worldwide rationing of the resources for public health systems, spur the use of economic analyses for the choice of strategies and technologies in the assessment and management of cancer patients. Incidence and clinical managing of tumors vary in different countries even if positron emission tomography (PET) with 2-deoxy-2-[18F]-fluoro-D-glucose (FDG) is becoming a routine clinical method for diagnosis, staging, treatment monitoring and follow-up in a variety of tumors. Available data indicate that PET can be considered a superior alternative or complementary tool to other well-established methods. However, in spite of the above and of the rapidly increasing number of PET centers in Europe, USA and Japan, only a few studies have dealt with some of the economic aspects raised by the clinical use of PET because of differences in values of reimbursements and health costs. The main aim of this study is to propose and discuss an economic model of analysis for PET applications in the field of detection and management of pulmonary tumors., Methods: In this study 2 assessments were performed by decision tree analysis on the economic impact of the availability of PET on decision-making processes for 2 conditions: solitary pulmonary nodules assessment and non-small-cell lung cancer (NSCLC) staging. In order to define a methodology consistent with the system of reimbursement and the prevalent clinical views of the Italian National Health Service, data on costs, death probability, and life expectancy were gathered from the literature and from the Italian system of reimbursement (ROD-DRGs)., Results: The results of the cost minimization analysis demonstrate that the use of PET in the diagnostic path for the workup of patients with SPN reduces the overall diagnostic costs, by approximately 50 Euro per patient, by reducing inappropriate invasive diagnostic investigation and their complications. The results of the cost effectiveness analysis demonstrate that the use of PET in the diagnostic path for the staging of patients with NSCLC reduces the overall diagnostic costs by approximately 108 Euro for added year, by reducing inappropriate surgical interventions and their complications., Conclusion: Both analyses are based on standard methods used in the literature, so our conclusions can be compared with results and assessments of similar studies in different countries and health care systems. Also in the Italian case, the use of an economic assessment provides relevant information on the efficacy and effectiveness of PET.

Movement disorders, including Parkinson's disease and parkinsonian syndromes, e.g. progressive supranuclear palsy, multiple system atrophy, and Lewy body dementia, may be difficult to differentiate among each other at an early stage, since they may share similar clinical features and response to dopaminergic drugs. As new tracers for imaging the dopamine transporters become available, the use of positron emission tomography (PET) for the differential diagnosis of movement disorders is gaining clinical relevance. Visual interpretation is generally used for PET image analysis. However, the use of some form of less subjective analysis is desirable in order to detect subtle changes that may be difficult to identify by visual interpretation and to achieve an operator independent analysis. To this end this study was aimed at assessing the feasibility of using statistical parametric mapping (SPM) for the clinical evaluation of single PET scans performed with 2-beta-carbomethoxy-3-beta-(4-fluorophenyl)-tropane ( C-beta-CIT-FE). Eleven healthy volunteers and five patients with movement disorders (Parkinson's disease, essential tremor, PSP and Lewy body dementia) were included in this study. Each subject underwent a PET study after i.v. injection of C-beta-CIT-FE. The PET images of C-beta-CIT-FE distribution acquired between 60 and 90 min were spatially fitted into the Talairach and Tournoux space. A template of normal C-beta-CIT-FE distribution was derived from studies in the 11 normal control subjects. Different patterns of reduction of the uptake of the tracer were detected in the basal ganglia of the five patients, in relation to each pathological condition. The patterns of distribution were all consistent with the severity and type of disease. The results of this study demonstrate the feasibility of differentiating among different states of dopaminergic impairment, due to Parkinson's disease and parkinsonian syndromes, by using PET scans with C-beta-CIT-FE and by using the SPM procedure for analysis of the data.

The assessment of neurochemical processes in vivo has received much attention in the past decade as techniques such as positron or single photon emission tomography (PET and SPET), and magnetic resonance spectroscopy (MRS) have become more available. With PET and SPET, basic processes, such as blood flow and oxygen or glucose metabolism, can be regionally assessed, along with more specific functions such as the production, release, and reuptake of neurotransmitters and their occupancy of specific receptors. At the same time, MRS can reveal changes in concentration of several hydrogenate compounds in the brain. All these methods have been extensively applied for research in neurology, and some applications have reached the clinical level, namely for the study of degenerative diseases, motor-neuron diseases, movement disorders, cerebrovascular diseases, and epilepsy. This article focuses on the most relevant information that can be obtained with these complementary techniques to help clinicians in the assessment of neurological diseases.

Cancerous transformation entails major biochemical changes including modifications of the energy metabolism of the cell, e.g. utilisation of glucose and other substrates, protein synthesis, and expression of receptors and antigens. Tumour growth also leads to heterogeneity in blood flow owing to focal necrosis, angiogenesis and metabolic demands, as well as disruption of transport mechanisms of substrates across cell membranes and other physiological boundaries such as the blood-brain barrier. All these biochemical, histological and anatomical changes can be assessed with emission tomography, X-ray computed tomography (CT), magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). Whereas anatomical imaging is aimed at the diagnosis of brain tumours, biochemical imaging is better suited for tissue characterisation. The identification of a tumoural mass and the assessment of its size and vascularisation are best achieved with X-ray CT and MRI, while biochemical imaging can provide additional information that is crucial for tumour classification, differential diagnosis and follow-up. As the assessment of variables such as water content, appearance of cystic lesions and location of the tumour are largely irrelevant for tissue characterisation, a number of probes have been employed for the assessment of the biochemical features of tumours. Since biochemical changes may be related to the growth rate of cancer cells, they can be thought of as markers of tumour cell proliferation. Biochemical imaging with radionuclides of processes that occur at a cellular level provides information that complements findings obtained by anatomical imaging aimed at depicting structural, vascular and histological changes. This review focusses on the clinical application of anatomical brain imaging and biochemical assessment with positron emission tomography, single-photon emission tomography and MRS in the diagnosis of primary brain tumours, as well as in follow-up.

Emission tomography techniques and, in particular, positron emission tomography (PET) enable the in vivo study of several physiological and neurochemical variables in human subjects using methods originally developed for quantitative autoradiography. In particular, PET allows one to evaluate in human subjects: (a) the effect of specific neurochemical challenges on regional brain function at rest or under activation; (b) the activity of neurotransmitters and the regional expression of specific molecular targets during pathology including their modulation by drug treatment; (c) the kinetics of drug disposition and activity directly in the target organ. This is of primary interest in the field of biological psychiatry and in psychoactive drugs development, where it is particularly difficult to reproduce human diseases using animal models in view of the peculiarity of this field and the large heterogeneity of each psychiatric illness also inside the same clinical definition. The aim of this paper is to review the principal strategies and the main results of the use of PET in psychopharmacology., (Copyright 2001 Academic Press.)

Unlabelled: This study compared the multiring detector (Ring-PET) and the dual-head coincidence imaging system (DH-PET) for staging/ restaging neoplastic patients before or after surgery or radiochemotherapy., Methods: Seventy patients with suspected tumor recurrence or metastatic dissemination received an intravenous dose of 18F-fluorodeoxyglucose (FDG) under overnight fasting and were studied in sequence with a dedicated positron emission tomograph with Ring-PET and a DH-PET. Ring-PET studies were performed 45-75 min postinjection and were followed by a DH-PET scan approximately 3 h postinjection. Number and location of the hypermetabolic lesions detected on DH-PET and Ring-PET reconstructed images were blindly assessed by three independent observers., Results: DH-PET identified all 14 head lesions detected by Ring-PET, 53 of 63 thoracic lesions and 36 of 45 abdominal lesions. Of the 19 lesions not identified by DH-PET, 6 were smaller than 10 mm, 8 were between 10 and 15 mm and 1 was 18 mm; dimensions of 4 bone lesions were not available. A concordant restaging, based on location and number of lesions detected, was found in all 14 patients with head tumors, in 28 of 30 patients with thoracic tumors and in 24 of 26 patients with abdominal tumors., Conclusion: We found a good agreement between Ring-PET and DH-PET assessment of oncologic patients in detecting hypermetabolic lesions > or = 10-15 mm.

Background: To assess the potential usefulness of 18F-FDG/PET and spiral-CT images concurrent assessment and coregistration in staging mediastinal lymph node involvement in patients with non small cell lung cancer., Methods: 28 patients waiting to undergo surgical treatment underwent spiral-CT and PET examinations on the same day. The results of the two studies were interpreted separately, together (CT&PET) and following their fusion in a single image (CT+PET). Results of spiral-CT, PET, CT&PET and CT+PET were assessed with respect to the histological diagnosis., Results: A correct assessment of mediastinal lymph nodes was achieved by spiral-CT in 21 of the 28 patients, in 22 of the 28 patients by PET, in 24 patients by CT&PET and in 25 patients by CT+PET., Conclusions: CT+PET is more accurate than spiral-CT and PET alone in staging mediastinal lymph node involvement in lung cancer patients, with possible implications for their prognosis and therapy.

Purpose: We investigated 201Tl myocardial uptake with(out) nonuniform attenuation compensation in ischemic myocardiopathy patients. The segmental patterns of the two types of SPECT images were compared with PET [13N]NH3 studies performed in the same patient. PET images were taken as reference and the diagnostic accuracy of SPECT with(out) attenuation correction was evaluated., Material and Methods: During the SPECT study transmission and emission data were simultaneously recorded by a triple head gamma camera equipped with fan beam collimators and a 99mTc transmission line source (740MBq). SPECT and PET images, the former reconstructed with(out) attenuation correction, were corecorded and reoriented along the short axis. The left ventricular wall was divided into 11 segments and segmental activity normalized to maximum in each study., Results: Statistically significant differences were found between PET/(un)corrected SPECT ratios in posterior and septal segments. In these myocardial regions, attenuation correction compensates for attenuation artifacts, by correcting the underestimation of radioactivity concentration caused by radiation absorption. A statistically significant difference was also found in midventricular anterior and apical segments (p < .05). However, in these regions attenuation correction results in a decrease in corrected relative to uncorrected SPECT activity. The agreement rate with PET data is higher for corrected SPECT (mean differences were 3.12 +/- 11.51 and 2.19 +/- 8.63 for uncorrected versus corrected SPET). We had 50% positive and 77% negative predictive value without attenuation correction, versus up to 69% and 90%, respectively, with attenuation correction., Conclusions: The attenuation correction procedure with simultaneous transmission-emission effectively reduces attenuation artifacts in SPECT myocardial imaging. While diagnostic accuracy increases in posterior and septal myocardial regions, anterior and apical data need careful interpretation because a relative decrease in radioactivity concentration can be observed after attenuation correction.

Background: Previous studies have demonstrated that hibernating myocardium can be assessed by [18F]fluorodeoxyglucose ([18F]FDG) and positron emission tomography (PET). This study evaluated the use of [18F]FDG-PET for CABG related risk assessment in patients with coronary artery disease (CAD) and left ventricle dysfunction (LVD)., Methods: We retrospectively evaluated 241 to patients candidate CABG presenting with signs and symptoms of congestive heart failure (CHF) prevailing over ischemic signs. Of the 241 patients, 153 had undergone [18F]FDG-PET as well as conventional assessment: 110 out of 153 (group A) were operated because of PET evidence of hibernation. Of the 241 patients, 88 had not undergone [18F]FDG-PET: 86 out of 88 (group B) were operated on. The outcome of surgical patients was evaluated by considering all major perioperative complications including the use of mechanical and pharmacological support and in-hospital mortality. After hospital discharge, each patient was examined at 1, 4 and every 6 months thereafter., Results: Perioperative use of mechanical supports and inotropic drugs, was significantly lower for the PET selected group (A) than for the non PET selected group (B). Mortality within 30 days of surgery was 0.9% in group A and 19.8% in group B. The only predictors of perioperative outcome were the presence of hibernating tissue and the ejection fraction., Conclusions: [18F]FDG-PET prior to CABG can be crucial for the assessment of perioperative risk in patients with CAD.

In this paper a clustering technique is proposed for attenuation correction (AC) in positron emission tomography (PET). The method is unsupervised and adaptive with respect to counting statistics in the transmission (TR) images. The technique allows the classification of pre- or post-injection TR images into main tissue components in terms of attenuation coefficients. The classified TR images are then forward projected to generate new TR sinograms to be used for AC in the reconstruction of the corresponding emission (EM) data. The technique has been tested on phantoms and clinical data of brain, heart and whole-body PET studies. The method allows: (a) reduction of noise propagation from TR into EM images, (b) reduction of TR scanning to a few minutes (3 min) with maintenance of the quantitative accuracy (within 6%) of longer acquisition scans (15-20 min), (c) reduction of the radiation dose to the patient, (d) performance of quantitative whole-body studies.

The [18F]fluorodeoxyglucose ([18F]FDG) method for measuring brain metabolism has not the wide clinical application that one might expect, partly because of its high cost and the complexity of the quantification procedure, but also because of reporting techniques based on region of interest (ROI) analysis, which are time-consuming and not fully objective. In this paper we report a clinical validation of statistical parametric mapping (SPM) using rCMRglc (quantitative) and radioactivity distribution (nonquantitative) [18F]FDG PET data. We show that a 10-min noninteractive voxel-based SPM analysis on a standard workstation enables objective assessment, including localization in stereotactic space, of regional glucose consumption abnormalities, whose reliability can be assessed on statistical and clinical grounds. Clinical validity was established using a small series of patients with degenerative or developmental disorders, including probable Alzheimer's disease, progressive aphasia, multiple sclerosis, developmental specific language impairment, and epilepsy. Analysis of quantitative and nonquantitative data showed the same pattern of results, suggesting that, for clinical purposes, quantitation and invasive arterial cannulation can be avoided. This should facilitate a wider application of the technique and the extension of SPM clinical analysis to H215O PET or high resolution SPECT perfusion studies., (Copyright 1999 Academic Press.)

An improvement of regional and global left ventricle dysfunction can be achieved in patients with coronary artery disease either by coronary revascularization with percutaneous transluminal coronary angioplasty or coronary artery bypass grafting. Several techniques have been developed to identify dysfunctional but viable myocardium. In the last decade, positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) has been used for the detection of hibernating myocardium. It can accurately predict the recovery of abnormal wall motion in hibernating segments prior to surgery. In particular, assessment of viability with 18F-FDG is indicated in high-risk surgical candidates being considered for revascularization or transplantation. Moreover, patient selection criteria and economic consideration are also relevant for cost-effective use of the technique.

A method is presented for estimating the distributions of the components and parameters determined with spectral analysis when it is applied to a single data set. The method uses bootstrap resampling to simulate the effect of noise on the computed spectrum and to correct for possible bias in the estimates. A number of bootstrap procedures are reviewed, and one is selected for application to the kinetic analysis of positron emission tomography dynamic studies. The technique is shown to require minimal assumptions about noise in the measurements, and its small sample properties are established through Monte-Carlo simulations. The advantages and limitations of spectral analysis with bootstrap resampling for deriving inferences for tracer kinetic modeling are illustrated through sample analyses of time-activity curves for [18F]fluorodeoxyglucose and [15O]-labeled water.

The differential diagnosis among various types of non-functioning sellar and parasellar tumours is sometimes difficult using currently available methods of morphological imaging. The aim of this study was to define whether assessment of the uptake of [18F]fluoro-ethyl-spiperone (FESP) with positron emission tomography (PET) could be helpful for the differential diagnosis of pituitary adenomas and other parasellar lesions, and for establishing the appropriate therapeutic approach. The population examined comprised 16 patients with the diagnosis of primary tumour of the sellar/parasellar region who were waiting to undergo surgical treatment. The results demonstrated that PET with [18F]FESP is a very specific method for differentiating adenomas from craniopharyngiomas and meningiomas. The visual interpretation of images allows such differentiation at approximately 70 min after tracer injection. Semiquantitative analysis of the dynamic PET data confirmed the results of visual interpretation, demonstrating that the uptake of [18F]FESP was consistently (i.e. throughout the series) at least two- to threefold higher in non-functioning adenomas than in other parasellar tumours as early as 70 min after tracer injection, and that it increased still further thereafter. It is concluded that PET with [18F]FESP might be of clinical value in those cases in which the differential diagnosis among various histological types of sellar tumour is uncertain with conventional methods.

We assessed the relative usefulness of whole-body planar scintigraphy with 99Tcm-methoxyisobutyl isonitrile (99Tcm-MIBI), 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG-RS) rectilinear scanning and with diagnostic and therapeutic doses of 131I, for the detection of local recurrences and metastatic lesions in 12 patients with thyroid carcinoma and elevated thyroglobulin serum levels. All images were evaluated independently by three experienced observers to define the number and location of metastatic lesions. 18F-FDG-RS and 99Tcm-MIBI scintigraphy provided similar results, but the tracer that allowed the detection of the highest number of metastases was 99Tcm-MIBI. Both 99Tcm-MIBI scintigraphy and 18F-FDG-RS appear to be more sensitive than 131I scintigraphy for the detection of metastases of thyroid carcinoma. Tomographic acquisitions were also performed on a limited field of view in each subject and, as expected, 18F-FDG-PET was more sensitive than 18F-FDG-RS. 99Tcm-MIBI scintigraphy, a widely available and relatively non-expensive technique, therefore sems suitable for the assessment and follow-up of patients with metastatic thyroid carcinoma and does not require the withdrawal of hormone therapy for lesion imaging.

The aim of this study was to evaluate, in 16 patients with drug-resistant partial epilepsy who were waiting to undergo surgical treatment, the relation between positron emission tomography (PET) findings with fluorine-18 fluorodeoxyglucose ([18F]FDG) in the interictal state and the different stereo-electroencephalography (SEEG) patterns that characterize: (a) the epileptogenic zone (low-voltage fast-activity discharge before or concurrent with ictal clinical symptoms), (b) the irritative zone (spikes, spikes and waves, isolated or grouped in short bursts) and (c) the lesional zone (continuous, sometimes polyrhythmic slow waves or continuous delta waves or very important voltage depression). SEEG was performed following an individually defined electrode implantation strategy. Whereas at least one area of hypometabolism was detected by visual interpretation of PET/[18F]FDG images in all the subjects in the study, there was poor agreement between PET/[18F]FDG quantitative measures of regional metabolism and SEEG findings. Normal metabolic rates were found in up to 62% of the areas with abnormal SEEG activity, independent of the type of electrical activity, i.e. epileptogenic, irritative, or lesional, while abnormal metabolic rates were found in up to 23% of the areas with normal SEEG activity. In conclusion, whereas the visual interpretation of interictal studies of glucose utilization in our series of drug-resistant epileptic patients consistently allowed the localization of an area of temporal hypometabolism, the quantitative and regional metabolic analysis demonstrated that such a finding is not specifically related to any of the three very different SEEG patterns (epileptogenic, irritative, lesional) or combinations thereof. These results complement those of previous interictal and ictal single-photon emission tomographic studies and of receptor studies in epileptics, suggesting functional and biochemical heterogeneity within the interictal hypoperfused/hypometabolic area in epileptic patients, and contribute to the debate on the use and interpretation of interictal PET/[18F]FDG studies in patients with medically refractory partial seizures.

Quantitative positron emission tomography (PET) heart studies require the accurate localization of regions of interest (ROIs) on the myocardial wall (MW) and left ventricle (LV). The procedure is often inaccurate, especially when there is low tracer uptake. We implemented a data processing technique to improve the accuracy of the localization of ROIs on the MW and LV in fluorine-18 labelled deoxyglucose ([18F]FDG) PET heart studies. This technique combines transmission data, acquired before tracer administration and used for attenuation correction, and dynamic emission data (DY), acquired to obtain myocardial time-activity curves and used to calculate regional myocardial glucose utilization, to generate a new set of "transmission" images (TRDY) with enhanced contrast between MW and LV. These new transmission images identify the extravascular myocardial tissue and can be used for ROI placement. Validation of the method was performed in 25 patients, studied after an oral glucose load, by drawing irregular ROIs on three transaxial slices outlining the septum and anterior-apical and lateral wall on the last frame of the DY images (steady state) and then on the TRDY images. Two kinds of analysis were performed on a total of 225 myocardial segments: (1) mean counts per pixel in the DY images from ROIs independently drawn on DY and TRDY images were compared; (2) TRDY ROIs were copied onto DY images and repositioned in the event of mismatch between ROIs and myocardial tissue edge. Mean counts per pixel in the DY images from the original and the repositioned TRDY ROIs were compared. An excellent correlation was found in both cases (using TRDY and DY ROIs: y=0.908 x+0.068, r=0.97; using TRDY ROIs alone: y=0.975 x+0.006, r=0.99). This technique can be used for clinical applications in physiological and pathological conditions in which the myocardial [18F]FDG uptake is reduced or minimal, including diabetes and myocardial infarction.

Objectives: We evaluated the sensitivity and specificity of exercise-induced ST segment elevation for the detection of residual myocardial viability., Background: Assessment of residual viability after myocardial infarction is relevant for establishing indication for revascularization. We have previously shown that exercise-induced ST segment elevation is a marker of residual viability., Methods: We studied 34 patients with a previous Q wave myocardial infarction (anterior in 21, inferior in 13) of whom 18 (group A) had exercise-induced ST segment elevation in more than one lead (mean [+/- SD] 1.8 +/- 0.9 mm, range 1 to 4) and 16 (group B) did not. All patients underwent rest technetium-99m methoxyisobutyl isonitrile single-photon emission computed tomography (SPECT), fluorine-18 (F-18) fluorodeoxyglucose positron emission tomography and coronary angiography. The time elapsed between the infarction and the viability study was 72 +/- 108 days (range 15 to 400) in group A and 516 +/- 545 days (range 14 to 1,800) in group B., Results: The presence and site of previous infarction were confirmed by SPECT studies in all 34 patients. Uptake of F-18 fluorodeoxyglucose within the infarcted area was present in 18 of 18 patients in group A but in only 9 (56%) of 16 in group B (p < 0.01). In patients with an anterior infarction, the sensitivity, specificity and predictive accuracy of exercise-induced ST segment elevation for detection of residual viability were 82%, 100% and 86%, respectively (95% confidence intervals 46% to 83.5%, 59% to 100% and 55.6% to 87.1%, respectively)., Conclusions: Exercise-induced ST segment elevation in infarct-related leads has a high specificity and acceptable sensitivity for detection of residual viability within the infarcted area.

A method has been developed to match corresponding heart regions from functional echocardiographic (Echo) and metabolic fluorine-18-fluoro-2-deoxy-D-glucose ([18F]FDG) positron emission tomography (PET) studies in individual patients. Echo and PET images are spatially correlated by determining homologous anatomical landmarks (the two papillary muscles and the inferior junction of the right ventricle), identifiable in images obtained by both acquisition modalities. Echo-PET image registration is first performed in the plane identified by the three landmarks, using a rigid rotate-translate scale model. The registration parameters are then used to transform the whole PET volume. This allows a consistent Echo-PET regional analysis, according to a segmental subdivision of the heart. The technique was tested on patients. The overlay of Echo and PET registered images proved the reliability of realignment of the three markers and a good spatial correlation of myocardial walls. This approach to image registration could be applied to other acquisition modalities (such as magnetic resonance imaging and single-photon emission tomography), provided that the three anatomical landmarks are visualized.

The distinction between fibrotic and viable myocardium is a key issue in patients with coronary artery disease and left ventricular dysfunction. Metabolic imaging with positron emission tomography (PET) and labeled tracers, along with the study of myocardial perfusion, is now available to identify hibernating myocardium. However, PET imaging of myocardial metabolism is a high-cost and time-consuming technique, and requires an on-site cyclotron. The aim of this study is to test the reliability of dobutamine echocardiography (DE) compared with PET imaging, for the identification of hibernating myocardium. In 16 patients, scheduled for myocardial revascularization, left ventricular shapes were divided in eight segments both for echocardiographic and nuclear study evaluation. All patients underwent a technetium 99m MIBI single-photon emission tomography stress-rest study of perfusion, a fluorine-18-labeled deoxyglucose (FDG(/PET study of metabolism, and a DE test (baseline, at a 5 micrograms/kg/min infusion of dobutamine for 8 minutes and at a 10 micrograms/kg/min dose for additional 8 minutes). Neither myocardial ischemia nor arrhythmia occurred during the DE test. Baseline echocardiograms showed 90 segments with wall motion abnormalities: wall motion impairment was decreased or reversed in 33 of 90 segments; it remained unchanged in 57 of 90 segments. In 32 of 33 segments considered viable on the basis of DE and in 21 of 57 segments with unchanged kinesis, some degree of FDG was detected. Thus, sensitivity and specificity of DE compared with nuclear studies was 60% and 97% respectively. Moreover, a good correlation and agreement (kappa = 0.51) between DE and the presence of FDG were found. We conclude that DE is a safe and reliable test for the screening of hibernating myocardium in patients with chronic coronary artery disease and left ventricular dysfunction.

The distribution of 99mTc-methoxy-isobutyl-isonitrile (99mTc-MIBI), assessed by single photon emission computed tomography (SPECT) was compared to the distribution of 2-[18F]-2-deoxy-D-glucose ([18F]FDG) assessed with positron emission tomography (PET) under fasting conditions, in 21 patients with coronary artery disease (CAD) and severe left ventricular dysfunction in order to evaluate the potential usefulness of SPECT/99mTc-MIBI for the identification of viable myocardium. Stress and rest SPECT/99mTc-MIBI studies were scored based on the percent of 99mTc-MIBI uptake defined by semi-quantitative circumferential-profile analyses. PET metabolic studies with [18F]FDG under fasting conditions, were adopted as a standard of viability. The results of the comparison of 99mTc-MIBI and [18F]FDG distribution showed that among the segments with stress hypoperfusion, [18F]FDG uptake was present in 95% of the segments that had > 40% of the peak tracer uptake at the rest SPECT/99mTc-MIBI study. [18F]FDG uptake was also present, however, in 25% of the segments that had < 40% uptake at the rest SPECT/99mTc-MIBI scintigraphy. We conclude that in patients with CAD the pattern of 99mTc-MIBI distribution appears to underestimate the extent of viable myocardium but only in those regions that are very severely hypoperfused.

Cerebral PET with [18F]-2-fluoro-2-deoxy-D-glucose has been performed in four patients with neurofibromatosis type 1 (NF1) to assess the relation between cerebral metabolic activity, MRI, and the presence of neurological symptoms, including seizures, as well as mental and language retardation. Widespread hypometabolism occurred in three of the patients. The lesions on MRI, which were localised in the subcortical white matter and grey structures, had normal rates of glucose metabolism. This finding suggests that the abnormalities seen on MRI are not due to defective blood supply, localised oedema, or grey matter heterotopic foci as previously hypothesised. The presence of the hypometabolic areas seems to be inconsistently related to the occurrence of seizures and is not proportional to the degree of mental impairment. This study provides evidence of a widespread cerebral hypometabolism that is not related to the presence of MRI abnormalities; conversely normal metabolism was present in the areas with an abnormal MRI signal.

We report on a 13-year-old girl with late infantile neuronal ceroid lipofuscinosis (NCL) in whom PET scanning with [18F]-2-fluoro-2-deoxy-D-glucose ([18F]/FDG) was performed. Early psychomotor development was normal. At the age of 2 years, neurological signs such as hypotonia and incoordination appeared, followed by visual failure and ataxia. At the age of 4, funduscopic examination showed macular degeneration and papillary atrophy. At the age of 9, myoclonic jerks were observed; subsequently, generalized seizures together with failing vision, mental deterioration, and visual and auditory hallucinations appeared. Brain MRI showed severe cortical and subcortical atrophy. A skin biopsy detected the presence of 'finger-print' inclusions in the cytoplasm of smooth muscle fibers. Late infantile NCL (Jansky-Bielschowsky disease) was diagnosed. FDG/PET revealed a severe reduction of metabolism in all the cortical and subcortical structures. A regional analysis of the distribution of the tracer revealed marked bilateral hypometabolism, particularly in calcarine, lateral, occipital, and temporal cortices and in the thalamus.

A method for kinetic analysis of dynamic positron emission tomography (PET) data by linear programming that allows identification of the components of a measured PET signal without predefining a compartmental model has recently been proposed by Cunningham and co-workers. The method identifies a small subset of functions from a large input set of feasible functions that best fits the time course of total radioactivity measured by PET. To investigate in detail the properties of this technique, we applied it to PET studies with [18F]fluorodeoxyglucose, a tracer with well-characterized kinetic properties. We examined dynamically acquired data over various time intervals in many brain regions and found that the number of components identified by the method is stable and consistent with the presence of kinetic heterogeneity in every region. We optimized the method for determination of regional rates of glucose utilization; calculated rates were found to be somewhat dependent upon the treatment of noise in the measured tissue data and upon the time interval in which the data were collected. The application of a numerical filter to remove noise in the data resulted in values for regional cerebral glucose utilization that were stable with time and consistent with rates determined by the other established techniques. Based on the results of the current study, we expect that the spectral analysis technique will prove to be a highly flexible tool for kinetic analysis of other tracer compounds; it is capable of producing low-variance, time-stable estimates of physiological parameters when optimized for time interval of application, input spectrum of components, and processing of noise in the data.

The relationship between severity of coronary artery stenosis (CAS) and myocardial 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) uptake in the fasting state, assessed with positron emission tomography (PET), was examined in a series of 48 patients with CAS undergoing both studies for diagnostic purposes. The data analysis was based on the subdivision of the left ventricular myocardium into four segments defined in relation to ventricular vascularization: the anterior and septal segments, perfused by the left anterior descending artery; the lateral segment, perfused by the left circumflex; and the inferior segment, perfused by the right coronary artery. The 192 segments were grouped according to degree of CAS: I 0-50%, II 51-75%; III 76-90%; IV 91-99%; V and VI occluded coronary artery with good or poor collaterals, respectively. An 18F-FDG index was determined as the tissue/blood pool radioactivity ratio in each segment. The statistical analysis was performed by one-way ANOVA, multiple comparison tests and the chi-squared test. The proportion of segments with 18F-FDG uptake was also analysed for a linear trend across the ordered levels of CAS. The 18F-FDG index in groups I to V was significantly higher than in controls, but it was not different among the groups with CAS, except for group V versus I. However, the proportion of segments with enhanced 18F-FDG uptake was correlated to the degree of CAS. In cases of complete occlusion of a major afferent coronary artery, the proportion of segments with 18F-FDG uptake varied in relation to the presence of collaterals.(ABSTRACT TRUNCATED AT 250 WORDS)

Unlabelled: SPECT studies of regional cerebral perfusion with a high-resolution system were compared to PET studies of regional cerebral glucose utilization (rCMRglc) in 21 patients with probable Alzheimer's disease (AD). Ten normal subjects were also evaluated with SPECT and 10 with PET., Methods: rCMRglc (for PET) and counts (for SPECT) in the associative cortices were normalized to the average rCMRglc, and counts in the calcarine cortex and basal ganglia were considered as a "reference area" to obtain a ratio. The ratio differences between patients and controls were tested with ANOVA performed separately for PET and SPECT., Results: The difference between probable AD patients and controls was significant for both PET (p < 0.00001) and SPECT (p < 0.005); this difference was significant for the frontal, temporal and parietal cortices (p < 0.0001) for PET, and for the temporal (p < 0.005) and parietal (p < 0.001) cortices for SPECT. Temporo-parietal defects were detected in all subjects with PET and in 90% with SPECT., Conclusion: PET and SPECT are able to detect characteristic temporo-parietal abnormalities in probable AD. However, the presence of abnormalities in other associative areas is better evaluated with PET.

Areas of myocardial infarction may retain glycolytic activity and this finding is indicative of tissue viability and predictive of functional recovery after revascularization. In order to assess the relation between the time elapsed from the occurrence of acute myocardial infarction and persistence of myocardial metabolic activity in the infarcted tissue, we prospectively studied 65 patients with previous myocardial infarction diagnosed clinically and by electrocardiographic (Q wave) and enzymatic criteria. All patients underwent coronary angiography and contrast left ventriculography, evaluation of regional myocardial glucose metabolism (in the fasting state) by positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG), and assessment of myocardial perfusion by single photon emission computed tomography (SPECT) with technetium-99m methoxyisobutyl isonitrile (99mTc-MIBI). Based on the regional metabolic and perfusion findings, patients were divided into 2 groups, depending on the absence (group 1, 26 patients) or presence (group 2, 39 patients) of [18F]FDG uptake in the underperfused regions. Areas of underperfusion at rest, consistent with the clinically identified myocardial infarction site, were observed in all patients. Severity of coronary artery disease, presence of collaterals, number of hypocontractile segments, and wall motion score did not differ significantly in the 2 groups. The time elapsed from the infarction was significantly greater (1,860 +/- 1,333 days) in group 1 than in group 2 (92 +/- 115 days; p < 0.0001). Exercise caused an increase in severity and/or extent of resting perfusion abnormalities in a greater proportion of patients of group 1 (53% vs 23%).(ABSTRACT TRUNCATED AT 250 WORDS)

Positron emission tomography (PET) allows the non invasive and quantitative measurement of regional distribution of molecules labeled with positron emitting isotopes such as: nitrogen, oxygen, carbon and fluorine. The aim of the present paper is to review the applications of this methodology for the in vivo study of the kinetics and of the mechanism of action of drugs in humans.

Functional tissue heterogeneity, i.e., inclusion of tissues with different rates of blood flow and metabolism within a single region of interest, is an unavoidable problem with PET. Errors in determination of regional cerebral glucose utilization (rCMRglc) with [18F]FDG have resulted from the currently used simplifying assumption that all regions examined are homogeneous. We have established an optimal, yet practical procedure to minimize errors due to tissue heterogeneity in determination of rCMRglc. Effects of applying the three-rate constant kinetic model designed for homogeneous tissues with both dynamic and single-scan procedures and the Patlak plot were evaluated in normal subjects in experimental periods up to 120 min following tracer injection. The procedure with a single scan carried out any time within the interval between 60 and 120 min following tracer injection, combined with population average rate constants determined over a 120-min period, was found to be optimal for quantitative rCMRglc studies.

A procedure for patient repositioning and compensation for misalignment between transmission and emission data in positron emission tomography (PET) heart studies has been developed. Following the transmission scan (TR1), patients are moved from the scanner bed for the administration of the tracer, and repositioned when ready for the emission scan (EM1). A short postinjection transmission scan (TR2) is performed at the end of the EM1 study. TR1 and TR2 images are compared to recognize misalignment between transmission and emission studies. TR1 sinograms are compensated for misalignment to allow for a proper attenuation correction. The procedure has been tested on phantom and [18F]FDG PET heart studies. Misalignments down to 2.5 mm translation and 1 degree rotation in the transaxial plane and 4 mm in the axial direction can be recognized and compensated for. The procedure is suitable for clinical purposes, allowing reduction of patient time on the scanner bed, increased patient comfort and significant increase of patient throughput.

We tested the possibility of identifying areas of hibernating myocardium by the combined assessment of perfusion and metabolism using single photon emission tomography (SPET) with technetium-99m hexakis 2-methoxyisobutylisonitrile (99mTc-MIBI) and positron emission tomography (PET) with fluorine-18 fluoro-2-deoxy-D-glucose (18F-FDG). Segmental wall motion, perfusion and 18F-FDG uptake were scored in 5 segments in 14 patients with coronary artery disease (CAD), for a total number of 70 segments. Each subject underwent the following studies prior to and following coronary artery bypass grafting (CABG): first-pass radionuclide angiography, electrocardiography gated planar perfusion scintigraphy and SPET perfusion scintigraphy with 99mTc-MIBI and, after 16 h fasting, 18F-FDG/PET metabolic scintigraphy. Wall motion impairment was either decreased or completely reversed by CABG in 95% of the asynergic segments which exhibited 18F-FDG uptake, whereas it was unmodified in 80% of the asynergic segments with no 18F-FDG uptake. A stepwise multiple logistic analysis was carried out on the asynergic segments to estimate the postoperative probability of wall motion improvement on the basis of the preoperative regional perfusion and metabolic scores. The segments with the highest probability (96%) of functional recovery from preoperative asynergy after revascularization were those with a marked 18F-FDG uptake prior to CABG. High probabilities of functional recovery were also estimated for the segments presenting with moderate and low 18F-FDG uptake (92% and 79%, respectively). A low probability of functional recovery (13%) was estimated in the segments with no 18F-FDG uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

The remote effects of small unilateral cerebrovascular lesions confined to subcortical structures were evaluated by single photon emission computerized tomography (SPECT) and a CBF tracer, I-123 HIPDM. A CBF study was performed in 34 patients presenting with subcortical stroke either in the acute or in the chronic stages. Twenty-one of the 34 patients showed areas of cortical hypoperfusion ipsilateral to the subcortical lesion. In 14 patients, asymmetry of perfusion was also observed at the cerebellar level, perfusion being significantly reduced in the cerebellar hemisphere contralateral to the lesion. There was no correlation between the degree and extension of these remote effects and the type of stroke (ischemic or hemorrhagic), the patency of cerebral arteries, or the size and site of the lesion by transmissive computerized tomography (TCT). Subcortical hematomas showed a correlation between occurrence of remote effects and time interval from the onset of stroke, occurring more frequently in the acute phase. A correlation was observed between cortical and cerebellar remote effects and the severity of clinical presentation. The causes of remote effects are still unclear and have been extensively debated. Our data indicate that there is a relationship of remote effect to the neurological status. It is possible to show, by noninvasive, low-cost methods, remote CBF effects after stroke that may contribute to the assessment of brain functional impairment.

Positron emission tomography (PET) enables the study of neuropharmacological variables, such as regional receptor densities, alterations in receptor occupancy from endogenous neurotransmitters and exogenous drugs, and receptor plasticity in living human subjects. The purpose of this paper is to review the procedures currently used to study brain pharmacology based on the use of radioactive tracers and PET, and to identify open issues in this field. In particular, the article reviews methodology for tracer validation, including essential biochemistry and kinetic modeling, as well as present clinical applications of tracers used to study dopamine, opioid, benzodiazepine, and cholinergic receptors.

Regional cerebral and cerebellar blood flows were studied by N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-[123I]iodobenzyl)-1,3- propanediamine 2 HCl (I-123 HIPDM) and single-photon emission computerized tomography (SPECT) in a patient with an ischemic lesion of the pons. An asymmetry of perfusion of the cerebellar hemispheres, normal on transmission computerized tomography scan, was demonstrated by SPECT studies in the early acute phase and confirmed 15 days after. This finding may be related to the interruption of the corticopontocerebellar pathways.