Search

In this contribution, several opportunities and challenges for long axial field of view (LAFOV) PET are described. It is an anthology in which the main issues have been highlighted. A consolidated overview of the camera system implementation, business and financial plan, opportunities and challenges is provided. What the nuclear medicine and molecular imaging community can expect from these new PET/CT scanners is the delivery of more comprehensive information to the clinicians for advancing diagnosis, therapy evaluation and clinical research.

In recent in vivo studies using positron emission tomography (PET) our group demonstrated that the myocardial beta adrenoceptor (betaAR) density is reduced in arrhythmogenic right ventricular cardiomyopathy (ARVC) and idiopathic right ventricular outflow tract tachycardia (RVO-VT) associated with an increased presynaptic catecholamine washout. It was hypothesised that the reduction of myocardial betaAR density is secondary to an increase of local catecholamines in the myocardium resulting from the presynaptic dysfunction since circulating plasma catecholamines were demonstrated to be unchanged in these conditions. To further prove this hypothesis of an organ-limited adrenergic nervous dysfunction of the heart, this study aimed to investigate betaAR density in another thoracic organ, the lung.Pulmonary and myocardial betaAR density was measured in 7 ARVC patients, 8 RVO-VT patients and in a group of healthy controls (n = 13) using the non-selective beta-blocker [11C]-CGP 12177 and PET.Pulmonary betaAR density was similar in controls (12.4 +/- 1.7 pmol/g tissue), ARVC (11.6 +/- 1.7 pmol/g tissue, p = ns) and RVO-VT (12.8 +/- 2.0 pmol/g tissue, p = ns), whereas myocardial betaAR density was significantly reduced in ARVC (6.3 +/- 1.1 pmol/g tissue, p = 0.006) and RVO-VT (6.8 +/- 1.2 pmol/g tissue, p=0.02) as compared to controls (8.8+/-1.5 pmol/g tissue).The unchanged pulmonary betaAR density in the presence of a previously described significant reduction in myocardial betaAR density in the same patient principally supports our pathophysiological hypothesis that the myocardial betaAR density may be reduced in ARVC and RVO-VT because of an increase in local synaptic catecholamine levels due to an organ-limited presynaptic adrenergic dysfunction of the heart. Since in the present study only pulmonary betaAR density was measured, future functional studies excluding pulmonary betaAR desensitisation are required to finally prove the unchanged pulmonary sympathetic innervation in ARVC and RVO-VT.

Objective This [C-11]flumazenil (FMZ) study evaluates the performance of various parametric analysis methods and their ability to detect statistically significant group differences. Methods Dynamic 60-min FMZ scans were performed in eight healthy and nine individuals with major depressive disorder. Parametric volume of distribution (V-T) images were generated using a basis function method (BFM) implementation of the single tissue compartment model (1T) and Logan plot analysis, both with a metabolite-corrected arterial plasma input function. Parametric binding potential (BPND) images were generated using multilinear reference tissue methods (MRTM0-4), reference Logan and rec Results BFM was more accurate than Logan, but showed more variability. Both RPM methods and MRTM2 showed the best average correlation with the simplified reference tissue model. In using SPM, SUV and SUVr images provided the best contrast between groups in the parahippocampal gyri, but provided large underestimation and overestimation in quantitative comparisons. BFM and RPM methods allowed for the determination of perfusion effects. Conclusion Parametric Logan VT, MRTM2 and RPM1-2 BPND methods allow the best quantitative comparison of FMZ binding between groups and show good discriminating performance in SPM analysis. Nucl Med Commun 33:422-430 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Quantification of myocardial beta-adrenoceptor density (B-max) is of interest in cardiac diseases in which altered function of the sympathetic nervous system is thought to play a pathophysiological role. PET provides an unrivaled means of taking regional measurements of cardiac microcirculatory function, tissue metabolism and autonomic nervous system activity. Measurements in small regional areas may be biased because of increased noise levels. This study examined the parametric polar map approach for the regional quantification of B-max. Methods: Dynamic PE-T with parametric polar map imaging was performed in 10 healthy volunteers and 4 patients with hypertrophic cardiomyopathy using (S)-[C-11]-(4-(3-tertiarybutylamino-2-hydroxypropoxy)-benzidimazole-2)-o n hydrochloride (CGP)-12177 and a double-injection protocol. Time-activity curves were corrected for partial volume, spill-over and wall motion effects. The mean B-max of the left ventricle was calculated in two ways. First, the average time-activity curve of all segments, having the highest achievable signal-to-noise ratio, was used to calculate B-max(mTAC) (the myocardial beta-adrenoceptor density of the left ventricle calculated using the average time-activity curve). The bias in B-max(mTAC) introduced by noise is minimal. Second, an estimate of whole-heart receptor density was calculated using the polar map method by averaging the values of B-max obtained for 576 individual segments. In these calculations, three different filters (3 x 5, 3 x 9 and 3 x 13 segments) were used to smooth the time-activity curves before calculating B-max. Mean values of whole-left-ventricular receptor density obtained by averaging regional values using the different filters (B-max(PMF1/2/3)) were compared with B-max(mTAC) to assess bias introduced by the polar map approach. Segments with a calculated B-max outside the range 0.1-50 pmol/g were considered unreliable and were excluded from the analysis. Results: The differences between the two methods of calculating B-max were small (7.8%, 4.8% and 3.2%, with the three filters, respectively). Reliable results were obtained in >95% of the segments and in 9 volunteers and all 4 patients. Conclusion: When using PET for the quantification of beta-adrenoceptor density, the regional variation in B-max can be reliably assessed using the parametric polar map approach.

Using unitary transformations together with a previously described statistical theory for optimal linear dimension reduction it is shown how pixels in a sequence of images can be decomposed into a sum of variates, covariates, and residual vectors, with all covariances equal to zero. It is demonstrated that this decomposition is optimal with respect to noise. In addition, it results in simplified and well conditioned equations for dimension reduction and elimination of covariates. The factor images are not degraded by subdivision of the time intervals. In contrast to traditional factor analysis, the factors can be measured directly or calculated based on physiological models. This procedure not only solves the rotation problem associated with factor analysis, but also eliminates the need for calculation of the principal components altogether. Examples are given of factor images of the heart, generated from a dynamic study using oxygen-15-labelled water and positron emission tomography. As a special application of the method, it is shown that the factor images may reveal any contamination of the blood curve derived from the original dynamic images with myocardial activity.

The in vivo regional distribution of pulmonary beta-adrenoceptors was imaged and quantified in humans with the hydrophilic beta-adrenoceptor antagonist (S)-CGP-12177 labeled with carbon-11 {(S)-[C-11]CGP-121771 and positron emission tomography (PET). Six normal male volunteers and eight patients with hypertrophic cardiomyopathy were studied. PET scanning consisted of transmission (tissue density), (CO)-O-15 (blood volume), and (S)-[C-11]CGP-12177 (beta-adrenoceptor) emission scans. High-specific-activity (S)-[C-11]CGP-12177 (7.1 +/- 2.0 mug, 6.5 +/- 2.1 GBq/mumol) was given intravenously followed by a low-specific-activity (S)-[C-11]CGP12177 injection (34.0 +/- 4.8 mug, 2.3 +/- 0.8 GBq/mumol). Binding capacity (Bmax) was calculated in each region of interest as picomoles per gram by normalizing it to the local extravascular tissue density. In normal subjects, average Bmax for all regions of interest was 14.8 +/- 1.6 (SD) pmol/g, which is similar to previously reported in vitro values. In both groups there were no differences in beta-adrenoceptor density between peripheral and central regions nor between right and left lungs. In patients with hypertrophic cardiomyopathy, extravascular tissue density was 24% higher than in normal subjects; Bmax per milliliter thoracic volume was correspondingly higher but was not different from that in normal subjects when expressed per gram tissue (15.8 +/- 2.6 pmol/g). These data suggest that in vivo beta-adrenoceptor density may be quantifiable in humans with the use of PET. This should offer a means to study physiological regulation through repeat measurements.

[F-18]-fluorodeoxyglucose ([F-18]-FDG) uptake is enhanced in most malignant tumours which in turn can be measured using positron emission tomography (PET). A number of small clinical trials have indicated that quantification of the change in tumour [F-18]-FDG uptake may provide an early, sensitive, pharmacodynamic marker of the tumoricidal effect of anticancer drugs. This may allow for the introduction of subclinical response for anticancer drug evaluation in early clinical trials and improvements in patient management. For comparison of results from smaller clinical trials and larger-scale multicentre trials a consensus is desirable for: (i) common measurement criteria; and (ii) reporting of alterations in [F-18]-FDG uptake with treatment. This paper summarises the current status of the technique and recommendations on the measurement of [F-18]-FDG uptake for tumour response monitoring from a consensus meeting of the European Organization for Research and Treatment of Cancer (EORTC) PET study group held in Brussels in February 1998 and confirmed at a subsequent meeting in March 1999. (C) 1999 Elsevier Science Ltd. All rights reserved.

Recent studies in neurodegenerative conditions have increasingly highlighted that the same neuropathology can trigger different clinical phenotypes or, vice-versa, that similar phenotypes can be triggered by different neuropathologies. This evidence has called for the adoption of a pathology spectrum-based approach to study neurodegenerative proteinopathies. These conditions share brain deposition of abnormal protein aggregates, leading to aberrant biochemical, metabolic, functional, and structural changes. Positron emission tomography (PET) is a well-recognized and unique tool for the in vivo assessment of brain neuropathology, and novel PET techniques are emerging for the study of specific protein species. Today, key applications of PET range from early research and clinical diagnostic tools to their use in clinical trials for both participants screening and outcome evaluation. This position article critically reviews the role of distinct PET molecular tracers for different neurodegenerative proteinopathies, highlighting their strengths, weaknesses, and opportunities, with special emphasis on methodological challenges and future applications. (C) 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Verapamil alleviates symptoms in patients with hypertrophic cardiomyopathy (HCM), but the underlying mechanism of improvement remains speculative. Baseline and dipyridamole myocardial blood flow (MBF) were measured in 15 HCM patients (14 men, 42 +/- 10 years), before and after 4 weeks of verapamil SR 480 mg daily, using O-15 labelled water and positron emission tomography (PET). Subendocardial (endo) and subepicardial (epi) MBF was measured in the septum (thickness 25.4 +/- 5.8 mm). Pre-treatment baseline whole heart MBF was 1.02 +/- 0.28 ml/min/g and 1.01 +/- 0.30 ml/min/g on treatment (p = ns). Dipyridamole MBF was 1.39 +/- 0.31 ml/min/g off treatment and 1.23 +/- 0.34 ml/min/g on treatment (p = ns). Coronary flow reserve (dipyridamole/resting MBF) was 1.45 +/- 0.52 and 1.30 +/- 0.51, respectively (p = ns). At baseline, the septal endo/epi MBF ratio was uniform off and on treatment (1.13 +/- 0.18 vs 1.18 +/- 0.21, p = ns). Before treatment, the endo/epi ratio following dipyridamole decreased to 0.93 +/- 0.24 (p < 0.01 vs baseline) and 5/15 (33%) patients had a ratio < 0.8 which would suggest subendocardial underperfusion. During treatment, the endo/epi ratio following dipyridamole was no more different from baseline (1.06 +/- 0.24, p = ns vs baseline) and 2/14 (14%) patients had an endo/epi < 0.8. PET can be successfully used to determine transmural MBF in vivo in patients with hypertrophied ventricles. Despite symptomatic improvement, high dose verpamil therapy does not increase total MBF in patients with HCM but may improve septal transmural MBF distribution during dipyridamole in some patients.

Positron emission tomography (PET) in conjunction with (CO2)-O-15 or (H2O)-O-15 can be used to measure myocardial blood flow (MBF) and tissue fraction (TF), i.e, the fraction of the tissue mass in the volume of the region of interest. However, with (CO2)-O-15 inhalation, the tissue fraction in the septum is overestimated. Bolus injection of (H2O)-O-15 together with arterial cannulation gives very precise results but is invasive. The purpose of this study was to develop a method which circumvents these problems. A four-parameter model with parameters for MBF, TF and spill-over fractions from both left and right ventricular cavities was developed. This method was compared with a three-parameter model (no right ventricular cavity spill-over) in both septal and non-septal regions of interest for three different administration protocols: bolus injection of (H2O)-O-15, infusion of (H2O)-O-15 and inhalation of (CO2)-O-15. It was found that MBF can be measured with intravenous administration of (H2O)-O-15 without the requirement for arterial cannulation. The four-parameter protocol with bolus injection was stable in clinical studies. The four-parameter model proved essential for the septum, where it gave highly significantly better fits than did the three-parameter model (P

Objectives. This study investigated the neuronal reuptake of norepinephrine (uptake-1) and the beta-adrenoceptor density in patients,vith idiopathic right ventricular outflow tract tachycardia (RVO-VT). Background. Clinical findings, such as the inducibility of ventricular tachycardia by stress or catecholamine infusion, and the therapeutic efficacy of antiarrhythmic drugs with antiadrenergic properties suggest abnormalities of cardiac sympathetic innervation in patients,vith idiopathic RVO-VT. Methods. Eight patients with idiopathic RVO-VT and a total of 29 age-matched control subjects were investigated by positron emission tomography using [C-11] hydroxyephedrine (HED) (volume of distribution of [C-11]HED) to assess presynaptic norepinephrine reuptake; [C-11] CGP 12177 (maximal binding capacity of [C-11]CGP 12177) to measure postsynaptic beta-adrenoceptor density; and oxygen-15-labeled water for quantification of myocardial blood flow (MBF). Results. Both myocardial catecholamine reuptake and beta adrenoceptor density were significantly reduced in patients with idiopathic RVO-VT. The volume of distribution of [C-11]HED in patients with RVO-VT was (mean +/- SD) 41.0 +/- 13.5 versus 71.0 +/- 18.8 ml/g in control subjects (p < 0.002). The maximal binding capacity of the beta-adrenoceptor antagonist [C-11] CGP 12177 was 6.8 +/- 1.2 pmol/g in patients with RVO-VT versus 10.2 +/- 2.9 pmol/g in control subjects (p < 0.004). There were no significant differences in MBF at rest (0.98 +/- 0.14 vs. 0.97 +/- 0.24 ml/min per g, p = NS) between patients with RVO-VT and control subjects. Conclusions. The findings of the present study suggest that myocardial beta-adrenoceptor downregulation in patients with RVO-VT occurs subsequently to increased local synaptic catecholamine levels caused by impaired catecholamine reuptake.

The long-term consequences of CAD remain a prominent clinical problem. Particularly with new therapeutic strategies that reduce the mortality associated with acute coronary syndromes, more patients suffer from the long-term sequelae of this condition. In this setting, the identification of those segments of myocardium that appear dysfunctional distal to coronary stenoses and that can improve after coronary revascularization is of considerable clinical importance. Although the diagnostic and therapeutic aspects of this problem are clearly defined, the pathophysiological mechanisms underlying the dysfunctional myocardium are controversial. It was demonstrated more than 20 years ago1 2 that resting wall-motion abnormalities in patients with CAD can improve after administration of an inotropic agent or after coronary bypass. An article published in 1978 by Diamond et al3 presaged the concept of hibernating myocardium: “Reports of sometimes dramatic improvement in segmental left ventricular function following coronary bypass surgery, although not universal, leaves the clear implication that ischemic non-infarcted myocardium can exist in a state of function hibernation.” Rahimtoola, in an article published in 1985,4 popularized this concept and later suggested that “hibernating myocardium is a state of persistently impaired myocardial and left ventricular function at rest due to reduced coronary blood flow that can be partially or completely restored to normal either by improving blood flow or by reducing oxygen demand.”5 Since the introduction of the term “hibernation,”3 4 5 6 the clinical importance of reversible left ventricular dysfunction has been widely accepted. The concept of an adaptive process that decreases myocardial oxygen consumption in the presence of either chronically or intermittently reduced oxygen delivery has generated considerable clinical and experimental interest. Accordingly, our aims were to (1) review the current criteria of the definition of hibernating myocardium, (2) summarize recent clinical as well as experimental data pertaining to this subject, …

Background —The frequent provocation of ventricular tachycardia by stress or catecholamines and the efficacy of antiarrhythmic drugs with antiadrenergic properties suggest an involvement of the cardiac adrenergic system in arrhythmogenesis in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Previous studies demonstrated abnormalities of the presynaptic uptake-1 assessed by 123 I-MIBG–single-photon emission computed tomography. Methods and Results —This study investigated neuronal reuptake of norepinephrine (uptake-1) and β-adrenergic receptor density in 8 patients with ARVC and 29 age-matched control subjects. All subjects underwent positron emission tomography with the volume of distribution (V d ) of [ 11 C]hydroxyephedrine ( 11 C-HED) used to assess presynaptic norepinephrine reuptake, the maximum binding capacity (B max ) of [ 11 C]CGP-12177 ( 11 C-CGP-12177) to assess postsynaptic β-adrenergic receptor density, and [ 15 O]H 2 O for quantification of myocardial blood flow. Patients with ARVC demonstrated a highly significant global reduction in postsynaptic β-adrenergic receptor density compared with that in control subjects (B max of 11 C-CGP-12177: 5.9±1.3 vs 10.2±2.9 pmol/g tissue, P d of 11 C-HED: 59.1±25.2 vs 71.0±18.8 mL/g tissue, NS). There were no differences in myocardial blood flow between the groups, and plasma norepinephrine was within normal limits in patients and control subjects. Conclusions —The findings demonstrate a significant reduction of myocardial β-adrenergic receptor density in patients with ARVC. This may result from a secondary downregulation after increased local synaptic norepinephrine levels caused by increased firing rates of the efferent neurons or as the result of impaired presynaptic catecholamine reuptake. These findings give new insights into the pathophysiology of arrhythmogenesis in ARVC, with potential impact on diagnostic evaluation and therapeutic management.

The measurement of regional myocardial blood flow (MBF) with (H2O)-O-15 and PET requires an additional (CO)-O-15 blood-pool scan for the purpose of region of interest (ROI) definition. This additional scan results in a substantially increased radiation dose, study duration and risk of movement artifacts. Therefore, a method was developed to generate myocardial factor images directly from the dynamic (H2O)-O-15 study without the need for a (CO)-O-15 scan. Methods: The factor sinograms were generated by means of linear dimension reduction of the dynamic sinograms, where the required variate and covariate factors (myocardial and blood time-activity curves) were modeled from the lung time-activity curve. The factor images were generated by iterative reconstruction. Results: No significant difference was found between MBF values from ROls drawn on the traditional images (using the (CO)-O-15 scan) and those drawn on the factor images. Conclusion: It is possible to generate myocardial images directly from the dynamic (H2O)-O-15 study, so that the (CO)-O-15 scan can be omitted from MBF studies. The proposed method is robust and results in nearly optimal signal-to-noise ratios in the factor images.