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OBJECTIVES: The aim of this study was to compare the costs of a noninvasive cardiac magnetic resonance (CMR)-guided strategy versus 2 invasive strategies with and without fractional flow reserve (FFR). BACKGROUND: Coronary artery disease (CAD) is a major contributor to the public health burden. Stress perfusion CMR has excellent accuracy to detect CAD. International guidelines recommend as a first step noninvasive testing of patients in stable condition with known or suspected CAD. However, nonadherence in routine clinical practice is high. METHODS: In the EuroCMR (European Cardiovascular Magnetic Resonance) registry (n = 3,647, 59 centers, 18 countries) and the U.S.-based SPINS (Stress-CMR Perfusion Imaging in the United States) registry (n = 2,349, 13 centers, 11 states), costs were calculated for 12 health care systems (8 in Europe, the United States, 2 in Latin America, and 1 in Asia). Costs included diagnostic examinations (CMR and x-ray coronary angiography [CXA] with and without FFR), revascularizations, and complications during 1-year follow-up. Seven subgroup analyses covered low- to high-risk cohorts. Patients with ischemia-positive CMR underwent CXA and revascularization at the treating physician's discretion (CMR+CXA strategy). In the hypothetical invasive CXA+FFR strategy, costs were calculated for initial CXA and FFR in vessels with ≥50% stenoses, assuming the same proportion of revascularizations and complications as with the CMR+CXA strategy and FFR-positive rates as given in the published research. In the CXA-only strategy, costs included CXA and revascularizations of ≥50% stenoses. RESULTS: Consistent cost savings were observed for the CMR+CXA strategy compared with the CXA+FFR strategy in all 12 health care systems, ranging from 42% ± 20% and 52% ± 15% in low-risk EuroCMR and SPINS patients with atypical chest pain, respectively, to 31% ± 16% in high-risk SPINS patients with known CAD (P < 0.0001 vs 0 in all groups). Cost savings were even higher compared with CXA only, at 63% ± 11%, 73% ± 6%, and 52% ± 9%, respectively (P < 0.0001 vs 0 in all groups). CONCLUSIONS: In 12 health care systems, a CMR+CXA strategy yielded consistent moderate to high cost savings compared with a hypothetical CXA+FFR strategy over the entire spectrum of risk. Cost savings were consistently high compared with CXA only for all risk groups. ispartof: JACC-CARDIOVASCULAR IMAGING vol:15 issue:4 pages:607-625 ispartof: location:United States status: published

PURPOSE OF REVIEW: The association between hallucinations and sensory loss, especially vision- and hearing-impairment, has been firmly established over the past years. The deafferentation theory, a decrease of the threshold for activation in the brain and the consequential imbalance between excitatory and inhibitory brain networks, is hypothesized to underly this relationship. Here we review the studies investigating this theory with a focus on the most recent literature to better understand the contribution of sensory loss to hallucinations.RECENT FINDINGS: A large cross-sectional study has recently confirmed the relationship between auditory impairment and deafferentation. However, the underlying mechanisms of deafferentation are still under debate, with hyperexcitability and deviations in bottom-up and top-down processes being the most likely explanations. Social isolation following sensory impairment increases the risk for hallucinations. Better knowledge and awareness about the contribution of deafferentation and loneliness would benefit diagnosis and treatment of hallucinations.SUMMARY: Studies imply activity in higher order areas, corresponding to the functional mapping of sensory system, and a general state of higher excitability as neurobiological explanation. Auditory deafferentation, tinnitus and other auditory hallucinations, likely lie on a continuum. Social isolation mediates psychotic symptoms in sensory-impaired individuals. Currently, there is no standard treatment for deafferentation hallucinations.

Genetic and phenotypic tumour heterogeneity is an important cause of therapy resistance. Moreover, non-uniform spatial drug distribution in cancer treatment may cause pseudo-resistance, meaning that a treatment is ineffective because the drug does not reach its target at sufficient concentrations. Together with tumour heterogeneity, non-uniform drug distribution causes "therapy heterogeneity": a spatially heterogeneous treatment effect. Spatial heterogeneity in drug distribution occurs on all scales ranging from interpatient differences to intratumour differences on tissue or cellular scale. Nanomedicine aims to improve the balance between efficacy and safety of drugs by targeting drug-loaded nanoparticles specifically to tumours. Spatial heterogeneity in nanoparticle and payload distribution could be an important factor that limits their efficacy in patients. Therefore, imaging spatial nanoparticle distribution and imaging the tumour environment giving rise to this distribution could help understand (lack of) clinical success of nanomedicine. Imaging the nanoparticle, drug and tumour environment can lead to improvements of new nanotherapies, increase understanding of underlying mechanisms of heterogeneous distribution, facilitate patient selection for nanotherapies and help assess the effect of treatments that aim to reduce heterogeneity in nanoparticle distribution.In this review, we discuss three groups of imaging modalities applied in nanomedicine research: non-invasive clinical imaging methods (nuclear imaging, MRI, CT, ultrasound), optical imaging and mass spectrometry imaging. Because each imaging modality provides information at a different scale and has its own strengths and weaknesses, choosing wisely and combining modalities will lead to a wealth of information that will help bring nanomedicine forward.

Over the last three decades, the brain's functional and structural imaging has become more prevalent in psychiatric research and clinical application. A substantial amount of psychiatric research is based on neuroimaging studies that aim to illuminate neural mechanisms underlying psychiatric disorders. Single-photon emission computed tomography (SPECT) is one of those developing brain imaging techniques among various neuroimaging technologies. Compared to PET, SPECT imaging is easy, less expensive, and practical for radioligand use. Current technologies increased the spatial accuracy of SPECT findings by combining the functional SPECT images with CT images. The radioligands bind to receptors such as 5-hydroxytryptamine 2A, and dopamine transporters can help us comprehend neural mechanisms of psychiatric disorders based on neurochemicals. This mini-review focuses on the SPECT-based neuroimaging approach to psychiatric disorders such as schizophrenia and major depressive disorder (MDD). Research-based SPECT findings of psychiatric disorders indicate that there are notable changes in biochemical components in certain disorders. Even though many studies support that SPECT can be used in psychiatric clinical practice, we still only use subjective diagnostic criteria such as the Diagnostic Statistical Manual of Mental Disorders (DSM-5). Glimpsing into the brain's biochemical world via SPECT in psychiatric disorders provides more information about the pathophysiology and future implication of neuroimaging techniques.

Purpose of review The association between hallucinations and sensory loss, especially vision- and hearing-impairment, has been firmly established over the past years. The deafferentation theory, a decrease of the threshold for activation in the brain and the consequential imbalance between excitatory and inhibitory brain networks, is hypothesized to underly this relationship. Here we review the studies investigating this theory with a focus on the most recent literature to better understand the contribution of sensory loss to hallucinations. Recent findings A large cross-sectional study has recently confirmed the relationship between auditory impairment and deafferentation. However, the underlying mechanisms of deafferentation are still under debate, with hyperexcitability and deviations in bottom-up and top-down processes being the most likely explanations. Social isolation following sensory impairment increases the risk for hallucinations. Better knowledge and awareness about the contribution of deafferentation and loneliness would benefit diagnosis and treatment of hallucinations. Summary Studies imply activity in higher order areas, corresponding to the functional mapping of sensory system, and a general state of higher excitability as neurobiological explanation. Auditory deafferentation, tinnitus and other auditory hallucinations, likely lie on a continuum. Social isolation mediates psychotic symptoms in sensory-impaired individuals. Currently, there is no standard treatment for deafferentation hallucinations.

Cardiac imaging has a pivotal role in the prevention, diagnosis and treatment of ischaemic heart disease. SPECT is most commonly used for clinical myocardial perfusion imaging, whereas PET is the clinical reference standard for the quantification of myocardial perfusion. MRI does not involve exposure to ionizing radiation, similar to echocardiography, which can be performed at the bedside. CT perfusion imaging is not frequently used but CT offers coronary angiography data, and invasive catheter-based methods can measure coronary flow and pressure. Technical improvements to the quantification of pathophysiological parameters of myocardial ischaemia can be achieved. Clinical consensus recommendations on the appropriateness of each technique were derived following a European quantitative cardiac imaging meeting and using a real-time Delphi process. SPECT using new detectors allows the quantification of myocardial blood flow and is now also suited to patients with a high BMI. PET is well suited to patients with multivessel disease to confirm or exclude balanced ischaemia. MRI allows the evaluation of patients with complex disease who would benefit from imaging of function and fibrosis in addition to perfusion. Echocardiography remains the preferred technique for assessing ischaemia in bedside situations, whereas CT has the greatest value for combined quantification of stenosis and characterization of atherosclerosis in relation to myocardial ischaemia. In patients with a high probability of needing invasive treatment, invasive coronary flow and pressure measurement is well suited to guide treatment decisions. In this Consensus Statement, we summarize the strengths and weaknesses as well as the future technological potential of each imaging modality., Cardiac imaging has a pivotal role in the prevention, diagnosis and treatment of ischaemic heart disease. In this Consensus Statement, the authors summarize the use of SPECT, PET, MRI, echocardiography, CT and invasive coronary flow and pressure measurement, and describe the relative strengths and weaknesses of each modality.

Genetic and phenotypic tumour heterogeneity is an important cause of therapy resistance. Moreover, non-uniform spatial drug distribution in cancer treatment may cause pseudo-resistance, meaning that a treatment is ineffective because the drug does not reach its target at sufficient concentrations. Together with tumour heterogeneity, non-uniform drug distribution causes "therapy heterogeneity": a spatially heterogeneous treatment effect. Spatial heterogeneity in drug distribution occurs on all scales ranging from interpatient differences to intratumour differences on tissue or cellular scale. Nanomedicine aims to improve the balance between efficacy and safety of drugs by targeting drug-loaded nanoparticles specifically to tumours. Spatial heterogeneity in nanoparticle and payload distribution could be an important factor that limits their efficacy in patients. Therefore, imaging spatial nanoparticle distribution and imaging the tumour environment giving rise to this distribution could help understand (lack of) clinical success of nanomedicine. Imaging the nanoparticle, drug and tumour environment can lead to improvements of new nanotherapies, increase understanding of underlying mechanisms of heterogeneous distribution, facilitate patient selection for nanotherapies and help assess the effect of treatments that aim to reduce heterogeneity in nanoparticle distribution. In this review, we discuss three groups of imaging modalities applied in nanomedicine research: non-invasive clinical imaging methods (nuclear imaging, MRI, CT, ultrasound), optical imaging and mass spectrometry imaging. Because each imaging modality provides information at a different scale and has its own strengths and weaknesses, choosing wisely and combining modalities will lead to a wealth of information that will help bring nanomedicine forward.

BACKGROUND Cardiac troponin T concentrations measured with high-sensitivity assays (hs-cTnT) provide important prognostic information for patients with stable coronary artery disease (CAD). However, whether hs-cTnT concentrations mainly reflect left ventricular (LV) remodeling or recurrent myocardial ischemia in this population is not known. METHODS We measured hs-cTnT concentrations in 619 subjects with suspected stable CAD in a prospectively designed multicenter study. We identified associations with indices of LV remodeling, as assessed by cardiac MRI and echocardiography, and evidence of myocardial ischemia diagnosed by single positron emission computed tomography. RESULTS Median hs-cTnT concentration was 7.8 ng/L (interquartile range, 4.8–11.6 ng/L), and 111 patients (18%) had hs-cTnT concentrations above the upper reference limit (>14 ng/L). Patients with hs-cTnT >14 ng/L had increased LV mass (144 ± 40 g vs 116 ± 34 g; P < 0.001) and volume (179 ± 80 mL vs 158 ± 44 mL; P = 0.006), lower LV ejection fraction (LVEF) (59 ± 14 vs 62 ± 11; P = 0.006) and global longitudinal strain (14.1 ± 3.4% vs 16.9 ± 3.2%; P < 0.001), and more reversible perfusion defects (P = 0.001) and reversible wall motion abnormalities (P = 0.008). Age (P = 0.009), estimated glomerular filtration rate (P = 0.01), LV mass (P = 0.003), LVEF (P = 0.03), and evidence of reversible myocardial ischemia (P = 0.004 for perfusion defects and P = 0.02 for LV wall motion) were all associated with increasing hs-cTnT concentrations in multivariate analysis. We found analogous results when using the revised US upper reference limit of 19 ng/L. CONCLUSIONS hs-cTnT concentrations reflect both LV mass and reversible myocardial ischemia in patients with suspected stable CAD.

Coronary artery disease (CAD) is a major cause of death and disability. Several diagnostic tests, such as myocardial perfusion scintigraphy (MPS), are accurate for the detection of CAD, as well as having prognostic value for the prediction of cardiovascular events. Nevertheless, the diagnostic and prognostic value of these tests should be cost-effective and should lead to improved clinical outcome. We have reviewed the literature on the cost-effectiveness of MPS in different circumstances: (i) the diagnosis and management of CAD; (ii) comparison with exercise electrocardiography (ECG) and other imaging tests; (iii) as gatekeeper to invasive coronary angiography (ICA), (iv) the impact of appropriate use criteria; (v) acute chest pain, and (vi) screening of asymptomatic patients with type-2 diabetes. In total 57 reports were included. Although most non-invasive imaging tests are cost-effective compared with alternatives, the data conflict on which non-invasive strategy is the most cost-effective. Different definitions of cost-effectiveness further confound the subject. Computer simulations of clinical diagnosis and management are influenced by the assumptions made. For instance, diagnostic accuracy is often defined against an anatomical standard that is wrongly assumed to be perfect. Conflicting data arise most commonly from these incorrect or differing assumptions.

Coronary artery disease (CAD) is a major cause of death and disability. Several diagnostic tests, such as myocardial perfusion scintigraphy (MPS), are accurate for the detection of CAD, as well as having prognostic value for the prediction of cardiovascular events. Nevertheless, the diagnostic and prognostic value of these tests should be cost-effective and should lead to improved clinical outcome. We have reviewed the literature on the cost-effectiveness of MPS in different circumstances: (i) the diagnosis and management of CAD; (ii) comparison with exercise electrocardiography (ECG) and other imaging tests; (iii) as gatekeeper to invasive coronary angiography (ICA), (iv) the impact of appropriate use criteria; (v) acute chest pain, and (vi) screening of asymptomatic patients with type-2 diabetes. In total 57 reports were included. Although most non-invasive imaging tests are cost-effective compared with alternatives, the data conflict on which non-invasive strategy is the most cost-effective. Different definitions of cost-effectiveness further confound the subject. Computer simulations of clinical diagnosis and management are influenced by the assumptions made. For instance, diagnostic accuracy is often defined against an anatomical standard that is wrongly assumed to be perfect. Conflicting data arise most commonly from these incorrect or differing assumptions.

Coronary artery disease (CAD) is a major cause of death and disability. Several diagnostic tests, such as myocardial perfusion scintigraphy (MPS), are accurate for the detection of CAD, as well as having prognostic value for the prediction of cardiovascular events. Nevertheless, the diagnostic and prognostic value of these tests should be cost-effective and should lead to improved clinical outcome. We have reviewed the literature on the cost-effectiveness of MPS in different circumstances: (i) the diagnosis and management of CAD; (ii) comparison with exercise electrocardiography (ECG) and other imaging tests; (iii) as gatekeeper to invasive coronary angiography (ICA), (iv) the impact of appropriate use criteria; (v) acute chest pain, and (vi) screening of asymptomatic patients with type-2 diabetes. In total 57 reports were included. Although most non-invasive imaging tests are cost-effective compared with alternatives, the data conflict on which non-invasive strategy is the most cost-effective. Different definitions of cost-effectiveness further confound the subject. Computer simulations of clinical diagnosis and management are influenced by the assumptions made. For instance, diagnostic accuracy is often defined against an anatomical standard that is wrongly assumed to be perfect. Conflicting data arise most commonly from these incorrect or differing assumptions.

Coronary artery disease (CAD) is a major cause of death and disability. Several diagnostic tests, such as myocardial perfusion scintigraphy (MPS), are accurate for the detection of CAD, as well as having prognostic value for the prediction of cardiovascular events. Nevertheless, the diagnostic and prognostic value of these tests should be cost-effective and should lead to improved clinical outcome. We have reviewed the literature on the cost-effectiveness of MPS in different circumstances: (i) the diagnosis and management of CAD; (ii) comparison with exercise electrocardiography (ECG) and other imaging tests; (iii) as gatekeeper to invasive coronary angiography (ICA), (iv) the impact of appropriate use criteria; (v) acute chest pain, and (vi) screening of asymptomatic patients with type-2 diabetes. In total 57 reports were included. Although most non-invasive imaging tests are cost-effective compared with alternatives, the data conflict on which non-invasive strategy is the most cost-effective. Different definitions of cost-effectiveness further confound the subject. Computer simulations of clinical diagnosis and management are influenced by the assumptions made. For instance, diagnostic accuracy is often defined against an anatomical standard that is wrongly assumed to be perfect. Conflicting data arise most commonly from these incorrect or differing assumptions.

The antagonistic effects of caffeine on adenosine receptors are a possible cause of false-negative stress perfusion imaging. The purpose of this study was to determine the effects of coffee intake

The trade-off between resolution and count sensitivity dominates the performance of standard gamma cameras and dictates the need for relatively high doses of radioactivity of the used radiopharmaceuticals in order to limit image acquisition duration. The introduction of cadmium-zinc-telluride (CZT)-based cameras may overcome some of the limitations against conventional gamma cameras. CZT cameras used for the evaluation of myocardial perfusion have been shown to have a higher count sensitivity compared to conventional single photon emission computed tomography (SPECT) techniques. CZT image quality is further improved by the development of a dedicated three-dimensional iterative reconstruction algorithm, based on maximum likelihood expectation maximization (MLEM), which corrects for the loss in spatial resolution due to line response function of the collimator. All these innovations significantly reduce imaging time and result in a lower patient's radiation exposure compared with standard SPECT. To guide current and possible future users of the CZT technique for myocardial perfusion imaging, the Cardiovascular Committee of the European Association of Nuclear Medicine, starting from the experience of its members, has decided to examine the current literature regarding procedures and clinical data on CZT cameras. The committee hereby aims 1) to identify the main acquisitions protocols; 2) to evaluate the diagnostic and prognostic value of CZT derived myocardial perfusion, and finally 3) to determine the impact of CZT on radiation exposure.

The trade-off between resolution and count sensitivity dominates the performance of standard gamma cameras and dictates the need for relatively high doses of radioactivity of the used radiopharmaceuticals in order to limit image acquisition duration. The introduction of cadmium-zinc-telluride (CZT)-based cameras may overcome some of the limitations against conventional gamma cameras. CZT cameras used for the evaluation of myocardial perfusion have been shown to have a higher count sensitivity compared to conventional single photon emission computed tomography (SPECT) techniques. CZT image quality is further improved by the development of a dedicated three-dimensional iterative reconstruction algorithm, based on maximum likelihood expectation maximization (MLEM), which corrects for the loss in spatial resolution due to line response function of the collimator. All these innovations significantly reduce imaging time and result in a lower patient's radiation exposure compared with standard SPECT. To guide current and possible future users of the CZT technique for myocardial perfusion imaging, the Cardiovascular Committee of the European Association of Nuclear Medicine, starting from the experience of its members, has decided to examine the current literature regarding procedures and clinical data on CZT cameras. The committee hereby aims 1) to identify the main acquisitions protocols; 2) to evaluate the diagnostic and prognostic value of CZT derived myocardial perfusion, and finally 3) to determine the impact of CZT on radiation exposure.

Apathy can be described as a loss of goal-directed purposeful behavior and is common in a variety of neurological and psychiatric disorders. Although previous studies investigated associations between abnormal brain functioning and apathy, it is unclear whether the neural basis of apathy is similar across different pathological conditions. The purpose of this systematic review was to provide an extensive overview of the neuroimaging literature on apathy including studies of various patient populations, and evaluate whether the current state of affairs suggest disorder specific or shared neural correlates of apathy. Results suggest that abnormalities within fronto-striatal circuits are most consistently associated with apathy across the different pathological conditions. Of note, abnormalities within the inferior parietal cortex were also linked to apathy, a region previously not included in neuroanatomical models of apathy. The variance in brain regions implicated in apathy may suggest that different routes towards apathy are possible. Future research should investigate possible alterations in different processes underlying goal-directed behavior, ranging from intention and goal-selection to action planning and execution. (C) 2016 Published by Elsevier Ltd.

Apathy can be described as a loss of goal-directed purposeful behavior and is common in a variety of neurological and psychiatric disorders. Although previous studies investigated associations between abnormal brain functioning and apathy, it is unclear whether the neural basis of apathy is similar across different pathological conditions. The purpose of this systematic review was to provide an extensive overview of the neuroimaging literature on apathy including studies of various patient populations, and evaluate whether the current state of affairs suggest disorder specific or shared neural correlates of apathy. Results suggest that abnormalities within fronto-striatal circuits are most consistently associated with apathy across the different pathological conditions. Of note, abnormalities within the inferior parietal cortex were also linked to apathy, a region previously not included in neuroanatomical models of apathy. The variance in brain regions implicated in apathy may suggest that different routes towards apathy are possible. Future research should investigate possible alterations in different processes underlying goal-directed behavior, ranging from intention and goal-selection to action planning and execution. (C) 2016 Published by Elsevier Ltd.

Perfusion-cardiovascular MR (CMR) imaging has been shown to reliably identify patients with suspected or known coronary artery disease (CAD), who are at risk for future cardiac events and thus, allows for guiding therapy including revascularizations. Accordingly, it is an ideal test to exclude prognostically relevant coronary artery disease. Several guidelines, such as the ESC guidelines, currently recommend CMR as non-invasive testing in patients with stable chest pain. CMR has as an advantage over the more conventional pathways as it lacks radiation and it potentially reduces costs.

Background. Caffeine is one of the most widely consumed stimulants worldwide. It is a well-recognized antagonist of adenosine and a potential cause of false-negative functional measurements during vasodilator myocardial perfusion. The aim of this systematic review is to summarize the evidence regarding the effects of caffeine intake on functional measurements of myocardial perfusion in patients with suspected coronary artery disease. Pubmed, Web of Science, and Embase were searched using a predefined electronic search strategy. Participants—healthy subjects or patients with known or suspected CAD. Comparisons—recent caffeine intake versus no caffeine intake. Outcomes—measurements of functional myocardial perfusion. Study design—observational. Fourteen studies were deemed eligible for this systematic review. There was a wide range of variability in study design with varying imaging modalities, vasodilator agents, serum concentrations of caffeine, and primary outcome measurements. The available data indicate a significant influence of recent caffeine intake on cardiac perfusion measurements during adenosine and dipyridamole induced hyperemia. These effects have the potential to affect the clinical decision making by re-classification to different risk-categories.

Background. Caffeine is one of the most widely consumed stimulants worldwide. It is a well-recognized antagonist of adenosine and a potential cause of false-negative functional measurements during vasodilator myocardial perfusion. The aim of this systematic review is to summarize the evidence regarding the effects of caffeine intake on functional measurements of myocardial perfusion in patients with suspected coronary artery disease. Pubmed, Web of Science, and Embase were searched using a predefined electronic search strategy. Participantshealthy subjects or patients with known or suspected CAD. Comparisonsrecent caffeine intake versus no caffeine intake. Outcomesmeasurements of functional myocardial perfusion. Study designobservational. Fourteen studies were deemed eligible for this systematic review. There was a wide range of variability in study design with varying imaging modalities, vasodilator agents, serum concentrations of caffeine, and primary outcome measurements. The available data indicate a significant influence of recent caffeine intake on cardiac perfusion measurements during adenosine and dipyridamole induced hyperemia. These effects have the potential to affect the clinical decision making by re-classification to different risk-categories.

Purpose Traditionally, interpretation of myocardial perfusion imaging (MPI) is based on visual assessment. Computer-based automated analysis might be a simple alternative obviating the need for extensive reading experience. Therefore, the aim of the present study was to compare the diagnostic performance of automated analysis with that of expert visual reading for the detection of obstructive coronary artery disease (CAD). Methods 206 Patients (64% men, age 58.2 ± 8.7 years) with suspected CAD were included prospectively. All patients underwent 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) and invasive coronary angiography with fractional flow reserve (FFR) measurements. Non-corrected (NC) and attenuation-corrected (AC) SPECT images were analyzed both visually as well as automatically by commercially available SPECT software. Automated analysis comprised a segmental summed stress score (SSS), summed difference score (SDS), stress total perfusion deficit (S-TPD), and ischemic total perfusion deficit (I-TPD), representing the extent and severity of hypoperfused myocardium. Subsequently, software was optimized with an institutional normal database and thresholds. Diagnostic performances of automated and visual analysis were compared taking FFR as a reference. Results Sensitivity did not differ significantly between visual reading and most automated scoring parameters, except for SDS, which was significantly higher than visual assessment (p

Because ? cameras are generally susceptible to environmental conditions and system vulnerabilities they require routine evaluation of uniformity performance. The metrics for such evaluations are commonly pixel value based. Although these metrics are typically successful at identifying regional nonuniformities they often do not adequately reflect subtle periodic structures; therefore additional visual inspections are required. The goal of this project was to develop test and validate a new uniformity analysis metric capable of accurately identifying structures and patterns present in nuclear medicine flood field uniformity images. Methods: A new uniformity assessment metric termed the structured noise index (SNI) was based on the 2 dimensional noise power spectrum (NPS). The contribution of quantum noise was subtracted from the NPS of a floodfield uniformity image resulting in an NPS representing image artifacts. A visual response filter function was then applied to both the original NPS and the artifact NPS. A single quantitative score was calculated on the basis of the magnitude of the artifact. To verify the validity of the SNI an observer study was performed with 5 expert nuclear medicine physicists. The correlation between the SNI and the visual score was assessed with Spearman rank correlation analysis. The SNI was also compared with pixel value based assessment metrics modeled on the National Electrical Manufacturers Association standard for integral uniformity in both the useful field of view (UFOV) and the central field of view (CFOV). Results: The SNI outperformed the pixel value based metrics in terms of its correlation with the visual score (r values for the SNI integral UFOV and integral CFOV were 0.86 0.59 and 0.58 respectively). The SNI had 100 sensitivity for identifying both structured and nonstructured nonuniformities; for the integral UFOV and CFOV metrics the sensitivities were only 62 and 54 respectively. The overall positive predictive value of the SNI was 87; for the integral UFOV and CFOV metrics the positive predictive values were only 67 and 50 respectively. Conclusion: The SNI accurately identified both structured and nonstructured flood field nonuniformities and correlated closely with expert visual assessment. Compared with traditional pixel value based analysis the SNI showed superior performance in terms of its correlation with visual perception. The SNI method is effective for detecting and quantifying visually apparent nonuniformities and may reduce the need for more subjective visual analyses. Copyright © 2014 by the Society of Nuclear Medicine and Molecular Imaging Inc.

Methylphenidate (MPH) occupies brain striatal dopamine transporters (DATs) and is an effective treatment for attention deficit hyperactivity disorder (ADHD). However, patients with ADHD and comorbid cocaine dependence do not benefit significantly from treatment with MPH. To better understand the neurobiology of this phenomenon, we examined DAT availability and the effects of MPH treatment on DAT occupancy in ADHD patients with and without cocaine dependence. ADHD patients without a comorbid substance use disorder (N=16) and ADHD patients with comorbid cocaine dependence (N=8) were imaged at baseline and after two weeks MPH treatment using single photon emission computed tomography (SPECT) with the DAT tracer [I-123]FP-CIT. Changes in ADHD symptoms were measured with the ADHD symptom rating scale (ASRS). At baseline, we observed lower striatal DAT availability in ADHD patients with cocaine dependence. Following fixed MPH treatment, MPH occupied significantly less striatal DATs in cocaine-dependent than in non-cocaine dependent ADHD patients. There were no significant correlations between baseline DAT availability or DAT occupancy by MPH and ADHD symptom improvement. However, we did find significant correlations between DAT occupancy by MPH and decreases in impulsivity scores and years of cocaine use. These preliminary findings suggest that low DAT occupancy is not the reason why ADHD patients with cocaine dependence do not benefit from MPH treatment. It also suggests that higher dosages of MPH in these patients are probably not the solution and that medications directed at other pharmacological targets should be considered in these comorbid ADHD patients. This trial is registered at the Dutch Trial Register, www.trialregister.nl, under Trial ID number NTR3127. (C) 2013 Elsevier B.V. and ECNP. All rights reserved.

Purpose: To determine the optimal timing of arterial first pass computed tomography (CT) myocardial perfusion imaging (CTMPI) based on dynamic CTMPI acquisitions.Methods and materials: Twenty-five patients (59 + 8.4 years, 14 male)underwent adenosine-stress dynamic CTMPI on second-generation dual-source CT in shuttle mode (30 s at 100 kV and 300 mAs). Stress perfusion magnetic resonance imaging (MRI) was used as reference standard for differentiation of non-ischemic and ischemic segments. The left ventricle (LV) wall was manually segmented according to the AHA 16-segment model. Hounsfield units (HU) in myocardial segments and ascending (AA) and descending aorta (AD) were monitored over time. Time difference between peak AA and peak AD and peak myocardial enhancement was calculated, as well as the, time delay from fixed HU thresholds of 150 and 250 HU in the AA and AD to a minimal difference of 15 HU between normal and ischemic segments. Furthermore, the duration of the 15 HU difference between ischemic and non-ischemic segments was calculated.Results: Myocardial ischemia was observed by MRI in 10 patients (56.3 +/- 9.0 years; 8 male). The delay between the maximum HU in the AA and AD and maximal HU in the non-ischemic segments was 2.8 s [2.2-4.3] and 0.0 s [0.0-2.8], respectively. Differentiation between ischemic and non-ischemic myocardial segments in CT was best during a time window of 8.6 +/- 3.8 s. Time delays for AA triggering were 4.5 s [2.2-5.6] and 2.2 s [0-2.8] for the 150 HU and 250 HU thresholds, respectively. While for AD triggering, time delays were 2.4 s [0.0-4.8] and 0.0 s [-2.2-2.6] for the 150 HU and 250 HU thresholds, respectively.Conclusion: In CTMPI, the differentiation between normal and ischemic myocardium is best accomplished during a time interval of 8.6 + 3.8 s. This time window can be utilized by a test bolus or bolus tracking in the AA or AD using the time delays identified here. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Predicting and anticipating disturbances in higher level gait is particularly relevant for patients with dementia as higher level gait appears to be closely related to higher level cognitive functioning. A phenomenon that could contribute to the understanding and prediction of disturbances in higher level gait and gait-related motor activity in the various subtypes of dementia is paraphrased as 'last in-first out'. 'Last in-first out' refers to the principle that neural circuits that mature late in development are the most vulnerable to neurodegeneration. The strength of relating symptoms to the 'last in-first out' principle is that a future symptom can be predicted and anticipated in a therapeutic way, even if the disease process has not already started.Therefore, the aim of this review is to provide new strategies for rehabilitation of higher level gait disturbances in dementia based upon the 'last in-first out' principle. These new strategies emerge from five neural networks: the superior longitudinal fasciculus, the uncinate fasciculus, the fronto-cerebellar and fronto-striatal connections, and the cingulum. (C) 2010 Elsevier Ltd. All rights reserved.

Predicting and anticipating disturbances in higher level gait is particularly relevant for patients with dementia as higher level gait appears to be closely related to higher level cognitive functioning. A phenomenon that could contribute to the understanding and prediction of disturbances in higher level gait and gait-related motor activity in the various subtypes of dementia is paraphrased as 'last in-first out'. 'Last in-first out' refers to the principle that neural circuits that mature late in development are the most vulnerable to neurodegeneration. The strength of relating symptoms to the 'last in-first out' principle is that a future symptom can be predicted and anticipated in a therapeutic way, even if the disease process has not already started. Therefore, the aim of this review is to provide new strategies for rehabilitation of higher level gait disturbances in dementia based upon the 'last in-first out' principle. These new strategies emerge from five neural networks: the superior longitudinal fasciculus, the uncinate fasciculus, the fronto-cerebellar and fronto-striatal connections, and the cingulum. (C) 2010 Elsevier Ltd. All rights reserved.

Objectives To develop recommendations for the diagnosis, prevention and treatment of neuropsychiatric systemic lupus erythematosus (NPSLE) manifestations.Methods The authors compiled questions on prevalence and risk factors, diagnosis and monitoring, therapy and prognosis of NPSLE. A systematic literature search was performed and evidence was categorised based on sample size and study design.Results Systemic lupus erythematosus (SLE) patients are at increased risk of several neuropsychiatric manifestations. Common (cumulative incidence >5%) manifestations include cerebrovascular disease (CVD) and seizures; relatively uncommon (1-5%) are severe cognitive dysfunction, major depression, acute confusional state (ACS), peripheral nervous disorders psychosis. Strong risk factors (at least fivefold increased risk) are previous or concurrent severe NPSLE (for cognitive dysfunction, seizures) and antiphospholipid antibodies (for CVD, seizures, chorea). The diagnostic work-up of suspected NPSLE is comparable to that in patients without SLE who present with the same manifestations, and aims to exclude causes unrelated to SLE. Investigations include cerebrospinal fluid analysis (to exclude central nervous system infection), EEG (to diagnose seizure disorder), neuropsychological tests (to assess cognitive dysfunction), nerve conduction studies (for peripheral neuropathy) and MRI (T1/T2, fluid-attenuating inversion recovery, diffusion-weighted imaging, enhanced T1 sequence). Glucocorticoids and immunosuppressive therapy are indicated when NPSLE is thought to reflect an inflammatory process (optic neuritis, transverse myelitis, peripheral neuropathy, refractory seizures, psychosis, ACS) and in the presence of generalised lupus activity. Antiplatelet/anticoagulation therapy is indicated when manifestations are related to antiphospholipid antibodies, particularly thrombotic CVD.Conclusions Neuropsychiatric manifestations in SLE patients should be first evaluated and treated as in patients without SLE, and secondarily attributed to SLE and treated accordingly.

ObjectivesTo develop recommendations for the diagnosis, prevention and treatment of neuropsychiatric systemic lupus erythematosus (NPSLE) manifestations.MethodsThe authors compiled questions on prevalence and risk factors, diagnosis and monitoring, therapy and prognosis of NPSLE. A systematic literature search was performed and evidence was categorised based on sample size and study design.ResultsSystemic lupus erythematosus (SLE) patients are at increased risk of several neuropsychiatric manifestations. Common (cumulative incidence >5%) manifestations include cerebrovascular disease (CVD) and seizures; relatively uncommon (1–5%) are severe cognitive dysfunction, major depression, acute confusional state (ACS), peripheral nervous disorders psychosis. Strong risk factors (at least fivefold increased risk) are previous or concurrent severe NPSLE (for cognitive dysfunction, seizures) and antiphospholipid antibodies (for CVD, seizures, chorea). The diagnostic work-up of suspected NPSLE is comparable to that in patients without SLE who present with the same manifestations, and aims to exclude causes unrelated to SLE. Investigations include cerebrospinal fluid analysis (to exclude central nervous system infection), EEG (to diagnose seizure disorder), neuropsychological tests (to assess cognitive dysfunction), nerve conduction studies (for peripheral neuropathy) and MRI (T1/T2, fluid-attenuating inversion recovery, diffusion-weighted imaging, enhanced T1 sequence). Glucocorticoids and immunosuppressive therapy are indicated when NPSLE is thought to reflect an inflammatory process (optic neuritis, transverse myelitis, peripheral neuropathy, refractory seizures, psychosis, ACS) and in the presence of generalised lupus activity. Antiplatelet/anticoagulation therapy is indicated when manifestations are related to antiphospholipid antibodies, particularly thrombotic CVD.ConclusionsNeuropsychiatric manifestations in SLE patients should be first evaluated and treated as in patients without SLE, and secondarily attributed to SLE and treated accordingly.

Objective The aim of this study was to evaluate the value of attenuation correction (AC) of Tc-99m tetrofosmin single-photon emission tomography (SPECT) imaging for the assessment of left ventricular ejection fraction (LVEF).Methods Attenuation corrected and non-attenuation corrected (NC) resting Tc-99m tetrofosmin SPECT were compared for the assessment of LVEF. Planar multi-gated radionuclide angiography (MUGA) served as the reference for LVEF assessment. Patients (n = 56) with left ventricular dysfunction who underwent MUGA and rest gated Tc-99m tetrofosmin SPECT within I month were included.Results The average LVEF on NC gated SPECT was 37.4 +/- 11.8% and on AC SPECT 38.5 +/- 13.4% (P = NS). The absolute mean difference of the LVEF between the MUGA and NC gated SPECT and AC gated SPECT was -0.2% (95% CI -1.7 to 1.3) and -1.3% (95% Cl -2.7 to 0.03), respectively (P = NS both vs. MUGA). The correlation between NC gated SPECT and AC gated SPECT versus MUGA measurement was high with a correlation coefficient of 0.89 (P Conclusions Profile AC gated Tc-99m tetrofosmin SPECT agrees well with MUGA and NC gated Tc-99m tetrofosmin SPECT for the assessment of LVEF. EDVs and ESVs are significantly higher with AC gated SPECT when compared with NC gated SPECT.

A comprehensive review is undertaken of the methods available for 3D whole-heart first-pass perfusion (FPP) and their application to date, with particular focus on possible acceleration techniques. Following a summary of the parameters typically desired of 3D FPP methods, the review explains the mechanisms of key acceleration techniques and their potential use in FPP for attaining 3D acquisitions. The mechanisms include rapid sequences, non-Cartesian k-space trajectories, reduced k-space acquisitions, parallel imaging reconstructions and compressed sensing. An attempt is made to explain, rather than simply state, the varying methods with the hope that it will give an appreciation of the different components making up a 3D FPP protocol. Basic estimates demonstrating the required total acceleration factors in typical 3D FPP cases are included, providing context for the extent that each acceleration method can contribute to the required imaging speed, as well as potential limitations in present 3D FPP literature. Although many 3D FPP methods are too early in development for the type of clinical trials required to show any clear benefit over current 2D FPP methods, the review includes the small but growing quantity of clinical research work already using 3D FPP, alongside the more technical work. Broader challenges concerning FPP such as quantitative analysis are not covered, but challenges with particular impact on 3D FPP methods, particularly with regards to motion effects, are discussed along with anticipated future work in the field.

Since the publication of the European Association of Nuclear Medicine (EANM) procedural guidelines for radionuclide myocardial perfusion imaging (MPI) in 2005, many small and some larger steps of progress have been made, improving MPI procedures. In this paper, the major changes from the updated 2015 procedural guidelines are highlighted, focusing on the important changes related to new instrumentation with improved image information and the possibility to reduce radiation exposure, which is further discussed in relation to the recent developments of new International Commission on Radiological Protection (ICRP) models. Introduction of the selective coronary vasodilator regadenoson and the use of coronary CT-contrast agents for hybrid imaging with SPECT/CT angiography are other important areas for nuclear cardiology that were not included in the previous guidelines. A large number of minor changes have been described in more detail in the fully revised version available at the EANM home page: http://eanm.org/publications/guidelines/2015_07_EANM_FINAL_myocardial_perfusion_guideline.pdf .

Purpose: F-18-FDG PET is an important modality for myocardial viability assessment in patients with left ventricular (LV) dysfunction. Dual-isotope simultaneous acquisition (DISA) SPECT may be an alternative to PET. The aim of this study was to compare the diagnostic performance of PET and DISA SPECT for the prediction of improvement in regional and global LV function as well as LV reverse remodelling after revascularization.Methods: Patients (n= 47) with chronic coronary artery disease and LV dysfunction underwent DISA SPECT ( with Tc-99m-sestamibi and F-18-FDG) and PET ( with N-13-ammonia and F-18-FDG) on the same day to assess viability. All patients underwent revascularization and recovery of function was derived from serial magnetic resonance imaging studies.Results: Of 264 revascularized, dysfunctional segments, 143 (54%) improved in function. For prediction of improvement in regional LV function, PET and DISA SPECT had similar sensitivity (90% versus 89%, NS) and specificity (86% versus 86%, NS). For prediction of improvement in global LV function, sensitivity was 83% for DISA SPECT and 86% for PET (p= NS), whereas both modalities had a specificity of 100%. Finally, sensitivity and specificity for the prediction of LV reverse remodelling were also similar for DISA SPECT and PET.Conclusion: In patients undergoing revascularization, DISA SPECT and PET predict the improvement in regional and global LV function and LV remodelling equally well post revascularization.

Objectives: Fluorine-18 fluorodeoxyglucose (FDG) SPECT has emerged as an alternative to dedicated PET imaging. However, it remains uncertain whether FDG SPECT is an as accurate for viability assessment as FDG PET in patients with severely reduced left ventricular function. The aim of the study was to assess the diagnostic accuracy of FDG SPECT in a head-to-head comparison with FDG PET, and divide the patients according to the severity of left ventricular dysfunction. Methods: A total of 47 patients, with a history of myocardial infarction underwent FDG/perfusion (Tc-99m-sestamibi or Tl-201) SPECT as well as FDG/N-13-ammonia PET. The patients were divided into 2 subgroups based on the left ventricular ejection fraction (LVEF) (35% cutoff). The left ventricular myocardium was divided into 13 segments, and each segment was classified as viable or scar using a semi-quantitative scoring system based on defect severity and the presence or absence of perfusion-FDG mismatch. Results: Of the 47 patients studied, 23 had LVEF = 35% (high LVEF group; mean 47 +/- 6%). In the low LVEF group, 213 segments (71%) were dysfunctional, as compared to 102 (33%) in the high LVEF group. The agreement for detection of viability between PET and SPECT in the low LVEF group was 82% (kappa 0.63), which was not different from the agreement in the high LVEF group (85%, kappa 0.66, p = 0.42 versus low LVEF group). Conclusions: The results indicate that FDG SPECT can be used for tissue viability assessment regardless of the severity of left ventricular dysfunction.

Objectives: Fluorine-18 fluorodeoxyglucose (FDG) SPECT has emerged as an alternative to dedicated PET imaging. However, it remains uncertain whether FDG SPECT is an as accurate for viability assessment as FDG PET in patients with severely reduced left ventricular function. The aim of the study was to assess the diagnostic accuracy of FDG SPECT in a head-to-head comparison with FDG PET, and divide the patients according to the severity of left ventricular dysfunction. Methods: A total of 47 patients, with a history of myocardial infarction underwent FDG/perfusion (Tc-99m-sestamibi or Tl-201) SPECT as well as FDG/N-13-ammonia PET. The patients were divided into 2 subgroups based on the left ventricular ejection fraction (LVEF) (35% cutoff). The left ventricular myocardium was divided into 13 segments, and each segment was classified as viable or scar using a semi-quantitative scoring system based on defect severity and the presence or absence of perfusion-FDG mismatch. Results: Of the 47 patients studied, 23 had LVEF = 35% (high LVEF group; mean 47 +/- 6%). In the low LVEF group, 213 segments (71%) were dysfunctional, as compared to 102 (33%) in the high LVEF group. The agreement for detection of viability between PET and SPECT in the low LVEF group was 82% (kappa 0.63), which was not different from the agreement in the high LVEF group (85%, kappa 0.66, p = 0.42 versus low LVEF group). Conclusions: The results indicate that FDG SPECT can be used for tissue viability assessment regardless of the severity of left ventricular dysfunction.

Purpose: Dual-isotope simultaneous acquisition (DISA) single-photon emission computed tomography ( SPECT) is an attractive technique as it permits assessment of both myocardial glucose metabolism and perfusion within a single session, but few data on its accuracy for the assessment of viability are available as yet. In the present study, DISA SPECT was compared with positron emission tomography ( PET) for the detection of myocardial viability in normal and dysfunctional left ventricular (LV) myocardium.Methods: Fifty-eight patients with chronic coronary artery disease and LV dysfunction ( LV ejection fraction 33 +/- 12%) were studied. Patients underwent a 1-day dipyridamole stress Tc-99m-sestamibi/F-18-fluorodeoxyglucose ((18)FDG) DISA SPECT and N-13-ammonia/(18)FDG PET protocol. Within 1 week, resting MRI was performed to assess contractile function. Comparison of PET and SPECT data was performed using both visual and quantitative analysis.Results: The correlation of normalised activities of the flow tracers Tc-99m-sestamibi and N-13-ammonia was good (r = 0.82; pConclusion: This study shows an overall good agreement between Tc-99m-sestamibi/(18)FDG DISA SPECT and PET for the assessment of myocardial viability in patients with severe LV dysfunction. Quantitative or visual analysis of the SPECT data did not influence the agreement with PET, suggesting that visual assessment may be sufficient for clinical purposes.

Planar gated blood-pool imaging (GBPI) is a standard method for non-invasive assessment of left ventricular (LV) function. Gated blood-pool single photon emission computed tomographic (GBPS) data acquisition can be accomplished in the same time as GBPI, with the benefit of enabling visualization of all cardiac chambers simultaneously. The purpose of this investigation was to evaluate the degree to which automated and manual LVEF calculations agree with one another and with conventional GBPI LVEF measurements. GBPI studies were performed in 22 consecutive, unselected patients, followed by GBPS data acquisition. GBPS left ventricular ejection fraction (LVEF) calculations were performed by available software (NuSMUGA, Northwestern University, Chicago, IL) automatically and manually, using all LV gated short axis slices. Automatic LVEF assessed by GBPS correlated well with conventional planar GBPI (r = 0.88, P

Planar gated blood-pool imaging (GBPI) is a standard method for non-invasive assessment of left ventricular (LV) function. Gated blood-pool single photon emission computed tomographic (GBPS) data acquisition can be accomplished in the same time as GBPI, with the benefit of enabling visualization of all cardiac chambers simultaneously. The purpose of this investigation was to evaluate the degree to which automated and manual LVEF calculations agree with one another and with conventional GBPI LVEF measurements. GBPI studies were performed in 22 consecutive, unselected patients, followed by GBPS data acquisition. GBPS left ventricular ejection fraction (LVEF) calculations were performed by available software (NuSMUGA, Northwestern University, Chicago, IL) automatically and manually, using all LV gated short axis slices. Automatic LVEF assessed by GBPS correlated well with conventional planar GBPI (r = 0.88, P

Background Currently, the rat has been a useful animal model in brain stimulation research. Nevertheless, extrapolating results from rodent repetitive Transcranial Magnetic Stimulation (rTMS) research to humans contains several hurdles. This suggests the desperate need for a large animal model in translational rTMS research. The dog would be a valid choice, not only due to the fact that humans and dogs share a neurophysiological background, but a similar neuropathological background as well. Hypothesis In order to evaluate the feasibility of the canine rTMS animal model, this study aimed to evaluate the neurophysiological response in dogs on a, clinically used, accelerated high frequency (aHF) rTMS protocol. This aHF-rTMS (20 Hz) protocol was performed under anaesthesia or sedation and either 20 sessions or 5 sessions were given to each dog. Methods 21 healthy dogs were randomly subjected to one of the four aHF-rTMS protocols (1 sham and 3 active protocols). For each dog, the perfusion indices (PI), of a [99mTc]HMPAO scan at 4 time points, for the left frontal cortex (stimulation target) were calculated for each protocol. Results Concerning sham stimulation, the average PI remained at the baseline level. The main result was the presence of a direct transitory increase in rCBF at the stimulation site, both under anaesthesia and sedation. Nevertheless the measured increase in rCBF was higher but shorter duration under sedation. The magnitude of this increase was not influenced by number of sessions. No changes in rCBF were found in remote brain regions. Conclusion This study shows that, despite the influence of anaesthesia and sedation, comparable and clinically relevant effects on the rCBF can be obtained in dogs. Since less methodological hurdles have to be overcome and comparable results can be obtained, it would be acceptable to put the dog forward as an alternative translational rTMS animal model.

Background: Cost-effectiveness is an increasingly important factor in the choice of a test or therapy. Objective: To assess the cost-effectiveness of various methods routinely used for the diagnosis of stable coronary disease in Portugal. Methods: Seven diagnostic strategies were assessed. The cost-effectiveness of each strategy was defined as the cost per correct diagnosis (inclusion or exclusion of obstructive coronary artery disease) in a symptomatic patient. The cost and effectiveness of each method were assessed using Bayesian inference and decision-making tree analyses, with the pretest likelihood of disease ranging from 10\% to 90\%. Results: The cost-effectiveness of diagnostic strategies was strongly dependent on the pretest likelihood of disease. In patients with a pretest likelihood of disease of 0. In patients with a pretest likelihood of disease of >= 60\%, up-front invasive coronary angiography appears to be the most cost-effective strategy. Conclusions: Diagnostic algorithms that include cardiac computed tomography angiography are the most cost-effective in symptomatic patients with suspected stable coronary artery disease and a pretest likelihood of disease of = 60\%), up-front invasive coronary angiography appears to be the most cost-effective strategy. In all pretest likelihoods of disease, strategies based on ischemia appear to be more expensive and less effective compared with those based on anatomical tests. publishersversion published

The modulating effects of serotonin on dopamine neurotransmission are not well understood, particularly in acute psychotic states. Positron emission tomography was used to examine the effect of psilocybin on the in vivo binding of [C-11]raclopride to D-2-dopamine receptors in the striatum in healthy volunteers after placebo and a psychotomimetic dose of psilocybin (n = 7). Psilocybin is a potent indoleamine hallucinogen and a mixed 5-HT2A and 5-HT1A receptor agonist. Psilocybin administration (0.25 mg/kg p.o.) produced changes in mood, disturbances in thinking, illusions, elementary and complex visual hallucinations and impaired ego-functioning. Psilocybin significantly decreased [C-11]raclopride receptor binding potential (BP) bilaterally in the caudate nucleus (19%) and putamen. (20%) consistent with an increase in endogenous dopamine. Changes in [C-11]raclopride BP in the ventral striatum correlated with depersonalization associated with euphoria. Together with previous reports of 5-HT receptor involvement in striatal dopamine release, it is concluded that stimulation of both 5-HT2A and 5-HT1A receptors may be important for the modulation of striatal dopamine release in acute psychoses. The present results indirectly support the hypothesis of a serotonin-dopamine dysbalance in schizophrenia and suggest that psilocybin is a valuable tool in the analysis of serotonin-dopamine interactions in acute psychotic states. (C) 1999 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.

Context.-Cardiac imaging has advanced rapidly, providing clinicians with several choices for evaluating patients with suspected coronary artery disease, but few studies compare modalities directly..-To review the contemporary literature and to compare the diagnostic performance of exercise echocardiography (ECHO) and exercise single-photon emission computed tomography (SPECT) imaging in the diagnosis of coronary artery disease.Data Sources.-Studies published between January 1990 and October 1997 identified from MEDLINE search; bibliographies of reviews and original articles; and suggestions from experts in each area.Study Selection.-Articles were included if they discussed exercise ECHO and/or exercise SPECT imaging with thallous chloride TI 201 (thallium)or technetium Tc 99m sestamibi for detection and/or evaluation of coronary artery disease, if data on coronary angiography were presented as the reference test, and if the absolute numbers of true-positive, false-negative, true-negative, and false-positive observations were available or derivable from the data presented. Studies performed exclusively in patients after myocardia infarction, after percutaneous transluminal coronary angioplasty, after coronary artery bypass grafting, or with recent unstable coronary syndromes were excluded.Data Extraction.-ClinicaI variables, technical factors, and test performance were independently extracted by 2 reviewers on a standardized spreadsheet. Discrepancies were resolved by consensus.Results.-Forty-four articles met inclusion criteria. in pooled data weighted by the sample size of each study, exercise ECHO had a sensitivity of 85% (95% confidence interval [CI], 83%-87%) with a specificity of 77% (95% CI, 74%-80%). Exercise SPECT yielded a similar sensitivity of 87% (95% CI, 86%-88%) but a lower specificity of 64% (95% CI, 60%-68%), In a summary receiver operating characteristic model comparing exercise ECHO performance to exercise SPECT, exercise ECHO was associated with significantly better discriminatory power (parameter estimate, 1.18; 95% CI, 0.71-1.65), when adjusted for age, publication year, and a setting including known coronary artery disease for SP ECT studies. In models comparing the discriminatory abilities of exercise ECHO and exercise SPECT vs exercise testing without imaging, both ECHO and SPECT performed significantly better than exercise testing. The incremental improvement in performance was greater for ECHO (3.43; 95% CI, 2.74-4.11) than for SPECT (1.49; 95% CI, 0.91-2.08).Conclusions.-Exercise ECHO and exercise SPECT have similar sensitivities for the detection of coronary artery disease, but exercise ECHO has better specificity and, therefore, higher overall discriminatory capabilities as used in contemporary practice.

Context.-Cardiac imaging has advanced rapidly, providing clinicians with several choices for evaluating patients with suspected coronary artery disease, but few studies compare modalities directly. .-To review the contemporary literature and to compare the diagnostic performance of exercise echocardiography (ECHO) and exercise single-photon emission computed tomography (SPECT) imaging in the diagnosis of coronary artery disease. Data Sources.-Studies published between January 1990 and October 1997 identified from MEDLINE search; bibliographies of reviews and original articles; and suggestions from experts in each area. Study Selection.-Articles were included if they discussed exercise ECHO and/or exercise SPECT imaging with thallous chloride TI 201 (thallium)or technetium Tc 99m sestamibi for detection and/or evaluation of coronary artery disease, if data on coronary angiography were presented as the reference test, and if the absolute numbers of true-positive, false-negative, true-negative, and false-positive observations were available or derivable from the data presented. Studies performed exclusively in patients after myocardia infarction, after percutaneous transluminal coronary angioplasty, after coronary artery bypass grafting, or with recent unstable coronary syndromes were excluded. Data Extraction.-ClinicaI variables, technical factors, and test performance were independently extracted by 2 reviewers on a standardized spreadsheet. Discrepancies were resolved by consensus. Results.-Forty-four articles met inclusion criteria. in pooled data weighted by the sample size of each study, exercise ECHO had a sensitivity of 85% (95% confidence interval [CI], 83%-87%) with a specificity of 77% (95% CI, 74%-80%). Exercise SPECT yielded a similar sensitivity of 87% (95% CI, 86%-88%) but a lower specificity of 64% (95% CI, 60%-68%), In a summary receiver operating characteristic model comparing exercise ECHO performance to exercise SPECT, exercise ECHO was associated with significantly better discriminatory power (parameter estimate, 1.18; 95% CI, 0.71-1.65), when adjusted for age, publication year, and a setting including known coronary artery disease for SP ECT studies. In models comparing the discriminatory abilities of exercise ECHO and exercise SPECT vs exercise testing without imaging, both ECHO and SPECT performed significantly better than exercise testing. The incremental improvement in performance was greater for ECHO (3.43; 95% CI, 2.74-4.11) than for SPECT (1.49; 95% CI, 0.91-2.08). Conclusions.-Exercise ECHO and exercise SPECT have similar sensitivities for the detection of coronary artery disease, but exercise ECHO has better specificity and, therefore, higher overall discriminatory capabilities as used in contemporary practice.

Purpose: In iterative positron emission tomography (PET) image reconstruction, the statistical variability of the PET data precorrected for random coincidences or acquired in sufficiently high count rates can be properly approximated by a Gaussian distribution, which can lead to a penalized weighted least-squares (PWLS) cost function. In this study, the authors propose a proximal preconditioned gradient algorithm accelerated with ordered subsets (PPG-OS) for the optimization of the PWLS cost function and develop a framework to incorporate boundary side information into edge-preserving total variation (TV) and Huber regularizations.Methods: The PPG-OS algorithm is proposed to address two issues encountered in the optimization of PWLS function with edge-preserving regularizers. First, the second derivative of this function (Hessian matrix) is shift-variant and ill-conditioned due to the weighting matrix (which includes emission data, attenuation, and normalization correction factors) and the regularizer. As a result, the paraboloidal surrogate functions (used in the optimization transfer techniques) end up with high curvatures and gradient-based algorithms take smaller step-sizes toward the solution, leading to a slow convergence. In addition, preconditioners used to improve the condition number of the problem, and thus to speed up the convergence, would poorly act on the resulting ill-conditioned Hessian matrix. Second, the PWLS function with a nondifferentiable penalty such as TV is not amenable to optimization using gradient-based algorithms. To deal with these issues and also to enhance edge-preservation of the TV and Huber regularizers by incorporating adaptively or anatomically derived boundary side information, the authors followed a proximal splitting method. Thereby, the optimization of the PWLS function is split into a gradient descent step (upgraded by preconditioning, step size optimization, and ordered subsets) and a proximal mapping associated with boundary weighted TV and Huber regularizers. The proximal mapping is then iteratively solved by dual formulation of the regularizers.Results: The convergence performance of the proposed algorithm was studied with three different diagonal preconditioners and compared with the state-of-the-art separable paraboloidal surrogates accelerated with ordered-subsets (SPS-OS) algorithm. In simulation studies using a realistic numerical phantom, it was shown that the proposed algorithm depicts a considerably improved convergence rate over the SPS-OS algorithm. Furthermore, the results of bias-variance and signal-to-noise evaluations showed that the proposed algorithm with anatomical edge information depicts an improved performance over conventional regularization. Finally, the proposed PPG-OS algorithm is used for image reconstruction of a clinical study with adaptively derived boundary edge information, demonstrating the potential of the algorithm for fast and edge-preserving PET image reconstruction.Conclusions: The proposed PPG-OS algorithm shows an improved convergence rate with the ability of incorporating additional boundary information in regularized PET image reconstruction. (c) 2013 American Association of Physicists in Medicine.

Purpose: In iterative positron emission tomography (PET) image reconstruction, the statistical variability of the PET data precorrected for random coincidences or acquired in sufficiently high count rates can be properly approximated by a Gaussian distribution, which can lead to a penalized weighted least-squares (PWLS) cost function. In this study, the authors propose a proximal preconditioned gradient algorithm accelerated with ordered subsets (PPG-OS) for the optimization of the PWLS cost function and develop a framework to incorporate boundary side information into edge-preserving total variation (TV) and Huber regularizations. Methods: The PPG-OS algorithm is proposed to address two issues encountered in the optimization of PWLS function with edge-preserving regularizers. First, the second derivative of this function (Hessian matrix) is shift-variant and ill-conditioned due to the weighting matrix (which includes emission data, attenuation, and normalization correction factors) and the regularizer. As a result, the paraboloidal surrogate functions (used in the optimization transfer techniques) end up with high curvatures and gradient-based algorithms take smaller step-sizes toward the solution, leading to a slow convergence. In addition, preconditioners used to improve the condition number of the problem, and thus to speed up the convergence, would poorly act on the resulting ill-conditioned Hessian matrix. Second, the PWLS function with a nondifferentiable penalty such as TV is not amenable to optimization using gradient-based algorithms. To deal with these issues and also to enhance edge-preservation of the TV and Huber regularizers by incorporating adaptively or anatomically derived boundary side information, the authors followed a proximal splitting method. Thereby, the optimization of the PWLS function is split into a gradient descent step (upgraded by preconditioning, step size optimization, and ordered subsets) and a proximal mapping associated with boundary weighted TV and Huber regularizers. The proximal mapping is then iteratively solved by dual formulation of the regularizers. Results: The convergence performance of the proposed algorithm was studied with three different diagonal preconditioners and compared with the state-of-the-art separable paraboloidal surrogates accelerated with ordered-subsets (SPS-OS) algorithm. In simulation studies using a realistic numerical phantom, it was shown that the proposed algorithm depicts a considerably improved convergence rate over the SPS-OS algorithm. Furthermore, the results of bias-variance and signal-to-noise evaluations showed that the proposed algorithm with anatomical edge information depicts an improved performance over conventional regularization. Finally, the proposed PPG-OS algorithm is used for image reconstruction of a clinical study with adaptively derived boundary edge information, demonstrating the potential of the algorithm for fast and edge-preserving PET image reconstruction. Conclusions: The proposed PPG-OS algorithm shows an improved convergence rate with the ability of incorporating additional boundary information in regularized PET image reconstruction. (c) 2013 American Association of Physicists in Medicine.

International audience; Cerebrovascular disease is recognized as a common cause of cognitive impairment and dementia, alone or coexisting with other neurodegenerative diseases, mostly Alzheimer's disease. Vascular cognitive impairment (VCI) is a part of the heterogenous disorders group related to cerebral vessel disease. Although age is one of the most important risk factors for VCI, other common cardiovascular risk factors are also involved. By investigating these risk factors, a high proportion of these cognitive disorders can be prevented and/or delayed. Until now, only treatment of rnidlife arterial hypertension has been recognized as a preventing factor of vascular dementia. Brain MRI is becoming the method of choice to investigate cerebral vascular pathologies. However, this form of morphological imaging remains inadequate and does not provide useful functional information during VCI exploration, despite which functional imaging such as brain perfusion single-photon computed tomography, performed in baseline conditions and/or after an acetazolamide challenge, is underutilized in VCI exploration. The common strategies for VCI screening have not been standardized until now, and therefore further long-term imaging studies are needed to establish early diagnostic protocols. The present review summarizes the potential benefits of brain perfusion single-photon computed tomography imaging and possible scintigraphic quantification of cerebral hemodynamic reserves in investigation of VCI. Nucl Med Commun 33:571-580 (c) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Aims The role of coronary artery disease (CAD) in atrial fibrillation (AF) is poorly investigated. This study investigated the value of myocardial perfusion single-photon emission computed tomography (SPECT) in the assessment of risk of CAD in patients with a history of AF. Methods and results Out of consecutive patients without previous coronary angiogram or history of CAD referred for SPECT, patients with a history of AF ( n = 129) were compared with age- and gender-matched controls ( n = 124). Primary endpoint was positive SPECT, i.e. unambiguous signs of ischaemia. There was no significant difference with regard to positive SPECT outcome between AF patients and controls (14 patients, 11% vs. 21 patients, 17%; P = 0.16). Coronary angiography (CAG) performed after SPECT demonstrated a higher yield of positive SPECT regarding significant CAD in control patients (10 out of 15 patients, 67%) than in AF patients (2 out of 13 patients, 15%; P = 0.006). Conclusion Positive SPECT outcome was similar in patients with AF and in controls. Nevertheless, in AF patients a positive SPECT outcome was less often related to significant CAD in those patients who subsequently underwent CAG. These results emphasize the need for new non-invasive techniques to adequately assess the risk of significant CAD in AF patients.

Coronary artery disease is a major cause of morbidity and mortality in the elderly population. As a result of ageing of the population and better medical, interventional and surgical treatment of patients with coronary artery disease, more and more elderly patients are referred to the cardiology department for diagnostic work-up. Stress testing, in combination with myocardial perfusion imaging, is routinely used in elderly patients, a population in which the diagnosis of significant coronary artery disease is often challenging because of atypical symptomatology. Since the introduction of technetium-99m ligands for myocardial perfusion imaging, it is possible to perform electrocalrdiogram-gated perfusion imaging. This not only improves the specificity of the test for coronary artery disease detection, but also enables the simultaneous assessment of left ventricular functional parameters. This article briefly overviews the possible stress modalities, diagnostic accuracy and prognostic value of myocardial perfusion imaging in elderly patients.

Objectives: Fluorine-18 fluorodeoxyglucose (FDG) SPECT has emerged as an alternative to dedicated PET imaging. However, it remains uncertain whether FDG SPECT is an as accurate for viability assessment as FDG PET in patients with severely reduced left ventricular function. The aim of the study was to assess the diagnostic accuracy of FDG SPECT in a head-to-head comparison with FDG PET, and divide the patients according to the severity of left ventricular dysfunction. Methods: A total of 47 patients, with a history of myocardial infarction underwent FDG/perfusion (Tc-99m-sestamibi or Tl-201) SPECT as well as FDG/N-13-ammonia PET. The patients were divided into 2 subgroups based on the left ventricular ejection fraction (LVEF) (35% cutoff). The left ventricular myocardium was divided into 13 segments, and each segment was classified as viable or scar using a semi-quantitative scoring system based on defect severity and the presence or absence of perfusion-FDG mismatch. Results: Of the 47 patients studied, 23 had LVEF = 35% (high LVEF group; mean 47 +/- 6%). In the low LVEF group, 213 segments (71%) were dysfunctional, as compared to 102 (33%) in the high LVEF group. The agreement for detection of viability between PET and SPECT in the low LVEF group was 82% (kappa 0.63), which was not different from the agreement in the high LVEF group (85%, kappa 0.66, p = 0.42 versus low LVEF group). Conclusions: The results indicate that FDG SPECT can be used for tissue viability assessment regardless of the severity of left ventricular dysfunction.

Background. Perfusion and functional data obtained during gated single photon emission computed tomography (SPECT) have proven prognostic value in the middle-aged patient population. The aim of this study was to investigate whether perfusion and functional cardiac gated SPECT data have prognostic value in patients aged 75 years or older. Methods and Results. We studied clinical and gated SPECT predictors of cardiac and all-cause death in 294 patients aged 75 years or older with known or suspected coronary artery disease who were referred for tetrofosmin cardiac gated SPECT imaging. Summed perfusion scores were calculated in a 17-segment model by use of commercially available software (4D-MSPECT). Left ventricular functional data were calculated by use of QGS gated SPECT software. The median age of the study population was 78 years (range, 75-91 years). There were 160 men (54%) and 134 women (46%). During a median follow-up of 25.9 months (range, 1.8-36 months), 47 patients (16%) died (27 cardiac deaths). Ina multivariate Cox proportional hazards regression analysis, the summed rest score (chi(2) gain = 8.0, P = .009), transient ischemic dilatation index (chi(2) gain = 6.3, P = .012), and resting left ventricular ejection fraction (chi(2) gain = 7.0, P = .030) were independent predictors of all-cause death. The summed rest score (chi(2) gain = 8.2, P = .004) and resting end-systolic volume (chi(2) gain = 13.7, P = .005) were independent predictors of cardiac death. Conclusions. This study showed that gated SPECT left ventricular functional data assessed during myocardial gated SPECT provide independent and incremental information above clinical and perfusion SPECT data for the prediction of cardiac and all-cause death in patients aged 75 years or older referred for myocardial SPECT imaging.