Neural substrate for the engagement of the ventral visual stream in motor control in the macaque monkey.

The present study aimed to describe the cortical connectivity of a sector located in the ventral bank of the superior temporal sulcus in the macaque (intermediate area TEa and TEm [TEa/m]), which appears to represent the major source of output of the ventral visual stream outside the temporal lobe. The retrograde tracer wheat germ agglutinin was injected in the intermediate TEa/m in four macaque monkeys. The results showed that 58-78% of labeled cells were located within ventral visual stream areas other than the TE complex. Outside the ventral visual stream, there were connections with the memory-related medial temporal area 36 and the parahippocampal cortex, orbitofrontal areas involved in encoding subjective values of stimuli for action selection, and eye- or hand-movement related parietal (LIP, AIP, and SII), prefrontal (12r, 45A, and 45B) areas, and a hand-related dysgranular insula field. Altogether these data provide a solid substrate for the engagement of the ventral visual stream in large scale cortical networks for skeletomotor or oculomotor control. Accordingly, the role of the ventral visual stream could go beyond pure perceptual processes and could be also finalized to the neural mechanisms underlying the control of voluntary motor behavior.

Stable Isotopes for Tracing Mammalian-Cell Metabolism In Vivo.

Metabolism is at the cornerstone of all cellular functions and mounting evidence of its deregulation in different diseases emphasizes the importance of a comprehensive understanding of metabolic regulation at the whole-organism level. Stable-isotope measurements are a powerful tool for probing cellular metabolism and, as a result, are increasingly used to study metabolism in in vivo settings. The additional complexity of in vivo metabolic measurements requires paying special attention to experimental design and data interpretation. Here, we review recent work where in vivo stable-isotope measurements have been used to address relevant biological questions within an in vivo context, summarize different experimental and data interpretation approaches and their limitations, and discuss future opportunities in the field.

Repeated passive heat treatment increases muscle tissue capillarization, but does not affect postprandial muscle protein synthesis rates in healthy older adults.

Prolonged passive heat treatment (PHT) has been suggested to trigger skeletal muscle adaptations that may improve muscle maintenance in older individuals. To assess the effects of PHT on skeletal muscle tissue capillarization, perfusion capacity, protein synthesis rates, hypertrophy and leg strength, 14 older adults (9 males, 5 females; 73 ± 6 years) underwent 8 weeks of PHT (infrared sauna: 3× per week, 45 min at ∼60°C). Before and after PHT we collected muscle biopsies to assess skeletal muscle capillarization and fibre cross-sectional area (CSA). Basal and postprandial muscle tissue perfusion kinetics and protein synthesis rates were assessed using contrast-enhanced ultrasound and primed continuous l-[ring-13C6]phenylalanine infusions, respectively. One-repetition maximum (1RM) leg strength and vastus lateralis muscle CSA were assessed. Type I and type II muscle fibre capillarization strongly increased following PHT (capillary-to-fibre perimeter exchange index: +31 ± 18 and +33 ± 30%, respectively; P < 0.001). No changes were observed in basal (0.24 ± 0.27 vs. 0.18 ± 0.11 AU; P = 0.266) or postprandial (0.20 ± 0.12 vs. 0.18 ± 0.14 AU; P = 0.717) microvascular blood flow following PHT. Basal (0.048 ± 0.014 vs. 0.051 ± 0.019%/h; P = 0.630) and postprandial (0.041 ± 0.012 vs. 0.051 ± 0.024%/h; P = 0.199) muscle protein synthesis rates did not change in response to prolonged PHT. Furthermore, no changes in vastus lateralis muscle CSA (15.3 ± 4.6 vs. 15.2 ± 4.6 cm2; P = 0.768) or 1RM leg strength (46 ± 12 vs. 47 ± 12 kg; P = 0.087) were observed over time. In conclusion, prolonged PHT increases muscle tissue capillarization but this does not improve muscle microvascular blood flow or increase muscle protein synthesis rates in healthy, older adults. Prolonged PHT does not induce skeletal muscle hypertrophy or increase leg strength in healthy, older adults. KEY POINTS: Repeated exposure to heat has been suggested to trigger skeletal muscle adaptive responses. We investigated the effect of 8 weeks of whole-body passive heat treatment (PHT; infrared sauna: 3× per week for 45 min at ∼60°C) on skeletal muscle tissue capillarization, perfusion capacity, basal, and postprandial muscle protein synthesis rates, muscle (fibre) hypertrophy, and leg strength in healthy, older adults. Prolonged PHT increases muscle tissue capillarization, but this does not improve muscle microvascular blood flow or increase muscle protein synthesis rates. Despite increases in muscle tissue capillarization, prolonged PHT does not suffice to induce skeletal muscle hypertrophy or increase leg strength in healthy, older adults.

Delayed and diminished postprandial lactate shuttling in healthy older men and women.

Lactate, a product of glycolysis, is formed under aerobic conditions. Extensive work has shown lactate flux in young and exercising humans; however, the effect of age is not known. We tested the hypothesis that postprandial lactate shuttling (PLS) would be diminished in older adults. We used [3-13C]lactate and [6,6-2H]glucose tracers, an oral glucose tolerance test (OGTT), and arterialized blood sampling to determine postprandial lactate rates of appearance (Ra), disappearance (Rd), and oxidation (Rox) in 15 young (28.1 ± 1.4 yr) and 13 older (70.6 ± 2.4 yr) healthy men and women. In young participants, fasting blood [lactate] (≈0.5 mM) rose after the glucose challenge, peaked at 15 min, dipped to a nadir at 30 min, and rose again peaking at 60 min (≈1.0 mM). Initial responses in lactate Ra of older participants were delayed and diminished until 90 min rising by 0.83 mg·kg-1·min-1. Lactate Rox was higher throughout the entire trial in young participants by a difference of ∼0.5 mg·kg-1·min-1. Initial peaks in lactate Ra and concentration in all volunteers demonstrated the presence of an enteric PLS following an OGTT. Notably, in the systemic, but not enteric, PLS phase, lactate Ra correlated highly with glucose Rd (r2 = 0.92). Correspondence of second peaks in lactate Ra and concentration and glucose Rd shows dependence of lactate Ra on glucose Rd. Although results show both enteric and systemic PLS phases in young and older study cohorts, metabolic responses were delayed and diminished in healthy older individuals.NEW & NOTEWORTHY We used isotope tracers, an oral glucose tolerance test, and arterialized blood sampling to determine postprandial lactate flux rates in healthy young and older men and women. Lactate rates of appearance and oxidation and the lactate-pyruvate exchange were delayed and diminished in both enteric and systemic postprandial lactate shuttle phases in older participants.

Intraoperative image-guidance during robotic surgery: is there clinical evidence of enhanced patient outcomes?

BACKGROUND: To date, the benefit of image guidance during robot-assisted surgery (IGS) is an object of debate. The current study aims to address the quality of the contemporary body of literature concerning IGS in robotic surgery throughout different surgical specialties. METHODS: A systematic review of all English-language articles on IGS, from January 2013 to March 2023, was conducted using PubMed, Cochrane library's Central, EMBASE, MEDLINE, and Scopus databases. Comparative studies that tested performance of IGS vs control were included for the quantitative synthesis, which addressed outcomes analyzed in at least three studies: operative time, length of stay, blood loss, surgical margins, complications, number of nodal retrievals, metastatic nodes, ischemia time, and renal function loss. Bias-corrected ratio of means (ROM) and bias-corrected odds ratio (OR) compared continuous and dichotomous variables, respectively. Subgroup analyses according to guidance type (i.e., 3D virtual reality vs ultrasound vs near-infrared fluoresce) were performed. RESULTS: Twenty-nine studies, based on 11 surgical procedures of three specialties (general surgery, gynecology, urology), were included in the quantitative synthesis. IGS was associated with 12% reduction in length of stay (ROM 0.88; p = 0.03) and 13% reduction in blood loss (ROM 0.87; p = 0.03) but did not affect operative time (ROM 1.00; p = 0.9), or complications (OR 0.93; p = 0.4). IGS was associated with an estimated 44% increase in mean number of removed nodes (ROM 1.44; p < 0.001), and a significantly higher rate of metastatic nodal disease (OR 1.82; p < 0.001), as well as a significantly lower rate of positive surgical margins (OR 0.62; p < 0.001). In nephron sparing surgery, IGS significantly decreased renal function loss (ROM 0.37; p = 0.002). CONCLUSIONS: Robot-assisted surgery benefits from image guidance, especially in terms of pathologic outcomes, namely higher detection of metastatic nodes and lower surgical margins. Moreover, IGS enhances renal function preservation and lowers surgical blood loss.

A strategy to build a library of oil tracers by oleophilic silica-encapsulated DNA nanoparticles.

Artificially synthesized DNA is involved in the construction of a library of oil tracers due to their unlimited number and no-biological toxicity. The strategy of the construction is proposed by oleophilic Silica-encapsulated DNA nanoparticles, which offers fresh thinking in developing novel tracers, sensors, and molecular machines in engineering & applied sciences based on artificially synthesized DNA blocks.

Functional imaging and anatomical connections in squirrel monkeys reveal parietal-frontal circuits underlying eye movements.

The posterior parietal cortex (PPC) of squirrel monkeys contains subregions where long trains of intracortical microstimulation evoke complex, behaviorally meaningful movements. Recently, we showed that such stimulation of a part of the PPC in the caudal lateral sulcus (LS) elicits eye movements in these monkeys. Here, we studied the functional and anatomical connections of this oculomotor region we call parietal eye field (PEF) with frontal eye field (FEF) and other cortical regions in 2 squirrel monkeys. We demonstrated these connections with intrinsic optical imaging and injections of anatomical tracers. Optical imaging of frontal cortex during stimulation of the PEF evoked focal functional activation within FEF. Tracing studies confirmed the functional PEF-FEF connections. Moreover, tracer injections revealed PEF connections with other PPC regions on the dorsolateral and medial brain surface, cortex in the caudal LS, and visual and auditory cortical association areas. Subcortical projections of PEF were primarily with superior colliculus, and pontine nuclei as well as nuclei of the dorsal posterior thalamus and caudate. These findings suggest that PEF in squirrel monkey is homologous to lateral intraparietal (LIP) area of macaque, supporting the notion that these brain circuits are organized similarly to mediate ethologically relevant oculomotor behaviors.

Integrated approach to understand the multiple natural and anthropogenic stresses on intensively irrigated coastal aquifer in the Mediterranean region.

Understanding the major factors influencing groundwater chemistry and its evolution in irrigation areas is crucial for efficient irrigation management. Major ions and isotopes (δD-H2O together with δ18O-H2O) were used to identify the natural and anthropogenic factors contributing to groundwater salinization in the shallow aquifer of the Wadi Guenniche Plain (WGP) in the Mediterranean region of Tunisia. A comprehensive geochemical investigation of groundwater was conducted during both the low irrigation season (L-IR) and the high irrigation season (H-IR). The results show that the variation range and average concentrations of almost all the ions in both the L-IR and H-IR seasons are high. The groundwater in both seasons is characterized by high electrical conductivity and CaMgCl/SO4 and NaCl types. The dissolution of halite and gypsum, the precipitation of calcite and dolomite, and Na-Ca exchange are the main chemical reactions in the geochemical evolution of groundwater in the Wadi Guenniche Shallow Aquifer (WGSA). Stable isotopes of hydrogen and oxygen (δ18O-H2O and δD-H2O) indicate that groundwater in WGSA originated from local precipitation. In the H-IR season, the δ18O-H2O and δD-H2O values indicate that the groundwater experienced noticeable evaporation. The enriched isotopic signatures reveal that the WGSA's groundwater was influenced by irrigation return flow and seawater intrusion. The proportions of mixing with seawater were found to vary between 0.12% and 5.95%, and between 0.13% and 8.42% during the L-IR and H-IR seasons, respectively. Irrigation return flow and the associated evaporation increase the dissolved solids content in groundwater during the irrigation season. The long-term human activities (fertilization, irrigation, and septic waste infiltration) are the main drives of the high nitrate-N concentrations in groundwater. In coastal irrigation areas suffering from water scarcity, these results can help planners and policy makers understand the complexities of groundwater salinization to enable more sustainable management and development.

Novel Diagnostic Methods for Infective Endocarditis.

Infective endocarditis (IE) remains a dangerous disease and continues to have a high mortality rate. Unfortunately, despite continuous improvements in diagnostic methods, in many cases, blood cultures remain negative, and the pathogen causing endocarditis is unknown. This makes targeted therapy and the selection of appropriate antibiotics impossible. Therefore, we present what methods can be used to identify the pathogen in infective endocarditis. These are mainly molecular methods, including PCR and MGS, as well as imaging methods using radiotracers, which offer more possibilities for diagnosing IE. However, they are still not widely used in the diagnosis of IE. The article summarizes in which cases we should choose them and what we are most hopeful about in further research into the diagnosis of IE. In addition, registered clinical trials that are currently underway for the diagnosis of IE are also presented.

A Novel Luciferase-Based Reporter Gene Technology for Simultaneous Optical and Radionuclide Imaging of Cells.

Multimodality reporter gene imaging combines the sensitivity, resolution and translational potential of two or more signals. The approach has not been widely adopted by the animal imaging community, mainly because its utility in this area is unproven. We developed a new complementation-based reporter gene system where the large component of split NanoLuc luciferase (LgBiT) presented on the surface of cells (TM-LgBiT) interacts with a radiotracer consisting of the high-affinity complementary HiBiT peptide labeled with a radionuclide. Radiotracer uptake could be imaged in mice using SPECT/CT and bioluminescence within two hours of implanting reporter-gene-expressing cells. Imaging data were validated by ex vivo biodistribution studies. Following the demonstration of complementation between the TM-LgBiT protein and HiBiT radiotracer, we validated the use of the technology in the highly specific in vivo multimodal imaging of cells. These findings highlight the potential of this new approach to facilitate the advancement of cell and gene therapies from bench to clinic.

Assessment of soil erosion in the Upper Citarum watershed for sustainability of the Saguling reservoir: unmixing model approach.

The Citarum watershed and the Saguling reservoir are vital natural resources in Indonesia, affecting the livelihood of West Java and the DKI Jakarta population. This study aimed to assess the soil erosion in the Upper Citarum watershed and identify its source. The study used the fallout radionuclide technique, geochemical tracers, and an unmixing model to measure soil erosion and the contribution of suspended sediment sources due to erosion. Soil bulk transects and surface soil were sampled using a coring tool on the Ciwidey and Cisangkuy sub-watersheds. Riverbank and suspended sediment samples were collected from tributaries and rivers. With 137Cs, 40% of the samples had values below the minimum detectable activity, and vice versa for 210Pbex, all samples are detectable. For mitigation, bare land needs to be recovered due to its erosion (25.6 t ha-1 year-1) exceeding the tolerance erosion value (17 t ha-1 year-1). Statistically, Mg and Na were the most appropriate composite tracers for suspended sediment contribution. The unmixing model predicted the sediment contributors from bare land (58%), the riverbank (32.7%), and plantation land (9.3%). Proper land conservation could reduce sediment supply by almost 14.7% and extend the reservoir's life. This is the first study to report the feasibility of the unmixing model in Indonesia.

Relationship between hepatic and mitochondrial ceramides: a novel in vivo method to track ceramide synthesis.

Ceramides (CERs) are key intermediate sphingolipids implicated in contributing to mitochondrial dysfunction and the development of multiple metabolic conditions. Despite the growing evidence of CER role in disease risk, kinetic methods to measure CER turnover are lacking, particularly using in vivo models. The utility of orally administered 13C3, 15N l-serine, dissolved in drinking water, was tested to quantify CER 18:1/16:0 synthesis in 10-week-old male and female C57Bl/6 mice. To generate isotopic labeling curves, animals consumed either a control diet or high-fat diet (HFD; n = 24/diet) for 2 weeks and varied in the duration of the consumption of serine-labeled water (0, 1, 2, 4, 7, or 12 days; n = 4 animals/day/diet). Unlabeled and labeled hepatic and mitochondrial CERs were quantified using liquid chromatography tandem MS. Total hepatic CER content did not differ between the two diet groups, whereas total mitochondrial CERs increased with HFD feeding (60%, P < 0.001). Within hepatic and mitochondrial pools, HFD induced greater saturated CER concentrations (P < 0.05) and significantly elevated absolute turnover of 16:0 mitochondrial CER (mitochondria: 59%, P < 0.001 vs. liver: 15%, P = 0.256). The data suggest cellular redistribution of CERs because of the HFD. These data demonstrate that a 2-week HFD alters the turnover and content of mitochondrial CERs. Given the growing data on CERs contributing to hepatic mitochondrial dysfunction and the progression of multiple metabolic diseases, this method may now be used to investigate how CER turnover is altered in these conditions.

Metformin and exercise effects on postprandial insulin sensitivity and glucose kinetics in pre-diabetic and diabetic adults.

The potential interaction between metformin and exercise on glucose-lowering effects remains controversial. We studied the separated and combined effects of metformin and/or exercise on fasting and postprandial insulin sensitivity in individuals with pre-diabetes and type 2 diabetes (T2D). Eight T2D adults (60 ± 4 yr) with overweight/obesity (32 ± 4 kg·m-2) under chronic metformin treatment (9 ± 6 yr; 1281 ± 524 mg·day-1) underwent four trials; 1) taking their habitual metformin treatment (MET), 2) substituting during 96 h their metformin medication by placebo (PLAC), 3) placebo combined with 50 min bout of high-intensity interval exercise (PLAC + EX), and 4) metformin combined with exercise (MET + EX). Plasma glucose kinetics using stable isotopes (6,6-2H2 and [U-13C] glucose), and glucose oxidation by indirect calorimetry, were assessed at rest, during exercise, and in a subsequent oral glucose tolerance test (OGTT). Postprandial glucose and insulin concentrations were analyzed as mean and incremental area under the curve (iAUC), and insulin sensitivity was calculated (i.e., MATSUDAindex and OGISindex). During OGTT, metformin reduced glucose iAUC (i.e., MET and MET + EX lower than PLAC and PLAC + EX, respectively; P = 0.023). MET + EX increased MATSUDAindex above PLAC (4.8 ± 1.4 vs. 3.3 ± 1.0, respectively; P = 0.018) and OGISindex above PLAC (358 ± 52 vs. 306 ± 46 mL·min-1·m-2, respectively; P = 0.006). Metformin decreased the plasma appearance of the ingested glucose (Ra OGTT; MET vs. PLAC, -3.5; 95% CI -0.1 to -6.8 µmol·kg-1·min-1; P = 0.043). Metformin combined with exercise potentiates insulin sensitivity during an OGTT in individuals with pre-diabetes and type 2 diabetes. Metformin's blood glucose-lowering effect seems mediated by decreased oral glucose entering the circulation (gut-liver effect) an effect partially blunted after exercise.NEW & NOTEWORTHY Metformin is the most prescribed oral antidiabetic medicine in the world but its mechanism of action and its interactions with exercise are not fully understood. Our stable isotope tracer data suggested that metformin reduces the rates of oral glucose entering the circulation (gut-liver effect). Exercise, in turn, tended to reduce postprandial insulin blood levels potentiating metformin improvements in insulin sensitivity. Thus, exercise potentiates metformin improvements in glycemic control and should be advised to metformin users.

How can I measure brain acetylcholine levels in vivo? Advantages and caveats of commonly used approaches.

The neurotransmitter acetylcholine (ACh) plays a central role in the regulation of multiple cognitive and behavioral processes, including attention, learning, memory, motivation, anxiety, mood, appetite, and reward. As a result, understanding ACh dynamics in the brain is essential for elucidating the neural mechanisms underlying these processes. In vivo measurements of ACh in the brain have been challenging because of the low concentrations and rapid turnover of this neurotransmitter. Here, we review a number of techniques that have been developed to measure ACh levels in the brain in vivo. We follow this with a deeper focus on use of genetically encoded fluorescent sensors coupled with fiber photometry, an accessible technique that can be used to monitor neurotransmitter release with high temporal resolution and specificity. We conclude with a discussion of methods for analyzing fiber photometry data and their respective advantages and disadvantages. The development of genetically encoded fluorescent ACh sensors is revolutionizing the field of cholinergic signaling, allowing temporally precise measurement of ACh release in awake, behaving animals. Use of these sensors has already begun to contribute to a mechanistic understanding of cholinergic modulation of complex behaviors.

Deuterated water as a substrate-agnostic isotope tracer for investigating reversibility and thermodynamics of reactions in central carbon metabolism.

Stable isotope tracers are a powerful tool for the quantitative analysis of microbial metabolism, enabling pathway elucidation, metabolic flux quantification, and assessment of reaction and pathway thermodynamics. 13C and 2H metabolic flux analysis commonly relies on isotopically labeled carbon substrates, such as glucose. However, the use of 2H-labeled nutrient substrates faces limitations due to their high cost and limited availability in comparison to 13C-tracers. Furthermore, isotope tracer studies in industrially relevant bacteria that metabolize complex substrates such as cellulose, hemicellulose, or lignocellulosic biomass, are challenging given the difficulty in obtaining these as isotopically labeled substrates. In this study, we examine the potential of deuterated water (2H2O) as an affordable, substrate-neutral isotope tracer for studying central carbon metabolism. We apply 2H2O labeling to investigate the reversibility of glycolytic reactions across three industrially relevant bacterial species -C. thermocellum, Z. mobilis, and E. coli-harboring distinct glycolytic pathways with unique thermodynamics. We demonstrate that 2H2O labeling recapitulates previous reversibility and thermodynamic findings obtained with established 13C and 2H labeled nutrient substrates. Furthermore, we exemplify the utility of this 2H2O labeling approach by applying it to high-substrate C. thermocellum fermentations -a setting in which the use of conventional tracers is impractical-thereby identifying the glycolytic enzyme phosphofructokinase as a major bottleneck during high-substrate fermentations and unveiling critical insights that will steer future engineering efforts to enhance ethanol production in this cellulolytic organism. This study demonstrates the utility of deuterated water as a substrate-agnostic isotope tracer for examining flux and reversibility of central carbon metabolic reactions, which yields biological insights comparable to those obtained using costly 2H-labeled nutrient substrates.

Stochastic simulation algorithm for isotope-based dynamic flux analysis.

Carbon isotope labeling method is a standard metabolic engineering tool for flux quantification in living cells. To cope with the high dimensionality of isotope labeling systems, diverse algorithms have been developed to reduce the number of variables or operations in metabolic flux analysis (MFA), but lacks generalizability to non-stationary metabolic conditions. In this study, we present a stochastic simulation algorithm (SSA) derived from the chemical master equation of the isotope labeling system. This algorithm allows to compute the time evolution of isotopomer concentrations in non-stationary conditions, with the valuable property that computational time does not scale with the number of isotopomers. The efficiency and limitations of the algorithm is benchmarked for the forward and inverse problems of 13C-DMFA in the pentose phosphate pathways, and is compared with EMU-based methods for NMFA and MFA including the central carbon metabolism. Overall, SSA constitutes an alternative class to deterministic approaches for metabolic flux analysis that is well adapted to comprehensive dataset including parallel labeling experiments, and whose limitations associated to the sampling size can be overcome by using Monte Carlo sampling approaches.

A third of the radiotracer dose: two decades of progress in pediatric [18F]fluorodeoxyglucose PET/CT and PET/MR imaging.

OBJECTIVES: To assess the evolution of administered radiotracer activity for F-18-fluorodeoxyglucose (18F-FDG) PET/CT or PET/MR in pediatric patients (0-16 years) between years 2000 and 2021. METHODS: Pediatric patients (≤ 16 years) referred for 18F-FDG PET/CT or PET/MR imaging of the body during 2000 and 2021 were retrospectively included. The amount of administered radiotracer activity in megabecquerel (MBq) was recorded, and signal-to-noise ratio (SNR) was measured in the right liver lobe with a 4 cm3 volume of interest as an indicator for objective image quality. Descriptive statistics were computed. RESULTS: Two hundred forty-three children and adolescents underwent a total of 466 examinations. The median injected 18F-FDG activity in MBq decreased significantly from 296 MBq in 2000-2005 to 100 MBq in 2016-2021 (p < 0.001), equaling approximately one-third of the initial amount. The median SNR ratio was stable during all years with 11.7 (interquartile range [IQR] 10.7-12.9, p = 0.133). CONCLUSIONS: Children have benefited from a massive reduction in the administered 18F-FDG dose over the past 20 years without compromising objective image quality. CLINICAL RELEVANCE STATEMENT: Radiotracer dose was reduced considerably over the past two decades of pediatric F-18-fluorodeoxyglucose PET/CT and PET/MR imaging highlighting the success of technical innovations in pediatric PET imaging. KEY POINTS: • The evolution of administered radiotracer activity for F-18-fluorodeoxyglucose (18F-FDG) PET/CT or PET/MR in pediatric patients (0-16 years) between 2000 and 2021 was assessed. • The injected tracer activity decreased by 66% during the study period from 296 megabecquerel (MBq) to 100 MBq (p < 0.001). • The continuous implementation of technical innovations in pediatric hybrid 18F-FDG PET has led to a steady decrease in the amount of applied radiotracer, which is particularly beneficial for children who are more sensitive to radiation.

Hybrid imaging of neuroendocrine tumors in the heart: Union is strength.

Cardiac neuroendocrine tumors (NETs) are particularly rare tumors that can lead to a very poor clinical outcome, partly because of metastases but mainly because of manifestations of the hormonal activity they exhibit. Prompt diagnosis is important in order to start the most effective treatment for their removal or management, with the fewest complications. They are often difficult to diagnose, especially in their early stages. One of the reasons for this is that the heart is an organ with a high rate of metabolism and is located in close proximity to other high-metabolism organs. In addition, the anatomic location and their small size render their diagnosis extremely challenging. In recent years, hybrid imaging methods have revolutionized the diagnostic approach to oncology patients and have established a place in the diagnosis of cardiac NETs, because they provide both anatomical and functional information at the same time. Positron emission tomography/computed tomography (PET/CT), PET/magnetic resonance imaging (PET/MRI) and single-photon emission computed tomography/CT (SPECT/CT) are widely used in clinical practice because of the very important metabolic information, the high sensitivity and specificity. However, prospective studies are needed to confirm the true clinical and prognostic value of various hybrid imaging diagnostic techniques in cardiac NETs.

A longitudinal pilot study to assess temporal changes in coronary arterial 18F-sodium fluoride uptake.

PURPOSE: How coronary arterial 18F-sodium fluoride (18F-NaF) uptake on positron emission tomography changes over the long term and what clinical factors impact the changes remain unclear. We sought to investigate the topics in this study. METHODS: We retrospectively studied 15 patients with ≥1 coronary atherosclerotic lesion/s detected on cardiac computed tomography who underwent baseline and follow-up (interval of >3 years) 18F-NaF positron emission tomography/computed tomography scans. Focal 18F-NaF uptake in each lesion was quantified using maximum tissue-to-background ratio (TBRmax). The temporal change in TBRmax was assessed using a ratio of follow-up to baseline TBRmax (R-TBRmax). RESULTS: A total of 51 lesions were analyzed. Mean R-TBRmax was 0.96 ± 0.21. CT-based lesion features (location, obstructive stenosis, plaque types, features of high-risk plaque) did not correlate with an increase in R-TBRmax. In multivariate analysis, baseline TBRmax significantly correlated with higher follow-up TBRmax (ß = 0.57, P < 0.0001), and the presence of diabetes mellitus significantly correlated with both higher follow-up TBRmax (ß = 0.34, P = 0.001) and elevated R-TBRmax (ß = 0.40, P = 0.003). CONCLUSION: Higher coronary arterial 18F-NaF uptake is likely to remain continuously high. Diabetes mellitus affects the long-term increase in coronary arterial 18F-NaF uptake.

Imaging of cardiac sympathetic dysfunction with 18F-FDOPA PET/CT in patients with heart failure: a pilot study.

BACKGROUND: Routine use of cardiac sympathetic imaging in HF has been limited by the lower availability/sensitivity of radiotracers. This study was aimed to assess the feasibility of 18F-FDOPA (commonly available PET-radiotracer) in assessment of cardiac autonomic dysfunction. METHODS: Twenty-four controls (46.5 ± 11.1 years, 16men) and 24 patients (43.5 ± 11.0 years, 18men) with diagnosed HF (Framingham-Criteria) underwent cardiac-PET/CT. Region(s) Of Interest were drawn over entire left ventricular myocardium (LV), individual walls, and mediastinum (M). Coefficient of Variation (CV) was calculated from individual wall counts. RESULTS: HF patients had significantly lower myocardial 18F-FDOPA uptake (P < .001, independent t test) than controls [32.4% ± 9.5% global reduction; highest in apex (39.9% ± 7.0%)]. A cut-off of LV/M ≤ 1.68 could differentiate patients from controls with sensitivity and specificity of 100% and 95.8%, respectively. LV/M correlated positively with EF (Pearson coefficient = 0.460, P .031). During follow-up, 3 patients were lost to follow-up, 4 died (survival-20.5 ± 4 months), 2 worsened, and 15 remained stable/showed mild improvement. Patients who worsened/died during follow-up had higher CV than those with stable/improving symptoms [0.16 ± 0.05 vs 0.11 ± 0.05, P value .069 (independent t test); Cox regression P = .084]. CONCLUSION: Myocardial 18F-FDOPA uptake in patients with HF is significantly reduced. Higher reduction is seen in those with lower EF. CV, a maker of regional heterogeneity, is a potential prognostic marker.