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Abstract: Purpose: The aim of this study was to compare the ability of 18F-FDG PET and iron contrast-enhanced MRI with a novel USPIO (P904) to assess change in plaque inflammation induced by atorvastatin and dietary change in a rabbit model of atherosclerosis using a combined PET/MR scanner. Materials and methods: Atherosclerotic rabbits underwent USPIO-enhanced MRI and 18F-FDG PET in PET/MR hybrid system at baseline and were then randomly divided into a progression group (high cholesterol diet) and a regression group (chow diet and atorvastatin). Each group was scanned again 6 months after baseline imaging. R2* (i.e. 1/T2*) values were calculated pre/post P904 injection. 18F-FDG PET data were analyzed by averaging the mean Standard Uptake Value (SUVmean) over the abdominal aorta. The in vivo imaging was then correlated with matched histological sections stained for macrophages. Results: 18F-FDG PET showed strong FDG uptake in the abdominal aorta and P904 injection revealed an increase in R2* values in the aortic wall at baseline. At 6 months, SUVmean values measured in the regression group showed a significant decrease from baseline (p = 0.015). In comparison, progression group values remained constant (p = 0.681). R2* values showed a similar decreasing trend in the regression group suggesting less USPIO uptake in the aortic wall. Correlations between SUVmean or Change in R2* value and macrophages density (RAM-11 staining) were good (R 2 = 0.778 and 0.707 respectively). Conclusion: This experimental study confirms the possibility to combine two functional imaging modalities to assess changes in the inflammation of atherosclerotic plaques. 18F-FDG-PET seems to be more sensitive than USPIO P904 to detect early changes in plaque inflammation. [Copyright &y& Elsevier]

Excess cortisol is associated with more severe cognitive decline, Alzheimer's disease, and related dementia phenotypes. The intracellular enzyme 11β-HSD1 regenerates active cortisol from inactive cortisone. In this current issue, high regional brain occupancy of Xanamemtrademark, determined by [11C]TARACT PET imaging of 11β-HSD1, in cognitively normal individuals and mild cognitive impartment/Alzheimer's disease (AD) patients is presented. In the future, comprehensive kinetic modeling using arterial sampling for occupancy studies, and whole-body PET imaging of 11β-HSD1 enzyme levels, in combination with stable isotope studies of cortisol metabolism, can provide broad insight into enzyme levels and activity in AD and other relevant diseases.

The rapid and continual development of a number of radiopharmaceuticals targeting different receptor, enzyme and small molecule systems has fostered Positron Emission Tomography (PET) imaging of endocrine system actions in vivo in the human brain for several decades. PET radioligands have been developed to measure changes that are regulated by hormone action (e.g., glucose metabolism, cerebral blood flow, dopamine receptors) and actions within endocrine organs or glands such as steroids (e.g., glucocorticoids receptors), hormones (e.g., estrogen, insulin), and enzymes (e.g., aromatase). This systematic review is targeted to the neuroendocrinology community that may be interested in learning about positron emission tomography (PET) imaging for use in their research. Covering neuroendocrine PET research over the past half century, researchers and clinicians will be able to answer the question of where future research may benefit from the strengths of PET imaging., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Solid Organ Transplant (SOT) recipients are at significant higher risk for COVID-19 and due to immunosuppressive medication, the immunogenicity after vaccination is suboptimal. In the previous studies, booster method showed significant benefit in this population. In the current study, we compared using a mix-and-match method vs. same vaccine as a third dose in SOT recipients. This was a patient-blinded, single center, randomized controlled trial comparing BNT162b2 vs. JNJ-78436735 vaccine as the third dose after two doses of BNT162b2 vaccine. We included adult SOT recipients with functional graft who had received two doses of BNT162b2 vaccine. Participants were randomly assigned to receive either BNT162b2 or JNJ-78436735 in one-to-one ratio. Primary outcome was SARS-CoV-2 IgG positivity at 1 month after the third dose. Sixty SOT recipients, including 36 kidney, 12 liver, 2 lung, 3 heart, and 5 combined transplants, were enrolled, and 57 recipients were analyzed per protocol. There were no statistically significant differences between the two vaccine protocols for IgG positivity (83.3% vs. 85.2% for BNT162b2 and JNJ-78436735, respectively, p = 0.85, Odds Ratio 0.95, 95% Confidence Interval 0.23-4.00). Comparison of the geometric mean titer demonstrated a higher trend with BNT162b2 ( p = 0.09). In this pilot randomized controlled trial comparing mix and match method vs. uniform vaccination in SOT recipients, both vaccines were safely used. Since this was a small sample sized study, there was no statistically significant difference in immunogenicity; though, the mix and match method showed relatively lower geometric mean titer, as compared to uniform vaccine. Further studies need to be conducted to determine duration of this immunogenicity. Clinical Trial Registration : https://clinicaltrials.gov/ct2/show/NCT05047640?term=20210641&draw=2&rank=1, identifier 20210641., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Natori, Martin, Mattiazzi, Arosemena, Ortigosa-Goggins, Shobana, Roth, Kupin, Burke, Ciancio, Morsi, Phancao, Munagala, Butrous, Manickavel, Sinha, Sota, Pallikkuth, Bini, Simkins, Anjan, Vianna and Guerra.)

Objective: To determine if statewide marijuana laws impact upon the detection of drugs and alcohol in victims of motor vehicle collisions (MVC)., Methods: A retrospective analysis of data collected at trauma centers in Arizona, California, Ohio, Oregon, New Jersey, and Texas between 2006 and 2018 was performed. The percentage of patients testing positive for marijuana tetrahydrocannabinol (THC) was compared to the percentage of patients driving under the influence of alcohol (blood alcohol level >0.08 g/dL) that were involved in an MVC., Results: The data were analyzed to evaluate the trends in THC and alcohol use in victims of MVC, related to marijuana legalization. The change in incidence of THC detection (percentage) over the time period where data were available are as follows: Arizona 9.5% (0.4 to 9.9), California 5.4% (20.8 to 26.2), Ohio 5.9% (6.7 to 12.6), Oregon 3% (3.0 to 6.0), New Jersey 2.3% (2.7 to 5.0), and Texas 15.3% (3.0 to 18.3). Alcohol use did not change over time in most states. There did not appear to be a relationship between the legalization of marijuana and the likelihood of finding THC in patients admitted after MVC. In fact, in Texas, where marijuana remains illegal, there was the largest change in detection of THC., Conclusions: There was no apparent increase in the incidence of driving under the influence of marijuana after legalization. In addition, the changes in marijuana legislation did not appear to impact alcohol use.

Noninvasive quantitative imaging of beta-cells can provide information on changes in cellular transporters, receptors, and signaling proteins that may affect function and/or loss of mass, both of which contribute to the loss of insulin secretion and glucose regulation of patients with type 1 or type 2 diabetes (T1D/T2D). We have developed and optimized the use of two positron emission tomography (PET) radioligands, [ 18 F]FP-(+)-DTBZ and [ 11 C](+)-PHNO, targeting beta-cell VMAT2 and dopamine (D2/D3) receptors, respectively. Here we describe our optimized methodology for the clinical use of these two tracers for quantitative PET imaging of beta-cell biomarkers in vivo. We also briefly discuss our previous results and their implications and value towards extending the use of PET radioligand beyond the original goal of quantitative imaging of beta-cell mass to the potential to provide insight into the biology of beta-cell loss of mass and/or function and to evaluate the efficacy of therapeutics to prevent or restore functional beta-cell mass., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Neuronal damage and synapse loss in the spinal cord (SC) have been implicated in spinal cord injury (SCI) and neurodegenerative disorders such as Amyotrophic Lateral Sclerosis (ALS). Current standards of diagnosis for SCI include CT or MRI imaging to evaluate injury severity. The current study explores the use of PET imaging with [ 11 C]UCB-J, which targets the synaptic vesicle protein 2A (SV2A), in the human spinal cord, as a way to visualize synaptic density and integrity in vivo., Results: First, simulations of baseline and blocking [ 11 C]UCB-J HRRT scans were performed, based on SC dimensions and SV2A distribution to predict V T , V ND , and V S values. Next, human baseline and blocking [ 11 C]UCB-J HRRT images were used to estimate these values in the cervical SC (cSC). Simulation results had excellent agreement with observed values of V T , V ND , and V S from the real human data, with baseline V T , V ND , and V S of 3.07, 2.15, and 0.92 mL/cm 3 , respectively, with a BP ND of 0.43. Lastly, we explored full SC imaging with whole-body images. Using automated SC regions of interest (ROIs) for the full SC, cSC, and thoracic SC (tSC), the distribution volume ratio (DVR) was estimated using the brain gray matter as a reference region to evaluate SC SV2A density relative to the brain. In full body imaging, DVR values of full SC, cSC, and tSC were 0.115, 0.145, and 0.112, respectively. Therefore, measured [ 11 C]UCB-J uptake, and thus SV2A density, is much lower in the SC than in the brain., Conclusions: The results presented here provide evidence for the feasibility of SV2A PET imaging in the human SC, however, specific binding of [ 11 C]UCB-J is low. Ongoing and future work include further classification of SV2A distribution in the SC as well as exploring higher-affinity PET radioligands for SC imaging., (© 2022. The Author(s).)

PET imaging of small animals is often used for assessing biodistribution of a novel radioligand and pharmacology in small animal models of disease. PET acquisition and processing settings may affect reference region or image-derived input function (IDIF) kinetic modeling estimates. We examined four different factors in comparing quantitative results: 1) effect of reconstruction algorithm, 2) number of MAP iterations, 3) strength of the MAP prior, and 4) Attenuation and scatter. The effect of these parameters has not been explored for small-animal reference region and IDIF kinetic modeling approaches. Dynamic PET/CT scans were performed in 3 species with 3 different tracers: house sparrows with [ 11 C]raclopride, rats with [ 18 F]AS2471907 (11 β HSD1) and mice with [ 11 C]UCB-J (SV2A). FBP yielded lower kinetic modeling estimates compared to 3D-OSEM-MAP reconstructions, in sparrow and rat studies. Target resolutions (MAP prior strength) of 1.5 and 3.0mm demonstrated reduced V T in rats but only 3.0mm reduced BP ND in sparrows. Therefore, use of the highest target resolution (0.8mm) is warranted. We demonstrated using kinetic modeling that forgoing CT-based attenuation and scatter correction may be appropriate to improve animal throughput when using short-lived radioisotopes in sparrows and mice. This work provides recommendations and a framework for future optimization of kinetic modeling for preclinical PET methodology with novel radioligands.

Context: The neural regulation of appetite and energy homeostasis significantly overlaps with the neurobiology of stress. Frequent exposure to repeated acute stressors may cause increased allostatic load and subsequent dysregulation of the cortico-limbic striatal system leading to inefficient integration of postprandial homeostatic and hedonic signals. It is therefore important to understand the neural mechanisms by which stress generates alterations in appetite that may drive weight gain., Objective: To determine glucocorticoid effects on metabolic, neural and behavioral factors that may underlie the association between glucocorticoids, appetite and obesity risk., Methods: A randomized double-blind cross-over design of overnight infusion of hydrocortisone or saline followed by a fasting morning perfusion magnetic resonance imaging to assess regional cerebral blood flow (CBF) was completed. Visual Analog Scale (VAS) hunger, cortisol and metabolic hormones were also measured., Results: Hydrocortisone relative to saline significantly decreased whole brain voxel based CBF responses in the hypothalamus and related cortico-striatal-limbic regions. Hydrocortisone significantly increased hunger VAS pre-scan, insulin, glucose and leptin, but not other metabolic hormones versus saline CBF groups. Hydrocortisone related increases in hunger were predicted by less reduction of CBF (hydrocortisone minus saline) in the medial OFC, medial brainstem and thalamus, left primary sensory cortex and right superior and medial temporal gyrus. Hunger ratings were also positively associated with plasma insulin on hydrocortisone but not saline day., Conclusions: Increased glucocorticoids at levels akin to those experienced during psychological stress, result in increased fasting hunger and decreased regional cerebral blood flow in a distinct brain network of prefrontal, emotional, reward, motivation, sensory and homeostatic regions that underlie control of food intake., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

Bariatric surgery, initially understood as restricting or bypassing the amount of food that reaches the stomach to reduce food intake and/or increase malabsorption of food to promote weight loss, is now recognized to also affect incretin signaling in the gut and promote improvements in system-wide metabolism. Positron emission tomography (PET) is an imaging technique whereby patients are injected with picomolar concentrations of radioactive molecules, below the threshold of having physiological effects, to measure spatial distributions of blood flow, metabolism, receptor, and enzyme pharmacology. Recent advances in both whole-body PET imaging and radioligand development will allow for novel research that may help clarify the roles of peripheral and central receptor/enzyme systems in treating obesity with bariatric surgery., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Context: Cortisol, a glucocorticoid steroid stress hormone, is primarily responsible for stimulating gluconeogenesis in the liver and promoting adipocyte differentiation and maturation. Prolonged excess cortisol leads to visceral adiposity, insulin resistance, hyperglycemia, memory dysfunction, cognitive impairment, and more severe Alzheimer's disease phenotypes. The intracellular enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes the conversion of inactive cortisone to active cortisol; yet the amount of 11β-HSD1 in the brain has not been quantified directly in vivo., Objective: We analyzed positron emission tomography (PET) scans with an 11β-HSD1 inhibitor radioligand in twenty-eight individuals (23 M/5F): 10 lean, 13 overweight, and 5 obese individuals. Each individual underwent PET imaging on the high-resolution research tomograph PET scanner after injection of 11 C-AS2471907 (n = 17) or 18 F-AS2471907 (n = 11). Injected activity and mass doses were 246 ± 130 MBq and 0.036 ± 0.039 μg, respectively, for 11 C-AS2471907, and 92 ± 15 MBq and 0.001 ± 0.001 μg for 18 F-AS2471907. Correlations of mean whole brain and regional distribution volume (V T ) with body mass index (BMI) and age were performed with a linear regression model., Results: Significant correlations of whole brain mean V T with BMI and age (V T  = 15.23-0.63 × BMI + 0.27 × Age, p = 0.001) were revealed. Age-adjusted mean whole brain V T values were significantly lower in obese individuals. Post hoc region specific analyses revealed significantly reduced mean V T values in the thalamus (lean vs. overweight and lean vs. obese individuals). Caudate, hypothalamus, parietal lobe, and putamen also showed lower V T value in obese vs. lean individuals. A significant age-associated increase of 2.7 mL/cm 3 per decade was seen in BMI-corrected mean whole brain V T values., Conclusions: In vivo PET imaging demonstrated, for the first time, correlation of higher BMI (obesity) with lower levels of the enzyme 11β-HSD1 in the brain and correlation of increased 11β-HSD1 levels in the brain with advancing age.

The ability to quantify synaptic density in vivo in human adults and adolescents is of vital importance to understanding neuropsychiatric disorders. Here, we performed whole-body scans to determine organ radiation dosimetry of 11 C-UCB-J in humans., Methods: Dynamic whole-body PET scans were performed in four healthy adults after injection of 11 C-UCB-J. Regions of interest (ROIs) were drawn manually for the brain, heart, stomach, kidneys, liver, pancreas, spleen, gallbladder, lungs, urinary bladder, and intestines. ROIs were applied to dynamic images to generate time-activity curves (TACs). Decay correction was removed from TACs, and the area under the curve (AUC) for each ROI was calculated. AUCs were then normalized by injected activity and organ volumes to produce radioligand residence times for each organ. These times were then used as input into the OLINDA/EXM 1.0 software to determine the total radiation dose in each organ and the effective dose for these OLINDA models: 55-kg female, 70-kg male, and 15-year-old adolescent., Results: Visual evaluation detected high uptake in the liver, brain, gallbladder, gastrointestinal tract, and urinary bladder. The dose-limiting organ was the urinary bladder for adult males (0.0224 mSv/MBq) and liver for adult females (0.0248 mSv/MBq) with single-study dose limits of 2239 MBq and 2017 MBq 11 C-UCB-J, respectively. For adolescents, the large intestine was the dose-limiting organ (0.0266 mSv/MBq) with a single-study dose limit of 188 MBq., Conclusions: 11 C-UCB-J dosimetry in adults is consistent with those for many carbon-11-labeled ligands. Overall, 11 C-UCB-J can be used safely in adolescents, as in adults, to measure synaptic density in various neuropsychiatric and other relevant disorders.

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes enzymatic conversion of cortisone into the stress hormone cortisol. This first-in-human brain imaging study characterizes the kinetic modeling and test-retest reproducibility of [ 18 F]AS2471907, a novel PET radiotracer for 11β-HSD1. Eight individuals underwent one 180-min ( n  = 4) or two 240-min ( n  = 4) [ 18 F]AS2471907 PET brain scans (12 total) acquired on the high-resolution research tomograph (HRRT) scanner with arterial blood sampling. Imaging data were modeled with 1-tissue (1T) and 2-tissue (2T) compartment models and with multilinear analysis (MA1) to estimate [ 18 F]AS2471907 availability ( V T ). [ 18 F]AS2471907 demonstrated high, heterogeneous uptake throughout the brain. Of the compartment models, 2T best described [ 18 F]AS2471907 data. Estimates of V T were highly correlated between 2T and MA1 ( t*  = 30 min) with MA1 yielding V T values ranging from 3.2 ± 1.0 mL/cm 3 in the caudate to 15.7 ± 4.2 mL/cm 3 in the occipital cortex. The median absolute test-retest variability of 16 ± 5% and high intraclass correlation coefficient (ICC) values of 0.67-0.97 across regions indicate fair test-retest reliability but large intersubject variability. V T estimates using 180 min were within 10% of estimates using full acquisition time. In summary, [ 18 F]AS2471907 exhibits reasonable kinetic properties for imaging 11β-HSD1 in human brain.

Type 1 diabetes mellitus (T1DM) has traditionally been characterized by a complete destruction of β-cell mass (BCM); however, there is growing evidence of possible residual BCM present in T1DM. Given the absence of in vivo tools to measure BCM, routine clinical measures of β-cell function (e.g., C-peptide release) may not reflect BCM. We previously demonstrated the potential utility of PET imaging with the dopamine D 2 and D 3 receptor agonist 3,4,4a,5,6,10b-hexahydro-2 H -naphtho[1,2- b ][1,4]oxazin-9-ol ( 11 C-(+)-PHNO) to differentiate between healthy control (HC) and T1DM individuals. Methods: Sixteen individuals participated (10 men, 6 women; 9 HCs, 7 T1DMs). The average duration of diabetes was 18 ± 6 y (range, 14-30 y). Individuals underwent PET/CT scanning with a 120-min dynamic PET scan centered on the pancreas. One- and 2-tissue-compartment models were used to estimate pancreas and spleen distribution volume. Reference region approaches (spleen as reference) were also investigated. Quantitative PET measures were correlated with clinical outcome measures. Immunohistochemistry was performed to examine colocalization of dopamine receptors with endocrine hormones in HC and T1DM pancreatic tissue. Results: C-peptide release was not detectable in any T1DM individuals, whereas proinsulin was detectable in 3 of 5 T1DM individuals. Pancreas SUV ratio minus 1 (SUVR-1) (20-30 min; spleen as reference region) demonstrated a statistically significant reduction (-36.2%) in radioligand binding (HCs, 5.6; T1DMs, 3.6; P = 0.03). Age at diagnosis correlated significantly with pancreas SUVR-1 (20-30 min) ( R 2 = 0.67, P = 0.025). Duration of diabetes did not significantly correlate with pancreas SUVR-1 (20-30 min) ( R 2 = 0.36, P = 0.16). Mean acute C-peptide response to arginine at maximal glycemic potentiation did not significantly correlate with SUVR-1 (20-30 min) ( R 2 = 0.57, P = 0.05), nor did mean baseline proinsulin ( R 2 = 0.45, P = 0.10). Immunohistochemistry demonstrated colocalization of dopamine D 3 receptor and dopamine D 2 receptor in HCs. No colocalization of the dopamine D 3 receptor or dopamine D 2 receptor was seen with somatostatin, glucagon, or polypeptide Y. In a separate T1DM individual, no immunostaining was seen with dopamine D 3 receptor, dopamine D 2 receptor, or insulin antibodies, suggesting that loss of endocrine dopamine D 3 receptor and dopamine D 2 receptor expression accompanies loss of β-cell functional insulin secretory capacity. Conclusion: Thirty-minute scan durations and SUVR-1 provide quantitative outcome measures for 11 C-(+)-PHNO, a dopamine D 3 receptor-preferring agonist PET radioligand, to differentiate BCM in T1DM and HCs., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

Nanotherapy has recently emerged as an experimental treatment option for atherosclerosis. To fulfill its promise, robust noninvasive imaging approaches for subject selection and treatment evaluation are warranted. To that end, we present here a positron emission tomography (PET)-based method for quantification of liposomal nanoparticle uptake in the atherosclerotic vessel wall. We evaluated a modular procedure to label liposomal nanoparticles with the radioisotope zirconium-89 ( 89 Zr). Their biodistribution and vessel wall targeting in a rabbit atherosclerosis model was evaluated up to 15 days after intravenous injection by PET/computed tomography (CT) and PET/magnetic resonance imaging (PET/MRI). Vascular permeability was assessed in vivo using three-dimensional dynamic contrast-enhanced MRI (3D DCE-MRI) and ex vivo using near-infrared fluorescence (NIRF) imaging. The 89 Zr-radiolabeled liposomes displayed a biodistribution pattern typical of long-circulating nanoparticles. Importantly, they markedly accumulated in atherosclerotic lesions in the abdominal aorta, as evident on PET/MRI and confirmed by autoradiography, and this uptake moderately correlated with vascular permeability. The method presented herein facilitates the development of nanotherapy for atherosclerotic disease as it provides a tool to screen for nanoparticle targeting in individual subjects' plaques.

11 C-UCB-J is a new PET tracer for synaptic density imaging. Recently, we conducted 11 C-UCB-J PET on patients with mild cognitive impairment or early Alzheimer disease (AD) and found a 41% decrease in specific binding in the hippocampus compared with healthy subjects. We hypothesized that 11 C-UCB-J may have potential to be a general biomarker for evaluating AD treatment effects via monitoring of synaptic density changes. In this study, we performed longitudinal 11 C-UCB-J PET on AD mice to measure the treatment effects of saracatinib, which previously demonstrated synaptic changes with postmortem methods. Methods: Nine wild-type (WT) mice and 9 amyloid precursor protein and presenilin 1 double-transgenic (APPswe/PS1ΔE9 [APP/PS1]) mice underwent 3 11 C-UCB-J PET measurements: at baseline, after treatment, and during drug washout. After baseline measurements, saracatinib, a Fyn kinase inhibitor currently in clinical development for AD treatment, was administered by oral gavage for 41 ± 11 d. Treatment-phase measurements were performed on the last day of treatment, and washout-phase measurements occurred more than 27 d after the end of treatment. SUVs from 30 to 60 min after injection of 11 C-UCB-J were calculated and normalized by the whole-brain (WB) or brain stem (BS) average values as SUV ratio (SUVR (WB) or SUVR-1 (BS) ). Results: Hippocampal SUVR (WB) at baseline was significantly lower in APP/PS1 than WT mice (APP/PS1: 1.11 ± 0.04, WT: 1.15 ± 0.02, P = 0.033, unpaired t test). Using SUVR-1 (BS) in the hippocampus, there was also a significant difference at baseline (APP/PS1: 0.48 ± 0.13, WT: 0.65 ± 0.10, P = 0.017, unpaired t test). After treatment with saracatinib, hippocampal SUVR (WB) in APP/PS1 mice was significantly increased ( P = 0.037, paired t test). A trend-level treatment effect was seen with hippocampal SUVR-1 (BS). Saracatinib treatment effects may persist, as there were no significant differences between WT and APP/PS1 mice after drug washout. Conclusion: On the basis of the 11 C-UCB-J PET results, hippocampal synaptic density was lower in APP/PS1 mice than in WT mice at baseline, and this deficit was normalized by treatment with saracatinib. These results support the use of 11 C-UCB-J PET to identify disease-specific synaptic deficits and to monitor treatment effects in AD., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

Aims/hypothesis: The progressive loss of beta cell function is part of the natural history of type 2 diabetes. Autopsy studies suggest that this is, in part, due to loss of beta cell mass (BCM), but this has not been confirmed in vivo. Non-invasive methods to quantify BCM may contribute to a better understanding of type 2 diabetes pathophysiology and the development of therapeutic strategies. In humans, the localisation of vesicular monoamine transporter type 2 (VMAT2) in beta cells and pancreatic polypeptide cells, with minimal expression in other exocrine or endocrine pancreatic cells, has led to its development as a measure of BCM. We used the VMAT2 tracer [ 18 F]fluoropropyl-(+)-dihydrotetrabenazine to quantify BCM in humans with impaired glucose tolerance (prediabetes) or type 2 diabetes, and in healthy obese volunteers (HOV)., Methods: Dynamic positron emission tomography (PET) data were obtained for 4 h with metabolite-corrected arterial blood measurement in 16 HOV, five prediabetic and 17 type 2 diabetic participants. Eleven participants (six HOV and five with type 2 diabetes) underwent two abdominal PET/computed tomography (CT) scans for the assessment of test-retest variability. Standardised uptake value ratio (SUVR) was calculated in pancreatic subregions (head, body and tail), with the spleen as a reference region to determine non-specific tracer uptake at 3-4 h. The outcome measure SUVR minus 1 (SUVR-1) accounts for non-specific tracer uptake. Functional beta cell capacity was assessed by C-peptide release following standard (arginine stimulus test [AST]) and acute insulin response to the glucose-enhanced AST (AIRargMAX). Pearson correlation analysis was performed between the binding variables and the C-peptide AUC post-AST and post-AIRargMAX., Results: Absolute test-retest variability (aTRV) was ≤15% for all regions. Variability and overlap of SUVR-1 was measured in all groups; HOV and participants with prediabetes and with type 2 diabetes. SUVR-1 showed significant positive correlations with AIRargMAX (all groups) in all pancreas subregions (whole pancreas p = 0.009 and pancreas head p = 0.009; body p = 0.019 and tail p = 0.023). SUVR-1 inversely correlated with HbA 1c (all groups) in the whole pancreas (p = 0.033) and pancreas head (p = 0.008). SUVR-1 also inversely correlated with years since diagnosis of type 2 diabetes in the pancreas head (p = 0.049) and pancreas tail (p = 0.035)., Conclusions/interpretation: The observed correlations of VMAT2 density in the pancreas and pancreas regions with years since diagnosis of type 2 diabetes, glycaemic control and beta cell function suggest that loss of BCM contributes to deficient insulin secretion in humans with type 2 diabetes.

Type 1 diabetes mellitus (T1DM) is characterized by a loss of β-cells in the islets of Langerhans of the pancreas and subsequent deficient insulin secretion in response to hyperglycemia. Development of an in vivo test to measure β-cell mass (BCM) would greatly enhance the ability to track diabetes therapies. β-cells and neurologic tissues have common cellular receptors and transporters, therefore, we screened brain radioligands for their ability to identify β-cells. Methods: We examined a β-cell gene atlas for endocrine pancreas receptor targets and cross-referenced these targets with brain radioligands that were available at our institution. Twelve healthy control subjects and 2 T1DM subjects underwent dynamic PET/CT scans with 6 tracers. Results: The D 2 /D 3 receptor agonist radioligand 11 C-(+)-4-propyl-9-hydroxynaphthoxazine (PHNO) was the only radioligand to demonstrate sustained uptake in the pancreas with high contrast versus abdominal organs such as the kidneys, liver, and spleen, based on the first 30 min of data. Mean SUV from 20 to 30 min demonstrated high uptake of 11 C-(+)-PHNO in healthy controls (SUV, 13.8) with a 71% reduction in a T1DM subject with undetectable levels of C-peptide (SUV, 4.0) and a 20% reduction in a T1DM subject with fasting C-peptide level of 0.38 ng/mL (SUV, 11.0). SUV in abdominal organs outside the pancreas did not show measurable differences between the control and T1DM subjects, suggesting that the changes in SUV of 11 C-(+)-PHNO may be specific to changes in the pancreas between healthy controls and T1DM subjects. When D 3 and D 2 antagonists were used in nonhuman primates, specific pancreatic binding (SUVR-1) of 11 C-PHNO was reduced by 57% and 38%, respectively. Conclusion: 11 C-(+)-PHNO is a potential marker of BCM, with 2:1 binding of D 3 receptors over D 2 receptors. Further in vitro and in vivo studies to establish D 2 /D 3 receptor specificity to β-cells is warranted to characterize 11 C-(+)-PHNO as a candidate for clinical measurement of BCM in healthy control and diabetic subjects., (© 2018 by the Society of Nuclear Medicine and Molecular Imaging.)

Recent work suggests that diet affects brain metabolism thereby impacting cognitive function. Our objective was to determine if a western diet altered brain metabolism, increased blood-brain barrier (BBB) transport and inflammation, and induced cognitive impairment in C57BL/6 (WT) mice and low-density lipoprotein receptor null (LDLr -/-) mice, a model of hyperlipidemia and cognitive decline. We show that a western diet and LDLr -/- moderately influence cognitive processes as assessed by Y-maze and radial arm water maze. Also, western diet significantly increased BBB transport, as well as microvessel factor VIII in LDLr -/- and microglia IBA1 staining in WT, both indicators of activation and neuroinflammation. Interestingly, LDLr -/- mice had a significant increase in 18F- fluorodeoxyglucose uptake irrespective of diet and brain 1H-magnetic resonance spectroscopy showed increased lactate and lipid moieties. Metabolic assessments of whole mouse brain by GC/MS and LC/MS/MS showed that a western diet altered brain TCA cycle and β-oxidation intermediates, levels of amino acids, and complex lipid levels and elevated proinflammatory lipid mediators. Our study reveals that the western diet has multiple impacts on brain metabolism, physiology, and altered cognitive function that likely manifest via multiple cellular pathways.

Objectives: The goal of this study was to develop and validate a noninvasive imaging tool to visualize the in vivo behavior of high-density lipoprotein (HDL) by using positron emission tomography (PET), with an emphasis on its plaque-targeting abilities., Background: HDL is a natural nanoparticle that interacts with atherosclerotic plaque macrophages to facilitate reverse cholesterol transport. HDL-cholesterol concentration in blood is inversely associated with risk of coronary heart disease and remains one of the strongest independent predictors of incident cardiovascular events., Methods: Discoidal HDL nanoparticles were prepared by reconstitution of its components apolipoprotein A-I (apo A-I) and the phospholipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine. For radiolabeling with zirconium-89 ((89)Zr), the chelator deferoxamine B was introduced by conjugation to apo A-I or as a phospholipid-chelator (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-deferoxamine B). Biodistribution and plaque targeting of radiolabeled HDL were studied in established murine, rabbit, and porcine atherosclerosis models by using PET combined with computed tomography (PET/CT) imaging or PET combined with magnetic resonance imaging. Ex vivo validation was conducted by radioactivity counting, autoradiography, and near-infrared fluorescence imaging. Flow cytometric assessment of cellular specificity in different tissues was performed in the murine model., Results: We observed distinct pharmacokinetic profiles for the two (89)Zr-HDL nanoparticles. Both apo A-I- and phospholipid-labeled HDL mainly accumulated in the kidneys, liver, and spleen, with some marked quantitative differences in radioactivity uptake values. Radioactivity concentrations in rabbit atherosclerotic aortas were 3- to 4-fold higher than in control animals at 5 days' post-injection for both (89)Zr-HDL nanoparticles. In the porcine model, increased accumulation of radioactivity was observed in lesions by using in vivo PET imaging. Irrespective of the radiolabel's location, HDL nanoparticles were able to preferentially target plaque macrophages and monocytes., Conclusions: (89)Zr labeling of HDL allows study of its in vivo behavior by using noninvasive PET imaging, including visualization of its accumulation in advanced atherosclerotic lesions. The different labeling strategies provide insight on the pharmacokinetics and biodistribution of HDL's main components (i.e., phospholipids, apo A-I)., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

With the introduction of clinical PET/magnetic resonance (MR) systems, novel attenuation correction methods are needed, as there are no direct MR methods to measure the attenuation of the objects in the field of view (FOV). A unique challenge for PET/MR attenuation correction is that coils for MR data acquisition are located in the FOV of the PET camera and could induce significant quantitative errors. In this review, current methods and techniques to correct for the attenuation of a variety of coils are summarized and evaluated., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Errors in quantification of carotid positron emission tomography (PET) in simultaneous PET/magnetic resonance (PET/MR) imaging when not incorporating bone in MR-based attenuation correction (MRAC) maps, and possible solutions, remain to be fully explored. In this study, we demonstrated techniques to improve carotid vascular PET/MR quantification by adding a bone tissue compartment to MRAC maps and deriving continuous Dixon-based MRAC (MRACCD) maps. We demonstrated the feasibility of applying ultrashort echo time-based bone segmentation and generation of continuous Dixon MRAC to improve PET quantification on five subjects. We examined four different MRAC maps: system standard PET/MR MRAC map (air, lung, fat, soft tissue) (MRACPET/MR), standard PET/MR MRAC map with bone (air, lung, fat, soft tissue, bone) (MRACPET/MRUTE), MRACCD map (no bone) and continuous Dixon-based MRAC map with bone (MRACCDUTE). The same PET emission data was then reconstructed with each respective MRAC map and a CTAC map (PETPET/MR, PETPET/MRUTE, PETCD, PECDUTE) to assess effects of the different attenuation maps on PET quantification in the carotid arteries and neighboring tissues. Quantitative comparison of MRAC attenuation values for each method compared to CTAC showed small differences in the carotid arteries with UTE-based segmentation of bone included and/or continuous Dixon MRAC; however, there was very good correlation for all methods in the voxel-by-voxel comparison. ROI-based analysis showed a similar trend in the carotid arteries with the lowest correlation to PETCTAC being PETPETMR and the highest correlation to PETCTAC being PETCDUTE. We have demonstrated the feasibility of applying UTE-based segmentation and continuous Dixon MRAC maps to improve carotid PET/MR vascular quantification.

The purpose of the study was to evaluate the effect of attenuation of MR coils on quantitative carotid PET/MR exams. Additionally, an automated attenuation correction method for flexible carotid MR coils was developed and evaluated. The attenuation of the carotid coil was measured by imaging a uniform water phantom injected with 37 MBq of 18F-FDG in a combined PET/MR scanner for 24 min with and without the coil. In the same session, an ultra-short echo time (UTE) image of the coil on top of the phantom was acquired. Using a combination of rigid and non-rigid registration, a CT-based attenuation map was registered to the UTE image of the coil for attenuation and scatter correction. After phantom validation, the effect of the carotid coil attenuation and the attenuation correction method were evaluated in five subjects. Phantom studies indicated that the overall loss of PET counts due to the coil was 6.3% with local region-of-interest (ROI) errors reaching up to 18.8%. Our registration method to correct for attenuation from the coil decreased the global error and local error (ROI) to 0.8% and 3.8%, respectively. The proposed registration method accurately captured the location and shape of the coil with a maximum spatial error of 2.6 mm. Quantitative analysis in human studies correlated with the phantom findings, but was dependent on the size of the ROI used in the analysis. MR coils result in significant error in PET quantification and thus attenuation correction is needed. The proposed strategy provides an operator-free method for attenuation and scatter correction for a flexible MRI carotid surface coil for routine clinical use.

The purpose of this study was to develop and validate low dose (18)F-FDG-PET acquisition protocols for detection of inflamed carotid plaques specifically for simultaneous PET/MR imaging. The hypothesis was that increasing the duration of the PET acquisition to match that of the MR acquisition might allow for the use of lower levels of the radiotracer, while preserving quantification and image quality. Seven subjects were scanned twice at least one week apart on a simultaneous PET/MR scanner using either the standard clinical dose of (18)F-FDG (373 ± 63 MBq) for 8 minutes or a low dose (93 ± 17 MBq) for 75 minutes. A maximum absolute percent difference of only 4.17% and 7.49% in the left and right carotid TBR was found between the standard dose and four time points of the low dose acquisitions (8, 24, 45, 75 minutes). Only the 8-minute low dose PET data was significantly different in terms of SNR (P = 0.009; % difference = -51%) and qualitative image quality evaluation (P = 0.0005; % difference = -45%). Our preliminary findings indicate that up to 75% reduction of the clinical standard (18)F-FDG dose could be achieved using the proposed acquisition scheme while maintaining accurate quantification and SNR.

Current PET/MR systems employ segmentation of MR images and subsequent assignment of empirical attenuation coefficients for quantitative PET reconstruction. In this study we examine the differences in the quantification of (18)F-FDG uptake in the carotid arteries between PET/MR and PET/CT scanners. Five comparisons were performed to asses differences in PET quantification: i) PET/MR MR-based AC (MRAC) versus PET/MR CTAC, ii) PET/MR MRAC versus PET/CT, iii) PET/MR MRAC with carotid coil versus PET/MR MRAC without coil, iv) PET/MR MRAC scan 2 versus PET/MR MRAC scan 1, and v) PET/MR CTAC versus PET/CT. Standardized uptakes values (SUV) mean and SUV maximum were calculated for six regions-of-interests: left and right carotid arteries, left and right lungs, spine and muscle. Pearson's Correlation and Bland-Altman plots were used to compare SUV mean and maximum within each ROI of each patient. PET/MR emission data reconstructed with MRAC versus PET/MR emission data reconstructed with CTAC had percent differences of SUV mean ranging from -2.0% (Absolute Difference, -0.02) to 7.4% (absolute difference, 0.06). Percent differences within the carotid arteries proved to correlate well with differences of SUV mean of 5.4% (Absolute Difference, 0.07) in the left carotid and 2.7% (Absolute Difference, 0.03) in the right carotid. Pearson's correlation and Bland-Altman of PET/MR with MRAC versus PET/MR with CTAC showed high correlation between SUV mean (R(2)=0.80, mean difference 0.03 ± 0.18 SUV, p=0.3382), demonstrating excellent correlation within ROIs analyzed. The results of this study support the use of (18)F-FDG PET/MR for quantitative measure of inflammation in the carotid arteries.

Introduction: Attenuation correction for magnetic resonance (MR) coils is a new challenge that came about with the development of combined MR and positron emission tomography (PET) imaging. This task is difficult because such coils are not directly visible on either PET or MR acquisitions with current combined scanners and are therefore not easily localized in the field of view. This issue becomes more evident when trying to localize flexible MR coils (eg, cardiac or body matrix coil) that change position and shape from patient to patient and from one imaging session to another. In this study, we proposed a novel method to localize and correct for the attenuation and scatter of a flexible MR cardiac coil, using MR fiducial markers placed on the surface of the coil to allow for accurate registration of a template computed tomography (CT)-based attenuation map., Materials and Methods: To quantify the attenuation properties of the cardiac coil, a uniform cylindrical water phantom injected with 18F-fluorodeoxyglucose (18F-FDG) was imaged on a sequential MR/PET system with and without the flexible cardiac coil. After establishing the need to correct for the attenuation of the coil, we tested the feasibility of several methods to register a precomputed attenuation map to correct for the attenuation. To accomplish this, MR and CT visible markers were placed on the surface of the cardiac flexible coil. Using only the markers as a driver for registration, the CT image was registered to the reference image through a combination of rigid and deformable registration. The accuracy of several methods was compared for the deformable registration, including B-spline, thin-plate spline, elastic body spline, and volume spline. Finally, we validated our novel approach both in phantom and patient studies., Results: The findings from the phantom experiments indicated that the presence of the coil resulted in a 10% reduction in measured 18F-FDG activity when compared with the phantom-only scan. Local underestimation reached 22% in regions of interest close to the coil. Various registration methods were tested, and the volume spline was deemed to be the most accurate, as measured by the Dice similarity metric. The results of our phantom experiments showed that the bias in the 18F-FDG quantification introduced by the presence of the coil could be reduced by using our registration method. An overestimation of only 1.9% of the overall activity for the phantom scan with the coil attenuation map was measured when compared with the baseline phantom scan without coil. A local overestimation of less than 3% was observed in the ROI analysis when using the proposed method to correct for the attenuation of the flexible cardiac coil. Quantitative results from the patient study agreed well with the phantom findings., Conclusions: We presented and validated an accurate method to localize and register a CT-based attenuation map to correct for the attenuation and scatter of flexible MR coils. This method may be translated to clinical use to produce quantitatively accurate measurements with the use of flexible MR coils during MR/PET imaging.

Unlabelled: Quantitative PET imaging relies on accurate attenuation correction. Recently, there has been growing interest in combining state-of-the-art PET systems with MR imaging in a sequential or fully integrated setup. As CT becomes unavailable for these systems, an alternative approach to the CT-based reconstruction of attenuation coefficients (μ values) at 511 keV must be found. Deriving μ values directly from MR images is difficult because MR signals are related to the proton density and relaxation properties of tissue. Therefore, most research groups focus on segmentation or atlas registration techniques. Although studies have shown that these methods provide viable solutions in particular applications, some major drawbacks limit their use in whole-body PET/MR. Previously, we used an annulus-shaped PET transmission source inside the field of view of a PET scanner to measure attenuation coefficients at 511 keV. In this work, we describe the use of this method in studies of patients with the sequential time-of-flight (TOF) PET/MR scanner installed at the Icahn School of Medicine at Mount Sinai, New York, NY., Methods: Five human PET/MR and CT datasets were acquired. The transmission-based attenuation correction method was compared with conventional CT-based attenuation correction and the 3-segment, MR-based attenuation correction available on the TOF PET/MR imaging scanner., Results: The transmission-based method overcame most problems related to the MR-based technique, such as truncation artifacts of the arms, segmentation artifacts in the lungs, and imaging of cortical bone. Additionally, the TOF capabilities of the PET detectors allowed the simultaneous acquisition of transmission and emission data. Compared with the MR-based approach, the transmission-based method provided average improvements in PET quantification of 6.4%, 2.4%, and 18.7% in volumes of interest inside the lung, soft tissue, and bone tissue, respectively., Conclusion: In conclusion, a transmission-based technique with an annulus-shaped transmission source will be more accurate than a conventional MR-based technique for measuring attenuation coefficients at 511 keV in future whole-body PET/MR studies.

Objectives: The application of attenuation correction for combined magnetic resonance/positron emission tomography (MR/PET) systems is still a major challenge for accurate quantitative PET. Computed tomographic attenuation correction (CTAC) is the current clinical standard for PET/computed tomographic (CT) scans. Magnetic resonance, unlike CT, has no direct information about photon attenuation but, rather, proton densities. On combined MR/PET scanners, MR-based attenuation correction (MRAC) consists of assigning empirical attenuation coefficients to MR signal intensities. The objective of the current study was to evaluate the MRAC implemented on the combined MR/PET scanner versus the CTAC with the same PET data in an animal model., Materials and Methods: Acquisition was performed using a clinically approved sequential MR/PET scanner (Philips Ingenuity TF). Computed tomographic and MR/PET images of 20 New Zealand White rabbits were retrospectively analyzed. The animals were positioned on a customized animal bed to avoid movement between the CT and MR/PET scanners. Positron emission tomographic images from both methods (MRAC and CTAC) were generated. Voxel-by-voxel and region-of-interest (ROI) analyses were performed to determine differences in standardized uptake values (SUV). Regions of interest were drawn on the coregistered CT images for the aorta, liver, kidney, spine, and soft tissue (muscle) and superimposed on the PET images., Results: The voxel-by-voxel comparison of PET showed excellent correlation between MRAC and CTAC SUV values (R = 0.99; P < 0.0001). The mean of the difference of SUVs between all respective MRAC and CTAC voxels was -0.94% (absolute difference [AD] ± SD, -0.06 ± 0.30), confirming slight underestimation of MRAC. The ROI-based comparison similarly showed that MRAC SUV values were underestimated compared with CTAC SUV values. The mean difference between MRAC and CTAC for all ROIs was 10.8% (AD, -0.08 ± 0.06; R = 0.99; P < 0.0001) and -9.7% (AD, -0.15 ± 0.12; R = 0.99; P < 0.0001) for the SUV mean (SUV mean) and the SUV maximum (SUV max), respectively. The highest differences were found in the spine (SUV mean -26.1% [-0.11]) and areas close to large bones such as the back muscles (SUV mean, -16.8% [-0.04])., Conclusions: In this study, we have compared MRAC and CTAC methods for PET attenuation correction in an animal model. We have confirmed that the MRAC method implemented on a sequential MR/PET scanner underestimates PET values by less than 10% in most regions, except the areas containing or close to large bone structures such as the spine or the back muscles. Bone segmentation is therefore suggested to be included in the MR attenuation map to minimize the quantification error of MRAC methods compared with the clinical standard CTAC. Further clinical studies need to be carried out to validate the clinical use of MRAC.

Confocal mosaicing microscopy enables rapid imaging of large areas of fresh tissue, without the processing that is necessary for conventional histology. Mosaicing may offer a means to perform rapid histology at the bedside. A possible barrier toward clinical acceptance is that the mosaics are based on a single mode of grayscale contrast and appear black and white, whereas histology is based on two stains (hematoxylin for nuclei, eosin for cellular cytoplasm and dermis) and appears purple and pink. Toward addressing this barrier, we report advances in digital staining: fluorescence mosaics that show only nuclei, are digitally stained purple and overlaid on reflectance mosaics, which show only cellular cytoplasm and dermis, and are digitally stained pink. With digital staining, the appearance of confocal mosaics mimics the appearance of histology. Using multispectral analysis and color matching functions, red, green, and blue (RGB) components of hematoxylin and eosin stains in tissue were determined. The resulting RGB components were then applied in a linear algorithm to transform fluorescence and reflectance contrast in confocal mosaics to the absorbance contrast seen in pathology. Optimization of staining with acridine orange showed improved quality of digitally stained mosaics, with good correlation to the corresponding histology.

Merkel cell carcinoma (MCC) is the eponym for primary cutaneous neuroendocrine carcinoma. Recently, a new polyoma virus has been identified that is clonally integrated in the genome of the majority of MCCs, with truncating mutations in the viral large T antigen gene. We examined the presence of Merkel cell polyomavirus (MCV) in a set of 17 frozen tumor samples by quantitative polymerase chain reaction; 15 of them (88%) were positive. Sections from corresponding archival material were analyzed by immunohistochemistry (IHC) with the novel monoclonal antibody CM2B4, generated against a predicted antigenic epitope on the MCV T antigen, and tested for the expression of cytokeratin 20 (CK20). Sufficient archival material for IHC was available in only 15 of the 17 cases whose frozen tissue samples had been studied by polymerase chain reaction. Of the 15 tumors analyzed immunohistochemically, 10 (67%) showed positive labeling with CM2B4, 14 (93%) expressed CK20. A tissue microarray of 36 MCCs, 7 combined squamous and neuroendocrine carcinomas of the skin, and 26 pulmonary neuroendocrine carcinomas were also examined by IHC. Of the 36 MCCs assembled on a microarray, 32 (89%) tumors expressed CK20, and 27 (75%) were immunoreactive with CM2B4. The skin tumors with a combined squamous and neuroendocrine phenotype and all pulmonary neuroendocrine carcinomas failed to react with CM2B4. Our study shows that CM2B4 is a useful reagent for the diagnosis of MCC. It labels the majority of MCCs, but fails to react with pulmonary neuroendocrine carcinomas. We also found that neuroendocrine carcinomas of the skin arising in association with a squamous cell carcinoma seem to be independent of MCV.

Viral gastroenteritis are a problem of public health because of the high rate of morbidity and mortality, particularly in children. Among the etiologic agents, human Astroviruses are the third agents most often incriminated after Rotaviruses and Caliciviruses. Symptoms of gastroenteritis caused by Astroviruses are generally moderated compared with those observed with Rotaviruses and rarely involve hospitalization. In sub-Saharan Africa, particularly in Côte d'Ivoire, the majority of viral gastroenteritis is attributed to Rotavirus with rates varying from 20 to 26%. No study on the circulation of human Astroviruses has been carried out in Côte d'Ivoire. Our objective was to detect human Astroviruses in the diarrhoeal stools in Abidjan. Seventy-two samples of human diarrhoeal stools were collected in ambulatory patients. This population was made up of 44 patients from 0 to 15 and 28 patients over 15 years old. The concentration of the viral particles of the samples was followed by the extraction of the RNA by the modified method of Boom. The extracted RNA were amplified by RT-PCR by using specific primers targeting a portion of the 3' end of the open reading frame ORF la of the genome of human Astroviruses. The amplified fragment was 192 pb. The genome of human Astroviruses was detected in 3 stools out of the 72 samples. That is a frequency of 4%. Among these 3 stools, 2 came from 4 month and 3 year-old children and the 3rd stool came from a 33 year-old patient. For the first time this survey has pointed out the circulation of human Astroviruses in the Côte d'Ivoire population. This survey also showed that human Astroviruses could be found in children as well as in adults.

The Côte-d'Ivoire Pasteur Institute unit of Tuberculous and Nontuberculous Mycobacteria carried out 600 smears stained by Ziehl-Neelsen in 200 immigrant candidates for the U.S.A. The sputa of 44 of them were put in culture on Lowenstein-Jensen medium. Eight (4%) candidates had active pulmonary tuberculosis among whom 5 had smear negative sputum. The pulmonary tuberculosis active detection performed on target population with accessible and sensitive tool can contribute to strengthen the fight against tuberculosis in endemic areas.