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The classical intent of PET imaging is to obtain the most accurate estimate of the amount of positron-emitting radiotracer in the smallest possible volume element located anywhere in the imaging subject at any time using the least amount of radioactivity. Reaching this goal, however, is confounded by an enormous array of interlinked technical issues that limit imaging system performance. As a result, advances in PET, human or animal, are the result of cumulative innovations across each of the component elements of PET, from data acquisition to image analysis. In the report that follows, we trace several of these advances across the imaging process with a focus on small animal PET.

Background: Patients with osteoblastic bone metastases are candidates for radium-223 ((223)RaCl(2)) therapy and may undergo sodium fluoride-18 ((18)F-NaF) positron emission tomography-computed tomography imaging to identify bone lesions. (18)F-NaF has been shown to predict (223)RaCl(2) uptake, but intratumor distributions of these two agents remain unclear. In this study, the authors evaluate the spatial distribution and relative uptakes of (18)F-NaF and (223)RaCl(2) in Hu09-H3 human osteosarcoma mouse xenograft tumors at macroscopic and microscopic levels to better quantify their correlation. Materials and Methods: (18)F-NaF and (223)RaCl(2) were co-injected into Hu09-H3 xenograft tumor severe combined immunodeficient mice. Tumor content was determined from in vivo biodistributions and visualized by PET, single photon emission computed tomography, and CT imaging. Intratumor distributions were visualized by quantitative autoradiography of tumor tissue sections and compared to histology of the same or adjacent sections. Results: (18)F and (223)Ra accumulated in proportional amounts in whole Hu09-H3 tumors (r(2) = 0.82) and in microcalcified regions within these tumors (r(2) = 0.87). Intratumor distributions of (18)F and (223)Ra were spatially congruent in these microcalcified regions. Conclusions: (18)F-NaF and (223)RaCl(2) uptake are strongly correlated in heterogeneously distributed microcalcified regions of Hu09-H3 xenograft tumors, and thus, tumor accumulation of (18)F is predictive of (223)Ra accumulation. Hu09-H3 xenograft tumors appear to possess certain histopathological features found in patients with metastatic bone disease and may be useful in clarifying the relationship between administered (223)Ra dose and therapeutic effect.

INTRODUCTION: A study of (211)Pb contamination caused by the outgassing of (219)Rn from (223)Ra in dry, liquid, and murine tissues samples has been made to help design proper handling procedures for (223)Ra in preclinical biodistribution work. MATERIALS AND METHODS: (211)Pb activity levels were measured from (223)Ra in dry, liquid, and tissue samples using aspiration and autoradiography techniques. RESULTS: Using aspiration techniques on dry samples of (223)Ra, an average (219)Rn outgassing rate of 51% ± 21% was measured with one measurement reaching as high as 81%. 31% ± 4% (211)Pb contamination was measured within a 4.3 cm radius of a dry (223)Ra source placed inside a 10-cm-diameter petri dish where the lip of the petri dish contained the (219)Rn dissemination. Without the containment of the petri dish, (219)Rn can reach as far as 7.8 cm from the source with trace levels spreading further. Using aspiration techniques on liquid samples of (223)Ra, outgassing rates of (219)Rn were 0.9% ± 0.3%. The outgassing levels in harvested organs from a biodistribution were as high as 10.1% ± 0.4% for an intraperitoneally injected mouse and 0.204% ± 0.006% for an intravenously injected mouse. The outgassing of the intravenously injected mouse carcass was less than 0.1%. CONCLUSION: In dry form, the high levels of (219)Rn outgassing from a (223)Ra source necessitate the use of ventilated biohoods when handling or preparing dry (223)Ra from source vials. The very low levels of (219)Rn outgassing from (223)Ra liquid sources reduces exposure to (219)Rn by a factor of 50. (219)Rn exposure from murine organ tissue reaches levels of 10% when handling organs from an intraperitoneal injection and less than 0.2% for an intravenous injection.

The primary aim of this study was to investigate the pharmacokinetics ofTen consecutive patients with biopsy-proven high-risk prostate cancer underwent a dynamicHigh-risk primary prostate cancer is readily identified on dynamic and static, delayed

This article presents the results of a computational investigation of an integrated propeller test case using the HPCMP CREATETM-AV Kestrel simulation tools. There is a renewed interest in propeller-driven aircraft for unmanned aerial vehicles, electric aircraft, and flying taxies. Computational resources can significantly accelerate the generation of aerodynamic models for these vehicles and reduce the development cost if the prediction tools can accurately predict the aircraft/propeller aerodynamic interactions. Unfortunately, limited propeller experimental data are available to validate computational methods. An American Institute of Aeronautics and Astronautics (AIAA) workshop was therefore established to address this problem. The objective of this workshop was to generate an open access-powered wind tunnel test database for computational validation of propeller effects on the wing aerodynamics, specifically for wing-tip-mounted propellers. The propeller selected for the workshop has four blades and a diameter of 16.2 in. The wing has a root and tip chord of 11.6 and 8.6 in, respectively. Two different simulation approaches were used: one using a single grid including wind tunnel walls and the second using a subset grid overset to an adaptive Cartesian grid that fills the space between the near-body grid and wind tunnel walls. The predictions of both approaches have been compared with available experimental data from the Lockheed Martin low-speed wind tunnel to investigate the grid resolution required for accurate prediction of flowfield data. The results show a good agreement for all tested conditions. The measured and predicted data show that wing aerodynamic performance is improved by the spinning tip-mounted propeller.

This paper describes a heuristic approach to feedback flow control and illustrates its use for two flowfields: the flow around a tangent ogive at large angles of attack and the shear layer behind a...

Experiments were conducted on a flexible, finite-span cyber–physical wing model in the wind tunnel to study the structural kinematics for a wing undergoing stall flutter. The wing model was designed to be weak in torsion and stiff in bending to exhibit stall flutter oscillations. The physical deformation of the wing surface was mapped at 38%, 58%, 78%, and 98% span using a stereo vision motion tracking system. From these measurements, the wing motion is decomposed and shown to consist of a principally torsional (pitching) oscillation consistent with the first mode for a cantilevered beam in free vibration. A two equation empirical model of the wing motion was then developed and compared to the measured stall flutter motion.

The fluid–structure interactions of a finite aspect ratio, cantilevered, flexible wing were investigated using a cyber-physical system to virtually augment the torsional dynamics of the wing. Cyber-physical systems (CPS), which have recently been pursued by a small number of research groups, have proven to be a very useful mechanism to interrogate the fluid–structure interaction parameter space. The premise of a CPS is to use dynamic feedback control to make a system behave according to desired equations of motion. Systems are composed of embedded hardware and software coupled with real-time computing to give the user the flexibility to quickly explore a range of structural parameters. With the advancement of modern control theory, robotics and embedded systems, CPSs integrate both simulation and physical properties into a smart structure which can be used to push the boundaries of research investigations. The CPS in this work allows for the investigation of dynamic aeroelastic instabilities of a three-dimensional, flexible, rectangular planform wing. Two dynamic instability regimes are observed: first, stall flutter, in which the torsional or pitch mode is excited through the dynamic stall process, and second, coupled (or classical) flutter, in which the pitch mode couples with the bending mode. By varying the torsional stiffness and therefore the frequency of torsional versus bending oscillations of the wing, both of these regimes can be attained at the same aerodynamic conditions using the CPS.

The focus of this work is on the computational methodology for aerodynamic modeling of ram-air parachutes and increasing confidence and understanding in their concept designs including new parachute control methods. The complex geometries of ram-air parachutes are modeled by two-dimensional rigid airfoil geometries with or without trailing-edge deflections and bleed air spoilers. The aerodynamic forces are then calculated from steady or unsteady Reynolds-averaged Navier–Stokes simulations using Cobalt and Kestrel flow solvers. The effects of the grid size and type, the time step, and the choice of solver parameters are investigated. The flow solvers are then used to study the flow around three-dimensional wings with open/closed ram-air inlets by comparing lift and drag coefficients with available experimental data. The results show that computational fluid dynamics simulations are a valuable aid in understanding the flow structure of ram-air parachutes, which resemble a rectangular wing with open inlets. ...

This work presents a step toward bridging the gap between flight dynamics simulation of ram-air parachutes and high-fidelity computational fluid dynamics. Today's parachute design codes mainly rely on the empirical or semi-empirical methods generated from wind tunnel experiments and drop tests. The outcome of this study will hopefully help to reduce the cost of experiments and drop testing in the design of future canopies and to better understand the aerodynamic characteristics of these geometries. In this work, the parachute geometries were modeled as rigid rectangular wings with an aspect ratio of two and zero anhedral angle. The wings have seven opening cells and the trailing edge is deflected or not deflected. To validate computational methods, the aerodynamic predictions of similar wings, but with closed and round inlets, are compared with experimental data available from the Subsonic Wind Tunnel at United States Air Force Academy. Total lift and drag force coefficients were measured at a Reynolds number of 1.4 million. The results show that computational predictions of fine (closed-inlet) grids match the experimental data very well up to the stall angle. Both experiments and simulations show that closed wings have sharp stalling characteristics. The aerodynamics of closed wings up to stall can be approximated by linear functions and their derivatives. The closed wings show a negative static stability with respect to changes in the angle of attack. The open wings, on other hand, have positive static stability in the longitudinal and lateral directions. The open wings exhibit highly nonlinear unsteady aerodynamic characteristics; they also stall earlier and have higher drag values than the closed wings. The aerodynamic derivatives of open and closed wings were estimated using a linear regression method and training data simulated in small-amplitude oscillations in pitch, yaw, and roll directions. While the open wings have large oscillations in aerodynamic coefficients over the yawing and rolling hysteresis loops, lateral aerodynamic derivatives of the open and closed wings are similar. Finally, the results show that model predictions are reasonably accurate for use in flight-dynamics simulations.

This work provides an overview of the grid quality and resolution effects on the aerodynamic modeling of ram-air parachute canopies. The computational-fluid-dynamics simulations of this work were performed using the Cobalt flow solver, which is a three-dimensional code, but it was run in a two-dimensional mode for canopy sections with open and closed inlets. Previous simulation results of these geometries showed that grid independence is achieved for the closed and open airfoils with grids containing around half a million and 2 million cells, respectively. Previous grids were either hybrid with prismatic layers near the walls or multiblock structured using algebraic grid generators. The results presented in this work show that grid independence of both geometries can be achieved with much coarser grids. These grids, however, were generated with good smoothness, wall orthogonality, and skewness qualities. The results show that the grid quality value is mainly related to the grid smoothness and does not dep...

Objective: (18)F-albumin, a vascular imaging agent, may have potential to assess tumor responses to anti-angiogenic therapies. In these studies tumor distribution volume of (18)F-albumin were first determined in various human tumor xenografts from biodistribtuion measurments and then one of the tumor type was used to evaluate changes in (18)F-albumin uptake in anti-angiognic tumor model. Method: (18)F-albumin was synthesized via conjugation of 6-[(18)F]fluoronicotinic acid-2,3,5,6-tetrafluorophenyl ester, [(18)F]F-Py-TFP, with rat albumin. From the biodistribution of (18)F-albumin in various human tumor xenografts tumor distribution volumes (DVs; tumor(%ID/g):blood(%ID/g)) were first determined at various time points. Then, the ability of (18)F-albumin to detect tumor angiogenic inhibition in one of these tumor types (U87MG) following treatment with sunitinib was evaluated by position emission tomography (PET) imaging at 0, 7, 14, and 21 days post treatment. Caliper measurements of tumor dimensions were also made at these same times. At Day 21, following imaging, biodistributions, autoradiography of tumor tissues and tumor blood vessel counts (CD31 IHC) were performed. Results: (18)F-albumin retention in various tumors steadily increased over time with U87MG tumor exhibiting the highest uptake (DV) at all times. Significant decreases in (18)F-albumin DVs were observed one week post-treatement (−39%) vs. controls whereas tumor caliper volumes were not significantly decreased until days 14 and 21. At day 21 the significant decrease in DVs in the treatment group (−44%) paralleled biodistribution DV measurements and was consistent with autoradiography and CD31 IHC findings. Conclusion: These data suggest that (18)F-albumin DVs obtained by imaging may serve as an early biomarker of the effectiveness of anti-angiogenic therapy and thus aid in patient management and treatment planning.

We sought to develop a practical, reproducible and clinically translatable method of radiolabeling serum albumins with fluorine-18 for use as a PET blood pool imaging agent in animals and man. Fluorine-18 radiolabeled fluoronicotinic acid-2,3,5,6-tetrafluorophenyl ester, [(18)F]F-Py-TFP was prepared first by the reaction of its quaternary ammonium triflate precursor with [(18)F]tetrabutylammonium fluoride ([(18)F]TBAF) according to a previously published method for peptides, with minor modifications. The incubation of [(18)F]F-Py-TFP with rat serum albumin (RSA) in phosphate buffer (pH9) for 15 min at 37-40 °C produced fluorine-18-radiolabeled RSA and the product was purified using a mini-PD MiniTrap G-25 column. The overall radiochemical yield of the reaction was 18-35% (n=30, uncorrected) in a 90-min synthesis. This procedure, repeated with human serum albumin (HSA), yielded similar results. Fluorine-18-radiolabeled RSA demonstrated prolonged blood retention (biological half-life of 4.8 hours) in healthy awake rats. The distribution of major organ radioactivity remained relatively unchanged during the 4 hour observation periods either by direct tissue counting or by dynamic PET whole-body imaging except for a gradual accumulation of labeled metabolic products in the bladder. This manual method for synthesizing radiolabeled serum albumins uses fluorine-18, a widely available PET radionuclide, and natural protein available in both pure and recombinant forms which could be scaled up for widespread clinical applications. These preclinical biodistribution and PET imaging results indicate that [(18)F]RSA is an effective blood pool imaging agent in rats and might, as [(18)F]HSA, prove similarly useful as a clinical imaging agent.

Aerosol aerodynamic particle size is known to affect deposition patterns of inhaled aerosol particles, as well as the virulence of inhaled bioaerosol particles. While a significant amount of work has been performed to describe the deposition of aerosol particles in the human respiratory tract, only a limited amount of work has been performed to describe the deposition of aerosol particles in the respiratory tract of nonhuman primates, an animal model commonly utilized in pharmacological and toxicological studies, especially in the biodefense field. In this study, anesthetized rhesus macaques inhaled radiolabeled aerosols with MMADs of 1.7, 3.6, 7.4 and 11.8 µm to characterize regional deposition patterns. The results demonstrate that the regional deposition pattern shifts as particle size increases, with greater deposition in more proximal regions of the respiratory tract and decreased deposition in the pulmonary region. The results of this study extend the findings of previous studies which demonstrated a similar shift in the deposition pattern as a function of particle size by providing greater resolution of deposition patterns. These data on regional deposition patterns provide a starting point to begin to explore potential mechanisms responsible for the differences in virulence of infectious bioaerosols as a function of particle size and deposition pattern reported in previous studies. Additionally, the data are useful to assess the performance of various deposition models that have been published in the literature.

Introduction Equilibrium single-photon radionuclide imaging methods for assessing cardiac function and the integrity of the vascular system have long been in use for both clinical and research purposes. However, positron-emitting blood pool agents that could provide PET equivalents to these (and other) clinical procedures have not yet been adopted despite technical imaging advantages offered by PET. Our goal was to develop a PET blood pool tracer that not only meets necessary in vivo biological requirements but can be produced with an uncomplicated and rapid synthesis method which would facilitate clinical translation. Herein, albumin labeled with fluorine-18 was synthesized using a one-pot method and evaluated in vitro and in vivo in rats. Methods A ligand (NODA-Bz-TFPE), containing NODA attached to a tetrafluorophenylester (TFPE) via a phenyl linker (Bz), was labeled with aluminum fluoride (Al[18F]F). Conjugation of the serum albumin with the ligand (Al[18F]F-NODA-Bz-TFPE), followed by purification (size exclusion chromatography), yielded the final product (Al[18F]F-NODA-Bz-RSA/HSA). In vitro stability was evaluated in human serum albumin by HPLC. Rat biodistributions and whole-body PET imaging over a 4 h time course were used for the in vivo evaluation. Results This synthesis exhibited an overall radiochemical yield of 45 ± 10% (n = 30), a 50-min radiolabeling time, a radiochemical purity >99% and apparent stability up to 4 h in human serum. Blood had the highest retention of Al[18F]F-NODA-Bz-RSA at all times with a blood half-life of 5.2 h in rats. Al[18F]F-NODA-Bz-RSA distribution in most rat tissues remained relatively constant for up to 1 h, indicating that the tissue radioactivity content represents the respective tissue plasma volume. Dynamic whole-body PET images were in agreement with these findings. Conclusions A new ligand has been developed and radiolabeled with Al[18F]F that allows rapid (50-min) preparation of fluorine-18 serum albumin in one-pot. In addition to increased synthetic efficiency, the construct appears to be metabolically stable in rats. This method could encourage wider use of PET to quantify cardiac function and tissue vascular integrity in both research and clinical settings.

Real-time bioimaging of infectious disease processes may aid countermeasure development and lead to an improved understanding of pathogenesis. However, few studies have identified biomarkers for monitoring infections usingin vivoimaging. Previously, we demonstrated that positron emission tomography/computed tomography (PET/CT) imaging with [18F]-fluorodeoxyglucose (FDG) can monitor monkeypox disease progressionin vivoin nonhuman primates (NHPs). In this study, we investigated [18F]-FDG-PET/CT imaging of immune processes in lymphoid tissues to identify patterns of inflammation in the monkepox NHP model and to determine the value of [18F]-FDG-PET/CT as a biomarker for disease and treatment outcomes. Quantitative analysis of [18F]-FDG-PET/CT images revealed differences between moribund and surviving animals at two sites vital to the immune response to viral infections, bone marrow and lymph nodes (LNs). Moribund NHPs demonstrated increased [18F]-FDG uptake in bone marrow 4 days postinfection compared to surviving NHPs. In surviving, treated NHPs, increase in LN volume correlated with [18F]-FDG uptake and peaked 10 days postinfection, while minimal lymphadenopathy and higher glycolytic activity were observed in moribund NHPs early in infection. Imaging data were supported by standard virology, pathology, and immunology findings. Even with the limited number of subjects, imaging was able to differentiate the difference between disease outcomes, warranting additional studies to demonstrate whether [18F]-FDG-PET/CT can identify other, subtler effects. Visualizing altered metabolic activity at sites involved in the immune response by [18F]-FDG-PET/CT imaging is a powerful tool for identifying key disease-specific time points and locations that are most relevant for pathogenesis and treatment.IMPORTANCEPositron emission tomography and computed tomography (PET/CT) imaging is a universal tool in oncology and neuroscience. The application of this technology to infectious diseases is far less developed. We used PET/CT imaging with [18F]-labeled fluorodeoxyglucose ([18F]-FDG) in monkeys after monkeypox virus exposure to monitor the immune response in lymphoid tissues. In lymph nodes of surviving monkeys, changes in [18F]-FDG uptake positively correlated with enlargement of the lymph nodes and peaked on day 10 postinfection. In contrast, the bone marrow and lymph nodes of nonsurvivors showed increased [18F]-FDG uptake by day 4 postinfection with minimal lymph node enlargement, indicating that elevated cell metabolic activity early after infection is predictive of disease outcome. [18F]-FDG-PET/CT imaging can provide real-time snapshots of metabolic activity changes in response to viral infections and identify key time points and locations most relevant for monitoring the development of pathogenesis and for potential treatment to be effective.

The asymmetric vortex regime of a von Karman ogive with fineness ratio of 3.5 is experimentally studied at a Reynolds number of 156,000. Both port and starboard plasma actuators are used to introduce fluidic disturbances at the tip of the ogive which are amplified through the flow's convective instability and produce a deterministic port or starboard asymmetric vortex state (i.e. side force). Accurate control or manipulation of this asymmetric vortex state holds the potential for increased maneuverability and stability characteristics of slender flight vehicles at high angle of attack. Open-loop experimental tests are used to understand and quantify the vortex dynamics due to actuation inputs. Linear time invariant models provide a suitable model structure to replicate the vortex dynamics and allow for simulation and closed-loop control design. Standard PID control is designed and implemented. A closed-loop simulation shows arbitrary side force tracking with adequate disturbance rejection.

Fully coupled CFD-CSD simulations using HPCMP CREATE-AV Kestrel were performed to compute the dynamic aeroelastic behavior of a torsion ally flexible, finite aspect ratio NACA0018 wing. The uncontrolled dynamic instability resulted a very periodic limit cycle oscillation largely governed by the dynamic stall phenomenon. Three-dimensional effects due to the span wise twist variation produces a localized stalled region which is bound by small interior angles of attack and the wing tip vortex outboard. The flow field at various phases throughout the limit cycle oscillation of the flow field are shown to characterize the three dimensional flow structures. The coherence and development of a leading edge vortex is reduced due to the three-dimensionality of the problem. In addition to the uncontrolled case, the ability to suppress flutter through momentum addition through a blowing port at 75 span is detailed. By varying the amount of momentum addition added through a slot, varying control authority to suppress the aeroelastic instability is observed. In particular, two flow states are attained for depending on the magnitude of momentum addition.