bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Channel Diameter on Heat Transfer Characteristics of Two-Phase Flow in Microchannels
Authors: Choo Kyosung , Trainer Daniel , Kim Sung Jin
Published: March 2011

The heat transfer and fluid flow characteristics of non-boiling two-phase flow in microchannels were experimentally investigated. The effects of channel diameter (140, 222, 334, and 506 μm) on the Nusselt number were considered. Air and water were used as the working fluids. Results were presented for the Nusselt number over a wide range of gas superficial velocity (1.24–40.1 m/s), liquid superficial velocity (0.57–2.13 m/s), and wall heat flux (0.34–0.95 MW/m2). The results showed that the Nusselt number increased with increasing gas flow rate for the 506 μm and 334 μm channels, while the Nusselt number decreased with increasing gas flow for the 222 μm and 140 μm channels. Based on these experimental results, a transition channel diameter of about 235 μm to 260 μm, which distinguishes microchannels from minichannels, was suggested. By observing two-phase flow patterns within the microchannels, viscosity and surface tension were identified as the key factors that caused the heat transfer characteristics to change. In addition, new correlations for the forced convection Nusselt number were developed.
The Effective Thermal Conductivity of Water Based Alumina Nanofluids in the Fully Developed Laminar Flow in a Circular Tube Under a Constant Wall Heat Flux Condition
Authors: Na Young Su , Lee Joon Sik , Kihm Kenneth D.
Published: March 2011

The effective thermal conductivities of dispersed Alumina nanoparticles in DI water are measured under convective flow conditions to compare with those measured at static conditions. The considered particle volume fractions of the nanafluids are 2% and 4%. The measurements are conducted in the fully developed laminar flow in a circular tube subjected to constant surface heat flux. Results show that the augmentation of the effective thermal conductivity of Alumina nanofluids under the convective flow condition is smaller than that at the static condition. It can be explained by the migration of dispersed nanoparticles in the base fluid under the convective flow condition. Due to the particle movement to the center of the tube by thermophoretic diffusion, the particle concentration near the heating wall is getting lower than the uniform concentration at the static condition. Hence, the heat conduction from the heating wall to convective nanofluid becomes lower than that at the static condition.
Analysis and simulation of generating terahertz surface waves on a tapered field emission tip
Authors: Hagmann Mark J. , Kumar Gagan , Pandey Shashank , Nahata Ajay
Published: March 2011

Finite difference-time domain simulations and analytical solutions show that terahertz transverse-magnetic surface waves are generated on a tapered field emitter tip by an oscillating terahertz current at the apex, where this current may be caused by photomixing with two lasers in laser-assisted field emission. The tip is modeled as a paraboloid so the analytical solution for the electromagnetic fields may be determined in paraboloidal coordinates using a basis of regular and irregular Coulomb wave functions. The simulations and analytical solutions show that there are quasistationary region and transitional region as the surface waves are generated by the oscillating current at the apex and then propagate on the tapered field emitter tip.
Organ doses for reference adult male and female undergoing computed tomography estimated by Monte Carlo simulations
Authors: Lee Choonsik , Kim Kwang Pyo , Long Daniel , Fisher Ryan , Tien Chris , Simon Steven L. , Bouville Andre , Bolch Wesley E.
Published: March 2011

Purpose:

To develop a computed tomography (CT) organ dose estimation method designed to readily provide organ doses in a reference adult male and female for different scan ranges to investigate the degree to which existing commercial programs can reasonably match organ doses defined in these more anatomically realistic adult hybrid phantoms

Methods:

The x‐ray fan beam in the SOMATOM Sensation 16 multidetector CT scanner was simulated within the Monte Carlo radiation transport codeMCNPX2.6. The simulated CT scanner model was validated through comparison with experimentally measured lateral free‐in‐air dose profiles and computed tomography dose index (CTDI) values. The reference adult male and female hybrid phantoms were coupled with the established CT scanner model following arm removal to simulate clinical head and other body region scans. A set of organ dose matrices were calculated for a series of consecutive axial scans ranging from the top of the head to the bottom of the phantoms with a beam thickness of 10 mm and the tube potentials of 80, 100, and 120 kVp. The organ doses for head, chest, and abdomen/pelvis examinations were calculated based on the organ dose matrices and compared to those obtained from two commercial programs, CT‐EXPO and CTDOSIMETRY. Organ dose calculations were repeated for an adult stylized phantom by using the same simulation method used for the adult hybrid phantom.

Results:

Comparisons of both lateral free‐in‐air dose profiles and CTDI values through experimental measurement with the Monte Carlo simulations showed good agreement to within 9%. Organ doses for head, chest, and abdomen/pelvis scans reported in the commercial programs exceeded those from the Monte Carlo calculations in both the hybrid and stylized phantoms in this study, sometimes by orders of magnitude.

Conclusions:

The organ dose estimation method and dose matrices established in this study readily provides organ doses for a reference adult male and female for different CT scan ranges and technical parameters. Organ doses from existing commercial programs do not reasonably match organ doses calculated for the hybrid phantoms due to differences in phantom anatomy, as well as differences in organ dose scaling parameters. The organ dose matrices developed in this study will be extended to cover different technical parameters, CT scanner models, and various age groups.
Concurrent quantification of multiple nanoparticle bound states
Authors: Rauwerdink Adam M. , Weaver John B.
Published: March 2011

Purpose:

The binding of nanoparticles toin vivo targets impacts their use for medical imaging, therapy, and the study of diseases and disease biomarkers. Though an array of techniques can detect binding in vitro, the search for a robust in vivo method continues. The spectral response of magnetic nanoparticles can be influenced by a variety of changes in their physical environment including viscosity and binding. Here, the authors show that nanoparticles in these different environmental states produce spectral responses, which are sufficiently unique to allow for simultaneous quantification of the proportion of nanoparticles within each state.

Methods:

The authors measured the response to restricted Brownian motion using an array of magnetic nanoparticle designs. With a chosen optimal particle type, the authors prepared particle samples in three distinct environmental states. Various combinations of particles within these three states were measured concurrently and the authors attempted to solve for the quantity of particles within each physical state.

Results:

The authors found the spectral response of the nanoparticles to be sufficiently unique to allow for accurate quantification of up to three bound states with errors on the order of 1.5%. Furthermore, the authors discuss numerous paths for translating these measurements toin vivo applications.

Conclusions:

Multiple nanoparticle environmental states can be concurrently quantified using the spectral response of the particles. Such an ability, if translated to thein vivo realm, could provide valuable information about the fate of nanoparticles in vivo or improve the efficacy of nanoparticle based treatments.
Shortening treatment time in robotic radiosurgery using a novel node reduction technique
Authors: van de Water Steven , Hoogeman Mischa S. , Breedveld Sebastiaan , Heijmen Ben J. M.
Published: March 2011

Purpose:

The fraction duration of robotic radiosurgery treatments can be reduced by generating more time‐efficient treatment plans with a reduced number of node positions, beams, and monitor units (MUs). Node positions are preprogramed locations where the robot can position the focal spot of the x‐ray beam. As the time needed for the robot to travel between node positions takes up a large part of the treatment time, the aim of this study was to develop and evaluate a node reduction technique in order to reduce the treatment time per fraction for robotic radiosurgery.

Methods:

Node reduction was integrated into the inverse planning algorithm, developed in‐house for the robotic radiosurgery modality. It involved repeated inverse optimization, each iteration excluding low‐contribution node positions from the planning and resampling new candidate beams from the remaining node positions. Node reduction was performed until the exclusion of a single node position caused a constraint violation, after which the shortest treatment plan was selected retrospectively. Treatment plans were generated with and without node reduction for two lung cases of different complexity, one oropharyngeal case and one prostate case. Plan quality was assessed using the number of node positions, beams and MUs, and the estimated treatment time per fraction. All treatment plans had to fulfill all clinical dose constraints. Extra constraints were added to maintain the low‐dose conformality and restrict skin doses during node reduction.

Results:

Node reduction resulted in 12 residual node positions, on average (reduction by 77%), at the cost of an increase in the number of beams and total MUs of 28% and 9%, respectively. Overall fraction durations (excluding patient setup) were shortened by 25% (range of 18%–40%), on average. Dose distributions changed only little and dose in low‐dose regions was effectively restricted by the additional constraints.

Conclusions:

The fraction duration of robotic radiosurgery treatments can be reduced considerably by node reduction with minimal changes in dosimetrical plan quality. Additional constraints are required to guarantee low‐dose conformality and to avoid unacceptable skin dose.
Ultrafast convolution/superposition using tabulated and exponential kernels on GPU
Authors: Chen Quan , Chen Mingli , Lu Weiguo
Published: March 2011

Purpose:

Collapsed‐cone convolution/superposition (CCCS) dose calculation is the workhorse for IMRT dose calculation. The authors present a novel algorithm for computing CCCS dose on the modern graphic processing unit (GPU).

Methods:

The GPU algorithm includes a novel TERMA calculation that has no write‐conflicts and has linear computation complexity. The CCCS algorithm uses either tabulated or exponential cumulative‐cumulative kernels (CCKs) as reported in literature. The authors have demonstrated that the use of exponential kernels can reduce the computation complexity by order of a dimension and achieve excellent accuracy. Special attentions are paid to the unique architecture of GPU, especially the memory accessing pattern, which increases performance by more than tenfold.

Results:

As a result, the tabulated kernel implementation in GPU is two to three times faster than other GPU implementations reported in literature. The implementation of CCCS showed significant speedup on GPU over single core CPU. On tabulated CCK, speedups as high as 70 are observed; on exponential CCK, speedups as high as 90 are observed.

Conclusions:

Overall, the GPU algorithm using exponential CCK is 1000–3000 times faster over a highly optimized single‐threaded CPU implementation using tabulated CCK, while the dose differences are within 0.5% and 0.5 mm. This ultrafast CCCS algorithm will allow many time‐sensitive applications to use accurate dose calculation.
Objective characterization of GE Discovery CT750 HD scanner: Gemstone spectral imaging mode
Authors: Zhang Da , Li Xinhua , Liu Bob
Published: March 2011

Purpose:

To objectively characterize the performance of the gemstone spectral imaging (GSI) mode of GE CT750 HD scanner from a user's perspective.

Methods:

A regular scan protocol that approximates the adult abdomen scan protocol frequently used in the authors' institute was selected as the baseline, and a GSI protocol (preset 11) that is similar to the regular protocol and has a moderate dose level was compared to the baseline protocol. The resolving power of both protocols was characterized in terms of modulation transfer functions and high contrast resolution bar readings. Their noise characteristics were studied through noise power spectra, and their low contrast detectability was compared via contrast‐to‐noise ratio. Material decomposition capability of GSI was evaluated by scanning iodine solutions of 9–24 mg/ml iodine concentration in a Gammex CT phantom and by examining the estimated iodine concentration. In addition, a formula describing the dependency of HU in iodine enhanced area on GSI monochromatic energies and iodine concentrations was provided and the theoretical values were compared with the measured results.

Results:

The resolutions levels of 50%, 10%, and 5% MTF of GSI monochromatic images at 65 keV agree with those of the regular protocol within 0.1 lp/cm. GSI monochromatic images at 65 keV demonstrated the lowest noise level among GSI images of different monochromatic energies and showed very similar noise magnitude and noise power distribution as compared to the regular protocol images. The CNR of 60 and 65 keV GSI monoimages are approximately 100% of those of the regular protocol images. Estimated iodine concentration levels agreed with the actual values within 2% when the iodine solutions were placed at 3, 9, 12 o'clock positions of the phantom; when iodine solutions were placed at the phantom center and at 6 o'clock position, higher discrepancies of 2%–10% were observed. The observed dependency of HU on keV and iodine concentration levels agreed with the expectation from x‐ray attenuations.

Conclusions:

Equivalent performances were observed in the comparison between GSI 65 keV monochromatic images and images from a regular abdomen scan protocol. This suggests the possibility of GSI to be employed in routine abdominal scans, which would potentially offer more information through its capabilities of material decomposition.
Material separation in x‐ray CT with energy resolved photon‐counting detectors
Authors: Wang Xiaolan , Meier Dirk , Taguchi Katsuyuki , Wagenaar Douglas J. , Patt Bradley E. , Frey Eric C.
Published: March 2011

Purpose:

The objective of the study was to demonstrate that, in x‐ray computed tomography (CT), more than two types of materials can be effectively separated with the use of an energy resolved photon‐counting detector and classification methodology. Specifically, this applies to the case when contrast agents that contain K‐absorption edges in the energy range of interest are present in the object. This separation is enabled via the use of recently developed energy resolved photon‐counting detectors with multiple thresholds, which allow simultaneous measurements of the x‐ray attenuation at multiple energies.

Methods:

To demonstrate this capability, we performed simulations and physical experiments using a six‐threshold energy resolved photon‐counting detector. We imaged mouse‐sized cylindrical phantoms filled with several soft‐tissue‐like and bone‐like materials and with iodine‐based and gadolinium‐based contrast agents. The linear attenuation coefficients were reconstructed for each material in each energy window and were visualized as scatter plots between pairs of energy windows. For comparison, a dual‐kVp CT was also simulated using the same phantom materials. In this case, the linear attenuation coefficients at the lower kVp were plotted against those at the higher kVp.

Results:

In both the simulations and the physical experiments, the contrast agents were easily separable from other soft‐tissue‐like and bone‐like materials, thanks to the availability of the attenuation coefficient measurements at more than two energies provided by the energy resolved photon‐counting detector. In the simulations, the amount of separation was observed to be proportional to the concentration of the contrast agents; however, this was not observed in the physical experiments due to limitations of the real detector system. We used the angle between pairs of attenuation coefficient vectors in either the 5‐D space (for non‐contrast‐agent materials using energy resolved photon‐counting acquisition) or a 2‐D space (for contrast agents using energy resolved photon‐counting acquisition and all materials using dual‐kVp acquisition) as a measure of the degree of separation. Compared to dual‐kVp techniques, an energy resolved detector provided a larger separation and the ability to separate different target materials using measurements acquired in different energy window pairs with a single x‐ray exposure.

Conclusions:

We concluded that x‐ray CT with an energy resolved photon‐counting detector with more than two energy windows allows the separation of more than two types of materials, e.g., soft‐tissue‐like, bone‐like, and one or more materials with K‐edges in the energy range of interest. Separating material types using energy resolved photon‐counting detectors has a number of advantages over dual‐kVp CT in terms of the degree of separation and the number of materials that can be separated simultaneously.
When is better best? A multiobjective perspective
Authors: Phillips Mark H. , Holdsworth Clay
Published: March 2011

Purpose:

To identify the most informative methods for reporting results of treatment planning comparisons.

Methods:

Seven articles from the past year ofInternational Journal of Radiation Oncology Biology Physics reported on comparisons of treatment plans for IMRT and IMAT. The articles were reviewed to identify methods of comparisons. Decision theoretical concepts were used to evaluate the study methods and highlight those that provide the most information.

Results:

None of the studies examined the correlation between objectives. Statistical comparisons provided some information but not enough to provide support for a robust decision analysis.

Conclusions:

The increased use of treatment planning studies to evaluate different methods in radiation therapy requires improved standards for designing the studies and reporting the results.
Current status and future perspective of flattening filter free photon beams
Authors: Georg Dietmar , Knöös Tommy , McClean Brendan
Published: March 2011

Purpose:

Flattening filters (FFs) have been considered as an integral part of the treatment head of a medical accelerator for more than 50 years. The reasons for the longstanding use are, however, historical ones. Advanced treatment techniques, such as stereotactic radiotherapy or intensity modulated radiotherapy have stimulated the interest in operating linear accelerators in a flattening filter free (FFF) mode. The current manuscript reviews treatment head physics of FFF beams, describes their characteristics and the resulting potential advantages in their medical use, and closes with an outlook.

Methods:

A number of dosimetric benefits have been determined for FFF beams, which range from increased dose rate and dose per pulse to favorable output ratio in‐air variation with field size, reduced energy variation across the beam, and reduced leakage and out‐of‐field dose, respectively. Finally, the softer photon spectrum of unflattened beams has implications on imaging strategies and radiation protection.

Results:

The dosimetric characteristics of FFF beams have an effect on treatment delivery, patient comfort, dose calculation accuracy, beam matching, absorbed dose determination, treatment planning, machine specific quality assurance, imaging, and radiation protection. When considering conventional C‐arm linacs in a FFF mode, more studies are needed to specify and quantify the clinical advantages, especially with respect to treatment plan quality and quality assurance.

Conclusions:

New treatment units are already on the market that operate without a FF or can be operated in a dedicated clinical FFF mode. Due to the convincing arguments of removing the FF, it is expected that more vendors will offer dedicated treatment units for advanced photon beam therapy in the near future. Several aspects related to standardization, dosimetry, treatment planning, and optimization need to be addressed in more detail in order to facilitate the clinical implementation of unflattened beams.
Technical Note: Determining regions of interest for CCD camera‐based fiber optic luminescence dosimetry by examining signal‐to‐noise ratio
Authors: Klein David M. , Therriault‐Proulx Francois , Archambault Louis , Briere Tina M. , Beaulieu Luc , Beddar A. Sam
Published: March 2011

Purpose:

The goal of this work was to develop a method for determining regions of interest (ROIs) based on signal‐to‐noise ratio (SNR) for the analysis of charge‐coupled device (CCD) images used in luminescence‐based radiation dosimetry.

Methods:

The ROI determination method was developed using images containing high‐and low‐intensity signals taken with a CCD‐based, fiber optic plastic scintillation detector system. A series of threshold intensity values was defined for each signal, and ROIs were fitted around the pixels that exceeded each threshold. The SNR for each ROI was calculated and the relationship between SNR and ROI area was examined.

Results:

The SNR was found to increase rapidly over small ROIs for both signal levels. After reaching a maximum, the SNR of the low‐intensity signal decreased steadily over larger ROIs, but the high‐intensity SNR did not decrease appreciably over the ROI sizes studied. The spatial extent of the normalized images showed intensity independence, suggesting that a fixed ROI is useful for varying signal levels.

Conclusions:

The method described here constitutes a simple yet effective method for defining ROIs based on SNR that could enhance the low‐level detection capabilities of CCD‐based luminescence dosimetry systems.
Evaluation of a CdTe semiconductor based compact gamma camera for sentinel lymph node imaging
Authors: Russo Paolo , Curion Assunta S. , Mettivier Giovanni , Esposito Michela , Aurilio Michela , Caracò Corradina , Aloj Luigi , Lastoria Secondo
Published: March 2011

Purpose:

The authors assembled a prototype compact gamma‐ray imaging probe (MediPROBE) for sentinel lymph node (SLN) localization. This probe is based on a semiconductor pixel detector. Its basic performance was assessed in the laboratory and clinically in comparison with a conventional gamma camera.

Methods:

The room‐temperature CdTe pixel detector (1 mm thick) has square pixels arranged with a pitch (sensitive area ), coupled pixel‐by‐pixel via bump‐bonding to the Medipix2 photon‐counting readout CMOS integrated circuit. The imaging probe is equipped with a set of three interchangeable knife‐edge pinhole collimators (0.94, 1.2, or 2.1 mm effective diameter at 140 keV) and its focal distance can be regulated in order to set a given field of view (FOV). A typical FOV of 70 mm at 50 mm skin‐to‐collimator distance corresponds to a minification factor 1:5. The detector is operated at a single low‐energy threshold of about 20 keV.

Results:

For, at 50 mm distance, a background‐subtracted sensitivity of and a system spatial resolution of 5.5 mm FWHM were obtained for the 0.94 mm pinhole; corresponding values for the 2.1 mm pinhole were and 12.6 mm. The dark count rate was 0.71 cps. Clinical images in three patients with melanoma indicate detection of the SLNs with acquisition times between 60 and 410 s with an injected activity of 26 MBq and prior localization with standard gamma camera lymphoscintigraphy.

Conclusions:

The laboratory performance of this imaging probe is limited by the pinhole collimator performance and the necessity of working in minification due to the limited detector size. However, in clinical operative conditions, the CdTe imaging probe was effective in detecting SLNs with adequate resolution and an acceptable sensitivity. Sensitivity is expected to improve with the future availability of a larger CdTe detector permitting operation at shorter distances from the patient skin.
On the relationships between electron spot size, focal spot size, and virtual source position in Monte Carlo simulations
Authors: Sterpin E. , Chen Y. , Lu W. , Mackie T. R. , Olivera G. H. , Vynckier S.
Published: March 2011

Purpose:

Every year, new radiotherapy techniques including stereotactic radiosurgery using linear accelerators give rise to new applications of Monte Carlo (MC) modeling. Accurate modeling requires knowing the size of the electron spot, one of the few parameters to tune in MC models. The resolution of integrated megavoltage imaging systems, such as the tomotherapy system, strongly depends on the photon spot size which is closely related to the electron spot. The aim of this article is to clarify the relationship between the electron spot size and the photon spot size (i.e., thefocal spot size) for typical incident electron beam energies and target thicknesses.

Methods:

Three electron energies (3, 5.5, and 18 MeV), four electron spot sizes (, 0.5, 1, and 1.5 mm), and two tungsten target thicknesses (0.15 and 1 cm) were considered. The formation of the photon beam within the target was analyzed through electron energy deposition with depth, as well as photon production at several phase‐space planes placed perpendicular to the beam axis, where only photons recorded for the first time were accounted for. Photon production was considered for “newborn” photons intersecting a plane at the isocenter (85 cm from source). Finally, virtual source position and “effective” focal spot size were computed by backprojecting all the photons from the bottom of the target intersecting a plane. The virtual source position and focal spot size were estimated at the plane position where the latter is minimal.

Results:

In the relevant case of considering only photons intersecting the plane, the results unambiguously showed that the effective photon spot is created within the first 0.25 mm of the target and that electron and focal spots may be assumed to be equal within 3–4%.

Conclusions:

In a good approximation photon spot size equals electron spot size for high energy X‐ray treatments delivered by linear accelerators.
Investigation of a breathing surrogate prediction algorithm for prospective pulmonary gating
Authors: White Benjamin M. , Low Daniel A. , Zhao Tianyu , Wuenschel Sara , Lu Wei , Lamb James M. , Mutic Sasa , Bradley Jeffrey D. , El Naqa Issam
Published: March 2011

Purpose:

A major challenge of four dimensional computed tomography (4DCT) in treatment planning and delivery has been the lack of respiration amplitude and phase reproducibility during image acquisition. The implementation of a prospective gating algorithm would ensure that images would be acquired only during user‐specified breathing phases. This study describes the development and testing of an autoregressive moving average (ARMA) model for human respiratory phase prediction under quiet respiration conditions.

Methods:

A total of 47 4DCT patient datasets and synchronized respiration records was utilized in this study. Three datasets were used in model development and were removed from further evaluation of the ARMA model. The remaining 44 patient datasets were evaluated with the ARMA model for prediction time steps from 50 to 1000 ms in increments of 50 and 100 ms. Thirty‐five of these datasets were further used to provide a comparison between the proposed ARMA model and a commercial algorithm with a prediction time step of 240 ms.

Results:

The optimal number of parameters for the ARMA model was based on three datasets reserved for model development. Prediction error was found to increase as the prediction time step increased. The minimum prediction time step required for prospective gating was selected to be half of the gantry rotation period. The maximum prediction time step with a conservative 95% confidence criterion was found to be 0.3 s. The ARMA model predicted peak inhalation and peak exhalation phases significantly better than the commercial algorithm. Furthermore, the commercial algorithm had numerous instances of missed breath cycles and falsely predicted breath cycles, while the proposed model did not have these errors.

Conclusions:

An ARMA model has been successfully applied to predict human respiratory phase occurrence. For a typical CT scanner gantry rotation period of 0.4 s (0.2 s prediction time step), the absolute error was relatively small, at peak inhalation and at peak exhalation. The application of the ARMA model for prospective pulmonary gating has been demonstrated.
Patient radiation dose audits for fluoroscopically guided interventional procedures
Authors: Balter Stephen , Rosenstein Marvin , Miller Donald L. , Schueler Beth , Spelic David
Published: March 2011

Purpose:

Quality management for any use of medical x‐ray imaging should include monitoring of radiation dose. Fluoroscopically guided interventional (FGI) procedures are inherently clinically variable and have the potential for inducing deterministic injuries in patients. The use of a conventional diagnostic reference level is not appropriate for FGI procedures. A similar but more detailed quality process for management of radiation dose in FGI procedures is described.

Methods:

A method that takes into account both the inherent variability of FGI procedures and the risk of deterministic injuries from these procedures is suggested. The substantial radiation dose level (SRDL) is an absolute action level (with regard to patient follow‐up) below which skin injury is highly unlikely and above which skin injury is possible. The quality process for FGI procedures collects data from all instances of a given procedure from a number of facilities into an advisory data set (ADS). An individual facility collects a facility data set (FDS) comprised of all instances of the same procedure at that facility. The individual FDS is then compared to the multifacility ADS with regard to the overall shape of the dose distributions and the percent of instances in both the ADS and the FDS that exceed the SRDL.

Results:

Samples of an ADS and FDS for percutaneous coronary intervention, using the dose metric of reference air kerma (i.e., the cumulative air kerma at the reference point), are used to illustrate the proposed quality process for FGI procedures. Investigation is warranted whenever the FDS is noticeably different from the ADS for the specific FGI procedure and particularly in two circumstances: (1) When the facility's local median exceeds the 75th percentile of the ADS and (2) when the percent of instances where exceeds the facility‐selected SRDL is greater for the FDS than for the ADS.

Conclusions:

Analysis of the two data sets (ADS and FDS) and of the percent of instances that exceed the SRDL provides a means for the facility to better manage radiation dose (and therefore both deterministic and stochastic radiation risk) to the patient during FGI procedures.
Quantification of prostate deformation due to needle insertion during TRUS‐guided biopsy: Comparison of hand‐held and mechanically stabilized systems
Authors: De Silva Tharindu , Fenster Aaron , Bax Jeffrey , Romagnoli Cesare , Izawa Jonathan , Samarabandu Jagath , Ward Aaron D.
Published: March 2011

Purpose:

Prostate biopsy is the clinical standard for the definitive diagnosis of prostate cancer. To overcome the limitations of 2D TRUS‐guided biopsy systems when targeting preplanned locations, systems have been developed with 3D guidance to improve the accuracy of cancer detection. Prostate deformation due to needle insertion and biopsy gun firing is a potential source of error that can cause target misalignments during biopsies.

Methods:

The authors used nonrigid registration of 2D TRUS images to quantify the deformation that occurs during the needle insertion and the biopsy gun firing procedure and compare this effect in biopsies performed using a hand‐held TRUS probe to those performed using a mechanically assisted 3D TRUS‐guided biopsy system. The authors calculated a spatially varying 95% confidence interval on the prostate tissue motion and analyzed this motion both as a function of distance to the biopsy needle and as a function of distance to the lower piercing point of the prostate. The former is relevant because biopsy targets lie along the needle axis, and the latter is of particular importance due to the reported high concentration of prostate cancer in the peripheral zone, a substantial portion of which lies on the posterior side of the prostate where biopsy needles enter the prostate after penetrating the rectal wall during transrectal biopsy.

Results:

The results show that for both systems, the tissue deformation is such that throughout the length of the needle axis, including regions proximal to the lower piercing point, spherical tumors with a radius of 2.1 mm or more can be sampled with 95% confidence under the assumption of zero error elsewhere in the biopsy system. More deformation was observed in the direction orthogonal to the needle axis compared to the direction parallel to the needle axis; this is of particular importance given the long, narrow shape of the biopsy core. The authors measured lateral tissue motion proximal to the needle axis of not more than 1.5 mm, with 95% confidence. The authors observed a statistically significant and clinically insignificant maximum difference of 0.38 mm in the deformation, resulting from the hand‐held and mechanically assisted systems along the needle axis, and the mechanical system resulted in a lower relative increase in deformation proximal to the needle axis during needle insertion, as well as lower variability of deformation during biopsy gun firing.

Conclusions:

Given the clinical need to biopsy tumors of volume greater than or equal to, corresponding to spherical tumors with a radius of 5 mm or more, the tissue motion induced by needle insertion and gun firing is an important consideration when setting the design specifications for TRUS‐guided prostate biopsy systems.
PAMELA Measurements of Cosmic-Ray Proton and Helium Spectra
Authors: Adriani O. , Barbarino G. C. , Bazilevskaya G. A. , Bellotti R. , Boezio M. , Bogomolov E. A. , Bonechi L. , Bongi M. , Bonvicini V. , Borisov S. , Bottai S. , Bruno A. , Cafagna F. , Campana D. , Carbone R. , Carlson P. , Casolino M. , Castellini G. , Consiglio L. , De Pascale M. P. , De Santis C. , De Simone N. , Di Felice V. , Galper A. M. , Gillard W. , Grishantseva L. , Jerse G. , Karelin A. V. , Koldashov S. V. , Krutkov S. Y. , Kvashnin A. N. , Leonov A. , Malakhov V. , Malvezzi V. , Marcelli L. , Mayorov A. G. , Menn W. , Mikhailov V. V. , Mocchiutti E. , Monaco A. , Mori N. , Nikonov N. , Osteria G. , Palma F. , Papini P. , Pearce M. , Picozza P. , Pizzolotto C. , Ricci M. , Ricciarini S. B. , Rossetto L. , Sarkar R. , Simon M. , Sparvoli R. , Spillantini P. , Stozhkov Y. I. , Vacchi A. , Vannuccini E. , Vasilyev G. , Voronov S. A. , Yurkin Y. T. , Wu J. , Zampa G. , Zampa N. , Zverev V. G.
Published: March 2011

Satellite measurements challenge the current understanding of cosmic-ray acceleration and propagation in our Galaxy.
Atherosclerosis Drug Development in Jeopardy: The Need for Predictive Biomarkers of Treatment Response
Authors: Fryburg David A. , Vassileva Maria T.
Published: March 2011

The Atherosclerosis Working Group proposes the creation of an in silico model to identify biomarker panels for use in clinical trials.
A Two-Step Toward Personalized Therapies for Prostate Cancer
Authors: Goldstein Andrew S. , Zong Yang , Witte Owen N.
Published: March 2011

Therapeutic targeting of two proteins that drive tumorigenesis suggests personalized medicine is a possibility for prostate cancer.
Coronary Artery Disease Decoded
Authors: Damani Samir
Published: March 2011

The p21 region of chromosome 9 modulates inflammatory responses in coronary artery disease.
Longitudinal Analysis of Pneumococcal Antibodies during Community-Acquired Pneumonia Reveals a Much Higher Involvement of Streptococcus pneumoniae than Estimated by Conventional Methods Alone
Authors: van Mens Suzan P. , Meijvis Sabine C. A. , Endeman Henrik , van Velzen-Blad Heleen , Biesma Douwe H. , Grutters Jan C. , Vlaminckx Bart J. M. , Rijkers Ger T.
Published: March 2011

In up to half of all cases of community-acquired pneumonia (CAP), no pathogen can be identified with conventional diagnostic methods. The most common identified causative agent isStreptococcus pneumoniae. In this study, pneumococcal antibody responses during CAP were analyzed to estimate the contribution of the pneumococcus to all cases of CAP for epidemiological purposes. Pneumococcal antibodies against 14 different serotypes were measured in serum of hospitalized CAP patients. Patients participated in one of two consecutive clinical trials in a general 600-bed teaching hospital in the Netherlands (between October 2004 and June 2009). A significant pneumococcal immune response was defined as at least a 2-fold increase in antibody concentrations against a single serotype between an early (day 1) and a late (day 30) serum sample of each patient with an end concentration above 0.35 μg/ml. A total of 349 adult CAP patients participated in two consecutive clinical trials. For 200 patients, sufficient serum samples were available to determine antibody responses: 62 pneumococcal pneumonia patients, 57 nonpneumococcal pneumonia patients, and 81 patients with an unidentified causative agent. A significant immune response was detected in 45% (28/62 patients) of pneumococcal pneumonia patients, in 5% (3/57) of nonpneumococcal pneumonia patients, and in 28% (23/81) of patients with an unidentified causative agent. The estimated contribution of pneumococci in patients with an unidentified causative agent was calculated to be 57% (95% confidence interval, 36 to 86%). A substantial fraction of pneumococcal pneumonia patients do not elicit a serotype-specific immune response.
Immunodominance of HLA-A2-Restricted Hepatitis C Virus-Specific CD8
+
T Cell Responses Is Linked to Naïve-Precursor Frequency
Authors: Schmidt Julia , Neumann-Haefelin Christoph , Altay Tayibe , Gostick Emma , Price David A. , Lohmann Volker , Blum Hubert E. , Thimme Robert
Published: March 2011

The impact of naïve-precursor frequency on human virus-specific CD8
+
T cell immunodominance is not well understood. Using a recently developed major histocompatibility complex (MHC) class I tetramer enrichment protocol, we found a conserved hierarchy and a >10-fold difference in naïve-precursor frequencies across three HLA-A2-restricted hepatitis C virus (HCV)-specific epitopes. Importantly, the NS3
1406
epitope with the highest naïve-precursor frequency in healthy donors was also the most frequently targeted epitope in a large cohort of chronically HCV-infected patients, both
ex vivo
and after
in vitro
stimulation. These results indicate for the first time that immunodominance in a human viral infection is linked to naïve-precursor frequency.
Clonal Sequences Recovered from Plasma from Patients with Residual HIV-1 Viremia and on Intensified Antiretroviral Therapy Are Identical to Replicating Viral RNAs Recovered from Circulating Resting CD4
+
T Cells
Authors: Anderson Jeffrey A. , Archin Nancie M. , Ince William , Parker Daniel , Wiegand Ann , Coffin John M. , Kuruc JoAnn , Eron Joseph , Swanstrom Ronald , Margolis David M.
Published: March 2011

Despite successful antiretroviral therapy (ART), low-level viremia (LLV) may be intermittently detected in most HIV-infected patients. Longitudinal blood plasma and resting CD4
+
T cells were obtained from two patients on suppressive ART to investigate the source of LLV. Single-genome sequencing of HIV-1
env
from LLV plasma was performed, and the sequences were compared to sequences recovered from limiting-dilution outgrowth assays of resting CD4
+
T cells. The circulating LLV virus clone was identical to virus recovered from outgrowth assays from pools of millions of resting CD4
+
T cells. Understanding the sources of LLV requires evaluation of all possible reservoirs of persistent HIV infection.
Transmission of Murine Cytomegalovirus in Breast Milk: a Model of Natural Infection in Neonates
Authors: Wu Carol A. , Paveglio Sara A. , Lingenheld Elizabeth G. , Zhu Li , Lefrançois Leo , Puddington Lynn
Published: March 2011

Vertical transmission of viruses in breast milk can expose neonates to infectious pathogens at a time when the capacity of their immune system to control infections is limited. We developed a mouse model to study the outcomes of acquisition of murine cytomegalovirus (MCMV) when neonates are breastfed by mothers with acute or latent infection. Breast milk leukocytes collected from lactating mice were examined for the presence of MCMV IE-1 mRNA by reverse transcription-PCR (RT-PCR) with Southern analysis. As determined by this criterion, breast milk leukocytes from both acute and latent mothers were positive for MCMV. This mimics the outcome seen in humans with latent cytomegalovirus infection, where reactivation of virus occurs specifically in the lactating mammary gland. Interestingly, intraperitoneal injection of breast milk collected from mothers with latent infection was sufficient to transfer MCMV to neonatal mice, demonstrating that breast milk was a source of virus. Furthermore, we found that MCMV was transmitted from infected mothers to breastfed neonates, with MCMV IE-1 mRNA or infectious virus present in multiple organs, including the brain. In fact, 1 day of nursing was sufficient to transmit MCMV from latent mothers to breastfed neonatal mice. Together, these data validate this mouse model of vertical transmission of MCMV from mothers with acute or latent MCMV infection to breastfed neonates. Its relevance to human disease should prove useful in future studies designed to elucidate the immunological and pathological ramifications of neonatal infection acquired via this natural route.
FUSE Binding Protein 1 Interacts with Untranslated Regions of Japanese Encephalitis Virus RNA and Negatively Regulates Viral Replication
Authors: Chien Hsu-Ling , Liao Ching-Len , Lin Yi-Ling
Published: March 2011

The untranslated regions (UTRs) located at the 5′ and 3′ ends of the Japanese encephalitis virus (JEV) genome, a positive-sense RNA, are involved in viral translation, the initiation of RNA synthesis, and the packaging of nascent virions. The cellular and viral proteins that participate in these processes are expected to interact with the UTRs. In this study, we used biotinylated RNA-protein pulldown and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) analyses to identify that the far upstream element (FUSE) binding protein 1 (FBP1) binds with JEV 5′ and 3′ UTRs. The impact of FBP1 on JEV infection was determined in cells with altered FBP1 expression. JEV replication was enhanced by knockdown and reduced by the overexpression of FBP1, indicating a negative role for FBP1 in JEV infection. FBP1, a nuclear protein, was redistributed to the perinuclear region and appeared as cytoplasmic foci that partially colocalized with JEV RNA in the early stage of JEV infection. By using a JEV replicon reporter assay, FBP1 appeared to suppress JEV protein expression mediated by the 5′ and 3′ UTRs. Thus, we suggest that FBP1 binds with the JEV UTR RNA and functions as a host anti-JEV defense molecule by repressing viral protein expression.
Human Adenovirus Type 5 Induces Cell Lysis through Autophagy and Autophagy-Triggered Caspase Activity
Authors: Jiang Hong , White Erin J. , Ríos-Vicil Christian I. , Xu Jing , Gomez-Manzano Candelaria , Fueyo Juan
Published: March 2011

Oncolytic adenoviruses, such as Delta-24-RGD, are promising therapies for patients with brain tumor. Clinical trials have shown that the potency of these cancer-selective adenoviruses should be increased to optimize therapeutic efficacy. One potential strategy is to increase the efficiency of adenovirus-induced cell lysis, a mechanism that has not been clearly described. In this study, for the first time, we report that autophagy plays a role in adenovirus-induced cell lysis. At the late stage after adenovirus infection, numerous autophagic vacuoles accompany the disruption of cellular structure, leading to cell lysis. The virus induces a complete autophagic process from autophagosome initiation to its turnover through fusion with the lysosome although the formation of the autophagosome is sufficient for virally induced cell lysis. Importantly, downmodulation of autophagy genes (
ATG5
or
ATG10
) rescues the infected cells from being lysed by the virus. Moreover, autophagy triggers caspase activity via the extrinsic FADD/caspase 8 pathway, which also contributes to adenovirus-mediated cell lysis. Therefore, our study implicates autophagy and caspase activation as part of the mechanism for cell lysis induced by adenovirus and suggests that manipulation of the process is a potential strategy to optimize clinical efficacy of oncolytic adenoviruses.
Protein pUL128 of Human Cytomegalovirus Is Necessary for Monocyte Infection and Blocking of Migration
Authors: Straschewski Sarah , Patrone Marco , Walther Paul , Gallina Andrea , Mertens Thomas , Frascaroli Giada
Published: March 2011

We have previously shown that only endotheliotropic strains of human cytomegalovirus (HCMV), such as TB40E, infect monocytes and impair their chemokine-driven migration. The proteins encoded by the UL128-131A region (UL128, UL130, and UL131A) of the HCMV genome, which assemble into a pentameric gH-gL-UL128-UL130-UL131A envelope complex, have been recognized as determinants for HCMV endothelial cell tropism. The genes for these proteins are typically inactivated by mutations in all fibroblast-adapted strains that have lost the diversified tropism of clinical isolates. By using mutant HCMV reconstituted from TB40E-derived bacterial artificial chromosomes (BAC) encoding a wild-type (wt) or mutated form of UL128, we show here that UL128-131A products are essential determinants of infection in monocytes and that pUL128, in particular, can block chemokine-driven motility. The virus BAC4, encoding wt UL128, established infection in monocytes, induced the intracellular retention of several chemokine receptors, and rendered monocytes unresponsive to different chemokines. In contrast, the virus BAC1, encoding a mutated UL128, failed to infect monocytes and to downregulate chemokine receptors. BAC1-exposed monocytes did not express immediate-early (IE) products, retained virions in cytoplasmic vesicles, and exhibited normal chemokine responsiveness. A potential role of second-site mutations in the observed phenotype was excluded by using the revertant viruses BAC1rep and BAC4mut. By incubating noninfected monocytes with soluble recombinant pUL128, we observed both the block of migration and the chemokine receptor internalization. We propose that among the gH-gL-UL128-UL130-UL131A complex subunits, the UL128 protein is the one that triggers monocyte paralysis.