bluuebunny/crossref_metadata_2025_split huggingface dataset:
4DCT‐based measurement of changes in pulmonary function following a course of radiation therapy
Authors: Ding Kai , Bayouth John E. , Buatti John M. , Christensen Gary E. , Reinhardt Joseph M. 
Published: March 2010

Purpose:Radiation therapy (RT) for lung cancer is commonly limited to subtherapeutic doses due to unintended toxicity to normal lung tissue. Reducing the frequency of occurrence and magnitude of normal lung function loss may benefit from treatment plans that incorporate the regional lung and radiation dose information. In this article, the authors propose a method that quantitatively measures the regional changes in lung tissue function following a course of radiation therapy by using 4DCT and image registration techniques.Methods:4DCT data sets before and after RT from two subjects are used in this study. Nonlinear 3D image registration is applied to register an image acquired near end inspiration to an image acquired near end expiration to estimate the pulmonary function. The Jacobian of the image registration transformation, indicating local lung expansion or contraction, serves as an index of regional pulmonary function. Approximately 120 annotated vascular bifurcation points are used as landmarks to evaluate registration accuracy. The authors compare regional pulmonary function before and after RT to the planned radiation dose at different locations of the lung.Results:In all registration pairs, the average landmark distances after registration are on the order of 1 mm. The pulmonary function change as indicated by the Jacobian change ranges from −0.15 to 0.1 in the contralateral lung and −0.22 to 0.23 in the ipsilateral lung for subject A, and ranges from −0.4 to 0.39 in the contralateral lung and −0.25 to 0.5 in the ipsilateral lung for subject B. Both of the subjects show larger range of the increase in the pulmonary function in the ipsilateral lung than the contralateral lung. For lung tissue regions receiving a radiation dose larger than 24 Gy, a decrease in pulmonary function was observed. For regions receiving a radiation dose smaller than 24 Gy, either an increase or a decrease in pulmonary function was observed. The relationship between the pulmonary function change and the radiation dose varies at different locations.Conclusions:With the use of 4DCT and image registration techniques, the pulmonary function prior to and following a course of radiation therapy can be measured. In the preliminary application of this approach for two subjects, changes in pulmonary function were observed with a weak correlation between the dose and pulmonary function change. In certain sections of the lung, detected locally compromised pulmonary function may have resulted from radiation injury.
Radiation dose reduction using a CdZnTe‐based computed tomography system: Comparison to flat‐panel detectors
Authors: Le Huy Q. , Ducote Justin L. , Molloi Sabee 
Published: March 2010

Purpose:Although x‐ray projection mammography has been very effective in early detection of breast cancer, its utility is reduced in the detection of small lesions that are occult or in dense breasts. One drawback is that the inherent superposition of parenchymal structures makes visualization of small lesions difficult. Breast computed tomography using flat‐panel detectors has been developed to address this limitation by producing three‐dimensional data while at the same time providing more comfort to the patients by eliminating breast compression. Flat panels are charge integrating detectors and therefore lack energy resolution capability. Recent advances in solid state semiconductor x‐ray detector materials and associated electronics allow the investigation of x‐ray imaging systems that use a photon counting and energy discriminating detector, which is the subject of this article.Methods:A small field‐of‐view computed tomography (CT) system that uses CdZnTe (CZT) photon counting detector was compared to one that uses a flat‐panel detector for different imaging tasks in breast imaging. The benefits afforded by the CZT detector in the energy weighting modes were investigated. Two types of energy weighting methods were studied: Projection based and image based. Simulation and phantom studies were performed with a 2.5 cm polymethyl methacrylate (PMMA) cylinder filled with iodine and calcium contrast objects. Simulation was also performed on a 10 cm breast specimen.Results:The contrast‐to‐noise ratio improvements as compared to flat‐panel detectors were 1.30 and 1.28 (projection based) and 1.35 and 1.25 (image based) for iodine over PMMA and hydroxylapatite over PMMA, respectively. Corresponding simulation values were 1.81 and 1.48 (projection based) and 1.85 and 1.48 (image based). Dose reductions using the CZT detector were 52.05% and 49.45% for iodine and hydroxyapatite imaging, respectively. Image‐based weighting was also found to have the least beam hardening effect.Conclusions:The results showed that a CT system using an energy resolving detector reduces the dose to the patient while maintaining image quality for various breast imaging tasks.
Zero‐shift thimble ionization chamber
Authors: Tessier Frédéric , Hooten Brian D. , McEwen Malcolm R. 
Published: March 2010

Purpose:Verify experimentally the theoretical prediction of F. Tessier and I. Kawrakow [Med. Phys. 37, 96–107 (2010)] that it is possible to design a thimble ionization chamber with no shift in its effective point of measurement (EPOM), i.e., a chamber that provides a measure of the dose to the medium at the location of its central axis.Methods:Measure dose from a 25 MV photon beam incident on water with an Exradin A1SL ionization chamber inside a thin sleeve (as a means of effectively increasing the thimble wall thickness). The depth‐dose curve is compared to that obtained using a well‐characterized PTW Roos parallel‐plate chamber.Results:With an appropriate increase in thimble wall thickness, the EPOM shift of the Exradin A1SL vanishes. Further increase of the wall thickness yields a chamber with a positive (downstream) shift in its point of measurement.Conclusions:It is possible to design a thimble ionization chamber with a zero EPOM shift by adjusting the wall thickness.
Analysis of dose to patient, spouse/caretaker, and staff, from an implanted trackable radioactive fiducial for use in the radiation treatment of prostate cancera)
Authors: Neustadter David , Barnea Gideon , Stokar Saul , Corn Ben 
Published: March 2010

Purpose:A fiducial tracking system based on a novel radioactive tracking technology is being developed for real‐time target tracking in radiation therapy. In this study, the authors calculate the radiation dose to the patient, the spouse/caretaker, and the medical staff that would result from a Ir192 radioactive fiducial marker permanently implanted in the prostate of a radiation therapy patient.Methods:Local tissue dose was calculated by Monte Carlo simulation. The patient's whole body effective dose equivalent was calculated by summing the doses to the sensitive organs. Exposure of the spouse/caretaker was calculated from the NRC guidelines. Exposure of the medical staff was based on estimates of proximity to and time spent with the patient.Results:The local dose is below 40 Gy at 5 mm from the marker and below 10 Gy at 10 mm from the marker. The whole body effective dose equivalent to the patient is 64 mSv. The dose to the spouse/caretaker is 0.25 mSv. The annual exposures of the medical staff are 0.2 mSv for a doctor performing implantations and 0.34 mSv for a radiation therapist positioning patients for therapy.Conclusions:The local dose is not expected to have any clinically significant effect on the surrounding tissue which is irradiated during therapy. The dose to the patient is small in comparison to the whole body dose received from the therapy itself. The exposure of all other people is well below the recommended limits. The authors conclude that there is no radiation exposure related contraindication for use of this technology in the radiation treatment of prostate cancer.
Effect of repeated x‐ray exposure on the resolution of amorphous selenium based x‐ray imagers
Authors: Kabir M. Z. , Chowdhury L. , DeCrescenzo G. , Tousignant O. , Kasap S. O. , Rowlands J. A. 
Published: March 2010

Purpose:A numerical model and the experimental methods to study the x‐ray exposure dependent change in the modulation transfer function (MTF) of amorphous selenium (a‐Se) based active matrix flat panel imagers (AMFPIs) are described. The physical mechanisms responsible for the x‐ray exposure dependent change in MTF are also investigated.Methods:A numerical model for describing the x‐ray exposure dependent MTF of a‐Se based AMFPIs has been developed. The x‐ray sensitivity and MTF of an a‐Se AMFPI have been measured as a function of exposure. The instantaneous electric field and free and trapped carrier distributions in the photoconductor layer are obtained by numerically solving the Poisson's equation, continuity equations, and trapping rate equations using the backward Euler finite difference method. From the trapped carrier distributions, a method for calculating the MTF due to incomplete charge collection is proposed.Results:The model developed in this work and the experimental data show a reasonably good agreement. The model is able to simultaneously predict the dependence of the sensitivity and MTF on accumulated exposure at different applied fields and bias polarities, with the same charge transport parameters that are typical of the particular a‐Se photoconductive layer that is used in these AMFPIs. Under negative bias, the MTF actually improves with the accumulated x‐ray exposure while the sensitivity decreases. The MTF enhancement with exposure decreases with increasing applied field.Conclusions:The most prevalent processes that control the MTF under negative bias are the recombination of drifting holes with previously trapped electrons (electrons remain in deep traps due to their long release times compared with the time scale of the experiments) and the deep trapping of drifting holes and electrons.
Comparison of Elekta VMAT with helical tomotherapy and fixed field IMRT: Plan quality, delivery efficiency and accuracy
Authors: Rao Min , Yang Wensha , Chen Fan , Sheng Ke , Ye Jinsong , Mehta Vivek , Shepard David , Cao Daliang 
Published: March 2010

Purpose:Helical tomotherapy (HT) and volumetric modulated arc therapy (VMAT) are arc‐based approaches to IMRT delivery. The objective of this study is to compare VMAT to both HT and fixed field IMRT in terms of plan quality, delivery efficiency, and accuracy.Methods:Eighteen cases including six prostate, six head‐and‐neck, and six lung cases were selected for this study. IMRT plans were developed using direct machine parameter optimization in the treatment planning system. HT plans were developed using a Hi‐Art II planning station. VMAT plans were generated using both the SmartArc IMRT module and a home‐grown arc sequencing algorithm. VMAT and HT plans were delivered using Elekta's PreciseBeam VMAT® linac control system (Elekta AB, Stockholm, Sweden) and a TomoTherapy Hi‐Art II system (TomoTherapy Inc., Madison, WI), respectively. Treatment plan quality assurance (QA) for VMAT was performed using the IBA MatriXX™ system while an ion chamber and films were used for HT plan QA.Results:The results demonstrate that both VMAT and HT are capable of providing more uniform target doses and improved normal tissue sparing as compared with fixed field IMRT. In terms of delivery efficiency, VMAT plan deliveries on average took 2.2 min for prostate and lung cases and 4.6 min for head‐and‐neck cases. These values increased to 4.7 and 7.0 min for HT plans.Conclusions:Both VMAT and HT plans can be delivered accurately based on their own QA standards. Overall, VMAT was able to provide approximately a 40% reduction in treatment time while maintaining comparable plan quality to that of HT.
Application of the continuity equation to a breathing motion model
Authors: Low Daniel A. , Zhao Tianyu , White Benjamin , Yang Deshan , Mutic Sasa , Noel Camille E. , Bradley Jeffrey D. , Parikh Parag J. , Lu Wei 
Published: March 2010

Purpose:To quantitatively test a breathing motion model using the continuity equation and clinical data.Methods:The continuity equation was applied to a lung tissue and lung tumor free breathing motion model to quantitatively test the model performance. The model used tidal volume and airflow as the independent variables and the ratio of motion to tidal volume and motion to airflow were defined asandvector fields, respectively. The continuity equation resulted in a prediction that the volume integral of the divergence of thevector field was 1.11 for all patients. The integral of the divergence of thevector field was expected to be zero.Results:For 35 patients, thevector field prediction was, encompassing the expected value. For thevector field prediction, the average value was.Conclusions:These results provide quantitative evidence that the breathing motion model yields accurate predictions of breathing dynamics.
Quality Monitoring of HIV-1-Infected and Uninfected Peripheral Blood Mononuclear Cell Samples in a Resource-Limited Setting
Authors: Olemukan Robert E. , Eller Leigh Anne , Ouma Benson J. , Etonu Ben , Erima Simon , Naluyima Prossy , Kyabaggu Denis , Cox Josephine H. , Sandberg Johan K. , Wabwire-Mangen Fred , Michael Nelson L. , Robb Merlin L. , de Souza Mark S. , Eller Michael A. 
Published: March 2010

ABSTRACTHuman immunodeficiency virus type 1 (HIV-1) vaccine and natural history studies are critically dependent on the ability to isolate, cryopreserve, and thaw peripheral blood mononuclear cell (PBMC) samples with a high level of quality and reproducibility. Here we characterize the yield, viability, phenotype, and function of PBMC from HIV-1-infected and uninfected Ugandans and describe measures to ascertain reproducibility and sample quality at the sites that perform cryopreservation. We have developed a comprehensive internal quality control program to monitor processing, including components of method validation. Quality indicators for real-time performance assessment included the time from venipuncture to cryopreservation, time for PBMC processing, yield of PBMC from whole blood, and viability of the PBMC before cryopreservation. Immune phenotype analysis indicated lowered B-cell frequencies following processing and cryopreservation for both HIV-1-infected and uninfected subjects (P< 0.007), but all other major lymphocyte subsets were unchanged. Long-term cryopreservation did not impact function, as unstimulated specimens exhibited low background and all specimens responded to staphylococcal enterotoxin B (SEB) by gamma interferon and interleukin-2 production, as measured by intracellular cytokine staining. Samples stored for more than 3 years did not decay with regard to yield or viability, regardless of HIV-1 infection status. These results demonstrate that it is possible to achieve the high level of quality necessary for vaccine trials and natural history studies in a resource-limited setting and provide strategies for laboratories to monitor PBMC processing performance.
FINDING POPULAR PLACES
Authors: BENKERT MARC , DJORDJEVIC BOJAN , GUDMUNDSSON JOACHIM , WOLLE THOMAS 
Published: March 2010

Widespread availability of location aware devices (such as GPS receivers) promotes capture of detailed movement trajectories of people, animals, vehicles and other moving objects. We investigate spatio-temporal movement patterns in large tracking data sets, i.e. in large sets of polygonal paths. Specifically, we study so-called 'popular places', that is, regions that are visited by many entities. Given a set of polygonal paths with a total of [Formula: see text] vertices, we look at the problem of computing such popular places in two different settings. For the discrete model, where only the vertices of the polygonal paths are considered, we propose an [Formula: see text] algorithm; and for the continuous model, where also the straight line segments between the vertices of a polygonal path are considered, we develop an [Formula: see text] algorithm. We also present lower bounds and hardness results.
Complementary Actions of Inhibitors of Angiopoietin-2 and VEGF on Tumor Angiogenesis and Growth
Authors: Hashizume Hiroya , Falcón Beverly L. , Kuroda Takashi , Baluk Peter , Coxon Angela , Yu Dongyin , Bready James V. , Oliner Jonathan D. , McDonald Donald M. 
Published: March 2010

Abstract
Inhibition of angiopoietin-2 (Ang2) can slow tumor growth, but the underlying mechanism is not fully understood. Because Ang2 is expressed in growing blood vessels and promotes angiogenesis driven by vascular endothelial growth factor (VEGF), we asked whether the antitumor effect of Ang2 inhibition results from reduced sprouting angiogenesis and whether the effect is augmented by inhibition of VEGF from tumor cells. Using Colo205 human colon carcinomas in nude mice as a model, we found that selective inhibition of Ang2 by the peptide-Fc fusion protein L1-7(N) reduced the number of vascular sprouts by 46% and tumor growth by 62% over 26 days. Strikingly, when the Ang2 inhibitor was combined with a function-blocking anti-VEGF antibody, the number of sprouts was reduced by 82%, tumor vascularity was reduced by 67%, and tumor growth slowed by 91% compared with controls. The reduction in tumor growth was accompanied by decreased cell proliferation and increased apoptosis. We conclude that inhibition of Ang2 slows tumor growth by limiting the expansion of the tumor vasculature by sprouting angiogenesis, in a manner that is complemented by concurrent inhibition of VEGF and leads to reduced proliferation and increased apoptosis of tumor cells. Cancer Res; 70(6); 2213–23
CD44 Attenuates Activation of the Hippo Signaling Pathway and Is a Prime Therapeutic Target for Glioblastoma
Authors: Xu Yin , Stamenkovic Ivan , Yu Qin 
Published: March 2010

Abstract
Glioblastoma multiforme (GBM) is the most aggressive brain tumor that, by virtue of its resistance to chemotherapy and radiotherapy, is currently incurable. Identification of molecules whose targeting may eliminate GBM cells and/or sensitize glioblastoma cells to cytotoxic drugs is therefore urgently needed. CD44 is a major cell surface hyaluronan receptor and cancer stem cell marker that has been implicated in the progression of a variety of cancer types. However, the major downstream signaling pathways that mediate its protumor effects and the role of CD44 in the progression and chemoresponse of GBM have not been established. Here we show that CD44 is upregulated in GBM and that its depletion blocks GBM growth and sensitizes GBM cells to cytotoxic drugs in vivo. Consistent with this observation, CD44 antagonists potently inhibit glioma growth in preclinical mouse models. We provide the first evidence that CD44 functions upstream of the mammalian Hippo signaling pathway and that CD44 promotes tumor cell resistance to reactive oxygen species–induced and cytotoxic agent–induced stress by attenuating activation of the Hippo signaling pathway. Together, our results identify CD44 as a prime therapeutic target for GBM, establish potent antiglioma efficacy of CD44 antagonists, uncover a novel CD44 signaling pathway, and provide a first mechanistic explanation as to how upregulation of CD44 may constitute a key event in leading to cancer cell resistance to stresses of different origins. Finally, our results provide a rational explanation for the observation that functional inhibition of CD44 augments the efficacy of chemotherapy and radiation therapy. Cancer Res; 70(6); 2455–64
Suppression of Tumor Growth and Metastasis by Simultaneously Blocking Vascular Endothelial Growth Factor (VEGF)–A and VEGF-C with a Receptor-Immunoglobulin Fusion Protein
Authors: Zhang Dapeng , Li Bohua , Shi Jingping , Zhao Lei , Zhang Xunming , Wang Chong , Hou Sheng , Qian Weizhu , Kou Geng , Wang Hao , Guo Yajun 
Published: March 2010

Abstract
The major cause of cancer mortality is the metastatic spread of tumor cells that can occur via multiple routes, including the vascular system and the lymphatic system. In this study, we developed an IgG-like fusion protein molecule [vascular endothelial growth factor (VEGF) receptor 31–immunoglobulin (VEGFR31-Ig)] which could simultaneously bind the angiogenic growth factor VEGF-A and the lymphangiogenic growth factor VEGF-C. Importantly, VEGFR31-Ig exhibited VEGF-A–binding affinity similar to that of VEGFTrap, the most potent VEGF-A binder, and VEGF-C–binding affinity comparable with that of the soluble fusion protein VEGFR3-Ig (sVEGFR3). Pharmacokinetic analysis in mice showed that VEGFR31-Ig had improved pharmacokinetic properties compared with either VEGFTrap or sVEGFR3. In a highly metastatic human hepatocellular carcinoma (HCCLM3) model in severe combined immunodeficient mice, VEGFR31-Ig potently blocked both tumor angiogenesis and lymphangiogenesis, effectively inhibiting primary tumor growth and metastasis to lungs and lymph nodes. In contrast, VEGFTrap only suppressed primary tumor growth and metastasis to lungs by inhibiting tumor angiogenesis, whereas VEGFR3 was only effective in suppressing tumor metastasis to lymph nodes by blocking tumor lymphangiogenesis. Although a combination of VEGFTrap (25 mg/kg twice weekly) and sVEGFR3 (25 mg/kg twice weekly) can achieve the same therapeutic effect as VEGFR31-Ig (25 mg/kg twice weekly) in the HCCLM3 xenograft mouse model, developing two separate receptor-Ig fusion proteins for clinical use as combination therapy is impractical, mainly owing to regulatory hurdles and cost. Taken together, the VEGFR31-Ig fusion protein presented here has been suggested to have great potential for the treatment of metastatic cancer. Cancer Res; 70(6); 2495–503