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At least 1,603 records · Page 89

Stereotactic Ablative Radiation Therapy for Subcentimeter Lung Tumors: Clinical, Dosimetric, and Image Guidance Considerations

Purpose: Use of stereotactic ablative radiation therapy (SABR) for subcentimeter lung tumors is controversial. We report our outcomes for tumors with diameter ≤1 cm and their visibility on cone beam computed tomography (CBCT) scans and retrospectively evaluate the planned dose using a deterministic dose calculation algorithm (Acuros XB [AXB]). Methods and Materials: We identified subcentimeter tumors from our institutional SABR database. Tumor size was remeasured on an artifact-free phase of the planning 4-dimensional (4D)-CT. Clinical plan doses were generated using either a pencil beam convolution or an anisotropic analytic algorithm (AAA). All AAA plans were recalculated using AXB, and differences among D95 and mean dose for internal target volume (ITV) and planning target volume (PTV) on the average intensity CT dataset, as well as for gross tumor volume (GTV) on the end respiratory phases were reported. For all AAA patients, CBCT scans acquired during each treatment fraction were evaluated for target visibility. Progression-free and overall survival rates were calculated using the Kaplan-Meier method. Results: Thirty-five patients with 37 subcentimeter tumors were eligible for analysis. For the 22 AAA plans recalculated using AXB, Mean D95 ± SD values were 2.2 ± 4.4% (ITV) and 2.5 ± 4.8% (PTV) lower using AXB; whereas mean doses were 2.9 ± 4.9% (ITV) and 3.7 ± 5.1% (PTV) lower. Calculated AXB doses were significantly lower in one patient (difference in mean ITV and PTV doses, as well as in mean ITV and PTV D95 ranged from 22%-24%). However, the end respiratory phase GTV received at least 95% of the prescription dose. Review of 92 CBCT scans from all AAA patients revealed that the tumor was visualized in 82 images, and its position could be inferred in other images. The 2-year local progression-free survival was 100%. Conclusions: Patients with subcentimeter lung tumors are good candidates for SABR, given the dosimetry, ability to localize tumors with image guidance, and excellent local control.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

MO-A-BRD-05: Evaluation of Composed Lung Ventilation with 4DCT and Image Registration

Purpose: Regional pulmonary function can be derived using fourdimensional computed tomography (4DCT) combined with deformable image registration. However, only peak inhale and exhale phases have been used thus far while the lung ventilation during intermediate phases is not considered. In our previous work, we have investigated the spatiotemporal heterogeneity of lung ventilation and its dependence on respiration effort. In this study, composed ventilation is introduced using all inspiration phases and compared to direct ventilation. Both methods are evaluated against Xe-CT derived ventilation. Methods: Using an in-house tissue volume preserving deformable image registration, unlike the direct ventilation method, which computes from end expiration to end inspiration, Jacobian ventilation maps were computed from one inhale phase to the next and then composed from all inspiration steps. The two methods were compared in both patients prior to RT and mechanically ventilated sheep subjects. In addition, they wereassessed for the correlation with Xe-CT derived ventilation in sheep subjects. Annotated lung landmarks were used to evaluate the accuracy of original and composed deformation field. Results: After registration, the landmark distance for composed deformation field was always higher than that for direct deformation field (0IN to 100IN average in human: 1.03 vs 1.53, p=0.001, and in sheep: 0.80 vs0.94, p=0.009), and both increased with longer phase interval. Direct and composed ventilation maps were similar in both sheep (gamma pass rate 87.6) and human subjects (gamma pass rate 71.9),and showed consistent pattern from ventral to dorsal when compared to Xe-CT derived ventilation. Correlation coefficient between Xe-CT and composed ventilation was slightly better than the direct method but not significant (average 0.89 vs 0.85, p=0.135). Conclusion: More strict breathing control in sheep subjects may explain higher similarity between direct and composed ventilation. When compared to Xe-CT ventilation, no significant difference was found for the composed method. NIH Grant: R01 CA166703.

60 APPLIED LIFE SCIENCES↗

Proteomic Retrieval from Nucleic Acid Depleted Space-Flown Human Cells

Compared to experiments utilizing humans in microgravity, cell-based approaches to questions about subsystems of the human system afford multiple advantages, such as crew safety and the ability to achieve statistical significance. To maximize the science return from flight samples, an optimized method was developed to recover protein from samples depleted of nucleic acid. This technique allows multiple analyses on a single cellular sample and when applied to future cellular investigations could accelerate solutions to significant biomedical barriers to human space exploration. Cell cultures grown in American Fluoroseal bags were treated with an RNA stabilizing agent (RNAlater - Ambion), which enabled both RNA and immunoreactive protein analyses. RNA was purified using an RNAqueous(registered TradeMark) kit (Ambion) and the remaining RNA free supernatant was precipitated with 5% trichloroacetic acid. The precipitate was dissolved in SDS running buffer and tested for protein content using a bicinchoninic acid assay (1) (Sigma). Equal loads of protein were placed on SDS-PAGE gels and either stained with CyproOrange (Amersham) or transferred using Western Blotting techniques (2,3,4). Protein recovered from RNAlater-treated cells and stained with protein stain, was measured using Imagequant volume measurements for rectangles of equal size. BSA treated in this way gave quantitative data over the protein range used (Fig 1). Human renal cortical epithelial (HRCE) cells (5,6,7) grown onboard the International Space Station (ISS) during Increment 3 and in ground control cultures exhibited similar immunoreactivity profiles for antibodies to the Vitamin D receptor (VDR) (Fig 2), the beta isoform of protein kinase C (PKC ) (Fig 3), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (Fig 4). Parallel immunohistochemical studies on formalin-fixed flight and ground control cultures also showed positive immunostaining for VDR and other biomarkers (Fig 5). These results are consistent with data from additional antigenic recovery experiments performed on human Mullerian tumor cells cultured in microgravity (8).

Hammond, D. K.↗

Phase II Trial of Radiosurgery to Magnetic Resonance Spectroscopy-Defined High-Risk Tumor Volumes in Patients With Glioblastoma Multiforme

Purpose: To determine the efficacy of a Gamma Knife stereotactic radiosurgery (SRS) boost to areas of high risk determined by magnetic resonance spectroscopy (MRS) functional imaging in addition to standard radiotherapy for patients with glioblastoma (GBM). Methods and Materials: Thirty-five patients in this prospective Phase II trial underwent surgical resection or biopsy for a GBM followed by SRS directed toward areas of MRS-determined high biological activity within 2 cm of the postoperative enhancing surgical bed. The MRS regions were determined by identifying those voxels within the postoperative T2 magnetic resonance imaging volume that contained an elevated choline/N-acetylaspartate ratio in excess of 2:1. These voxels were marked, digitally fused with the SRS planning magnetic resonance image, targeted with an 8-mm isocenter per voxel, and treated using Radiation Therapy Oncology Group SRS dose guidelines. All patients then received conformal radiotherapy to a total dose of 60 Gy in 2-Gy daily fractions. The primary endpoint was overall survival. Results: The median survival for the entire cohort was 15.8 months. With 75% of recursive partitioning analysis (RPA) Class 3 patients still alive 18 months after treatment, the median survival for RPA Class 3 has not yet been reached. The median survivals for RPA Class 4, 5, and 6 patients were 18.7, 12.5, and 3.9 months, respectively, compared with Radiation Therapy Oncology Group radiotherapy-alone historical control survivals of 11.1, 8.9, and 4.6 months. For the 16 of 35 patients who received concurrent temozolomide in addition to protocol radiotherapeutic treatment, the median survival was 20.8 months, compared with European Organization for Research and Treatment of Cancer historical controls of 14.6 months using radiotherapy and temozolomide. Grade 3/4 toxicities possibly attributable to treatment were 11%. Conclusions: This represents the first prospective trial using selective MRS-targeted functional SRS combined with radiotherapy for patients with GBM. This treatment is feasible, with acceptable toxicity and patient survivals higher than in historical controls. This study can form the basis for a multicenter, randomized trial.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

SU-F-P-64: The Impact of Plan Complexity Parameters On the Plan Quality and Deliverability of Volumetric Modulated Arc Therapy with Canonical Correlation Analysis

Purpose: To evaluate the impact of complexity indices on the plan quality and deliverability of volumetric modulated arc therapy (VMAT), and to determine the most significant parameters in the generation of an ideal VMAT plan. Methods: A multi-dimensional exploratory statistical method, canonical correlation analysis (CCA) was adopted to study the correlations between VMAT parameters of complexity, quality and deliverability, as well as their contribution weights with 32 two-arc VMAT nasopharyngeal cancer (NPC) patients and 31 one-arc VMAT prostate cancer patients. Results: The MU per arc (MU/Arc) and MU per control point (MU/CP) of NPC were 337.8±25.2 and 3.7±0.3, respectively, which were significantly lower than those of prostate cancer patients (MU/Arc : 506.9±95.4, MU/CP : 5.6±1.1). The plan complexity indices indicated that two-arc VMAT plans were more complex than one-arc VMAT plans. Plan quality comparison confirmed that one-arc VMAT plans had a high quality than two-arc VMAT plans. CCA results implied that plan complexity parameters were highly correlated with plan quality with the first two canonical correlations of 0.96, 0.88 (both p<0.001) and significantly correlated with deliverability with the first canonical correlation of 0.79 (p<0.001), plan quality and deliverability was also correlated with the first canonical correlation of 0.71 (p=0.02). Complexity parameters of MU/CP, segment area (SA) per CP, percent of MU/CP less 3 and planning target volume (PTV) were weighted heavily in correlation with plan quality and deliveability . Similar results obtained from individual NPC and prostate CCA analysis. Conclusion: Relationship between complexity, quality, and deliverability parameters were investigated with CCA. MU, SA related parameters and PTV volume were found to have strong effect on the plan quality and deliverability. The presented correlation among different quantified parameters could be used to improve the plan quality and the efficiency of the radiotherapy process when creating a complex VMAT plan.

60 APPLIED LIFE SCIENCES↗

Arc-Fault Primer: Numerical, Analytical, and Experimental Characteristics of Initiation and Sustainment of Arc Plasmas (DRAFT)

While arc-faults are rare in electrical installations, many documented events have led to fires that resulted in significant damage to energy-generation, commercial and residential systems, as well as surrounding structures, in both the United States and abroad. Arc-plasma discharges arise over time due to a variety of reliability issues related to cable material degradation, electrical and mechanical stresses or acute conductive wiring dislocations. These may lead to discontinuity between energized conductors, facilitating arcing events and fires. Arc-flash events rapidly release significant energy in a localized volume, where the electric arc experiences a reduction in resistance. This facilitates a reduction in electrical resistance as the arc temperature and pressure can increase rapidly. Strong pressure waves, electromagnetic interference (EMI), and intense light from an arc pose a threat to electrical worker safety and system equipment. This arc-fault primer provides basic fundamental insight into arc-fault plasma discharges, and an overview of direct current (DC) and alternating current (AC) arc-fault phenomena. This primer also covers pressure waves and EMI arc-fault hazard analyses related to incident energy prediction and potential damage analysis. Mitigation strategies are also discussed related to engineering design and employment of protective devices including arc-fault circuit interrupters (AFCIs). Best practices related to worker safety are also covered, especially as they pertain to electrical codes and standards, particularly Institute of Electrical and Electronics Engineers (IEEE) 1584 and National Fire Protection Agency (NFPA) 70E. Throughout the primer various modelling and test capabilities at Sandia National Laboratories are also covered, especially as they relate to novel methods of arc-fault/arc-flash characterization and mitigation approaches. Herein, this work describes methods for producing and characterizing controlled, sustained arcs at atmospheric pressures as well as methods for mitigation with novel materials.

42 ENGINEERING↗

Evolving Design Criteria for Very Large Aperture Space-Based Telescopes and Their Influence on the Need for Integrated Tools in the Optimization Process

NASA's Advanced Mirror Technology Development (AMTD) program has been developing the means to design and build the future generations of space based telescopes. With the nearing completion of the James Webb Space Telescope (JWST), the astrophysics community is already starting to define the requirements for follow on observatories. The restrictions of available launch vehicles and the possibilities of planned future vehicles have fueled the competition between monolithic primaries (with better optical quality) and segmented primaries (with larger apertures, but with diffraction, costs and figure control issues). Regardless of the current shroud sizes and lift capacities, these competing architectures share the need for rapid design tools. As part of the AMTD program a number of tools have been developed and tested to speed up the design process. Starting with the Arnold Mirror Modeler (which creates Finite Element Models (FEM) for structural analysis) and now also feeds these models into thermal stability analyses. They share common file formats and interchangeable results. During the development of the program, numerous trade studies were created for 4 meter and 8 meter monolithic primaries, complete with support systems. Evaluation of these results has led to a better understanding of how the specification drives the results. This paper will show some of the early trade studies for typical specification requirements such as lowest mirror bending frequency and suspension system lowest frequency. The results use representative allowable stress values for each mirror substrate material and construction method and generic material properties. These studies lead to some interesting relationships between feasible designs and the realities of actually trying to build these mirrors. Much of the traditional specifications were developed for much smaller systems, where the mass and volume of the primary where a small portion of the overall satellite. JWST shows us that as the aperture grows, the primary takes up the majority of the mass and volume and the established rules need to be adjusted. For example, a small change in lowest frequency requirement can change the cost by millions of dollars.

Space-based telescopes↗

Evolving Design Criteria for Very Large Aperture Space Based Telescopes and Their Influence on the Need for Integrated Tools in the Optimization Process

NASA's Advanced Mirror Technology Development (AMTD) program has been developing the means to design and build the future generations of space based telescopes. With the nearing completion of the James Webb Space Telescope (JWST), the astrophysics community is already starting to define the requirements for follow-on observatories. The restrictions of available launch vehicles and the possibilities of planned future vehicles have fueled the competition between monolithic primaries (with better optical quality) and segmented primaries (with larger apertures, but with diffraction, costs and figure control issues). Regardless of the current shroud sizes and lift capacities, these competing architectures share the need for rapid design tools. As part of the AMTD program a number of tools have been developed and tested to speed up the design process. Starting with the Arnold Mirror Modeler (which creates Finite Element Models (FEM) for structural analysis) and now also feeds these models into thermal stability analyses. They share common file formats and interchangeable results. During the development of the program, numerous trade studies were created for 4-meter and 8-meter monolithic primaries, complete with support systems. Evaluation of these results has led to a better understanding of how the specification drives the results. This paper will show some of the early trade studies for typical specification requirements such as lowest mirror bending frequency and suspension system lowest frequency. The results use representative allowable stress values for each mirror substrate material and construction method and generic material properties. These studies lead to some interesting relationships between feasible designs and the realities of actually trying to build these mirrors. Much of the traditional specifications were developed for much smaller systems, where the mass and volume of the primary where a small portion of the overall satellite. JWST shows us that as the aperture grows, the primary takes up the majority of the mass and volume and the established rules need to be adjusted. For example, a small change in lowest frequency requirement can change the cost by millions of dollars. The paper uses numerous trade studies created during the software development phase of the Arnold Mirror Modeler to illustrate the influences of system specifications on the design space. The future telescopes will require better performance, stability and documented feasibility to meet the hurdles of today's budget and schedules realities. AMTD is developing the tools, but the basic system planning mentality also has to adopt to the requirements of these very large and complex physical structures.

Arnold, William R., Sr.↗

Particle Loading Dynamics of SRNL Electrostatic Particle Collectors - 19398

The Department of Energy is interested in decontamination methods and tools for the removal of airborne radioactive particulate from facilities prior to decommissioning. Electrostatic particle collectors (EPCs) have historically been used industrially to scrub particles from air streams for large scale operations, and Savannah River National Laboratory (SRNL) researchers have expanded on the fundamental collection capabilities of EPCs to develop unique samplers focused on particulate effluent collection. One distinct advantage of an electrostatic particle collection over filtration or inertial impaction-based methods is the low pressure drop associated with prolonged use of EPCs. Electrostatic particle collectors previously developed by SRNL have proven effective in the collection of atmospheric aerosols in multiple field trials, and their applicability as a decontamination method for airborne particulates. Initial experiments using aerosolized NaCl were performed to determine EPC collection efficiencies, the times required to achieve a desired particle loading, and the size distribution of collected particulates. The amount of NaCl collected on Si substrates was found to increase linearly with time (∼ 2 mg per hour) and showed little sign of change after 24 hours of collection. Experiments showed that NaCl, or a similar aerosol, would likely continue to collect unperturbed until physical limitations within the EPC are reached. Collection efficiencies (i.e., the number of particles collected vs. the number of particles entering the EPC) were calculated independently using an assessment scheme based on Particle Depletion Dynamics (PDD) and by Computer Controlled Scanning Electron Microscope (CCSEM) analysis of collection substrates for a range of particle sizes. For the ACE 2.0 with a corona voltage of 15 kV, collection efficiencies were determined using PDD to be 54, 29, and 13% for the flow rates 100, 300, and 490 L/min respectively. While CCSEM data suggests a very high collection efficiency for the MiniACE, the static sampling rate of 28.1 L/min (1 ft{sup 3}/min) was found to be too low volume for PDD to provide statistically meaningful data. Number density maps of NaCl particles detected via CCSEM revealed that particles are preferentially collected near the EPC inlet (i.e., opposite the direction of airflow) when using slower flow rates. Particles collected using higher flow rates (e.g., 300 and 490 L/min) were collected more evenly across the substrate. When segregated by size, smaller (e.g., 200-500 nm) particles are collected evenly across the collection substrates. As particle sizes increase they are collected preferentially near the EPC inlet, but not in sufficient quantity to obstruct airflow and hinder long-term operations. Subsequent deployment of the SRNL developed system into plutonium-238 contaminated hot cells will be performed at Savannah River Site Building 235-F. Presented in this work are the testing and considerations utilized by SRNL to show this technique as a viable means of rapidly decontaminating airborne contaminated areas. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

CO 2 capture in the sustainable wheat-derived activated microporous carbon compartments

Here, microporous carbon compartments (MCCs) were developed via controlled carbonization of wheat flour producing large cavities that allow CO 2 gas molecules to access micropores and adsorb effectively. KOH activation of MCCs was conducted at 700 °C with varying mass ratios of KOH/C ranging from 1 to 5, and the effects of activation conditions on the prepared carbon materials in terms of the characteristics and behavior of CO 2 adsorption were investigated. Textural properties, such as specific surface area and total pore volume, linearly increased with the KOH/C ratio, attributed to the development of pores and enlargement of pores within carbon. The highest CO 2 adsorption capacities of 5.70 mol kg -1 at 0 °C and 3.48 mol kg -1 at 25 °C were obtained for MCC activated with a KOH/C ratio of 3 (MCC-K3). In addition, CO 2 adsorption uptake was significantly dependent on the volume of narrow micropores with a pore size of less than 0.8 nm rather than the volume of larger pores or surface area. MCC-K3 also exhibited excellent cyclic stability, facile regeneration, and rapid adsorption kinetics. As compared to the pseudofirst-order model, the pseudo-second-order kinetic model described the experimental adsorption data methodically.

54 ENVIRONMENTAL SCIENCES↗

Controlling the column spacing in isothermal magnetic advection to enable tunable heat and mass transfer

Isothermal magnetic advection (IMA) is a recently discovered method of inducing highly organized, non-contact flow lattices in suspensions of magnetic particles, using only uniform ac magnetic fields of modest strength. The initiation of these vigorous flows requires neither a thermal gradient nor a gravitational field, and so can be used to transfer heat and mass in circumstances where natural convection does not occur. These advection lattices are comprised of a square lattice of antiparallel flow columns. If the column spacing is sufficiently large compared to the column length and the flow rate within the columns is sufficiently large, then one would expect efficient transfer of both heat and mass. Otherwise, the flow lattice could act as a countercurrent heat exchanger and only mass will be efficiently transferred. Although this latter case might be useful for feeding a reaction front without extracting heat, it is likely that most interest will be focused on using IMA for heat transfer. In this paper, we explore the various experimental parameters of IMA to determine which of these can be used to control the column spacing. These parameters include the field frequency, strength, and phase relation between the two field components, the liquid viscosity, and particle volume fraction. Finally, we find that the column spacing can easily be tuned over a wide range to enable the careful control of heat and mass transfer.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

TU-F-17A-03: An Analytical Respiratory Perturbation Model for Lung Motion Prediction

Purpose: Breathing irregularity is common, causing unreliable prediction in tumor motion for correlation-based surrogates. Both tidal volume (TV) and breathing pattern (BP=ΔVthorax/TV, where TV=ΔVthorax+ΔVabdomen) affect lung motion in anterior-posterior and superior-inferior directions. We developed a novel respiratory motion perturbation (RMP) model in analytical form to account for changes in TV and BP in motion prediction from simulation to treatment. Methods: The RMP model is an analytical function of patient-specific anatomic and physiologic parameters. It contains a base-motion trajectory d(x,y,z) derived from a 4-dimensional computed tomography (4DCT) at simulation and a perturbation term Δd(ΔTV,ΔBP) accounting for deviation at treatment from simulation. The perturbation is dependent on tumor-specific location and patient-specific anatomy. Eleven patients with simulation and treatment 4DCT images were used to assess the RMP method in motion prediction from 4DCT1 to 4DCT2, and vice versa. For each patient, ten motion trajectories of corresponding points in the lower lobes were measured in both 4DCTs: one served as the base-motion trajectory and the other as the ground truth for comparison. In total, 220 motion trajectory predictions were assessed. The motion discrepancy between two 4DCTs for each patient served as a control. An established 5D motion model was used for comparison. Results: The average absolute error of RMP model prediction in superior-inferior direction is 1.6±1.8 mm, similar to 1.7±1.6 mm from the 5D model (p=0.98). Some uncertainty is associated with limited spatial resolution (2.5mm slice thickness) and temporal resolution (10-phases). Non-corrected motion discrepancy between two 4DCTs is 2.6±2.7mm, with the maximum of ±20mm, and correction is necessary (p=0.01). Conclusion: The analytical motion model predicts lung motion with accuracy similar to the 5D model. The analytical model is based on physical relationships, requires no training, and therefore is potentially more resilient to breathing irregularities. On-going investigation introduces airflow into the RMP model for improvement. This research is in part supported by NIH (U54CA137788/132378). AY would like to thank MSKCC summer medical student research program supported by National Cancer Institute and hosted by Department of Medical Physics at MSKCC.

60 APPLIED LIFE SCIENCES↗

Completion Effects on Diagnosing Multistage Facture Treatments with Distributed Temperature Sensing

Summary Distributed temperature sensing (DTS) is a valuable tool to diagnose multistage hydraulic fracture treatments. When a stage interval is shut in, the clusters that take more fluid during pumping warm up more slowly. Therefore, the fluid volume injected into each cluster can be quantitatively interpreted by numerical inversion of the warm-back temperature behavior. This general concept assumes that the different warm-back behavior is controlled by only the injected fluid volume; however, recent observations of DTS data indicate that completion configurations significantly influence the warm-back behavior. This paper investigates the completion effects on the DTS interpretation. In ideal conditions, when a stage is fractured, the upstream stage intervals should show an almost uniform temperature that is close to the injected fluid temperature. This is due to the high fluid velocity of injected fluid in the wellbore, and the upstream intervals have not been perforated (noncommunicating intervals), so the only heat transfer is heat conduction between the wellbore fluid and the surrounding reservoir. But the field DTS data show considerably irregular variations in temperature along the upstream stage intervals. These variations are caused by the completion effects. The nonuniform temperature profile is caused by different heat transfer behavior induced by completion hardware along the production casing string, such as joints, clamps, and blast protectors, and by the sensing cable location in the cement, as well as the cement quality. Because the varying heat transfer behavior impacts the warm-back behavior as well as the temperature profile, the completion effects need to be considered in DTS interpretation. A method of DTS interpretation considering the completion effects to diagnose multistage fracture treatments was developed. Because the heat transfer between a wellbore and a reservoir depends on the overall heat transfer coefficient describing heat conduction through the completion in a forward model, this parameter needs to be tuned all along the wellbore. To calibrate the completion effect, the temperature inversion is conducted using the temperature measured at a stage interval that is upstream of a stage interval currently being treated. Because the interpreted stage interval is not perforated at that time, the thermal behavior at the noncommunicating interval is governed by only the heat conduction through the completion environment. Once the effective values of the overall heat transfer coefficient are estimated along the interpreted stage interval, they can be assumed to be constant physical parameters. Then, the fluid volume distribution is interpreted by using the effective overall heat transfer coefficient profile along each interval. This study provides a field application of the developed interpretation method. The new interpretation method provides more accurate diagnosis of fracture treatments by DTS interpretation.

Engineering↗

Submaximal delayed-onset muscle soreness: correlations between MR imaging findings and clinical measures

PURPOSE: To assess correlations between muscle edema on magnetic resonance (MR) images and clinical indexes of muscle injury in delayed-onset muscle soreness (DOMS) produced by submaximal exercise protocols. MATERIALS AND METHODS: Sixteen subjects performed 36 elbow flexions ("biceps curls") at one of two submaximal workloads that emphasized eccentric contractions. Changes in MR imaging findings, plasma levels of creatine kinase, and pain scores were correlated. RESULTS: Both exercise protocols produced DOMS in all subjects. The best correlation was between change in creatine kinase level and volume of muscle edema on MR images, regardless of the workload. Correlations tended to be better with the easier exercise protocol. CONCLUSION: Whereas many previous studies of DOMS focused on intense exercise protocols to ensure positive results, the present investigation showed that submaximal workloads are adequate to produce DOMS and that correlations between conventionally measured indexes of injury may be enhanced at lighter exercise intensities.

Clinical Trial↗

Clinical Implications of the Tumor Volume Reduction Rate in Head-and-Neck Cancer During Definitive Intensity-Modulated Radiotherapy for Organ Preservation

Purpose: To investigate the prognostic value of the volume reduction rate (VRR) in patients with head-and-neck cancer treated with intensity-modulated radiotherapy (IMRT). Methods and Materials: Seventy-six patients with oropharyngeal cancer (OPC) and another 76 with hypopharyngeal cancer (HPC) were enrolled in volumetric analysis. All patients received allocated radiotherapy courses. Adaptive computed tomography was done 4 to 5 weeks after the start of IMRT. Primary tumor volume measurement was derived using separate images for the pretreatment gross tumor volume (pGTV) and the interval gross tumor volume. Results: In the OPC group, the pGTV ranged from 6.6 to 242.6 mL (mean, 49.9 mL), whereas the value of the VRR ranged from 0.014 to 0.74 (mean, 0.43). In HPC patients, the pGTV ranged from 4.1 to 152.4 mL (mean, 35.6 mL), whereas the VRR ranged from -1.15 to 0.79 (mean, 0.33). Multivariate analysis of the primary tumor relapse-free survival for OPC revealed three prognostic factors: T4 tumor (p = 0.0001, hazard ratio 7.38), pGTV {>=}20 mL (p = 0.01, hazard ratio 10.61), and VRR <0.5 (p = 0.001, hazard ratio 6.49). Multivariate analysis of the primary tumor relapse-free survival for HPC showed two prognostic factors: pGTV {>=}30 mL (p = 0.001, hazard ratio 2.87) and VRR <0.5 (p = 0.03, hazard ratio 2.25). Conclusion: The VRR is an outcome predictor for local control in OPC and HPC patients treated with IMRT. Those with large tumor volumes or a VRR <0.5 should be considered for a salvage operation or a dose-escalation scheme.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Quantitation of Human Papillomavirus DNA in Plasma of Oropharyngeal Carcinoma Patients

Purpose: To determine whether human papillomavirus (HPV) DNA can be detected in the plasma of patients with HPV-positive oropharyngeal carcinoma (OPC) and to monitor its temporal change during radiotherapy. Methods and Materials: We used polymerase chain reaction to detect HPV DNA in the culture media of HPV-positive SCC90 and VU147T cells and the plasma of SCC90 and HeLa tumor-bearing mice, non-tumor-bearing controls, and those with HPV-negative tumors. We used real-time quantitative polymerase chain reaction to quantify the plasma HPV DNA in 40 HPV-positive OPC, 24 HPV-negative head-and-neck cancer patients and 10 non-cancer volunteers. The tumor HPV status was confirmed by p16{sup INK4a} staining and HPV16/18 polymerase chain reaction or HPV in situ hybridization. A total of 14 patients had serial plasma samples for HPV DNA quantification during radiotherapy. Results: HPV DNA was detectable in the plasma samples of SCC90- and HeLa-bearing mice but not in the controls. It was detected in 65% of the pretreatment plasma samples from HPV-positive OPC patients using E6/7 quantitative polymerase chain reaction. None of the HPV-negative head-and-neck cancer patients or non-cancer controls had detectable HPV DNA. The pretreatment plasma HPV DNA copy number correlated significantly with the nodal metabolic tumor volume (assessed using {sup 18}F-deoxyglucose positron emission tomography). The serial measurements in 14 patients showed a rapid decline in HPV DNA that had become undetectable at radiotherapy completion. In 3 patients, the HPV DNA level had increased to a discernable level at metastasis. Conclusions: Xenograft studies indicated that plasma HPV DNA is released from HPV-positive tumors. Circulating HPV DNA was detectable in most HPV-positive OPC patients. Thus, plasma HPV DNA might be a valuable tool for identifying relapse.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

WE-FG-BRA-04: A Portable Confocal Microscope to Image Live Cell Damage Response Induced by Therapeutic Radiation

Purpose: To construct a custom and portable fluorescence confocal laser-scanning microscope (FCLSM) that can be placed in the path of therapeutic radiation beams to study real-time radiation-induced damage response in live cells. Methods: We designed and constructed a portable FCLSM with three laser diodes for excitation (405, 488, and 635 nm). An objective lens focuses the excitation light and collects fluorescence from the sample. A pair of galvanometer mirrors scans/collects the laser beam/fluorescence along the focal plane (x/y-directions). A stepper motor stage scans in the axial direction and positions the x/y of the image field. Barrier filters and dichroic mirrors are used to route the spectral emission bands to the appropriate photodetector. An avalanche photodiode collects near-infrared fluorescence; a photodiode collects back-reflected 635 nm light; and a photomultiplier tube collects green fluorescence in the range of eGFP/eYFP. A 200-µm diameter pinhole was used to implement the confocal geometry for near-infrared and red channels and a 150-µm diameter pinhole for the green channel. Data acquisition and system control were achieved using a high-throughput data acquisition card. In-house software developed in LabVIEW was used to control the hardware, collect data from the photodetectors and reconstruct the confocal images. Results: 6 frames/s can be acquired for a 25 µm{sup 2} (128×128 pixels) field of view, visualizing the entire volume of the cell nucleus (∼10 µm depth) in <10 s. To demonstrate the usefulness of our FCLSM, we imaged gold nanoshells in live cells, radiation-induced damage in fibrosarcoma cells expressing eGFP tagged to a DNA repair protein, and neurons expressing eGFP. The system can also image particle tracks in fluorescent nuclear track detectors. Conclusion: We developed a versatile and portable FCLSM that allows radiobiology studies in live cells exposed to therapeutic radiation. The FCLSM can be placed in any vertical beam line for top-to-bottom exposures. This research was supported by the Sister Institution Network Fund and the Center for Radiation Oncology Research at The University of Texas MD Anderson Cancer Center and Cancer Prevention and Research Institute of Texas. Gabriel Sawakuchi has research support from Elekta Inc.

60 APPLIED LIFE SCIENCES↗

Reno-protective effects of TAK-242 on acute kidney injury in a rat model

Highlights: • Acute kidney inschemia/reperfusion (I/R) injury is characterized by an abrupt loss of kidney function. • TAK-242 is a selective inhibitor of the Toll-like receptor 4, which may cause kidney damage via aldosterone-induced pathway. • Administration of TAK-242 may act as a reno-protective agent in reducing overall kidney damage following ischemia/reperfusion injury. • IL-18, MDA and NGAL are useful biomarkers of kidney damage following ischemia/reperfusion injury . Acute kidney inschemia/reperfusion (I/R) injury is characterized by an abrupt loss of kidney function, resulting in the retention of urea and other nitrogenous waste products and in the dysregulation of extracellular volume and electrolytes. Despite the advances in therapeutic techniques, the mortality and morbidity of patients remain high and have not appreciably improved. This study aims to evaluate the potential protective effect of TAK-242 on renal ischemia/reperfusion injury using an animal model. Thirty-five adult male Sprague-dawely rats (weighing 200–300), were assigned randomly into the following experimental groups (n = 7 in each group), Control (I/R), Sham (negative control), TAK-242 (5 mg/kg body weight), TAK-242 (10 mg/kg body weight) and Vehicle (DMSO). Rats were exposed to a 30 min of ischemia then 3 h of reperfusion. At the end of reperfusion phase, rats were sacrificed then plasma, serum and tissue samples were obtained to measure markers of kidney oxidative stress and inflammation. Plasma levels of neutrophil gelatinase-associated lipocalin (NGAL), and tissue levels of interleukin-18 (IL-18) and malondialdehyde (MDA) were significantly lower in TAK-242 pretreated groups than the vehicle group and the control group (p < 0.05). Furthermore; serum levels of urea and creatinine were significantly lower in the TAK-242 pretreated groups as compared to the control group (p < 0.05). We conclude that administration of TAK-242 can be useful preventive method in attenuating the degree of acute kidney injury during ischemic reperfusion process as shown by a significant reduction of urinary inflammatory markers as well as significant reduction of urea and creatinine levels.

60 APPLIED LIFE SCIENCES↗