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At least 505 records · Page 28

SU-E-J-167: Dosimetric Consequences From Minimal Displacements in APBI with SAVI Applicators

Purpose: To determine the importance of providing proper solid immobilization in every fraction of treatment in APBI with brachytherapy. Methods: 125 patients treated with APBI brachytherapy with SAVI applicators at SFRO Boca Raton, from 2013–2015 were considered for this retrospective study. The CT scans of each patient, which were taken before each treatment, were imported in to the Oncentra treatment planning system. Then they were compared with the initial CT scan which was used for the initial plan. Deviation in displacements in reference to ribs and skin surface was measured and dosimetric evaluations respective to the initial image were performed. Results: Small deviations in displacements were observed from the SAVI applicator to the ribs and the skin surface. Dosimetric evaluations revealed, very small changes in the inter-fractionation position make significant differences in the maximum dose to critical organs. Additionally, the volume of the cavity also changed between fractions. As a Result, the maximum dose manifested variance between 10% and 32% in ribs and skin surface respectively. Conclusion: It appears that taking a CT scan before each treatment is necessary to minimize the risk of delivering undesired high doses to the critical organs. This study indicates, in 30% of the cases re-planning was necessary between treatments. We conclude that, treatment planning teams should evaluate the placement of the device by analyzing the CT images before each treatment and they must be prepared for re-planning if needed. This study also reveals the urgent need of improving the immobilization methods with APBI when treating with the SAVI applicator.

60 APPLIED LIFE SCIENCES↗

SU-E-T-547: Modeling Biological Response to Proton Irradiation and Evaluating Its Potential Clinical Consequences

Purpose: In addition to physical uncertainties, proton therapy may also be associated with biologic uncertainties. Currently a generic RBE value of 1.1 is used for treatment planning. In this work the effects of variable RBE, in comparison to a fixed RBE, were evaluated by calculating the effective dose for proton treatments. Methods: The repair misrepair fixation (RMF) model was used to calculate variable proton RBEs. The RBE weighted spread-out Bragg peak (SOBP) dose in water phantom was calculated using Monte Carlo simulation and compared to 1.1 weighted SOBP dose. A head and neck proton treatment was used to evaluate the potential effects, by comparing the head and neck treatment plan computed with a commercial treatment planning system that incorporates fixed RBE of 1.1 and a Monte Carlo treatment planning system that incorporates variable RBE. Results: RBE calculations along the depth of SOBP showed that the RBE at the entrance is approximately 1 and reaches 1.1 near the center of the SOBP. However, in distal regions the RBE rises to higher values (up to 3.5 depending on the cell type). Comparison of commercial treatment plans using a fixed RBE of 1.1 and Monte Carlo using variable RBE showed noticeable differences in the effective dose distributions. Conclusion: The comparison of the treatment planning with fixed and variable RBE shows that using commercial treatment planning systems that incorporate fixed RBE (1.1) could Result in overestimation of the effective dose to part of head and neck target volumes, while underestimating the effective dose to the normal tissue beyond the tumor. The accurate variable RBE as a function of proton beam energy in patient should be incorporated in treatment planning to improve the accuracy of effective dose calculation.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Consequences of air around an ionization chamber: Are existing solid phantoms suitable for reference dosimetry on an MR-linac?

Purpose: A protocol for reference dosimetry for the MR-linac is under development. The 1.5 T magnetic field changes the mean path length of electrons in an air-filled ionization chamber but has little effect on the electron trajectories in a surrounding phantom. It is therefore necessary to correct the response of an ionization chamber for the influence of the magnetic field. Solid phantoms are used for dosimetry measurements on the MR-linac, but air is present between the chamber wall and phantom insert. This study aimed to determine if this air influences the ion chamber measurements on the MR-linac. The absolute response of the chamber and reproducibility of dosimetry measurements were assessed on an MR-linac in solid and water phantoms. The sensitivity of the chamber response to the distribution of air around the chamber was also investigated. Methods: Measurements were performed on an MR-linac and replicated on a conventional linac for five chambers. The response of three waterproof chambers was measured with air and with water between the chamber and the insert to measure the influence of the air volume on absolute chamber response. The distribution of air around the chamber was varied indirectly by rotating each chamber about the longitudinal chamber axis in a solid phantom and a water phantom (waterproof chambers only) and measuring the angular dependence of the chamber response, and varied directly by displacing the chamber in the phantom insert using a paper shim positioned at different orientations between the chamber casing and the insert. Results: The responses of the three waterproof chambers measured on the MR-linac were 0.7%–1.2% higher with water than air in the chamber insert. The responses of the chambers on the conventional linac changed by less than 0.3% when air in the insert was replaced with water. The angular dependence of the chambers ranged from 0.6% to 1.9% in the solid phantom on the MR-linac but was less than 0.5% in water on the MR-linac and less than 0.3% in the solid phantom on the conventional linac. Inserting a shim around the chamber induced changes of the chamber response in a magnetic field of up to 2.2%, but the change in chamber response on the conventional linac was less than 0.3%. Conclusions: The interaction between the magnetic field and secondary electrons in the air around the chamber reduces the charge collected from 0.7% to 1.2%. The large angular dependence of ion chambers measured in the plastic phantom in a magnetic field appears to arise from a change of air distribution as the chamber is moved within the insert, rather than an intrinsic isotropy of the chamber sensitivity to radiation. It is recommended that reference dosimetry measurements on the MR-linac can be performed only in water, rather than in existing plastic phantoms.

60 APPLIED LIFE SCIENCES↗

SU-F-J-87: Impact Of The Dosimetric Consequences From Minimal Displacements Throughout The Treatment Time In APBI With SAVI Applicators

Purpose: To assess the variation in dose received by the organs at risk (OARs) due to inter-fractional motion by SAVI to determine the importance of providing proper immobilization Methods: An analysis of 15 patients treated with SAVI applicators were considered for this study. Treatment planning teams did not see significant changes in their CT scans through scout images and initial treatment plan was used for the entire treatment. These scans, taken before each treatment were imported in to the treatment planning system and were fused together with respective to the applicator, using landmark registration. Dosimetric evaluations were performed. Dose received by skin, ribs and PTV(Planning target volume) respect to the initial treatment plan were measured. Results: Contours of the OARs were not similar with the initial image. Deduction in volumes of PTV and cavity, small deviations in displacements from the applicator to the OARs, difference in doses received by the OARs between treatments were noticed. The maximum, minimum, average doses varied between 10% to 20% 5% to 8% and 15% to 20% in ribs and skin. The 0.1cc doses to OARs showed an average change of 10% of the prescribed dose. PTV was receiving a different dose than the estimated dose Conclusion: The variation in volumes and isodoses related to the OARs, PTV receiving a lesser dose than the prescribed dose indicate that the estimated doses are different from the received dose. This study reveals the urgent need of improving the immobilization methods. Taking a CT scan before each treatment and replanning is helpful to minimize the risk of delivering undesired high doses to the OARs. Patient positioning, motion, respiration, observer differences and time lap between the planning and treating can arise more complications. VacLock, Positioning cushions, Image guided brachytherapy and adjustable registration should be used for further improvements.

60 APPLIED LIFE SCIENCES↗

SU-G-IeP4-13: PET Image Noise Variability and Its Consequences for Quantifying Tumor Hypoxia

Purpose: The values in a PET image which represent activity concentrations of a radioactive tracer are influenced by a large number of parameters including patient conditions as well as image acquisition and reconstruction. This work investigates noise characteristics in PET images for various image acquisition and image reconstruction parameters. Methods: Different phantoms with homogeneous activity distributions were scanned using several acquisition parameters and reconstructed with numerous sets of reconstruction parameters. Images from six PET scanners from different vendors were analyzed and compared with respect to quantitative noise characteristics. Local noise metrics, which give rise to a threshold value defining the metric of hypoxic fraction, as well as global noise measures in terms of noise power spectra (NPS) were computed. In addition to variability due to different reconstruction parameters, spatial variability of activity distribution and its noise metrics were investigated. Patient data from clinical trials were mapped onto phantom scans to explore the impact of the scanner’s intrinsic noise variability on quantitative clinical analysis. Results: Local noise metrics showed substantial variability up to an order of magnitude for different reconstruction parameters. Investigations of corresponding NPS revealed reconstruction dependent structural noise characteristics. For the acquisition parameters, noise metrics were guided by Poisson statistics. Large spatial non-uniformity of the noise was observed in both axial and radial direction of a PET image. In addition, activity concentrations in PET images of homogeneous phantom scans showed intriguing spatial fluctuations for most scanners. The clinical metric of the hypoxic fraction was shown to be considerably influenced by the PET scanner’s spatial noise characteristics. Conclusion: We showed that a hypoxic fraction metric based on noise characteristics requires careful consideration of the various dependencies in order to justify its quantitative validity. This work may result in recommendations for harmonizing QA of PET imaging for multi-institutional clinical trials.

60 APPLIED LIFE SCIENCES↗

TU-AB-BRA-11: Indications for Online Adaptive Radiotherapy Based On Dosimetric Consequences of Interfractional Pancreas-To-Duodenum Motion in MRI-Guided Pancreatic Radiotherapy

Purpose: Dose limiting structures, such as the duodenum, render the treatment of pancreatic cancer challenging. In this multi-institutional study, we assess dosimetric differences caused by interfraction pancreas-to-duodenum motion using MR-IGRT to determine the potential impact of adaptive replanning. Methods: Ten patients from two institutions undergoing MRI-guided radiotherapy with conventional fractionation (n=5) or SBRT (n=5) for pancreatic cancer were included. Initial plans were limited by duodenal dose constraints of 50 Gy (0.5 cc)/31 Gy (0.1 cc) for conventional/SBRT with prescriptions of 30 Gy/5 fractions (SBRT) and 40–50 Gy/25 fractions (conventional). Daily volumetric MR images were acquired under treatment conditions on a clinical MR-IGRT system. The correlation was assessed between interfractional GTV-to-duodenum positional variation and daily recalculations of duodenal dose metrics. Positional variation was quantified as the interfraction difference in Hausdorff distance from simulation baseline (ΔHD) between the GTV and proximal duodenal surface, or volume overlap between GTV and duodenum for cases with HD{sub 0}=0 (GTV abutting duodenum). Adaptation was considered indicated when daily positional variations enabled dose escalation to the target while maintaining duodenal constraints. Results: For fractions with ΔHD>0 (n=14, SBRT only), the mean interfraction duodenum dose decrease from simulation to treatment was 44±53 cGy (maximum 136 cGy). A correlation was found between ΔHD and dosimetric difference (R{sup 2}=0.82). No correlation was found between volume of overlap and dosimetric difference (R{sup 2}=0.31). For 89% of fractions, the duodenum remained overlapped with the target and the duodenal dose difference was negligible. The maximum observed indication for adaptation was for interfraction ΔHD=11.6 mm with potential for adaptive dose escalation of 136 cGy. Conclusion: This assessment showed that Hausdorff distance was a reasonable metric to use to determine the indication for adaptation. Adaptation was potentially indicated in 11% of the treatments (fractions where GTV-to-duodenum distance increased from simulation), with a feasible average dose escalation of 7.0%. MB, LH, JO, RK, PP: research and/or travel funding from ViewRay Inc. PP: research grant from Varian Medical Systems and Philips Healthcare.

60 APPLIED LIFE SCIENCES↗

Computation and consequences of high order amplitude- and parameter-dependent tune shifts in storage rings for high precision measurements

Nonlinear effects of the various electric field and magnetic field components of storage rings to confine the particles and bend their trajectory can cause substantial amplitude-dependent tune shifts within the beam. Furthermore, tune shifts are often sensitive to variations of system parameters, e.g. total particle momentum offsets $δp$. Such amplitude- and parameter-dependent tune shifts influence the dynamics and stability of a beam in particle storage rings. Thus, it is critical for high precision measurements to analyze and understand these influences. On this basis, we present in this paper normal form methods for the calculation of high order amplitude and system parameter dependencies of the horizontal and vertical tunes in storage rings using the differential algebra (DA) framework within COSY INFINITY. A storage ring is simulated using COSY INFINITY to generate a DA Poincaré return map describing the transverse phase space behavior after each revolution in the storage ring. The map is expanded around the parameter-dependent closed orbit of the system before transforming the resulting map into normal form coordinates to extract the high order tune dependencies on the phase space amplitude and variation in the system parameters. As a specific example, a storage ring similar to the Storage Ring of the Muon g-2 Experiment at Fermilab (E989) is investigated.

43 PARTICLE ACCELERATORS↗

Physiological Responses of C4 Perennial Bioenergy Grasses to Climate Change: Causes, Consequences, and Constraints

C 4 perennial bioenergy grasses are an economically and ecologically important group whose responses to climate change will be important to the future bioeconomy. These grasses are highly productive and frequently possess large geographic ranges and broad environmental tolerances, which may contribute to the evolution of ecotypes that differ in physiological acclimation capacity and the evolution of distinct functional strategies. C 4 perennial bioenergy grasses are predicted to thrive under climate change—C 4 photosynthesis likely evolved to enhance photosynthetic efficiency under stressful conditions of low [CO 2 ], high temperature, and drought—although few studies have examined how these species will respond to combined stresses or to extremes of temperature and precipitation. Important targets for C 4 perennial bioenergy production in a changing world, such as sustainability and resilience, can benefit from combining knowledge of C 4 physiology with recent advances in crop improvement, especially genomic selection.

Plant Sciences↗

Sea Level Rise in the CESM Large Ensemble: The Role of Individual Climate Forcings and Consequences for the Coming Decades

The emergence of a spatial pattern in the externally forced response (FR) of dynamic sea level (DSL) during the altimeter era has recently been demonstrated using climate models but our understanding of its initial emergence, drivers, and implications for the future is poor. Here the anthropogenic forcings of the DSL pattern are explored using the Community Earth System Model Large Ensemble (CESM-LE) and Single-Forcing Large Ensemble, a newly available set of simulations where values of individual forcing agents remain fixed at 1920 levels, allowing for an estimation of their effects. Statistically significant contributions to the DSL FR are identified for greenhouse gases (GHGs) and industrial aerosols (AERs), with particularly strong contributions resulting from AERs in the mid-twentieth century and GHGs in the late twentieth and twenty-first century. Secondary, but important, contributions are identified for biomass burning aerosols in the equatorial Atlantic Ocean in the mid-twentieth century, and for stratospheric ozone in the Southern Ocean during the late twentieth century. Key to understanding regional DSL patterns are ocean heat content and salinity anomalies, which are driven by surface heat and freshwater fluxes, ocean dynamics, and the spatial structure of seawater thermal expansivity. Finally, potential implications for the interpretation of DSL during the satellite era and the longer records from tide gauges are suggested as a topic for future research.

54 ENVIRONMENTAL SCIENCES↗

Dataset for manuscript "Consequences of the failure of equipartition for the p-V behavior of liquid water and the hydration free energy components of a small protein"

Previously, we showed that in the molecular dynamics simulation of a rigid model of water it is necessary to use an integration time-step dt that is less than or equal to 0.5 fs to ensure equipartition between translational and rotational modes. We extended that study in the NVT ensemble to NpT conditions and to an aqueous protein. We study neat liquid water with the rigid, SPC/E model and the protein BBA (PDB ID: 1FME) solvated in the rigid, TIP3P model. We examined integration time-steps ranging from 0.5 fs to 4.0 fs for various thermostat plus barostat combinations. We find that a small time-step, dt, is necessary to ensure consistent prediction of the simulation volume. Hydrogen mass repartitioning alleviates the problem somewhat, but is ineffective for the typical time-step used with this approach. The compressibility, a measure of volume fluctuations, is seen to be sensitive to dt. Using the mean volume estimated from the NpT simulation, we examined the electrostatic and van der Waals contribution to the hydration free energy of the protein in the NVT ensemble. These contributions are also sensitive to dt. In going from a time-step of 2 fs to a time-step of 0.5 fs, the change in the net electrostatic plus van der Waals contribution to the hydration of BBA is already in excess of the folding free energy reported for this protein. The data-set contains the simulation metadata and log files that support the claims noted above.

59 BASIC BIOLOGICAL SCIENCES↗

Origins and consequences of asymmetric nano-FTIR interferograms

Infrared scattering-type near-field optical microscopy, IR s-SNOM, and its broadband variant, nano-FTIR, are pioneering, flagship techniques for their ability to provide molecular identification and material optical property information at a spatial resolution well below the far-field diffraction limit, typically less than 25 nm. While s-SNOM and nano-FTIR instrumentation and data analysis have been discussed previously, there is a lack of information regarding experimental parameters for the practitioner, especially in the context of previously developed frameworks. Like conventional FTIR spectroscopy, the critical component of a nano-FTIR instrument is an interferometer. However, unlike FTIR spectroscopy, the resulting interference patterns or interferograms are typically asymmetric. Here, we unambiguously describe the origins of asymmetric interferograms recorded with nano-FTIR instruments, give a detailed analysis of potential artifacts, and recommend optimal instrument settings as well as data analysis parameters.

47 OTHER INSTRUMENTATION↗

The Phenazine 2-Hydroxy-Phenazine-1-Carboxylic Acid Promotes Extracellular DNA Release and Has Broad Transcriptomic Consequences in Pseudomonas chlororaphis 30–84

Enhanced production of 2-hydroxy-phenazine-1-carboxylic acid (2-OH-PCA) by the biological control strain Pseudomonas chlororaphis 30–84 derivative 30-84O* was shown previously to promote cell adhesion and alter the three-dimensional structure of surfaceattached biofilms compared to the wild type. The current study demonstrates that production of 2-OH-PCA promotes the release of extracellular DNA, which is correlated with the production of structured biofilm matrix. Moreover, the essential role of the extracellular DNA in maintaining the mass and structure of the 30–84 biofilm matrix is demonstrated. To better understand the role of different phenazines in biofilm matrix production and gene expression, transcriptomic analyses were conducted comparing gene expression patterns of populations of wild type, 30-84O* and a derivative of 30–84 producing only PCA (30-84PCA) to a phenazine defective mutant (30-84ZN) when grown in static cultures. RNA-Seq analyses identified a group of 802 genes that were differentially expressed by the phenazine producing derivatives compared to 30-84ZN, including 240 genes shared by the two 2-OH-PCA producing derivatives, the wild type and 30-84O*. A gene cluster encoding a bacteriophage- derived pyocin and its lysis cassette was upregulated in 2-OH-PCA producing derivatives. A holin encoded in this gene cluster was found to contribute to the release of eDNA in 30–84 biofilm matrices, demonstrating that the influence of 2-OH-PCA on eDNA production is due in part to cell autolysis as a result of pyocin production and release. The results expand the current understanding of the functions different phenazines play in the survival of bacteria in biofilm-forming communities.

59 BASIC BIOLOGICAL SCIENCES↗

As if Biomarker Discovery Isn't Hard Enough: the Consequences of Poorly Characterized Reagents

The advent of high throughput omic technologies over the past two decades has driven a vast expansion in the search for clinical biomarkers, as manifested by the plethora of publications on biomarker discovery (over 8,600) listed on PubMed since 2000. Unfortunately, the same time period has seen a relative dearth of clinically validated biomarkers that have received FDA approval; only 10 new cancer biomarkers have been approved by the FDA in the same time period [1].

biomarker discovery↗