MV Treatment Research Articles

Feasibility of real-time motion management with helical tomotherapy.

This study investigates the potential application of image-based motion tracking and real-time motion correction to a helical tomotherapy system. A kV x-ray imaging system was added to a helical tomotherapy system, mounted 90 degrees offset from the MV treatment beam, and an optical camera system was mounted above the foot of the couch. This experimental system tracks target motion by acquiring an x-ray image every few seconds during gantry rotation. For respiratory (periodic) motion, software correlates internal target positions visible in the x-ray images with marker positions detected continuously by the camera, and generates an internal-external correlation model to continuously determine the target position in three-dimensions (3D). Motion correction is performed by continuously updating jaw positions and MLC leaf patterns to reshape (effectively re-pointing) the treatment beam to follow the 3D target motion. For motion due to processes other than respiration (e.g., digestion), no correlation model is used - instead, target tracking is achieved with the periodically acquired x-ray images, without correlating with a continuous camera signal. The system's ability to correct for respiratory motion was demonstrated using a helical treatment plan delivered to a small (10 mm diameter) target. The phantom was moved following a breathing trace with an amplitude of 15 mm. Film measurements of delivered dose without motion, with motion, and with motion correction were acquired. Without motion correction, dose differences within the target of up to 30% were observed. With motion correction enabled, dose differences in the moving target were less than 2%. Nonrespiratory system performance was demonstrated using a helical treatment plan for a 55 mm diameter target following a prostate motion trace with up to 14 mm of motion. Without motion correction, dose differences up to 16% and shifts of greater than 5 mm were observed. Motion correction reduced these to less than a 6% dose difference and shifts of less than 2 mm. Real-time motion tracking and correction is technically feasible on a helical tomotherapy system. In one experiment, dose differences due to respiratory motion were greatly reduced. Dose differences due to nonrespiratory motion were also reduced, although not as much as in the respiratory case due to less frequent tracking updates. In both cases, beam-on time was not increased by motion correction, since the system tracks and corrects for motion simultaneously with treatment delivery.

Effects of Exogenous Melatonin on Methyl Viologen-Mediated Oxidative Stress in Apple Leaf.

Oxidative stress is a major source of damage of plants exposed to adverse environments. We examined the effect of exogenous melatonin (MT) in limiting of oxidative stress caused by methyl viologen (MV; paraquatin) in apple leaves (Malus domestica Borkh.). When detached leaves were pre-treated with melatonin, their level of stress tolerance increased. Under MV treatment, melatonin effectively alleviated the decrease in chlorophyll concentrations and maximum potential Photosystem II efficiency while also mitigating membrane damage and lipid peroxidation when compared with control leaves that were sprayed only with water prior to the stress experiment. The melatonin-treated leaves also showed higher activities and transcripts of antioxidant enzymes superoxide dismutase, peroxidase, and catalase. In addition, the expression of genes for those enzymes was upregulated. Melatonin-synthesis genes MdTDC1, MdT5H4, MdAANAT2, and MdASMT1 were also upregulated under oxidative stress in leaves but that expression was suppressed in response to 1 mM melatonin pretreatment during the MV treatments. Therefore, we conclude that exogenous melatonin mitigates the detrimental effects of oxidative stress, perhaps by slowing the decline in chlorophyll concentrations, moderating membrane damage and lipid peroxidation, increasing the activities of antioxidant enzymes, and changing the expression of genes for melatonin synthesis.

Systematic intrafraction shifts of mediastinal lymph node targets between setup imaging and radiation treatment delivery in lung cancer patients

Background and purposeInternal target motion results in geometrical uncertainties in lung cancer radiotherapy. In this study, we determined the intrafraction motion and baseline shifts of mediastinal lymph node (LN) targets between setup imaging and treatment delivery. Material and methodsTen lung cancer patients with 2–4 fiducial markers implanted in LN targets received intensity-modulated radiotherapy with a daily setup cone-beam CT (CBCT) scan used for online soft-tissue match on the primary tumor. At a total of 122 fractions, 5 Hz fluoroscopic kV images were acquired orthogonal to the MV treatment beam during treatment delivery. Offline, the 3D trajectory of the markers was determined from their projected trajectory in the CBCT projections and in the intra-treatment kV images. Baseline shifts and changes in the respiratory motion amplitude between CBCT and treatment delivery were determined from the 3D trajectories. ResultsSystematic mean LN baseline shifts of 2.2 mm in the cranial direction (standard deviation (SD): 1.8 mm) and 1.0 mm in the posterior direction (SD: 1.2 mm) occurred between CBCT imaging and treatment delivery. The mean motion amplitudes during CBCT and treatment delivery agreed within 0.2 mm in all directions. ConclusionsSystematic cranial and posterior intrafraction baseline shifts between CBCT and treatment delivery were observed for mediastinal LN targets. Intrafraction motion amplitudes were stable.

Current modulated volume-of-interest imaging for kilovoltage intrafaction monitoring of the prostate.

The focus of this work was to improve the available kV image quality for continuous intrafraction monitoring of the prostate during volumetric modulated arc therapy. This is investigated using a novel blade collimation system enabling tube current modulated (TCM) volume-of-interest (VOI) imaging of prostate fiducial markers during radiotherapy, and Monte Carlo simulation of MV scatter. A four-blade dynamic kV collimator was used to track a VOI containing gold fiducial markers embedded in a dynamic pelvis phantom during gantry rotation. For each fiducial, a VOI margin around each marker was set to be 2σ of the population covariance matrix characterizing prostate motion. This was used to conform to a single or several fiducials and compared to a static field. DRRs were used to calculate the kV attenuation for each VOI as a function of angle and used to optimize x-ray tube current during acquisition. Image quality was assessed with regard to contrast-to-noise ratio (CNR), fiducial detectability, and imaging dose. Monte Carlo simulations in EGSnrc were used to calculate the imaging dose to the phantom and MV scatter fluence to the imaging panel. Fiducials can be accurately located using a VOI containing a single or several fiducials using a relatively high constant kV output. However, when using a 6 × 6 cm2 field the dose can be upwards of 1.5 Gy in bone for constant kV output and 3.1 Gy when applying TCM at 1 Hz imaging over the course of 40 fractions. This can be mitigated through tailoring the imaging field to a single or several fiducials, in which the integral dose is reduced by a factor of 15.6 and 3.7, respectively. For a constant MV treatment field size, the scattered fluence reaching the kV panel varies by less than a factor of two for a completely rotation of the gantry. However, the MV scatter spectrum overlaps with the detector response for a deleterious effect, with a peak MV scatter energy of approximately 100 keV. TCM can be used to overcome the variability in image quality throughout the rotation and therefore improve fiducial CNR and detectability during periods of high kV attenuation. The combination of VOI and TCM introduces an advantageous approach in intrafraction monitoring of the prostate during radiotherapy by both reducing and localizing the imaging dose, while improving image quality and fiducial detectability during periods of high kV attenuation. In addition, the influence of MV scatter has been shown to be most important in low attenuation regions, with a variation by a factor of two.

Effects of different winter cover crops on soil organic carbon in a double cropping rice paddy field.

In a double cropping rice field experiment, effects of five winter cover crops on the total organic carbon (TOC), active organic carbon (AOC), carbon pool management index (CPMI) and organic carbon storage were studied in three soil layers (0-5, 5-10 and 10-20 cm).Winter cover crops of ryegrass (Ry), Chinese milk vetch (Mv), potato (Po), and rape (Ra) between two rice crops were compared with fallow as control (CK). The results showed that the TOC and AOC contents under Ry, Mv, Po and Ra treatments were higher than those of CK in all three la-yers. Meanwhile, the TOC and AOC contents in Po treatment were higher than those of other treatments. Compared with CK, the AOC, activity index (AI), carbon pool index (CPI) and CPMI in the soil were improved through the recycling of winter cover crops straw. The AOC, AI, CPI and CPMI in the studied layers increased in order of Po>Mv>Ry>Ra>CK. The results indicated that the recycling of winter cover crops straw promoted the storage of SOC in the 0-20 cm soil profile as compared with CK. The strongest effect of the winter cover crops on the SOC storage occurred in Mv treatment, followed by Mv and Po treatments, and the SOC storage increased with the increasing soil depth.

Optimization of photon beam energies in gold nanoparticle enhanced arc radiation therapy using Monte Carlo methods

As a recent area of development in radiation therapy, gold nanoparticle (GNP) enhanced radiation therapy has shown potential to increase tumour dose while maintaining acceptable levels of healthy tissue toxicity. In this study, the effect of varying photon beam energy in GNP enhanced arc radiation therapy (GEART) is quantified through the introduction of a dose scoring metric, and GEART is compared to a conventional radiotherapy treatment. The PENELOPE Monte Carlo code was used to model several simple phantoms consisting of a spherical tumour containing GNPs (concentration: 15 mg Au g−1 tumour, 0.8 mg Au g−1 normal tissue) in a cylinder of tissue. Several monoenergetic photon beams, with energies ranging from 20 keV to 6 MeV, as well as 100, 200, and 300 kVp spectral beams, were used to irradiate the tumour in a 360° arc treatment. A dose metric was then used to compare tumour and tissue doses from GEART treatments to a similar treatment from a 6 MV spectrum. This was also performed on a simulated brain tumour using patient computed tomography data. GEART treatments showed potential over the 6 MV treatment for many of the simulated geometries, delivering up to 88% higher mean dose to the tumour for a constant tissue dose, with the effect greatest near a source energy of 50 keV. This effect is also seen with the inclusion of bone in a brain treatment, with a 14% increase in mean tumour dose over 6 MV, while still maintaining acceptable levels of dose to the bone and brain.

Comparison of Bolus Materials to Highly Absorbent Polypropylene and Rayon Cloth

This study assesses the utility of a highly absorbent polypropylene and rayon cloth (HAPRC) as a bolus material in radiation therapy. A comparison of various bolus materials used clinically at our center to the test bolus material, water-saturated HAPRC, was conducted. The reproducibility of the physical density was assessed by computerized tomography (CT) scanning the water-saturated HAPRC on a uniform density block phantom on multiple occasions, allowing the cloth to dry fully between subsequent CT scans. The cloth was found to have a consistent physical density between 0.8 and 1.0 g/cm3. To evaluate the dosimetric impact of the various bolus materials, metal oxide semiconductor field effect transistor dosimetry measurements were performed for a 6 MV treatment beam on the anterior surface of an anthropomorphic thorax phantom. The ability of the bolus material to conform to an irregular surface was assessed by CT scanning the various bolus materials overlaying the nose of an anthropomorphic head phantom and another irregularly shaped test object. The HAPRC conforms well to irregular contours and is relatively inexpensive compared to Superflab and thermoplastic sheets. Before implementing the material into the clinical setting, an appropriate process for laundering the material should be determined, for hygienic reasons.

TH-AB-202-01: Daily Lung Tumor Motion Characterization On EPIDs Using a Markerless Tiling Model

Purpose: Tracking lung tumor motion in real time allows for target dose escalation while simultaneously reducing dose to sensitive structures, thus increasing local control without increasing toxicity. We present a novel intra-fractional markerless lung tumor tracking algorithm using MV treatment beam images acquired during treatment delivery. Strong signals superimposed on the tumor significantly reduced the soft tissue resolution; while different imaging modalities involved introduce global imaging discrepancies. This reduced the comparison accuracies. A simple yet elegant Tiling algorithm is reported to overcome the aforementioned issues. Methods: MV treatment beam images were acquired continuously in beam's eye view (BEV) by an electronic portal imaging device (EPID) during treatment and analyzed to obtain tumor positions on every frame. Every frame of the MV image was simulated by a composite of two components with separate digitally reconstructed radiographs (DRRs): all non-moving structures and the tumor. This Titling algorithm divides the global composite DRR and the corresponding MV projection into sub-images called tiles. Rigid registration is performed independently on tile-pairs in order to improve local soft tissue resolution. This enables the composite DRR to be transformed accurately to match the MV projection and attain a high correlation value through a pixel-based linear transformation. The highest cumulative correlation for all tile-pairs achieved over a user-defined search range indicates the 2-D coordinates of the tumor location on the MV projection. Results: This algorithm was successfully applied to cine-mode BEV images acquired during two SBRT plans delivered five times with different motion patterns to each of two phantoms. Approximately 15000 beam's eye view images were analyzed and tumor locations were successfully identified on every projection with a maximum/average error of 1.8 mm / 1.0 mm. Conclusion: Despite the presence of strong anatomical signal overlapping with tumor images, this markerless detection algorithm accurately tracks intrafractional lung tumor motions. This project is partially supported by an Elekta research grant

SU‐G‐BRA‐09: Estimation of Motion Tracking Uncertainty for Real‐Time Adaptive Imaging

Purpose:kV fluoroscopic imaging combined with MV treatment beam imaging has been investigated for intrafractional motion monitoring and correction. It is, however, subject to additional kV imaging dose to normal tissue. To balance tracking accuracy and imaging dose, we previously proposed an adaptive imaging strategy to dynamically decide future imaging type and moments based on motion tracking uncertainty. kV imaging may be used continuously for maximal accuracy or only when the position uncertainty (probability of out of threshold) is high if a preset imaging dose limit is considered. In this work, we propose more accurate methods to estimate tracking uncertainty through analyzing acquired data in real‐time.Methods:We simulated motion tracking process based on a previously developed imaging framework (MV + initial seconds of kV imaging) using real‐time breathing data from 42 patients. Motion tracking errors for each time point were collected together with the time point's corresponding features, such as tumor motion speed and 2D tracking error of previous time points, etc. We tested three methods for error uncertainty estimation based on the features: conditional probability distribution, logistic regression modeling, and support vector machine (SVM) classification to detect errors exceeding a threshold.Results:For conditional probability distribution, polynomial regressions on three features (previous tracking error, prediction quality, and cosine of the angle between the trajectory and the treatment beam) showed strong correlation with the variation (uncertainty) of the mean 3D tracking error and its standard deviation: R‐square = 0.94 and 0.90, respectively. The logistic regression and SVM classification successfully identified about 95% of tracking errors exceeding 2.5mm threshold.Conclusion:The proposed methods can reliably estimate the motion tracking uncertainty in real‐time, which can be used to guide adaptive additional imaging to confirm the tumor is within the margin or initialize motion compensation if it is out of the margin.

SU‐F‐J‐15: The Use of CBCT for Dose Calculations in H/N Patients: Impact of Limited FOV

Purpose:To investigate the impact of limited superior and inferior (SI) field‐of‐view (FOV) associated with on‐board kV CBCT images for dose calculation.Methods:First, a (10×10) cm2 continuous arc 6 MV treatment plan was calculated for fourteen virtual water phantoms of varying SI thicknesses (5 to 15 cm) to replicate the FOV effect. In addition, 70 Gy VMAT plans from two H/N patients were calculated on their corresponding planning CT (pCT) and first fraction CBCT image volumes. For the phantom, the mean dose difference (full vs. limited FOV phantom) was calculated for each axial plane for each size phantom to determine the error with distance from the SI boundary, as a function of dose at the FOV edge. For the clinical cases, the absolute difference between CBCT and pCT dose was calculated for each voxel within the CBCT FOV and evaluated relative to CBCT SI boundary.Results:Phantom calculations showed that mean error was less than 5% for all planes whenever the CBCT border received less than 35 Gy or, otherwise, in planes at least 1.5 cm inside the CBCT SI FOV. Maximum pCT‐calculated doses differences in the axial plane of the superior CBCT FOV border was 4 Gy for Patient 1 and 55 Gy for Patient 2, and the corresponding maximum error in the same planes were 2% and 24%, respectively. Maximum pCT‐calculated dose 1 cm inferior to the superior FOV border was 7 Gy and 72 Gy, with a corresponding error of 0.5% and 2.5%.Conclusion:CBCT images may be used as a surrogate for full CT images with the following limitations: low dose (<50% of prescription dose) at the FOV edge, or greater than 1.5 cm material thickness between the CBCT border and the axial plane of interest.This work was partially funded by NIH P01CA059827.

Bixin protects mice against ventilation-induced lung injury in an NRF2-dependent manner.

Mechanical ventilation (MV) is a therapeutic intervention widely used in the clinic to assist patients that have difficulty breathing due to lung edema, trauma, or general anesthesia. However, MV causes ventilator-induced lung injury (VILI), a condition characterized by increased permeability of the alveolar-capillary barrier that results in edema, hemorrhage, and neutrophil infiltration, leading to exacerbated lung inflammation and oxidative stress. This study explored the feasibility of using bixin, a canonical NRF2 inducer identified during the current study, to ameliorate lung damage in a murine VILI model. In vitro, bixin was found to activate the NRF2 signaling pathway through blockage of ubiquitylation and degradation of NRF2 in a KEAP1-C151 dependent manner; intraperitoneal (IP) injection of bixin led to pulmonary upregulation of the NRF2 response in vivo. Remarkably, IP administration of bixin restored normal lung morphology and attenuated inflammatory response and oxidative DNA damage following MV. This observed beneficial effect of bixin derived from induction of the NRF2 cytoprotective response since it was only observed in Nrf2+/+ but not in Nrf2−/− mice. This is the first study providing proof-of-concept that NRF2 activators can be developed into pharmacological agents for clinical use to prevent patients from lung injury during MV treatment.

Effect of chemical fertilization and green manure on the abundance and community structure of ammonia oxidizers in a paddy soil

Ammonia oxidization is a critical step in the soil N cycle and can be affected by the fertilization regimes. Chinese milk-vetch (Astragalus sinicus L., MV) is a major green manure of rice (Oryza sativa L.) fields in southern China, which is recommended as an important agronomic practice to improve soil fertility. Soil chemical properties, abundance and community structures of ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA) in a MV-rice rotation field under different fertilization regimes were investigated. The field experiment included six treatments: control, without MV and chemical fertilizer (CK); 100% chemical fertilizer (NPK); 18 000 kg MV ha-1 plus 100% chemical fertilizer (NPKM1); 18 000 kg MV ha-1 plus 40% chemical fertilizer (NPKM2); 18 000 kg MV ha-1 alone (MV); and 18 000 kg MV ha-1 plus 40% chemical fertilizer plus straw (NPKMS). Results showed that NPKMS treatment could improve the soil fertility greatly although the application of 60% chemical fertilizer. The abundance of AOB only in the MV treatment had significant difference with the control; AOA were more abundant than AOB in all corresponding treatments. The NPKMS treatment had the highest AOA abundance (1.19 x 108 amoA gene copies g-1) and the lowest abundance was recorded in the CK treatment (3.21 x 107 amoA gene copies g-1). The abundance of AOA was significantly positively related to total N, available N, NH4+-N, and NO3--N. The community structure of AOA exhibited little variation among different fertilization regimes, whereas the community structure of AOB was highly responsive. Phylogenetic analysis showed that all AOB sequences were affiliated with Nitrosospira or Nitrosomonas and all AOA denaturing gradient gel electrophoresis (DGGE) bands belonged to the soil and sediment lineage. These findings could be fundamental to improve our understanding of AOB and AOA in the N cycle in the paddy soil.

SU-E-J-56: Static Gantry Digital Tomosynthesis From the Beam's-Eye-View

Purpose We have designed a novel TumoTrak™ x-ray system that delivers 19 distinct kV views with the linac gantry stationary. It images MV treatment beam above and below the patient with a kV tomosysthesis slice image from the therapy beam’s-eye-view. Results will be high quality images without MLC shadowing for notable improvements relative to conventional fluoroscopic MV imaging and fluoroscopic kV imaging. Methods A complete design has a kV electron beam multisource X-ray tube that fits around the MV treatment beam path, with little interference with normal radiotherapy and unblocked by the multi-leaf-collimator. To simulate digital tomosynthesis, we used cone-beam CT projection data from a lung SBRT patient. These data were acquired at 125 kVp and 11 fps (0.4 mAs per projection). We chose 19 projections evenly spaced over 27° around one of the treatment angles (240°). Digital tomosynthesis reconstruction of a slice through the tumor was performed using iterative reconstruction. The visibility of the lesion was assessed for the reconstructed digital tomosynthesis (DTS), using fluoroscopy MV images acquired during radiation therapy, and a kV single projection image acquired at the same angle as the treatment field (240°). Results The fluoroscopic DTS images provide the best tumor contrast, surpassing themore » conventional radiographic and the in-treatment MV portal images. The electron beam multisource X-ray tube design has been completed and the tube is being fabricated. The estimated time to cycle through all 19 projections is 700 ms, enabling high frame-rate imaging. While the initial proposed use case is for image guided and gated treatment delivery, the enhanced imaging will also deliver superior radiographic images for patient setup. Conclusion The proposed device will deliver high quality planar images from the beam’s-eye-view without MLC obstruction. The prototype has been designed and is being assembled with first imaging scheduled for May 2015. L. Partain, J. Kwon, D. Boyd: NIH/SBIR R43CA192489-01. J. Rottmann, G. Zentai, R. Berbeco: NIH/NCI 1R01CA188446-01. R. Berbeco: E. Research Grant, Varian Medical Systems.« less

Arabidopsis Qc-SNARE gene AtSFT12 is involved in salt and osmotic stress responses and Na(+) accumulation in vacuoles.

AtSFT12, an Arabidopsis Qc-SNARE protein, is localized to Golgi organelles and is involved in salt and osmotic stress responses via accumulation of Na (+) in vacuoles. To reduce the detrimental effects of environmental stresses, plants have evolved many defense mechanisms. Here, we identified an Arabidopsis Qc-SNARE gene, AtSFT12, involved in salt and osmotic stress responses using an activation-tagging method. Both activation-tagged plants and overexpressing transgenic plants (OXs) of the AtSFT12 gene were tolerant to high concentrations of NaCl, LiCl, and mannitol, whereas loss-of-function mutants were sensitive to NaCl, LiCl, and mannitol. AtSFT12 transcription increased under NaCl, ABA, cold, and mannitol stresses but not MV treatment. GFP-fusion AtSFT12 protein was juxtaposed with Golgi marker, implying that its function is associated with Golgi-mediated transport. Quantitative measurement of Na(+) using induced coupled plasma atomic emission spectroscopy revealed that AtSFT12 OXs accumulated significantly more Na(+) than WT plants. In addition, Na(+)-dependent fluorescence analysis of Sodium Green showed comparatively higher Na(+) accumulation in vacuoles of AtSFT12 OX cells than in those of WT plant cells after salt treatments. Taken together, our findings suggest that AtSTF12, a Golgi Qc-SNARE protein, plays an important role in salt and osmotic stress responses and functions in the salt stress response via sequestration of Na(+) in vacuoles.

MO‐PIS‐Exhibit Hall‐01: Tools for TG‐142 Linac Imaging QA I

Partners in Solutions is an exciting new program in which AAPM partners with our vendors to present practical “hands‐on” information about the equipment and software systems that we use in our clinics. The therapy topic this year is solutions for TG‐142 recommendations for linear accelerator imaging QA. Note that the sessions are being held in a special purpose room built on the Exhibit Hall Floor, to encourage further interaction with the vendors.Automated Imaging QA for TG‐142 with RITPresentation Time: 2:45 – 3:15 PMThis presentation will discuss software tools for automated imaging QA and phantom analysis for TG‐142. All modalities used in radiation oncology will be discussed, including CBCT, planar kV imaging, planar MV imaging, and imaging and treatment coordinate coincidence. Vendor supplied phantoms as well as a variety of third‐party phantoms will be shown, along with appropriate analyses, proper phantom setup procedures and scanning settings, and a discussion of image quality metrics. Tools for process automation will be discussed which include: RIT Cognition (machine learning for phantom image identification), RIT Cerberus (automated file system monitoring and searching), and RunQueueC (batch processing of multiple images). In addition to phantom analysis, tools for statistical tracking, trending, and reporting will be discussed. This discussion will include an introduction to statistical process control, a valuable tool in analyzing data and determining appropriate tolerances.An Introduction to TG‐142 Imaging QA Using Standard Imaging ProductsPresentation Time: 3:15 – 3:45 PMMedical Physicists want to understand the logic behind TG‐142 Imaging QA. What is often missing is a firm understanding of the connections between the EPID and OBI phantom imaging, the software “algorithms” that calculate the QA metrics, the establishment of baselines, and the analysis and interpretation of the results. The goal of our brief presentation will be to establish and solidify these connections.Our talk will be motivated by the Standard Imaging, Inc. phantom and software solutions. We will present and explain each of the image quality metrics in TG‐142 in terms of the theory, mathematics, and algorithms used to implement them in the Standard Imaging PIPSpro software. In the process, we will identify the regions of phantom images that are analyzed by each algorithm. We then will discuss the process of the creation of baselines and typical ranges of acceptable values for each imaging quality metric.

SU‐E‐J‐36: Combining CBCT Dose Into IMRT Treatment Planning

Purpose:Cone beam CT (CBCT) is increasingly used in patient setup for IMRT. Daily CBCT may provide effective localization, however, it introduces concern over excessive imaging dose. Previous studies investigated the calculation of excess CBCT dose, however, no study has yet treated this dose as a source of therapeutic radiation, optimized in consideration of PTV and OARs constrains. Here we present a novel combined MV+kV inverse optimization engine to weave the CBCT and MV dose together such that CBCT dose is used for both imaging and therapeutic purposes. This may mitigate some of the excess imaging dose effects of daily CBCT and allow complete evaluation of the CBCT dose prior to treatment.Methods:The EGSnrc Monte Carlo system was used to model a Varian Trilogy CBCT system and 6 MV treatment beam. Using the model, the dose to patient from treatment beam and imaging beam was calculated for ten patients. The standard IMRT objective function was modified to include CBCT dose. Treatment plan optimization using the MOSEK optimization tool was performed retrospectively with and without assuming kV radiation dose from CBCT, assuming one CBCT per fraction.Results:Across ten patients, the CBCT delivered peaks of between .4% and 3.0% of the prescription dose to the PTV, with average CBCT dose to the PTV between .3% and .8%. By including CBCT dose to skin as a constraint during optimization, peak skin dose is reduced by between 1.9% and 7.4%, and average skin dose is reduced by .2% to 3.3%.Conclusions:Pre‐treatment CBCT may deliver a substantial amount of radiation dose to the target volume. By considering CBCT dose to skin at the point of treatment planning, it is possible to reduce patient skin dose from current clinical levels, and to provide patient treatment with the improved accuracy that daily CBCT provides.

TH‐C‐12A‐10: Surface Dose Enhancement Using Novel Hybrid Electron and Photon Low‐Z Therapy Beams: Monte Carlo Simulation

Purpose:The introduction of the TrueBeam linac platform provides access to an in‐air target assembly making it possible to apply novel treatments using multiple target designs. One such novel treatment uses multiple low‐Z targets to enhance surface dose replacing the use of synthetic tissue equivalent material (bolus). This treatment technique will decrease the common dosimetric and set up errors prevalent in using physical treatment accessories like bolus. The groundwork for a novel treatment beam used to enhance surface dose to within 80‐100% of the dose at dmax by utilizing low‐Z (Carbon) targets of various percent CSDA range thickness operated at 2.5–4 MeV used in conjunction with a clinical 6 MV beam is presented herein.Methods:A standard Monte Carlo model of a Varian Clinac accelerator was developed to manufacturers specifications. Simulations were performed using Be, C, AL, and C, as potential low‐Z targets, placed in the secondary target position. The results determined C to be the target material of choice. Simulations of 15, 30 and 60% CSDA range C beams were propagated through slab phantoms. The resulting PDDs were weighted and combined with a standard 6 MV treatment beam. Versions of the experimental targets were installed into a 2100C Clinac and the models were validated.Results:Carbon was shown to be the low‐Z material of choice for this project. Using combinations of 15, 30, 60% CSDA beams operated at 2.5 and 4 MeV in combination with a standard 6 MV treatment beam the surface dose was shown to be enhanced to within 80–100% the dose at dmax.Conclusion:The modeled low‐Z beams were successfully validated using machined versions of the targets. Water phantom measurements and slab phantom simulations show excellent correlation. Patient simulations are now underway to compare the use of bolus with the proposed novel beams.NSERC

TH‐E‐17A‐10: Markerless Lung Tumor Tracking Based On Beams Eye View EPID Images

Purpose:Dynamic tumor tracking or motion compensation techniques have proposed to modify beam delivery following lung tumor motion on the flight. Conventional treatment plan QA could be performed in advance since every delivery may be different. Markerless lung tumor tracking using beams eye view EPID images provides a best treatment evaluation mechanism. The purpose of this study is to improve the accuracy of the online markerless lung tumor motion tracking method.Methods:The lung tumor could be located on every frame of MV images during radiation therapy treatment by comparing with corresponding digitally reconstructed radiograph (DRR). A kV‐MV CT corresponding curve is applied on planning kV CT to generate MV CT images for patients in order to enhance the similarity between DRRs and MV treatment images. This kV‐MV CT corresponding curve was obtained by scanning a same CT electron density phantom by a kV CT scanner and MV scanner (Tomotherapy) or MV CBCT. Two sets of MV DRRs were then generated for tumor and anatomy without tumor as the references to tracking the tumor on beams eye view EPID images.Results:Phantom studies were performed on a Varian TrueBeam linac. MV treatment images were acquired continuously during each treatment beam delivery at 12 gantry angles by iTools. Markerless tumor tracking was applied with DRRs generated from simulated MVCT. Tumors were tracked on every frame of images and compared with expected positions based on programed phantom motion. It was found that the average tracking error were 2.3 mm.Conclusion:This algorithm is capable of detecting lung tumors at complicated environment without implanting markers. It should be noted that the CT data has a slice thickness of 3 mm. This shows the statistical accuracy is better than the spatial accuracy.This project has been supported by a Varian Research Grant.

Combined MV + kV inverse treatment planning for optimal kV dose incorporation in IGRT

Despite the existence of real-time kV intra-fractional tumor tracking strategies for many years, clinical adoption has been held back by concern over the excess kV imaging dose cost to the patient when imaging in continuous fluoroscopic mode. This work aims to solve this problem by investigating, for the first time, the use of convex optimization tools to optimally integrate this excess kV imaging dose into the MV therapeutic dose in order to make real-time kV tracking clinically feasible. Phase space files modeling both a 6 MV treatment beam and a kV on-board-imaging beam of a commercial LINAC were generated with BEAMnrc, and used to generate dose influence matrices in DOSXYZnrc for ten previously treated lung cancer patients. The dose optimization problem for IMRT, formulated as a quadratic problem, was modified to include additional constraints as required for real-time kV intra-fractional tracking. An interior point optimizer was used to solve the modified optimization problem. It was found that when using large kV imaging apertures during fluoroscopic tracking, combined MV + kV optimization lead to a 0.5%–5.17% reduction in the total number of monitor units assigned to the MV beam due to inclusion of the kV dose over the ten patients. This was accompanied by a reduction of up to 42% of the excess kV dose compared to standard MV IMRT with kV tracking. For all kV field sizes considered, combined MV + kV optimization provided prescription dose to the treatment volume coverage equal to the no-imaging case, yet superior to standard MV IMRT with non-optimized kV fluoroscopic tracking. With combined MV + kV optimization, it is possible to quantify in a patient specific way the dosimetric effect of real-time imaging on the patient. Such information is necessary when substantial kV imaging is performed.

Therapeutic use of stem cell transplantation for cell replacement or cytoprotective effect of microvesicle released from mesenchymal stem cell.

Idiopathic pulmonary fibrosis (IPF) is the most common and severe type of idiopathic interstitial pneumonias (IIP), and which is currently no method was developed to restore normal structure and function. There are several reports on therapeutic effects of adult stem cell transplantations in animal models of pulmonary fibrosis. However, little is known about how mesenchymal stem cell (MSC) can repair the IPF. In this study, we try to provide the evidence to show that transplanted mesenchymal stem cells directly replace fibrosis with normal lung cells using IPF model mice. As results, transplanted MSC successfully integrated and differentiated into type II lung cell which express surfactant protein. In the other hand, we examine the therapeutic effects of microvesicle treatment, which were released from mesenchymal stem cells. Though the therapeutic effects of MV treatment is less than that of MSC treatment, MV treat-ment meaningfully reduced the symptom of IPF, such as collagen deposition and inflammation. These data suggest that stem cell transplantation may be an effective strategy for the treatment of pulmonary fibrosis via replacement and cytoprotective effect of microvesicle released from MSCs.