Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “RESPIRATION”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,387 records · Page 77
All sourcesNASA NTRSDOE OSTI
DOE OSTI2020

Wavelength- and irradiance-dependent changes in intracellular nitric oxide level

Photobiomodulation (PBM) refers to beneficial effects of low energy light absorption. Although there is a large and growing body of literature describing down-stream physiological benefits of PBM, there is limited understanding of the molecular mechanisms that initiate and mediate these effects at the level of photon absorption. At present, the leading hypothesis is that light absorption induces release of nitric oxide (NO) from the active site of cytochrome c oxidase (COX), allowing it to bind O 2 instead. This is believed to increase mitochondrial respiration, and result in greater overall health of the cell due to increased ATP production. Aim: Although NO itself is a powerful signaling molecule involved in a host of biological responses, less attention has been devoted to the mechanisms of NO release and subsequent effects on cell signaling. The purpose of this work is to investigate wavelength-specific effects on intracellular NO release in living cells. Approach: We have conducted in depth dosimetry analyses of NO production and function in an in vitro retinal model in response to low energy exposure to one or more wavelengths of laser light. Results: We found statistically significant wavelength-dependent elevations (10-30%) in intracellular NO levels following laser exposures at 447, 532, 635 or 808 nm. Sequential or simultaneous exposures to light at two different wavelengths enhanced the NO modulation up to 50% of unexposed controls. Additionally, the immediate increases in cellular NO levels were independent of the function of nitric oxide synthase, depended greatly on the substrate source of electrons entering the electron transport chain, and did not result in increased levels of cGMP. Conclusions: This study concludes the simple model of light-mediated release of NO from COX is unlikely to explain the wide variety of PBM effects reported in the literature. Our multi-wavelength method provides a novel tool for studying immediate and early mechanisms of PBM, as well as exploring intracellular NO signaling networks.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2014

Towards local progression estimation of pulmonary emphysema using CT

Purpose: Whole lung densitometry on chest CT images is an accepted method for measuring tissue destruction in patients with pulmonary emphysema in clinical trials. Progression measurement is required for evaluation of change in health condition and the effect of drug treatment. Information about the location of emphysema progression within the lung may be important for the correct interpretation of drug efficacy, or for determining a treatment plan. The purpose of this study is therefore to develop and validate methods that enable the local measurement of lung density changes, which requires proper modeling of the effect of respiration on density. Methods: Four methods, all based on registration of baseline and follow-up chest CT scans, are compared. The first naïve method subtracts registered images. The second employs the so-called dry sponge model, where volume correction is performed using the determinant of the Jacobian of the transformation. The third and the fourth introduce a novel adaptation of the dry sponge model that circumvents its constant-mass assumption, which is shown to be invalid. The latter two methods require a third CT scan at a different inspiration level to estimate the patient-specific density-volume slope, where one method employs a global and the other a local slope. The methods were validated on CT scans of a phantom mimicking the lung, where mass and volume could be controlled. In addition, validation was performed on data of 21 patients with pulmonary emphysema. Results: The image registration method was optimized leaving a registration error below half the slice increment (median 1.0 mm). The phantom study showed that the locally adapted slope model most accurately measured local progression. The systematic error in estimating progression, as measured on the phantom data, was below 2 gr/l for a 70 ml (6%) volume difference, and 5 gr/l for a 210 ml (19%) difference, if volume correction was applied. On the patient data an underlying linearity assumption relating lung volume change with density change was shown to hold (fitR{sup 2} = 0.94), and globalized versions of the local models are consistent with global results (R{sup 2} of 0.865 and 0.882 for the two adapted slope models, respectively). Conclusions: In conclusion, image matching and subsequent analysis of differences according to the proposed lung models (i) has good local registration accuracy on patient data, (ii) effectively eliminates a dependency on inspiration level at acquisition time, (iii) accurately predicts progression in phantom data, and (iv) is reasonably consistent with global results in patient data. It is therefore a potential future tool for assessing local emphysema progression in drug evaluation trials and in clinical practice.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

SU-D-18A-07: Towards 6-Degree-Of-Freedom Real-Time Motion Management in Cancer Radiotherapy

Purpose: Lung tumor motion has been identified as a major issue that deteriorates treatment efficacy for radiotherapy, especially for SBRT. As tighter PTV margins are applied due to translational compensation, tumor rotation will become the dominant factor limiting tumor targeting accuracy. This is the world-first study quantifies lung tumor rotation by utilizing kV images with fiducial markers and a step towards 6-degree-of-freedom real-time cancer radiotherapy. Methods: Three or four gold coils were implanted as tumor surrogates in 3 lung cancer patients. 50 fractions of 8- minute, 10 Hz 4D CBCT projections were acquired for the patients immediately prior or after radiotherapy. The fiducial marker positions are segmented, reconstructed and used to determine tumour rotation by the iterative closest point algorithm. Different data acceptance and filtering methods were applied to accept data or smooth the marker trajectory. Results: The average rotation angles around the left/ right (LR), superior/inferior (SI), anterior/posterior (AP) rotations were found to be 0.8±4.2, -0.8±4.5 and 1.7±3.1 degrees respectively. For 28% of the treatment time, the lung tumors rotated more than 5° around the SI axis. Respiration-induced rotational motion was detected in 2 of the 3 lung patients. This can be explained by the patient developed atelectasis during the treatment period. Interestingly, no heart beating component of rotation was observed in the power spectrum. Different rotational types were observed within the patient cohort with large variations in the magnitude of the rotation between patients. Conclusions: For the first time, continuous tumor rotation has been measured for lung patients with gold fiducial markers. Tumors were found to undergo rotations of more than 5° for almost a third of the total treatment time. The study also demonstrated the feasibility of using continuously kV images for real-time lung tumour motion adaptive radiotherapy which can potentially reduce treatment margins and side effects. The authors acknowledge the financial support of an NHMRC Australia Fellowship.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

SU-E-J-89: Motion Effects On Organ Dose in Respiratory Gated Stereotactic Body Radiation Therapy

Purpose: Existing reports on gated radiation therapy focus mainly on optimizing dose delivery to the target structure. This work investigates the motion effects on radiation dose delivered to organs at risk (OAR) in respiratory gated stereotactic body radiation therapy (SBRT). A new algorithmic tool of dose analysis is developed to evaluate the optimality of gating phase for dose sparing on OARs while ensuring adequate target coverage. Methods: Eight patients with pancreatic cancer were treated on a phase I prospective study employing 4DCT-based SBRT. For each patient, 4DCT scans are acquired and sorted into 10 respiratory phases (inhale-exhale- inhale). Treatment planning is performed on the average CT image. The average CT is spatially registered to other phases. The resultant displacement field is then applied on the plan dose map to estimate the actual dose map for each phase. Dose values of each voxel are fitted to a sinusoidal function. Fitting parameters of dose variation, mean delivered dose and optimal gating phase for each voxel over respiration cycle are mapped on the dose volume. Results: The sinusoidal function accurately models the dose change during respiratory motion (mean fitting error 4.6%). In the eight patients, mean dose variation is 3.3 Gy on OARs with maximum of 13.7 Gy. Two patients have about 100cm{sup 3} volumes covered by more than 5 Gy deviation. The mean delivered dose maps are similar to plan dose with slight deformation. The optimal gating phase highly varies across the patient, with phase 5 or 6 on about 60% of the volume, and phase 0 on most of the rest. Conclusion: A new algorithmic tool is developed to conveniently quantify dose deviation on OARs from plan dose during the respiratory cycle. The proposed software facilitates the treatment planning process by providing the optimal respiratory gating phase for dose sparing on each OAR.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

SU-E-J-133: Evaluation of Inter- and Intra-Fractional Pancreas Tumor Residual Motions with Abdominal Compression

Purpose: Abdominal compression (AC) has been widely used to reduce pancreas motion due to respiration for pancreatic cancer patients undergoing stereotactic body radiotherapy (SBRT). However, the inter-fractional and intra-fractional patient motions may degrade the treatment. The purpose of this work is to study daily CBCT projections and 4DCT to evaluate the inter-fractional and intra-fractional pancreatic motions. Methods: As a standard of care at our institution, 4D CT scan was performed for treatment planning. At least two CBCT scans were performed for daily treatment. Retrospective studies were performed on patients with implanted internal fiducial markers or surgical clips. The initial motion pattern was obtained by extracting marker positions on every phase of 4D CT images. Daily motions were presented by marker positions on CBCT scan projection images. An adaptive threshold segmentation algorithm was used to extract maker positions. Both marker average positions and motion ranges were compared among three sets of scans, 4D CT, positioning CBCT, and conformal CBCT, for inter-fractional and intra-fractional motion variations. Results: Data from four pancreatic cancer patients were analyzed. These patients had three fiducial markers implanted. All patients were treated by an Elekta Synergy with single fraction SBRT. CBCT projections were acquired by XVI. Markers were successfully detected on most of the projection images. The inter-fractional changes were determined by 4D CT and the first CBCT while the intra-fractional changes were determined by multiple CBCT scans. It is found that the average motion range variations are within 2 mm, however, the average marker positions may drift by 6.5 mm. Conclusion: The patients respiratory motion variation for pancreas SBRT with AC was evaluated by detecting markers from CBCT projections and 4DCT, both the inter-fraction and intra-fraction motion range change is small but the drift of marker positions may be comparable to motion ranges.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

SU-E-T-133: Dosimetric Impact of Scan Orientation Relative to Target Motion During Spot Scanning Proton Therapy

Purpose: This study seeks to evaluate the dosimetric effects of intra-fraction motion during spot scanning proton beam therapy as a function of beam-scan orientation and target motion amplitude. Method: Multiple 4DCT scans were collected of a dynamic anthropomorphic phantom mimicking respiration amplitudes of 0 (static), 0.5, 1.0, and 1.5 cm. A spot-scanning treatment plan was developed on the maximum intensity projection image set, using an inverse-planning approach. Dynamic phantom motion was continuous throughout treatment plan delivery.The target nodule was designed to accommodate film and thermoluminescent dosimeters (TLD). Film and TLDs were uniquely labeled by location within the target. The phantom was localized on the treatment table using the clinically available orthogonal kV on-board imaging device. Film inserts provided data for dose uniformity; TLDs provided a 3% precision estimate of absolute dose. An inhouse script was developed to modify the delivery order of the beam spots, to orient the scanning direction parallel or perpendicular to target motion.TLD detector characterization and analysis was performed by the Imaging and Radiation Oncology Core group (IROC)-Houston. Film inserts, exhibiting a spatial resolution of 1mm, were analyzed to determine dose homogeneity within the radiation target. Results: Parallel scanning and target motions exhibited reduced target dose heterogeneity, relative to perpendicular scanning orientation. The average percent deviation in absolute dose for the motion deliveries relative to the static delivery was 4.9±1.1% for parallel scanning, and 11.7±3.5% (p<<0.05) for perpendicularly oriented scanning. Individual delivery dose deviations were not necessarily correlated to amplitude of motion for either scan orientation. Conclusions: Results demonstrate a quantifiable difference in dose heterogeneity as a function of scan orientation, more so than target amplitude. Comparison to the analyzed planar dose of a single field hint that multiple-field delivery alters intra-fraction beam-target motion synchronization and may mitigate heterogeneity, though further study is warranted.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

SU-E-T-350: Verification of Gating Performance of a New Elekta Gating Solution: Response Kit and Catalyst System

Purpose: In this work, we have tested the performance of new respiratory gating solutions for Elekta linacs. These solutions include the Response gating and the C-RAD Catalyst surface mapping system.Verification measurements have been performed for a series of clinical cases. We also examined the beam on latency of the system and its impact on delivery efficiency. Methods: To verify the benefits of tighter gating windows, a Quasar Respiratory Motion Platform was used. Its vertical-motion plate acted as a respiration surrogate and was tracked by the Catalyst system to generate gating signals. A MatriXX ion-chamber array was mounted on its longitudinal-moving platform. Clinical plans are delivered to a stationary and moving Matrix array at 100%, 50% and 30% gating windows and gamma scores were calculated comparing moving delivery results to the stationary result. It is important to note that as one moves to tighter gating windows, the delivery efficiency will be impacted by the linac's beam-on latency. Using a specialized software package, we generated beam-on signals of lengths of 1000ms, 600ms, 450ms, 400ms, 350ms and 300ms. As the gating windows get tighter, one can expect to reach a point where the dose rate will fall to nearly zero, indicating that the gating window is close to beam-on latency. A clinically useful gating window needs to be significantly longer than the latency for the linac. Results: As expected, the use of tighter gating windows improved delivery accuracy. However, a lower limit of the gating window, largely defined by linac beam-on latency, exists at around 300ms. Conclusion: The Response gating kit, combined with the C-RAD Catalyst, provides an effective solution for respiratorygated treatment delivery. Careful patient selection, gating window design, even visual/audio coaching may be necessary to ensure both delivery quality and efficiency. This research project is funded by Elekta.

07 ISOTOPE AND RADIATION SOURCES↗
DOE OSTI2015

SU-D-207-03: Development of 4D-CBCT Imaging System with Dual Source KV X-Ray Tubes

Purpose: The purposes of this work are to develop 4D-CBCT imaging system with orthogonal dual source kV X-ray tubes, and to determine the imaging doses from 4D-CBCT scans. Methods: Dual source kV X-ray tubes were used for the 4D-CBCT imaging. The maximum CBCT field of view was 200 mm in diameter and 150 mm in length, and the imaging parameters were 110 kV, 160 mA and 5 ms. The rotational angle was 105°, the rotational speed of the gantry was 1.5°/s, the gantry rotation time was 70 s, and the image acquisition interval was 0.3°. The observed amplitude of infrared marker motion during respiration was used to sort each image into eight respiratory phase bins. The EGSnrc/BEAMnrc and EGSnrc/DOSXYZnrc packages were used to simulate kV X-ray dose distributions of 4D-CBCT imaging. The kV X-ray dose distributions were calculated for 9 lung cancer patients based on the planning CT images with dose calculation grid size of 2.5 x 2.5 x 2.5 mm. The dose covering a 2-cc volume of skin (D2cc), defined as the inner 5 mm of the skin surface with the exception of bone structure, was assessed. Results: A moving object was well identified on 4D-CBCT images in a phantom study. Given a gantry rotational angle of 105° and the configuration of kV X-ray imaging subsystems, both kV X-ray fields overlapped at a part of skin surface. The D2cc for the 4D-CBCT scans was in the range 73.8–105.4 mGy. Linear correlation coefficient between the 1000 minus averaged SSD during CBCT scanning and D2cc was −0.65 (with a slope of −0.17) for the 4D-CBCT scans. Conclusion: We have developed 4D-CBCT imaging system with dual source kV X-ray tubes. The total imaging dose with 4D-CBCT scans was up to 105.4 mGy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

SU-E-T-439: Fundamental Verification of Respiratory-Gated Spot Scanning Proton Beam Therapy

Purpose: The spot-scanning proton beam irradiation with respiratory gating technique provides quite well dose distribution and requires both dosimetric and geometric verification prior to clinical implementation. The purpose of this study is to evaluate the impact of gating irradiation as a fundamental verification. Methods: We evaluated field width, flatness, symmetry, and penumbra in the gated and non-gated proton beams. The respiration motion was distinguished into 3 patterns: 10, 20, and 30 mm. We compared these contents between the gated and non-gated beams. A 200 MeV proton beam from PROBEAT-III unit (Hitachi Co.Ltd) was used in this study. Respiratory gating irradiation was performed by Quasar phantom (MODUS medical devices) with a combination of dedicated respiratory gating system (ANZAI Medical Corporation). For radiochromic film dosimetry, the calibration curve was created with Gafchromic EBT3 film (Ashland) on FilmQA Pro 2014 (Ashland) as film analysis software. Results: The film was calibrated at the middle of spread out Bragg peak in passive proton beam. The field width, flatness and penumbra in non-gated proton irradiation with respiratory motion were larger than those of reference beam without respiratory motion: the maximum errors of the field width, flatness and penumbra in respiratory motion of 30 mm were 1.75% and 40.3% and 39.7%, respectively. The errors of flatness and penumbra in gating beam (motion: 30 mm, gating rate: 25%) were 0.0% and 2.91%, respectively. The results of symmetry in all proton beams with gating technique were within 0.6%. Conclusion: The field width, flatness, symmetry and penumbra were improved with the gating technique in proton beam. The spot scanning proton beam with gating technique is feasible for the motioned target.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

SU-E-T-503: Intensity Modulated Proton Therapy (IMPT) Versus Intensity Modulated X-Ray Therapy (IMRT) for Patient with Hepatocellular Carcinoma: A Dosimetric Comparison

Purpose This study compares the dosimetric parameters in treatment of unresectable hepatocellular carcinoma between intensity modulated proton therapy (IMPT) and intensity modulated x-ray radiation therapy (IMRT). Methods and Materials: We studied four patients treated at our institution. All patients were simulated supine with 4D-CT using a GE light speed simulator with a maximum slice thickness of 3mm. The average CT and an internal target volume to account for respiration motion were used for planning. Both IMRT and IMPT plans were created using Elekta’s CMSXiO treatment planning system (TPS). The prescription dose was 58.05 CGE in 15 fractions. The IMRT plans had five beams with combination of co-planar and non-co-planar. The IMPT plans had 2 to 3 beams. Dose comparison was performed based on the averaged results of the four patients. Results The mean dose and V95% to PTV were 58.24CGE, 98.57% for IMPT, versus 57.34CGE and 96.68% for IMRT, respectively. The V10, V20, V30 and mean dose of the normal liver for IMPT were 23.10%, 18.61%, 13.75% and 9.78 CGE; and 47.19%, 37.55%, 22.73% and 17.12CGE for IMRT. The spinal cord didn’t receive any dose in IMPT technique, but received a maximum of 18.77CGE for IMRT. The IMPT gave lower maximum dose to the stomach as compared to IMRT (19.26 vs 26.35CGE). V14 for left and right kidney was 0% and 2.32% for IMPT and 3.89% and 29.54% for IMRT. The mean dose, V35, V40 and V45 for small bowl were similar in both techniques, 0.74CGE, 6.27cc, 4.85cc and 3.53 cc for IMPT, 3.47CGE, 9.73cc, 7.61cc 5.35cc for IMRT. Conclusion Based on this study, IMPT plans gave less dose to the critical structures such as normal liver, kidney, stomach and spinal cord as compared to IMRT plans, potentially leading to less toxicity and providing better quality of life for patients.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

SU-E-T-755: Timing Characteristics of Proton and Carbon Ion Treatments Using a Synchrotron and Modulated Scanning

Purpose: The time required to deliver a treatment impacts not only the number of patients that can be treated each day but also the accuracy of delivery due to potential movements of patient tissues. Both macroscopic and microscopic timing characteristics of a beam delivery system were studied to examine their impacts on patient treatments. Methods: 35 patients were treated during a clinical trial to demonstrate safety and efficacy of a Siemens Iontris system prior to receiving approval from the Chinese Food and Drug Administration. The system has a variable cycle time and can provide proton beams from 48 to 221 MeV/n and carbon ions from 86 to 430 MeV/n. A modulated scanning beam delivery technique is used where the beam remains stationary at each spot aiming location and is not turned off while the spot quickly moves from one aiming location to the next. The treatment log files for 28 of the trial patients were analyzed to determine several timing characteristics. Results: The average portal time per target dose was 172.5 s/Gy for protons and 150.7 s/Gy for carbon ions. The maximum delivery time for any portal was less than 300 s. The average dwell time per spot was 12 ms for protons and 3.0 ms for carbon ions. The number of aiming positions per energy layer varied from 1 to 258 for protons and 1 to 621 for carbon ions. The average spill time and cycle time per energy layer were 1.20 and 2.68 s for protons and 0.95 and 4.73 s for carbon ions respectively. For 3 of the patients, the beam was gated on and off to reduce the effects of respiration. Conclusion: For a typical target volume of 153 cc as used in this clinical trial, the portal delivery times were acceptable.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

TU-E-213-03: Tools for Ensuring Quality and Safety

Purpose: To develop the first 4D robust optimization (RO) method accounting for respiratory motion and evaluate its potential to improve plan robustness and optimality compared to 3D RO and PTV-based optimization. Methods: A set of 4D CT images are used to track respiratory motion and deformation of tumors and organs. For each of 10 respiration phases, dose distributions for nine different uncertainty scenarios including the nominal one, those incorporating ±5mm setup uncertainties long x, y and z directions and ±3.5% range uncertainties are calculated. All 90 dose distributions are simultaneously optimized to achieve full dose coverage of 10 CTVs and sparing of normal structures. ITV-based 3D RO and PTV-based optimization based on the average CT are also carried for the same patient using same dose volume constrains. After optimization, 4D robustness evaluation was performed for all resulting plans. The CTV coverage and the sparing of normal tissue in 10 phases are evaluated and compared among the three methods. The widths of DVH bands represent the robustness of dose distributions in the structures. Results: For one patient studied so far, the worst case CTV coverage by the prescription dose among all 90 scenarios is: 99% for 4D RO; 88.9% for 3D RO, and 85.2% for PTV based optimization. 4D RO also results in best robustness with the narrowest DVH’ bandwidths for the CTV. 4D and 3D RO have similar organ sparing while PTV based optimization results in worst organ sparing. Conclusion: 4D robust optimization which accounts for anatomy motion and deformation in the optimization process, significantly improves plan robustness and achieves higher quality treatment plans for lung cancer patients. The method is being evaluated for multiple patients with different tumor and motion characteristics.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

WE-EF-303-05: Development and Commissioning of Real-Time Imaging Function for Respiratory-Gated Spot-Scanning Proton Beam Therapy

Purpose: To realize real-time-image gated proton beam therapy (RGPT) for treating mobile tumors. Methods: The rotating gantry of spot scanning proton beam therapy has been designed to equip two x-ray fluoroscopy devices that enable real-time imaging of the internal fiducial markers during respiration. Three-dimensional position of the fiducial marker located near the tumor can be calculated from the fluoroscopic images obtained from orthogonal directions and therapeutic beam is gated only when the fiducial marker is within the predefined gating window. Image acquisition rate can be selected from discrete value ranging from 0.1 Hz to 30 Hz. In order to confirm the effectiveness of RGPT and apply it clinically, clinical commissioning was conducted. Commissioning tests were categorized to main three parts including geometric accuracy, temporal accuracy and dosimetric evaluation. Results: Developed real-time imaging function has been installed and its basic performances have been confirmed. In the evaluation of geometric accuracy, coincidence of three-dimensional treatment room coordinate system and imaging coordinate system was confirmed to be less than 1 mm. Fiducial markers (gold sphere and coil) were able to be tracked in simulated clinical condition using an anthropomorphic chest phantom. In the evaluation of temporal accuracy, latency from image acquisition to gate on/off signal was about 60 msec in typical case. In dosimetric evaluation, treatment beam characteristics including beam irradiation position and dose output were stable in gated irradiation. Homogeneity indices to the mobile target were 0.99 (static), 0.89 (w/o gating, motion is parallel to direction of scan), 0.75 (w/o gating, perpendicular), 0.98 (w/ gating, parallel) and 0.93 (w/ gating, perpendicular). Dose homogeneity to the mobile target can be maintained in RGPT. Conclusion: Real-time imaging function utilizing x-ray fluoroscopy has been developed and commissioned successfully in order to realize RGPT. Funding Support: This research was partially supported by Japan Society for the Promotion of Science (JSPS) through the FIRST Program. Conflict of Interest: Prof. Shirato has research fund from Hitachi Ltd, Mitsubishi Heavy Industries Ltd and Shimadzu Corporation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Dosimetric verification of lung cancer treatment using the CBCTs estimated from limited-angle on-board projections

Purpose: Lung cancer treatment is susceptible to treatment errors caused by interfractional anatomical and respirational variations of the patient. On-board treatment dose verification is especially critical for the lung stereotactic body radiation therapy due to its high fractional dose. This study investigates the feasibility of using cone-beam (CB)CT images estimated by a motion modeling and free-form deformation (MM-FD) technique for on-board dose verification. Methods: Both digital and physical phantom studies were performed. Various interfractional variations featuring patient motion pattern change, tumor size change, and tumor average position change were simulated from planning CT to on-board images. The doses calculated on the planning CT (planned doses), the on-board CBCT estimated by MM-FD (MM-FD doses), and the on-board CBCT reconstructed by the conventional Feldkamp-Davis-Kress (FDK) algorithm (FDK doses) were compared to the on-board dose calculated on the “gold-standard” on-board images (gold-standard doses). The absolute deviations of minimum dose (ΔD{sub min}), maximum dose (ΔD{sub max}), and mean dose (ΔD{sub mean}), and the absolute deviations of prescription dose coverage (ΔV{sub 100%}) were evaluated for the planning target volume (PTV). In addition, 4D on-board treatment dose accumulations were performed using 4D-CBCT images estimated by MM-FD in the physical phantom study. The accumulated doses were compared to those measured using optically stimulated luminescence (OSL) detectors and radiochromic films. Results: Compared with the planned doses and the FDK doses, the MM-FD doses matched much better with the gold-standard doses. For the digital phantom study, the average (± standard deviation) ΔD{sub min}, ΔD{sub max}, ΔD{sub mean}, and ΔV{sub 100%} (values normalized by the prescription dose or the total PTV) between the planned and the gold-standard PTV doses were 32.9% (±28.6%), 3.0% (±2.9%), 3.8% (±4.0%), and 15.4% (±12.4%), respectively. The corresponding values of FDK PTV doses were 1.6% (±1.9%), 1.2% (±0.6%), 2.2% (±0.8%), and 17.4% (±15.3%), respectively. In contrast, the corresponding values of MM-FD PTV doses were 0.3% (±0.2%), 0.9% (±0.6%), 0.6% (±0.4%), and 1.0% (±0.8%), respectively. Similarly, for the physical phantom study, the average ΔD{sub min}, ΔD{sub max}, ΔD{sub mean}, and ΔV{sub 100%} of planned PTV doses were 38.1% (±30.8%), 3.5% (±5.1%), 3.0% (±2.6%), and 8.8% (±8.0%), respectively. The corresponding values of FDK PTV doses were 5.8% (±4.5%), 1.6% (±1.6%), 2.0% (±0.9%), and 9.3% (±10.5%), respectively. In contrast, the corresponding values of MM-FD PTV doses were 0.4% (±0.8%), 0.8% (±1.0%), 0.5% (±0.4%), and 0.8% (±0.8%), respectively. For the 4D dose accumulation study, the average (± standard deviation) absolute dose deviation (normalized by local doses) between the accumulated doses and the OSL measured doses was 3.3% (±2.7%). The average gamma index (3%/3 mm) between the accumulated doses and the radiochromic film measured doses was 94.5% (±2.5%). Conclusions: MM-FD estimated 4D-CBCT enables accurate on-board dose calculation and accumulation for lung radiation therapy. It can potentially be valuable for treatment quality assessment and adaptive radiation therapy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SIFT-based dense pixel tracking on 0.35 T cine-MR images acquired during image-guided radiation therapy with application to gating optimization

Purpose: To first demonstrate the viability of applying an image processing technique for tracking regions on low-contrast cine-MR images acquired during image-guided radiation therapy, and then outline a scheme that uses tracking data for optimizing gating results in a patient-specific manner. Methods: A first-generation MR-IGRT system—treating patients since January 2014—integrates a 0.35 T MR scanner into an annular gantry consisting of three independent Co-60 sources. Obtaining adequate frame rates for capturing relevant patient motion across large fields-of-view currently requires coarse in-plane spatial resolution. This study initially (1) investigate the feasibility of rapidly tracking dense pixel correspondences across single, sagittal plane images (with both moderate signal-to-noise and spatial resolution) using a matching objective for highly descriptive vectors called scale-invariant feature transform (SIFT) descriptors associated to all pixels that describe intensity gradients in local regions around each pixel. To more accurately track features, (2) harmonic analysis was then applied to all pixel trajectories within a region-of-interest across a short training period. In particular, the procedure adjusts the motion of outlying trajectories whose relative spectral power within a frequency bandwidth consistent with respiration (or another form of periodic motion) does not exceed a threshold value that is manually specified following the training period. To evaluate the tracking reliability after applying this correction, conventional metrics—including Dice similarity coefficients (DSCs), mean tracking errors (MTEs), and Hausdorff distances (HD)—were used to compare target segmentations obtained via tracking to manually delineated segmentations. Upon confirming the viability of this descriptor-based procedure for reliably tracking features, the study (3) outlines a scheme for optimizing gating parameters—including relative target position and a tolerable margin about this position—derived from a probability density function that is constructed using tracking results obtained just prior to treatment. Results: The feasibility of applying the matching objective for SIFT descriptors toward pixel-by-pixel tracking on cine-MR acquisitions was first retrospectively demonstrated for 19 treatments (spanning various sites). Both with and without motion correction based on harmonic analysis, sub-pixel MTEs were obtained. A mean DSC value spanning all patients of 0.916 ± 0.001 was obtained without motion correction, with DSC values exceeding 0.85 for all patients considered. While most patients show accurate tracking without motion correction, harmonic analysis does yield substantial gain in accuracy (defined using HDs) for three particularly challenging subjects. An application of tracking toward a gating optimization procedure was then demonstrated that should allow a physician to balance beam-on time and tissue sparing in a patient-specific manner by tuning several intuitive parameters. Conclusions: Tracking results show high fidelity in assessing intrafractional motion observed on cine-MR acquisitions. Incorporating harmonic analysis during a training period improves the robustness of the tracking for challenging targets. The concomitant gating optimization procedure should allow for physicians to quantitatively assess gating effectiveness quickly just prior to treatment in a patient-specific manner.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2016

SU-D-207A-05: Investigating Sparse-Sampled MRI for Motion Management in Thoracic Radiotherapy

Purpose: Sparse sampling and reconstruction-based MRI techniques represent an attractive strategy to achieve sufficiently high image acquisition speed while maintaining image quality for the task of radiotherapy guidance. In this study, we examine rapid dynamic MRI using a sparse sampling sequence k-t BLAST in capturing motion-induced, cycle-to-cycle variations in tumor position. We investigate the utility of long-term MRI-based motion monitoring as a means of better characterizing respiration-induced tumor motion compared to a single-cycle 4DCT. Methods: An MRI-compatible, programmable, deformable lung motion phantom with eleven 1.5 ml water marker tubes was placed inside a 3.0 T whole-body MR scanner (Philips Ingenia). The phantom was programmed with 10 lung tumor motion traces previously recorded using the Synchrony system. 2D+t image sequences of a coronal slice were acquired using a balanced-SSFP sequence combined with k-t BLAST (accn=3, resolution=0.66×0.66×5 mm3; acquisition time = 110 ms/slice). kV fluoroscopic (ground truth) and 4DCT imaging was performed with the same phantom setup and motion trajectories. Marker positions in all three modalities were segmented and tracked using an opensource deformable image registration package, NiftyReg. Results: Marker trajectories obtained from rapid MRI exhibited <1 mm error compared to kv Fluoro trajectories in the presence of complex motion including baseline shifts and changes in respiratory amplitude, indicating the ability of MRI to monitor motion with adequate geometric fidelity for the purpose of radiotherapy guidance. In contrast, the trajectory derived from 4DCT exhibited significant errors up to 6 mm due to cycle-to-cycle variations and baseline shifts. Consequently, 4DCT was found to underestimate the range of marker motion by as much as 50%. Conclusion: Dynamic MRI is a promising tool for radiotherapy motion management as it permits for longterm, dose-free, soft-tissue-based monitoring of motion, yielding richer and more accurate information about tumor position and motion range compared to the current state-of-the-art, 4DCT. This work was partially supported through research funding from National Institutes of Health (R01CA169102).

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-D-207A-06: Pediatric Abdominal Organ Motion Quantified Via a Novel 4D MRI Method

Purpose: To develop a 4D MRI method for assessing respiration-induced abdominal organ motion in children receiving radiation therapy. Methods: A 4D MRI using internal image-based respiratory surrogate has been developed and implemented on a clinical scanner (1.5T Siemens Avanto). Ten patients (younger group: N=6, 2–5 years, anesthetized; older group: N=4, 11–15 years) with neuroblastoma, Wilm’s tumor rhabdomyosarcoma, or desmoplastic small round cell tumor received free breathing 4D MRI scans for treatment planning. Coronal image slices of the entire abdomen were retrospectively constructed in 10 respiratory phases. A B-spline deformable registration (Metz et al. 2011) was performed on 4D datasets to automatically derive motion trajectories of selected anatomical landmarks, including the dome and the center of the liver, and the superior edges of kidneys and spleen. The extents of the motion in three dimensions (anteroposterior, AP; mediolateral, ML; superoinferior, SI) and the correlations between organ motion trajectories were quantified. Results: The 4D MRI scans were successfully performed in <20 minutes for all patients without the use of any external device. Organ motion extents were larger in adolescents (kidneys: 3–13 mm SI, liver and spleen: 6–18 mm SI) than in younger children (kidneys:<3mm in all directions; liver and spleen: 1–8 mm SI, 1–5 mm ML and AP). The magnitude of respiratory motion in some adolescents may warrant special motion management. Motion trajectories were not synchronized across selected anatomical landmarks, particularly in the ML and AP directions, indicating inter- and intra-organ variations of the respiratory-induced motion. Conclusion: The developed 4D MRI acquisition and motion analysis methods provide a non-ionizing, non-invasive approach to automatically measure the organ motion trajectory in the pediatric abdomen. It is useful for defining ITV and PRV, monitoring changes in target motion patterns during the treatment course, and studying interplay effects in proton scanning.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-F-I-11: Software Development for 4D-CBCT Research of Real-Time-Image Gated Spot Scanning Proton Therapy

Purpose: To acquire correct information for inside the body in patient positioning of Real-time-image Gated spot scanning Proton Therapy (RGPT), utilization of tomographic image at exhale phase of patient respiration obtained from 4-dimensional Cone beam CT (4D-CBCT) has been desired. We developed software named “Image Analysis Platform” for 4D-CBCT researches which has technique to segment projection-images based on 3D marker position in the body. The 3D marker position can be obtained by using two axes CBCT system at Hokkaido University Hospital Proton Therapy Center. Performance verification of the software was implemented. Methods: The software calculates 3D marker position retrospectively by using matching positions on pair projection-images obtained by two axes fluoroscopy mode of CBCT system. Log data of 3D marker tracking are outputted after the tracking. By linking the Log data and gantry-angle file of projection-image, all projection-images are equally segmented to spatial five-phases according to marker 3D position of SI direction and saved to specified phase folder. Segmented projection-images are used for CBCT reconstruction of each phase. As performance verification of the software, test of segmented projection-images was implemented for sample CT phantom (Catphan) image acquired by two axes fluoroscopy mode of CBCT. Dummy marker was added on the images. Motion of the marker was modeled to move in 3D space. Motion type of marker is sin4 wave function has amplitude 10.0 mm/5.0 mm/0 mm, cycle 4 s/4 s/0 s for SI/AP/RL direction. Results: The marker was tracked within 0.58 mm accuracy in 3D for all images, and it was confirmed that all projection-images were segmented and saved to each phase folder correctly. Conclusion: We developed software for 4D-CBCT research which can segment projection-image based on 3D marker position. It will be helpful to create high quality of 4D-CBCT reconstruction image for RGPT.

60 APPLIED LIFE SCIENCES↗