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Dosimetric comparison of lung stereotactic body radiotherapy treatment plans using averaged computed tomography and end-exhalation computed tomography images: Evaluation of the effect of different dose-calculation algorithms and prescription methods

The purpose of this article is to quantitatively evaluate differences in dose distributions calculated using various computed tomography (CT) datasets, dose-calculation algorithms, and prescription methods in stereotactic body radiotherapy (SBRT) for patients with early-stage lung cancer. Data on 29 patients with early-stage lung cancer treated with SBRT were retrospectively analyzed. Averaged CT (Ave-CT) and expiratory CT (Ex-CT) images were reconstructed for each patient using 4-dimensional CT data. Dose distributions were initially calculated using the Ave-CT images and recalculated (in the same monitor units [MUs]) by employing Ex-CT images with the same beam arrangements. The dose-volume parameters, including D{sub 95}, D{sub 90}, D{sub 50}, and D{sub 2} of the planning target volume (PTV), were compared between the 2 image sets. To explore the influence of dose-calculation algorithms and prescription methods on the differences in dose distributions evident between Ave-CT and Ex-CT images, we calculated dose distributions using the following 3 different algorithms: x-ray Voxel Monte Carlo (XVMC), Acuros XB (AXB), and the anisotropic analytical algorithm (AAA). We also used 2 different dose-prescription methods; the isocenter prescription and the PTV periphery prescription methods. All differences in PTV dose-volume parameters calculated using Ave-CT and Ex-CT data were within 3 percentage points (%pts) employing the isocenter prescription method, and within 1.5%pts using the PTV periphery prescription method, irrespective of which of the 3 algorithms (XVMC, AXB, and AAA) was employed. The frequencies of dose-volume parameters differing by >1%pt when the XVMC and AXB were used were greater than those associated with the use of the AAA, regardless of the dose-prescription method employed. All differences in PTV dose-volume parameters calculated using Ave-CT and Ex-CT data on patients who underwent lung SBRT were within 3%pts, regardless of the dose-calculation algorithm or the dose-prescription method employed.

61 RADIATION PROTECTION AND DOSIMETRY↗

Physiologically guided approach to characterizing respiratory motion

Purpose: To characterize radiation therapy patient breathing patterns based on measured external surrogate information. Methods: Breathing surrogate data were collected during 4DCT from a cohort of 50 patients including 28 patients with lung cancer and 22 patients without lung cancer. A spirometer and an abdominal pneumatic bellows were used as the surrogates. The relationship between these measurements was assumed to be linear within a small phase difference. The signals were correlated and drift corrected using a previously published method to convert the signal into tidal volume. The airflow was calculated with a first order time derivative of the tidal volume using a window centered on the point of interest and with a window length equal to the CT gantry rotation period. The airflow was compared against the tidal volume to create ellipsoidal patterns that were binned into 25 ml × 25 ml/s bins to determine the relative amount of time spent in each bin. To calculate the variability of the maximum inhalation tidal volume within a free-breathing scan timeframe, a metric based on percentile volume ratios was defined. The free breathing variability metric (κ) was defined as the ratio between extreme inhalation tidal volumes (defined as >93 tidal volume percentile of the measured tidal volume) and normal inhalation tidal volume (defined as >80 tidal volume percentile of the measured tidal volume). Results: There were three observed types of volume-flow curves, labeled Types 1, 2, and 3. Type 1 patients spent a greater duration of time during exhalation withκ = 1.37 ± 0.11. Type 2 patients had equal time duration spent during inhalation and exhalation with κ = 1.28 ± 0.09. The differences between the mean peak exhalation to peak inhalation tidal volume, breathing period, and the 85th tidal volume percentile for Type 1 and Type 2 patients were statistically significant at the 2% significance level. The difference between κ and the 98th tidal volume percentile for Type 1 and Type 2 patients was found to be statistically significant at the 1% significance level. Three patients did not display a breathing stability curve that could be classified as Type 1 or Type 2 due to chaotic breathing patterns. These patients were classified as Type 3 patients. Conclusions: Based on an observed volume-flow curve pattern, the cohort of 50 patients was divided into three categories called Type 1, Type 2, and Type 3. There were statistically significant differences in breathing characteristics between Type 1 and Type 2 patients. The use of volume-flow curves to classify patients has been demonstrated as a physiological characterization metric that has the potential to optimize gating windows in radiation therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

TU-A-12A-01: Consistency of Lung Expansion and Contraction During Respiration: Implications for Quantitative Imaging

Purpose: Four-dimensional computed tomography (4DCT) can be used to evaluate longitudinal changes in pulmonary function. The sensitivity of such measurements to identify function change may be improved with reproducible breathing patterns. The purpose of this study was to determine if inhale was more consistent than exhale, i.e., lung expansion during inhalation compared to lung contraction during exhalation. Methods: Repeat 4DCT image data acquired within a short time interval from 8 patients. Using a tissue volume preserving deformable image registration algorithm, Jacobian ventilation maps in two scanning sessions were computed and compared on the same coordinate for reproducibility analysis. Equivalent lung volumes (ELV) were used for 5 subjects and equivalent title volumes (ETV) for the 3 subjects who experienced a baseline shift between scans. In addition, gamma pass rate was calculated from a modified gamma index evaluation between two ventilation maps, using acceptance criterions of 2mm distance-to-agreement and 5% ventilation difference. The gamma pass rates were then compared using paired t-test to determine if there was a significant difference. Results: Inhalation was more reproducible than exhalation. In the 5 ELV subjects 78.5% of the lung voxels met the gamma criteria for expansion during inhalation when comparing the two scans, while significantly fewer (70.9% of the lung voxels) met the gamma criteria for contraction during exhalation (p = .027). In the 8 total subjects analyzed the average gamma pass rate for expansion during inhalation was 75.2% while for contraction during exhalation it was 70.3%; which trended towards significant (p = .064). Conclusion: This work implies inhalation is more reproducible than exhalation, when equivalent respiratory volumes are considered. The reason for this difference is unknown. Longitudinal investigation of pulmonary function change based on inhalation images appears appropriate for Jacobian-based measure of lung tissue expansion. NIH Grant: R01 CA166703.

60 APPLIED LIFE SCIENCES↗

A planning study investigating dual-gated volumetric arc stereotactic treatment of primary renal cell carcinoma

This is a planning study investigating the dosimetric advantages of gated volumetric-modulated arc therapy (VMAT) to the end-exhale and end-inhale breathing phases for patients undergoing stereotactic treatment of primary renal cell carcinoma. VMAT plans were developed from the end-inhale (VMATinh) and the end-exhale (VMATexh) phases of the breathing cycle as well as a VMAT plan and 3-dimensional conformal radiation therapy plan based on an internal target volume (ITV) (VMATitv). An additional VMAT plan was created by giving the respective gated VMAT plan a 50% weighting and summing the inhale and exhale plans together to create a summed gated plan. Dose to organs at risk (OARs) as well as comparison of intermediate and low-dose conformity was evaluated. There was no difference in the volume of healthy tissue receiving the prescribed dose for the planned target volume (PTV) (CI100%) for all the VMAT plans; however, the mean volume of healthy tissue receiving 50% of the prescribed dose for the PTV (CI50%) values were 4.7 (± 0.2), 4.6 (± 0.2), and 4.7 (± 0.6) for the VMATitv, VMATinh, and VMATexh plans, respectively. The VMAT plans based on the exhale and inhale breathing phases showed a 4.8% and 2.4% reduction in dose to 30 cm{sup 3} of the small bowel, respectively, compared with that of the ITV-based VMAT plan. The summed gated VMAT plans showed a 6.2% reduction in dose to 30 cm{sup 3} of the small bowel compared with that of the VMAT plans based on the ITV. Additionally, when compared with the inhale and the exhale VMAT plans, a 4% and 1.5%, respectively, reduction was observed. Gating VMAT was able to reduce the amount of prescribed, intermediate, and integral dose to healthy tissue when compared with VMAT plans based on an ITV. When summing the inhale and exhale plans together, dose to healthy tissue and OARs was optimized. However, gating VMAT plans would take longer to treat and is a factor that needs to be considered.

61 RADIATION PROTECTION AND DOSIMETRY↗

SU-E-J-236: Audiovisual Biofeedback Improves Breath-Hold Lung Tumor Position Reproducibility Measured with 4D MRI

Purpose: Audiovisual biofeedback breath-hold (AVBH) was employed to reproduce tumor position on inhale and exhale breath-holds for 4D tumor information. We hypothesize that lung tumor position will be more consistent using AVBH compared with conventional breath-hold (CBH). Methods: Lung tumor positions were determined for seven lung cancer patients (age: 25 – 74) during to two separate 3T MRI sessions. A breathhold training session was performed prior to the MRI sessions to allow patients to become comfortable with AVBH and their exhale and inhale target positions. CBH and AVBH 4D image datasets were obtained in the first MRI session (pre-treatment) and the second MRI session (midtreatment) within six weeks of the first session. Audio-instruction (MRI: Siemens Skyra) in CBH and verbal-instruction (radiographer) in AVBH were used. A radiation oncologist contoured the lung tumor using Eclipse (Varian Medical Systems); tumor position was quantified as the centroid of the contoured tumor after rigid registration based on vertebral anatomy across two MRI sessions. CBH and AVBH were compared in terms of the reproducibility assessed via (1) the difference between the two exhale positions for the two sessions and the two inhale positions for the sessions. (2) The difference in amplitude (exhale to inhale) between the two sessions. Results: Compared to CBH, AVBH improved the reproducibility of two exhale (or inhale) lung tumor positions relative to each other by 33%, from 6.4±5.3 mm to 4.3±3.0 mm (p=0.005). Compared to CBH, AVBH improved the reproducibility of exhale and inhale amplitude by 66%, from 5.6±5.9 mm to 1.9±1.4 mm (p=0.005). Conclusions: This study demonstrated that audiovisual biofeedback can be utilized for improving the reproducibility of breath-hold lung tumor position. These results are advantageous towards achieving more accurate emerging radiation treatment planning methods, in addition to imaging and treatment modalities utilizing breath-hold procedures.

60 APPLIED LIFE SCIENCES↗

TH-CD-207A-04: Optimized Respiratory Gating for Abnormal Breathers in Pancreatic SBRT

Purpose: Pancreatic SBRT is uniquely challenging due to both the erratic/unstable motion of the pancreas and the close proximity of the radiosensitive small bowel. Respiratory gating can mitigate this effect, but the irregularity of motion severely affects traditional phase-based gating. The purpose of this study was to analyze real-time motion data of pancreatic tumors to optimize the efficacy and accuracy of respiratory gating, with the overall goal of enabling dose escalated pancreatic SBRT. Methods: Fifteen pancreatic SBRT patients received 30–33 Gy in 5 fractions on a Varian TrueBeam STx unit. Abdominal compression was used to reduce the amplitude of tumor motion, and daily cone-beam computed tomography (CBCT) scans were acquired prior to each treatment for target localization purposes. For this study, breathing data (phase and amplitude) were collected during each CBCT scan using Varian’s Real-Time Position Management system. An in-house template matching technique was used to track the superior-inferior motion of implanted fiducial markers in CBCT projection images. Using tumor motion and breathing data, phase-based or amplitude-based respiratory gating was simulated for all 75 fractions, targeting either end-exhalation or end-inhalation phases of breathing. Results: For the average patient, gating at end-exhalation offered the best reductions in effective motion for equal duty cycles. However, optimal central phase angle varied widely (range: 0–92%, mean±SD: 49±12%), and phase-based gating windows typically associated with end-exhalation (i.e., “30–70%”) were rarely ideal. Amplitude-based gating significantly outperformed phase-based gating, with average effective ranges for amplitude-based gating 25% lower than phase-based gating ranges (as much as 73% lower). Amplitude-based gating was consistently better suited to accommodate abnormal breathing patterns. For both phase-based and amplitude-based gating, end-exhalation provided significantly better results than end-inhalation. Conclusion: Amplitude-based gating reliably outperformed phase-based gating, and end-exhalation was more suitable than end-inhalation. These results will be used to guide future dose-escalation trials. Research funding provided by Varian Medical Systems to Miften and Jones.

60 APPLIED LIFE SCIENCES↗

MO-FG-BRA-08: Swarm Intelligence-Based Personalized Respiratory Gating in Lung SAbR

Purpose: Respiratory gating is widely deployed as a clinical motion-management strategy in lung radiotherapy. In conventional gating, the beam is turned on during a pre-determined phase window; typically, around end-exhalation. In this work, we challenge the notion that end-exhalation is always the optimal gating phase. Specifically, we use a swarm-intelligence-based, inverse planning approach to determine the optimal respiratory phase and MU for each beam with respect to (i) the state of the anatomy at each phase and (ii) the time spent in that state, estimated from long-term monitoring of the patient’s breathing motion. Methods: In a retrospective study of five lung cancer patients, we compared the dosimetric performance of our proposed personalized gating (PG) with that of conventional end-of-exhale gating (CEG) and a previously-developed, fully 4D-optimized plan (combined with MLC tracking delivery). For each patient, respiratory phase probabilities (indicative of the time duration of the phase) were estimated over 2 minutes from lung tumor motion traces recorded previously using the Synchrony system (Accuray Inc.). Based on this information, inverse planning optimization was performed to calculate the optimal respiratory gating phase and MU for each beam. To ensure practical deliverability, each PG beam was constrained to deliver the assigned MU over a time duration comparable to that of CEG delivery. Results: Maximum OAR sparing for the five patients achieved by the PG and the 4D plans compared to CEG plans was: Esophagus Dmax [PG:57%, 4D:37%], Heart Dmax [PG:71%, 4D:87%], Spinal cord Dmax [PG:18%, 4D:68%] and Lung V13 [PG:16%, 4D:31%]. While patients spent the most time in exhalation, the PG-optimization chose end-exhale only for 28% of beams. Conclusion: Our novel gating strategy achieved significant dosimetric improvements over conventional gating, and approached the upper limit represented by fully 4D optimized planning while being significantly simpler and more clinically translatable. This work was partially supported through research funding from National Institutes of Health (R01CA169102) and Varian Medical Systems, Palo Alto, CA, USA.

60 APPLIED LIFE SCIENCES↗

Dose Escalated Liver Stereotactic Body Radiation Therapy at the Mean Respiratory Position

Purpose: The dosimetric impact of dose probability based planning target volume (PTV) margins for liver cancer patients receiving stereotactic body radiation therapy (SBRT) was compared with standard PTV based on the internal target volume (ITV). Plan robustness was evaluated by accumulating the treatment dose to ensure delivery of the intended plan. Methods and Materials: Twenty patients planned on exhale CT for 27 to 50 Gy in 6 fractions using an ITV-based PTV and treated free-breathing were retrospectively evaluated. Isotoxic, dose escalated plans were created on midposition computed tomography (CT), representing the mean breathing position, using a dose probability PTV. The delivered doses were accumulated using biomechanical deformable registration of the daily cone beam CT based on liver targeting at the exhale or mean breathing position, for the exhale and midposition CT plans, respectively. Results: The dose probability PTVs were on average 38% smaller than the ITV-based PTV, enabling an average ± standard deviation increase in the planned dose to 95% of the PTV of 4.0 ± 2.8 Gy (9 ± 5%) on the midposition CT (P<.01). For both plans, the delivered minimum gross tumor volume (GTV) doses were greater than the planned nominal prescribed dose in all 20 patients and greater than the planned dose to 95% of the PTV in 18 (90%) patients. Nine patients (45%) had 1 or more GTVs with a delivered minimum dose more than 5 Gy higher with the midposition CT plan using dose probability PTV, compared with the delivered dose with the exhale CT plan using ITV-based PTV. Conclusions: For isotoxic liver SBRT planned and delivered at the mean respiratory, reduced dose probability PTV enables a mean escalation of 4 Gy (9%) in 6 fractions over ITV-based PTV. This may potentially improve local control without increasing the risk of tumor underdosing.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Impact of CT attenuation correction method on quantitative respiratory-correlated (4D) PET/CT imaging

Purpose: Respiratory-correlated positron emission tomography (PET/CT) 4D PET/CT is used to mitigate errors from respiratory motion; however, the optimal CT attenuation correction (CTAC) method for 4D PET/CT is unknown. The authors performed a phantom study to evaluate the quantitative performance of CTAC methods for 4D PET/CT in the ground truth setting. Methods: A programmable respiratory motion phantom with a custom movable insert designed to emulate a lung lesion and lung tissue was used for this study. The insert was driven by one of five waveforms: two sinusoidal waveforms or three patient-specific respiratory waveforms. 3DPET and 4DPET images of the phantom under motion were acquired and reconstructed with six CTAC methods: helical breath-hold (3DHEL), helical free-breathing (3DMOT), 4D phase-averaged (4DAVG), 4D maximum intensity projection (4DMIP), 4D phase-matched (4DMATCH), and 4D end-exhale (4DEXH) CTAC. Recovery of SUV{sub max}, SUV{sub mean}, SUV{sub peak}, and segmented tumor volume was evaluated as RC{sub max}, RC{sub mean}, RC{sub peak}, and RC{sub vol}, representing percent difference relative to the static ground truth case. Paired Wilcoxon tests and Kruskal–Wallis ANOVA were used to test for significant differences. Results: For 4DPET imaging, the maximum intensity projection CTAC produced significantly more accurate recovery coefficients than all other CTAC methods (p < 0.0001 over all metrics). Over all motion waveforms, ratios of 4DMIP CTAC recovery were 0.2 ± 5.4, −1.8 ± 6.5, −3.2 ± 5.0, and 3.0 ± 5.9 for RC{sub max}, RC{sub peak}, RC{sub mean}, and RC{sub vol}. In comparison, recovery coefficients for phase-matched CTAC were −8.4 ± 5.3, −10.5 ± 6.2, −7.6 ± 5.0, and −13.0 ± 7.7 for RC{sub max}, RC{sub peak}, RC{sub mean}, and RC{sub vol}. When testing differences between phases over all CTAC methods and waveforms, end-exhale phases were significantly more accurate (p = 0.005). However, these differences were driven by the patient-specific respiratory waveforms; when testing patient and sinusoidal waveforms separately, patient waveforms were significantly different between phases (p < 0.0001) while the sinusoidal waveforms were not significantly different (p = 0.98). When considering only the subset of 4DMATCH images that corresponded to the end-exhale image phase, 4DEXH, mean and interquartile range were similar to 4DMATCH but variability was considerably reduced. Conclusions: Comparative advantages in accuracy and precision of SUV metrics and segmented volumes were demonstrated with the use of the maximum intensity projection and end-exhale CT attenuation correction. While respiratory phase-matched CTAC should in theory provide optimal corrections, image artifacts and differences in implementation of 4DCT and 4DPET sorting can degrade the benefit of this approach. These results may be useful to guide the implementation, analysis, and development of respiratory-correlated thoracic PET/CT in the radiation oncology and diagnostic settings.

60 APPLIED LIFE SCIENCES↗

Portable Unit for Metabolic Analysis

The Portable Unit for Metabolic Analysis (PUMA) is an instrument that measures several quantities indicative of human metabolic function. Specifically, this instrument makes time-resolved measurements of temperature, pressure, flow, and the partial pressures of oxygen and carbon dioxide in breath during both inhalation and exhalation. Portable instruments for measuring these quantities have been commercially available, but the response times of those instruments are too long to enable temporal resolution of phenomena on the time scales of human respiration cycles. In contrast, the response time of the PUMA is significantly shorter than characteristic times of human respiration phenomena, making it possible to analyze varying metabolic parameters, not only on sequential breath cycles but also at successive phases of inhalation and exhalation within the same breath cycle. In operation, the PUMA is positioned to sample breath near the subject s mouth. Commercial off-the-shelf sensors are used for three of the measurements: a miniature pressure transducer for pressure, a thermistor for temperature, and an ultrasonic sensor for flow. Sensors developed at Glenn Research Center are used for measuring the partial pressures of oxygen and carbon dioxide: The carbon dioxide sensor exploits the relatively strong absorption of infrared light by carbon dioxide. Light from an infrared source passes through the stream of inhaled or exhaled gas and is focused on an infrared- sensitive photodetector. The oxygen sensor exploits the effect of oxygen in quenching the fluorescence of ruthenium-doped organic molecules in a dye on the tip of an optical fiber. A blue laser diode is used to excite the fluorescence, and the optical fiber carries the fluorescent light to a photodiode, the temporal variation of the output of which bears a known relationship with the rate of quenching of fluorescence and, hence, with the partial pressure of oxygen. The outputs of the sensors are digitized, preprocessed by a small onboard computer, and then sent wirelessly to a desktop computer, where the collected data are analyzed and displayed. In addition to the raw data on temperature, pressure, flow, and mole fractions of oxygen and carbon dioxide, the display can include volumetric oxygen consumption, volumetric carbon dioxide production, respiratory equivalent ratio, and volumetric flow rate of exhaled gas.

Dietrich, Daniel L.↗

Radiological risk assessment of environmental radon

Measurements of radon gas ({sup 222}Rn) in the environmental are important to assess indoor air quality and to study the potential risk to human health. Generally known that exposure to radon is considered the second leading cause of lung cancer after smoking. The environmental radon concentration depends on the {sup 226}Ra concentration, indoor atmosphere, cracking on rocks and building materials. This study was carried out to determine the indoor radon concentration from selected samples of tin tailings (amang) and building materials in an airtight sealed homemade radon chamber. The radiological risk assessment for radon gas was also calculated based on the annual exposure dose, effective dose equivalent, radon exhalation rates and fatal cancer risk. The continuous radon monitor Sun Nuclear model 1029 was used to measure the radon concentration emanates from selected samples for 96 hours. Five types of tin tailings collected from Kampar, Perak and four samples of building materials commonly used in Malaysia dwellings or building constructions were analysed for radon concentration. The indoor radon concentration determined in ilmenite, monazite, struverite, xenotime and zircon samples varies from 219.6 ± 76.8 Bq m{sup −3} to 571.1 ± 251.4 Bq m{sup −3}, 101.0 ± 41.0 Bq m{sup −3} to 245.3 ± 100.2 Bq m{sup −3}, 53.1 ± 7.5 Bq m{sup −3} to 181.8 ± 9.7 Bq m{sup −3}, 256.1 ± 59.3 Bq m{sup −3} to 652.2 ± 222.2 Bq m{sup −3} and 164.5 ± 75.9 Bq m{sup −3} to 653.3 ± 240.0 Bq m{sup −3}, respectively. Whereas, in the building materials, the radon concentration from cement brick, red-clay brick, gravel aggregate and cement showed 396.3 ± 194.3 Bq m{sup −3}, 192.1 ± 75.4 Bq m{sup −3}, 176.1 ± 85.9 Bq m{sup −3} and 28.4 ± 5.7 Bq m{sup −3}, respectively. The radon concentration in tin tailings and building materials were found to be much higher in xenotime and cement brick samples than others. All samples in tin tailings were exceeded the action level for radon gas of 148 Bq m{sup −3} proposed by EPA except monazite 0.15 kg, struverite 0.15 kg and 0.25 kg. Whereas, all building material samples have exceeded the radon concentration in concrete and building materials of 3 to 7 Bq m{sup −3} estimated by ICRP. The annual effective dose, effective dose equivalent, and radon exhalation rates in tin tailings were calculated to be in the range of 2.47 to 11.46 mSv, 5.94 to 1090.56 mSv y{sup −1}, and 0.23 to 1.18 mBq kg{sup −1} h{sup −1}. For building materials, the calculated risk assessment of the annual effective dose, effective dose equivalent, radon exhalation rates and fatal cancer risk were 0.72 to 10.00 mSv, 1.73 to 24.00 mSv y{sup −1}, 0.010 to 0.06 mBq kg{sup −1} h{sup −1} and 40 to 550 chances of persons will suffer the cancer per million (1 × 10{sup 6}), respectively.

61 RADIATION PROTECTION AND DOSIMETRY↗

SU-E-J-261: Statistical Analysis and Chaotic Dynamics of Respiratory Signal of Patients in BodyFix

Purpose: To quantify respiratory signal of patients in BodyFix undergoing 4DCT scan with and without immobilization cover. Methods: 20 pairs of respiratory tracks recorded with RPM system during 4DCT scan were analyzed. Descriptive statistic was applied to selected parameters of exhale-inhale decomposition. Standardized signals were used with the delay method to build orbits in embedded space. Nonlinear behavior was tested with surrogate data. Sample entropy SE, Lempel-Ziv complexity LZC and the largest Lyapunov exponents LLE were compared. Results: Statistical tests show difference between scans for inspiration time and its variability, which is bigger for scans without cover. The same is for variability of the end of exhalation and inhalation. Other parameters fail to show the difference. For both scans respiratory signals show determinism and nonlinear stationarity. Statistical test on surrogate data reveals their nonlinearity. LLEs show signals chaotic nature and its correlation with breathing period and its embedding delay time. SE, LZC and LLE measure respiratory signal complexity. Nonlinear characteristics do not differ between scans. Conclusion: Contrary to expectation cover applied to patients in BodyFix appears to have limited effect on signal parameters. Analysis based on trajectories of delay vectors shows respiratory system nonlinear character and its sensitive dependence on initial conditions. Reproducibility of respiratory signal can be evaluated with measures of signal complexity and its predictability window. Longer respiratory period is conducive for signal reproducibility as shown by these gauges. Statistical independence of the exhale and inhale times is also supported by the magnitude of LLE. The nonlinear parameters seem more appropriate to gauge respiratory signal complexity since its deterministic chaotic nature. It contrasts with measures based on harmonic analysis that are blind for nonlinear features. Dynamics of breathing, so crucial for 4D-based clinical technologies, can be better controlled if nonlinear-based methodology, which reflects respiration characteristic, is applied. Funding provided by Varian Medical Systems via Investigator Initiated Research Project.

60 APPLIED LIFE SCIENCES↗

Xenon Recovery at Room Temperature using Metal-Organic Frameworks

Xenon is known to be a very efficient anesthetic gas but its cost prohibits the wider use in medical industry and other potential applications. It has been shown that Xe recovery and recycle from anesthetic gas mixture can significantly reduce its cost as anesthetic. The current technology uses series of adsorbent columns followed by low temperature distillation to recover Xe, which is expensive to use in medical facilities. Herein, we propose much efficient and simpler system to recover and recycle Xe from simulant exhale anesthetic gas mixture at room temperature using metal organic frameworks. Among the MOFs tested, PCN-12 exhibits unprecedented performance with high Xe capacity, Xe/N2 and Xe/O2 selectivity at room temperature. The in-situ synchrotron measurements suggest the Xe is occupied in the small pockets of PCN-12 compared to unsaturated metal centers (UMCs). Computational modeling of adsorption further supports our experimental observation of Xe binding sites in PCN-12.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

The influence of respiratory motion on CT image volume definition

Purpose: Radiotherapy treatments are based on geometric and density information acquired from patient CT scans. It is well established that breathing motion during scan acquisition induces motion artifacts in CT images, which can alter the size, shape, and density of a patient's anatomy. The aim of this work is to examine and evaluate the impact of breathing motion on multislice CT imaging with respiratory synchronization (4DCT) and without it (3DCT). Methods: A specific phantom with a movable insert was used. Static and dynamic phantom acquisitions were obtained with a multislice CT. Four sinusoidal breath patterns were simulated to move known geometric structures longitudinally. Respiratory synchronized acquisitions (4DCT) were performed to generate images during inhale, intermediate, and exhale phases using prospective and retrospective techniques. Static phantom data were acquired in helical and sequential mode to define a baseline for each type of respiratory 4DCT technique. Taking into account the fact that respiratory 4DCT is not always available, 3DCT helical image studies were also acquired for several CT rotation periods. To study breath and acquisition coupling when respiratory 4DCT was not performed, the beginning of the CT image acquisition was matched with inhale, intermediate, or exhale respiratory phases, for each breath pattern. Other coupling scenarios were evaluated by simulating different phantom and CT acquisition parameters. Motion induced variations in shape and density were quantified by automatic threshold volume generation and Dice similarity coefficient calculation. The structure mass center positions were also determined to make a comparison with their theoretical expected position. Results: 4DCT acquisitions provided volume and position accuracies within ±3% and ±2 mm for structure dimensions >2 cm, breath amplitude ≤15 mm, and breath period ≥3 s. The smallest object (1 cm diameter) exceeded 5% volume variation for the breath patterns of higher frequency and amplitude motion. Larger volume differences (>10%) and inconsistencies between the relative positions of objects were detected in image studies acquired without respiratory control. Increasing the 3DCT rotation period caused a higher distortion in structures without obtaining their envelope. Simulated data showed that the slice acquisition time should be at least twice the breath period to average object movement. Conclusions: Respiratory 4DCT images provide accurate volume and position of organs affected by breath motion detecting higher volume discrepancies as amplitude length or breath frequency are increased. For 3DCT acquisitions, a CT should be considered slow enough to include lesion envelope as long as the slice acquisition time exceeds twice the breathing period. If this requirement cannot be satisfied, a fast CT (along with breath-hold inhale and exhale CTs to estimate roughly the ITV) is recommended in order to minimize structure distortion. Even with an awareness of a patient's respiratory cycle, its coupling with 3DCT acquisition cannot be predicted since patient anatomy is not accurately known.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

SU-E-J-78: Internal Target Volume Delineation for Lung Tumors in Patients Treated with Robotic Radiosurgery

Purpose: To compare different approaches for Internal Target Volume (ITV) delineation for patients treated with fiducial-free robotic radiosurgery for primary and metastatic lung tumors. Methods: Ten patients undergoing Lung-Optimized Treatment (LOT) for robotic radiosurgery were imaged with inhale and exhale breath-hold CT scans and 8-phase 4DCT scan. We evaluated the differences in internal target volume (ITV) delineated using three approaches: 1) maximum intensity projection (MIP) images reconstructed from 4DCT scan (ITV-MIP); 2) linear interpolation of Gross Tumor Volumes (GTV) segmented on inhale and exhale breath-hold scans (ITV-BH); 3) linear interpolation of GTV segmented on inhale and exhale phases of 4DCT scan (ITV-2Phase). All contours were independently generated by the same radiation oncologist using lung window settings. Patients had ITV-MIP volumes ranging from 1.5 to 146.9 cc (mean 36.8 cc) located in various parts of the lung. Volume overlap and matching index (MI) were calculated and compared. The MI between two volumes was defined as the ratio of their intersection to their union. MI of 1 indicates the volumes are identical; MI of 0 indicates that there is no overlap. Results: The three approaches generated very different results. The average (SD) MI for ITV-MIP and ITV-BH was 0.52 (0.24); for ITV-MIP and ITV-2Phase it was 0.69 (0.13); and for ITV-BH and ITV-2Phase was 0.57 (0.21), (ANOVA, p=0.16). Relative to the ITV-MIP, the percentage of volume overlap was 72% (26%) and 90% (7%) for ITV-BH and ITV-2Phase, respectively (t-test, p=0.05). Conclusion: Differences between ITV-BH and ITV-MIP are due to inconsistent lung filling at breath-hold and nonlinear tumor motion. Therefore, methods to check breath-hold scanning against regular patient breathing patterns should be developed. Whenever possible, ITV-BH generated by the LOT workflow should be verified by 4DCT data.

60 APPLIED LIFE SCIENCES↗

TU-F-17A-08: The Relative Accuracy of 4D Dose Accumulation for Lung Radiotherapy Using Rigid Dose Projection Versus Dose Recalculation On Every Breathing Phase

Purpose: To investigate the accuracy of 4D dose accumulation using projection of dose calculated on the end-exhalation, mid-ventilation, or average intensity breathing phase CT scan, versus dose accumulation performed using full Monte Carlo dose recalculation on every breathing phase. Methods: Radiotherapy plans were analyzed for 10 patients with stage I-II lung cancer planned using 4D-CT. SBRT plans were optimized using the dose calculated by a commercially-available Monte Carlo algorithm on the end-exhalation 4D-CT phase. 4D dose accumulations using deformable registration were performed with a commercially available tool that projected the planned dose onto every breathing phase without recalculation, as well as with a Monte Carlo recalculation of the dose on all breathing phases. The 3D planned dose (3D-EX), the 3D dose calculated on the average intensity image (3D-AVE), and the 4D accumulations of the dose calculated on the end-exhalation phase CT (4D-PR-EX), the mid-ventilation phase CT (4D-PR-MID), and the average intensity image (4D-PR-AVE), respectively, were compared against the accumulation of the Monte Carlo dose recalculated on every phase. Plan evaluation metrics relating to target volumes and critical structures relevant for lung SBRT were analyzed. Results: Plan evaluation metrics tabulated using 4D-PR-EX, 4D-PR-MID, and 4D-PR-AVE differed from those tabulated using Monte Carlo recalculation on every phase by an average of 0.14±0.70 Gy, - 0.11±0.51 Gy, and 0.00±0.62 Gy, respectively. Deviations of between 8 and 13 Gy were observed between the 4D-MC calculations and both 3D methods for the proximal bronchial trees of 3 patients. Conclusions: 4D dose accumulation using projection without re-calculation may be sufficiently accurate compared to 4D dose accumulated from Monte Carlo recalculation on every phase, depending on institutional protocols. Use of 4D dose accumulation should be considered when evaluating normal tissue complication probabilities as well as in clinical situations where target volumes are directly inferior to mobile critical structures.

60 APPLIED LIFE SCIENCES↗

SU-F-207-13: Comparison of Four Dimensional Computed Tomography (4D CT) Versus Breath Hold Images to Determine Pulmonary Nodule Elasticity

Purpose: Elasticity may distinguish malignant from benign pulmonary nodules. To compare determining of malignant pulmonary nodule (MPN) elasticity from four dimensional computed tomography (4D CT) images versus inhale/exhale breath-hold CT images. Methods: We analyzed phase 00 and 50 of 4D CT and deep inhale and natural exhale of breath-hold CT images of 30 MPN treated with stereotactic ablative radiotherapy (SABR). The radius of the smallest MPN was 0.3 cm while the biggest one was 2.1 cm. An intensity based deformable image registration (DIR) workflow was applied to the 4D CT and breath-hold images to determine the volumes of the MPNs and a 1 cm ring of surrounding lung tissue (ring) in each state. Next, an elasticity parameter was derived by calculating the ratio of the volume changes of MPN (exhale:inhale or phase50:phase00) to that of a 1 cm ring of lung tissue surrounding the MPN. The proposed formulation of elasticity enables us to compare volume changes of two different MPN in two different locations of lung. Results: The calculated volume ratio of MPNs from 4D CT (phase50:phase00) and breath-hold images (exhale:inhale) was 1.00±0.23 and 0.95±0.11, respectively. It shows the stiffness of MPN and comparably bigger volume changes of MPN in breath-hold images because of the deeper degree of inhalation. The calculated elasticity of MPNs from 4D CT and breath-hold images was 1.12±0.22 and 1.23±0.26, respectively. For five patients who have had two MPN in their lung, calculated elasticity of tumor A and tumor B follows same trend in both 4D CT and breath-hold images. Conclusion: We showed that 4D CT and breath-hold images are comparable in the ability to calculate the elasticity of MPN. This study has been supported by Department of Defense LCRP 2011 #W81XWH-12-1-0286.

60 APPLIED LIFE SCIENCES↗