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At least 55 records · Page 3

SU-G-BRB-07: Developing a QA Procedure for Gated VMAT SABR Treatments Using 10 MV Beam in Flattening-Filter Free Mode

Purpose: To develop a QA procedure for gated VMAT stereotactic ablative radiotherapy (SABR) treatments. Methods: An interface was constructed to attach the translational stage of a Quasar respiratory motion phantom to a pinpoint ion chamber insert and move the ion chamber inside an ArcCheck diode array. The Quasar phantom controller used a patient specific breathing pattern to translate the ion chamber in a superior-inferior direction inside the ArcCheck. An amplitude-based RPM tracking system was specified to turn the beam on during the exhale phase of the breathing pattern. SABR plans were developed using Eclipse for liver PTVs ranging in size from 3-12 cm in diameter using a 2-arc VMAT technique. Dose was measured in the middle of the penumbra region, where the high dose gradient allowed for sensitive detection of any inaccuracies in gated dose delivery. The overall fidelity of the dose distribution was confirmed using ArcCheck. The sensitivity of the gating QA procedure was investigated with respect to the following four parameters: PTV size, duration of exhale, baseline drift, and gating window size. Results: The difference between the measured dose to a point in the penumbra and the Eclipse calculated dose was under 2% for small residual motions. The QA procedure was independent of PTV size and duration of exhale. Baseline drift and gating window size, however, significantly affected the penumbral dose measurement, with differences of up to 30% compared to Eclipse. Conclusion: This study described a highly sensitive QA procedure for gated VMAT SABR treatments. The QA outcome was dependent on the gating window size and baseline drift. Analysis of additional patient breathing patterns will be required to determine a clinically relevant gating window size and an appropriate tolerance level for this procedure.

60 APPLIED LIFE SCIENCES↗

INSPIRE Phase I Development

Sandia National Laboratories (Sandia) and Makel Engineering, Inc developed a pathway towards an advanced multi-modal sensor system suitable for in-situ analysis of exhaled volatile organic compounds (VOCs) for pilots, divers and field patients. Our proposed In-Mask Sensors for Physiological Investigation of Respiratory Exhalation - INSPIRE, will combine micro-gas chromatograph (microGC) and miniature ion mobility spectrometer (IMS) for detection of trace amounts of exhaled breath VOCs with miniature solid state sensors for inorganic compounds found in breath such as oxygen, carbon dioxide, moisture and the inert gases nitrogen, argon and helium. To develop clear developmental pathway towards that goal Sandia demonstrated a new version of its ion-mobility spectrometer detection technology for VOC detection, while Makel demonstrated detection of inorganics and concepts for mask integration. Sandia demonstrated detection of many compounds from the EPA TO-15 Test Mixture, which is representative of many classes of compounds found in air, and can be purchased as a gas standard from a variety of suppliers. The work demonstrated for phase I was sufficient to move the team into phase II of the program, where a full prototype unit will be developed. This CRADA provided clear value to the taxpayer by allowing a US small business to continue to phase II of a competitive STTR proposal for the Air Force. This process will help to transition Sandia’s technology into the marketplace to address a clear DoD requirement.

Moorman, Matthew↗

Modeling Pancreatic Tumor Motion Using 4-Dimensional Computed Tomography and Surrogate Markers

Purpose: To assess intrafractional positional variations of pancreatic tumors using 4-dimensional computed tomography (4D-CT), their impact on gross tumor volume (GTV) coverage, the reliability of biliary stent, fiducial seeds, and the real-time position management (RPM) external marker as tumor surrogates for setup of respiratory gated treatment, and to build a correlative model of tumor motion. Methods and Materials: We analyzed the respiration-correlated 4D-CT images acquired during simulation of 36 patients with either a biliary stent (n=16) or implanted fiducials (n=20) who were treated with RPM respiratory gated intensity modulated radiation therapy for locally advanced pancreatic cancer. Respiratory displacement relative to end-exhalation was measured for the GTV, the biliary stent, or fiducial seeds, and the RPM marker. The results were compared between the full respiratory cycle and the gating interval. Linear mixed model was used to assess the correlation of GTV motion with the potential surrogate markers. Results: The average ± SD GTV excursions were 0.3 ± 0.2 cm in the left-right direction, 0.6 ± 0.3 cm in the anterior-posterior direction, and 1.3 ± 0.7 cm in the superior-inferior direction. Gating around end-exhalation reduced GTV motion by 46% to 60%. D95% was at least the prescribed 56 Gy in 76% of patients. GTV displacement was associated with the RPM marker, the biliary stent, and the fiducial seeds. The correlation was better with fiducial seeds and with biliary stent. Conclusions: Respiratory gating reduced the margin necessary for radiation therapy for pancreatic tumors. GTV motion was well correlated with biliary stent or fiducial seed displacements, validating their use as surrogates for daily assessment of GTV position during treatment. A patient-specific internal target volume based on 4D-CT is recommended both for gated and not-gated treatment; otherwise, our model can be used to predict the degree of GTV motion.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Accuracy of Routine Treatment Planning 4-Dimensional and Deep-Inspiration Breath-Hold Computed Tomography Delineation of the Left Anterior Descending Artery in Radiation Therapy

Purpose: To assess the feasibility of radiation therapy treatment planning 4-dimensional computed tomography (4DCT) and deep-inspiration breath-hold (DIBH) CT to accurately contour the left anterior descending artery (LAD), a primary indicator of radiation-induced cardiac toxicity for patients undergoing radiation therapy. Methods and Materials: Ten subjects were prospectively imaged with a cardiac-gated MRI protocol to determine cardiac motion effects, including the displacement of a region of interest comprising the LAD. A series of planar views were obtained and resampled to create a 3-dimensional (3D) volume. A 3D optical flow deformable image registration algorithm determined tissue displacement during the cardiac cycle. The measured motion was then used as a spatial boundary to characterize motion blurring of the radiologist-delineated LAD structure for a cohort of 10 consecutive patients enrolled prospectively on a breast study including 4DCT and DIBH scans. Coronary motion–induced blurring artifacts were quantified by applying an unsharp filter to accentuate the LAD structure despite the presence of motion blurring. The 4DCT maximum inhalation and exhalation respiratory phases were coregistered to determine the LAD displacement during tidal respiration, as visualized in 4DCT. Results: The average 90th percentile heart motion for the region of interest was 0.7 ± 0.1 mm (left–right [LR]), 1.3 ± 0.6 mm (superior–inferior [SI]), and 0.6 ± 0.2 mm (anterior–posterior [AP]) in the cardiac-gated MRI cohort. The average relative increase in the number of voxels comprising the LAD contour was 69.4% ± 4.5% for the DIBH. The LAD volume overestimation had the dosimetric impact of decreasing the reported mean LAD dose by 23% ± 9% on average in the DIBH. During tidal respiration the average relative LAD contour increase was 69.3% ± 5.9% and 67.9% ± 4.6% for inhalation and exhalation respiratory phases, respectively. The average 90th percentile LAD motion was 4.8 ± 1.1 mm (LR), 0.9 ± 0.4 mm (SI), and 1.9 ± 0.6 mm (AP) for the 4DCT cohort, in the absence of cardiac gating. Conclusions: An anisotropic margin of 2.7 mm (LR), 4.1 mm (SI), and 2.4 mm (AP) was quantitatively determined to account for motion blurring and patient setup error while placing minimum constraint on the plan optimization.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Assessment of Lung Tumour Motion and Volume Size Dependencies Using Various Evaluation Measures

The purpose of the study was to assess internal target volume changes through the breathing cycle and associated tumour motion for lung patients and to establish possible correlations between different parameters. Respiration-induced volume changes with breathing cycle and the associated tumour motion were analyzed for 11 patients. Selected phases were the maximum and average intensity projections and the 10 phases of equal duration and separation obtained through the respiratory cycle. Tumour centre of mass (COM) motion planes were generated using least square fitting, and their angles and orientations were then compared between the cases studied. Trajectories that are composed by the points of COM location in different phases were identified, and their interrelation was assessed through different similarity measures. The results were used to determine if there is any correlation between parameters chosen and if the margins conventionally used for the planning target volume creation successfully encompassed lung tumour motion and volume change. The results show that the extent of tumour motion was related to its volume and location. The tumour displacement was predominantly left and inferior. Planar fitting to COM motion data through respiratory phases demonstrated some correlation in best fit motion plane positions between different data sets. In the plane fit comparison, for each patient, the lower root mean square error values showed that a good planar fit can be achieved for the COM motion path. The evaluation of the inhale and exhale trajectories may allow, for certain tumour locations and size, contouring on only inhalation or exhalation phases, knowing that tumour motion will be adequately covered on the other phases. Taking all the data into account and knowing the tumour size and location, a good estimate can be made of the motion plane position in the three-dimensional space and the required dosimetric margins.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Venous catheterization with ultrasound navigation

By ultrasound scanning it was determined that respiratory movements made by chest of healthy and sick person are accompanied by respiratory chest rise of internal jugular veins. During the exhalation of an individual diameter of his veins increases and during the breath it decreases down to the complete disappearing if their lumen. Change of the diameter of internal jugular veins in different phases can influence significantly the results of vein puncture and cauterization in patients. The purpose of this research is development of the method increasing the efficiency and safety of cannulation of internal jugular veins by the ultrasound visualization. We suggested the method of catheterization of internal jugular veins by the ultrasound navigation during the execution of which the puncture of venous wall by puncture needle and the following conduction of J-guide is carried out at the moment of patient’s exhalation. This method decreases the risk of complications development during catheterization of internal jugular vein due to exclusion of perforating wound of vein and subjacent tissues and anatomical structures.

42 ENGINEERING↗

SU-E-J-267: Weekly Volumetric and Dosimetric Changes in Adaptive Conformal Radiotherapy of Non-Small-Cell-Lung Cancer Using 4D CT and Gating

Purpose: This study was to evaluate the significance of weekly imageguided patient setup and to assess the volumetric and dosimetric changes in no-small-cell-lung cancer (NSCLC) patients treated with adaptive conformal radiotherapy (CRT). Methods: 9 NSCLC patients treated with 3D CRT underwent 4D CT-on-rail every five fractions. ITV was generated from three phases of the 4DCT (the end of exhalation, 25% before and after the end of exhalation). The margin of ITV to PTV is 5mm. 6 weekly CTs were acquired for each patient. The weekly CTs were fused with the planning CT by vertebrae. The couch shift was recorded for each weekly CT to evaluate the setup error. The gross tumor volumes (GTVs) were contoured on weekly CT images by a physician. Beams from the original plans were applied to weekly CTs to calculate the delivered doses. All patients underwent replanning after 20 fractions. Results: Among the total 54 CTs, the average setup error was 2.0± 1.7, 2.6± 2.1, 2.7± 2.2 mm in X, Y, and Z direction, respectively. The average volume of the primary GTV was reduced from 42.45 cc to 22.78 cc (47.04%) after 6 weeks. The maximal volume regression occurred between 15 and 20 fractions. Adaptive radiation therapy (ART) reduced the V20 and V5 of the lung by 33.5% and 16.89%, respectively. ART also reduced Dmean and D1/3 of the heart by 31.7% and 32.32%, respectively. Dmax of the spinal cord did not vary much during the treatment course. Conclusion: 5 mm margin is sufficient for 4D weekly CTguided radiotherapy in lung cancer. Tumor regression was observed in the majority of patients. ART significantly reduced the OARs dose. Our preliminary results indicated that an off-line ART approach is appropriate in clinical practice.

60 APPLIED LIFE SCIENCES↗

SU-E-T-179: Exploring Appropriate Offset Values for Pencil Beam and Monte Carlo Dose Optimization in Lung Stereotactic Body Radiotherapy Encompassing the Effects of Respiration and Tumor Location

Purpose: Exploring appropriate offset values in dose optimization with pencil beam (PB) algorithm to minimize dosimetric differences with plans calculated with Monte Carlo (MC) for lung cancer treatment with Stereotactic Body Radiotherapy (SBRT). Methods: 20 cases of Non-Small Cell Lung Cancer, treated with gated full motion range SBRT were selected. According to the proximity of the Gross Tumor Volume (GTV) to the chest wall, two groups are defined: peripherally located when GTV merges with the chest wall for at least 50% of the lesion diameter, and centrally located when the GTV is surrounded by lung tissue. Treatment plans were created on 4D average intensity projection (AIP) CT set with Brainlab iPlanDose 4.1.2 planning system. The D97 of PTV was normalized to 50Gy using the fast PB and compared with MC. The optimized plan was then recomputed over each 4D respiratory phase, and compared with MC using the same plan MU's. Results: The mean difference in the PB and MC D97 of the ITV was 10.5% (±0.8%) of the prescription dose (50Gy). PB algorithm showed 2.3–2.4% less overestimation to the D97 of the ITV, when comparing to MC, in the maximum exhalation phase than in the maximal inhalation phase. Significantly smaller dose difference between PB and MC is also shown in plans for peripheral lesions (7.7 ± 0.7%) versus for central lesions (12.7±0.8%) (p< 0.01). Conclusion: The dosimetric differences between PB and MC can be reasonably predicted depending on the location of lesion in the lung, and may be used as offset value in dose optimization with PB. Since the maximal exhalation phase demonstrates less dose discrepancy between the two algorithms than that in maximal inhalation phase, caution is suggested when the latter is included as a major phase portion in the respiration gated lung SBRT.

60 APPLIED LIFE SCIENCES↗

BRAVE_EBC-TMT.1.0

Exhaled breath condensate (EBC) represents a low-cost and non-invasive means of examining respiratory health. EBC has been used to discover and validate exhaled volatile and non-volatile biomarkers of disease related to the respiratory system distress such as asthma, COPD, lung cancer, and secondary infections. One newly emerging utilization of EBC, is proteomics analysis, which can provide an unbiased snapshot into ongoing biological processes in the airway. Fully characterizing the biological landscape of EBC collections is challenging though, due to sample variability, and low detection sensitivity. EBC is primarily composed of condensed water, causing technical challenges with detecting key macromolecules from the dilute sample matrix; therefore, high sensitivity techniques are required to unlock the full capability of EBC as a method for non-invasive biomarker detection. To overcome some of these technical challenges for proteomic analyses, we applied our recently developed microscale proteomic techniques and developed a novel TMT based approach which enabled reliable, relative quantification with significantly improved detection of low abundance peptides/proteins across multiple healthy volunteer EBC samples. Our EBC collection design includes longitudinal EBC collections from five individual healthy volunteers on three separate days of the week with triplicate, back-to-back donations each day. Here, we report a total of 235 quantifiable proteins corresponding to 1,877 non-redundant peptides for evaluating sample collection reproducibility and establishing a healthy (human host) baseline EBC biomarker proteome studies. This work will pave the way for further investigations of EBC protein expression profiles and showcase the value of using non-invasive collection method techniques for clinically relevant biomarker discovery. This research was supported by the LDRD Biomedical Resilience And Readiness in AdVerse Operating Environments (BRAVE) Project (73748), and was conducted at Pacific Northwest National Laboratory (PNNL) in Richland, WA. PNNL is a multiprogram national laboratory operated by Battelle for the Department of Energy (DOE) under Contract DE-AC05-76RLO 1830.

59 BASIC BIOLOGICAL SCIENCES↗

Polycyclic aromatic hydrocarbons and cannabinoids in secondhand cannabis smoke

The legalization of cannabis is exposing more people to secondhand smoke (SHS) generated during cannabis use. Given the serious health effects caused by tobacco SHS, there is a need to assess the potential health effects of exposure to cannabis SHS. As a step toward this, we measured the concentrations of cannabinoids, nicotine and polycyclic aromatic hydrocarbons (PAHs) in air samples collected in public places where cannabis was being consumed. These were compared with concentrations in exhaled aerosols from cannabis smoking and vaping, and in tobacco SHS. Tetrahydrocannabinol concentrations were 22 to 255 µg/m 3 in field samples, below the threshold for psychoactive effects. Nicotine concentrations in field samples did not exceed 1 µg/m 3 . The total PAH concentrations in field samples were from 3.2 to 80.5 ng/m 3 , depending on location type. By contrast, PAH levels averaged 72 ng/m 3 in tobacco SHS and 220 ng/m 3 in the more concentrated, exhaled cannabis aerosols. A total of 22 different PAHs were identified in field samples of cannabis aerosols, from which benz[a]anthracene (B[a]A) was present in the highest concentrations. The PAH profile of cannabis aerosols was different from that of tobacco SHS. A preliminary cancer risk evaluation showed that the dose associated with inhalation of cannabis SHS during an 8-h work shift exceeded the California No Significant Risk Level for B[a]A at all venues where cannabis was consumed primarily via smoking. In summary, the consumption of cannabis, by smoking and by vaporizing, can create aerosols that contain carcinogenic PAHs. Thus breathing secondhand cannabis aerosols increases exposure to carcinogens.

Aerosol↗

Quantification of Esophageal Tumor Motion on Cine-Magnetic Resonance Imaging

Purpose: To quantify the movement of esophageal tumors noninvasively on cine-magnetic resonance imaging (MRI) by use of a semiautomatic method to visualize tumor movement directly throughout multiple breathing cycles. Methods and Materials: Thirty-six patients with esophageal tumors underwent MRI. Tumors were located in the upper (8), middle (7), and lower (21) esophagus. Cine-MR images were collected in the coronal and sagittal plane during 60 seconds at a rate of 2 Hz. An adaptive correlation filter was used to automatically track a previously marked reference point. Tumor movement was measured in the craniocaudal (CC), left–right (LR), and anteroposterior (AP) directions and its relationship along the longitudinal axis of the esophagus was investigated. Results: Tumor registration within the individual images was typically done at a millisecond time scale. The mean (SD) peak-to-peak displacements in the CC, AP, and LR directions were 13.3 (5.2) mm, 4.9 (2.5) mm, and 2.7 (1.2) mm, respectively. The bandwidth to cover 95% of excursions from the mean position (c95) was also calculated to exclude outliers caused by sporadic movements. The mean (SD) c95 values were 10.1 (3.8) mm, 3.7 (1.9) mm, and 2.0 (0.9) mm in the CC, AP, and LR dimensions. The end-exhale phase provided a stable position in the respiratory cycle, compared with more variety in the end-inhale phase. Furthermore, lower tumors showed more movement than did higher tumors in the CC and AP directions. Conclusions: Intrafraction tumor movement was highly variable between patients. Tumor position proved the most stable during the respiratory cycle in the end-exhale phase. A better understanding of tumor motion makes it possible to individualize radiation delivery strategies accordingly. Cine-MRI is a successful noninvasive modality to analyze motion for this purpose in the future.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Accumulated Delivered Dose Response of Stereotactic Body Radiation Therapy for Liver Metastases

Purpose: To determine whether the accumulated dose using image guided radiation therapy is a stronger predictor of clinical outcomes than the planned dose in stereotactic body radiation therapy (SBRT) for liver metastases. Methods and Materials: From 2003 to 2009, 81 patients with 142 metastases were treated in institutional review board–approved SBRT studies (5-10 fractions). Patients were treated during free breathing (with or without abdominal compression) or with controlled exhale breath-holding. SBRT was planned on a static exhale computed tomography (CT) scan, and the minimum planning target volume dose to 0.5 cm{sup 3} (minPTV) was recorded. The accumulated minimum dose to the 0.5 cm{sup 3} gross tumor volume (accGTV) was calculated after performing dose accumulation from exported image guided radiation therapy data sets registered to the planning CT using rigid (2-dimensional MV/kV orthogonal) or deformable (3-dimensional/4-dimensional cone beam CT) image registration. Univariate and multivariate Cox regression models assessed the factors influencing the time to local progression (TTLP). Hazard ratios for accGTV and minPTV were compared using model goodness-of-fit and bootstrapping. Results: Overall, the accGTV dose exceeded the minPTV dose in 98% of the lesions. For 5 to 6 fractions, accGTV doses of >45 Gy were associated with 1-year local control of 86%. On univariate analysis, the cancer subtype (breast), smaller tumor volume, and increased dose were significant predictors for improved TTLP. The dose and volume were uncorrelated; the accGTV dose and minPTV dose were correlated and were tested separately on multivariate models. Breast cancer subtype, accGTV dose (P<.001), and minPTV dose (P=.02) retained significance in the multivariate models. The univariate hazard ratio for TTLP for 5-Gy increases in accGTV versus minPTV was 0.67 versus 0.74 (all patients; 95% confidence interval of difference 0.03-0.14). Goodness-of-fit testing confirmed the accGTV dose as a stronger dose–response predictor than the minPTV dose. Conclusions: The accGTV dose is a better predictor of TTLP than the minPTV dose for liver metastasis SBRT. The use of modern image guided radiation therapy in future analyses of dose–response outcomes should increase the concordance between the planned and delivered doses.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Changes in Liver Volume Observed Following Sorafenib and Liver Radiation Therapy

Purpose: The purpose of this study was to quantify unexpected liver volume reductions in patients treated with sorafenib prior to and during liver radiation therapy (RT). Methods and Materials: Fifteen patients were treated in a phase 1 study of sorafenib for 1 week, followed by concurrent sorafenib-RT (in 6 fractions). Patients had either focal cancer (treated with stereotactic body RT [SBRT]) or diffuse disease (treated with whole-liver RT). Liver volumes were contoured and recorded at planning (day 0) from the exhale CT. After 1 week of sorafenib (day 8), RT image guidance at each fraction was performed using cone beam CT (CBCT). Planning liver contours were propagated and modified on the reconstructed exhale CBCT. This was repeated in 12 patients treated with SBRT alone without sorafenib. Three subsequent patients (2 sorafenib-RT and 1 non-sorafenib) were also assessed with multiphasic helical breath-hold CTs. Results: Liver volume reductions on CBCT were observed in the 15 sorafenib-RT patients (median decrease of 68 cc, P=.02) between day 0 and 8; greater in the focal (P=.025) versus diffuse (P=.52) cancer stratum. Seven patients (47%) had reductions larger than the 95% intraobserver contouring error. Liver reductions were also observed from multiphasic CTs in the 2 additional sorafenib-RT patients between days 0 and 8 (decreases of 232.5 cc and 331.7 cc, respectively) and not in the non-sorafenib patient (increase of 92 cc). There were no significant changes in liver volume between planning and first RT in 12 patients with focal cancer treated with SBRT alone (median increase, 4.8 cc, P=.86). Conclusions: Liver volume reductions were observed after 7 days of sorafenib, prior to RT, most marked in patients with focal liver tumors, suggesting an effect of sorafenib on normal liver. Careful assessment of potential liver volume changes immediately prior to SBRT may be necessary in patients in sorafenib or other targeted therapies.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Nonlocal Means Denoising of Self-Gated and k-Space Sorted 4-Dimensional Magnetic Resonance Imaging Using Block-Matching and 3-Dimensional Filtering: Implications for Pancreatic Tumor Registration and Segmentation

Purpose: To denoise self-gated k-space sorted 4-dimensional magnetic resonance imaging (SG-KS-4D-MRI) by applying a nonlocal means denoising filter, block-matching and 3-dimensional filtering (BM3D), to test its impact on the accuracy of 4D image deformable registration and automated tumor segmentation for pancreatic cancer patients. Methods and Materials: Nine patients with pancreatic cancer and abdominal SG-KS-4D-MRI were included in the study. Block-matching and 3D filtering was adapted to search in the axial slices/frames adjacent to the reference image patch in the spatial and temporal domains. The patches with high similarity to the reference patch were used to collectively denoise the 4D-MRI image. The pancreas tumor was manually contoured on the first end-of-exhalation phase for both the raw and the denoised 4D-MRI. B-spline deformable registration was applied to the subsequent phases for contour propagation. The consistency of tumor volume defined by the standard deviation of gross tumor volumes from 10 breathing phases (σ-GTV), tumor motion trajectories in 3 cardinal motion planes, 4D-MRI imaging noise, and image contrast-to-noise ratio were compared between the raw and denoised groups. Results: Block-matching and 3D filtering visually and quantitatively reduced image noise by 52% and improved image contrast-to-noise ratio by 56%, without compromising soft tissue edge definitions. Automatic tumor segmentation is statistically more consistent on the denoised 4D-MRI (σ-GTV = 0.6 cm{sup 3}) than on the raw 4D-MRI (σ-GTV = 0.8 cm{sup 3}). Tumor end-of-exhalation location is also more reproducible on the denoised 4D-MRI than on the raw 4D-MRI in all 3 cardinal motion planes. Conclusions: Block-matching and 3D filtering can significantly reduce random image noise while maintaining structural features in the SG-KS-4D-MRI datasets. In this study of pancreatic tumor segmentation, automatic segmentation of GTV in the registered image sets is shown to be more consistent on the denoised 4D-MRI than on the raw 4D-MRI.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Computational Fluid Dynamics Modeling of Bacillus anthracis Spore Deposition in Rabbit and Human Respiratory Airways

Three-dimensional computational fluid dynamics and Lagrangian particle deposition models were developed to compare the deposition of aerosolized Bacillus anthracis spores in the respiratory airways of a human with that of the rabbit, a species commonly used in the study of anthrax disease. The respiratory airway geometries for each species were derived from computed tomography (CT) or µCT images. Both models encompassed airways that extended from the external nose to the lung with a total of 272 outlets in the human model and 2878 outlets in the rabbit model. All simulations of spore deposition were conducted under transient, inhalation-exhalation breathing conditions using average species-specific minute volumes. The highest exposure concentration was modeled in the rabbit based upon prior acute inhalation studies. For comparison, human simulation was also conducted at the same concentration. Results demonstrated that regional spore deposition patterns were sensitive to airway geometry and ventilation profiles. Due to the complex airway geometries in the rabbit nose, higher spore deposition efficiency was predicted in the upper conducting airways compared to the human at the same air concentration of anthrax spores. As a result, higher particle deposition was predicted in the conducting airways and deep lung of the human compared to the rabbit lung due to differences in airway branching pattern. This information can be used to refine published and ongoing biokinetic models of inhalation anthrax spore exposures, which currently estimate deposited spore concentrations based solely upon exposure concentrations and inhaled doses that do not factor in species-specific anatomy and physiology.

bacillus anthracis↗

Tumor control probability and the utility of 4D vs 3D dose calculations for stereotactic body radiotherapy for lung cancer

Four-dimensional (4D) dose calculations for lung cancer radiotherapy have been technically feasible for a number of years but have not become standard clinical practice. The purpose of this study was to determine if clinically significant differences in tumor control probability (TCP) exist between 3D and 4D dose calculations so as to inform the decision whether 4D dose calculations should be used routinely for treatment planning. Radiotherapy plans for Stage I-II lung cancer were created for 8 patients. Clinically acceptable treatment plans were created with dose calculated on the end-exhale 4D computed tomography (CT) phase using a Monte Carlo algorithm. Dose was then projected onto the remaining 9 phases of 4D-CT using the Monte Carlo algorithm and accumulated onto the end-exhale phase using commercially available deformable registration software. The resulting dose-volume histograms (DVH) of the gross tumor volume (GTV), planning tumor volume (PTV), and PTV{sub setup} were compared according to target coverage and dose. The PTV{sub setup} was defined as a volume including the GTV and a margin for setup uncertainties but not for respiratory motion. TCPs resulting from these DVHs were estimated using a wide range of alphas, betas, and tumor cell densities. Differences of up to 5 Gy were observed between 3D and 4D calculations for a PTV with highly irregular shape. When the TCP was calculated using the resulting DVHs for fractionation schedules typically used in stereotactic body radiation therapy (SBRT), the TCP differed at most by 5% between 4D and 3D cases, and in most cases, it was by less than 1%. We conclude that 4D dose calculations are not necessary for most cases treated with SBRT, but they might be valuable for irregularly shaped target volumes. If 4D calculations are used, 4D DVHs should be evaluated on volumes that include margin for setup uncertainty but not respiratory motion.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Broadband tunable source of mid-IR laser radiation for photoacoustic spectroscopy

Control over volatile products of metabolic processes in human body in exhaled air is a promising method for noninvasive medical diagnostics. The mid-IR range (2–12 μm) is of great interest for diagnostic applications of the exhaled air spectral analysis. Laser optoacoustic spectroscopy is quite attractive for detecting a large set of gaseous substances; however, high-power sources of tunable radiation are required to increase the method sensitivity. We consider the possibility of using a parametric light generator based on a BaGa{sub 4}Se{sub 7} crystal as a broadband tunable mid-IR laser source for laser optoacoustic spectroscopy. (paper)

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Experimental evaluations of the accuracy of 3D and 4D planning in robotic tracking stereotactic body radiotherapy for lung cancers

Purpose: Due to the complexity of 4D target tracking radiotherapy, the accuracy of this treatment strategy should be experimentally validated against established standard 3D technique. This work compared the accuracy of 3D and 4D dose calculations in respiration tracking stereotactic body radiotherapy (SBRT). Methods: Using the 4D planning module of the CyberKnife treatment planning system, treatment plans for a moving target and a static off-target cord structure were created on different four-dimensional computed tomography (4D-CT) datasets of a thorax phantom moving in different ranges. The 4D planning system used B-splines deformable image registrations (DIR) to accumulate dose distributions calculated on different breathing geometries, each corresponding to a static 3D-CT image of the 4D-CT dataset, onto a reference image to compose a 4D dose distribution. For each motion, 4D optimization was performed to generate a 4D treatment plan of the moving target. For comparison with standard 3D planning, each 4D plan was copied to the reference end-exhale images and a standard 3D dose calculation was followed. Treatment plans of the off-target structure were first obtained by standard 3D optimization on the end-exhale images. Subsequently, they were applied to recalculate the 4D dose distributions using DIRs. All dose distributions that were initially obtained using the ray-tracing algorithm with equivalent path-length heterogeneity correction (3D{sub EPL} and 4D{sub EPL}) were recalculated by a Monte Carlo algorithm (3D{sub MC} and 4D{sub MC}) to further investigate the effects of dose calculation algorithms. The calculated 3D{sub EPL}, 3D{sub MC}, 4D{sub EPL}, and 4D{sub MC} dose distributions were compared to measurements by Gafchromic EBT2 films in the axial and coronal planes of the moving target object, and the coronal plane for the static off-target object based on the {gamma} metric at 5%/3mm criteria ({gamma}{sub 5%/3mm}). Treatment plans were considered acceptable if the percentage of pixels passing {gamma}{sub 5%/3mm} (P{sub {gamma}<1}) {>=} 90%. Results: The averaged P{sub {gamma}<1} values of the 3D{sub EPL}, 3D{sub MC}, 4D{sub EPL}, and 4D{sub MC} dose calculation methods for the moving target plans are 95%, 95%, 94%, and 95% for reproducible motion, and 95%, 96%, 94%, and 93% for nonreproducible motion during actual treatment delivery. The overall measured target dose distributions are in better agreement with the 3D{sub MC} dose distributions than the 4D{sub MC} dose distributions. Conversely, measured dose distributions agree much better with the 4D{sub EPL/MC} than the 3D{sub EPL/MC} dose distributions in the static off-target structure, resulting in higher P{sub {gamma}<1} values with 4D{sub EPL/MC} (91%) vs 3D{sub EPL} (24%) and 3D{sub MC} (25%). Systematic changes of target motion reduced the averaged P{sub {gamma}<1} to 47% and 53% for 4D{sub EPL} and 4D{sub MC} dose calculations, and 22% for 3D{sub EPL/MC} dose calculations in the off-target films. Conclusions: In robotic tracking SBRT, 4D treatment planning was found to yield better prediction of the dose distributions in the off-target structure, but not necessarily in the moving target, compared to standard 3D treatment planning, for reproducible and nonreproducible target motion. It is important to ensure on a patient-by-patient basis that the cumulative uncertainty associated with the 4D-CT artifacts, deformable image registration, and motion variability is significantly smaller than the cumulative uncertainty occurred in standard 3D planning in order to make 4D planning a justified option.

60 APPLIED LIFE SCIENCES↗