Script-based implementation of automatic grid placement for lattice stereotactic body radiation therapy.

Background and purpose: Spatially fractionated radiation therapy (SFRT) has demonstrated promising clinical response in treating large tumors with heterogeneous dose distributions. Lattice stereotactic body radiation therapy (SBRT) is an SFRT technique that leverages inverse optimization to precisely localize regions of high and lose dose within disease. The aim of this study was to evaluate an automated heuristic approach to sphere placement in lattice SBRT treatment planning. Materials and methods: A script-based algorithm for sphere placement in lattice SBRT based on rules described by protocol was implemented within a treatment planning system. The script was applied to 22 treated cases and sphere distributions were compared with manually placed spheres in terms of number of spheres, number of protocol violations, and time required to place spheres. All cases were re-planned using script-generated spheres and plan quality was compared with clinical plans. Results: The mean number of spheres placed excluding those that violate rules was greater using the script (13.8) than that obtained by either dosimetrist (10.8 and 12.0, p < 0.001 and p = 0.003) or physicist (12.7, p = 0.061). The mean time required to generate spheres was significantly less using the script (2.5 min) compared to manual placement by dosimetrists (25.0 and 29.9 min) and physicist (19.3 min). Plan quality indices were similar in all cases with no significant differences, and OAR constraints remained met on all plans except two. Conclusion: A script placed spheres for lattice SBRT according to institutional protocol rules. The script-produced placement was superior to that of manually-specified spheres, as characterized by sphere number and rule violations.

Clinical application of a template-guided automated planning routine.

PURPOSE: Determine the dosimetric quality and the planning time reduction when utilizing a template-based automated planning application. METHODS: A software application integrated through the treatment planning system application programing interface, QuickPlan, was developed to facilitate automated planning using configurable templates for contouring, knowledge-based planning structure matching, field design, and algorithm settings. Validations are performed at various levels of the planning procedure and assist in the evaluation of readiness of the CT image, structure set, and plan layout for automated planning. QuickPlan is evaluated dosimetrically against 22 hippocampal-avoidance whole brain radiotherapy patients. The required times to treatment plan generation are compared for the validations set as well as 10 prospective patients whose plans have been automated by QuickPlan. RESULTS: The generations of 22 automated treatment plans are compared against a manual replanning using an identical process, resulting in dosimetric differences of minor clinical significance. The target dose to 2% volume and homogeneity index result in significantly decreased values for automated plans, whereas other dose metric evaluations are nonsignificant. The time to generate the treatment plans is reduced for all automated plans with a median difference of 9' 50″ ± 4' 33″. CONCLUSIONS: Template-based automated planning allows for reduced treatment planning time with consistent optimization structure creation, treatment field creation, plan optimization, and dose calculation with similar dosimetric quality. This process has potential expansion to numerous disease sites.

Technical Report: Development and Implementation of an Open Source Template Interpretation Class Library for Automated Treatment Planning.

PURPOSE: Widespread implementation of automated treatment planning in radiation therapy remains elusive owing to variability in clinic and physician preferences, making it difficult to ensure consistent plan parameters. We have developed an open-source class library with the aim to improve efficiency and consistency for automated treatment planning in radiation therapy. METHODS AND MATERIALS: An open-source class library has been developed that interprets clinical templates within a commercial treatment planning system into a treatment plan for automated planning. This code was leveraged for the automated planning of 39 patients and retrospectively compared with the 78 clinically approved manual plans. RESULTS: From the initial 39 patients, 74 of 78 plans were successfully generated without manual intervention. The target dose was more homogeneous for automated plans, with an average homogeneity index of 3.30 for manual plans versus 3.11 for automated plans (P = .107). The generalized equivalent uniform dose (gEUD) was decreased in the femurs and rectum for automated plans, with a mean gEUD of 3746 cGy versus 3338 cGy (P ≤ 0.001) and 5761 cGy versus 5634 cGy (P ≤ 0.001) for the femurs and rectum, respectively. Dose metrics for the bladder and rectum (V6500 cGy and V4000 cGy) showed recognizable but insignificant improvements. All automated plans delivered for quality assurance passed a gamma analysis (>95%), with an average composite pass rate of 99.3% for pelvis plans and 98.8% for prostate plans. Deliverability parameters such as total monitor units and aperture complexity indicated deliverable plans. CONCLUSIONS: Prostate cancer and pelvic node radiation therapy can be automated using volumetric modulated arc therapy planning and clinical templates based on a standardized clinical workflow. The class library developed in this study conveniently interfaced between the plan template and the treatment planning system to automatically generate high-quality plans on customizable templates.

Application programming interface guided QA plan generation and analysis automation.

PURPOSE: Linear accelerator quality assurance (QA) in radiation therapy is a time consuming but fundamental part of ensuring the performance characteristics of radiation delivering machines. The goal of this work is to develop an automated and standardized QA plan generation and analysis system in the Oncology Information System (OIS) to streamline the QA process. METHODS: Automating the QA process includes two software components: the AutoQA Builder to generate daily, monthly, quarterly, and miscellaneous periodic linear accelerator QA plans within the Treatment Planning System (TPS) and the AutoQA Analysis to analyze images collected on the Electronic Portal Imaging Device (EPID) allowing for a rapid analysis of the acquired QA images. To verify the results of the automated QA analysis, results were compared to the current standard for QA assessment for the jaw junction, light-radiation coincidence, picket fence, and volumetric modulated arc therapy (VMAT) QA plans across three linacs and over a 6-month period. RESULTS: The AutoQA Builder application has been utilized clinically 322 times to create QA patients, construct phantom images, and deploy common periodic QA tests across multiple institutions, linear accelerators, and physicists. Comparing the AutoQA Analysis results with our current institutional QA standard the mean difference of the ratio of intensity values within the field-matched junction and ball-bearing position detection was 0.012 ± 0.053 (P = 0.159) and is 0.011 ± 0.224 mm (P = 0.355), respectively. Analysis of VMAT QA plans resulted in a maximum percentage difference of 0.3%. CONCLUSION: The automated creation and analysis of quality assurance plans using multiple APIs can be of immediate benefit to linear accelerator quality assurance efficiency and standardization. QA plan creation can be done without following tedious procedures through API assistance, and analysis can be performed inside of the clinical OIS in an automated fashion.

Portal dosimetry scripting application programming interface (PDSAPI) for Winston-Lutz test employing ceramic balls.

PURPOSE: Stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT) treatments require a high degree of accuracy. Mechanical, imaging, and radiation isocenter coincidence is especially important. As a common method, the Winston-Lutz (WL) test plays an important role. However, weekly or daily WL test can be very time consuming. We developed novel methods using Portal Dosimetry Scripting Application Programming Interface (PDSAPI) to facilitate the test as well as documentation. METHODS: Winston-Lutz PDSAPI was developed and tested on our routine weekly WL imaging. The results were compared against two commercially available software RIT (Radiological Imaging Technology, Colorado Springs, CO) and DoseLab (Varian Medical Systems, Inc. Palo Alto, CA). Two manual methods that served as ground truth were used to verify PDSAPI results. Twenty WL test image data sets (10 fields per tests, and 200 images in total) were analyzed by these five methods in this report. RESULTS: More than 99.5% of WL PDSAPI 1D shifts agreed with each of four other methods within ±0.33 mm, which is roughly the pixel width of a-Si 1200 portal imager when source to imager distance (SID) is at 100 cm. 1D shifts agreement for ±0.22 mm and 0.11 mm were 96% and 63%, respectively. Same trend was observed for 2D displacement. CONCLUSIONS: Winston-Lutz PDSAPI delivers similar accuracy as two commercial applications for WL test. This new application can save time spent transferring data and has the potential to implement daily WL test with reasonable test time. It also provides the data storage capability, and enables easy access to imaging and shift data.

Automated and robust beam data validation of a preconfigured ring gantry linear accelerator using a 1D tank with synchronized beam delivery and couch motions.

PURPOSE: To develop an efficient and automated methodology for beam data validation for a preconfigured ring gantry linear accelerator using scripting and a one-dimensional (1D) tank with automated couch motions. MATERIALS AND METHODS: Using an application programming interface, a program was developed to allow the user to choose a set of beam data to validate with measurement. Once selected the program generates a set of instructions for radiation delivery with synchronized couch motions for the linear accelerator in the form of an extensible markup language (XML) file to be delivered on the ring gantry linear accelerator. The user then delivers these beams while measuring with the 1D tank and data logging electrometer. The program also automatically calculates this set of beams on the measurement geometry within the treatment planning system (TPS) and extracts the corresponding calculated dosimetric data for comparison to measurement. Once completed the program then returns a comparison of the measurement to the predicted result from the TPS to the user and prints a report. In this work lateral, longitudinal, and diagonal profiles were taken for fields sizes of 6 × 6, 8 × 8, 10 × 10, 20 × 20, and 28 × 28 cm2 at depths of 1.3, 5, 10, 20, and 30 cm. Depth dose profiles were taken for all field sizes. RESULTS: Using this methodology, the TPS was validated to agree with measurement. All compared points yielded a gamma value less than 1 for a 1.5%/1.5 mm criteria (100% passing rate). Off axis profiles had >98.5% of data points producing a gamma value <1 with a 1%/1 mm criteria. All depth profiles produced 100% of data points with a gamma value <1 with a 1%/1 mm criteria. All data points measured were within 1.5% or 2 mm distance to agreement. CONCLUSIONS: This methodology allows for an increase in automation in the beam data validation process. Leveraging the application program interface allows the user to use a single system to create the measurement files, predict the result, and then compare to actual measurement increasing efficiency and reducing the chance for user input errors.

Equivalency of beam scan data collection using a 1D tank and automated couch movements to traditional 3D tank measurements.

This work shows the feasibility of collecting linear accelerator beam data using just a 1-D water tank and automated couch movements with the goal to maximize the cost effectiveness in resource-limited clinical settings. Two commissioning datasets were acquired: (a) using a standard of practice 3D water tank scanning system (3DS) and (b) using a novel technique to translate a commercial TG-51 complaint 1D water tank via automated couch movements (1DS). The Extensible Markup Language (XML) was used to dynamically move the linear accelerator couch position (and thus the 1D tank) during radiation delivery for the acquisition of inline, crossline, and diagonal profiles. Both the 1DS and 3DS datasets were used to generate beam models (BM1 DS and BM3 DS ) in a commercial treatment planning system (TPS). 98.7% of 1DS measured points had a gamma value (2%/2 mm) < 1 when compared with the 3DS. Static jaw defined field and dynamic MLC field dose distribution comparisons for the TPS beam models BM1 DS and BM3 DS had 3D gamma values (2%/2 mm) < 1 for all 24,900,000 data points tested and >99.5% pass rate with gamma value (1%/1 mm) < 1. In conclusion, automated couch motions and a 1D scanning tank were used to collect commissioning beam data with accuracy comparable to traditionally acquired data using a 3D scanning system. TPS beam models generated directly from 1DS measured data were clinically equivalent to a model derived from 3DS data.

Technical Note: Direct measurement of continuous TMR data with a 1D tank and automated couch movements.

PURPOSE: Real-time dynamic control of the linear accelerator, couch, and imaging parameters during radiation delivery was investigated as a novel technique for acquiring tissue maximum ratio (TMR) data. METHODS: TrueBeam Developer Mode (Varian Medical Systems, Palo Alto, CA, USA) was used to control the linear accelerator using the Extensible Markup Language (XML). A single XML file was used to dynamically manipulate the machine, couch, and imaging parameters during radiation delivery. A TG-51 compliant 1D water tank was placed on the treatment couch, and used to position a detector at isocenter at a depth of 24.5 cm. A depth scan was performed towards the water surface. Via XML control, the treatment couch vertical position was simultaneously lowered at the same rate, maintaining the detector position at isocenter, allowing for the collection of TMR data. To ensure the detector remained at isocenter during the delivery, the in-room camera was used to monitor the detector. Continuous kV fluoroscopic images during 10 test runs further confirmed this result. TMR data at multiple Source to Detector Distances (SDD) and scan speeds were acquired to investigate their impact on the TMR data. Percentage depth dose (PDD) scans (for conversion to TMR) along with traditional discrete TMR data were acquired as a standard for comparison. RESULTS: More than 99.8% of the measured points had a gamma value (1%/1 mm) < 1 when compared with discrete or PDD converted TMR data. Fluoroscopic images showed that the concurrent couch and tank movements resulted in SDD errors < 1 mm. TMRs acquired at SDDs of 99, 100, and 101 cm showed differences less than 0.004. CONCLUSION: TrueBeam Developer Mode was used to collect continuous TMR data with the same accuracy as traditionally collected discrete data, but yielded higher sampled resolution and reduced acquisition time. This novel method does not require the modification of any equipment and does not use a 3D tank or reservoir.

NIBBS-search for fast and accurate prediction of phenotype-biased metabolic systems.

Understanding of genotype-phenotype associations is important not only for furthering our knowledge on internal cellular processes, but also essential for providing the foundation necessary for genetic engineering of microorganisms for industrial use (e.g., production of bioenergy or biofuels). However, genotype-phenotype associations alone do not provide enough information to alter an organism's genome to either suppress or exhibit a phenotype. It is important to look at the phenotype-related genes in the context of the genome-scale network to understand how the genes interact with other genes in the organism. Identification of metabolic subsystems involved in the expression of the phenotype is one way of placing the phenotype-related genes in the context of the entire network. A metabolic system refers to a metabolic network subgraph; nodes are compounds and edges labels are the enzymes that catalyze the reaction. The metabolic subsystem could be part of a single metabolic pathway or span parts of multiple pathways. Arguably, comparative genome-scale metabolic network analysis is a promising strategy to identify these phenotype-related metabolic subsystems. Network Instance-Based Biased Subgraph Search (NIBBS) is a graph-theoretic method for genome-scale metabolic network comparative analysis that can identify metabolic systems that are statistically biased toward phenotype-expressing organismal networks. We set up experiments with target phenotypes like hydrogen production, TCA expression, and acid-tolerance. We show via extensive literature search that some of the resulting metabolic subsystems are indeed phenotype-related and formulate hypotheses for other systems in terms of their role in phenotype expression. NIBBS is also orders of magnitude faster than MULE, one of the most efficient maximal frequent subgraph mining algorithms that could be adjusted for this problem. Also, the set of phenotype-biased metabolic systems output by NIBBS comes very close to the set of phenotype-biased subgraphs output by an exact maximally-biased subgraph enumeration algorithm ( MBS-Enum ). The code (NIBBS and the module to visualize the identified subsystems) is available at http://freescience.org/cs/NIBBS.

Efficient α, ß-motif finder for identification of phenotype-related functional modules.

BACKGROUND: Microbial communities in their natural environments exhibit phenotypes that can directly cause particular diseases, convert biomass or wastewater to energy, or degrade various environmental contaminants. Understanding how these communities realize specific phenotypic traits (e.g., carbon fixation, hydrogen production) is critical for addressing health, bioremediation, or bioenergy problems. RESULTS: In this paper, we describe a graph-theoretical method for in silico prediction of the cellular subsystems that are related to the expression of a target phenotype. The proposed (α, ß)-motif finder approach allows for identification of these phenotype-related subsystems that, in addition to metabolic subsystems, could include their regulators, sensors, transporters, and even uncharacterized proteins. By comparing dozens of genome-scale networks of functionally associated proteins, our method efficiently identifies those statistically significant functional modules that are in at least α networks of phenotype-expressing organisms but appear in no more than ß networks of organisms that do not exhibit the target phenotype. It has been shown via various experiments that the enumerated modules are indeed related to phenotype-expression when tested with different target phenotypes like hydrogen production, motility, aerobic respiration, and acid-tolerance. CONCLUSION: Thus, we have proposed a methodology that can identify potential statistically significant phenotype-related functional modules. The functional module is modeled as an (α, ß)-clique, where α and ß are two criteria introduced in this work. We also propose a novel network model, called the two-typed, divided network. The new network model and the criteria make the problem tractable even while very large networks are being compared. The code can be downloaded from http://www.freescience.org/cs/ABClique/

Dietary modification and moderate antioxidant supplementation differentially affect serum carotenoids, antioxidant levels and markers of oxidative stress in older humans.

Oxidative stress is thought to be a factor in the progression of chronic diseases, and even the aging process itself. We examined the effect of two moderate vitamin, mineral and phytochemical supplements and a dietary intervention on markers of oxidative stress and antioxidant status in older humans. Subjects (n = 60, 65-85 y old) were enrolled in a 5-wk, double-blind, placebo-controlled study. The subjects were randomly assigned to a group with one of four interventions: antioxidant supplement capsule, antioxidant supplement tablet, high carotenoid diet or placebo. Postintervention serum levels of some of the supplemented carotenoids and alpha-tocopherol were higher in all treated groups compared with the placebo group and with preintervention levels within groups. Markers of oxidative stress or antioxidant capacity were not significantly different from preintervention levels, although the diet and supplement capsule groups had lower levels of some of those markers than the placebo group postintervention. The results suggest that both moderate antioxidant supplementation and a diet high in carotenoids elevate serum carotenoids and antioxidant levels in an older adult population, although with different specific effects.

Oxidative stress in humans training in a cold, moderate altitude environment and their response to a phytochemical antioxidant supplement.

OBJECTIVE: This study examined the effectiveness of an antioxidant mixture containing vitamin E, beta-carotene, ascorbic acid, selenium, alpha-lipoic acid, N-acetyl 1-cysteine, catechin, lutein, and lycopene to reduce oxidative stress in US Marines undergoing 24 days of cold-weather field training at a moderate altitude. METHODS: Forty physically active male volunteers (ages 18-40) were randomly assigned to a treatment (antioxidant) group (n = 21) or a control (placebo) group (n = 19). Breath pentane (BP), serum lipid hydroperoxides (LPO), urine malondialdehyde (MDA), urine 8-hydroxy deoxyguanosine (8-OHdG), ferric-reducing ability of plasma (FRAP), and serum and urine oxygen radical absorption capacity (ORAC) were measured as indicators of oxidative stress and antioxidant status. Urine was sampled at days 0, 12, and 24. Serum and breath were sampled on days 0 and 24. RESULTS: Both groups exhibited increased levels of oxidative stress after 24 days of field training, as indicated by an increased LPO, pentane, and 8-OHdG. There was no significant difference between the treatment and placebo groups at day 24; however, there was some indication that test subjects with initially low antioxidant capacity (ORAC) may have benefited from the antioxidant supplement. CONCLUSIONS: An increased level of oxidative stress was associated with high levels of physical exertion of training in a cold environment at moderate altitude. The antioxidant mixture tested did not attenuate the mean oxidative stress levels in the entire group of test subjects, but it may have reduced the oxidative stress of some individuals with low initial antioxidant status.