Evaluation of a method to measure fluorescent cell burden in complex culture systems.

Purpose. This work introduces and evaluates a method for accurate in-vitro measurement of fluorescent cell burden in complex 3D-culture conditions.Methods.The Fluorescent Cell Burden (FCB) method was developed to analyze the burden of 4T1 mCherry-expressing cells grown in an organotypic co-culture model of brain metastasis using 400µm rat brain slices. As a first step, representative simulated image-data accurately reflecting the 4T1 experimental data, but with known ground truth burden, were created. The FCB method was then developed in the CellProfiler software to measure the integrated intensity and area of the colonies in the simulated image data. Parameters in the pipeline were varied to span the experimentally observed range (e.g. of cell colony size) and the result compared with simulation ground truth to evaluate and optimize FCB performance. The optimized CellProfiler pipeline was then applied to the original 4T1 tumor cell images to determine colony growth with time, and re-applied with upper and lower bound parameters to determine uncertainty estimates.Results.The FCB method measured integrated intensity across 10 simulated images with an accuracy of 99.23% ± 0.75%. When colony density was increased by increasing colony number to 450, 600, and 750, the FCB measurement was 98.68%, 100.9%, 97.6% and 113.5% of the true value respectively. For the increasing number of cells plated on the rat brain slices, the integrated intensity increased nearly linearly with cell count except for at high cell counts, where it is hypothesized that shadowing from clumped cells causes a sub-linear relationship.Conclusion. The FCB method accurately measured an integrated fluorescent light intensity to within 5% of ground truth for a wide range of simulated image data spanning the range of observed variability in experimental data. The method is readily customizable to in-vitro studies requiring estimation of fluorescent tumor cell burden.

Fit-for-purpose characterization of air-liquid-interface (ALI) in vitro exposure systems for e-vapor aerosol.

Air-liquid-interface (ALI) exposure systems deliver aerosol to the apical surface of cells which mimics the in vivo inhalation exposure conditions. It is necessary, however, to quantify the delivered amount of aerosol for ALI-based in vitro toxicity assessment. In this study, we evaluated two commercially available ALI exposure systems, a Vitrocell® Ames 48 (Ames 48) and a Vitrocell® 24/48 (VC 24/48), and the Vitrocell® VC1/7 smoking machine using a cig-a-like cartridge-based e-vapor device with a prototype formulation (containing 4% nicotine by weight). We characterized aerosol particle-size distribution, aerosol mass, and major chemical components (nicotine, propylene glycol, and glycerol) at the generation source and verified the repeatability of the aerosol generation. We determined aerosol delivery at the ALI by gravimetric analysis of mass collected on Cambridge filter pads and analytical quantitation of the buffer medium which showed that both aerosol mass and nicotine to an exposure insert linearly increased up to 400 puffs. The delivered aerosol mass covered a wide range of 0.8-3.4 mg per insert in the Ames 48 with variability (relative standard deviation, RSD) up to 12% and 1.1-6.4 mg per insert in the VC 24/48 with variability up to 15%. The delivered nicotine ranged approximately up to 200 µg per insert in both exposure systems. These results provided operation and aerosol delivery information of these ALI exposure systems for subsequent in vitro testing of e-vapor aerosols.

Machine intelligence identifies soluble TNFa as a therapeutic target for spinal cord injury.

Traumatic spinal cord injury (SCI) produces a complex syndrome that is expressed across multiple endpoints ranging from molecular and cellular changes to functional behavioral deficits. Effective therapeutic strategies for CNS injury are therefore likely to manifest multi-factorial effects across a broad range of biological and functional outcome measures. Thus, multivariate analytic approaches are needed to capture the linkage between biological and neurobehavioral outcomes. Injury-induced neuroinflammation (NI) presents a particularly challenging therapeutic target, since NI is involved in both degeneration and repair. Here, we used big-data integration and large-scale analytics to examine a large dataset of preclinical efficacy tests combining five different blinded, fully counter-balanced treatment trials for different acute anti-inflammatory treatments for cervical spinal cord injury in rats. Multi-dimensional discovery, using topological data analysis (TDA) and principal components analysis (PCA) revealed that only one showed consistent multidimensional syndromic benefit: intrathecal application of recombinant soluble TNFα receptor 1 (sTNFR1), which showed an inverse-U dose response efficacy. Using the optimal acute dose, we showed that clinically-relevant 90 min delayed treatment profoundly affected multiple biological indices of NI in the first 48 h after injury, including reduction in pro-inflammatory cytokines and gene expression of a coherent complex of acute inflammatory mediators and receptors. Further, a 90 min delayed bolus dose of sTNFR1 reduced the expression of NI markers in the chronic perilesional spinal cord, and consistently improved neurological function over 6 weeks post SCI. These results provide validation of a novel strategy for precision preclinical drug discovery that is likely to improve translation in the difficult landscape of CNS trauma, and confirm the importance of TNFα signaling as a therapeutic target.

Variability of TSNA in U.S. Tobacco and Moist Smokeless Tobacco Products.

Tobacco-specific nitrosamines (TSNAs) have been of concern to the public health community for decades and their reduction through agricultural practices, plant breeding, and tobacco processing has also been a decades-long industry effort. Despite those efforts, TSNAs, though lower, continue to be constituents of concern in tobacco products. This paper examines the TSNA levels of dark air-cured, dark fire-cured, and burley tobaccos purchased in the United States by U.S. Smokeless Tobacco Company LLC (USSTC) and of nine finished USSTC moist smokeless tobacco products. TSNA values of the incoming purchased tobaccos and the finished products showed considerable variability. For the incoming tobaccos, the coefficient of variation was generally more than 100 % for each tobacco type and for each of the measured TSNAs. The relative TSNA variability of the finished tobacco products was also considerable, averaging approximately 25 %. It was also found that the measured values for the finished products averaged well above the proposed FDA NNN proposed product standard of 1.0 µg/g dry weight. Because of the large variability in NNN values, products would have to average well below FDA's proposed product standard to be consistently compliant.

Visual body size norms and the under-detection of overweight and obesity.

Objectives: The weight status of men with overweight and obesity tends to be visually underestimated, but visual recognition of female overweight and obesity has not been formally examined. The aims of the present studies were to test whether people can accurately recognize both male and female overweight and obesity and to examine a visual norm-based explanation for why weight status is underestimated. Methods: The present studies examine whether both male and female overweight and obesity are visually underestimated (Study 1), whether body size norms predict when underestimation of weight status occurs (Study 2) and whether visual exposure to heavier body weights adjusts visual body size norms and results in underestimation of weight status (Study 3). Results: The weight status of men and women with overweight and obesity was consistently visually underestimated (Study 1). Body size norms predicted underestimation of weight status (Study 2) and in part explained why visual exposure to heavier body weights caused underestimation of overweight (Study 3). Conclusions: The under-detection of overweight and obesity may have been in part caused by exposure to larger body sizes resulting in an upwards shift in the range of body sizes that are perceived as being visually 'normal'.

Long-term organ damage accrual and safety in patients with SLE treated with belimumab plus standard of care.

OBJECTIVE: To examine long-term organ damage and safety following treatment with belimumab plus standard of care (SoC) in patients with systemic lupus erythematosus (SLE). METHODS: Pooled data were examined from two ongoing open-label studies that enrolled patients who completed BLISS-52 or BLISS-76. Patients received belimumab every four weeks plus SoC. SLICC Damage Index (SDI) values were assessed every 48 weeks (study years) following belimumab initiation (baseline). The primary endpoint was change in SDI from baseline at study years 5-6. Incidences of adverse events (AEs) were reported for the entire study period. RESULTS: The modified intent-to-treat (MITT) population comprised 998 patients. At baseline, 940 (94.2%) were female, mean (SD) age was 38.7 (11.49) years, and disease duration was 6.7 (6.24) years. The mean (SD) SELENA-SLEDAI and SDI scores were 8.2 (4.18) and 0.7 (1.19), respectively; 411 (41.2%) patients had organ damage (SDI = 1: 235 (23.5%); SDI ≥ 2: 176 (17.6%)) prior to belimumab. A total of 427 (42.8%) patients withdrew overall; the most common reasons were patient request (16.8%) and AEs (8.5%).The mean (SD) change in SDI was +0.2 (0.48) at study years 5-6 (n = 403); 343 (85.1%) patients had no change from baseline in SDI score (SDI +1: 46 (11.4%), SDI +2: 13 (3.2%), SDI +3: 1 (0.2%)). Of patients without organ damage at baseline, 211/241 (87.6%) had no change in SDI and the mean change (SD) in SDI was +0.2 (0.44). Of patients with organ damage at baseline, 132/162 (81.5%) had no change in SDI and the mean (SD) change in SDI was +0.2 (0.53). The probability of not having a worsening in SDI score was 0.88 (95% CI: 0.85, 0.91) and 0.75 (0.67, 0.81) in those without and with baseline damage, respectively (post hoc analysis).Drug-related AEs were reported for 433 (43.4%) patients; infections/infestations (282, 28.3%) and gastrointestinal disorders (139, 13.9%) were the most common. CONCLUSION: Patients with SLE treated with long-term belimumab plus SoC had a low incidence of organ damage accrual and no unexpected AEs. High-risk patients with pre-existing organ damage also had low accrual, suggesting a favorable effect on future damage development.

Treatment Planning and Delivery of Whole Brain Irradiation with Hippocampal Avoidance in Rats.

BACKGROUND: Despite the clinical benefit of whole brain radiotherapy (WBRT), patients and physicians are concerned by the long-term impact on cognitive functioning. Many studies investigating the molecular and cellular impact of WBRT have used rodent models. However, there has not been a rodent protocol comparable to the recently reported Radiation Therapy Oncology Group (RTOG) protocol for WBRT with hippocampal avoidance (HA) which is intended to spare cognitive function. The aim of this study was to develop a hippocampal-sparing WBRT protocol in Wistar rats. METHODS: The technical and clinical challenges encountered in hippocampal sparing during rat WBRT are substantial. Three key challenges were identified: hippocampal localization, treatment planning, and treatment localization. Hippocampal localization was achieved with sophisticated imaging techniques requiring deformable registration of a rat MRI atlas with a high resolution MRI followed by fusion via rigid registration to a CBCT. Treatment planning employed a Monte Carlo dose calculation in SmART-Plan and creation of 0.5 cm thick lead blocks custom-shaped to match DRR projections. Treatment localization necessitated the on-board image-guidance capability of the XRAD C225Cx micro-CT/micro-irradiator (Precision X-Ray). Treatment was accomplished with opposed lateral fields with 225 KVp X-rays at a current of 13 mA filtered through 0.3 mm of copper using a 40x40 mm square collimator and the lead blocks. A single fraction of 4 Gy was delivered (2 Gy per lateral field) with a 41 second beam on time per field at a dose rate of 304.5 cGy/min. Dosimetric verification of hippocampal sparing was performed using radiochromic film. In vivo verification of HA was performed after delivery of a single 4 Gy fraction either with or without HA using γ-H2Ax staining of tissue sections from the brain to quantify the amount of DNA damage in rats treated with HA, WBRT, or sham-irradiated (negative controls). RESULTS: The mean dose delivered to radiochromic film beneath the hippocampal block was 0.52 Gy compared to 3.93 Gy without the block, indicating an 87% reduction in the dose delivered to the hippocampus. This difference was consistent with doses predicted by Monte Carlo dose calculation. The Dose Volume Histogram (DVH) generated via Monte Carlo simulation showed an underdose of the target volume (brain minus hippocampus) with 50% of the target volume receiving 100% of the prescription isodose as a result of the lateral blocking techniques sparing some midline thalamic and subcortical tissue. Staining of brain sections with anti-phospho-Histone H2A.X (reflecting double-strand DNA breaks) demonstrated that this treatment protocol limited radiation dose to the hippocampus in vivo. The mean signal intensity from γ-H2Ax staining in the cortex was not significantly different from the signal intensity in the cortex of rats treated with WBRT (5.40 v. 5.75, P = 0.32). In contrast, the signal intensity in the hippocampus of rats treated with HA was significantly lower than rats treated with WBRT (4.55 v. 6.93, P = 0.012). CONCLUSION: Despite the challenges of planning conformal treatments for small volumes in rodents, our dosimetric and in vivo data show that WBRT with HA is feasible in rats. This study provides a useful platform for further application and refinement of the technique.

Computational modeling of nanoscale and microscale particle deposition, retention and dosimetry in the mouse respiratory tract.

Comparing effects of inhaled particles across rodent test systems and between rodent test systems and humans is a key obstacle to the interpretation of common toxicological test systems for human risk assessment. These comparisons, correlation with effects and prediction of effects, are best conducted using measures of tissue dose in the respiratory tract. Differences in lung geometry, physiology and the characteristics of ventilation can give rise to differences in the regional deposition of particles in the lung in these species. Differences in regional lung tissue doses cannot currently be measured experimentally. Regional lung tissue dosimetry can however be predicted using models developed for rats, monkeys, and humans. A computational model of particle respiratory tract deposition and clearance was developed for BALB/c and B6C3F1 mice, creating a cross-species suite of available models for particle dosimetry in the lung. Airflow and particle transport equations were solved throughout the respiratory tract of these mice strains to obtain temporal and spatial concentration of inhaled particles from which deposition fractions were determined. Particle inhalability (Inhalable fraction, IF) and upper respiratory tract (URT) deposition were directly related to particle diffusive and inertial properties. Measurements of the retained mass at several post-exposure times following exposure to iron oxide nanoparticles, micro- and nanoscale C60 fullerene, and nanoscale silver particles were used to calibrate and verify model predictions of total lung dose. Interstrain (mice) and interspecies (mouse, rat and human) differences in particle inhalability, fractional deposition and tissue dosimetry are described for ultrafine, fine and coarse particles.

An investigation of a PRESAGE® in vivo dosimeter for brachytherapy.

Determining accurate in vivo dosimetry in brachytherapy treatment with high dose gradients is challenging. Here we introduce, investigate, and characterize a novel in vivo dosimeter and readout technique with the potential to address this problem. A cylindrical (4 mm × 20 mm) tissue equivalent radiochromic dosimeter PRESAGE® in vivo (PRESAGE®-IV) is investigated. Two readout methods of the radiation induced change in optical density (OD) were investigated: (i) volume-averaged readout by spectrophotometer, and (ii) a line profile readout by 2D projection imaging utilizing a high-resolution (50 micron) telecentric optical system. Method (i) is considered the gold standard when applied to PRESAGE® in optical cuvettes. The feasibility of both methods was evaluated by comparison to standard measurements on PRESAGE® in optical cuvettes via spectrophotometer. An end-to-end feasibility study was performed by a side-by-side comparison with TLDs in an (192)Ir HDR delivery. 7 and 8 Gy was delivered to PRESAGE®-IV and TLDs attached to the surface of a vaginal cylinder. Known geometry enabled direct comparison of measured dose with a commissioned treatment planning system. A high-resolution readout study under a steep dose gradient region showed 98.9% (5%/1 mm) agreement between PRESAGE®-IV and Gafchromic® EBT2 Film. Spectrometer measurements exhibited a linear dose response between 0-15 Gy with sensitivity of 0.0133 ± 0.0007 ΔOD/(Gy ⋅ cm) at the 95% confidence interval. Method (ii) yielded a linear response with sensitivity of 0.0132 ± 0.0006 (ΔOD/Gy), within 2% of method (i). Method (i) has poor spatial resolution due to volume averaging. Method (ii) has higher resolution (∼1 mm) without loss of sensitivity or increased noise. Both readout methods are shown to be feasible. The end-to-end comparison revealed a 2.5% agreement between PRESAGE®-IV and treatment plan in regions of uniform high dose. PRESAGE®-IV shows promise for in vivo dose verification, although improved sensitivity would be desirable. Advantages include high-resolution, convenience and fast, low-cost readout.

Investigating end-to-end accuracy of image guided radiation treatment delivery using a micro-irradiator.

There is significant interest in delivering precisely targeted small-volume radiation treatments, in the pre-clinical setting, to study dose-volume relationships with tumour control and normal tissue damage. For these studies it is vital that image guidance systems and target positioning are accurately aligned (IGRT), in order to deliver dose precisely and accurately according to the treatment plan. In this work we investigate the IGRT targeting accuracy of the X-RAD 225 Cx system from Precision X-Ray using high-resolution 3D dosimetry techniques. Small cylindrical PRESAGE® dosimeters were used with optical-CT readout (DMOS) to verify the accuracy of 2.5, 1.0, and 5.0 mm X-RAD cone attachments. The dosimeters were equipped with four target points, visible on both CBCT and optical-CT, at which a 7-field coplanar treatment plan was delivered with the respective cone. Targeting accuracy (distance to agreement between the target point and delivery isocenter) and cone alignment (isocenter precision under gantry rotation) were measured using the optical-CT images. Optical-CT readout of the first 2.5 mm cone dosimeter revealed a significant targeting error of 2.1 ± 0.6 mm and a cone misalignment of 1.3 ± 0.1 mm. After the IGRT hardware and software had been recalibrated, these errors were reduced to 0.5 ± 0.1 and 0.18 ± 0.04 mm respectively, within the manufacturer specified 0.5 mm. Results from the 1.0 mm cone were 0.5 ± 0.3 mm targeting accuracy and 0.4 ± 0.1 mm cone misalignment, within the 0.5 mm specification. The results from the 5.0 mm cone were 1.0 ± 0.2 mm targeting accuracy and 0.18 ± 0.06 mm cone misalignment, outside of accuracy specifications. Quality assurance of small field IGRT targeting and delivery accuracy is a challenging task. The use of a 3D dosimetry technique, where targets are visible on both CBCT and optical-CT, enabled identification and quantification of a targeting error in 3D. After correction, the targeting accuracy of the irradiator was verified to be within 0.5 mm (or 1.0 mm for the 5.0 mm cone) and the cone alignment was verified to be within 0.2 mm (or 0.4 mm for the 1.0 mm cone). The PRESAGE®/DMOS system proved valuable for end-to-end verification of small field IGRT capabilities.

The effect of motion on IMRT - looking at interplay with 3D measurements.

Six base of skull IMRT treatment plans were delivered to 3D dosimeters within the RPC Head and Neck Phantom for QA verification. Isotropic 2mm 3D data was obtained using the DLOS-PRESAGE system and compared to an Eclipse (Varian) treatment plan. Normalized Dose Distribution pass rates were obtained for a number of criteria. High quality 3D dosimetry data was observed from the DLOS system, illustrated here through colormaps, isodose lines, profiles, and NDD 3D maps. Excellent agreement with the planned dose distributions was also observed with NDD analysis revealing > 90% NDD pass rates [3%, 2mm], noise < 0.5%. This paper focuses on a detailed exploration of the quality and use of 3D dosimetry data obtained with the DLOS-PRESAGE system.

Investigating the reproducibility of a complex multifocal radiosurgery treatment.

Stereotactic radiosurgery has become a widely used technique to treat solid tumors and secondary metastases of the brain. Multiple targets can be simultaneously treated with a single isocenter in order to reduce the set-up time to improve patient comfort and workflow. In this study, a 5-arc multifocal RapidArc treatment was delivered to multiple PRESAGE® dosimeters in order to explore the repeatability of the treatment. The three delivery measurements agreed well with each other, with less than 3% standard deviation of dose in the target. The deliveries also agreed well with the treatment plan, with gamma passing rates greater than 90% (5% dose-difference, and 2 mm distance-to-agreement criteria). The optical-CT PRESAGE® system provided a reproducible measurement for treatment verification, provided measurements were made immediately following treatment.

Customising PRESAGE® for diverse applications.

PRESAGE® is a solid radiochromic dosimeter consisting of a polyurethane matrix, a triarylmethane leuco dye, and a trihalomethane initiator. Varying the composition and/or relative amounts of these constituents can affect the dose sensitivity, post-irradiation stability, and physical properties of the dosimeter. This allows customisation of PRESAGE® to meet application-specific requirements, such as low sensitivity for high dose applications, stability for remote dosimetry, optical clearing for reusability, and tissue-like elasticity for deformable dosimetry. This study evaluates five hard, non-deformable PRESAGE® formulations and six deformable PRESAGE® formulations and characterizes them for dose sensitivity and stability. Results demonstrated sensitivities in the range of 0.0029 - 0.0467 ΔOD/(Gy·cm) for hard formulations and 0.0003 - 0.0056 ΔOD/(Gy·cm) for deformable formulations. Exceptional stability was seen in both standard and low sensitivity non-deformable formulations, with promising applications for remote dosimetry. Deformable formulations exhibited potential for reusability with strong post-irradiation optical clearing. Tensile compression testing of the deformable formulations showed elastic response consistent with soft tissues, with further testing required for direct comparison. These results demonstrate that PRESAGE® dosimeters have the flexibility to be adapted for a wide spectrum of clinical applications.

Comprehensive quality assurance for base of skull IMRT.

Six base of skull IMRT treatment plans were delivered to Presage dosimeters within the RPC Head and Neck Phantom for quality assurance (QA) verification. Isotropic 2mm 3D data were acquired by optical-CT scanning with the DLOS system (Duke Large Optical-CT Scanner) and compared to the Eclipse (Varian) treatment plan. Normalized Dose Distribution (NDD) pass rates were obtained for a number of criteria. High quality 3D dosimetry data was observed from the DLOS system, illustrated here through colormaps, isodose lines, and profiles. Excellent agreement with the planned dose distributions was also observed with NDD analysis revealing > 90% pass rates (with criteria 3%, 2mm), and noise < 0.5%. The results comprehensively confirm the high accuracy of base-of-skull IMRT treatment in our clinic.

Evaluation of a clinically intuitive quality assurance method.

There is a pressing need for clinically intuitive quality assurance methods that report metrics of relevance to the likely impact on tumor control of normal tissue injury. This paper presents a preliminary investigation into the accuracy of a novel "transform method" which enables a clinically relevant analysis through dose-volume-histograms (DVHs) and dose overlays on the patient's CT data. The transform method was tested by inducing a series of known mechanical and delivery errors onto simulated 3D dosimetry measurements of six different head-and-neck IMRT treatment plans. Accuracy was then examined through the comparison of the transformed patient dose distributions and the known actual patient dose distributions through dose-volume histograms and normalized dose difference analysis. Through these metrics, the transform method was found to be highly accurate in predicting measured patient dose distributions for these types of errors.

How accurate is image guided radiation therapy (IGRT) delivered with a micro-irradiator?

There is significant interest in delivering precisely targeted small-volume radiation treatments, in the pre-clinical setting, to study dose-volume relationships with tumor control and normal tissue damage. In this work we investigate the IGRT targeting accuracy of the XRad225Cx system from Precision x-Ray using high resolution 3D dosimetry techniques. Initial results revealed a significant targeting error of about 2.4mm. This error was reduced to within 0.5mm after the IGRT hardware and software had been recalibrated. The facility for 3D dosimetry was essential to gain a comprehensive understanding of the targeting error in 3D.

Preliminary investigation and application of a novel deformable PRESAGE® dosimeter.

Deformable 3D dosimeters have potential applications in validating deformable dose mapping algorithms. This study evaluates a novel deformable PRESAGE® dosimeter and its application toward validating the deformable algorithm employed by VelocityAI. The deformable PRESAGE® dosimeter exhibited a linear dose response with a sensitivity of 0.0032 ΔOD/(Gy/cm). Comparison of an experimental dosimeter irradiated with an MLC pencilbeam checkerboard pattern under lateral compression up to 27% to a non-deformed control dosimeter irradiated with the same pattern verified dose tracking under deformation. CTs of the experimental dosimeter prior to and during compression were exported into VelocityAI and used to map an Eclipse dose distribution calculated on the compressed dosimeter to its original shape. A comparison between the VelocityAI dose distribution and the distribution from the dosimeter showed field displacements up to 7.3 mm and up to a 175% difference in field dimensions. These results highlight the need for validating deformable dose mapping algorithms to ensure patient safety and quality of care.

Towards comprehensive characterization of Cs-137 Seeds using PRESAGE® dosimetry with optical tomography.

We describe a method to directly measure the radial dose and anisotropy functions of brachytherapy sources using polyurethane based dosimeters read out with optical CT. We measured the radial dose and anisotropy functions for a Cs-137 source using a PRESAGE® dosimeter (9.5cm diameter, 9.2cm height) with a 0.35cm channel drilled for source placement. The dosimeter was immersed in water and irradiated to 5.3Gy at 1cm. Pre- and post-irradiation optical CT scans were acquired with the Duke Large field of view Optical CT Scanner (DLOS) and dose was reconstructed with 0.5mm isotropic voxel size. The measured radial dose factor matched the published fit to within 3% for radii between 0.5-3.0cm, and the anisotropy function matched to within 4% except for θ near 0° and 180° and radii >3cm. Further improvements in measurement accuracy may be achieved by optimizing dose, using the high dynamic range scanning capability of DLOS, and irradiating multiple dosimeters. Initial simulations indicate an 8 fold increase in dose is possible while still allowing sufficient light transmission during optical CT. A more comprehensive measurement may be achieved by increasing dosimeter size and flipping the source orientation between irradiations.

Locating, quantifying and characterising radiation hazards in contaminated nuclear facilities using a novel passive non-electrical polymer based radiation imaging device.

This paper provides a summary of recent trials which took place at the US Department of Energy Oak Ridge National Laboratory (ORNL) during December 2010. The overall objective for the trials was to demonstrate that a newly developed technology could be used to locate, quantify and characterise the radiological hazards within two separate ORNL hot cells (B and C). The technology used, known as RadBall(®), is a novel, passive, non-electrical polymer based radiation detection device which provides a 3D visualisation of radiation from areas where effective measurements have not been previously possible due to lack of access. This is particularly useful in the nuclear industry prior to the decommissioning of facilities where the quantity, location and type of contamination are often unknown. For hot cell B, the primary objective of demonstrating that the technology could be used to locate, quantify and characterise three radiological sources was met with 100% success. Despite more challenging conditions in hot cell C, two sources were detected and accurately located. To summarise, the technology performed extremely well with regards to detecting and locating radiation sources and, despite the challenging conditions, moderately well when assessing the relative energy and intensity of those sources. Due to the technology's unique deployability, non-electrical nature and its directional awareness the technology shows significant promise for the future characterisation of radiation hazards prior to and during the decommissioning of contaminated nuclear facilities.

TU-E-BRB-09: Validation of Multi-Focal Stereotactic Radiosurgery with Volumetric Modulated Arc Therapy with High-Resolution 3D Dosimetry.

PURPOSE: Volumetric modulated arc therapy (VMAT) enables stereotactic radiosurgery (SRS) treatment for multiple lesions with a single isocenter setup. Dosimetry verification is highly challenging however, and the purpose of this study is to validate this new treatment using novel 3D dosimetry techniques, with potential for dramatically more comprehensive verification than possible with conventional approaches. METHODS: A cylindrical PRESAGE dosimeter was inserted into an RPC type head phantom for treatment validation. The phantom was immobilized with an SRS U-frame system and a set of simulation CT images was acquired with a SRS localizer. A 5-arc VMAT multi-focal SRS plan was created to treat 5 intracranial lesions simultaneously. A set of cone-beam CT (CBCT) images was then acquired to localize the isocenter, and the VMAT plan delivered to the combined phantom. The PRESAGE dosimeter was then removed and scanned by optical-computed-tomography (optical-CT). The 3D PRESAGE dose measurement was reconstructed with 1 mm resolution. Another PRESAGE insert with a pre-drilled ion chamber channel was placed in the phantom and an SRS ion chamber was mounted for an absolute dose measurement. The phantom was again localized with CBCT and the VMAT plan was delivered. The dose measured with the ion chamber was compared with calculated dose. RESULTS: The mean planned and PRESAGE measured doses to target 1 were 12.1Gy and 12.2 Gy, 18.7 Gy and 18.5 Gy for target 2, 18.6 Gy and 18.4 Gy for target 3, 15.5 Gy and 15.4 Gy for target 4, 18.7 Gy and 19.0 Gy for target 5. The 3D gamma passing rate was 95.6% for 3% and 1mm. The ion chamber measured dose was within 1% of the planned dose. CONCLUSIONS: Our 3D PRESAGE dose measurement shows that multi-focal VMAT is a valid technique for single isocenter SRS treatment of multiple lesions. This research is partially supported by NCI R01CA100835. This research is partially supported by NCI R01CA100835.