bluuebunny/crossref_metadata_2025 huggingface dataset:
TU‐D‐BRA‐01: Treating a Moving Target under the Guidance of Hybrid kV and MV Imaging
Authors: Wiersma R
Published: August 2010

In recent years, MV and kV electronic flat panel imaging devices have become commonplace equipment installed on the gantry of many newer medical LINACs. Such imaging devices are now routinely used in the clinic for verification of correct initial patient setup before start of a treatment fraction. This is done through MV portal images, 2D kV fluoroscopic images, or cone‐beam CT. However, these amorphous‐silicon detectors have not been used to their full potential. With high resolution imaging capture rates of ∼ 10 frames per second, the role of these MV and kV detectors can be additionally expanded to include real‐time target tracking during the actual radiation treatment delivery process.

This lecture will provide an overview of recent research in the use of MV and kV imagers for real‐time tracking purposes. In addition, an explanation of the basic theory and methods necessary to perform real‐time tracking will be discussed.

Learning Objectives:

1. Fundamentals of MV and kV flat panel detectors.

2. Image processing and prediction methods used for real‐time MV and kV intheclinic.

3. Issues involved in implementing hybrid MV and kV in the clinic.
WE‐A‐204B‐01: Possible Causes for the Reduced Efficacy of US Based Image Guided Treatment of Prostate Cancer with External Beam Radiation Therapy
Authors: Van den Heuvel F
Published: August 2010

Ultrasound systems have been in use to provide image guided radiation therapy for more than a decade. They have been instrumental in changing the treatment paradigm in which it became accepted to take a longer time to visualize the internal organs in order to facilitate more precise treatments. Indeed the first results led to the generation of on‐line correction protocols and the notion that it was possible to treat tumors using smaller margins. Prostate treatments were the most popular to be used with this approach, although other organs could be targeted too.

After its introduction questions arose regarding the reliability of this approach. A number of groups reported discrepancies independently of each other as well as providing different explanations. Unfortunately, a consensus as to why exactly these problems occur is lacking.

This paper investigates the causes for the variations observed by:

1. Revisiting the original data and conclusions,

2. Re‐interpret the data in view of the current state of knowledge regarding intra‐fractional motion,

3. Observe how the current updates in technology affect the efficacy, and

4. Introduce newer developments in ultrasound technology pertaining to its use in radiation oncology.

It is the goal of this presentation to elucidate a number of techniques used in the analysis:

1. How to compare sets of positioning data and perform robust statistical data‐analysis

2. Interpret organ motion to yield margin sizes to compensate for setup and patient motion

3. Learn about the main modes of motion of different organs during treatments

4. Learn the different parameters affecting the measurement using ultrasound to perform absolute positioning

5. Learn about comparing images stemming from different modalities.
WE‐A‐204B‐03: Image Guidance of Focused Ultrasound
Authors: Pauly K Butts
Published: August 2010

Ultrasound can be focused to interact with tissues and deliver drugs deep within the body, without damage to overlying tissues. Image guidance is important for targeting therapy, ensuring treatment and safety, and for assessing therapy. Ultrasound imaging, magnetic resonance imaging, optical imaging, and PET are all being developed and evaluated for these tasks. This presentation will describe some current research areas in the image guidance of focused ultrasound.

For tissue ablation, it is critically important to monitor tissue temperature. This is possible with both ultrasound imaging and MRI. A current research area concerns thermal ablations of moving organs, such as the liver and kidneys. We have developed a method for FUS ablation of abdominal organs including real‐time MR thermometry, organ and transducer tracking, and beam steering.

There are a number of methods under investigation for the visualization of ablated tissue. Both ultrasound‐based and MR‐based acoustic radiation force imaging (ARFI) methods are potential candidates. ARFI relies on tissue displacement by the ultrasound beam, which is related to the tissue stiffness. Evaluating the change in tissue stiffness provides the spatial extent of the thermal ablation. Other evaluative imaging includes contrast enhanced MRI, which visualizes disruption of perfusion, and diffusion‐weighted MRI, which demonstrates a 30% decrease in ADC in the ablated tissue.

The displacement visualized with ARFI is also proportional to the ultrasound intensity. Therefore, visualization of the focal spot can be done without a significant temperature rise. In the MR‐guided neurosurgical applications of focused ultrasound, this could allow the focal spot to be visualized more safely than with a small temperature rise required for MR thermometry visualization. In addition, it provides a means for image feedback when correcting phase aberrations from the skull.

For drug delivery, image monitoring of delivery is being developed with MRI, PET, and optical imaging. Blood‐brain barrier opening can be detected with uptake of a gadolinium contrast agent on MR‐images. Investigators at UC Davis have shown that the drug shell can be visualized with PET, while the contents are visualized with optical imaging, to enable visualization of the drug release.

Learning Objectives:

1. Understand the basis for acoustic radiation force imaging and its applications

2. Understand the current research in the image guidance of focused ultrasound
WE‐C‐204B‐02: Disparity between 4DCT and CBCT Reconstruction of Internal Target Volumes
Authors: Watkins WT , Kauweloa K , Park J , Lewis J , Song WY
Published: August 2010

Purpose: Internal target volumes (ITVs) generated from different imaging modalities may not be identical. These differences could be due to inherent limitations in image reconstruction, and in this study we investigate the differences between 4DCT‐MIP generated ITVs and CBCT reconstructions of moving targets. Methods/Materials: A cork lung phantom with three embedded targets was attached to a programmable motion platform to simulate lung and tumor motion. Ideal sinusoidal motion and other simulated patterns were used to compare ITV dimensions reconstructed from 4DCT and CBCT. Four 4DCT and ten CBCT generated ITVs from four lung cancer patients were also compared using a physician's contour as ground truth. Results: CBCT targets along the direction of motion were consistently smaller than the 4DCT equivalents (by 0.49 +/− 0.50 cm) in the phantom measurements. The amplitude was varied during a single scan from 1 to 4 cm, and both 4DCT and CBCT under‐represented the ground truth dimension by 2.13 (+/−0.64) cm and 2.69 (+/−0.50) cm. Patient lung tumors did not reveal a similar pattern of smaller ITVs from CBCT. Lateral motion due to proximity to the heart resulted in lateral discrepancies for two patients, with CBCT ITV 0.32 cm and 0.68 cm larger than the 4DCT ITV. For the two other patients, the CBCT ITV was larger along the tumor's primary direction of motion. Conclusions: Even under ideal periodic motion, CBCT generated ITVs can deviate from their 4DCT counterparts. These variations are often assumed to be due to physiological changes, but may actually occur due to limitations in CBCT reconstruction. If irregular motion in actual patient cases is observed, the discrepancy between the 4DCT ITV and the CBCT counterpart can be greater than 5mm and adaptive re‐optimization based on CBCT ITV may not be beneficial.
WE‐C‐204B‐03: 4D Treatment Delivery to Account for Motion, Rotation, and Deformation of Tumors and Normal Tissues
Authors: Suh Y , Cho B , Sawant A , Keall P
Published: August 2010

Purpose: To experimentally investigate 4D treatment delivery to account for motion, rotation, and deformation of tumors and normal tissues. Method and Materials: A 4D treatment plan was generated as a function of respiratory phase for an elliptical tumor that translates, rotates, deforms, and exhibits motion hysteresis throughout the respiratory cycle. A programmable motion platform with a marker block simulates the tumor motion. An independent patient position monitoring system monitors motion of marker block and provides 3D position and respiratory phase information in real time for the dynamic MLC motion‐tracking software. Using the position and phase information and the 4D treatment plan, the dynamic MLC motion‐tracking software repositions and/or reshapes the radiation beams to deliver treatment. An MV imager operating in a cine mode was used to acquire images to quantify tumor motion, rotation, and deformation. 4D treatment delivery was performed when the target motion during treatment delivery was the same as, smaller than, and larger than during imaging. For comparison, static delivery of treatment plans for each of the respiratory phases was performed. Results: The elliptical tumor segmented from MV images between 4D and static delivery showed the difference of centroid positions less than 5 mm, rotation less than 10 degrees, and major and minor axis lengths less than 2 mm each. 4D treatment delivery was comparable to static delivery of each phase treatment plan, demonstrating the ability of dynamic MLC to account for changes in anatomic motion, rotation, and deformation by varying MLC leaves as a function of phase. Conclusion: 4D treatment plans generated to account for motion, rotation, and deformation of tumors and normal tissues within a respiratory cycle at the planning stage can be delivered while still accounting for different target motion during delivery at the delivery stage. Research supported by NIH/NCIR01‐93626 and Varian Medical Systems
WE‐C‐204B‐04: Image‐Based Scoring of Radiation Injury in Lung for Dose‐Effect Correlations: Analysis of Sources of Uncertainties
Authors: Lee S , Stroian G , Naqa I El , Seuntjens J
Published: August 2010

Purpose: To investigate the robustness and uncertainties of an automated method of quantifying radiation‐induced lung injuries (pneumonitis and fibrosis) from CT image density changes and to correlate the probabilities for the injuries with radiation dose at different post‐radiation time points.Methods and Materials: Using multi‐resolution affine optimization technique, post‐radiotherapy (RT) diagnostic CT images were registered to planning CT images. Following the registration and patient tissue‐based CT number calibration, a change in physical density at each voxel position of the post‐RT CT was evaluated and the voxels which density change is considered pathological was segmented as injury. The PTV was excluded from the analysis due to the lack of functional information to differentiate between recurrence and injury. Retrospective patient dose calculations using the anisotropic analytical method (AAA) and the Monte‐Carlo (MC) were performed. The segmented injury was spatially correlated to the dose distributions to deduce a patient‐specific dose‐response relationship for the radiation‐induced injury. Results: Probability of lung injury as a function of dose and post‐treatment time is patient‐dependent and can be up to 70% at the highest dose. Due to the inaccuracy of the affine registration, the injury segmentation was manually corrected for the misalignment of normal tissue features, which gave rise to a case‐dependent uncertainty of up to 10%. Inter‐patient variability in CT calibration contributed by 4% or less to the uncertainty on the complication probability and was dependent on dose. Finally, dose calculation from direct MC simulation occasionally yielded a significantly modified complication probability than using the AAA model suggesting that dose calculation accuracy is important in the accuracy of dose‐response model of lung. Conclusion: The presented method facilitates dose‐response analysis in normal lung tissues if the accuracy in image registration and dose calculation can be assured and will provide options to complication‐driven treatment planning.
WE‐C‐204B‐06: Tumor Specific Reconstruction of Motion Probability Density Function from 4DCT
Authors: Watkins WT , Lewis J , Park J , Li R , Jiang SB , Song WY
Published: August 2010

Purpose: The actual delivered dose to a moving tumor can deviate from prescribed dose not only during each fraction, but during each IMRT field. This deviation can be anticipated and incorporated into a treatment plan if the tumor specific motion probability density function (PDF) is accurately identified. In this study, a novel technique in determining the actual, tumor specific PDF of a moving gross tumor volume (GTV) is described and confirmed through phantom experiments using a quantitative approach of 4DCT imaging. Methods and Materials: We hypothesize that a PDF of the GTV can be obtained through weighted sums of phase‐sorted 4DCT images. Experimental validation is performed using a lung phantom attached to a programmable motion platform. The ground truth motion PDF of the targets was calculated through convolution of the motion pattern and the GTV dimension along the direction of motion. These PDF convolutions are compared to the normalized, reconstructed CT numbers obtained from averaging ten phase sorted 4DCT images after background subtraction. Results: The PDF reconstructed from averaged, weighted sets of 4DCT images was almost identical to the ground truth PDF in all comparisons made. Through sums of phase sorted 4DCT images, the resulting CT number represents a relative probability of finding some portion of the GTV in each geometric location (or voxel). In physical phantom reconstructions, the Pearson correlation coefficient between CT‐based PDF and the ground truth PDF was greater than .97 in all cases considered. An actual patient PDF was also evaluated in frontal and sagittal planes. Conclusions: Combining phase sorted CT images is an effective method in obtaining the actual tumor PDF as seen by an IMRT field. With the patient specific PDF, treatment planning to ensure proper target coverage can be achieved through intra‐field modulation, dose rate, and monitoring initial beam‐on phase.
WE‐D‐BRA‐01: Stereotactic Body Radiotherapy (SBRT): Technical and Clinical Considerations
Authors: Kavanagh B , Chetty IJ , Balter JM , Solberg TD
Published: August 2010

Stereotactic Body Radiotherapy (SBRT) has now been applied clinically for more than a decade. The accumulation of published technical and clinical studies currently available has offered insights into both the efficacy and special concerns associated with the delivery of SBRT to different sites. The safe and effective delivery of SBRT requires careful attention to tumor motion management, special dosimetric and planning challenges, and commissioning of dedicated equipment and quality assurance. This session will provide an overview of these important technical considerations as well as a survey of clinical outcomes reported based on the use of SBRT in the treatment of different tumor sites.

Learning Objectives:

1. Describe available methods for motion management and the rational selection of planning margins

2. Discuss techniques for SBRT treatment planning and the impact of dose calculation algorithm

3. Describe key elements of commissioning, patient‐specific QA, and routine periodic machine performance QA

4. Review clinical observations reported after SBRT for lung, liver, pancreas, spine, head & neck, and prostate
WE‐D‐BRB‐01: Experimental Characterization of the Low‐Dose Envelope of Spot Scanning Proton Beams
Authors: Sawakuchi G , Zhu X , Poenisch F , Suzuki K , Ciangaru G , Titt U , Anand A , Mohan R , Gillin M , Sahoo N
Published: August 2010

Purpose: To measure the low‐dose envelope of spot scanning proton pencil beams. Method and Materials: Measurements were performed in the spot scanning proton pencil beam nozzle at M. D. Anderson Cancer Center. We directly measured the low‐dose envelope by measuring single pencil beams' lateral profiles at central axis to relative dose levels that were a factor of 10−4 lower than the central axis dose. We also indirectly measure the low‐dose envelope by measuring the effect of the filed size on central axis point doses using a plane parallel ionization chamber. Results: For lowest (72.5 MeV) and highest (221.8 MeV) energy beams in‐air at isocenter plane, the full width (FW) at half maximum ranged from 1.26 ± 0.02 cm to 3.43 ± 0.02 cm; the FW at 1% maximum ranged from 3.99 ± 0.25 cm to 11.41± 0.25 cm; and the FW at 0.1% maximum ranged from 6.6 ± 0.5 cm to 17.9 ± 0.5 cm, respectively. The effect of the field size on central axis point doses showed strong dependence with energy and depth. Conclusion: We showed that it is possible to accurately measure the low‐dose envelope down to a dose level of 10−4 of the central axis dose using standard dosimetric equipment. Because of the large lateral extent of the beams, care should be taken when measuring integral depth doses, which are input parameters for analytical dose calculation algorithms. Additionally, we observed that the in‐air fluence of the pencil beams has various components due to scattering in the beam line and cannot be accurately described by a single Gaussian function. Finally, we showed that because of the low‐dose envelope, the dose output's dependence on field size can vary for fields as large as 20 cm × 20 cm.
WE‐D‐204C‐01: Opportunities and Considerations for Multi‐institutional Clinical Trials Research
Authors: Deye J , Ibbott G , Michalski J , Tucker S , Xiao Y , Deasy J
Published: August 2010

The physicist role in clinical trials is sometimes confined to participation in filling out questionnaires, reviewing treatment plans, performing phantom studies, and verifying export of the correct information to the clinical trial group. However, participation in clinical trials research can be a rewarding and productive endeavor. The focus of this session is to highlight for investigators the potential and rewards of such research.

In this session, experts will present on different roles in supporting and conducting clinical trials research and secondary analyses. First, the role of the National Institute of Health in supporting clinical trials research will be described. Then, the richness of the data collected by the Radiological Physics Center (RPC) to support quality in clinical trials since its inception in 1968 will be described. The RPC has provided quality independent audits of delivered dose, design of phantoms, and other clinical trials support. More recently, the Advanced Technology Consortium (ATC) has been collecting digital 3D data to support clinical trials research for prospective and retrospective trials. Considerations with respect to the quality of data needed for retrospective analyses will then be discussed. Finally, individual investigators will share their experiences in 1) conducting research as a member of a clinical trials group and 2) furthering that research as an independent investigator supported by an NIH R‐01 grant.

The panel discussion will provide an opportunity for investigators to ask questions about the nuts and bolts of becoming active in clinical trials support ‐ and ultimately in clinical trials research.

Learning Objectives:

1. NIH mechanisms for funding clinical trials research

2. Examples of the RPC's database in support of clinical trials

3. Potential opportunities to conduct clinical trials research through the ATC

4. Ways to improve the quality of data acquired during clinical trials

5. Examples of research in the RTOG utilizing multi‐modality imaging

6. Examples of improved biological models utilizing multi‐institutional data
WE‐E‐204B‐04: TiO2 Nanotube Field Emitter as a New Cold Cathode for X‐Ray Generation
Authors: Alivov Y , Molloi S
Published: August 2010

Introduction/Purpose: Titanium dioxide (TiO2) nanotubes (NTs) grown by anodization are proposed as a new candidate for a cold cathode X‐ray source. This kind of oxide nanotube can potentially be an excellent choice to overcome the major limitations that exist in relation to carbon nanotubes (CNT). Being an oxide, TiO2 is not affected by residual oxygen present in the tube in contrast to CNTs, which can severely degrade from exposure to oxygen. Second, since TiO2 nanotubes are grown on a titanium (Ti) sheet as the latter oxidizes, a good electrical contact between TiO2 nanotube film and conductive Ti substrate is guaranteed. On the other hand, poor electrical contact between CNT and deposited substrate causes heating effects. The goal of this work was to simulate the effect of the NT parameters on field TiO2 NT emission properties. Methods: The field emission from two sources was considered: 1) from the top of NTs, and 2) the bottom of the NTs which serve as a thin semiconductor layer. Numerical calculations were performed to study the dependence of field emission on NT parameters for each emission mechanism. The calculations were performed in Matlab. Results: It is shown that the current decreased significantly with an increase of NT diameter, while it increased with the height of NTs. The rate of current increase with diameter is stronger for smaller diameter NTs. Regarding field emission from the bottom of the TiO2 layer, this current is strongly dependent on the TiO2 layer thickness and decreases as the latter increases. This current linearly increases with an increase of TiO2 electron charge carrier concentration. Conclusions: Effect of TiO2 NT geometrical and physical parameters on field emission can be simulated and the results can be used as a guide for design purposes.
TH‐C‐BRB‐03: On the Suitability of Using NanoDot for Measuring Dose Distributions Resulting from KV‐CBCT Acquisitions
Authors: Ding G , Coffey C
Published: August 2010

Purpose: There is a growing need to determine radiation exposure and dose distributions resulting from an image‐guidance procedure. Although Monte Carlo simulations are capable to calculate the dose distributions experimental measurements remain the gold standards to validate the accuracy of calculations. This study investigated the suitability of nanoDot dosimeters for measuring accumulative dose at several locations simultaneously to determine 3D dose distributions resulting from a kilovoltage cone‐beam CT (kV‐CBCT) scan. Method and Materials: The nanoDot dosimeters read with a microStar reader by Landauer were used in the study. The system can be calibrated to measure dose from kilovoltage to megavoltage energy beams. The manufacturer provides a set of calibration dosimeters for 80 kVp x‐rays. The accuracy of the nanoDot dosimeters for absorbed dose measurements for kV‐CBCT scans was validated by using an ionization chamber in which the air‐kerma calibration factors were traceable to National Standards Laboratory. The relative dose distributions measured with nanoDot were compared with Monte Carlo calculated dose distributions in a PLASTIC WATER® LR phantom. Results: Seven nanoDot dosimeters were placed at different locations to determine dose distributions resulting from each kV‐CBCT scan protocol. There are five different kV‐CBCT scan protocols in the Varian OBI 1.4 system including Head Low‐dose Thorax Pelvis and Pelvis Spot Light with two different Bow‐tie filters. Both absolute and relative dose distributions were investigated. The dose values measured from 35 points generally agree with that of Monte Carlo calculations within 2–4%. Conclusion: The nanoDot dosimeters have been shown to be very suitable detectors for measuring 3D dose distributions resulting from kV‐CBCT scans due to its small size the ease of use good reproducibility and manageable photon energy dependence.

Conflict of Interest: The microStar reader used in the research was provided by Landauer Inc. Glenwood IL
TH‐D‐BRB‐06: Fast and Accurate Monte Carlo‐Based Simulation of Dynamic Jaw Helical TomoTherapy
Authors: Sterpin E , Lu W , Mackie T , Olivera G , Vynckier S
Published: August 2010

Purpose: Design an accurate and efficient Monte Carlo (MC)‐based model for the future dynamic jaws feature of TomoTherapy which involves very small fields (< 1cm). In a previous study it was shown that one can simulate any field size from the 5 cm phase‐space file (PSF) using pre‐calculated intensity and angular longitudinal distributions. The present work extends TomoPen a MC model of TomoTherapy based on Penelope to dynamic jaw motion through two steps: (1) design a simplified and efficient MC model to calculate longitudinal and angular distributions and (2) interpolate and incorporate those distributions during an actual dynamic delivery. Material and methods: In the simplified MC model a full‐MC PSF is stored just above the jaws keeping future changes in target position accountable. The particles are duplicated according to cylindrical symmetry and only photon interactions are simulated through the jaws. Longitudinal intensity and angular distributions are then computed and stored for future interpolation and dynamic simulation. The integration over other dimensions (energy transverse direction…) ensures good statistics. Results: Using simple analytical modifiers of the 5 cm PSF it is straightforward to extend TomoPen to dynamic jaw simulation with similar accuracy as compared to full MC generated PSFs. Distributions computed with full MC or the simplified model showed no significant difference the quality of the interpolation being the only remaining potential source of discrepancies. Conclusions: A fast and comprehensive approach for efficient dynamic jaw simulation was devised. After building a database of intensity and angular distributions one can simulate dynamic jaws motion for all the field sizes with a single PSF keeping the same speed of TomoPen i.e. around 6 hours per treatment plan on a single CPU. Research sponsored by TomoTherapy Corporation
TH‐D‐BRB‐08: The Effect of Transverse Magnetic Fields on a Simulated In‐Line 6 MV Linac
Authors: St. Aubin J , Steciw S , Fallone B
Published: August 2010

Purpose: The linac waveguide is subjected to large magnetic fringe fields in a linac‐MR hybrid system. An investigation is performed to determine the effect of transverse magnetic fields on a simulated in‐line 6 MV medical linac. Method and Materials: The program PARMELA was used calculate the electron beam loss per cavity with the linac waveguide subjected to external transverse fields. BEAMnrc and DOSXYZnrc were used to calculate the effect on 40×40 and 20×20 cm2 field dose profiles and depth dose curves with the linac submersed in a transverse magnetic field. DOSRZnrc was used to determine the heating per cavity as a result of the beam loss and COMSOL was used to determine the resulting cavity resonant frequency changes due to cavity heating. Lastly a calculation of leakage radiation caused by the excessive beam loss was performed using BEAMnrc. Results: The beam loss was calculated to be 5±1 22±1 and 49±1% over nominal for 2 4 and 6 G magnetic fields respectively. The transverse magnetic fields caused a shifting of the electron spatial distribution at the target which resulted in a lateral shift of the dose profiles making 14.4% of all points fail a 1%/1mm acceptance criterion at a 6 G field. Through asymmetric jaw positions the lateral shift in the dose profiles was reduced such that only 0.5% of all points failed. The frequency of the accelerating mode changed by 0.03 Hz due to heating and a total leakage radiation of 0.007% of the radiation field was calculated. Conclusion: The 6 MV linac investigated showed sufficient tolerance to be used in transverse magnetic fields larger than earth's field. The shifts observed in the dose profiles were reduced through asymmetric jaw positions such that only 0.5 % of the points failed a 1 %/ 1 mm criterion at 6 G.
TH‐D‐204B‐02: Compressed Sensing as Applied to Computed Tomography
Authors: Pan X
Published: August 2010

There have been significant advances in algorithm development for image reconstruction in cone‐beam computed tomography (CBCT) in recent years. The newly developed algorithms not only are likely to impact on the existing CBCT systems and imaging protocols but also more importantly allow the design and establishment of innovative emerging CBCT imaging approaches and applications. The presentation will focus on discussing some of these algorithms and illustrating their potential implications for CT applications by using diagnosis and radiotherapy imaging examples. Emphasis will be placed on identifying and clarifying a number of issues such as the relationship between the Nyquist sampling theorem and compressive sensing approach which seem to be confusing. Evaluation of algorithm performance will also be a focus of discussion in the presentation. It will be explained that the “mathematic exactness” of an algorithm could be an irrelevant metric for meaningfully assessing the algorithm's utility in its practical applications followed by discussion of potential methods for carrying out a performance evaluation of algorithms in CBCT.
Poster — Thur Eve — 05: Semi‐Automated Segmentation of Lung Tumours on CT Scans Using Level Set Sparse Field Active Model
Authors: Awad J , Wilson L , Parraga G , Fenster A
Published: August 2010

We present a semi‐automated algorithm for segmenting lung tumours on chest computed tomography (CT) images to be utilized for monitoring tumour response or progression. Seven lung tumours were evaluated; each tumour was radially sliced into 10 slices for a total of 70 radial slices, and manually segmented. The manual segmentations were used as the ground truth for evaluating the proposed algorithm. The tumour image on each radial slice was classified into two categories: (1) well‐defined boundaries, located centrally in the lung parenchyma without significant vasculature; and (2) vascularized or juxtapleural (VJ). To segment the well‐defined boundaries, a shape constrained multi‐thresholding technique with one user‐defined seed point on the tumour is applied. For vascularized and juxtapleural tumours, this multi‐thresholding technique provided an initial contour that was deformed by a level set sparse field active model to produce the final segmentation for these tumours. The dice index (DI) measure was adopted to evaluate the segmentation results. The average and standard deviation values of the DI for the well‐defined and VJ images were 96.32 ± 1.12% and 95.19 ± 1.58%, respectively. The DI overall average and standard deviation of the 70 slices was 95.50 ± 1.55%. The preliminary results show that using the proposed algorithm produced accurate results.
Poster — Thur Eve — 13: Monitoring the Breathing Patterns of Lung Patients throughout the Course of Treatment — Preliminary Experience with the RADPOS System
Authors: Cherpak AJ , Cygler JE , Andrusyk S , Pantarotto J , MacRae R , Perry G
Published: August 2010

The RADPOS system is a new in vivo dosimetry tool that combines a MOSFET dosimeter with an electromagnetic positioning sensor to allow for simultaneous measurement in real‐time of dose and spatial coordinates at a specific location. A study is currently underway using the RADPOS system during the 4DCT and external beam treatments of lung cancer patients. Each day, RADPOS detectors are positioned at marked points on the patient's chest and abdomen while a fourth detector is placed on the CT or treatment couch for reference. Position coordinates of the sensors are read in real‐time at a rate of 20–25 Hz and total dose is read at the end of each treatment fraction. Measurements have been completed on 11 patients during the 4DCT and 7–16 treatment fractions. The standard deviation of the average dose measured at each point ranged from 3.0 to 13.7 cGy (7.7 to 14.0%) at CT zero and from 2.5 to 11.1 cGy (2.8 to 9.2%) at the site of the tumour. Variations in amplitude of breathing motion have been found to be patient‐specific. Some patients had very consistent breathing patterns, with interfraction variations in average amplitude and period as low as 11.4% and 4.2% respectively, while others had variations as high as 38.9% and 50.0% . Daily set‐up of the RADPOS system was completed quickly, requiring minimal additional time for each scheduled treatment fraction. Acknowledgements: This project is supported by grants from HTX and ORCC Foundation. Financial and technical support from Best Medical Canada is also acknowledged.
Poster — Thur Eve — 15: Surface Dosimetric Performance of Superposition‐Convolution Algorithms in Tangential Photon Beams: A Monte Carlo Evaluation
Authors: Chow J , Jiang R
Published: August 2010

Surface dosimetry predicted by the analytical anisotropic algorithm (AAA) and collapsed cone convolution (CCC) algorithm was evaluated using oblique (5° and 45°) tangential photon beams (6 and 15 MV) with different field sizes (4 × 4, 7 × 7 and 10 × 10 cm2), produced by a Varian 21EX linac. Surface dose or phantom skin profiles, at a distance of 2 mm from the solid water phantom lateral surface to mimic skin doses, were calculated by the AAA, CCC and Monte Carlo simulation (EGSnrc‐based code) used as a benchmark for comparison. It was found that doses in the phantom skin profiles were underestimated with small fields for the 6 and 15 MV photon beams, when the gantry angle was set to 5° clockwise. The mean dose differences for the 6 MV (4 × 4 cm2) photon beams were −15.1% (SD = 3.6%) and −3.7% (SD = 1.5%) for the AAA and CCC, while those for the 15 MV (7 × 7 cm2) beams were −12% (SD = 3.5%) and −7.6% (SD = 2%) when compared to Monte Carlo simulations. For larger gantry angle of 45°, the AAA and CCC were found overestimating doses in the phantom skin profiles with different field sizes and beam energies. As surface dose with oblique tangential photon beam is important in radiation treatment sites such as breast, chest wall and sarcoma, the dosimetry data in this study are worthwhile to be considered, when carrying out quality assurance and commissioning for treatment planning systems.
Poster — Thur Eve — 16: Dependences of Mucosal Dose on Small Photon Beams: A Monte Carlo Study
Authors: Chow J , Owrangi A , Grigorov G
Published: August 2010

This study investigates the dependences of the mucosal dose in the oral or nasal cavity on the small photon fields with different beam energies, beam angles and mucosa thicknesses. Phase space files of 6 and 18 MV photon beams (field size = 1× 1 cm2), produced by a Varian 21EX linac, were generated using the EGSnrc‐based BEAMnrc code. Mucosa phantoms (mucosa thickness = 1, 2 and 3 mm) with and without a bone under the mucosa were irradiated by photon beams with gantry angles varying from 0 to 30 deg. Doses along the central beam axis in the mucosa were calculated. For the 6 MV photon beams, it was found that the dose at the mucosa‐bone interface increased by 44.9% − 41.7%, when the mucosa thickness increased from 1 to 3 mm for the beam angle ranging from 0 to 30 deg. These values were lower than those (58.8% − 53.6%) for the 18 MV photon beams. For both the 6 and 18 MV photon beams, depth doses in the mucosa were found to increase with an increase of the beam angle. For the dose ratio (mucosal dose with bone to dose at the same point without bone), the dose enhancement due to the bone backscatter increased with a decrease of mucosa thickness, and was more significant at both the air‐mucosa and mucosa‐bone interface. The dosimetric information in this study is useful when searching for an optimized treatment strategy to minimize the mucosal complications in the head‐and‐neck IMRT.
Poster — Thur Eve — 61: Intensity Modulated Radiation Therapy: The Relationship between Planar Dose Map Verification and Dosimetric Outcome
Authors: Rangel A , Dunscombe P
Published: August 2010

This work analyses the consequences of random and systematic dose differences in the comparison of calculated against measured planar dose distributions for IMRT from the perspective of a surrogate of the treatment outcome: Equivalent Uniform Dose (EUD). In‐house software was developed to incorporate normally distributed errors in the fluence maps of 3 head and neck (H&N) and 3 prostate plans and simulate dose differences that appear randomly across the planar dose maps. The plans with random errors were grouped according to the following passing rates: 1) 90–95%, 2)85–90% and 3)80–85% during patient specific quality control. The passing criteria included a 3% absolute dose, 3 mm distance to agreement (DTA), and a minimum dose difference of 2 cGy. A systematic 1% dose error could also be incorporated by altering the MUs of each plan with random errors. The impact of random errors on the prescribed EUDs of H&N plans ranged from −2.7 to −1.3% for the CTV and −1.0 to 0.6 Gy for the OARs while in prostate plans they ranged from −1.6 to −0.6% for the CTV and −1.2 to −0.4 Gy for the OARs over the range examined. The criterion of 90% passing rate for 3% absolute dose and 3 mm DTA kept the effects of random errors within a dosimetric goal of 2% change in prescribed EUDs of the targets and 2 Gy for the OARs. Systematic errors, if present, may cause larger effects on clinical dosimetry while still meeting patient specific quality control tolerances.
Poster — Thur Eve — 62: Analysis of a Photoacoustic Imaging System by Singular Value Decomposition
Authors: Roumeliotis M , Stodilka RZ , Anastasio MA , Carson JJL
Published: August 2010

Photoacoustic imaging (PAI) is a hybrid imaging modality capable of producing contrast similar to optical imaging techniques but with increased penetration depth and resolution in turbid media by encoding the optical information as acoustic waves. PAI employs a pulsed laser to diffusely irradiate a volume of interest making the resulting images inherently three‐dimensional. While PAI is a relatively new field, potential applications include the characterization of tumours surrounded by soft tissue, such as breast tissue, as well as imaging vasculature structure. We have developed a PAI system that utilizes a staring, hemispherical array of detectors combined with parallel data acquisition and an iterative image reconstruction algorithm to produce three‐dimensional photoacoustic images using only a single laser pulse. Since our imaging system collects a limited number of data projections and has a shift‐variant response through object space, our objective was to characterize system performance beyond classic metrics such as sensitivity, resolution and contrast by implementing singular value decomposition. Using a robotically placed photoacoustic point source we experimentally captured the imaging operator over a defined object space. Decomposition of the imaging operator was done via singular value decomposition and provided insight into the capability of the PAI system to reconstruct objects and the inherent sensitivity of the PAI system to those objects. Preliminary reconstruction of simple objects is shown utilizing the calibration data in our reconstruction algorithm.
Genetic Determinants Involved in the Susceptibility of
Pseudomonas aeruginosa
to β-Lactam Antibiotics
Authors: Alvarez-Ortega Carolina , Wiegand Irith , Olivares Jorge , Hancock Robert E. W. , Martínez José Luis
Published: August 2010

The resistome of
P. aeruginosa
for three β-lactam antibiotics, namely, ceftazidime, imipenem, and meropenem, was deciphered by screening a comprehensive PA14 mutant library for mutants with increased or reduced susceptibility to these antimicrobials. Confirmation of the phenotypes of all selected mutants was performed by Etest. Of the total of 78 confirmed mutants, 41 demonstrated a reduced susceptibility phenotype and 37 a supersusceptibility (i.e., altered intrinsic resistance) phenotype, with 6 mutants demonstrating a mixed phenotype, depending on the antibiotic. Only three mutants demonstrated reduced (PA0908) or increased (
glnK
and
ftsK
) susceptibility to all three antibiotics. Overall, the mutant profiles of susceptibility suggested distinct mechanisms of action and resistance for the three antibiotics despite their similar structures. More detailed analysis indicated important roles for novel and known β-lactamase regulatory genes, for genes with likely involvement in barrier function, and for a range of regulators of alginate biosynthesis.
Increased Temperature Enhances the Antimicrobial Effects of Daptomycin, Vancomycin, Tigecycline, Fosfomycin, and Cefamandole on Staphylococcal Biofilms
Authors: Hajdu Stefan , Holinka Johannes , Reichmann Sonja , Hirschl Alexander M. , Graninger Wolfgang , Presterl Elisabeth
Published: August 2010

Implant-related infections are serious complications of trauma and orthopedic surgery and are most difficult to treat. The bacterial biofilms of 34 clinical
Staphylococcus
sp. isolates (
Staphylococcus aureus
,
n
= 14; coagulase-negative staphylococci,
n
= 19) were incubated with daptomycin (DAP; 5, 25, or 100 mg/liter), vancomycin (VAN; 5, 25, or 100 mg/liter), tigecycline (TGC; 1, 5, or 25 mg/liter), fosfomycin (FOM; 100, 250, or 1,000 mg/liter), and cefamandole (FAM; 50, 100, or 500 mg/liter) for 24 h at three different ambient temperatures: 35°C, 40°C, and 45°C. To quantify the reduction of the biomass, the optical density ratio (ODr) of stained biofilms and the number of growing bacteria were determined. Increasing the temperature to 45°C or to 40°C during incubation with FAM, FOM, TGC, VAN, or DAP led to a significant but differential reduction of the thickness of the staphylococcal biofilms compared to that at 35°C (
P
< 0.05). Growth reduction was enhanced for DAP at 100 mg/liter at 35°C, 40°C, and 45°C (log count reductions, 4, 3.6, and 3.3, respectively;
P
< 0.05). A growth reduction by 2 log counts was detected for FAM at a concentration of 500 mg/liter at 40°C and 45°C (
P
= 0.01). FOM at 1,000 mg/liter reduced the bacterial growth by 1.2 log counts (not significant). The antibacterial activity of antimicrobial agents is significantly but differentially enhanced by increasing the ambient temperature and using high concentrations. Adjuvant hyperthermia may be of value in the treatment of biofilm-associated implant-related infections.
Bioavailability and Population Pharmacokinetics of Voriconazole in Lung Transplant Recipients
Authors: Han Kelong , Capitano B. , Bies R. , Potoski B. A. , Husain S. , Gilbert S. , Paterson D. L. , McCurry K. , Venkataramanan R.
Published: August 2010

This study was undertaken to characterize the pharmacokinetics and bioavailability of voriconazole in adult lung transplant patients during the early postoperative period, identify factors significantly associated with various pharmacokinetic parameters, and make recommendations for adequate dosing regimens. Thirteen lung transplant patients received two intravenous infusions (6 mg/kg, twice daily [b.i.d.]) immediately posttransplant followed by oral doses (200 mg, b.i.d.) for prophylaxis. Blood samples (9/interval) were collected during one intravenous and one oral dosing interval from each patient. Voriconazole plasma concentrations were measured by high-pressure liquid chromatography (HPLC). NONMEM was used to develop pharmacokinetic models, evaluate covariate relationships, and perform Monte Carlo simulations. There was a good correlation (
R
2
= 0.98) between the area under the concentration-time curve specific for the dose evaluated (AUC
0-∞
) and trough concentrations. A two-compartment model adequately described the data. Population estimates of bioavailability, clearance,

V
c

, and

V
p

were 45.9%, 3.45 liters/h, 54.7 liters, and 143 liters. Patients with cystic fibrosis (CF) exhibited a significantly lower bioavailability (23.7%,
n
= 3) than non-CF patients (63.3%,
n
= 10). Bioavailability increased with postoperative time and reached steady levels in about 1 week.

V
p

increased with body weight. Bioavailability of voriconazole is substantially lower in lung transplant patients than non-transplant subjects but significantly increases with postoperative time. CF patients exhibit significantly lower bioavailability and exposure of voriconazole and therefore need higher doses. Intravenous administration of voriconazole during the first postoperative day followed by oral doses of 200 mg or 400 mg appeared to be the optimal dosing regimen. However, voriconazole levels should be monitored, and the dose should be individualized based on trough concentrations as a good measure of drug exposure.
Limited Role of Secreted Aspartyl Proteinases Sap1 to Sap6 in
Candida albicans
Virulence and Host Immune Response in Murine Hematogenously Disseminated Candidiasis
Authors: Correia Alexandra , Lermann Ulrich , Teixeira Luzia , Cerca Filipe , Botelho Sofia , Gil da Costa Rui M. , Sampaio Paula , Gärtner Fátima , Morschhäuser Joachim , Vilanova Manuel , Pais Célia
Published: August 2010

Candida albicans
secreted aspartyl proteinases (Saps) are considered virulence-associated factors. Several members of the Sap family were claimed to play a significant role in the progression of candidiasis established by the hematogenous route. This assumption was based on the observed attenuated virulence of
sap
-null mutant strains. However, the exclusive contribution of
SAP
genes to their attenuated phenotype was not unequivocally confirmed, as the Ura status of these mutant strains could also have contributed to the attenuation. In this study, we have reassessed the importance of
SAP1
to
SAP6
in a murine model of hematogenously disseminated candidiasis using
sap
-null mutant strains not affected in their
URA3
gene expression and compared their virulence phenotypes with those of Ura-blaster
sap
mutants. The median survival time of BALB/c mice intravenously infected with a mutant strain lacking
SAP1
to
SAP3
was equivalent to that of mice infected with wild-type strain SC5314, while those infected with mutant strains lacking
SAP5
showed slightly extended survival times. Nevertheless, no differences could be observed between the wild type and a Δ
sap456
mutant in their abilities to invade mouse kidneys. Likewise, a deficiency in
SAP4
to
SAP6
had no noticeable impact on the immune response elicited in the spleens and kidneys of
C. albicans
-infected mice. These results contrast with the behavior of equivalent Ura-blaster mutants, which presented a significant reduction in virulence. Our results suggest that Sap1 to Sap6 do not play a significant role in
C. albicans
virulence in a murine model of hematogenously disseminated candidiasis and that, in this model, Sap1 to Sap3 are not necessary for successful
C. albicans
infection.
The
Staphylococcus aureus
Lipoprotein SitC Colocalizes with Toll-Like Receptor 2 (TLR2) in Murine Keratinocytes and Elicits Intracellular TLR2 Accumulation
Authors: Müller P. , Müller-Anstett M. , Wagener J. , Gao Q. , Kaesler S. , Schaller M. , Biedermann T. , Götz F.
Published: August 2010

SitC is one of the predominant lipoproteins in
Staphylococcus aureus
. Recently, SitC was shown to be capable of stimulating Toll-like receptor 2 (TLR2), but the mechanism of TLR2 activation by SitC has not been analyzed in detail so far. In this study, we purified C-terminally His-tagged SitC (SitC-His) from
Staphylococcus aureus
. SitC-His induced interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) release in human monocytes and also NF-κB activation in TLR2-transfected HEK293 cells, indicating TLR2-specific activation. SitC not only induced a TLR2-dependent release of IL-6 in primary murine keratinocytes (MKs) but also induced intracellular accumulation of TLR2, which was time and concentration dependent. Cy2-labeled SitC-His colocalized specifically with TLR2 in MKs and was also internalized in TLR2 knockout MKs, suggesting a TLR2-independent uptake. Neither activation nor colocalization of SitC-His was observed with TLR4 or Nod2. The results show that the native lipoprotein SitC-His specifically colocalizes with TLR2, is internalized by host cells, induces proinflammatory cytokines, and triggers intracellular accumulation of TLR2.