bluuebunny/crossref_metadata_2025 huggingface dataset:
SU‐FF‐T‐198: Efficient and Automated MLC QA at Variable Gantry Angles for IMRT QA
Authors: Shukla H , Bayouth J
Published: July 2007

Purpose: The success of an IMRT program depends upon the accuracy of the Multi‐leaf Collimator's (MLC). The usual QA and calibration of MLC's are carried out at a gantry angle of 0°. We have developed a tool, which efficiently and accurately, measures the MLC offsets from desired position at different gantry angles. Materials/Methods: Data was acquired on a Siemens Oncor linear accelerator, which was equipped with an EPID for a period of 6 weeks. The geometric corrections are applied to the images at the imaging workstation. The EPID was exposed to 5 strips of width equal to 2cm. Data was obtained at various gantry angles. The data was compared with the template and later evaluated with software developed in Matlab 7.1. We compared the results from two edge detection algorithms, ‘Sobel’ and ‘Canny’. Data was obtained to verify the accuracy of the auto initialization process. Results: Time require to obtain and analyze MLC strip data at gantry angles of 0°, 90°, 180°, 270° was 12 minutes. It was observed that the overall effect gantry angle on error distribution is not significant, i.e. it's within ± 2mm. Effect of leaf position on error distribution, Pre and post AI, and weekly drifts were evaluated. It was observed that the percentage of leaves with a cumulative error less than 1mm at gantry angle of 0 and 180 was 80 %, while that for gantry angle of 90 and 270 was 72%. Conclusion: The tool helps the physicist and service engineer regarding the frequency and magnitude of AI/Calibration required. Currently the service engineer enters the leaf offsets manually to correct the encoder, which is stored in an EPROM. We plan to enter the offsets directly from software presented here to the EPROM via the controller card.
SU‐FF‐T‐201: Estimating Rectal Complication in Prostate IMRT Treatment Planning Using Maximum Dose Gradient
Authors: Jiang R , Barnett R , Chow J , Chen J
Published: July 2007

Purpose: Optimize inverse planning for IMRT prostate by adjusting the DVH control points to achieve a higher dose gradient between the PTV and OAR. Method and Materials: Dose distributions were generated from a Pinnacle3 planning system for 15 patients using five‐field and seven‐field co‐planar IMRT techniques with an escalated dose of 82 Gy. Dose profiles taken through the isocenter in the transverse and sagittal planes were analyzed to find the relation of maximum dose gradient (MDG) and reliable rectal dose‐volume constraints for prostate patients. Results: The steeper dose profile and higher MDG around the posterior direction can be obtained by modifying the planning technique or adjusting rectal DVH control points. The seven‐field plan has a higher MDG than a five‐field plan in the region where the PTV and rectum overlap, and has a much lower dose between 40–70Gy. With the seven‐field plan, there is a natural reduction in the rectal percentage volumes; also it is possible to lower the rectal DVH control points further to obtain a better dose gradient without sacrificing or impacting on other constraints for any of the IMRT plans. The average rectal percentage volumes VD50, VD60 and VD70 decrease 37%, 38% and 26%, respectively for the five‐field plan by lowering rectal DVH control points, while for seven‐field plan, the rectal percentage volumes decrease 16%, 19% and 13% respectively. The NTCP was reduced with a higher MDG between PTV and rectum. Conclusion: Relative to a five‐field plan, the seven‐field plan demonstrates a higher MDG in the posterior direction causing lower rectal complications. To achieve the higher MDG, VD70, VD60 and VD50 of the rectal DVH are below 21%, 32% and 48%, respectively. These values are lower than RTOG guideline (25%, 35% and 55%, respectively) and do not compromise the dose distribution elsewhere.
SU‐FF‐T‐239: Gamma‐Test Equivalent Error Margins for Dosimetry Analysis
Authors: Chen Y , Jiang S , Ma C
Published: July 2007

Purpose: The γ‐test evaluates the difference between two dose distributions in dose‐spatial domain. Previous methods employing the γ‐test at a point to translate spatial variation to acceptable dose difference involve a test distribution and a reference dose. This work developed a method for dose comparison using pre‐calculated acceptable error margins based on one dose distribution. Method and Materials: The expected uncertainty for a reference dose distribution is predetermined without making relevance to another distribution. The error margin at a point is calculated using the γ‐index formula over a sphere of a radius being the maximum distance‐to‐agreement (MDAT). All dose values within the sphere, evaluated using a set of evenly distributed points, are acceptable, whereas appropriate dose margins, up to a maximum dose difference (MDD), are included. Comparison with another distribution is to check against the upper and lower bound of the error margins separately, so γ‐test equivalent failure can be discerned to hot and cold regions. The degree of failures can be analyzed quantitatively for determining how an agreement between the two distributions can be improved globally. For an application, we calculated the error margin of dose measurement for IMRT QA using the distribution of volume‐averaged chamber response. Results: The error margin for IMRT phantom measurement using an IC‐10 chamber was about ±4% for MDD=3% and MDAT=3 mm in a flat region. Asymmetric error margins were found in gradient regions. Expected range for the output measurement with a 1cm×1cm field was (−18.6%, 2.5%) for MDD=2%, MDAT=2 mm, and a measurement was −13.3% off. Conclusion: Using predetermined error margins for a reference distribution is equivalent to the γ‐test in dose comparison. The error margins are not skewed by another distribution and interpretable as expected uncertainty for statistical analysis. The expected values for a reproduced distribution can be different from the reference.
MO‐D‐M100J‐03: Reducing the Sensitivity of IMPT Treatment Plans to Setup Errors and Range Variations
Authors: Unkelbach J , Chan T C Y , Bortfeld T
Published: July 2007

Purpose: Intensity modulated proton therapy (IMPT) has the ability to deliver highly conformal dose distributions to tumors of complex shape. However, the accuracy of IMPT treatment plans is potentially compromised by various uncertainties, including setup errors and variations of the range of a proton beam in the patient. Method and Materials: We present two treatment planning concepts for IMPT which incorporate uncertainties into the optimization. The first approach minimizes the expectation value of the deviation of delivered dose and prescribed dose, assuming the delivered dose depends on several random variables that model the uncertainty. The second approach minimizes the maximal dose deviation that can occur. Results: It is shown that these methods can utilize the physical characteristics of the proton beam to make treatment plans relatively insensitive to a particular type of uncertainty.

A treatment plan optimized while accounting for range uncertainties avoids placing a bragg peak directly in front of the OAR. Instead, the lateral fall‐off of the pencil beam is utilized in order to avoid the risk of overdosing the OAR. In addition, the dose distributions delivered by individual beams are relatively homogeneous in beam direction. This ensures tumor coverage and homogeneity.

On the other hand, treatment plans optimized by accounting for setup errors (modeled as a rigid translation of the entire patient) utilize the distal fall‐off at a transition of OAR and tumor. In addition, the dose distributions delivered by individual beams avoid steep dose gradients perpendicular to the beam direction to ensure tumor homogeneity.

Robustness of a treatment plan with respect to both setup error and range variations is possible to a limited degree only, since both types or uncertainty favor conflictive treatment plans. Conclusion: The presented methods are valuable to make IMPT treatment plans insensitive to various types of uncertainty.
TU‐D‐L100F‐04: Current NIH and NCI Initiatives Using Imaging Biomarkers
Authors: Clarke L
Published: July 2007

Imaging as a biomarker for drug response is becoming an increasing important area of research. There are many sources of uncertainty in the use of imaging as a biomarker for the assessment of drug response. For example, biological variability is a factor that is drug, organ, tumor and patient dependent and thus best addressed through carefully designed clinical trials such as those proposed using and NCI and an NIH wide biomarker initiatives.

http://www.fda.gov/oc/mous/domestic/FDA‐NCI‐CMS.htm).

http://www.fnih.org/Biomarkers%20Consortium/Biomarkers_home.shtml.

However there is also measurement variability associated with the imaging data collection and analysis across different commercial platforms and uncertainty in the performance of different software tools employed to measure therapy response, such as the measurement of change in image‐related computer extracted features over time. These hardware and software sources of uncertainty often force an increase in the size of clinical drug trials, and ideally should not be a variable in measurement of drug response. The development of standardized methods to physically characterize these sources of uncertainty would stimulate the development of improved imaging methods and software tools as recommended by a recent Trans Agency Workshop organized by NIST:

http://usms.nist.gov/workshops/bioimaging.htm.

This presentation will review current and potential funding opportunities for medical physicists to become engaged in the development of imaging systems and methods and related imaging standards that have the potential of being used in imaging trials for drug and therapy response.
TU‐D‐BRB‐01: The Road to (Training and Practice Of) the Medical Physicist of the Future
Authors: Masten J , Limmer J , Gilley D , Herman M
Published: July 2007

There are a number of changes pending that will impact the practice of medical physics and those who are called “medical physicist.” Recent changes in the U.S. Nuclear Regulatory Commission (NRC) regulations have impacted the training and experience requirements for medical physicists to practice in programs licensed by the NRC and Agreement States. The pending CARE Act legislation in Congress will require that Providers utilize individuals, who meet Federal education and credentialing standards, to perform the technical components of medical imaging and radiation therapy in order to participate in federal health programs such as Medicare, Medicaid and other programs administered by the Department of Health and Human Services. These minimum standards may be met by states requiring licensure. After 2012, the American Board of Radiology (ABR) goal for eligibility for certification will require graduation from a CAMPEP‐accredited medical physics training program. All of these will impact how one qualifies to be a medical physicist and how they practice. This session will address these issues.

Speakers:

Jeffrey Masten, JD: Update and impact of the CARE Act.

Jeffrey Limmer, MS Ed, MSc, DABR, — Past methods used to promote licensure in the existing states and the differences and similarities in these regulations.

Debbie Gilley, — Review and Impact of Existing State Licensure and Differences in NRC and Agreement State Training and Experience Requirements.

Mike Herman, Ph.D. — Future certification and credentialing in the post‐CARE ra and post‐2012 ABR (activities of MPRTP and TG133).
TU‐D‐AUD‐03: Comparison Between the Lateral Penumbra of a Double Scattering Proton Beam and the Lateral Penumbra of a Scanning Beam
Authors: Safai S , Bortfeld T , Engelsman M
Published: July 2007

Purpose: Intensity modulated proton radiotherapy can reduce the dose to the critical structures by optimizing the distribution and intensity of the individual pencil beams. However, the finite size of a pencil beam and the scattering in air degrade the lateral penumbra in the patient, which could be inferior to the penumbra of a collimated scattered beam. In this study we compare the lateral penumbra of a pencil beam to the one of a collimated broad divergent beam, such as the one produced by a double scattering system, for different air gaps, range compensator (RC) thicknesses and pencil beam size (σ0). Method and Materials: The penumbra of the collimated broad divergent proton beam has been modeled using the generalized Fermi‐Eyges theory. The model was validated with measurements of the lateral profile in water. We analyzed 2400 treatment fields to establish typical clinical beam configurations such as air gap, RC‐thickness and collimator‐to‐patient distance (CSD), which we used to predict the penumbra (80% – 20%). Results: The model predicts the penumbra with accuracy of 0.3mm. The penumbra of a pencil beam at shallow depth is in general inferior to the penumbra of a collimated beam but is superior at larger depths. The penumbra equivalent depth (PED) exhibits a small dependence on the proton range, but it is strongly affected by the CSD. For CSD 10cm, RC‐thickness 6cm, and SSD 210cm, PED is 11cm for σ0=5mm. Conclusion: Given the source size and source position the model allows to predict the lateral penumbra of a double scattering system with good accuracy. Typically, for the configuration considered, for proton ranges larger than 11cm the pencil beam penumbra is superior to the collimated one. The inferiority at shallow depth can be compensated with a collimation of the scanning beam.
TU‐D‐AUD‐08: Monte Carlo Kernel‐Based Convolution‐Superposition Dose Calculation for Intensity‐Modulated Arc Therapy (IMAT)
Authors: Tang G , Earl M , Yu C , Naqvi S
Published: July 2007

Purpose: Dose calculations for intensity‐modulated arc therapy (IMAT) have traditionally been performed by approximating continuous arcs with multiple static beams. Not only that the calculated dose may not truthfully represent the delivered dose, but also the large number of beams used to approximate an arc requires very long calculation time. We propose to use our homegrown Monte Carlo (MC)/superposition dose calculation algorithm to compute doses for rotational delivery. Method and Materials: We first generate static IMRT plans with Pinnacle3 P3 IMRT module utilizing 36 equi‐spaced beams. The resulting intensity maps are inputted to the continuous intensity map optimization (CIMO) IMAT leaf sequencer. CIMO outputs deliverable arcs, each represented by aperture shapes spaced at 10‐degree intervals. The apertures are then interpolated at 1‐degree intervals. Dose calculations for both 36‐field plan and 351‐field plan (which closely represents the actual delivery) are performed using our homegrown MC‐based dose calculator. The time needed for calculating dose for the two plans are compared and the differences in dose distributions are also examined. Results and Conclusion: Four IMAT plans, a prostate, a head and neck, an orbit, and a brain, were selected for the study. Using history‐based sampling, the dose computation time only increased slightly for the 351‐beam plans. Each case took approximately 30 minutes to compute on a single CPU running Mac OSX. No significant differences in plan quality between the 36‐beam and the 351‐beam plans were observed. However, finger‐like artifacts at the lower isodose levels became evident when using 36 beams to approximate an arc. The dose calculation time using our MC‐based dose calculator is largely independent of the number of beam portals. For the cases studied, using 36 beams to approximate an arc delivery is sufficient, but more accurate calculation with finer angular spacing is achievable without a significant increase in computation time.
TU‐D‐M100F‐07: Simplified Clinical Quality Assurance for Helical Tomotherapy
Authors: Grant W , McGary J , Childress N , Cravens R , Krumbach T , Olivera G
Published: July 2007

Purpose: To evaluate a Web‐based Quality Assurance tool for maintaining the clinical integrity of the Tomotherapy machine. Method and Materials: This tool takes advantage of the output of the two distinct ion chamber systems on the Tomotherapy machine. One is the standard sealed ion chamber that resides in the head of a machine near the primary collimators and is used to calculate Monitor Units. The other is a set of pressurized Xenon detectors that are used for imaging. Both systems monitor ionizations independently and are rigidly attached so that their geometry is constant regardless of the orientation of the beam on the gantry which makes possible testing for both static and rotational modes. The collected data can be reviewed via a Web page and a downloadable Report in PDF format is available within seconds after collection of the data. Results: As an example, one performs a 200 second rotational delivery with the couch removed from the beam. The data are analyzed in both an integrated and pulse‐by pulse methodology to determine consistency between the two chamber systems, changes in output and changes in energy. The collected information is evaluated relative to a standard delivery created during machine commissioning. Comparison to standard ion chamber measurements in phantom under static conditions indicate that the analyses are consistent for calibration and more sensitive to energy changes than percentage depth dose measurements made in phantom. Additional information about the machine's performance is identified easily. Conclusion: New technology offers an opportunity to perform standard Quality Assurance tests in a new manner. The simple test described here is more sensitive and performed more quickly than traditional methodology. Other tests are possible. Conflict of Interest: Three authors are employees of Tomotherapy, Inc.
TU‐D‐L100E‐01: Mammography QA Workshop I & II
Authors: Jacobson D , Wu T , Geiser W , Spahn G
Published: July 2007

Purpose: To explore the impact of digital mammography on the practice of medical physics. Historical and new methods for providing scheduled and unscheduled mammography services for facilities using digital mammography will be presented. Method and Materials: Clinical medical physics services provided for digital mammography facilities from various manufacturers will be presented. Quality control activities approved by the FDA for each individual manufacturer will be compared. The status of a proposed “Alternative Standard” to allow for a more uniform approach to medical physics mammography services will be reviewed. Case studies will be presented demonstrating methods and cost considerations for providing medical physics services under the “minimum standard” (prescribed by MQSA regulations) and “best practices” model. Results: Medical physics services provided in the “minimum standard” and “best practices” model have implications for the quality and cost of mammography services. Conclusion: Medical physics services may be provided in a professional and valuable manner, using combinations of the minimum standard of practice and the “best practices” model. The professional medical physicist should consider multiple parameters when determining the appropriate model under which to deliver services.
TU‐EE‐A3‐04: Processing of Respiratory Signals From Tracking Systems for Motion Compensated IGRT
Authors: Ernst F , Bruder R , Schlaefer A
Published: July 2007

Purpose: Improving the quality of signals obtained with optical and magnetic tracking systems.Special focus is placed on the measurement of respiratory motion signals for motion compensated IGRT and the possibility of filtering this data to obtain low‐noise breathing signals. Method and Materials: The accuracy of five different tracking systems (NDI Polaris™, active and passive, Clarion MicronTracker™,BIG FP5000, NDI Aurora™) was examined by (a)tracking stationary markers over several hours, and (b) by attaching the markers to a Kuka KR16 robot to simulate human respiration.The à trous wavelet decomposition was used to decompose the measured signal into scales, and to remove scales related to high frequencies, i.e., noise. The method was applied to a sinusoidal signal with artificial noise modeled according to (a), to real measurements for a sinusoidal motion of the robot, and to a set of breathing motion data from an actual patient treated with the CyberKnife®. Motion prediction was applied to the data. Results: The error on the measurements of the stationary marker approaches a Gaussian distribution.For a tracking rate of 60 Hz, information related to breathing motion is represented by higher scales of the à trous wavelet decomposition. Removing the first three scales and resconstructing the signal from the remaining scales and trend it is possible to obtain close and smooth approximations of the original signal. The normalized RMS error for motion prediction is 0.3368 mm and 0.1378 mm for a simulated and the smoothed signal using normalized LMS prediction. Conclusion: Data from tracking devices is subject to device specific measurement noise. The à trous wavelet decomposition can be used to remove frequencies related to noise from measured breathing signals. The resulting signal is suitable for further processing, e.g., correlation with or prediction of tumor motion in the context of motion compensated IGRT.
TU‐EE‐A3‐06: Comparison of Prostate Localization with Online Ultrasound and Mega‐Voltage Cone‐Beam Computed Tomography
Authors: Miften M , Gayou O , Reitz B , Fuhrer R , Parda D
Published: July 2007

Purpose: To analyze the online image‐guided localization data from 846 ultrasound (US)and 350 MV‐CBCT couch alignments for patients undergoing IMRT of the prostate. Method and Materials: Daily volumetric MV‐CBCT and US images were acquired for 11 and 23 patients, respectively, after each patient was immobilized in a vacuum cradle and setup to skin markers as the center‐of‐mass. The couch shifts applied in the lateral (left‐right/LR), vertical (anterior‐posterior/AP), and longitudinal (superior‐inferior/SI) directions, along with the magnitude of the three‐dimensional (3D) shift vector, were analyzed and compared for both methods. The percentage of shifts larger than 5 mm in all directions was also compared. CTV‐to‐PTV expansion margins were estimated based on the localization data with US and CB image‐guidance. Results: Systematic and random shifts from CB versus US were: laterally, 1.6 ± 3.8 mm vs. − 0.7 ± 6.9 mm; vertically, − 0.9 ± 5.4 mm vs. − 0.2 ± 6.4 mm; longitudinally, −1.4 ± 2.9 mm vs. −2.9 ± 5.2 mm. The mean 3D shift distance was smaller using CB (6.6 ± 3.6 mm vs. 9.1 ± 6.5 mm) with a p‐value < 0.05. The US data show greater variability. The percentage of US shifts larger than 5 mm were 33%, 40%, and 31% in the LR, AP, and SI directions, respectively, compared to 17%, 31%, and 7% for CB. Conclusion: MV‐CBCT localization data suggest a different distribution of prostate center‐of‐mass shifts with smaller variability, compared to US. The online MV‐CBCT image‐guidance data show that for treatments that do not include daily prostate localization, one can use a CTV‐to‐PTV margin that is 2.5 mm smaller than the one suggested by US data, hence allowing more rectum and bladder sparing and potentially improving the therapeutic ratio.
TU‐EE‐A1‐02: Whole Procedure Accuracy of Gamma Knife Radiosurgery of Large Tumors Via Multiple Isocenter Delivery
Authors: Ma L , Chuang C , Petti P , Smith V , Verhey L
Published: July 2007

Purpose: Geometric accuracy of single‐isocenter Gamma Knife delivery has been well established to within 0.3 mm. The question frequently asked is the accuracy of the full‐procedure Gamma Knife treatments, particularly important for large tumors requiring multiple isocenter deliveries. In this study, we performed direct measurements to determine such accuracy. Method and Materials: An anthropomorphic head phantom with a central spherical target of 3.0 cm in diameter was employed for measurements. We placed the stereotactic frame on the phantom and followed identical imaging and treatment protocols for treatment planning and beam delivery. CT scans of varying slice thicknesses of 1 mm, 2 mm and 3 mm were acquired and used for treatment planning calculations. The phantom was irradiated using 16 isocenters delivered with Gamma Knife automatic patient positioning system (APS). Radiochromic films aligned with the center of the target were exposed. The isodose measurements were compared with the 3D dose calculations from the treatment planning system (Leksell GammaPlan Wizard 4C). Results: The overall agreements were found to be approximately 2 mm between the measurements and dose calculations. The agreement was slightly better (approximately 1.5 mm) for the peripheral isodose line (e.g., 50% of the maximum dose) but deteriorated significantly (2–4 mm) for low (e.g., 30% of the maximum dose) or high isodose lines (e.g., 80% of the maximum dose). The 2‐mm dose accuracy showed no dependence on the slice thickness of the CT studies. The 2mm overall accuracy is closely matched the dose grid box resolution of 1.8 mm that was needed to encompass the full target volume for calculations. Conclusion: Overall accuracy of Gamma Knife irradiation of a large target was found to be approximately 2 mm, regardless the slice thickness of acquired images. The dose grid resolution was likely the dominant factor contributing to this result.
TU‐EE‐A2‐02: Fractionated Grid Therapy in Treating Cervical Cancers: Hypo‐Fractionation Or Conventional Fractionation?
Authors: Zhang H , Wang J , Mayr N , Kong X , Yuan J , Gupta N , Lo S , Grecular J , Montebello J , Martin D , Yuh W
Published: July 2007

Purpose: To evaluate the hypo‐fractionated and conventionally fractionated grid therapy in treating cervical cancers. Material and methods: A Monte Carlo technique was employed to calculate dose distribution of a commercially available grid. Based on the previously validated Monte Carlo technique, our new study has considered the divergence of all holes and thus improved the accuracy of grid geometry description in the simulations. The linear‐quadratic (LQ) model is used to evaluate the therapeutic outcome of both the hypo‐fractionated (fewer fractions and higher dose/fraction, herein 15 Gy/fraction) and conventionally fractionated (2Gy/fraction) regimens using grid therapy to treat cervical tumors that were represented by different radio‐biological responses. Results: The dose profiles and 2D dose distributions at dmax (d=1.5 cm) and 5 cm depths in water were obtained. An excellent agreement of dose profiles between calculated and measured was confirmed. The tumor cell and normal tissue survival statistics of grid therapy for two types of treatment regimens were calculated using the 2‐D dose distributions at the depth of 5 cm, and the therapeutic ratios and equivalent open field doses were obtained. Conclusions: The consideration of the divergence of grid holes has improved the Monte Carlo simulation results. In both the hypo‐fractionated and conventionally fractionated regimens, the therapeutic ratio depends not only on the single α/β value, but also on the individual α and β values. There is a significant therapeutic advantage of grid therapy for treating the studied cervical cancer cells because of their large α/β values, and the normal tissue sparing effect for the hypo‐fractionation regimen with few fractions is comparable to the conventional fractionation regimen with many fractions. For the radiosensitive normal tissues, both regimens give almost the same results, but for the radio‐resistant normal tissue the conventional fractionation regimen is preferred to spare them.
WE‐D‐AUD‐06: In Vivo EPID Dosimetry for Large Scale Clinical IMRT Verification
Authors: Mans A , McDermott L , Wendling M , Stroom J , Sonke J‐J , Buijs M , Tielenburg R , Vijlbrief R , van Herk M , Mijnheer B
Published: July 2007

Purpose: To introduce 2D in vivo EPID dosimetry as a tool for IMRT verification in the clinic for all curative patients (about 2000/year) before the end of 2007; meanwhile replacing pre‐treatment dosimetry, reducing workload and improving efficiency. Method and Materials: EPID images are acquired per segment, and by means of a back‐projection algorithm converted to dose distributions in a plane intersecting the isocenter, perpendicular to the beam axis. In this plane, a 2D field‐by‐field comparison is performed between the back‐projected EPID and planned dose distributions, using the γ‐evaluation method with 3%/3mm of maximum dose as criteria. For each field the mean γ, maximum 1% γ, percentage of points in agreement, and the isocenter dose difference are reported. These numbers are fed into a decision rule setting limits on the approval of a treatment plan. Results: Currently, treatment plans of prostate, rectum, skull and liver cancer patients are already validated based on in vivo EPID measurements; for the other patient groups in vivo dosimetry is being introduced. Statistics for a group of 152 prostate patients, each having 3–5 EPID measurements thus filtering out random uncertainties, show an average mean γ‐value per patient of 0.41, and an average isocenter dose difference of −1.5% between EPID and plan. Clinically relevant errors were detected in four prostate plans, and these plans were replaced. Preliminary results for head&neck, breast and lung IMRT treatments show the feasibility of the method for these sites but inhomogeneity corrections need to be refined to improve accuracy. Conclusions: For a variety of treatment sites, 2D in vivo EPID dosimetry is now clinically used, or will be introduced soon, for IMRT verification of all curative patients. In this way, an efficient and accurate routine procedure has been developed for routine purposes providing the radiotherapy chain with an extra safety net.
WE‐E‐M100F‐05: Evaluation of Respiration‐Correlated Digital Tomosynthesis in the Thorax and Abdomen for Soft Tissue Visualization and Patient Positioning
Authors: Kriminski S , Lovelock D , Mageras G , Mostafavi H , Amols H
Published: July 2007

Purpose: To find optimal parameters for digital tomosynthesis (DTS) image reconstruction, to evaluate ability of respiration correlated DTS to reduce blur caused by respiratory motion, and to assess DTS imaging for soft tissue localization and patient positioning. Methods and Materials: Image acquisition for DTS used a gantry‐mounted kV on‐board imaging system (Varian Medical Systems). We did not acquire DTS separately, but instead simulated DTS acquisition by using projection images acquired for CBCT. DTS reconstruction consisted of backprojection followed by a deblurring operation removing out‐of‐plane objects. For tumors subject to respiratory motion we selected projection images according to an external respiratory monitor signal (Real‐time Position Management System, Varian Medical Systems). Reconstruction and registration of DTS images used vender research software. Results: Optimal DTS quality is achieved with a 6–9 cm long deblurring volume in the direction perpendicular to the image and 20–30° reconstruction arc lengths. Image blur increases with longer arc lengths, while for shorter arcs out of plane objects become more pronounced. RC DTS reconstruction from disjoint arcs containing 2–3 respiratory cycles is feasible, yields images with less motion blur, and allows visualization of tumor movement. Generally, DTS was capable to visualize lung tumors, bronchi, liver, kidneys and abdominal lymph nodes. Estimated 3D registration error of DTS to reference DTS generated from the plan CT DRRs was 3 mm, relative to cone‐beam CT as a standard. Registration of RC DTS of lung tumors was possible to within 2 mm. Conclusions: DTS is capable of soft tissue visualization and patient positioning, including tumors subject to respiratory motion. With several advantages over full rotation CBCT scan, such as much shorter acquisition time, smaller dose and relaxed clearance requirement, DTS can become an efficient imaging modality for image‐guided radiotherapy. Conflict of Interest: Research sponsored by NCI Grant P01‐CA59017 and Varian Medical Systems.
TH‐D‐M100J‐03: High‐Quality Four‐Dimensional CBCT Reconstruction with Virtual Projections
Authors: Li T , Papiez L , Timmerman R , Choy H , Koong A , Xing L
Published: July 2007

Purpose: Due to significantly reduced number of projections per phase, the quality of 4DCBCT images is often degraded by view‐aliasing artifacts. Acquisitions using slow‐gantry‐rotation or multiple‐gantry‐rotations can improve the 4D images, but at the cost of extra scan time, which may render them clinically impractical. Here we report a new progress in developing high‐quality 4DCBCT without prolonging the acquisition time. Method and Materials: The technique developed here is to reduce the view‐aliasing artifacts resulted from insufficient sampling by properly “borrowing” projections from other phases. To do so, a motion model linking the data of different phases is derived from deformable registrations of coarse (conventional) 4DCBCT phases with consideration of patient's simulation 4DCT. This 4D patient model allows us to properly transform projections from other phases onto the phase under reconstruction, leading to increased sampling in 4DCBCT. The proposed approach is quantitatively evaluated with motion phantoms and two clinical lung cases for a number of metrics, including RMSE of CT numbers, image uniformity, and contrast‐to‐noise‐ratio (CNR). Results: An important finding of this work is that, by the aid of “virtual projection” derived from coarse 4DCBCT and 4D (or breath‐hold 3D) simulation CT images, the 4DCBCT view‐aliasing artifacts can be dramatically reduced, resulting in greatly improved CT‐number accuracy, image uniformity and CNR in all testing cases. Compared with the conventional 4DCBCT, the overall reduction in CT number fluctuation is ∼38% and the CNR increase is ∼65%. Conclusion: Improving the trade‐off between image quality and scan time is the key to making 4D onboard imaging practical and clinically useful. A novel strategy for enhancing 4DCBCT images without increasing scan time and radiation dose has been developed for onboard CBCT imaging system. The method should find valuable applications in patient setup, dose verification in 4D, as well as adaptive radiation therapy in the future.
IMPROVING THE PERFORMANCE OF MULTI-OBJECTIVE EVOLUTIONARY ALGORITHMS USING THE ISLAND PARALLEL MODEL
Authors: MÁRQUEZ A. , GIL C. , BAÑOS R. , GÓMEZ J.
Published: July 2007

Recently, the research interest in multi-objective optimization has increased remarkably. Most of the proposed methods use a population of solutions that are simultaneously improved trying to approximate them to the Pareto-optimal front. When the population size increases, the quality of the solutions tends to be better, but the runtime is higher. This paper presents how to apply parallel processing to enhance the convergence to the Pareto-optimal front, without increasing the runtime. In particular, we present an island-based parallelization of five multi-objective evolutionary algorithms: NSGAII, SPEA2, PESA, msPESA, and a new hybrid version we propose. Experimental results in some test problems denote that the quality of the solutions tends to improve when the number of islands increases.
Crystallization in Amorphous States of Small Organic Molecules: In Relation to Hypothetical Glass-Transition Temperatures
Authors: Nakayama Hideyuki , Usui Hiroyuki , Ishii Kikujiro
Published: July 2007

We have studied, by Raman and X-ray measurements, the structural change in amorphous states of benzene and its derivatives prepared by the vacuum deposition on cold substrates. It has been found that these amorphous states crystallize without passing through the supercooled-liquid state when the temperature is raised. The observed crystallization temperature Tcryst is lower than the hypothetically reported glass-transition temperature Tg. The relation between the crystallization and the glass transition in amorphous states of small organic molecules is discussed.
Multidrug Resistance Proteins Do Not Predict Benefit of Adjuvant Chemotherapy in Patients with Completely Resected Non–Small Cell Lung Cancer: International Adjuvant Lung Cancer Trial Biologic Program
Authors: Filipits Martin , Haddad Vincent , Schmid Katharina , Huynh Anh , Dunant Ariane , André Fabrice , Brambilla Elisabeth , Stahel Rolf , Pignon Jean-Pierre , Soria Jean-Charles , Popper Helmut H. , Le Chevalier Thierry , Pirker Robert
Published: July 2007

Purpose: The purpose of our study was to determine whether multidrug resistance proteins (MRP) are of prognostic and/or predictive value in patients who were enrolled into the International Adjuvant Lung Cancer Trial (IALT).

Experimental Design: Expression of MRP1 and MRP2 was immunohistochemically assessed in tumor specimens obtained from 782 IALT patients. Prognostic and predictive analyses were based on Cox models adjusted for clinical and pathologic variables.

Results: MRP1 expression was considered positive in 364 (47%) patients and MRP2 expression in 313 (40%) patients. MRP2-positive patients had a significantly shorter overall survival than MRP2-negative patients in the total patient population [adjusted hazard ratio for death, 1.37; 95% confidence interval (95% CI), 1.09-1.72; P = 0.007]. There was no significant association between MRP1 expression and overall survival. Neither MRP1 nor MRP2 predicted response to adjuvant cisplatin-based chemotherapy.

Conclusions: MRP2 expression is an independent prognostic factor in patients with completely resected non–small cell lung cancer but neither MRP1 nor MRP2 was of predictive value in patients enrolled into the IALT.
Combined Therapeutic Effects of Vinblastine and Rapamycin on Human Neuroblastoma Growth, Apoptosis, and Angiogenesis
Authors: Marimpietri Danilo , Brignole Chiara , Nico Beatrice , Pastorino Fabio , Pezzolo Annalisa , Piccardi Federica , Cilli Michele , Di Paolo Daniela , Pagnan Gabriella , Longo Luca , Perri Patrizia , Ribatti Domenico , Ponzoni Mirco
Published: July 2007

Purpose: Vinblastine and rapamycin displayed synergistic inhibition of human neuroblastoma-related angiogenesis. Here, we studied the antitumor activity of vinblastine and rapamycin against human neuroblastoma.

Experimental Design: Cell proliferation, cell cycle progression, and apoptosis were evaluated by measuring 3H-thymidine incorporation, bromodeoxyuridine uptake, and phosphatidylserine exposure, respectively. The in vivo sensitivity of neuroblastoma cells to vinblastine and rapamycin was determined in orthotopic neuroblastoma-engrafted mice. Angiogenesis was assessed by the chick embryo chorioallantoic membrane assay.

Results: Each compound alone was able to induce a dose-dependent significant inhibition of cell proliferation, with a dramatically enhanced antiproliferative effect for the drugs used in combination. A marked G2-M cell cycle arrest with a nearly complete depletion of S phase was associated. The combined treatment triggered an increased apoptosis compared with either drug tested alone. A significant inhibition of tumor growth and microvessel area was obtained in neuroblastoma-bearing mice when treated with vinblastine or rapamycin alone, and a more dramatic effect with the combined treatment, compared with control mice. The therapeutic effectiveness, expressed as increased life span, was statistically improved by the combined therapy, compared with mice treated with either drug tested separately. Histologic evaluation of primary tumors showed that the combined treatment inhibited proliferation and angiogenesis and induced apoptosis. Combined treatment of neuroblastoma cells and neuroblastoma-bearing mice with vinblastine and rapamycin induced the down-modulation of both vascular endothelial growth factor production and vascular endothelial growth factor receptor 2 expression. In the chorioallantoic membrane assay, angiogenesis induced by human neuroblastoma biopsy specimens was significantly inhibited by vinblastine and rapamycin.

Conclusions: These results may be relevant to design new therapeutic strategies against neuroblastoma.
Histone Deacetylase Inhibitors Affect Dendritic Cell Differentiation and Immunogenicity
Authors: Nencioni Alessio , Beck Julia , Werth Daniela , Grünebach Frank , Patrone Franco , Ballestrero Alberto , Brossart Peter
Published: July 2007

Purpose: Histone deacetylases (HDAC) modulate gene transcription and chromatin assembly by modifying histones at the posttranscriptional level. HDAC inhibitors have promising antitumor activity and are presently explored in clinical studies. Cumulating evidence in animal models of immune disorders also suggests immunosuppressive properties for these small molecules, although the underlying mechanisms remain at present poorly understood. Here, we have evaluated the effects of two HDAC inhibitors currently in clinical use, sodium valproate and MS-275, on human monocyte-derived DCs.

Experimental Design: DCs were generated from monocytes through incubation with granulocyte macrophage colony-stimulating factor and interleukin-4. DC maturation was induced by addition of polyinosinic-polycytidylic acid. DC phenotype, immunostimulatory capacity, cytokine secretion, and migratory capacity were determined by flow cytometry, mixed leukocyte reaction, ELISA, and Transwell migration assay, respectively. Nuclear translocation of RelB, IFN regulatory factor (IRF)-3, and IRF-8 were determined by immunoblotting.

Results: HDAC inhibition skews DC differentiation by preventing the acquisition of the DC hallmark CD1a and by affecting the expression of costimulation and adhesion molecules. In addition, macrophage inflammatory protein-3β/chemokine, motif CC, ligand 19–induced migration, immunostimulatory capacity, and cytokine secretion by DCs are also profoundly impaired. The observed defects in DC function on exposure to HDAC inhibitors seem to reflect the obstruction of signaling through nuclear factor-κB, IRF-3, and IRF-8.

Conclusions: HDAC inhibitors exhibit strong immunomodulatory properties in human DCs. Our results support the evaluation of HDAC inhibitors in inflammatory and autoimmune disorders.
Chronic Kidney Disease
Authors: Schiffrin Ernesto L. , Lipman Mark L. , Mann Johannes F.E.
Published: July 2007

Accelerated cardiovascular disease is a frequent complication of renal disease. Chronic kidney disease promotes hypertension and dyslipidemia, which in turn can contribute to the progression of renal failure. Furthermore, diabetic nephropathy is the leading cause of renal failure in developed countries. Together, hypertension, dyslipidemia, and diabetes are major risk factors for the development of endothelial dysfunction and progression of atherosclerosis. Inflammatory mediators are often elevated and the renin-angiotensin system is frequently activated in chronic kidney disease, which likely contributes through enhanced production of reactive oxygen species to the accelerated atherosclerosis observed in chronic kidney disease. Promoters of calcification are increased and inhibitors of calcification are reduced, which favors metastatic vascular calcification, an important participant in vascular injury associated with end-stage renal disease. Accelerated atherosclerosis will then lead to increased prevalence of coronary artery disease, heart failure, stroke, and peripheral arterial disease. Consequently, subjects with chronic renal failure are exposed to increased morbidity and mortality as a result of cardiovascular events. Prevention and treatment of cardiovascular disease are major considerations in the management of individuals with chronic kidney disease.
Longitudinal modeling of developmental processes
Authors: Card Noel A. , Little Todd D.
Published: July 2007

Methods for analyzing longitudinal developmental data have increased in terms of quantity and complexity in the last few decades. In this article, we describe the advantages of longitudinal data, review the use of longitudinal data in current developmental research, and then preview the articles in this Special Issue. A survey of recently published literature indicates that longitudinal data are commonly used (due to several advantages over concurrent data) across domains of developmental research and vary tremendously in terms of time spans studied, the number and structure of data points, and the analytic strategies used. The articles included in this Special Issue reflect the diversity in usage within developmental research and provide didactic presentations of advanced methods of analyzing longitudinal data to answer important developmental questions.
On Political Institutions and Social Movement Dynamics: The Case of the United Nations and the Global Indigenous Movement
Authors: Morgan Rhiannon
Published: July 2007

In this article, I consider the institutional influence of the United Nations on the organizational structures, tactical repertoires, and claims of the global indigenous movement. A predominant sociological paradigm has tended to view a movement's being located in conventional political space as promoting its “institutionalization,” generally understood as a more or less determined process by which social movements undergoing organizational change eschew confrontational strategies and claims for more moderate approaches. This article illustrates that the consequences of interacting with institutions can be rather different than is expected from this paradigm, and thereby reinforces the need for a new approach allowing for more variation in terms of what takes place when social movements engage in conventional political activity.
Agriculture and environmental change at Qingpu, Yangtze delta region, China: a biomarker, stable isotope and palynological approach
Authors: Atahan Pia , Grice Kliti , Dodson John
Published: July 2007

Rice ( Oryza sp.) agriculture sustains vast numbers of people and, despite great advancements made in recent years, questions about its origins and spread throughout Asia remain unanswered. This study uses sedimentary biomarker, stable carbon isotope and palynological analyses to investigate early rice agriculture in the Yangtze delta, a region where rice agriculture emerged at least 7000 years ago. Accelerator mass spectrometer (AMS) 14C dating reveals the age of sedimentary section to be between c. 6000 and 1800 cal. BP. Widespread clearing of forest vegetation c. 2400 cal. BP, is the earliest major human influence detected in the Qingpu record. Following this, rice agriculture probably dominated the Qingpu area. Evidence supporting rice agriculture after c. 2400 cal. BP is provided by increased Poaceae and Cereal-type taxa, which occur with high concentrations of plant wax n-alkanes with a dominant C3 plant origin (C27—C31 with odd/even preference, δ 13C —29.8‰ to —36.3‰). Also, high concentrations of a C20 highly branched isoprenoid (HBI) thought to be from epiphytic algae associated with rice agriculture occur after c. 2400 cal. BP. 13C-depleted diploptene (in high concentrations) and 13C-depleted C31 3b-methyl-hopanes of methanotrophic bacterial origin also occur after c. 2400 cal. BP. The strong methane cycle detected in the trench sediment may have provided an alternative CO2 source for plants and algae associated with rice agriculture.