bluuebunny/crossref_metadata_2025 huggingface dataset:
SU‐FF‐T‐256: IMRT Inverse Planning with Voxel‐Based Penalty Scheme
Authors: Callaghan T , Levy D , Xing L
Published: July 2007

Purpose: A tacit assumption made in current inverse planning algorithms is that all points within a structure (target or sensitive organ) are equivalent, as reflected by the fact that the dose prescription, weighting factors and dose‐volume constraints are generally imposed a priori on a structure‐specific basis. This seriously limits the IMRT solution space and compromises the achievable dose distributions. The purpose of this study is to develop a novel IMRT inverse planning framework with a more general voxel‐specific penalty. Methods: Different from conventional inverse planning in which the same penalty (objective) function is used for all voxels, here we assign each voxel a penalty proportional to where Dc and D0 are computed and prescribed doses, respectively, and ni is a voxel‐specific exponent. In this way, we “break” the implicit constraint that a structure is a mathematically uniform entity with all voxels having the same “identity”. The seemingly insolvable task of determining a large number of voxel‐specific {ni} is dealt by heuristically relating them to the doses they receive. The optimization starts from a uniform value of and, during the iterative optimization process, the ni's are treated as parts of the system variables and are updated together with the beamlet weights. If a voxel is overdosed, for example, it means that the voxel is not penalized sufficiently and the algorithm will automatically increase the value of ni, and vice versa. Results: A voxel‐dependent penalty scheme is established for IMRT inverse planning. The formalism properly models the intra‐organ tradeoff and allows the optimizer to access solutions that would otherwise be inaccessible. Our phantom and clinical head‐and‐neck case studies show that much superior treatment plans can be obtained as compared with the conventional approaches. Conclusion: Voxel‐based penalty scheme leads to substantially improved IMRT dose distributions and allows us to maximally utilize the IMRT technology.
SU‐FF‐T‐257: IMRT Optimization Using a Shifted CTV‐Based Objective Function
Authors: Nguyen TB , Thomas SJ , Hoole ACF , Burnet NG
Published: July 2007

Purpose: The Planning Target Volume (PTV) is used to ensure that the CTV is adequately covered with the prescribed dose despite geometric uncertainties. Clinically, a plan is acceptable if the 95% isodose surface covers the PTV; therefore the objective function is currently formulated based on PTV for IMRT optimization. This study investigates the feasibility of using a CTV‐based objective function for IMRT optimization in shallow tumors where the PTV extends into build‐up region. Method and Materials: For a selected shallow tumor (Head & Neck) case, a conventional IMRT plan was optimized with a PTV‐based objective function using Newton's algorithm. The CTV‐PTV margin was 10mm. Additionally, a CTV‐based objective function calculated from 6 different isocenter shifts (10mm positive and negative on each axis) was used for optimization to generate another plan. To ensure that the treatment plan is acceptable for the whole range of possible movements, the resultant objective function is formulated so that the worst plan among shifted plans is acceptable:
urn:x-wiley:00942405:media:mp0918:mp0918-math-0001

The PTV DVH and CTV DVHs were analyzed for both plans. Results: Using PTV‐based optimization results in better PTV coverage than that of CTV‐based optimization: V95=93.4 % in comparison with V95=80.9%. However, in the case of CTV‐based optimization, the maximum dose of the CTV for all isocenter shifts is less than 108% in contrast with 136% using PTV‐based optimization. Furthermore, the intensity patterns from the CTV based optimization plan are less complex than those from the PTV‐based optimization.

Conclusion:The current method of optimization using a PTV‐objective function might lead to an overdosage of the CTV for shallow tumors due to the build‐up region. The CTV‐based objective function has been shown to be a possible solution in reducing the skin dose with IMRT optimization for shallow tumors where the PTV extends into the build up region.
SU‐FF‐T‐265: Initial Experience with a CyberKnife G4 System
Authors: Lo A , Djajaputra D , Yu C
Published: July 2007

Objective: A CyberKnife G4 system (Accuray Inc.) went clinical at our cancer center on Oct. 17, 2006. The G4 platform is built on a 6 MV X‐band linear accelerator mounted on a multi‐jointed manipulator with 600 MU/min dose rate, 50% higher than the CyberKnife G3 system. The G4 also features flush‐mounted, in‐floor x‐ray image detectors, providing an increase in treatment workspace and expanding the potential for extra‐cranial applications. Our experience with the G4 and its comparison to the G3 will be presented here. Methods: In two and half months of operation, 85 patients with 120 lesions and 223 fractions were treated with the G4 system. Pathologic diagnoses included acoustic neuroma, meningioma, trigeminal neuralgia, arteriovenous malformation, lung, pancreas, prostate, metastases and others. Of the 85 patients, 55 were tracking with 6D skull, 16 Xsight, 13 Synchrony and 1 Fiducial. Mean number of fractions per lesion was 2 (1 to 5), mean lesion volume was 15.2 cm3 (0.02 to 78.6 cm3) and mean prescription was 25.6 Gy (8 to 60 Gy) to the 78% isodose line (70–82%). Accuracy of beam delivery, system efficiency, E‐stop interruption, machine downtime, customer support and treatment planning system were analyzed. Results: Treatment in all patients was delivered as planned. The end‐to‐end accuracy was under 1.0 mm for all tracking modes. Improvements for the G4 system include an increase in treatment workspace, higher dose rate, enhanced power‐up and power‐down. Initially, the average treatment time was approximately 90 min (60 to 180 min), which was significant longer than our experience with G3. Cause of extended treatment time was identified and corrected. Conclusions: The CyberKnife G4 system offers the latest technology for frameless stereotactic radiosurgery. Our initial experience with this new CyberKnife G4 system was generally very positive.
SU‐GG‐AUD‐10: Quantitative Assessment of the Accuracy of Proton Beam Range Verification with PET/CT
Authors: Knopf A , Parodi K , Paganetti H , Cascio E , Bonab A , Bortfeld T
Published: July 2007

Purpose: At present the most promising method for an in vivo and noninvasive monitoring of radiation treatments with proton beams is positron emission tomography (PET). This study investigates the sensitivity and accuracy of the PET/CT treatment verification method in the presence of highly inhomogeneous tissue regions as well as in the presence of metallic implants. Method and Materials: A circular SOBP proton field has been delivered to a sophisticated in house designed phantom consisting of polymethyl methacrylate (PMMA), lung and bone equivalent slabs. The bone material contained authentic dental gold implants as well as tin lead alloy implants in different shapes. PET data were acquired in listmode starting within 15 min after irradiation at a commercial PET/CT scanner. The measured PET distributions were compared to full‐blown simulations of the PET signal based on Geant4 and FLUKA Monte Carlo (MC) codes. Results: Activation profiles were analyzed behind air‐lung, air‐bone and lung‐bone interfaces parallel to the beam as well as downstream interfaces angled at 6°. In general, a good agreement between measured and simulated PET distributions was found. Measured PET images reflected even small characteristic changes in the dose distribution. This showed the potential of PET/CT treatment verification in the presence of highly inhomogeneous tissue regions. CT artifacts due to metal implants can trick all dose calculation algorithms and lead to the prediction of a proton range overshoot behind metal implants, whereas in reality a range undershoot occurs. The PET/CT treatment verification method can detect such dose calculation errors. Conclusion: This preliminary study indicates the feasibility of PET/CT treatment verification to detect the full characteristic of the delivered dose distribution even in the presence of complex tissue inhomogeneities and metal implants.
MO‐A‐M100J‐03: Performance Evaluation for New‐Technology CT Systems: Cone Beam C‐Arm CT
Authors: Fahrig R
Published: July 2007

Conebeam CT using C‐arm mounted large area flat panels (FPs) is becoming more commonly used in neuro‐ and body‐interventional suites. The ability to visualize vascular geometry in 3D along with soft tissue during an intervention is providing information that may increase accuracy, shorten procedure time and may even change the course of treatment. However, acquisition of the projection data required for volume imaging requires dose to the patient, and understanding the trade‐offs between acquisition parameters, dose and image quality is critical to the appropriate adoption of this imaging technique.

Unlike conventional CT, the beam length in conebeam CT can cover the entire length of the object to be imaged or can be varied with the use of collimation, and the concept of CTDI is not, therefore, the metric of choice for measurement of dose. In addition, most C‐arm conebeam CT systems use a short‐scan (pi plus fan‐angle) acquisition, and the dose distribution within the object is not cylindrically symmetric. Finally, since FP design has been optimized for fluoroscopy, image quality when used for CT must be carefully evaluated.

This lecture will describe a dose metric that is appropriate for conebeam CT and allows direct comparison with the CTDIw of conventional CT. A perception study using the CATPHAN 600 phantom for a range of acquisition parameters will be described, and the relationships between kVp, image noise, dose and contrast perception will be discussed.

Research sponsored by Siemens Medical Solutions AG, AX Division, by NIH grant R01 EB003524 and by the Lucas Foundation.

Educational Objectives:

1. Understand how differences in acquisition geometry between conebeam and conventional CT affect dose distribution and dose measurement.

2. Understand how contrast perception in conebeam CT images depends on acquisition parameters.
MO‐A‐BRA‐01: New NCRP Report: General Report Background and Formulation
Authors: Deye J
Published: July 2007

This Report was prepared through a joint effort of the AAPM Task Group 57 and the NCRP Scientific Committee 46‐13. It addresses the structural shielding design and evaluation for medical use of megavoltage x rays and gamma rays for radiotherapy and supersedes related material in NCRP Report No. 49, which was issued in 1976.

This first presentation will review the general formalisms used for primary and secondary barrier designs at energies below and above the 10MeV maximum energy that was considered by the old Report 49. While most of the formalisms and data can be found in the published literature, the goal of the report was to bring together in one work all the required methods for shielding modern radiotherapy accelerators. This overview will be followed on the second day by a review of the methods and equipment that are necessary to survey the final facility and then the equations and data presented will be used extensively in the third day's presentation to work a number of detailed example calculations.

Learning Objectives:

1. Understand the history and rationale behind this report,

2. Understand the appropriate use of the equations and data for calculating shielding for medical accelerators,

3. Understand the limitations of the proposed methods.
MO‐B‐L100E: Magnitude of Medical Radiation Exposures to US population: Preliminary results from NCRP Scientific Committee 6‐2
Authors: Mahesh M
Published: July 2007

National Council of Radiation of Protection formed Scientific Committee 6.2 to work on the estimation of radiation exposure to the US population from all sources. The intended goal of the Committee is to update the NCRP report 93 published in 1987. One sub group of the sub committee was assigned with the medical exposure. The medical sub committee comprised of medical physicists, physicians, and other health physics experts.

The subcommittee examined variety of data sources including commercial surveys, Medicare, Veterans Administration and insurance carrier data. Radiation exposure to the US population from medical exposures was then estimated based on the number of medical procedures grouped by modality and body parts and the radiation doses associated with each procedure. The modality groups were CT, nuclear medicine, radiography, general and interventional fluoroscopy, dental radiography, bone‐densitometry and radiation therapy.

According to the preliminary results, the medical radiation exposure to US population has increased by nearly 6 times compared to the previous NCRP publication (NCRP 93). The conventional pie‐chart indicating 3 mSv from background radiation and 0.6 mSv from man‐made (medical) exposure will undergo major shape change as these preliminary results are finalized. The largest contributor to the collective dose to US population is seen with CT and Nuclear Medicine. CT scanning has increased nearly 10–11% annually in the US in the past two decade. The number of CT procedures has increased from 3 million CT scans in 1980 to more than 62 million CT scans in 2006. Similarly, the nuclear cardiac procedures have increased significantly in the last two decades.

The purpose of this talk is to provide an update on the results from the medical patient exposure subcommittee and to discuss the details on how the results were derived.

Learning Objectives:

1. To learn about the magnitude of medical radiation exposure to US population.

2. To familiarize with the types and distribution of medical imaging procedures in US.

3. To understand methods used in computing the radiation exposures to US population.
MO‐D‐L100J‐01: True 3D Contouring Via Efficient Spline Representation of Anatomy
Authors: Hibbard L , Han X , Brame S
Published: July 2007

Purpose: To make anatomy contouring more efficient by integrating contours drawn in any combination of transverse/sagittal/coronal (T/S/C) views and reconstructing the T contours from the surface defined by the drawn contours so that the user may draw/edit until the object is completed. Method and Materials: Our program performs the surface reconstruction by thin‐plate spline interpolation of points in the drawn contours. The surface is reconstructed as a variational implicit function, and runs in real‐time because we abstract the most shape‐informative points from the input contours. These points correspond to maxima in one of several functions of the second derivatives of the contour functions. We demonstrate contouring results for one of these methods—the scalar second derivative of the curve function. Before abstracting the shape salient points, contours are re‐computed to have consistent rotational directions, and to have origins placed consistently in the patient coordinate system. Since the contours' points are non‐uniform samples of the curve, each contour is reconstructed, using all input points, by B‐spline interpolation to resample the curve uniformly along the its length to compute the derivatives by finite differences. Results: We demonstrate in the supporting document: 1) the operation of the shape abstraction algorithm, and 2) the production of contours approximating the prostate from a single S and C contours, and 3) the production of contours in 270 T sections of a spinal canal from a single S and 4 C contours. Conclusion: We have developed a contouring program that integrates drawn contours in any combination of T/S/C views to create a coherent surface that is clipped to produce T contours at the appropriate image planes, so the user can and assess how much more drawing or editing is needed to make a satisfactory match to object boundaries visible in the image.

Sponsored by CMS, Inc.
MO‐D‐BRB‐02: Challenges of Introducing New Technology Into the Clinic
Authors: Klein E
Published: July 2007

Implementing new technologies into the clinic is challenging on many levels. Besides the obvious manpower issues, physicists are challenged with; unreasonable timelines driven by market competition, technical staff acceptance, incompatibilities of devices provided by multiple vendors, and the lack of opportunities for proper education. Vendors have capitalized on the open purse‐strings hospitals provide due to the healthy reimbursement for IMRT and IGRT (daily localization). Physicist must use tools such as the Abt studies to negotiate proper staffing before the technologies arrive. During this talk we will review some simple methods to justify staffing. Physicists should set realistic timelines that depend on the agreed on staffing levels including IT assistance, and on compatibility of all systems involved. We will review timelines that have been suggested for given technologies, along with time efforts from Washington University, including, MLC‐IMRT, Tomotherapy, OBI, CBCT, video surface imaging, gating, US localization, etc. Physicists must be the key decision makers in choosing a team of technical staff personal to be the initial implementers. We have found the initiation of a new technology is smoothest if the dosimetrists and therapists first involved are pro‐active and capable of implementing a new technology. Procedure writing should be a team effort to ensure there is ownership. Ongoing continuing education and scheduled migration of other support staff to operating the new technology should be the responsibility of the physicist in charge of the device or technique. This includes re‐education of all involved for new software releases or new processes. As daily localization empowers therapists to make decisions on shifting patients, physicists should work with clinicians to decide; what is the minimum shift required for a shift to take place, when is the shift too much, and whether re‐evaluation is required. Our protocols will be discussed. And finally, physicists should ensure they receive proper training beyond what the vendor provides. This may be in the form of legitimate courses and workshops, or visits to institutions using the new technology. To this end, the physics and radiotherapy community should address how new physicists (residencies), dosimetrists (MDCB), and therapists (testing out) are being trained and evaluated, and how experienced personal are being re‐trained for our new environments.

Learning Objectives: From this lecture, the physicists will learn how to:

1) estimate manpower needs,

2) formulate implementation timelines and tasks,

3) obtain the education necessary for the new technology.
MO‐D‐M100J‐07: Plan Space Modeling and Decision Support System for Multi‐Plan IMRT Framework
Authors: D'Souza W , Zhang H , Nazareth D , Shi L , Meyer R
Published: July 2007

Purpose: The conventional treatment planning paradigm involves a plan‐and‐evaluate followed by a modify‐if‐necessary approach. We describe an IMRT treatment planning framework in which multiple plans that differ in the input constraints are generated per case prior to evaluation. We also describe a decision‐support‐system (DSS) for evaluating and ranking multiple plans and hypothesize that the planning surface can be modeled using quadratic modeling. Methods and Materials: One hundred twenty‐five plans were generated sequentially for a head‐and‐neck case and a pelvic case by varying the dose‐volume constraints on each of the OARs. A DSS was used to rank plans according to DVH and equivalent uniform dose (EUD) values using composite criteria and pre‐emptive selection. Two methods for ranking treatment plans were evaluated: composite criteria and pre‐emptive selection. The planning surfaces corresponding to the 125‐plan sets were modeled using quadratic functions by formulating the problem as a linear program. Results: The DSS provides an interface for the comparison of multiple plan features. Plan ranking using both composite and pre‐emptive criteria resulted in the reduction of plan space to 1–3 “optimal” plans. The planning surface models had good predictive capability with respect to both DVH and EUD values with fit errors of < 6%. Models generated by minimizing the maximum relative error had significantly lower relative errors than models obtained by minimizing the sum of squared errors. The inter‐dependence of OAR‐OAR properties could be successfully inferred for both clinical cases through the use of contour plots, which represent projections through the multi‐dimensional plan property space. Conclusion: The DSS can be used to aid the planner in the selection of the most desirable plan. The collection of quadratic models constructed from the plan data in order to predict DVH and EUD values generally showed excellent agreement with the actual plan values.
MO‐E‐L100F‐01: Real‐Time Soft Tissue Elasticity Imaging with Ultrasound
Authors: Hall T
Published: July 2007

Methods for imaging the elastic properties of soft tissues have undergone rapid development in recent years. This is in part facilitated by the ever‐increasing capabilities of ultrasound imaging systems. This presentation will describe the basic mechanics of soft tissues and terminology used in elasticity imaging (e.g., stress, strain, elastic modulus). Key developments in motion tracking for elasticity imaging will be reviewed with emphasis on the current state of the art in motion tracking algorithms for accurate estimation of displacement fields. That discussion sets the stage for an analysis of observations of soft tissue mechanics as seen via real‐time elasticity (mechanical strain) images of breast tissues during relatively large deformations. For example, many benign lesions tend to lose contrast in strain images as deformation increases. That behavior can be understood given the measured mechanical properties of in vitro tissue samples. Unlike benign lesions most cancerous tumors tend to maintain a large negative contrast with increasing deformation, and that too can be understood from in vitro measurements. The utility of this information is summarized with a review of recent clinical trials of breast elasticity imaging. Specifically, a recent multi‐institutional, multi‐observer study has demonstrated that elasticity imaging increases the diagnostic confidence of breast ultrasound radiologists when attempting to classify a tumor as either “benign” or “malignant”. The presentation will conclude with a brief discussion of the prospects for future enhancements and improvements in elasticity image formation and information content.

Educational Objectives

1. Understand the basic vocabulary used to describe simple solid mechanics.

2. Understand the methods used to form real‐time elasticity images using ultrasound and the potential for significant improvements in the future.

3. Understand the basic criteria for interpreting breast elasticity images.
MO‐E‐M100J‐02: Functional Imaging
Authors: Xing L
Published: July 2007

Functional imaging is being increasingly used in radiation therapy for target definition and treatment planning. In this talk I will summarize recent advances in functional and molecular imaging techniques and discuss various issues related to the integration of the newly emerged imaging data into radiation therapy planning. In particular, techniques of time resolved 4D PET acquisition will be discussed and a few method of enhancing 4D PET images will be described. It is anticipated that the new imaging modalities will make significant impact in cancer diagnosis, staging, treatment planning, and monitoring of therapeutic response. The potential impact of biologically conformal radiation therapy (BCRT) or biologically guided radiation therapy (BGRT) will be discussed. Finally, issues related to the quality assurance of functional and molecular imaging and BCRT will also be addressed.

Educational Objectives:

1. Introduce the concept of functional and molecular imaging.

2. Illustrate the steps involved in integrating molecular imaging such as PET and MRSI into treatment planning process.

3. Introduce PET/MRI/MRSI and CT image fusion techniques (including deformable image registration).

4. 4D PET data acquisition and image enhancement.

5. Provide an overview on recent advances in PET/CT and MRSI, and update on the development of new PET tracers and data acquisition techniques.

This work was supported in part by NCI 5R01 CA98523‐01.
MO‐E‐M100J‐03: Gross Tumor Volume and Normal Structure Definition
Authors: Balter J
Published: July 2007

Regardless of the degree to which positioning is maintained later in treatment, the critical step in the radiation therapy process involves definition of the initial patient model. Many factors influence this process, most notably the sources of differential contrast in images used, the knowledge and experience of the users defining both normal tissue as well as targeted structures, and distracting factors such as organ movement and imaging artifacts. Significant attention has recently focused on the interobserver variation in target definition, with differences observed that exceed the gains expected through in‐room target localization and potentially through gating/tracking. While Radiation Oncology departments are consumers of advanced imaging information, we have yet to find ways to truly optimize imaging to aid in consistent definition of targeted and avoidance tissues.

The objectives of this talk are to:

1. Review the process of initial definition of target and avoidance tissues.

2. Discuss observed variances in target definition.

3. Describe the impact of motion and advances such as 4DCT in the process.

4. Suggest potential areas for improving consistency in these processes.
MO‐E‐M100J‐06: Intra‐Fraction Target‐Beam Positioning
Authors: Keall P , Sawant A
Published: July 2007

The problem of intrafraction tumor‐target positioning can be divided into two separate processes: (1) estimating the real‐time target position and (2) repositioning the beam to account for intrafraction target motion. Several solutions exist for both target position estimation and beam repositioning, however in principal any method of position estimation could be integrated with any method of beam repositioning. Note that beam repositioning can include moving the target to align with the beam (e.g. couch motion), which in the target reference is the same as moving the beam to align with the target.

There are several common features in target position estimation systems. First, that in the absence of a real‐time volumetric imaging system, the target position is estimated from surrogates and thus there is uncertainty in the position of the target with respect to the surrogates. Second, for all but EPID‐based methods target position estimation is independent of the treatment beam and therefore careful quality assurance is required to ensure the accurate position estimation with respect to the treatment beam.

There are also several common features of the beam repositioning systems. First, control systems with secondary feedback are required to ensure accurate and precise real time mechanical motion. Second, that there is a delay between the target motion and the beam repositioning. This delay causes delay‐time dependent errors which can be reduced with prediction algorithms.

The various target position estimation and beam repositioning processes either in development or available for clinical use will be described and contrasted.

Educational Objectives:

1. Understand the separation of the target position estimation and beam repositioning processes.

2. Understand the advantages and disadvantages of several real‐time target position estimation systems.

3. Understand the advantages and disadvantages of several beam repositioning systems.

Some research in this area at Stanford is supported by Varian Medical stems.
MO‐E‐AUD‐04: Automated Linear Accelerator Quality Assurance Using a Commercial Cylindrical Calibration Phantom
Authors: Mamalui‐Hunter M , Li H , Low D
Published: July 2007

Purpose: Precise mechanical operation of a linear accelerator is critical for accurate dose delivery. Available quantitative procedures for the linac mechanical quality assurance (QA) are time consuming and therefore conducted on a relatively infrequent basis. We present a method for evaluating the mechanical performance of a linac based on a series of projection portal images of a prototype cylindrical calibration phantom with embedded markers.

Method and Materials: We used non‐linear multiobjective optimization of information extracted from the images to determine a number of geometric parameters of interest. The markers detection included modeling the imager response to radiation beams where significantly non‐uniform background was expected. Results: The average results for the parameters of our geometric linac model were: gantry angle deviation 0.066 ± 0.085° (1 SD), gantry sag 0.026 ± 0.02°, imager in‐plane rotation 0.026 ± 0.055°, roll — 0.082 ± 0.16° and pitch −0.9 ± 0.604°, SDD 1489.7 ± 5 mm, SAD 998 .3 ± 1.7 mm, and the imager shift [− 0.66,3.9]±[0.30,1.6] mm. The results were corrected for the phantom center shift relative to the linac rotational center. The average rotational center was . The average couch height and angle variations were 0.15±0.9 mm and 0.154±0.1°, respectively. The image analysis quality was examined by comparing the detected set of marker coordinates to its simulated counterpart for three regions of the phantom image: central, near the edge and the intermediate region (relative to the central line of the cylinder). The upper limit of the mean difference was less than 0.25 mm with the cumulative mean of 0.146 mm and SD of 0.07 mm. The results of the primary optimization of directly detected marker coordinates virtually coincided with their counterparts based on the simulated coordinates for all the geometric parameters of the model.

Conclusion: This procedure is accurate and automated, which allows precise mechanic QA to be performed more frequently.

Conflict of Interest: partially supported by Varian Medical Systems.
WE‐D‐M100J‐05: Estimation of Tumor Control Probability Model Parameters for Early Stage Non‐Small‐Cell Lung Cancer (NSCLC)
Authors: Semenenko V , Gore E , Li X
Published: July 2007

Purpose: To estimate parameters for the tumor control probability (TCP) model based on the linear‐quadratic (LQ) cell survival formalism from published clinical data for early stage NSCLC and to investigate potential outcomes of alternate dose fractionation schemes. Method and Materials: A comprehensive literature search was performed to identify studies reporting local control after conventionally fractionated 3DCRT and hypofractionated stereotactic body radiation therapy (SBRT) for T1‐2N0M0 NSCLC. Parameters of the LQ‐based TCP model were estimated by fitting the selected clinical data sets using the maximum likelihood method. Fits were obtained and compared for three versions of the TCP model: without the time effect, with an exponential growth of clonogens, and with delayed onset of clonogen proliferation. Obtained parameter estimates were used to compare different fractionation schemes that take advantage of increase in tumor control as the overall treatment time is reduced. Results: A fit to the exponential growth model was significantly better (p < 0.0001) than a fit to the model with no time effect. Also, the model with delayed onset provided a significantly better fit (p = 0.0142) to the data than the exponential growth model assuming no delay in clonogen repopulation. Parameter estimates for the model with delayed onset were: α = 0.066 Gy−1, α/β = 21.1 Gy, γ = 1.85 Gy/day, Tk = 32.2 days, and k (the number of clonogens) = 6.3. Our analysis of different hypofractionated regiments confirms observations by others and suggests that a moderate reduction in the number of fractions (with the increase in the dose per fraction) may result in better tumor control for the same level of late complications.

Conclusion: The derived TCP model parameter estimates may prove useful for biologically based treatment planning of Stage I NSCLC, especially when unconventional fractionation schemes, such as in SBRT, are employed.
WE‐E‐M100F‐01: 3D Interfraction Position Verification for Patients Undergoing Partial Breast Irradiation: Comparing Digital Tomosynthesis to Cone‐Beam CT
Authors: Zhang J , Wu Q , Godfrey D , Yin F
Published: July 2007

Purpose: This clinical study evaluates digital tomosynthesis (DTS) technology for daily imaging guidance for partial breast irradiation (PBI) and compares its positioning accuracy to the 3D CBCT technique. Compared to CBCT, DTS offers lower imaging dose and the geometrical flexibility that particularly suits PBI. Methods and Material: Ten patients undergoing PBI were imaged using an on‐board‐imager mounted on a Varian 21EX linear accelerator. Following the initials setup using skin markers and 2D KV/MV radiographs, a CBCT scan was acquired to provide 3D positioning guidance. A subset of the CBCT projections were used to reconstruct a stack of DTS image slices using the Feldkamp filtered back‐projection algorithm. To optimize soft tissue contrast, the DTS images were reconstructed for the 45‐degree oblique view along which the tumor bed, breast tissues, bones, and lung were well separated. Coronal and sagittal DTS views were also reconstructed for comparison. The inter‐fraction position deviations between the 1st fraction and each of the subsequent fractions were measured by coronal‐DTS, sagittal‐DTS, oblique‐DTS and CBCT as four independent technologies. Differences between these technologies and their clinical impact were evaluated. The evaluator was well trained for DTS technology. Results: Eighty‐five imaging datasets were obtained from 10 patients. Surgical clips (when present) were visible in all three DTS views. The tumor bed had the best contrast in the oblique‐DTS. One‐dimensional positioning differences between DTS (averaged over 3 DTS views) and CBCT were ∼0.1 cm when surgical clips were used in the registration and ∼0.2 cm when the tumor bed were used in the registration. Conclusion: DTS is equivalent to CBDT as a 3D imaging technique for daily patient positioning of PBI but with less mechanical constraints and imaging dose.

Partially supported by a research grant from Varian Medical Systems.
WE‐E‐AUD‐03: Characterization of a Novel, Fast, In‐House, CCD‐Based Optical‐CT Scanner for 3D Dosimetry in Radiochromic Dosimeters
Authors: Sakhalkar H , Guo P , Adamovics J , Oldham M
Published: July 2007

Purpose: Practical tools for comprehensive three‐dimensional (3D) dosimetry are urgently needed. Here we evaluate a novel, in‐house, second‐generation optical‐computed tomography (optical‐CT) scanner for 3D‐dosimetry in PRESAGE™ dosimeters. Primary advantages over laser‐based, first‐generation scanners include much faster scanning times and potential for high resolution. Methods: The optical‐CT scanner performance was evaluated by comparing dose readout with that from the ‘gold‐standard’ first‐generation (MGS) scanner for three irradiation schemes of progressive complexity (a single rectangular‐beam, a 3D‐conformal and an IMRT treatment). The scanner incorporates a red‐filtered (633 nm) uniform area‐backlight, but is distinguished by incorporation of a customized tertiary telecentric lens‐system, which enables image formation with parallel light‐ray geometry. 2D projection images were acquired on a CCD camera of an irradiated PRESAGE™ cylinder (5 cm diameter). Multiple 2D projections over a 360°‐scan were used to reconstruct a 3D map of attenuation coefficients. Results: A complete set of high‐resolution (1392×1040 pixels, 50μm) projection images was acquired in ∼5 minutes with the new (CCD) scanner. This represents an improvement in speed of >2 orders of magnitude and potential for high‐resolution dosimetry compared to the first‐generation MGS scanner. The speed advantage for CCD‐scanner arises because, unlike the MGS scanner, an entire 2D‐projection is acquired in a single acquisition. Line profiles showed that 3D dose readout from the CCD scanner was in good agreement with independent readout from the MGS scanner as well as the calculated treatment plan for all three irradiation schemes. Gamma comparison indicated agreement with MGS readout within 4% dose‐difference and 4mm distance‐to‐agreement. While the signal‐to‐noise ratio for MGS scanner is better by a factor of 3, the attributes of faster speed and higher resolution are highly desirable for practical 3D‐dosimetry. Conclusion: This work demonstrates the feasibility of accurate 3D dosimetry with the new optical‐CT scanner used in combination with radiochromic (non‐scattering) dosimeters.
WE‐E‐L100E‐01: PET CT Workshop — PET/CT Scanner Offering From Different Manufacturers
Authors: Anderson J , Mawlawi O
Published: July 2007

The objectives of this workshop are to provide an overview of the different commercially available PET/CT scanners and to gain the necessary knowledge of PET/CT QC/QA procedures as well as the criteria needed for PET scanner accreditation and acceptance testing. The first objective will be met during the first day whereby three presentations will be provided covering the PET/CT scanner offerings from GE Health Care, Siemens Medical Solutions, and Philips Medical Systems respectively. The presentations will focus on PET scanner design, performance, and capabilities and will be given by respective users of the equipment rather than representatives of the manufacturers. The second objective will be met during the second day of the workshop, whereby four speakers will discuss topics on PET/CT QC/QA procedures, PET NEMA acceptance testing, PET ACR accreditation, and PET site shielding calculations and requirements.
Legionella pneumophila
in Cooling Towers: Fluctuations in Counts, Determination of Genetic Variability by Pulsed-Field Gel Electrophoresis (PFGE), and Persistence of PFGE Patterns
Authors: Ragull Sonia , Garcia-Nuñez Marian , Pedro-Botet Maria Luisa , Sopena Nieves , Esteve Maria , Montenegro Rafael , Sabrià Miquel
Published: June 2007

The concentrations of
Legionella pneumophila
in cooling towers may vary considerably over short periods of time, producing significant fluctuations throughout the year. Despite genetic variability, in small geographical areas the same indistinguishable pulsed-field gel electrophoresis patterns may be shared among different cooling towers and persist over time.
Effects of Intranasal Administration of a Leptin-Secreting
Lactococcus lactis
Recombinant on Food Intake, Body Weight, and Immune Response of Mice
Authors: Bermúdez-Humarán Luis G. , Nouaille Sébastien , Zilberfarb Vladimir , Corthier Gérard , Gruss Alexandra , Langella Philippe , Issad Tarik
Published: June 2007

Leptin is an adipocyte-derived pleiotropic hormone that modulates a large number of physiological functions, including control of body weight and regulation of the immune system. In this work, we show that a recombinant strain of the food-grade lactic acid bacterium
Lactococcus lactis
(LL-lep) can produce and efficiently secrete human leptin. The secreted leptin is a fully biologically active hormone, as demonstrated by its capacity to stimulate a STAT3 reporter gene in HEK293 cells transfected with the Ob-Rb leptin receptor. The immunomodulatory activity of leptin-secreting
L. lactis
was evaluated in vivo by coexpression with the human papillomavirus type 16 E7 protein. In C57BL/6 mice immunized intranasally with a recombinant
L. lactis
strain coproducing leptin and E7 antigen, the adaptive immune response was significantly higher than in mice immunized with recombinant
L. lactis
producing only E7 antigen, demonstrating adjuvanticity of leptin. We then analyzed the effects of intranasally administered LL-lep in obese
ob
/
ob
mice. We observed that daily administration of LL-lep to these mice significantly reduced body weight gain and food intake. These results demonstrate that leptin can be produced and secreted in an active form by
L. lactis
and that leptin-producing
L. lactis
regulates in vivo antigen-specific immune responses, as well as body weight and food consumption.
Interpreting Ecological Diversity Indices Applied to Terminal Restriction Fragment Length Polymorphism Data: Insights from Simulated Microbial Communities
Authors: Blackwood Christopher B. , Hudleston Deborah , Zak Donald R. , Buyer Jeffrey S.
Published: June 2007

Ecological diversity indices are frequently applied to molecular profiling methods, such as terminal restriction fragment length polymorphism (T-RFLP), in order to compare diversity among microbial communities. We performed simulations to determine whether diversity indices calculated from T-RFLP profiles could reflect the true diversity of the underlying communities despite potential analytical artifacts. These include multiple taxa generating the same terminal restriction fragment (TRF) and rare TRFs being excluded by a relative abundance (fluorescence) threshold. True community diversity was simulated using the lognormal species abundance distribution. Simulated T-RFLP profiles were generated by assigning each species a TRF size based on an empirical or modeled TRF size distribution. With a typical threshold (1%), the only consistently useful relationship was between Smith and Wilson evenness applied to T-RFLP data (TRF-
E
var
) and true Shannon diversity (
H
′), with correlations between 0.71 and 0.81. TRF-
H
′ and true
H
′ were well correlated in the simulations using the lowest number of species, but this correlation declined substantially in simulations using greater numbers of species, to the point where TRF-
H
′ cannot be considered a useful statistic. The relationships between TRF diversity indices and true indices were sensitive to the relative abundance threshold, with greatly improved correlations observed using a 0.1% threshold, which was investigated for comparative purposes but is not possible to consistently achieve with current technology. In general, the use of diversity indices on T-RFLP data provides inaccurate estimates of true diversity in microbial communities (with the possible exception of TRF-
E
var
). We suggest that, where significant differences in T-RFLP diversity indices were found in previous work, these should be reinterpreted as a reflection of differences in community composition rather than a true difference in community diversity.
Identification of Internal Transcribed Spacer Sequence Motifs in Truffles: a First Step toward Their DNA Bar Coding
Authors: El Karkouri Khalid , Murat Claude , Zampieri Elisa , Bonfante Paola
Published: June 2007

This work presents DNA sequence motifs from the internal transcribed spacer (ITS) of the nuclear rRNA repeat unit which are useful for the identification of five European and Asiatic truffles (
Tuber magnatum
,
T. melanosporum
,
T. indicum
,
T. aestivum
, and
T. mesentericum
). Truffles are edible mycorrhizal ascomycetes that show similar morphological characteristics but that have distinct organoleptic and economic values. A total of 36 out of 46 ITS1 or ITS2 sequence motifs have allowed an accurate in silico distinction of the five truffles to be made (i.e., by pattern matching and/or BLAST analysis on downloaded GenBank sequences and directly against GenBank databases). The motifs considered the intraspecific genetic variability of each species, including rare haplotypes, and assigned their respective species from either the ascocarps or ectomycorrhizas. The data indicate that short ITS1 or ITS2 motifs (≤50 bp in size) can be considered promising tools for truffle species identification. A dot blot hybridization analysis of
T. magnatum
and
T. melanosporum
compared with other close relatives or distant lineages allowed at least one highly specific motif to be identified for each species. These results were confirmed in a blind test which included new field isolates. The current work has provided a reliable new tool for a truffle oligonucleotide bar code and identification in ecological and evolutionary studies.
Distribution and Expression of Elicitin Genes in the Interspecific Hybrid OomycetePhytophthora alni
Authors: Ioos Renaud , Panabières Franck , Industri Benoît , Andrieux Axelle , Frey Pascal
Published: June 2007

Phytophthora alnisubsp.alni,P. alnisubsp.multiformis, andP. alnisubsp.uniformisare responsible for alder disease in Europe. Class I and II elicitin gene patterns ofP. alnisubsp.alni,P. alnisubsp.multiformis,P. alnisubsp.uniformis, and the phylogenetically close speciesP. cambivoraandP. fragariaewere studied through mRNA sequencing and 3′ untranslated region (3′UTR)-specific PCRs and sequencing. The occurrence of multiple 3′UTR sequences in association with identical elicitin-encoding sequences inP. alnisubsp.alniindicated duplication/recombination events. The mRNA pattern displayed byP. alnisubsp.alnidemonstrated that elicitin genes from all the parental genomes are actually expressed in this allopolyploid taxon. The complementary elicitin patterns resolved confirmed the possible involvement ofP. alnisubsp.multiformisandP. alnisubsp.uniformisin the genesis of the hybrid speciesP. alnisubsp.alni. The occurrence of multiple and common elicitin gene sequences throughoutP. cambivora,P. fragariae, andP. alnisensu lato, not observed in otherPhytophthoraspecies, suggests that duplication of these genes occurred before the radiation of these species.
Use of a Dominant
rpsL
Allele Conferring Streptomycin Dependence for Positive and Negative Selection in
Thermus thermophilus
Authors: Blas-Galindo Emilio , Cava Felipe , López-Viñas Eduardo , Mendieta Jesús , Berenguer José
Published: June 2007

A spontaneous
rpsL
mutant of
Thermus thermophilus
was isolated in a search for new selection markers for this organism. This new allele, named
rpsL1
, encodes a K47R/K57E double mutant S12 ribosomal protein that confers a streptomycin-dependent (SD) phenotype to
T. thermophilus
. Models built on the available three-dimensional structures of the 30S ribosomal subunit revealed that the K47R mutation directly affects the streptomycin binding site on S12, whereas the K57E does not apparently affect this binding site. Either of the two mutations conferred the SD phenotype individually. The presence of the
rpsL1
allele, either as a single copy inserted into the chromosome as part of suicide plasmids or in multicopy as replicative plasmids, produced a dominant SD phenotype despite the presence of a wild-type
rpsL
gene in a host strain. This dominant character allowed us to use the
rpsL1
allele not only for positive selection of plasmids to complement a kanamycin-resistant mutant strain, but also more specifically for the isolation of deletion mutants through a single step of negative selection on streptomycin-free growth medium.
Saccharomyces cerevisiaeSignature Genes for Predicting Nitrogen Deficiency during Alcoholic Fermentation
Authors: Mendes-Ferreira A. , del Olmo M. , García-Martínez J. , Jiménez-Martí E. , Leão C. , Mendes-Faia A. , Pérez-Ortín J. E.
Published: June 2007

Genome-wide analysis of the wine yeast strainSaccharomyces cerevisiaePYCC4072 identified 36 genes highly expressed under conditions of low or absent nitrogen in comparison with a nitrogen-replete condition. Reverse transcription-PCR analysis for four of these transcripts with this strain and its validation with another wine yeast strain underlines the usefulness of these signature genes for predicting nitrogen deficiency and therefore the diagnosis of wine stuck/sluggish fermentations.