Explore the vast range of titles available.

We describe the development and analysis of a new teletherapy modality that, through a novel approach to targeted radiation delivery, has the potential to provide greater conformality than conventional photon-based treatments. The proposed system uses an X-ray lens to reflect photons from a conventional X-ray tube toward a focal spot. The resulting dose distributions have a highly localized peak dose, with lower doses in the converging radiation cone. Physical principles governing the design of this system are presented, along with a series of measurements analyzing various characteristics of the converging beam. The beam was designed to be nearly monoenergetic (~ 59 keV), with an energy bandwidth of approximately 10 keV allowing for treatment energies lower than conventional therapies. The focal spot was measured to be approximately 2.5 cm long and 4 mm wide. Mounting the proposed X-ray delivery system on a robotic arm would allow sub-millimeter accuracy in focal spot positioning, resulting in highly conformal dose distribution via the optimal placement of individual focal spots within the target volume. Aspects of this novel radiation beam are discussed considering their possible clinical application as a treatment approach that takes maximum advantage of the unique properties afforded by converging X-ray beam therapy.

The physical properties of particles used in radiation therapy, such as protons, have been well characterized and their dose distributions are superior to photon-based treatments. However, proton therapy may also have inherent biologic advantages that have not been capitalized on. Unlike photon beams, the linear energy transfer (LET) and hence biologic effectiveness of particle beams varies along the beam path. Selective placement of areas of high effectiveness could enhance tumor cell kill and simultaneously spare normal tissues. However, previous methods for mapping spatial variations in biologic effectiveness are time-consuming and often yield inconsistent results with large uncertainties. Thus the data needed to accurately model relative biological effectiveness to guide novel treatment planning approaches are limited. We used Monte Carlo modeling and high-content automated clonogenic survival assays to spatially map the biologic effectiveness of scanned proton beams with high accuracy and throughput while minimizing biological uncertainties. We found that the relationship between cell kill, dose and LET, is complex and non-unique. Measured biologic effects were substantially greater than in most previous reports, and non-linear surviving fraction response was observed even for the highest LET values. Extension of this approach could generate data needed to optimize proton therapy plans incorporating variable RBE.

Bcl-xL plays a critical role in maintaining cell survival. However, the relationship between the potential interaction of Bcl-xL with other cytosolic proteins and the regulation of cell survival remains incompletely defined. We have identified translationally controlled tumor protein (TCTP), a multifunctional protein, as a novel antiapoptotic Bcl-xL-interacting protein. TCTP interacted in vivo and in vitro with Bcl-xL, and their sites have been mapped to an N-terminal region of TCTP and the Bcl-2 homology domain 3 of Bcl-xL. Consistent with a role in maintaining T-cell survival during activation, TCTP was significantly upregulated in murine T cells activated by T-cell antigen receptor (TCR) ligation and CD28 costimulation, which was correlated with the upregulation of Bcl-xL in activated T cells. Moreover, downregulation of TCTP expression by antisense technology in T cells results in the increase of T-cell apoptosis. Furthermore, the N-terminal region of TCTP was required for its ability to inhibit apoptosis. In conclusion, this study has demonstrated that an N-terminal region of a cytosolic protein, TCTP, is required for its binding to Bcl-xL and for its antiapoptotic activity.

Background To determine the optimal approach to delineating patient-specific internal gross target volumes (IGTV) from four-dimensional (4-D) computed tomography (CT) image data sets used in the planning of radiation treatment for lung cancers. Methods We analyzed 4D-CT image data sets of 27 consecutive patients with non-small-cell lung cancer (stage I: 17, stage III: 10). The IGTV, defined to be the envelope of respiratory motion of the gross tumor volume in each 4D-CT data set was delineated manually using four techniques: ( 1 ) combining the gross tumor volume (GTV) contours from ten respiratory phases (IGTV AllPhases ); ( 2 ) combining the GTV contours from two extreme respiratory phases (0% and 50%) (IGTV 2Phases ); ( 3 ) defining the GTV contour using the maximum intensity projection (MIP) (IGTV MIP ); and ( 4 ) defining the GTV contour using the MIP with modification based on visual verification of contours in individual respiratory phase (IGTV MIP-Modified ). Using the IGTV AllPhases as the optimum IGTV, we compared volumes, matching indices, and extent of target missing using the IGTVs based on the other three approaches. Results The IGTV MIP and IGTV 2Phases were significantly smaller than the IGTV AllPhases ( p < 0.006 for stage I and p < 0.002 for stage III). However, the values of the IGTV MIP-Modified were close to those determined from IGTV AllPhases ( p = 0.08). IGTV MIP-Modified also matched the best with IGTV AllPhases . Conclusion IGTV MIP and IGTV 2Phases underestimate IGTVs. IGTV MIP-Modified is recommended to improve IGTV delineation in lung cancer.

The Xstrahl 300 orthovoltage unit is designed to deliver kilovoltage radiation therapy using the appositional technique. However, it is not equipped with some typical linear accelerator features, such as mechanical distance indicator and crosshair projection, which are useful for facilitating equipment setup during various quality assurance (QA) and research activities. Therefore, we designed and constructed slip‐in devices to facilitate QA for dosimetric measurements of our Xstrahl 300 unit. These include: (a) an ion chamber positioning system for dosimetric measurements, (b) a mechanical pointer for setting dosimeter distance to a nominal 50 cm, and (c) a crosshair projector with built‐in light to facilitate alignment of dosimeter to the center of the radiation field. These devices provide a high degree of setup reproducibility thereby minimizing setup errors. We used these devices to perform QA of the Xstrahl 300 orthovoltage unit. One of the QA tests we perform is a constancy check of beam output and energy. Our data since start of clinical use of this unit (approximately 2.5 yr) show dose outputs to be remarkably reproducible (2σ = ±0.4%) for all three clinical beams (75, 125, and 250 kVp). These devices have provided both convenience and high‐precision during the unit’s commissioning, and continue to provide the same for various QA activities on the Xstrahl 300 orthovoltage unit.

Background Radiogenic second cancer is a common late effect in long term cancer survivors. Currently there are few methods or tools available to visually evaluate the spatial distribution of risks of radiogenic late effects in the human body. We developed a risk visualization method and demonstrated it for radiogenic second cancers in tissues and organs of one patient treated with photon volumetric modulated arc therapy and one patient treated with proton craniospinal irradiation. Methods Treatment plans were generated using radiotherapy treatment planning systems (TPS) and dose information was obtained from TPS. Linear non-threshold risk coefficients for organs at risk of second cancer incidence were taken from the Biological Effects of Ionization Radiation VII report. Alternative risk models including linear exponential model and linear plateau model were also examined. The predicted absolute lifetime risk distributions were visualized together with images of the patient anatomy. Results The risk distributions of second cancer for the two patients were visually presented. The risk distributions varied with tissue, dose, dose-risk model used, and the risk distribution could be similar to or very different from the dose distribution. Conclusions Our method provides a convenient way to directly visualize and evaluate the risks of radiogenic second cancer in organs and tissues of the human body. In the future, visual assessment of risk distribution could be an influential determinant for treatment plan scoring.

{\\bf Purpose}: To develop a first principle and multi-scale model for normal tissue complication probability (NTCP) as a function of dose and LET for proton and in general for particle therapy with a goal of incorporating nano-scale radio-chemical to macro-scale cell biological pathways, spanning from initial DNA damage to tissue late effects. {\\bf Methods}: The method is combination of analytical and multi-scale computational steps including (1) derivation of functional dependencies of NTCP on DNA driven cell lethality in nanometer and mapping to dose and LET in millimeter, and (2) 3D-surface fitting to Monte Carlo data set generated based on post radiation image change and gathered for a cohort of 14 pediatric patients treated by scanning beam of protons for ependymoma. We categorize voxel-based dose and LET associated with development of necrosis in NTCP. {\\bf Result}: Our model fits well the clinical data, generated for post radiation tissue toxicity and necrosis. The fitting procedure results in extraction of in-{\\it vivo} radio-biological \\(\\alpha\\)-\\(\\beta\\) indices and their numerical values. {\\bf Discussion and conclusion}: The NTCP model, explored in this work, allows to correlate the tissue toxicities to DNA initial damage, cell lethality and the properties and qualities of radiation, dose and LET.

We study a two-parameter family of Riemann problems for the unsteady transonic small disturbance (UTSD) equation, also called the two-dimensional Burgers equation. The two parameters, a and b, which define oblique shock initial data, correspond to the slopes of the initial shock waves in the upper half-plane. For each a and b, the three constant states in the upper half-plane satisfy the Rankine-Hugoniot conditions across the shocks. This leads to a two-parameter family of oblique shock interaction problems. In this paper we present a numerical study of global solution behavior for the values of a and b in a previously obtained bifurcation diagram. Our study supplements the related theoretical results and conjectures recently obtained by S. Čanić and B. L. Keyfitz. We employ a high resolution numerical method which reveals fine solution structures. Our findings confirm theoretical results and conjectures about the solution patterns and deepen the understanding of the structure of several intricate wave interactions arising in this model.

Purpose Development of a design tool for IIR digital filters obtained from analog prototypes, which preserves simultaneously the amplitude and the group delay response. Design/methodology/approach A new s-to-z transform is developed based on a second order formula used for numerical integration of differential equations. Stability of the newly obtained transfer functions in the z- domain is proved to be preserved. Distortions introduced by the new transform into the original amplitude and group delay responses are studied. Findings The new formula, when implemented to all-pole prototypes, exhibits lower selectivity than the original while reducing the pass-band group delay distortions. In the same time its structure is importantly simpler than the functions obtained by the well-known bilinear transform. When implemented to a prototype having \"all kinds\" of transmission zeros the resulting filter has almost ideally the same characteristic as the prototype. Research limitations/implications The new transform may be used exclusively to synthesize even order filters. The new function is twice the order of the analog prototype. This kind of transformations are used to design IIR digital filters only. Low-pass transfer functions were studied being prototypes for all other cases. Originality/value This is a new result never mentioned in the literature. Its effectiveness is confined to a niche problem when simultaneous sharp selectivity and low group delay distortions are sought.

Efficient parallel algorithms for numerical solution of the second-order elliptic problem are considered in which Raviart-Thomas mixed finite element spaces of the lowest order are used for a saddle-point variational formulation of the original problem. The resulting indefinite linear system is reformulated either as a symmetric or non-symmetric positive definite system. In the symmetric reformulation, preconditioned conjugate gradient method is used to solve linear system; in non-symmetric reformulation generalized conjugate-gradient-like methods are used. We construct efficient solution procedures for preconditioner evaluation, and give an analysis of the convergence. A parallel version of the algorithm was obtained using the non-overlapping domain decomposition method proposed by Glowinski and Wheeler. For this method we propose an quasi-optimal pre-conditioner, for the subdomain interface problem. Numerical experiments from a parallel implementation on an Intel iPSC/860 hypercube computer are presented which show the method to be both efficient and scalable. The numerical examples also confirm the theoretical bounds of the condition number of the interface operator.