The performance of the progressive resolution optimizer (PRO) for RapidArc planning in targets with low-density media.

PubMed

Kan, Monica W K; Leung, Lucullus H T; Yu, Peter K N

2013-11-04

A new version of progressive resolution optimizer (PRO) with an option of air cavity correction has been implemented for RapidArc volumetric-modulated arc therapy (RA). The purpose of this study was to compare the performance of this new PRO with the use of air cavity correction option (PRO10_air) against the one without the use of the air cavity correction option (PRO10_no-air) for RapidArc planning in targets with low-density media of different sizes and complexities. The performance of PRO10_no-air and PRO10_air was initially compared using single-arc plans created for four different simple heterogeneous phantoms with virtual targets and organs at risk. Multiple-arc planning of 12 real patients having nasopharyngeal carcinomas (NPC) and ten patients having non-small cell lung cancer (NSCLC) were then performed using the above two options for further comparison. Dose calculations were performed using both the Acuros XB (AXB) algorithm with the dose to medium option and the analytical anisotropic algorithm (AAA). The effect of using intermediate dose option after the first optimization cycle in PRO10_air and PRO10_no-air was also investigated and compared. Plans were evaluated and compared using target dose coverage, critical organ sparing, conformity index, and dose homogeneity index. For NSCLC cases or cases for which large volumes of low-density media were present in or adjacent to the target volume, the use of the air cavity correction option in PRO10 was shown to be beneficial. For NPC cases or cases for which small volumes of both low- and high-density media existed in the target volume, the use of air cavity correction in PRO10 did not improve the plan quality. Based on the AXB dose calculation results, the use of PRO10_air could produce up to 18% less coverage to the bony structures of the planning target volumes for NPC cases. When the intermediate dose option in PRO10 was used, there was negligible difference observed in plan quality between optimizations with and without using the air cavity correction option.

RNAi screening of subtracted transcriptomes reveals tumor suppression by taurine-activated GABAA receptors involved in volume regulation

PubMed Central

van Nierop, Pim; Vormer, Tinke L.; Foijer, Floris; Verheij, Joanne; Lodder, Johannes C.; Andersen, Jesper B.; Mansvelder, Huibert D.; te Riele, Hein

2018-01-01

To identify coding and non-coding suppressor genes of anchorage-independent proliferation by efficient loss-of-function screening, we have developed a method for enzymatic production of low complexity shRNA libraries from subtracted transcriptomes. We produced and screened two LEGO (Low-complexity by Enrichment for Genes shut Off) shRNA libraries that were enriched for shRNA vectors targeting coding and non-coding polyadenylated transcripts that were reduced in transformed Mouse Embryonic Fibroblasts (MEFs). The LEGO shRNA libraries included ~25 shRNA vectors per transcript which limited off-target artifacts. Our method identified 79 coding and non-coding suppressor transcripts. We found that taurine-responsive GABAA receptor subunits, including GABRA5 and GABRB3, were induced during the arrest of non-transformed anchor-deprived MEFs and prevented anchorless proliferation. We show that taurine activates chloride currents through GABAA receptors on MEFs, causing seclusion of cell volume in large membrane protrusions. Volume seclusion from cells by taurine correlated with reduced proliferation and, conversely, suppression of this pathway allowed anchorage-independent proliferation. In human cholangiocarcinomas, we found that several proteins involved in taurine signaling via GABAA receptors were repressed. Low GABRA5 expression typified hyperproliferative tumors, and loss of taurine signaling correlated with reduced patient survival, suggesting this tumor suppressive mechanism operates in vivo. PMID:29787571

Dosimetric quality, accuracy, and deliverability of modulated radiotherapy treatments for spinal metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kairn, Tanya, E-mail: t.kairn@gmail.com; School of Chemistry, Physics, and Mechanical Engineering, Queensland University of Technology, Brisbane; Papworth, Daniel

2016-10-01

Cancer often metastasizes to the vertebra, and such metastases can be treated successfully using simple, static posterior or opposed-pair radiation fields. However, in some cases, including when re-irradiation is required, spinal cord avoidance becomes necessary and more complex treatment plans must be used. This study evaluated 16 sample intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) treatment plans designed to treat 6 typical vertebral and paraspinal volumes using a standard prescription, with the aim of investigating the advantages and limitations of these treatment techniques and providing recommendations for their optimal use in vertebral treatments. Treatment plan quality and beammore » complexity metrics were evaluated using the Treatment And Dose Assessor (TADA) code. A portal-imaging–based quality assurance (QA) system was used to evaluate treatment delivery accuracy, and radiochromic film measurements were used to provide high-resolution verification of treatment plan dose accuracy, especially in the steep dose gradient regions between each vertebral target and spinal cord. All treatment modalities delivered approximately the same doses and the same levels of dose heterogeneity to each planning target volume (PTV), although the minimum PTV doses in the vertebral plans were substantially lower than the prescription, because of the requirement that the plans meet a strict constraint on the dose to the spinal cord and cord planning risk volume (PRV). All plans met required dose constraints on all organs at risk, and all measured PTV-cord dose gradients were steeper than planned. Beam complexity analysis suggested that the IMRT treatment plans were more deliverable (less complex, leading to greater QA success) than the VMAT treatment plans, although the IMRT plans also took more time to deliver. The accuracy and deliverability of VMAT treatment plans were found to be substantially increased by limiting the number of monitor units (MU) per beam at the optimization stage, and thereby limiting beam modulation complexity. The VMAT arcs that were optimized with MU limitation had higher QA pass rates as well as higher modulation complexity scores (less complexity), lower modulation indices (less modulation), lower MU per beam, larger beam segments, and fewer small apertures than the VMAT arcs that were optimized without MU limitation. It is recommended that VMAT treatments for vertebral volumes, where the PTV abuts or surrounds the spinal cord, should be optimized with MU limitation. IMRT treatments may be preferable to the VMAT treatments, for dosimetry and deliverability reasons, but may be inappropriate for some patients because of their increased treatment delivery time.« less

4D Optimization of Scanned Ion Beam Tracking Therapy for Moving Tumors

PubMed Central

Eley, John Gordon; Newhauser, Wayne David; Lüchtenborg, Robert; Graeff, Christian; Bert, Christoph

2014-01-01

Motion mitigation strategies are needed to fully realize the theoretical advantages of scanned ion beam therapy for patients with moving tumors. The purpose of this study was to determine whether a new four-dimensional (4D) optimization approach for scanned-ion-beam tracking could reduce dose to avoidance volumes near a moving target while maintaining target dose coverage, compared to an existing 3D-optimized beam tracking approach. We tested these approaches computationally using a simple 4D geometrical phantom and a complex anatomic phantom, that is, a 4D computed tomogram of the thorax of a lung cancer patient. We also validated our findings using measurements of carbon-ion beams with a motorized film phantom. Relative to 3D-optimized beam tracking, 4D-optimized beam tracking reduced the maximum predicted dose to avoidance volumes by 53% in the simple phantom and by 13% in the thorax phantom. 4D-optimized beam tracking provided similar target dose homogeneity in the simple phantom (standard deviation of target dose was 0.4% versus 0.3%) and dramatically superior homogeneity in the thorax phantom (D5-D95 was 1.9% versus 38.7%). Measurements demonstrated that delivery of 4D-optimized beam tracking was technically feasible and confirmed a 42% decrease in maximum film exposure in the avoidance region compared with 3D-optimized beam tracking. In conclusion, we found that 4D-optimized beam tracking can reduce the maximum dose to avoidance volumes near a moving target while maintaining target dose coverage, compared with 3D-optimized beam tracking. PMID:24889215

4D optimization of scanned ion beam tracking therapy for moving tumors

NASA Astrophysics Data System (ADS)

Eley, John Gordon; Newhauser, Wayne David; Lüchtenborg, Robert; Graeff, Christian; Bert, Christoph

2014-07-01

Motion mitigation strategies are needed to fully realize the theoretical advantages of scanned ion beam therapy for patients with moving tumors. The purpose of this study was to determine whether a new four-dimensional (4D) optimization approach for scanned-ion-beam tracking could reduce dose to avoidance volumes near a moving target while maintaining target dose coverage, compared to an existing 3D-optimized beam tracking approach. We tested these approaches computationally using a simple 4D geometrical phantom and a complex anatomic phantom, that is, a 4D computed tomogram of the thorax of a lung cancer patient. We also validated our findings using measurements of carbon-ion beams with a motorized film phantom. Relative to 3D-optimized beam tracking, 4D-optimized beam tracking reduced the maximum predicted dose to avoidance volumes by 53% in the simple phantom and by 13% in the thorax phantom. 4D-optimized beam tracking provided similar target dose homogeneity in the simple phantom (standard deviation of target dose was 0.4% versus 0.3%) and dramatically superior homogeneity in the thorax phantom (D5-D95 was 1.9% versus 38.7%). Measurements demonstrated that delivery of 4D-optimized beam tracking was technically feasible and confirmed a 42% decrease in maximum film exposure in the avoidance region compared with 3D-optimized beam tracking. In conclusion, we found that 4D-optimized beam tracking can reduce the maximum dose to avoidance volumes near a moving target while maintaining target dose coverage, compared with 3D-optimized beam tracking.

Exploring the interactome: microfluidic isolation of proteins and interacting partners for quantitative analysis by electron microscopy.

PubMed

Giss, Dominic; Kemmerling, Simon; Dandey, Venkata; Stahlberg, Henning; Braun, Thomas

2014-05-20

Multimolecular protein complexes are important for many cellular processes. However, the stochastic nature of the cellular interactome makes the experimental detection of complex protein assemblies difficult and quantitative analysis at the single molecule level essential. Here, we present a fast and simple microfluidic method for (i) the quantitative isolation of endogenous levels of untagged protein complexes from minute volumes of cell lysates under close to physiological conditions and (ii) the labeling of specific components constituting these complexes. The method presented uses specific antibodies that are conjugated via a photocleavable linker to magnetic beads that are trapped in microcapillaries to immobilize the target proteins. Proteins are released by photocleavage, eluted, and subsequently analyzed by quantitative transmission electron microscopy at the single molecule level. Additionally, before photocleavage, immunogold can be employed to label proteins that interact with the primary target protein. Thus, the presented method provides a new way to study the interactome and, in combination with single molecule transmission electron microscopy, to structurally characterize the large, dynamic, heterogeneous multimolecular protein complexes formed.

Dosimetric comparison of single-beam multi-arc and 2-beam multi-arc VMAT optimization in the Monaco treatment planning system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kalet, Alan M., E-mail: amkalet@uw.edu; Seattle Cancer Care Alliance, Seattle, Washington; Richardson, Hannah L.

The purpose of this study was to evaluate the dosimetric and practical effects of the Monaco treatment planning system “max arcs-per-beam” optimization parameter in pelvic radiotherapy treatments. We selected for this study a total of 17 previously treated patients with a range of pelvic disease sites including prostate (9), bladder (1), uterus (3), rectum (3), and cervix (1). For each patient, 2 plans were generated, one using an arc-per-beam setting of “1” and another with an arc-per-beam setting of “2” using the volumes and constraints established from the initial clinical treatments. All constraints and dose coverage objects were kept themore » same between plans, and all plans were normalized to 99.7% to ensure 100% of the planning target volume (PTV) received 95% of the prescription dose. Plans were evaluated for PTV conformity, homogeneity, number of monitor units, number of control points, and overall plan acceptability. Treatment delivery time, patient-specific quality assurance procedures, and the impact on clinical workflow were also assessed. We found that for complex-shaped target volumes (small central volumes with extending arms to cover nodal regions), the use of 2 arc-per-beam (2APB) parameter setting achieved significantly lower average dose-volume histogram values for the rectum V{sub 20} (p = 0.0012) and bladder V{sub 30} (p = 0.0036) while meeting the high dose target constraints. For simple PTV shapes, we found reduced monitor units (13.47%, p = 0.0009) and control points (8.77%, p = 0.0004) using 2APB planning. In addition, we found a beam delivery time reduction of approximately 25%. In summary, the dosimetric benefit, although moderate, was improved over a 1APB setting for complex PTV, and equivalent in other cases. The overall reduced delivery time suggests that the use of mulitple arcs per beam could lead to reduced patient-on-table time, increased clinical throughput, and reduced medical physics quality assurance effort.« less

System and method for radiation dose calculation within sub-volumes of a monte carlo based particle transport grid

DOEpatents

Bergstrom, Paul M.; Daly, Thomas P.; Moses, Edward I.; Patterson, Jr., Ralph W.; Schach von Wittenau, Alexis E.; Garrett, Dewey N.; House, Ronald K.; Hartmann-Siantar, Christine L.; Cox, Lawrence J.; Fujino, Donald H.

2000-01-01

A system and method is disclosed for radiation dose calculation within sub-volumes of a particle transport grid. In a first step of the method voxel volumes enclosing a first portion of the target mass are received. A second step in the method defines dosel volumes which enclose a second portion of the target mass and overlap the first portion. A third step in the method calculates common volumes between the dosel volumes and the voxel volumes. A fourth step in the method identifies locations in the target mass of energy deposits. And, a fifth step in the method calculates radiation doses received by the target mass within the dosel volumes. A common volume calculation module inputs voxel volumes enclosing a first portion of the target mass, inputs voxel mass densities corresponding to a density of the target mass within each of the voxel volumes, defines dosel volumes which enclose a second portion of the target mass and overlap the first portion, and calculates common volumes between the dosel volumes and the voxel volumes. A dosel mass module, multiplies the common volumes by corresponding voxel mass densities to obtain incremental dosel masses, and adds the incremental dosel masses corresponding to the dosel volumes to obtain dosel masses. A radiation transport module identifies locations in the target mass of energy deposits. And, a dose calculation module, coupled to the common volume calculation module and the radiation transport module, for calculating radiation doses received by the target mass within the dosel volumes.

Volume hologram with random encoded reference beam for secure data encryption

NASA Astrophysics Data System (ADS)

Markov, Vladimir B.; Weber, David C.; Trolinger, James D.

2000-04-01

A method is presented to store biometric and/or other important information on an ID card in the form of a Card Hologram that cannot be read or duplicated without the use of a special Key Hologram that is secured inside of an automated reader. The Key Hologram produces the unique wavefront required to release the information contained in a complex, 3D diffraction pattern recorded in a volume hologram attached to the card. Experimental results are presented in which the image of an Air Force resolution target are recorded and reconstructed in a volume material using a random speckle wavefront and that cannot be viewed using a simple wavefront such as a collimated or diverging laser beam.

Volumetric-modulated arc therapy vs conventional fixed-field intensity-modulated radiotherapy in a whole-ventricular irradiation: A planning comparison study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sakanaka, Katsuyuki; Mizowaki, Takashi, E-mail: mizo@kuhp.kyoto-u.ac.jp; Sato, Sayaka

This study evaluated the dosimetric difference between volumetric-modulated arc therapy (VMAT) and conventional fixed-field intensity-modulated radiotherapy (cIMRT) in whole-ventricular irradiation. Computed tomography simulation data for 13 patients were acquired to create plans for VMAT and cIMRT. In both plans, the same median dose (100% = 24 Gy) was prescribed to the planning target volume (PTV), which comprised a tumor bed and whole ventricles. During optimization, doses to the normal brain and body were reduced, provided that the dose constraints of the target coverage were satisfied. The dose-volume indices of the PTV, normal brain, and body as well as monitor unitsmore » were compared between the 2 techniques by using paired t-tests. The results showed no significant difference in the homogeneity index (0.064 vs 0.065; p = 0.824) of the PTV and conformation number (0.78 vs 0.77; p = 0.065) between the 2 techniques. In the normal brain and body, the dose-volume indices showed no significant difference between the 2 techniques, except for an increase in the volume receiving a low dose in VMAT; the absolute volume of the normal brain and body receiving 1 Gy of radiation significantly increased in VMAT by 1.6% and 8.3%, respectively, compared with that in cIMRT (1044 vs 1028 mL for the normal brain and 3079.2 vs 2823.3 mL for the body; p<0.001). The number of monitor units to deliver a 2.0-Gy fraction was significantly reduced in VMAT compared with that in cIMRT (354 vs 873, respectively; p<0.001). In conclusion, VMAT delivers IMRT to complex target volumes such as whole ventricles with fewer monitor units, while maintaining target coverage and conformal isodose distribution comparable to cIMRT; however, in addition to those characteristics, the fact that the volume of the normal brain and body receiving a low dose would increase in VMAT should be considered.« less

Pre- and postoperative radiotherapy for extremity soft tissue sarcoma: Evaluation of inter-observer target volume contouring variability among French sarcoma group radiation oncologists.

PubMed

Sargos, P; Charleux, T; Haas, R L; Michot, A; Llacer, C; Moureau-Zabotto, L; Vogin, G; Le Péchoux, C; Verry, C; Ducassou, A; Delannes, M; Mervoyer, A; Wiazzane, N; Thariat, J; Sunyach, M P; Benchalal, M; Laredo, J D; Kind, M; Gillon, P; Kantor, G

2018-04-01

The purpose of this study was to evaluate, during a national workshop, the inter-observer variability in target volume delineation for primary extremity soft tissue sarcoma radiation therapy. Six expert sarcoma radiation oncologists (members of French Sarcoma Group) received two extremity soft tissue sarcoma radiation therapy cases 1: one preoperative and one postoperative. They were distributed with instructions for contouring gross tumour volume or reconstructed gross tumour volume, clinical target volume and to propose a planning target volume. The preoperative radiation therapy case was a patient with a grade 1 extraskeletal myxoid chondrosarcoma of the thigh. The postoperative case was a patient with a grade 3 pleomorphic undifferentiated sarcoma of the thigh. Contour agreement analysis was performed using kappa statistics. For the preoperative case, contouring agreement regarding GTV, gross tumour volume GTV, clinical target volume and planning target volume were substantial (kappa between 0.68 and 0.77). In the postoperative case, the agreement was only fair for reconstructed gross tumour volume (kappa: 0.38) but moderate for clinical target volume and planning target volume (kappa: 0.42). During the workshop discussion, consensus was reached on most of the contour divergences especially clinical target volume longitudinal extension. The determination of a limited cutaneous cover was also discussed. Accurate delineation of target volume appears to be a crucial element to ensure multicenter clinical trial quality assessment, reproducibility and homogeneity in delivering RT. radiation therapy RT. Quality assessment process should be proposed in this setting. We have shown in our study that preoperative radiation therapy of extremity soft tissue sarcoma has less inter-observer contouring variability. Copyright © 2018 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Patient-related factors influencing detectability of coronary arteries in 320-row CT angiography in infants with complex congenital heart disease.

PubMed

Yamasaki, Yuzo; Kawanami, Satoshi; Kamitani, Takeshi; Sagiyama, Koji; Shin, Seitaro; Hino, Takuya; Nagata, Hazumu; Yabuuchi, Hidetake; Nagao, Michinobu; Honda, Hiroshi

2018-05-05

To investigate the performance of second-generation 320-row computed tomographic (CT) angiography (CTA) in detecting coronary arteries and identify factors influencing visibility of the coronary arteries in infants with complex congenital heart disease (CHD). Data of 60 infants (aged 0-2 years, median 2 months) with complex CHD who underwent examination using 320-row CTA with low-dose prospective electrocardiogram-triggered volume target scanning were reviewed. The coronary arteries of each infant were assessed using a 0-4-point scoring system based on the number of coronary segments with a visible course. Clinical parameters, the CT value in the ascending aorta, image noise, and the radiation dose were subjected to univariate and multivariate analyses. The mean coronary score for all examinations was 2.6 ± 1.5 points. The mean attenuation in the ascending aorta was 306.7 ± 66.2 HU and the mean standard deviation was 21.7 ± 4.4. The mean effective radiation dose was 1.27 ± 0.39 mSv. Multivariate regression analysis showed significant correlations between coronary score and body weight (p < 0.05) and between coronary score and the CT value in the ascending aorta (p < 0.02). Second-generation 320-row CTA with prospective electrocardiogram-triggered volume target scanning and hybrid iterative reconstruction allows good visibility of the coronary arteries in infants with complex CHD. Body weight and the CT value in the ascending aorta are important factors influencing the visibility of the coronary arteries in infants.

The performance of the progressive resolution optimizer (PRO) for RapidArc planning in targets with low‐density media

PubMed Central

Leung, Lucullus H.T.; Yu, Peter K.N.

2013-01-01

A new version of progressive resolution optimizer (PRO) with an option of air cavity correction has been implemented for RapidArc volumetric‐modulated arc therapy (RA). The purpose of this study was to compare the performance of this new PRO with the use of air cavity correction option (PRO10_air) against the one without the use of the air cavity correction option (PRO10_no‐air) for RapidArc planning in targets with low‐density media of different sizes and complexities. The performance of PRO10_no‐air and PRO10_air was initially compared using single‐arc plans created for four different simple heterogeneous phantoms with virtual targets and organs at risk. Multiple‐arc planning of 12 real patients having nasopharyngeal carcinomas (NPC) and ten patients having non‐small cell lung cancer (NSCLC) were then performed using the above two options for further comparison. Dose calculations were performed using both the Acuros XB (AXB) algorithm with the dose to medium option and the analytical anisotropic algorithm (AAA). The effect of using intermediate dose option after the first optimization cycle in PRO10_air and PRO10_no‐air was also investigated and compared. Plans were evaluated and compared using target dose coverage, critical organ sparing, conformity index, and dose homogeneity index. For NSCLC cases or cases for which large volumes of low‐density media were present in or adjacent to the target volume, the use of the air cavity correction option in PROIO was shown to be beneficial. For NPC cases or cases for which small volumes of both low‐ and high‐density media existed in the target volume, the use of air cavity correction in PRO10 did not improve the plan quality. Based on the AXB dose calculation results, the use of PRO10_air could produce up to 18% less coverage to the bony structures of the planning target volumes for NPC cases. When the intermediate dose option in PRO10 was used, there was negligible difference observed in plan quality between optimizations with and without using the air cavity correction option. PACS number: 87.55.D‐, 87.55.de, 87.56.N‐

An installed nacelle design code using a multiblock Euler solver. Volume 1: Theory document

NASA Technical Reports Server (NTRS)

Chen, H. C.

1992-01-01

An efficient multiblock Euler design code was developed for designing a nacelle installed on geometrically complex airplane configurations. This approach employed a design driver based on a direct iterative surface curvature method developed at LaRC. A general multiblock Euler flow solver was used for computing flow around complex geometries. The flow solver used a finite-volume formulation with explicit time-stepping to solve the Euler Equations. It used a multiblock version of the multigrid method to accelerate the convergence of the calculations. The design driver successively updated the surface geometry to reduce the difference between the computed and target pressure distributions. In the flow solver, the change in surface geometry was simulated by applying surface transpiration boundary conditions to avoid repeated grid generation during design iterations. Smoothness of the designed surface was ensured by alternate application of streamwise and circumferential smoothings. The capability and efficiency of the code was demonstrated through the design of both an isolated nacelle and an installed nacelle at various flow conditions. Information on the execution of the computer program is provided in volume 2.

Waste treatment process for removal of contaminants from aqueous, mixed-waste solutions using sequential chemical treatment and crossflow microfiltration, followed by dewatering

DOEpatents

Vijayan, S.; Wong, C.F.; Buckley, L.P.

1994-11-22

In processes of this invention aqueous waste solutions containing a variety of mixed waste contaminants are treated to remove the contaminants by a sequential addition of chemicals and adsorption/ion exchange powdered materials to remove the contaminants including lead, cadmium, uranium, cesium-137, strontium-85/90, trichloroethylene and benzene, and impurities including iron and calcium. Staged conditioning of the waste solution produces a polydisperse system of size enlarged complexes of the contaminants in three distinct configurations: water-soluble metal complexes, insoluble metal precipitation complexes, and contaminant-bearing particles of ion exchange and adsorbent materials. The volume of the waste is reduced by separation of the polydisperse system by cross-flow microfiltration, followed by low-temperature evaporation and/or filter pressing. The water produced as filtrate is discharged if it meets a specified target water quality, or else the filtrate is recycled until the target is achieved. 1 fig.

Waste treatment process for removal of contaminants from aqueous, mixed-waste solutions using sequential chemical treatment and crossflow microfiltration, followed by dewatering

DOEpatents

Vijayan, Sivaraman; Wong, Chi F.; Buckley, Leo P.

1994-01-01

In processes of this invention aqueous waste solutions containing a variety of mixed waste contaminants are treated to remove the contaminants by a sequential addition of chemicals and adsorption/ion exchange powdered materials to remove the contaminants including lead, cadmium, uranium, cesium-137, strontium-85/90, trichloroethylene and benzene, and impurities including iron and calcium. Staged conditioning of the waste solution produces a polydisperse system of size enlarged complexes of the contaminants in three distinct configurations: water-soluble metal complexes, insoluble metal precipitation complexes, and contaminant-bearing particles of ion exchange and adsorbent materials. The volume of the waste is reduced by separation of the polydisperse system by cross-flow microfiltration, followed by low-temperature evaporation and/or filter pressing. The water produced as filtrate is discharged if it meets a specified target water quality, or else the filtrate is recycled until the target is achieved.

Theater-Level Gaming and Analysis Workshop for Force Planning. Volume II. Summary, Discussion of Issues and Requirements for Research. September 27- 29, 1977, Held at Xerox International Center for Training and Management Development, Leesburg, Virginia

DTIC Science & Technology

1981-05-01

be allocated to targets on the battlefield and in the rear area. The speaker describes the VECTOR I/NUCLEAR model, a combination of the UNICORN target...outlined. UNICORN is compatible with VECTOR 1 in level of detail. It is an expected value damage model and uses linear programming to optimize the...and a growing appreciation for the power of simulation in addressing large, complex problems, it was only a few short years before these games had

Radiotherapy Dose-Volume Effects on Salivary Gland Function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deasy, Joseph O., E-mail: jdeasy@radonc.wustl.ed; Moiseenko, Vitali; Marks, Lawrence

2010-03-01

Publications relating parotid dose-volume characteristics to radiotherapy-induced salivary toxicity were reviewed. Late salivary dysfunction has been correlated to the mean parotid gland dose, with recovery occurring with time. Severe xerostomia (defined as long-term salivary function of <25% of baseline) is usually avoided if at least one parotid gland is spared to a mean dose of less than {approx}20 Gy or if both glands are spared to less than {approx}25 Gy (mean dose). For complex, partial-volume RT patterns (e.g., intensity-modulated radiotherapy), each parotid mean dose should be kept as low as possible, consistent with the desired clinical target volume coverage. Amore » lower parotid mean dose usually results in better function. Submandibular gland sparing also significantly decreases the risk of xerostomia. The currently available predictive models are imprecise, and additional study is required to identify more accurate models of xerostomia risk.« less

Treatment planning with intensity modulated particle therapy for multiple targets in stage IV non-small cell lung cancer

NASA Astrophysics Data System (ADS)

Anderle, Kristjan; Stroom, Joep; Vieira, Sandra; Pimentel, Nuno; Greco, Carlo; Durante, Marco; Graeff, Christian

2018-01-01

Intensity modulated particle therapy (IMPT) can produce highly conformal plans, but is limited in advanced lung cancer patients with multiple lesions due to motion and planning complexity. A 4D IMPT optimization including all motion states was expanded to include multiple targets, where each target (isocenter) is designated to specific field(s). Furthermore, to achieve stereotactic treatment planning objectives, target and OAR weights plus objective doses were automatically iteratively adapted. Finally, 4D doses were calculated for different motion scenarios. The results from our algorithm were compared to clinical stereotactic body radiation treatment (SBRT) plans. The study included eight patients with 24 lesions in total. Intended dose regimen for SBRT was 24 Gy in one fraction, but lower fractionated doses had to be delivered in three cases due to OAR constraints or failed plan quality assurance. The resulting IMPT treatment plans had no significant difference in target coverage compared to SBRT treatment plans. Average maximum point dose and dose to specific volume in OARs were on average 65% and 22% smaller with IMPT. IMPT could also deliver 24 Gy in one fraction in a patient where SBRT was limited due to the OAR vicinity. The developed algorithm shows the potential of IMPT in treatment of multiple moving targets in a complex geometry.

Gadolinium sulfate modified by formate to obtain optimized magneto-caloric effect.

PubMed

Xu, Long-Yang; Zhao, Jiong-Peng; Liu, Ting; Liu, Fu-Chen

2015-06-01

Three new Gd(III) based coordination polymers [Gd2(C2H6SO)(SO4)3(H2O)2]n (1), {[Gd4(HCOO)2(SO4)5(H2O)6]·H2O}n (2), and [Gd(HCOO)(SO4)(H2O)]n (3) were obtained by modifying gadolinium sulfate. With the gradual increase of the volume ratio of HCOOH and DMSO in synthesis, the formate anions begin to coordinate with metal centers; this results in the coordination numbers of sulfate anion increasing and the contents of water and DMSO molecules decreasing in target complexes. Accordingly, spin densities both per mass and per volume were enhanced step by step, which are beneficial for the magneto-caloric effect (MCE). Magnetic studies reveal that with the more formate anions present, the larger the negative value of magnetic entropy change (-ΔSm) is. Complex 3 exhibits the largest -ΔSm = 49.91 J kg(-1) K(-1) (189.51 mJ cm(-3) K(-1)) for T = 2 K and ΔH = 7 T among three new complexes.

Closed-Loop Multitarget Optimization for Discovery of New Emulsion Polymerization Recipes

PubMed Central

2015-01-01

Self-optimization of chemical reactions enables faster optimization of reaction conditions or discovery of molecules with required target properties. The technology of self-optimization has been expanded to discovery of new process recipes for manufacture of complex functional products. A new machine-learning algorithm, specifically designed for multiobjective target optimization with an explicit aim to minimize the number of “expensive” experiments, guides the discovery process. This “black-box” approach assumes no a priori knowledge of chemical system and hence particularly suited to rapid development of processes to manufacture specialist low-volume, high-value products. The approach was demonstrated in discovery of process recipes for a semibatch emulsion copolymerization, targeting a specific particle size and full conversion. PMID:26435638

Improving the consistency in cervical esophageal target volume definition by special training.

PubMed

Tai, Patricia; Van Dyk, Jake; Battista, Jerry; Yu, Edward; Stitt, Larry; Tonita, Jon; Agboola, Olusegun; Brierley, James; Dar, Rashid; Leighton, Christopher; Malone, Shawn; Strang, Barbara; Truong, Pauline; Videtic, Gregory; Wong, C Shun; Wong, Rebecca; Youssef, Youssef

2002-07-01

Three-dimensional conformal radiation therapy requires the precise definition of the target volume. Its potential benefits could be offset by the inconsistency in target definition by radiation oncologists. In a previous survey of radiation oncologists, a large degree of variation in target volume definition of cervical esophageal cancer was noted for the boost phase of radiotherapy. The present study evaluated whether special training could improve the consistency in target volume definitions. A pre-training survey was performed to establish baseline values. This was followed by a special one-on-one training session on treatment planning based on the RTOG 94-05 protocol to 12 radiation oncologists. Target volumes were redrawn immediately and at 1-2 months later. Post-training vs. pre-training target volumes were compared. There was less variability in the longitudinal positions of the target volumes post-training compared to pre-training (p < 0.05 in 5 of 6 comparisons). One case had more variability due to the lack of a visible gross tumor on CT scans. Transverse contours of target volumes did not show any significant difference pre- or post-training. For cervical esophageal cancer, this study suggests that special training on protocol guidelines may improve consistency in target volume definition. Explicit protocol directions are required for situations where the gross tumor is not easily visible on CT scans. This may be particularly important for multicenter clinical trials, to reduce the occurrences of protocol violations.

Medical image segmentation based on SLIC superpixels model

NASA Astrophysics Data System (ADS)

Chen, Xiang-ting; Zhang, Fan; Zhang, Ruo-ya

2017-01-01

Medical imaging has been widely used in clinical practice. It is an important basis for medical experts to diagnose the disease. However, medical images have many unstable factors such as complex imaging mechanism, the target displacement will cause constructed defect and the partial volume effect will lead to error and equipment wear, which increases the complexity of subsequent image processing greatly. The segmentation algorithm which based on SLIC (Simple Linear Iterative Clustering, SLIC) superpixels is used to eliminate the influence of constructed defect and noise by means of the feature similarity in the preprocessing stage. At the same time, excellent clustering effect can reduce the complexity of the algorithm extremely, which provides an effective basis for the rapid diagnosis of experts.

Facial Contouring by Targeted Restoration of Facial Fat Compartment Volume: The Midface.

PubMed

Wang, Wenjin; Xie, Yun; Huang, Ru-Lin; Zhou, Jia; Tanja, Herrler; Zhao, Peijuan; Cheng, Chen; Zhou, Sizheng; Pu, Lee L Q; Li, Qingfeng

2017-03-01

Recent anatomical findings have suggested that facial fat distribution is complex and changes with age. Here, the authors developed a grafting technique based on the physiologic distribution and volume changes of facial fat compartments to achieve a youthful and natural-appearing face. Forty cadaveric hemifaces were used for the dissection of fat compartments and neurovascular structures in the midface area. Seventy-eight patients were treated for cheek atrophy using the authors' targeted restoration of midface fat compartment volume. The outcome was evaluated by a two-dimensional assessment, malar lipoatrophy assessment, and a satisfaction survey. The medial and lateral parts of the deep medial cheek fat compartment were separated by a septum arising from the lateral border of the levator anguli oris muscle. The angular vein traveled between the deep medial cheek fat compartment and the buccal fat pad, 12 mm from the maxilla. A total volume of 29.3 ml of fat was grafted per cheek for each patient. A 12-month follow-up revealed an average volume augmentation rate of 27.1 percent. Pleasing and elevated anterior projection of the cheek and ameliorated nasolabial groove were still obvious by 12 months after the procedure. In total, 95.2 percent of the patients were satisfied with their results. The present study provides the anatomical and clinical basis for the concept of compartmentally based fat grafting. It allows for the restoration of facial fat volume close to the physiologic state. With this procedure, a natural and youthful facial contour could be rebuilt with a high satisfaction rate. Therapeutic, IV.

OPS MCC level B/C formulation requirements: Area targets and space volumes processor

NASA Technical Reports Server (NTRS)

Bishop, M. J., Jr.

1979-01-01

The level B/C mathematical specifications for the area targets and space volumes processor (ATSVP) are described. The processor is designed to compute the acquisition-of-signal (AOS) and loss-of-signal (LOS) times for area targets and space volumes. The characteristics of the area targets and space volumes are given. The mathematical equations necessary to determine whether the spacecraft lies within the area target or space volume are given. These equations provide a detailed model of the target geometry. A semianalytical technique for predicting the AOS and LOS time periods is disucssed. This technique was designed to bound the actual visibility period using a simplified target geometry model and unperturbed orbital motion. Functional overview of the ATSVP is presented and it's detailed logic flow is described.

A proposed framework for consensus-based lung tumour volume auto-segmentation in 4D computed tomography imaging

NASA Astrophysics Data System (ADS)

Martin, Spencer; Brophy, Mark; Palma, David; Louie, Alexander V.; Yu, Edward; Yaremko, Brian; Ahmad, Belal; Barron, John L.; Beauchemin, Steven S.; Rodrigues, George; Gaede, Stewart

2015-02-01

This work aims to propose and validate a framework for tumour volume auto-segmentation based on ground-truth estimates derived from multi-physician input contours to expedite 4D-CT based lung tumour volume delineation. 4D-CT datasets of ten non-small cell lung cancer (NSCLC) patients were manually segmented by 6 physicians. Multi-expert ground truth (GT) estimates were constructed using the STAPLE algorithm for the gross tumour volume (GTV) on all respiratory phases. Next, using a deformable model-based method, multi-expert GT on each individual phase of the 4D-CT dataset was propagated to all other phases providing auto-segmented GTVs and motion encompassing internal gross target volumes (IGTVs) based on GT estimates (STAPLE) from each respiratory phase of the 4D-CT dataset. Accuracy assessment of auto-segmentation employed graph cuts for 3D-shape reconstruction and point-set registration-based analysis yielding volumetric and distance-based measures. STAPLE-based auto-segmented GTV accuracy ranged from (81.51  ±  1.92) to (97.27  ±  0.28)% volumetric overlap of the estimated ground truth. IGTV auto-segmentation showed significantly improved accuracies with reduced variance for all patients ranging from 90.87 to 98.57% volumetric overlap of the ground truth volume. Additional metrics supported these observations with statistical significance. Accuracy of auto-segmentation was shown to be largely independent of selection of the initial propagation phase. IGTV construction based on auto-segmented GTVs within the 4D-CT dataset provided accurate and reliable target volumes compared to manual segmentation-based GT estimates. While inter-/intra-observer effects were largely mitigated, the proposed segmentation workflow is more complex than that of current clinical practice and requires further development.

A proposed framework for consensus-based lung tumour volume auto-segmentation in 4D computed tomography imaging.

PubMed

Martin, Spencer; Brophy, Mark; Palma, David; Louie, Alexander V; Yu, Edward; Yaremko, Brian; Ahmad, Belal; Barron, John L; Beauchemin, Steven S; Rodrigues, George; Gaede, Stewart

2015-02-21

This work aims to propose and validate a framework for tumour volume auto-segmentation based on ground-truth estimates derived from multi-physician input contours to expedite 4D-CT based lung tumour volume delineation. 4D-CT datasets of ten non-small cell lung cancer (NSCLC) patients were manually segmented by 6 physicians. Multi-expert ground truth (GT) estimates were constructed using the STAPLE algorithm for the gross tumour volume (GTV) on all respiratory phases. Next, using a deformable model-based method, multi-expert GT on each individual phase of the 4D-CT dataset was propagated to all other phases providing auto-segmented GTVs and motion encompassing internal gross target volumes (IGTVs) based on GT estimates (STAPLE) from each respiratory phase of the 4D-CT dataset. Accuracy assessment of auto-segmentation employed graph cuts for 3D-shape reconstruction and point-set registration-based analysis yielding volumetric and distance-based measures. STAPLE-based auto-segmented GTV accuracy ranged from (81.51  ±  1.92) to (97.27  ±  0.28)% volumetric overlap of the estimated ground truth. IGTV auto-segmentation showed significantly improved accuracies with reduced variance for all patients ranging from 90.87 to 98.57% volumetric overlap of the ground truth volume. Additional metrics supported these observations with statistical significance. Accuracy of auto-segmentation was shown to be largely independent of selection of the initial propagation phase. IGTV construction based on auto-segmented GTVs within the 4D-CT dataset provided accurate and reliable target volumes compared to manual segmentation-based GT estimates. While inter-/intra-observer effects were largely mitigated, the proposed segmentation workflow is more complex than that of current clinical practice and requires further development.

A toolbox for discrete modelling of cell signalling dynamics.

PubMed

Paterson, Yasmin Z; Shorthouse, David; Pleijzier, Markus W; Piterman, Nir; Bendtsen, Claus; Hall, Benjamin A; Fisher, Jasmin

2018-06-18

In an age where the volume of data regarding biological systems exceeds our ability to analyse it, many researchers are looking towards systems biology and computational modelling to help unravel the complexities of gene and protein regulatory networks. In particular, the use of discrete modelling allows generation of signalling networks in the absence of full quantitative descriptions of systems, which are necessary for ordinary differential equation (ODE) models. In order to make such techniques more accessible to mainstream researchers, tools such as the BioModelAnalyzer (BMA) have been developed to provide a user-friendly graphical interface for discrete modelling of biological systems. Here we use the BMA to build a library of discrete target functions of known canonical molecular interactions, translated from ordinary differential equations (ODEs). We then show that these BMA target functions can be used to reconstruct complex networks, which can correctly predict many known genetic perturbations. This new library supports the accessibility ethos behind the creation of BMA, providing a toolbox for the construction of complex cell signalling models without the need for extensive experience in computer programming or mathematical modelling, and allows for construction and simulation of complex biological systems with only small amounts of quantitative data.

The Antiaircraft Journal. Volume 93, Number 2, March-April 1950

DTIC Science & Technology

1950-04-01

equipment. c. Aurora Borealis . d. Loran. 69. Only experienced men should attempt to repair radar . sets for, in addition to being a complex instrument...Defense Program. The Station Hospital at Fort Rosecrans, California, now provides facilities for San Diego reservists. Cells that were formerly used...RCH-APRIL, 1950 67. Pulse duration distortion causes targets to appear longer in range. 68. So far as is publicly known, the Aurora Borealis has no

The Dosimetric Consequences of Intensity Modulated Radiotherapy for Cervix Cancer: The Impact of Organ Motion, Deformation and Tumour Regression

NASA Astrophysics Data System (ADS)

Lim, Karen Siah Huey

Hypothesis: In intensity modulated radiotherapy (IMRT) for cervix cancer, the dose received by the tumour target and surrounding normal tissues is significantly different to that indicated by a single static plan. Rationale: The optimal use of IMRT in cervix cancer requires a greater attention to clinical target volume (CTV) definition and tumour & normal organ motion to assure maximum tumour control with the fewest side effects. Research Aims: 1) Generate consensus CTV contouring guidelines for cervix cancer; 2) Evaluate intra-pelvic tumour and organ dynamics during radiotherapy; 3) Analyze the dose consequences of intra-pelvic organ dynamics on different radiotherapy strategies. Results: Consensus CTV definitions were generated using experts-in-the-field. Substantial changes in tumour volume and organ motion, resulted in significant reductions in accumulated dose to tumour targets and variability in accumulated dose to surrounding normal tissues. Significance: Formalized CTV definitions for cervix cancer is important in ensuring consistent standards of practice. Complex and unpredictable tumour and organ dynamics mandates daily soft-tissue image guidance if IMRT is used. To maximize the benefits of IMRT for cervix cancer, a strategy of adaptation is necessary.

Planned Subtotal Resection of Vestibular Schwannoma Differs from the Ideal Radiosurgical Target Defined by Adaptive Hybrid Surgery.

PubMed

Sheppard, John P; Lagman, Carlito; Prashant, Giyarpuram N; Alkhalid, Yasmine; Nguyen, Thien; Duong, Courtney; Udawatta, Methma; Gaonkar, Bilwaj; Tenn, Stephen E; Bloch, Orin; Yang, Isaac

2018-06-01

To retrospectively compare ideal radiosurgical target volumes defined by a manual method (surgeon) to those determined by Adaptive Hybrid Surgery (AHS) operative planning software in 7 patients with vestibular schwannoma (VS). Four attending surgeons (3 neurosurgeons and 1 ear, nose, and throat surgeon) manually contoured planned residual tumors volumes for 7 consecutive patients with VS. Next, the AHS software determined the ideal radiosurgical target volumes based on a specified radiotherapy plan. Our primary measure was the difference between the average planned residual tumor volumes and the ideal radiosurgical target volumes defined by AHS (dRV AHS-planned ). We included 7 consecutive patients with VS in this study. The planned residual tumor volumes were smaller than the ideal radiosurgical target volumes defined by AHS (1.6 vs. 4.5 cm 3 , P = 0.004). On average, the actual post-operative residual tumor volumes were smaller than the ideal radiosurgical target volumes defined by AHS (2.2 cm 3 vs. 4.5 cm 3 ; P = 0.02). The average difference between the ideal radiosurgical target volume defined by AHS and the planned residual tumor volume (dRV AHS-planned ) was 2.9 ± 1.7 cm 3 , and we observed a trend toward larger dRV AHS-planned in patients who lost serviceable facial nerve function compared with patients who maintained serviceable facial nerve function (4.7 cm 3 vs. 1.9 cm 3 ; P = 0.06). Planned subtotal resection of VS diverges from the ideal radiosurgical target defined by AHS, but whether that influences clinical outcomes is unclear. Copyright © 2018 Elsevier Inc. All rights reserved.

Measurement of track structure parameters of low and medium energy helium and carbon ions in nanometric volumes

NASA Astrophysics Data System (ADS)

Hilgers, G.; Bug, M. U.; Rabus, H.

2017-10-01

Ionization cluster size distributions produced in the sensitive volume of an ion-counting wall-less nanodosimeter by monoenergetic carbon ions with energies between 45 MeV and 150 MeV were measured at the TANDEM-ALPI ion accelerator facility complex of the LNL-INFN in Legnaro. Those produced by monoenergetic helium ions with energies between 2 MeV and 20 MeV were measured at the accelerator facilities of PTB and with a 241Am alpha particle source. C3H8 was used as the target gas. The ionization cluster size distributions were measured in narrow beam geometry with the primary beam passing the target volume at specified distances from its centre, and in broad beam geometry with a fan-like primary beam. By applying a suitable drift time window, the effective size of the target volume was adjusted to match the size of a DNA segment. The measured data were compared with the results of simulations obtained with the PTB Monte Carlo code PTra. Before the comparison, the simulated cluster size distributions were corrected with respect to the background of additional ionizations produced in the transport system of the ionized target gas molecules. Measured and simulated characteristics of the particle track structure are in good agreement for both types of primary particles and for both types of the irradiation geometry. As the range in tissue of the ions investigated is within the typical extension of a spread-out Bragg peak, these data are useful for benchmarking not only ‘general purpose’ track structure simulation codes, but also treatment planning codes used in hadron therapy. Additionally, these data sets may serve as a data base for codes modelling the induction of radiation damages at the DNA-level as they almost completely characterize the ionization component of the nanometric track structure.

Frontal slab composite magnetic resonance neurography of the brachial plexus: implications for infraclavicular block approaches.

PubMed

Raphael, David T; McIntee, Diane; Tsuruda, Jay S; Colletti, Patrick; Tatevossian, Ray

2005-12-01

Magnetic resonance neurography (MRN) is an imaging method by which nerves can be selectively highlighted. Using commercial software, the authors explored a variety of approaches to develop a three-dimensional volume-rendered MRN image of the entire brachial plexus and used it to evaluate the accuracy of infraclavicular block approaches. With institutional review board approval, MRN of the brachial plexus was performed in 10 volunteer subjects. MRN imaging was performed on a GE 1.5-tesla magnetic resonance scanner (General Electric Healthcare Technologies, Waukesha, WI) using a phased array torso coil. Coronal STIR and T1 oblique sagittal sequences of the brachial plexus were obtained. Multiple software programs were explored for enhanced display and manipulation of the composite magnetic resonance images. The authors developed a frontal slab composite approach that allows single-frame reconstruction of a three-dimensional volume-rendered image of the entire brachial plexus. Automatic segmentation was supplemented by manual segmentation in nearly all cases. For each of three infraclavicular approaches (posteriorly directed needle below midclavicle, infracoracoid, or caudomedial to coracoid), the targeting error was measured as the distance from the MRN plexus midpoint to the approach-targeted site. Composite frontal slabs (coronal views), which are single-frame three-dimensional volume renderings from image-enhanced two-dimensional frontal view projections of the underlying coronal slices, were created. The targeting errors (mean +/- SD) for the approaches-midclavicle, infracoracoid, caudomedial to coracoid-were 0.43 +/- 0.67, 0.99 +/- 1.22, and 0.65 +/- 1.14 cm, respectively. Image-processed three-dimensional volume-rendered MNR scans, which allow visualization of the entire brachial plexus within a single composite image, have educational value in illustrating the complexity and individual variation of the plexus. Suggestions for improved guidance during infraclavicular block procedures are presented.

A high-throughput 2D-analytical technique to obtain single protein parameters from complex cell lysates for in silico process development of ion exchange chromatography.

PubMed

Kröner, Frieder; Elsäßer, Dennis; Hubbuch, Jürgen

2013-11-29

The accelerating growth of the market for biopharmaceutical proteins, the market entry of biosimilars and the growing interest in new, more complex molecules constantly pose new challenges for bioseparation process development. In the presented work we demonstrate the application of a multidimensional, analytical separation approach to obtain the relevant physicochemical parameters of single proteins in a complex mixture for in silico chromatographic process development. A complete cell lysate containing a low titre target protein was first fractionated by multiple linear salt gradient anion exchange chromatography (AEC) with varying gradient length. The collected fractions were subsequently analysed by high-throughput capillary gel electrophoresis (HT-CGE) after being desalted and concentrated. From the obtained data of the 2D-separation the retention-volumes and the concentration of the single proteins were determined. The retention-volumes of the single proteins were used to calculate the related steric-mass action model parameters. In a final evaluation experiment the received parameters were successfully applied to predict the retention behaviour of the single proteins in salt gradient AEC. Copyright © 2013 Elsevier B.V. All rights reserved.

A geometrically based method for automated radiosurgery planning.

PubMed

Wagner, T H; Yi, T; Meeks, S L; Bova, F J; Brechner, B L; Chen, Y; Buatti, J M; Friedman, W A; Foote, K D; Bouchet, L G

2000-12-01

A geometrically based method of multiple isocenter linear accelerator radiosurgery treatment planning optimization was developed, based on a target's solid shape. Our method uses an edge detection process to determine the optimal sphere packing arrangement with which to cover the planning target. The sphere packing arrangement is converted into a radiosurgery treatment plan by substituting the isocenter locations and collimator sizes for the spheres. This method is demonstrated on a set of 5 irregularly shaped phantom targets, as well as a set of 10 clinical example cases ranging from simple to very complex in planning difficulty. Using a prototype implementation of the method and standard dosimetric radiosurgery treatment planning tools, feasible treatment plans were developed for each target. The treatment plans generated for the phantom targets showed excellent dose conformity and acceptable dose homogeneity within the target volume. The algorithm was able to generate a radiosurgery plan conforming to the Radiation Therapy Oncology Group (RTOG) guidelines on radiosurgery for every clinical and phantom target examined. This automated planning method can serve as a valuable tool to assist treatment planners in rapidly and consistently designing conformal multiple isocenter radiosurgery treatment plans.

Random encoded reference beam for secure data storage in a holographic memory

NASA Astrophysics Data System (ADS)

Markov, Vladimir B.; Weber, David C.

2000-11-01

A method is presented to store biometric and/or other important information on an ID card in the form of a Card Hologram that cannot be read or duplicated without the use of a special Key Hologram that is secured inside of an automated reader. The Key Hologram produces the unique wavefront required to release the information contained in a complex, 3- D diffraction pattern recorded in a volume hologram attached to the card. Experimental results are presented in which the image of an Air Force resolution target are recorded and reconstructed in a volume material using a random speckle wavefront and that cannot be viewed using a simple wavefront such as a collimated or diverging laser beam.

Geometric parameter analysis to predetermine optimal radiosurgery technique for the treatment of arteriovenous malformation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mestrovic, Ante; Clark, Brenda G.; Department of Medical Physics, British Columbia Cancer Agency, Vancouver, British Columbia

2005-11-01

Purpose: To develop a method of predicting the values of dose distribution parameters of different radiosurgery techniques for treatment of arteriovenous malformation (AVM) based on internal geometric parameters. Methods and Materials: For each of 18 previously treated AVM patients, four treatment plans were created: circular collimator arcs, dynamic conformal arcs, fixed conformal fields, and intensity-modulated radiosurgery. An algorithm was developed to characterize the target and critical structure shape complexity and the position of the critical structures with respect to the target. Multiple regression was employed to establish the correlation between the internal geometric parameters and the dose distribution for differentmore » treatment techniques. The results from the model were applied to predict the dosimetric outcomes of different radiosurgery techniques and select the optimal radiosurgery technique for a number of AVM patients. Results: Several internal geometric parameters showing statistically significant correlation (p < 0.05) with the treatment planning results for each technique were identified. The target volume and the average minimum distance between the target and the critical structures were the most effective predictors for normal tissue dose distribution. The structure overlap volume with the target and the mean distance between the target and the critical structure were the most effective predictors for critical structure dose distribution. The predicted values of dose distribution parameters of different radiosurgery techniques were in close agreement with the original data. Conclusions: A statistical model has been described that successfully predicts the values of dose distribution parameters of different radiosurgery techniques and may be used to predetermine the optimal technique on a patient-to-patient basis.« less

Microfluidic Extraction of Biomarkers using Water as Solvent

NASA Technical Reports Server (NTRS)

Amashukeli, Xenia; Manohara, Harish; Chattopadhyay, Goutam; Mehdi, Imran

2009-01-01

A proposed device, denoted a miniature microfluidic biomarker extractor (mu-EX), would extract trace amounts of chemicals of interest from samples, such as soils and rocks. Traditionally, such extractions are performed on a large scale with hazardous organic solvents; each solvent capable of dissolving only those molecules lying within narrow ranges of specific chemical and physical characteristics that notably include volatility, electric charge, and polarity. In contrast, in the mu-EX, extractions could be performed by use of small amounts (typically between 0.1 and 100 L) of water as a universal solvent. As a rule of thumb, in order to enable solvation and extraction of molecules, it is necessary to use solvents that have polarity sufficiently close to the polarity of the target molecules. The mu-EX would make selection of specific organic solvents unnecessary, because mu-EX would exploit a unique property of liquid water: the possibility of tuning its polarity to match the polarity of organic solvents appropriate for extraction of molecules of interest. The change of the permittivity of water would be achieved by exploiting interactions between the translational states of water molecules and an imposed electromagnetic field in the frequency range of 300 to 600 GHz. On a molecular level, these interactions would result in disruption of the three-dimensional hydrogen-bonding network among liquid-water molecules and subsequent solvation and hydrolysis of target molecules. The mu-EX is expected to be an efficient means of hydrolyzing chemical bonds in complex macromolecules as well and, thus, enabling analysis of the building blocks of these complex chemical systems. The mu-EX device would include a microfluidic channel, part of which would lie within a waveguide coupled to an electronically tuned source of broad-band electromagnetic radiation in the frequency range from 300 to 600 GHz (see figure). The part of the microfluidic channel lying in the waveguide would constitute an interaction volume. The dimensions of the interaction volume would be chosen in accordance with the anticipated amount of solid sample material needed to ensure extraction of sufficient amount of target molecules for detection and analysis. By means that were not specified at the time of reporting the information for this article, the solid sample material would be placed in the interaction volume. Then the electromagnetic field would be imposed within the waveguide and water would be pumped through the interaction volume to effect the extraction.

Implications of improved diagnostic imaging of small nodal metastases in head and neck cancer: Radiotherapy target volume transformation and dose de-escalation.

PubMed

van den Bosch, Sven; Vogel, Wouter V; Raaijmakers, Cornelis P; Dijkema, Tim; Terhaard, Chris H J; Al-Mamgani, Abrahim; Kaanders, Johannes H A M

2018-05-03

Diagnostic imaging continues to evolve, and now has unprecedented accuracy for detecting small nodal metastasis. This influences the tumor load in elective target volumes and subsequently has consequences for the radiotherapy dose required to control disease in these volumes. Small metastases that used to remain subclinical and were included in elective volumes, will nowadays be detected and included in high-dose volumes. Consequentially, high-dose volumes will more often contain low-volume disease. These target volume transformations lead to changes in the tumor burden in elective and "gross" tumor volumes with implications for the radiotherapy dose prescribed to these volumes. For head and neck tumors, nodal staging has evolved from mere palpation to combinations of high-resolution imaging modalities. A traditional nodal gross tumor volume in the neck typically had a minimum diameter of 10-15 mm, while nowadays much smaller tumor deposits are detected in lymph nodes. However, the current dose levels for elective nodal irradiation were empirically determined in the 1950s, and have not changed since. In this report the radiobiological consequences of target volume transformation caused by modern imaging of the neck are evaluated, and theoretically derived reductions of dose in radiotherapy for head and neck cancer are proposed. The concept of target volume transformation and subsequent strategies for dose adaptation applies to many other tumor types as well. Awareness of this concept may result in new strategies for target definition and selection of dose levels with the aim to provide optimal tumor control with less toxicity. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

SMV⊥: Simplex of maximal volume based upon the Gram-Schmidt process

NASA Astrophysics Data System (ADS)

Salazar-Vazquez, Jairo; Mendez-Vazquez, Andres

2015-10-01

In recent years, different algorithms for Hyperspectral Image (HI) analysis have been introduced. The high spectral resolution of these images allows to develop different algorithms for target detection, material mapping, and material identification for applications in Agriculture, Security and Defense, Industry, etc. Therefore, from the computer science's point of view, there is fertile field of research for improving and developing algorithms in HI analysis. In some applications, the spectral pixels of a HI can be classified using laboratory spectral signatures. Nevertheless, for many others, there is no enough available prior information or spectral signatures, making any analysis a difficult task. One of the most popular algorithms for the HI analysis is the N-FINDR because it is easy to understand and provides a way to unmix the original HI in the respective material compositions. The N-FINDR is computationally expensive and its performance depends on a random initialization process. This paper proposes a novel idea to reduce the complexity of the N-FINDR by implementing a bottom-up approach based in an observation from linear algebra and the use of the Gram-Schmidt process. Therefore, the Simplex of Maximal Volume Perpendicular (SMV⊥) algorithm is proposed for fast endmember extraction in hyperspectral imagery. This novel algorithm has complexity O(n) with respect to the number of pixels. In addition, the evidence shows that SMV⊥ calculates a bigger volume, and has lower computational time complexity than other poular algorithms on synthetic and real scenarios.

Endoscopic Drainage of >50% of Liver in Malignant Hilar Biliary Obstruction Using Metallic or Fenestrated Plastic Stents

PubMed Central

Kerdsirichairat, Tossapol; Arain, Mustafa A; Attam, Rajeev; Glessing, Brooke; Bakman, Yan; Amateau, Stuart K; Freeman, Martin L

2017-01-01

Objectives: Endoscopic drainage of complex hilar tumors has generally resulted in poor outcomes. Drainage of >50% of liver volume has been proposed as optimal, but not evaluated using long multifenestrated plastic stents (MFPS) or self-expanding metal stents (SEMS). We evaluated outcomes of endoscopic drainage of malignant hilar strictures using optimal strategy and stents, and determined factors associated with stent patency, survival, and complications. Methods: Cross-sectional study was conducted at an academic center over 5 years. MFPS (10 French or 8.5 French) or open-cell SEMS were used for palliation of unresectable malignant hilar strictures, with imaging-targeted drainage of as many sectors as needed to drain >50% of viable liver volume. Risk factors were evaluated using regression analysis. The cumulative risk was assessed using Kaplan–Meier analysis. Results: 77 patients with malignant hilar biliary strictures (median Bismuth IV) underwent targeted stenting (41 MFPS and 36 SEMS). Comparing MFPS vs. SEMS, technical success (95.1 vs. 97.2%, P=0.64), clinical success (75.6 vs. 83.3%, P=0.40), frequency of multiple stents (23/41 vs. 25/36, P=0.19), survival and adverse events were similar, but stent patency was significantly shorter (P<0.0001). Factors associated with survival were Karnofsky score and serum bilirubin level at presentation. Outcomes were independent of Bismuth class with acceptable results in Bismuth III and IV. Conclusions: Endoscopic biliary drainage with MFPS or open-cell SEMS targeting >50% of viable liver resulted in effective palliation in patients with complex malignant hilar biliary strictures. Patency was shorter in the MFPS group, but similar survival and complications were found when comparing MFPS and SEMS group. PMID:28858292

Endoscopic Drainage of >50% of Liver in Malignant Hilar Biliary Obstruction Using Metallic or Fenestrated Plastic Stents.

PubMed

Kerdsirichairat, Tossapol; Arain, Mustafa A; Attam, Rajeev; Glessing, Brooke; Bakman, Yan; Amateau, Stuart K; Freeman, Martin L

2017-08-31

Endoscopic drainage of complex hilar tumors has generally resulted in poor outcomes. Drainage of >50% of liver volume has been proposed as optimal, but not evaluated using long multifenestrated plastic stents (MFPS) or self-expanding metal stents (SEMS). We evaluated outcomes of endoscopic drainage of malignant hilar strictures using optimal strategy and stents, and determined factors associated with stent patency, survival, and complications. Cross-sectional study was conducted at an academic center over 5 years. MFPS (10 French or 8.5 French) or open-cell SEMS were used for palliation of unresectable malignant hilar strictures, with imaging-targeted drainage of as many sectors as needed to drain >50% of viable liver volume. Risk factors were evaluated using regression analysis. The cumulative risk was assessed using Kaplan-Meier analysis. 77 patients with malignant hilar biliary strictures (median Bismuth IV) underwent targeted stenting (41 MFPS and 36 SEMS). Comparing MFPS vs. SEMS, technical success (95.1 vs. 97.2%, P=0.64), clinical success (75.6 vs. 83.3%, P=0.40), frequency of multiple stents (23/41 vs. 25/36, P=0.19), survival and adverse events were similar, but stent patency was significantly shorter (P<0.0001). Factors associated with survival were Karnofsky score and serum bilirubin level at presentation. Outcomes were independent of Bismuth class with acceptable results in Bismuth III and IV. Endoscopic biliary drainage with MFPS or open-cell SEMS targeting >50% of viable liver resulted in effective palliation in patients with complex malignant hilar biliary strictures. Patency was shorter in the MFPS group, but similar survival and complications were found when comparing MFPS and SEMS group.

Materials Informatics: The Materials ``Gene'' and Big Data

NASA Astrophysics Data System (ADS)

Rajan, Krishna

2015-07-01

Materials informatics provides the foundations for a new paradigm of materials discovery. It shifts our emphasis from one of solely searching among large volumes of data that may be generated by experiment or computation to one of targeted materials discovery via high-throughput identification of the key factors (i.e., “genes”) and via showing how these factors can be quantitatively integrated by statistical learning methods into design rules (i.e., “gene sequencing”) governing targeted materials functionality. However, a critical challenge in discovering these materials genes is the difficulty in unraveling the complexity of the data associated with numerous factors including noise, uncertainty, and the complex diversity of data that one needs to consider (i.e., Big Data). In this article, we explore one aspect of materials informatics, namely how one can efficiently explore for new knowledge in regimes of structure-property space, especially when no reasonable selection pathways based on theory or clear trends in observations exist among an almost infinite set of possibilities.

Water-filled balloon in the postoperative resection cavity improves dose distribution to target volumes in radiotherapy of maxillary sinus carcinoma.

PubMed

Zhang, Qun; Lin, Shi-Rong; He, Fang; Kang, De-Hua; Chen, Guo-Zhang; Luo, Wei

2011-11-01

Postoperative radiotherapy is a major treatment for patients with maxillary sinus carcinoma. However, the irregular resection cavity poses a technical difficulty for this treatment, causing uneven dose distribution to target volumes. In this study, we evaluated the dose distribution to target volumes and normal tissues in postoperative intensity-modulated radiotherapy (IMRT) after placing a water-filled balloon into the resection cavity. Three postoperative patients with advanced maxillary sinus carcinoma were selected in this trial. Water-filled balloons and supporting dental stents were fabricated according to the size of the maxillary resection cavity. Simulation CT scans were performed with or without water-filled balloons, IMRT treatment plans were established, and dose distribution to target volumes and organs at risk were evaluated. Compared to those in the treatment plan without balloons, the dose (D98) delivered to 98% of the gross tumor volume (GTV) increased by 2.1 Gy (P = 0.009), homogeneity index (HI) improved by 2.3% (P = 0.001), and target volume conformity index (TCI) of 68 Gy increased by 18.5% (P = 0.011) in the plan with balloons. Dosimetry endpoints of normal tissues around target regions in both plans were not significantly different (P > 0.05) except for the optic chiasm. In the plan without balloons, 68 Gy high-dose regions did not entirely cover target volumes in the ethmoid sinus, posteromedial wall of the maxillary sinus, or surgical margin of the hard palate. In contrast, 68 Gy high-dose regions entirely covered the GTV in the plan with balloons. These results suggest that placing a water-filled balloon in the resection cavity for postoperative IMRT of maxillary sinus carcinoma can reduce low-dose regions and markedly and simultaneously increase dose homogeneity and conformity of target volumes.

PET/CT-guided treatment planning for paediatric cancer patients: a simulation study of proton and conventional photon therapy

PubMed Central

Brodin, N P; Björk-Eriksson, T; Birk Christensen, C; Kiil-Berthelsen, A; Aznar, M C; Hollensen, C; Markova, E; Munck af Rosenschöld, P

2015-01-01

Objective: To investigate the impact of including fluorine-18 fludeoxyglucose (18F-FDG) positron emission tomography (PET) scanning in the planning of paediatric radiotherapy (RT). Methods: Target volumes were first delineated without and subsequently re-delineated with access to 18F-FDG PET scan information, on duplicate CT sets. RT plans were generated for three-dimensional conformal photon RT (3DCRT) and intensity-modulated proton therapy (IMPT). The results were evaluated by comparison of target volumes, target dose coverage parameters, normal tissue complication probability (NTCP) and estimated risk of secondary cancer (SC). Results: Considerable deviations between CT- and PET/CT-guided target volumes were seen in 3 out of the 11 patients studied. However, averaging over the whole cohort, CT or PET/CT guidance introduced no significant difference in the shape or size of the target volumes, target dose coverage, irradiated volumes, estimated NTCP or SC risk, neither for IMPT nor 3DCRT. Conclusion: Our results imply that the inclusion of PET/CT scans in the RT planning process could have considerable impact for individual patients. There were no general trends of increasing or decreasing irradiated volumes, suggesting that the long-term morbidity of RT in childhood would on average remain largely unaffected. Advances in knowledge: 18F-FDG PET-based RT planning does not systematically change NTCP or SC risk for paediatric cancer patients compared with CT only. 3 out of 11 patients had a distinct change of target volumes when PET-guided planning was introduced. Dice and mismatch metrics are not sufficient to assess the consequences of target volume differences in the context of RT. PMID:25494657

Projected Improvements in Accelerated Partial Breast Irradiation Using a Novel Breast Stereotactic Radiotherapy Device: A Dosimetric Analysis.

PubMed

Snider, James W; Mutaf, Yildirim; Nichols, Elizabeth; Hall, Andrea; Vadnais, Patrick; Regine, William F; Feigenberg, Steven J

2017-01-01

Accelerated partial breast irradiation has caused higher than expected rates of poor cosmesis. At our institution, a novel breast stereotactic radiotherapy device has demonstrated dosimetric distributions similar to those in brachytherapy. This study analyzed comparative dose distributions achieved with the device and intensity-modulated radiation therapy accelerated partial breast irradiation. Nine patients underwent computed tomography simulation in the prone position using device-specific immobilization on an institutional review board-approved protocol. Accelerated partial breast irradiation target volumes (planning target volume_10mm) were created per the National Surgical Adjuvant Breast and Bowel Project B-39 protocol. Additional breast stereotactic radiotherapy volumes using smaller margins (planning target volume_3mm) were created based on improved immobilization. Intensity-modulated radiation therapy and breast stereotactic radiotherapy accelerated partial breast irradiation plans were separately generated for appropriate volumes. Plans were evaluated based on established dosimetric surrogates of poor cosmetic outcomes. Wilcoxon rank sum tests were utilized to contrast volumes of critical structures receiving a percentage of total dose ( Vx). The breast stereotactic radiotherapy device consistently reduced dose to all normal structures with equivalent target coverage. The ipsilateral breast V20-100 was significantly reduced ( P < .05) using planning target volume_10mm, with substantial further reductions when targeting planning target volume_3mm. Doses to the chest wall, ipsilateral lung, and breast skin were also significantly lessened. The breast stereotactic radiotherapy device's uniform dosimetric improvements over intensity-modulated accelerated partial breast irradiation in this series indicate a potential to improve outcomes. Clinical trials investigating this benefit have begun accrual.

Meshless Modeling of Deformable Shapes and their Motion

PubMed Central

Adams, Bart; Ovsjanikov, Maks; Wand, Michael; Seidel, Hans-Peter; Guibas, Leonidas J.

2010-01-01

We present a new framework for interactive shape deformation modeling and key frame interpolation based on a meshless finite element formulation. Starting from a coarse nodal sampling of an object’s volume, we formulate rigidity and volume preservation constraints that are enforced to yield realistic shape deformations at interactive frame rates. Additionally, by specifying key frame poses of the deforming shape and optimizing the nodal displacements while targeting smooth interpolated motion, our algorithm extends to a motion planning framework for deformable objects. This allows reconstructing smooth and plausible deformable shape trajectories in the presence of possibly moving obstacles. The presented results illustrate that our framework can handle complex shapes at interactive rates and hence is a valuable tool for animators to realistically and efficiently model and interpolate deforming 3D shapes. PMID:24839614

International Spine Radiosurgery Consortium Consensus Guidelines for Target Volume Definition in Spinal Stereotactic Radiosurgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cox, Brett W., E-mail: coxb@mskcc.org; Spratt, Daniel E.; Lovelock, Michael

2012-08-01

Purpose: Spinal stereotactic radiosurgery (SRS) is increasingly used to manage spinal metastases. However, target volume definition varies considerably and no consensus target volume guidelines exist. This study proposes consensus target volume definitions using common scenarios in metastatic spine radiosurgery. Methods and Materials: Seven radiation oncologists and 3 neurological surgeons with spinal radiosurgery expertise independently contoured target and critical normal structures for 10 cases representing common scenarios in metastatic spine radiosurgery. Each set of volumes was imported into the Computational Environment for Radiotherapy Research. Quantitative analysis was performed using an expectation maximization algorithm for Simultaneous Truth and Performance Level Estimation (STAPLE)more » with kappa statistics calculating agreement between physicians. Optimized confidence level consensus contours were identified using histogram agreement analysis and characterized to create target volume definition guidelines. Results: Mean STAPLE agreement sensitivity and specificity was 0.76 (range, 0.67-0.84) and 0.97 (range, 0.94-0.99), respectively, for gross tumor volume (GTV) and 0.79 (range, 0.66-0.91) and 0.96 (range, 0.92-0.98), respectively, for clinical target volume (CTV). Mean kappa agreement was 0.65 (range, 0.54-0.79) for GTV and 0.64 (range, 0.54-0.82) for CTV (P<.01 for GTV and CTV in all cases). STAPLE histogram agreement analysis identified optimal consensus contours (80% confidence limit). Consensus recommendations include that the CTV should include abnormal marrow signal suspicious for microscopic invasion and an adjacent normal bony expansion to account for subclinical tumor spread in the marrow space. No epidural CTV expansion is recommended without epidural disease, and circumferential CTVs encircling the cord should be used only when the vertebral body, bilateral pedicles/lamina, and spinous process are all involved or there is extensive metastatic disease along the circumference of the epidural space. Conclusions: This report provides consensus guidelines for target volume definition for spinal metastases receiving upfront SRS in common clinical situations.« less

Effects of High Intensity Training and High Volume Training on Endothelial Microparticles and Angiogenic Growth Factors

PubMed Central

Achtzehn, Silvia; Schmitz, Theresa; Bloch, Wilhelm; Mester, Joachim; Werner, Nikos

2014-01-01

Aims Endothelial microparticles (EMP) are complex vesicular structures shed from activated or apoptotic endothelial cells. As endurance exercise affects the endothelium, the objective of the study was to examine levels of EMP and angiogenic growth factors following different endurance exercise protocols. Methods 12 subjects performed 3 different endurance exercise protocols: 1. High volume training (HVT; 130 min at 55% peak power output (PPO); 2. 4×4 min at 95% PPO; 3. 4×30 sec all-out. EMPs were quantified using flow cytometry after staining platelet-poor-plasma. Events positive for Annexin-V and CD31, and negative for CD42b, were classified as EMPs. Vascular endothelial growth factor (VEGF), migratory inhibiting factor (MIF) and hepatocyte growth factor (HGF) were determined by ELISA technique. For all these measurements venous blood samples were taken pre, 0′, 30′, 60′ and 180′ after each intervention. Furthermore, in vitro experiments were performed to explore the effect of collected sera on target endothelial functions and MP uptake capacities. Results VEGF and HGF significantly increased after HIT interventions. All three interventions caused a significant decrease in EMP levels post exercise compared to pre values. The sera taken after exercise increased the uptake of EMP in target endothelial cells compared to sera taken under resting conditions, which was shown to be phosphatidylserin-dependent. Increased EMP uptake was associated with an improved protection of target cells against apoptosis. Sera taken prior and after exercise promoted target endothelial cell migration, which was abrogated after inhibition of VEGF. Conclusion Physical exercise leads to decreased EMP levels and promotes a phosphatidylserin-dependent uptake of EMP into target endothelial cells, which is associated with a protection of target cells against apoptosis. PMID:24770423

Power law cross-correlations between price change and volume change of Indian stocks

NASA Astrophysics Data System (ADS)

Hasan, Rashid; Mohammed Salim, M.

2017-05-01

We study multifractal long-range correlations and cross-correlations of daily price change and volume change of 50 stocks that comprise Nifty index of National Stock Exchange, Mumbai, using MF-DFA and MF-DCCA methods. We find that the time series of price change are uncorrelated, whereas anti-persistent long-range multifractal correlations are found in volume change series. We also find antipersistent long-range multifractal cross-correlations between the time series of price change and volume change. As multifractality is a signature of complexity, we estimate complexity parameters of the time series of price change, volume change, and cross-correlated price-volume change by fitting the fourth-degree polynomials to their multifractal spectra. Our results indicate that the time series of price change display high complexity, whereas the time series of volume change and cross-correlated price-volume change display low complexity.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Yizhou, E-mail: yizhou.zhao@dal.ca; Moran, Kathryn; Yewondwossen, Mammo

Three-dimensional (3D) printing is suitable for the fabrication of complex radiotherapy bolus. Although investigated from dosimetric and feasibility standpoints, there are few reports to date of its use for actual patient treatment. This study illustrates the versatile applications of 3D printing in clinical radiation oncology through a selection of patient cases, namely, to create bolus for photon and modulated electron radiotherapy (MERT), as well as applicators for surface high-dose rate (HDR) brachytherapy. Photon boluses were 3D-printed to treat a recurrent squamous cell carcinoma (SCC) of the nasal septum and a basal cell carcinoma (BCC) of the posterior pinna. For amore » patient with a mycosis fungoides involving the upper face, a 3D-printed MERT bolus was used. To treat an SCC of the nose, a 3D-printed applicator for surface brachytherapy was made. The structures' fit to the anatomy and the radiotherapy treatment plans were assessed. Based on the treatment planning computed tomography (CT), the size of the largest air gap at the interface of the 3D-printed structure was 3 mm for the SCC of the nasal septum, 3 mm for the BCC of the pinna, 2 mm for the mycosis fungoides of the face, and 2 mm for the SCC of the nose. Acceptable treatment plans were obtained for the SCC of the nasal septum (95% isodose to 99.8% of planning target volume [PTV]), the BCC of the pinna (95% isodose to 97.7% of PTV), and the mycosis fungoides of the face (90% isodose to 92.5% of PTV). For the latter, compared with a plan with a uniform thickness bolus, the one featuring the MERT bolus achieved relative sparing of all the organs at risk (OARs) distal to the target volume, while maintaining similar target volume coverage. The surface brachytherapy plan for the SCC of the nose had adequate coverage (95% isodose to 95.6% of clinical target volume [CTV]), but a relatively high dose to the left eye, owing to its proximity to the tumor. 3D printing can be implemented effectively in the clinical setting to create highly conformal bolus for photon and MERT, as well as applicators for surface brachytherapy.« less

Ultimate detectability of volatile organic compounds: how much further can we reduce their ambient air sample volumes for analysis?

PubMed

Kim, Yong-Hyun; Kim, Ki-Hyun

2012-10-02

To understand the ultimately lowest detection range of volatile organic compounds (VOCs) in air, application of a high sensitivity analytical system was investigated by coupling thermal desorption (TD) technique with gas chromatography (GC) and time-of-flight (TOF) mass spectrometry (MS). The performance of the TD-GC/TOF MS system was evaluated using liquid standards of 19 target VOCs prepared in the range of 35 pg to 2.79 ng per μL. Studies were carried out using both total ion chromatogram (TIC) and extracted ion chromatogram (EIC) mode. EIC mode was used for calibration to reduce background and to improve signal-to-noise. The detectability of 19 target VOCs, if assessed in terms of method detection limit (MDL, per US EPA definition) and limit of detection (LOD), averaged 5.90 pg and 0.122 pg, respectively, with the mean coefficient of correlation (R(2)) of 0.9975. The minimum quantifiable mass of target analytes, when determined using real air samples by the TD-GC/TOF MS, is highly comparable to the detection limits determined experimentally by standard. In fact, volumes for the actual detection of the major aromatic VOCs like benzene, toluene, and xylene (BTX) in ambient air samples were as low as 1.0 mL in the 0.11-2.25 ppb range. It was thus possible to demonstrate that most target compounds including those in low abundance could be reliably quantified at concentrations down to 0.1 ppb at sample volumes of less than 10 mL. The unique sensitivity of this advanced analytical system can ultimately lead to a shift in field sampling strategy with smaller air sample volumes facilitating faster, simpler air sampling (e.g., use of gas syringes rather than the relative complexity of pumps or bags/canisters), with greatly reduced risk of analyte breakthrough and minimal interference, e.g., from atmospheric humidity. The improved detection limits offered by this system can also enhance accuracy and measurement precision.

Mapping the neglected space: gradients of detection revealed by virtual reality.

PubMed

Dvorkin, Assaf Y; Bogey, Ross A; Harvey, Richard L; Patton, James L

2012-02-01

Spatial neglect affects perception along different dimensions. However, there is limited availability of 3-dimensional (3D) methods that fully map out a patient's volume of deficit, although this could guide clinical management. To test whether patients with neglect exhibit simple contralesional versus complex perceptual deficits and whether deficits are best described using Cartesian (rectangular) or polar coordinates. Seventeen right-hemisphere persons with stroke (8 with a history of neglect) and 9 healthy controls were exposed to a 3D virtual environment. Targets placed in a dense array appeared one at a time in various locations. When tested using rectangular array of targets, subjects in the neglect group exhibited complex asymmetries across several dimensions in both reaction time and target detection rates. Paper-and-pencil tests only detected neglect in 4 of 8 of these patients. When tested using polar array of targets, 2 patients who initially appeared to perform poorly in both left and near space only showed a simple left-side asymmetry that depended almost entirely on the angle from the sagittal plane. A third patient exhibited left neglect irrespective of the arrangements of targets used. An idealized model with pure dependence on the polar angle demonstrated how such deficits could be misconstrued as near neglect if one uses a rectangular array. Such deficits may be poorly detected by paper-and-pencil tests and even by computerized tests that use regular screens. Assessments that incorporate 3D arrangements of targets enable precise mapping of deficient areas and detect subtle forms of neglect whose identification may be relevant to treatment strategies.

Synthesis and Characterization of Tricarbonyl-Re/Tc(I) Chelate Probes Targeting the G Protein-Coupled Estrogen Receptor GPER/GPR30

PubMed Central

Burai, Ritwik; Ramesh, Chinnasamy; Nayak, Tapan K.; Dennis, Megan K.; Bryant, Bj K.; Prossnitz, Eric R.; Arterburn, Jeffrey B.

2012-01-01

The discovery of the G protein-coupled estrogen receptor GPER (also GPR30) and the resulting development of selective chemical probes have revealed new aspects of estrogen receptor biology. The potential clinical relevance of this receptor has been suggested from numerous studies that have identified GPER expression in breast, endometrial, ovarian and other cancers. Thus GPER can be considered a candidate biomarker and target for non-invasive imaging and therapy. We have designed and synthesized a series of organometallic tricarbonyl-rhenium complexes conjugated to a GPER-selective small molecule derived from tetrahydro-3H-cyclopenta[c]quinoline. The activity and selectivity of these chelates in GPER-mediated signaling pathways were evaluated. These results demonstrate that GPER targeting characteristics depend strongly on the structure of the chelate and linkage. Ethanone conjugates functioned as agonists, a 1,2,3-triazole spacer yielded an antagonist, and derivatives with increased steric volume exhibited decreased activities. Promising GPER selectivity was observed, as none of the complexes interacted with the nuclear estrogen receptors. Radiolabeling with technetium-99m in aqueous media was efficient and gave radioligands with high radiochemical yields and purity. These chelates have favorable physicochemical properties, show excellent stability in biologically relevant media, exhibit receptor specificity and are promising candidates for continuing development as diagnostic imaging agents targeting GPER expression in cancer. PMID:23077529

An analytical model for pressure of volume fractured tight oil reservoir with horizontal well

NASA Astrophysics Data System (ADS)

Feng, Qihong; Dou, Kaiwen; Zhang, Xianmin; Xing, Xiangdong; Xia, Tian

2017-05-01

The property of tight oil reservoir is worse than common reservoir that we usually seen before, the porosity and permeability is low, the diffusion is very complex. Therefore, the ordinary depletion method is useless here. The volume fracture breaks through the conventional EOR mechanism, which set the target by amplifying the contact area of fracture and reservoir so as to improving the production of every single well. In order to forecast the production effectively, we use the traditional dual-porosity model, build an analytical model for production of volume fractured tight oil reservoir with horizontal well, and get the analytical solution in Laplace domain. Then we construct the log-log plot of dimensionless pressure and time by stiffest conversion. After that, we discuss the influential factors of pressure. Several factors like cross flow, skin factors and threshold pressure gradient was analyzed in the article. This model provides a useful method for tight oil production forecast and it has certain guiding significance for the production capacity prediction and dynamic analysis.

A Review of Electrical Impedance Spectrometry Methods for Parametric Estimation of Physiologic Fluid Volumes

NASA Technical Reports Server (NTRS)

Dewberry, B.

2000-01-01

Electrical impedance spectrometry involves measurement of the complex resistance of a load at multiple frequencies. With this information in the form of impedance magnitude and phase, or resistance and reactance, basic structure or function of the load can be estimated. The "load" targeted for measurement and estimation in this study consisted of the water-bearing tissues of the human calf. It was proposed and verified that by measuring the electrical impedance of the human calf and fitting this data to a model of fluid compartments, the lumped-model volume of intracellular and extracellular spaces could be estimated, By performing this estimation over time, the volume dynamics during application of stimuli which affect the direction of gravity can be viewed. The resulting data can form a basis for further modeling and verification of cardiovascular and compartmental modeling of fluid reactions to microgravity as well as countermeasures to the headward shift of fluid during head-down tilt or spaceflight.

SU-F-T-501: Dosimetric Comparison of Single Arc-Per-Beam and Two Arc-Per-Beam VMAT Optimization in the Monaco Treatment Planning System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kalet, A; Cao, N; Meyer, J

Purpose: The purpose of this study was to evaluate the dosimetric and practical effects of the Monaco treatment planning system “max arcs-per-beam” optimization parameter in pelvic radiotherapy treatments. Methods: A total of 17 previously treated patients were selected for this study with a range of pelvic disease site including prostate(9), bladder(1), uterus(3), rectum(3), and cervix(1). For each patient, two plans were generated, one using a arc-per-beam setting of ‘1’ and another with setting of ‘2’. The setting allows the optimizer to add a gantry direction change, creating multiple arc passes per beam sequence. Volumes and constraints established from the initialmore » clinical treatments were used for planning. All constraints and dose coverage objects were kept the same between plans, and all plans were normalized to 99.7% to ensure 100% of the PTV received 95% of the prescription dose. We evaluated the PTV conformity index, homogeneity index, total monitor units, number of control points, and various dose volume histogram (DVH) points for statistical comparison (alpha=0.05). Results: We found for the 10 complex shaped target volumes (small central volumes with extending bilateral ‘arms’ to cover nodal regions) that the use of 2 arcs-per-beam achieved significantly lower average DVH values for the bladder V20 (p=0.036) and rectum V30 (p=0.001) while still meeting the high dose target constraints. DVH values for the simpler, more spherical PTVs were not found significantly different. Additionally, we found a beam delivery time reduction of approximately 25%. Conclusion: In summary, the dosimetric benefit, while moderate, was improved over a 1 arc-per-beam setting for complex PTVs, and equivalent in other cases. The overall reduced delivery time suggests that the use of multiple arcs-per-beam could lead to reduced patient on table time, increased clinical throughput, and reduced medical physics quality assurance effort.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Avkshtol, V; Tanny, S; Reddy, K

Purpose: Stereotactic radiation therapy (SRT) provides an excellent alternative to embolization and surgical excision for the management of appropriately selected cerebral arteriovenous malformations (AVMs). The currently accepted standard for delineating AVMs is planar digital subtraction angiography (DSA). DSA can be used to acquire a 3D data set that preserves osseous structures (3D-DA) at the time of the angiography for SRT planning. Magnetic resonance imaging (MRI) provides an alternative noninvasive method of visualizing the AVM nidus with comparable spatial resolution. We utilized 3D-DA and T1 post-contrast MRI data to evaluate the differences in SRT target volumes. Methods: Four patients underwent 3D-DAmore » and high-resolution MRI. 3D T1 post-contrast images were obtained in all three reconstruction planes. A planning CT was fused with MRI and 3D-DA data sets. The AVMs were contoured utilizing one of the image sets at a time. Target volume, centroid, and maximum and minimum dimensions were analyzed for each patient. Results: Targets delineated using post-contrast MRI demonstrated a larger mean volume. AVMs >2 cc were found to have a larger difference between MRI and 3D-DA volumes. Larger AVMs also demonstrated a smaller relative uncertainty in contour centroid position (1 mm). AVM targets <2 cc had smaller absolute differences in volume, but larger differences in contour centroid position (2.5 mm). MRI targets demonstrated a more irregular shape compared to 3D-DA targets. Conclusions: Our preliminary data supports the use of MRI alone to delineate AVM targets >2 cc. The greater centroid stability for AVMs >2 cc ensures accurate target localization during image fusion. The larger MRI target volumes did not result in prohibitively greater volumes of normal brain tissue receiving the prescription dose. The larger centroid instability for AVMs <2 cc precludes the use of MRI alone for target delineation. We recommend incorporating a 3D-DA for these patients.« less

Single-Isocenter Multiple-Target Stereotactic Radiosurgery: Risk of Compromised Coverage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roper, Justin, E-mail: justin.roper@emory.edu; Department of Biostatistics and Bioinformatics, Winship Cancer Institute of Emory University, Atlanta, Georgia; Chanyavanich, Vorakarn

2015-11-01

Purpose: To determine the dosimetric effects of rotational errors on target coverage using volumetric modulated arc therapy (VMAT) for multitarget stereotactic radiosurgery (SRS). Methods and Materials: This retrospective study included 50 SRS cases, each with 2 intracranial planning target volumes (PTVs). Both PTVs were planned for simultaneous treatment to 21 Gy using a single-isocenter, noncoplanar VMAT SRS technique. Rotational errors of 0.5°, 1.0°, and 2.0° were simulated about all axes. The dose to 95% of the PTV (D95) and the volume covered by 95% of the prescribed dose (V95) were evaluated using multivariate analysis to determine how PTV coverage was relatedmore » to PTV volume, PTV separation, and rotational error. Results: At 0.5° rotational error, D95 values and V95 coverage rates were ≥95% in all cases. For rotational errors of 1.0°, 7% of targets had D95 and V95 values <95%. Coverage worsened substantially when the rotational error increased to 2.0°: D95 and V95 values were >95% for only 63% of the targets. Multivariate analysis showed that PTV volume and distance to isocenter were strong predictors of target coverage. Conclusions: The effects of rotational errors on target coverage were studied across a broad range of SRS cases. In general, the risk of compromised coverage increased with decreasing target volume, increasing rotational error and increasing distance between targets. Multivariate regression models from this study may be used to quantify the dosimetric effects of rotational errors on target coverage given patient-specific input parameters of PTV volume and distance to isocenter.« less

Simulating the Effect of Spectroscopic MRI as a Metric for Radiation Therapy Planning in Patients with Glioblastoma

PubMed Central

Cordova, J. Scott; Kandula, Shravan; Gurbani, Saumya; Zhong, Jim; Tejani, Mital; Kayode, Oluwatosin; Patel, Kirtesh; Prabhu, Roshan; Schreibmann, Eduard; Crocker, Ian; Holder, Chad A.; Shim, Hyunsuk; Shu, Hui-Kuo

2017-01-01

Due to glioblastoma’s infiltrative nature, an optimal radiation therapy (RT) plan requires targeting infiltration not identified by anatomical magnetic resonance imaging (MRI). Here, high-resolution, whole-brain spectroscopic MRI (sMRI) is used to describe tumor infiltration alongside anatomical MRI and simulate the degree to which it modifies RT target planning. In 11 patients with glioblastoma, data from preRT sMRI scans were processed to give high-resolution, whole-brain metabolite maps normalized by contralateral white matter. Maps depicting choline to N-Acetylaspartate (Cho/NAA) ratios were registered to contrast-enhanced T1-weighted RT planning MRI for each patient. Volumes depicting metabolic abnormalities (1.5−, 1.75−, and 2.0-fold increases in Cho/NAA ratios) were compared with conventional target volumes and contrast-enhancing tumor at recurrence. sMRI-modified RT plans were generated to evaluate target volume coverage and organ-at-risk dose constraints. Conventional clinical target volumes and Cho/NAA abnormalities identified significantly different regions of microscopic infiltration with substantial Cho/NAA abnormalities falling outside of the conventional 60 Gy isodose line (41.1, 22.2, and 12.7 cm3, respectively). Clinical target volumes using Cho/NAA thresholds exhibited significantly higher coverage of contrast enhancement at recurrence on average (92.4%, 90.5%, and 88.6%, respectively) than conventional plans (82.5%). sMRI-based plans targeting tumor infiltration met planning objectives in all cases with no significant change in target coverage. In 2 cases, the sMRI-modified plan exhibited better coverage of contrast-enhancing tumor at recurrence than the original plan. Integration of the high-resolution, whole-brain sMRI into RT planning is feasible, resulting in RT target volumes that can effectively target tumor infiltration while adhering to conventional constraints. PMID:28105468

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brualla, Lorenzo, E-mail: lorenzo.brualla@uni-due.de; Zaragoza, Francisco J.; Sempau, Josep

Purpose: External beam radiotherapy is the only conservative curative approach for Stage I non-Hodgkin lymphomas of the conjunctiva. The target volume is geometrically complex because it includes the eyeball and lid conjunctiva. Furthermore, the target volume is adjacent to radiosensitive structures, including the lens, lacrimal glands, cornea, retina, and papilla. The radiotherapy planning and optimization requires accurate calculation of the dose in these anatomical structures that are much smaller than the structures traditionally considered in radiotherapy. Neither conventional treatment planning systems nor dosimetric measurements can reliably determine the dose distribution in these small irradiated volumes. Methods and Materials: The Montemore » Carlo simulations of a Varian Clinac 2100 C/D and human eye were performed using the PENELOPE and PENEASYLINAC codes. Dose distributions and dose volume histograms were calculated for the bulbar conjunctiva, cornea, lens, retina, papilla, lacrimal gland, and anterior and posterior hemispheres. Results: The simulated results allow choosing the most adequate treatment setup configuration, which is an electron beam energy of 6 MeV with additional bolus and collimation by a cerrobend block with a central cylindrical hole of 3.0 cm diameter and central cylindrical rod of 1.0 cm diameter. Conclusions: Monte Carlo simulation is a useful method to calculate the minute dose distribution in ocular tissue and to optimize the electron irradiation technique in highly critical structures. Using a voxelized eye phantom based on patient computed tomography images, the dose distribution can be estimated with a standard statistical uncertainty of less than 2.4% in 3 min using a computing cluster with 30 cores, which makes this planning technique clinically relevant.« less

In search of the `impenetrable' volume of a molecule in a noncovalent complex

NASA Astrophysics Data System (ADS)

Murray, Jane S.; Politzer, Peter

2018-03-01

We propose to characterise the "impenetrable" volumes of molecules A and B in a complex A--B by finding that contour of its electronic density that separates the molecular surfaces of A and B but leaves them almost touching. The volume of the complex within that contour is always less than within the 0.001 au contour. The percent difference measures the interpenetration of the two molecules at equilibrium, and is found to directly correlate with the binding energy of the complex. We interpret the volume of each molecule that is enclosed by the almost-touching contour as that molecule's impenetrable volume relative to its particular partner. The percents by which the molecules' relative impenetrable volumes differ from their 0.001 au volumes in the free states also correlate with the strengths of the interactions. This allows the "absolute" impenetrable volume of any molecule to be estimated as ∼25% of its 0.001 au volume in the free state. However this absolute impenetrable volume is only approached by the molecule in a relatively strong interaction.

Dosimetric comparison of photon and proton treatment techniques for chondrosarcoma of thoracic spine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yadav, Poonam, E-mail: yadav@humonc.wisc.edu; Department of Medical Physics, University of Wisconsin, Madison, WI; University of Wisconsin Riverview Cancer Center, Wisconsin Rapids, WI

2013-10-01

Chondrosarcomas are relatively radiotherapy resistant, and also delivering high radiation doses is not feasible owing to anatomic constraints. In this study, the feasibility of helical tomotherapy for treatment of chondrosarcoma of thoracic spine is explored and compared with other available photon and proton radiotherapy techniques in the clinical setting. A patient was treated for high-grade chondrosarcoma of the thoracic spine using tomotherapy. Retrospectively, the tomotherapy plan was compared with intensity-modulated radiation therapy, dynamic arc photon therapy, and proton therapy. Two primary comparisons were made: (1) comparison of normal tissue sparing with comparable target volume coverage (plan-1), and (2) comparison ofmore » target volume coverage with a constrained maximum dose to the cord center (plan-2). With constrained target volume coverage, proton plans were found to yield lower mean doses for all organs at risk (spinal cord, esophagus, heart, and both lungs). Tomotherapy planning resulted in the lowest mean dose to all organs at risk amongst photon-based methods. For cord dose constrained plans, the static-field intensity-modulated radiation therapy and dynamic arc plans resulted target underdosing in 20% and 12% of planning target volume2 volumes, respectively, whereas both proton and tomotherapy plans provided clinically acceptable target volume coverage with no portion of planning target volume2 receiving less than 90% of the prescribed dose. Tomotherapy plans are comparable to proton plans and produce superior results compared with other photon modalities. This feasibility study suggests that tomotherapy is an attractive alternative to proton radiotherapy for delivering high doses to lesions in the thoracic spine.« less

Targeted cancer therapy based on single-wall carbon nanohorns with doxorubicin in vitro and in vivo

NASA Astrophysics Data System (ADS)

Ma, Xiaona; Shu, Chang; Guo, Jing; Pang, Lili; Su, Lin; Fu, Degang; Zhong, Wenying

2014-07-01

A new targeted drug delivery system (DDS) based on oxidized single-wall carbon nanohorns (oxSWCNHs) was developed. Sodium alginate (SA) was used to modify oxSWCNHs to improve its dispersibility and biocompatibility, the first time such a modification to oxSWCNHs was reported. The humanized anti-vascular endothelial growth factor (anti-VEGF) monoclonal antibody was bound to the SA as targeting group to selectively kill the tumor cells. Doxorubicin hydrochloride (DOX) was conjugated to oxSWCNHs in basic pH solution by π-π stacking, and its release was triggered by the lower pH as the micro-environment of the tumor. Quantitative analyses showed that the DOX@oxSWCNHs/SA complexes contained 1 g DOX per gram of oxSWCNHs. Cell experiment showed that the DOX@oxSWCNHs/SA-mAb effectively targeted the human breast adenocarcinoma (MCF-7) cells and rarely adhered to the human embryonic kidney 293 (HEK293) cells. And the anticancer effects of the complexes were higher than those of the free DOX. Pharmaceutical efficiency in vivo showed that the relative tumor volumes (RTV) of normal saline (NS) group, oxSWCNH/SA-mAb (2.5 mg/kg) group, DOX (2.5 mg/kg) group, and DOX@oxSWCNHs/SA-mAb (2.5 mg/kg) group were approximately 61, 56, 14, and 7.2, respectively. In addition, higher drug dose (5 mg/kg) of DOX@oxSWCNHs/SA-mAb resulted in a better antitumor activity. Histopathological studies in mice confirmed that the DOX@oxSWCNHs/SA-mAb complexes did not demonstrate any detectable hepatotoxicity, cardiotoxicity, and nephrotoxicity.

Model-specific selection of molecular targets for heart failure gene therapy

PubMed Central

Katz, Michael G.; Fargnoli, Anthony S.; Tomasulo, Catherine E.; Pritchette, Louella A.; Bridges, Charles R.

2013-01-01

Heart failure (HF) is a complex multifaceted problem of abnormal ventricular function and structure. In recent years, new information has been accumulated allowing for a more detailed understanding of the cellular and molecular alterations that are the underpinnings of diverse causes of HF, including myocardial ischemia, pressure-overload, volume-overload or intrinsic cardiomyopathy. Modern pharmacological approaches to treat HF have had a significant impact on the course of the disease, although they do not reverse the underlying pathological state of the heart. Therefore gene-based therapy holds a great potential as a targeted treatment for cardiovascular diseases. Here, we survey the relative therapeutic efficacy of genetic modulation of β-adrenergic receptor signaling, Ca2+ handling proteins and angiogenesis in the most common extrinsic models of HF. PMID:21954055

Helical tomotherapy in patients with breast cancer and complex treatment volumes.

PubMed

Cendales, Ricardo; Schiappacasse, Luis; Schnitman, Franco; García, Graciela; Marsiglia, Hugo

2011-04-01

To describe early clinical results of tomotherapy treatment in patients with breast cancer and complex treatment volumes. Ten patients were treated with tomotherapy between January 2009 and March 2010. Treatment planning objectives were to cover at least 95% of the planning target volume with the 95% isodose; to have a minimum dose of 90% and a maximum dose of 105%. All treatments included daily CT/megavoltage image guidance. Acute toxicity was recorded weekly. Six patients were treated because constraints were not accomplished for heart, lung or contralateral breast in a previous three-dimensional conformal plan; two for preexisting cardiac or pulmonary disease, and two more for bilateral breast irradiation. Treatment volumes included the whole breast in the majority of patients, as well as the supraclavicular and the internal mammary chain nodes when indicated. Most patients were older than 50 years, and had an early breast cancer, with positive oestrogen receptors, negative HER2 expression and a poorly differentiated, infiltrating ductal carcinoma. The majority of patients had received neoadjuvant chemotherapy associated to breast-conserving surgery and adjuvant hormonotherapy. Median homogeneity index was 1.09; median coverage index was 0.81. Median V20Gy and V10Gy for ipsilateral lung was 20% and 37.1% respectively. Median V25 and V35 for heart was 15% and 4% respectively. Median dose for contralateral breast was 7 Gy. Skin acute toxicity was grade 1 in 41.7% and grade 2 in 58.3%. Tomotherapy is a technique capable of delivering a well tolerated treatment with high homogeneity and coverage indexes and high capabilities for sparing the organs at risk in patients with anatomically complex breast cancer, bilateral breast cancer, indication for internal mammary chain node irradiation, cardiac toxicity derived from chemotherapy, or preexisting cardiac or pulmonary disease. Further studies are required to evaluate local control and late toxicity.

Trends in Medicare Service Volume for Cataract Surgery and the Impact of the Medicare Physician Fee Schedule.

PubMed

Gong, Dan; Jun, Lin; Tsai, James C

2017-08-01

To calculate the associations between Medicare payment and service volume for complex and noncomplex cataract surgeries. The 2005-2009 CMS Part B National Summary Data Files, CMS Part B Carrier Summary Data Files, and the Medicare Physician Fee Schedule. Conducting a retrospective, longitudinal analysis using a fixed-effects model of Medicare Part B carriers representing all 50 states and the District of Columbia from 2005 to 2009, we calculated the Medicare payment-service volume elasticities for noncomplex (CPT 66984) and complex (CPT 66982) cataract surgeries. Service volume data were extracted from the CMS Part B National Summary and Carrier Summary Data Files. Payment data were extracted from the Medicare Physician Fee Schedule. From 2005 to 2009, the proportion of total cataract services billed as complex increased from 3.2 to 6.7 percent. Every 1 percent decrease in Medicare payment was associated with a nonsignificant change in noncomplex cataract service volume (elasticity = 0.15, 95 percent CI [-0.09, 0.38]) but a statistically significant increase in complex cataract service volume (elasticity = -1.12, 95 percent CI [-1.60, -0.63]). Reduced Medicare payment was associated with a significant increase in complex cataract service volume but not in noncomplex cataract service volume, resulting in a shift toward performing a greater proportion of complex cataract surgeries from 2005 to 2009. © Health Research and Educational Trust.

The impact of PET/CT scanning on the size of target volumes, radiation exposure of organs at risk, TCP and NTCP, in the radiotherapy planning of non-small cell lung cancer.

PubMed

Vojtíšek, Radovan; Mužík, Jan; Slampa, Pavel; Budíková, Marie; Hejsek, Jaroslav; Smolák, Petr; Ferda, Jiří; Fínek, Jindřich

2014-05-01

To compare radiotherapy plans made according to CT and PET/CT and to investigate the impact of changes in target volumes on tumour control probability (TCP), normal tissue complication probability (NTCP) and the impact of PET/CT on the staging and treatment strategy. Contemporary studies have proven that PET/CT attains higher sensitivity and specificity in the diagnosis of lung cancer and also leads to higher accuracy than CT alone in the process of target volume delineation in NSCLC. Between October 2009 and March 2012, 31 patients with locally advanced NSCLC, who had been referred to radical radiotherapy were involved in our study. They all underwent planning PET/CT examination. Then we carried out two separate delineations of target volumes and two radiotherapy plans and we compared the following parameters of those plans: staging, treatment purpose, the size of GTV and PTV and the exposure of organs at risk (OAR). TCP and NTCP were also compared. PET/CT information led to a significant decrease in the sizes of target volumes, which had the impact on the radiation exposure of OARs. The reduction of target volume sizes was not reflected in the significant increase of the TCP value. We found that there is a very strong direct linear relationship between all evaluated dosimetric parameters and NTCP values of all evaluated OARs. Our study found that the use of planning PET/CT in the radiotherapy planning of NSCLC has a crucial impact on the precise determination of target volumes, more precise staging of the disease and thus also on possible changes of treatment strategy.

Consistency in seroma contouring for partial breast radiotherapy: Impact of guidelines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wong, Elaine K.; Truong, Pauline T.; Kader, Hosam A.

2006-10-01

Purpose: Inconsistencies in contouring target structures can undermine the precision of conformal radiation therapy (RT) planning and compromise the validity of clinical trial results. This study evaluated the impact of guidelines on consistency in target volume contouring for partial breast RT planning. Methods and Materials: Guidelines for target volume definition for partial breast radiation therapy (PBRT) planning were developed by members of the steering committee for a pilot trial of PBRT using conformal external beam planning. In phase 1, delineation of the breast seroma in 5 early-stage breast cancer patients was independently performed by a 'trained' cohort of four radiationmore » oncologists who were provided with these guidelines and an 'untrained' cohort of four radiation oncologists who contoured without guidelines. Using automated planning software, the seroma target volume (STV) was expanded into a clinical target volume (CTV) and planning target volume (PTV) for each oncologist. Means and standard deviations were calculated, and two-tailed t tests were used to assess differences between the 'trained' and 'untrained' cohorts. In phase 2, all eight radiation oncologists were provided with the same contouring guidelines, and were asked to delineate the seroma in five new cases. Data were again analyzed to evaluate consistency between the two cohorts. Results: The 'untrained' cohort contoured larger seroma volumes and had larger CTVs and PTVs compared with the 'trained' cohort in three of five cases. When seroma contouring was performed after review of contouring guidelines, the differences in the STVs, CTVs, and PTVs were no longer statistically significant. Conclusion: Guidelines can improve consistency among radiation oncologists performing target volume delineation for PBRT planning.« less

Magnetic Resonance Lymphography-Guided Selective High-Dose Lymph Node Irradiation in Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meijer, Hanneke J.M., E-mail: H.Meijer@rther.umcn.nl; Debats, Oscar A.; Kunze-Busch, Martina

2012-01-01

Purpose: To demonstrate the feasibility of magnetic resonance lymphography (MRL) -guided delineation of a boost volume and an elective target volume for pelvic lymph node irradiation in patients with prostate cancer. The feasibility of irradiating these volumes with a high-dose boost to the MRL-positive lymph nodes in conjunction with irradiation of the prostate using intensity-modulated radiotherapy (IMRT) was also investigated. Methods and Materials: In 4 prostate cancer patients with a high risk of lymph node involvement but no enlarged lymph nodes on CT and/or MRI, MRL detected pathological lymph nodes in the pelvis. These lymph nodes were identified and delineatedmore » on a radiotherapy planning CT to create a boost volume. Based on the location of the MRL-positive lymph nodes, the standard elective pelvic target volume was individualized. An IMRT plan with a simultaneous integrated boost (SIB) was created with dose prescriptions of 42 Gy to the pelvic target volume, a boost to 60 Gy to the MRL-positive lymph nodes, and 72 Gy to the prostate. Results: All MRL-positive lymph nodes could be identified on the planning CT. This information could be used to delineate a boost volume and to individualize the pelvic target volume for elective irradiation. IMRT planning delivered highly acceptable radiotherapy plans with regard to the prescribed dose levels and the dose to the organs at risk (OARs). Conclusion: MRL can be used to select patients with limited lymph node involvement for pelvic radiotherapy. MRL-guided delineation of a boost volume and an elective pelvic target volume for selective high-dose lymph node irradiation with IMRT is feasible. Whether this approach will result in improved outcome for these patients needs to be investigated in further clinical studies.« less

[Comparison of SIB-IMRT treatment plans for upper esophageal carcinoma].

PubMed

Fu, Wei-hua; Wang, Lv-hua; Zhou, Zong-mei; Dai, Jian-rong; Hu, Yi-min

2003-06-01

To implement simultaneous integrated boost intensity-modulated radiotherapy(SIB-IMRT) plans for upper esophageal carcinoma and investigate the dose profiles of tumor and electively treated region and the dose to organs at risk (OARs). SIB-IMRT plans were designed for two patients with upper esophageal carcinoma. Two target volumes were predefined: PTV1, the target volume of the primary lesion, which was given to 67.2 Gy, and PTV2, the target volume of electively treated region, which was given to 50.4 Gy. With the same dose-volume constraints, but different beams arrangements (3, 5, 7, or 9 equispaced coplanar beams), four plans were generated. Indices, including dose distribution, dose volume histogram (DVH) and conformity index, were used for comparison of these plans. The plan with three intensity-modulated beams could produce good dose distribution for the two target volumes. The dose conformity to targets and the dose to OARs were improved as the beam number increased. The dose distributions in targets changed little when the beam number increased from 7 to 9. Five to seven intensity-modulated beams can produce desirable dose distributions for simultaneous integrated boost (SIB) treatment for upper esophageal carcinoma. The primary tumor can get higher equivalent dose by SIB treatments. It is easier and more efficient to design plans with equispaced coplanar beams. The efficacy of SIB-IMRT remains to be determined by the clinical outcome.

P04.02 Analysis of 18F-DOPA PET imaging for target volume definition in patients with recurrent glioblastoma treated with proton therapy

PubMed Central

Amelio, D.; Scartoni, D.; Palucci, A.; Vennarini, S.; Giacomelli, I.; Lemoine, S.; Donner, D.; Farace, P.; Chierichetti, F.; Amichetti, M.

2017-01-01

Abstract Introduction: Target volume definition is of critical relevance when re-irradiation is delivered and steep dose gradient irradiation techniques, such as proton therapy (PT), are employed. Aim of the study is to investigate the impact of 18F-DOPA on target volume contouring in recurrent glioblastoma (rGBM) patients (pts) undergoing re-irradiation with PT. MATERIAL AND METHODS: We investigated the differences in volume and relationship of magnetic resonance imaging (MRI)- vs. DOPA PET-derived gross tumor volumes (GTVs) of 14 rGBM pts re-irradiated with PT between January and November 2016. All pts had been previously treated with photon radiotherapy (60 Gy) with concomitant and adjuvant temozolomide. All the pts received morphological MRI with contrast enhancement medium administration and 18F-DOPA PET-CT study. We used the pathological distribution of 18F-DOPA in brain tissue to identify the so-called Biological Tumor Volume (BTV). Such areas were assessed using a tumor to normal brain ratio > 2. Moreover, any area of contrast enhancement on MRI was used to identify the MRI-based GTV (MRGTV). Definitive GTV included MRGTV plus BTV. Clinical target volume was generated by adding to GTV a 3-mm uniform margin manually corrected in proximity of anatomical barriers. CTV was expanded by 4 mm to create planning target volume. All pts received 36 GyRBE in 18 fractions. Mean values of differently delineated GTVs were compared each other by paired Student’s t-test; p < 0.05 was considered significant. To further compare MRGTV and BTV, the overlapping (MRGTV ^ BTV) and the composite (MRGTV U BTV) volumes were calculated, and a concordance index (CI) was defined as the ratio between the overlap and composite volumes. Results: MRGTV (mean 14.9 ± 14.5 cc) was larger than BTV (mean 10.9 ± 9.8 cc) although this difference was not statistically significant. The composite volume (mean 20.9 ± 14.7 cc) was significantly larger than each single volume (p < 0.006). The overlapping volume (mean 5.7 ± 3.3 cc) was quite small compared to each single volume and suggest that relevant part of MRIGTV is not covered by BTV as well as that relevant part of BTV is not covered by MRGTV. In line with such results we recorded also a low CI (mean 0.26 ± 0.2). The PT irradiation of PET-integrated target volumes provided a median progression-free survival (PFS) of 6 months, while the 6-month PFS rate was 57%; median survival after PT was 8.7 months, while 9-month survival rate was 60%. Conclusions: Target volume definition for rGBM undergoing PT re-irradiation may yield significantly differing results depending upon the imaging modality used for target contouring. Our data suggest that 18F-DOPA PET can detect relevant non-enhancing pathological areas outside the conventional MRGTV ultimately yielding to larger volumes to be irradiated. Influence on clinical outcomes deserves further evaluation.

Noether charge, black hole volume, and complexity

NASA Astrophysics Data System (ADS)

Couch, Josiah; Fischler, Willy; Nguyen, Phuc H.

2017-03-01

In this paper, we study the physical significance of the thermodynamic volumes of AdS black holes using the Noether charge formalism of Iyer and Wald. After applying this formalism to study the extended thermodynamics of a few examples, we discuss how the extended thermodynamics interacts with the recent complexity = action proposal of Brown et al. (CA-duality). We, in particular, discover that their proposal for the late time rate of change of complexity has a nice decomposition in terms of thermodynamic quantities reminiscent of the Smarr relation. This decomposition strongly suggests a geometric, and via CA-duality holographic, interpretation for the thermodynamic volume of an AdS black hole. We go on to discuss the role of thermodynamics in complexity = action for a number of black hole solutions, and then point out the possibility of an alternate proposal, which we dub "complexity = volume 2.0". In this alternate proposal the complexity would be thought of as the spacetime volume of the Wheeler-DeWitt patch. Finally, we provide evidence that, in certain cases, our proposal for complexity is consistent with the Lloyd bound whereas CA-duality is not.

CTA with fluoroscopy image fusion guidance in endovascular complex aortic aneurysm repair.

PubMed

Sailer, A M; de Haan, M W; Peppelenbosch, A G; Jacobs, M J; Wildberger, J E; Schurink, G W H

2014-04-01

To evaluate the effect of intraoperative guidance by means of live fluoroscopy image fusion with computed tomography angiography (CTA) on iodinated contrast material volume, procedure time, and fluoroscopy time in endovascular thoraco-abdominal aortic repair. CTA with fluoroscopy image fusion road-mapping was prospectively evaluated in patients with complex aortic aneurysms who underwent fenestrated and/or branched endovascular repair (FEVAR/BEVAR). Total iodinated contrast material volume, overall procedure time, and fluoroscopy time were compared between the fusion group (n = 31) and case controls (n = 31). Reasons for potential fusion image inaccuracy were analyzed. Fusion imaging was feasible in all patients. Fusion image road-mapping was used for navigation and positioning of the devices and catheter guidance during access to target vessels. Iodinated contrast material volume and procedure time were significantly lower in the fusion group than in case controls (159 mL [95% CI 132-186 mL] vs. 199 mL [95% CI 170-229 mL], p = .037 and 5.2 hours [95% CI 4.5-5.9 hours] vs. 6.3 hours (95% CI 5.4-7.2 hours), p = .022). No significant differences in fluoroscopy time were observed (p = .38). Respiration-related vessel displacement, vessel elongation, and displacement by stiff devices as well as patient movement were identified as reasons for fusion image inaccuracy. Image fusion guidance provides added value in complex endovascular interventions. The technology significantly reduces iodinated contrast material dose and procedure time. Copyright © 2014 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Volume Transmission in Central Dopamine and Noradrenaline Neurons and Its Astroglial Targets.

PubMed

Fuxe, Kjell; Agnati, Luigi F; Marcoli, Manuela; Borroto-Escuela, Dasiel O

2015-12-01

Already in the 1960s the architecture and pharmacology of the brainstem dopamine (DA) and noradrenaline (NA) neurons with formation of vast numbers of DA and NA terminal plexa of the central nervous system (CNS) indicated that they may not only communicate via synaptic transmission. In the 1980s the theory of volume transmission (VT) was introduced as a major communication together with synaptic transmission in the CNS. VT is an extracellular and cerebrospinal fluid transmission of chemical signals like transmitters, modulators etc. moving along energy gradients making diffusion and flow of VT signals possible. VT interacts with synaptic transmission mainly through direct receptor-receptor interactions in synaptic and extrasynaptic heteroreceptor complexes and their signaling cascades. The DA and NA neurons are specialized for extrasynaptic VT at the soma-dendrtitic and terminal level. The catecholamines released target multiple DA and adrenergic subtypes on nerve cells, astroglia and microglia which are the major cell components of the trophic units building up the neural-glial networks of the CNS. DA and NA VT can modulate not only the strength of synaptic transmission but also the VT signaling of the astroglia and microglia of high relevance for neuron-glia interactions. The catecholamine VT targeting astroglia can modulate the fundamental functions of astroglia observed in neuroenergetics, in the Glymphatic system, in the central renin-angiotensin system and in the production of long-distance calcium waves. Also the astrocytic and microglial DA and adrenergic receptor subtypes mediating DA and NA VT can be significant drug targets in neurological and psychiatric disease.

3D-segmentation of the 18F-choline PET signal for target volume definition in radiation therapy of the prostate.

PubMed

Ciernik, I Frank; Brown, Derek W; Schmid, Daniel; Hany, Thomas; Egli, Peter; Davis, J Bernard

2007-02-01

Volumetric assessment of PET signals becomes increasingly relevant for radiotherapy (RT) planning. Here, we investigate the utility of 18F-choline PET signals to serve as a structure for semi-automatic segmentation for forward treatment planning of prostate cancer. 18F-choline PET and CT scans of ten patients with histologically proven prostate cancer without extracapsular growth were acquired using a combined PET/CT scanner. Target volumes were manually delineated on CT images using standard software. Volumes were also obtained from 18F-choline PET images using an asymmetrical segmentation algorithm. PTVs were derived from CT 18F-choline PET based clinical target volumes (CTVs) by automatic expansion and comparative planning was performed. As a read-out for dose given to non-target structures, dose to the rectal wall was assessed. Planning target volumes (PTVs) derived from CT and 18F-choline PET yielded comparable results. Optimal matching of CT and 18F-choline PET derived volumes in the lateral and cranial-caudal directions was obtained using a background-subtracted signal thresholds of 23.0+/-2.6%. In antero-posterior direction, where adaptation compensating for rectal signal overflow was required, optimal matching was achieved with a threshold of 49.5+/-4.6%. 3D-conformal planning with CT or 18F-choline PET resulted in comparable doses to the rectal wall. Choline PET signals of the prostate provide adequate spatial information amendable to standardized asymmetrical region growing algorithms for PET-based target volume definition for external beam RT.

A comparison of two dose calculation algorithms-anisotropic analytical algorithm and Acuros XB-for radiation therapy planning of canine intranasal tumors.

PubMed

Nagata, Koichi; Pethel, Timothy D

2017-07-01

Although anisotropic analytical algorithm (AAA) and Acuros XB (AXB) are both radiation dose calculation algorithms that take into account the heterogeneity within the radiation field, Acuros XB is inherently more accurate. The purpose of this retrospective method comparison study was to compare them and evaluate the dose discrepancy within the planning target volume (PTV). Radiation therapy (RT) plans of 11 dogs with intranasal tumors treated by radiation therapy at the University of Georgia were evaluated. All dogs were planned for intensity-modulated radiation therapy using nine coplanar X-ray beams that were equally spaced, then dose calculated with anisotropic analytical algorithm. The same plan with the same monitor units was then recalculated using Acuros XB for comparisons. Each dog's planning target volume was separated into air, bone, and tissue and evaluated. The mean dose to the planning target volume estimated by Acuros XB was 1.3% lower. It was 1.4% higher for air, 3.7% lower for bone, and 0.9% lower for tissue. The volume of planning target volume covered by the prescribed dose decreased by 21% when Acuros XB was used due to increased dose heterogeneity within the planning target volume. Anisotropic analytical algorithm relatively underestimates the dose heterogeneity and relatively overestimates the dose to the bone and tissue within the planning target volume for the radiation therapy planning of canine intranasal tumors. This can be clinically significant especially if the tumor cells are present within the bone, because it may result in relative underdosing of the tumor. © 2017 American College of Veterinary Radiology.

Quantitative analysis of treatment process time and throughput capacity for spot scanning proton therapy.

PubMed

Suzuki, Kazumichi; Palmer, Matthew B; Sahoo, Narayan; Zhang, Xiaodong; Poenisch, Falk; Mackin, Dennis S; Liu, Amy Y; Wu, Richard; Zhu, X Ronald; Frank, Steven J; Gillin, Michael T; Lee, Andrew K

2016-07-01

To determine the patient throughput and the overall efficiency of the spot scanning system by analyzing treatment time, equipment availability, and maximum daily capacity for the current spot scanning port at Proton Therapy Center Houston and to assess the daily throughput capacity for a hypothetical spot scanning proton therapy center. At their proton therapy center, the authors have been recording in an electronic medical record system all treatment data, including disease site, number of fields, number of fractions, delivered dose, energy, range, number of spots, and number of layers for every treatment field. The authors analyzed delivery system downtimes that had been recorded for every equipment failure and associated incidents. These data were used to evaluate the patient census, patient distribution as a function of the number of fields and total target volume, and equipment clinical availability. The duration of each treatment session from patient walk-in to patient walk-out of the spot scanning treatment room was measured for 64 patients with head and neck, central nervous system, thoracic, and genitourinary cancers. The authors retrieved data for total target volume and the numbers of layers and spots for all fields from treatment plans for a total of 271 patients (including the above 64 patients). A sensitivity analysis of daily throughput capacity was performed by varying seven parameters in a throughput capacity model. The mean monthly equipment clinical availability for the spot scanning port in April 2012-March 2015 was 98.5%. Approximately 1500 patients had received spot scanning proton therapy as of March 2015. The major disease sites treated in September 2012-August 2014 were the genitourinary system (34%), head and neck (30%), central nervous system (21%), and thorax (14%), with other sites accounting for the remaining 1%. Spot scanning beam delivery time increased with total target volume and accounted for approximately 30%-40% of total treatment time for the total target volumes exceeding 200 cm(3), which was the case for more than 80% of the patients in this study. When total treatment time was modeled as a function of the number of fields and total target volume, the model overestimated total treatment time by 12% on average, with a standard deviation of 32%. A sensitivity analysis of throughput capacity for a hypothetical four-room spot scanning proton therapy center identified several priority items for improvements in throughput capacity, including operation time, beam delivery time, and patient immobilization and setup time. The spot scanning port at our proton therapy center has operated at a high performance level and has been used to treat a large number of complex cases. Further improvements in efficiency may be feasible in the areas of facility operation, beam delivery, patient immobilization and setup, and optimization of treatment scheduling.

Investigating different computed tomography techniques for internal target volume definition.

PubMed

Yoganathan, S A; Maria Das, K J; Subramanian, V Siva; Raj, D Gowtham; Agarwal, Arpita; Kumar, Shaleen

2017-01-01

The aim of this work was to evaluate the various computed tomography (CT) techniques such as fast CT, slow CT, breath-hold (BH) CT, full-fan cone beam CT (FF-CBCT), half-fan CBCT (HF-CBCT), and average CT for delineation of internal target volume (ITV). In addition, these ITVs were compared against four-dimensional CT (4DCT) ITVs. Three-dimensional target motion was simulated using dynamic thorax phantom with target insert of diameter 3 cm for ten respiration data. CT images were acquired using a commercially available multislice CT scanner, and the CBCT images were acquired using On-Board-Imager. Average CT was generated by averaging 10 phases of 4DCT. ITVs were delineated for each CT by contouring the volume of the target ball; 4DCT ITVs were generated by merging all 10 phases target volumes. Incase of BH-CT, ITV was derived by boolean of CT phases 0%, 50%, and fast CT target volumes. ITVs determined by all CT and CBCT scans were significantly smaller (P < 0.05) than the 4DCT ITV, whereas there was no significant difference between average CT and 4DCT ITVs (P = 0.17). Fast CT had the maximum deviation (-46.1% ± 20.9%) followed by slow CT (-34.3% ± 11.0%) and FF-CBCT scans (-26.3% ± 8.7%). However, HF-CBCT scans (-12.9% ± 4.4%) and BH-CT scans (-11.1% ± 8.5%) resulted in almost similar deviation. On the contrary, average CT had the least deviation (-4.7% ± 9.8%). When comparing with 4DCT, all the CT techniques underestimated ITV. In the absence of 4DCT, the HF-CBCT target volumes with appropriate margin may be a reasonable approach for defining the ITV.

The Comparison Study of Quadratic Infinite Beam Program on Optimization Instensity Modulated Radiation Therapy Treatment Planning (IMRTP) between Threshold and Exponential Scatter Method with CERR® In The Case of Lung Cancer

NASA Astrophysics Data System (ADS)

Hardiyanti, Y.; Haekal, M.; Waris, A.; Haryanto, F.

2016-08-01

This research compares the quadratic optimization program on Intensity Modulated Radiation Therapy Treatment Planning (IMRTP) with the Computational Environment for Radiotherapy Research (CERR) software. We assumed that the number of beams used for the treatment planner was about 9 and 13 beams. The case used the energy of 6 MV with Source Skin Distance (SSD) of 100 cm from target volume. Dose calculation used Quadratic Infinite beam (QIB) from CERR. CERR was used in the comparison study between Gauss Primary threshold method and Gauss Primary exponential method. In the case of lung cancer, the threshold variation of 0.01, and 0.004 was used. The output of the dose was distributed using an analysis in the form of DVH from CERR. The maximum dose distributions obtained were on the target volume (PTV) Planning Target Volume, (CTV) Clinical Target Volume, (GTV) Gross Tumor Volume, liver, and skin. It was obtained that if the dose calculation method used exponential and the number of beam 9. When the dose calculation method used the threshold and the number of beam 13, the maximum dose distributions obtained were on the target volume PTV, GTV, heart, and skin.

SU-F-T-611: Critical Analysis and Efficacy of Linac Based (Beam Modulator) and Cyberknife Treatment Plans for Acoustic Neuroma/schwannoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

KP, Karrthick; Kataria, T; Thiyagarajan, R

Purpose: To study the critical analysis and efficacy of Linac and Cyberknife (CK) treatment plans for acoustic neuroma/schwannoma. Methods: Twelve of acoustic neuroma/schwannoma patients were taken for these study that. Treatment plans were generated in Multiplan treatment planning system (TPS) for CK using 5,7.5 and 10mm diameter collimators. Target volumes were in the range of 0.280 cc to 9.256 cc. Prescription dose (Rx) ranges from 1150cGy to 1950cGy delivered over 1 to 3 Fractions. For same patients stereotactic Volumetric modulated arc plans were generated using Elekta Linac with MLC thickness of 4mm in Monaco TPS. Appropriate calculation algorithms and gridmore » size were used with same Rx and organ at risk (OAR) constrains for both Linac and CK plans. Treatment plans were developed to achieve at least 95% of the target volume to receive the Rx. The dosimetric indices such as conformity index (CI), coverage, OAR dose and volume receiving 50% of Rx (V50%) were used to evaluate the plans. Results: Target volumes ranges from 0.280 cc to 3.5cc shows the CI of 1.16±0.109 and 1.53±0.360 for cyberknife and Linac plans respectively. For small volume targets, the OARs were well spared in CK plans. There are no significant differences in CI and OAR doses were observed between CK and Linac plans that have the target volume >3.5 cc. Perhaps the V50% were lesser in CK plans, and found to be 12.8± 8.4 and 22.8 ± 15.0 for CK and Linac respectively. Conclusion: The analysis shows the importance of collimator size for small volume targets. The target volumes >3.5 cc can be treated in Linac as comparable with CK. For targets <3.5cc CK plans showed superior plan quality with better CI and OAR sparing than the Linac based plans. Further studies may require evaluating the clinical advantage of CK robotic system.« less

SU-G-TeP2-08: Evaluation of Plastic Scintillator Detector for Small Field Stereotactic Patient-Specific Quality Assurance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qin, Y; Gardner, S; Huang, Y

Purpose: To evaluate the performance of a commercial plastic scintillator detector (PSD) for small-field stereotactic patient-specific quality assurance using flattening-filter-free (FFF) beams. Methods: A total of ten spherical targets (volume range:[0.03cc–2cc]) were planned using Dynamic Conformal Arc(DCA-10 plans) and Volumetric Modulated Arc Therapy(VMAT-10 plans) techniques in Eclipse(AAA v.11, 1mm dose calculation grid size). Additionally, 15 previously-treated cranial and spine SRS plans were evaluated (6 DCA, 9 VMAT, volume range:[0.04cc–119.02cc]). All measurements were acquired using Varian Edge equipped with HDMLC. Three detectors were used: PinPoint ion chamber (PTW;active volume 0.015cc), Exradin W1 PSD (Standard Imaging;active volume 0.002cc), and Gafchromic EBT3 filmmore » (Ashland). PinPoint and PSD were positioned perpendicular to beam axis in a Lucy phantom (Standard Imaging). Films were placed at isocenter in solid water. Calibration films were delivered for absolute dose analysis. Results: For large spherical targets(>1.5cc) with DCA, all detectors agreed within 1% of AAA calculations. As target volume decreased, PSD measured higher doses than AAA (maximum difference: 3.3% at 0.03cc target), while PinPoint chamber measured lower doses (maximum difference:-3.8% at 0.03cc target). Inter-detector differences between pinpoint and PSD increased with decreasing target size; differences>5% were observed for targets<0.09cc. Similar trends for inter-detector behavior were observed for clinical plans. For target sizes<0.08cc, PSD measured>5% higher dose than PinPoint chamber (maximum difference: 9.25% at 0.04cc target). Film demonstrated agreement of −0.19±1.47% with PSD for all spherical targets, and agreement within −0.98±2.25% for all 15 clinical targets. Unlike DCA, VMAT plans did not show improved AAA-to-detector agreements for large targets. Conclusion: For all targets, the PSD measurements agreed with film within 1.0%, on average. For small volume targets (<0.10cc), PSD agreed with film but measured significantly higher doses (>5%) compared with the pin point ion chamber. The plastic scintillator detector appears to be suitable for accurate measurements of small SRS targets.« less

Application of Quantitative Pharmacology Approaches in Bridging Pharmacokinetics and Pharmacodynamics of Domagrozumab From Adult Healthy Subjects to Pediatric Patients With Duchenne Muscular Disease.

PubMed

Bhattacharya, Indranil; Manukyan, Zorayr; Chan, Phylinda; Heatherington, Anne; Harnisch, Lutz

2017-10-12

Domagrozumab, a monoclonal antibody that binds to myostatin, is being developed for Duchenne muscular dystrophy (DMD) boys following a first-in-human study in healthy adults. Literature reporting pharmacokinetic parameters of monoclonal antibodies suggested that body-weight- and body-surface-area-adjusted clearance and volume of distribution estimates between adults and children are similar for subjects older than 6 years. Population modeling identified a Michaelis-Menten binding kinetics model to optimally characterize the target mediated drug disposition profile of domagrozumab and identified body mass index on the volume of distribution as the only significant covariate. Model parameters were predicted with high-precision pharmacokinetics (clearance 1.01 × 10 -4 L/[h·kg]; central volume of distribution 457 × 10 -4 L/kg; maximum elimination rate 17.5 × 10 -4 nmol/[h·kg], Km 10.6 nmol/L) and pharmacodynamics (myostatin turnover rate 457 × 10 -4 h -1 ; complex removal rate 90 × 10 -4 h -1 ; half-saturation constant 4.32 nmol/L) and were used to predict target coverage for dosage selection in the DMD population. Additionally, allometric approaches (estimated scaling exponents (standard error) for clearance and volume were 0.81 [0.01] and 0.98 [0.02], respectively) in conjunction with a separate analysis to obtain the population mean weight and standard deviation suggested that if dosed per body weight, an only 11% difference in clearance is expected between the heaviest and lightest patient, thus preventing the need for dose adjustment. In summary, quantitative approaches were instrumental in bridging and derisking the fast-track development of domagrozumab in DMD. © 2017, The American College of Clinical Pharmacology.

Early developmental gene enhancers affect subcortical volumes in the adult human brain.

PubMed

Becker, Martin; Guadalupe, Tulio; Franke, Barbara; Hibar, Derrek P; Renteria, Miguel E; Stein, Jason L; Thompson, Paul M; Francks, Clyde; Vernes, Sonja C; Fisher, Simon E

2016-05-01

Genome-wide association screens aim to identify common genetic variants contributing to the phenotypic variability of complex traits, such as human height or brain morphology. The identified genetic variants are mostly within noncoding genomic regions and the biology of the genotype-phenotype association typically remains unclear. In this article, we propose a complementary targeted strategy to reveal the genetic underpinnings of variability in subcortical brain volumes, by specifically selecting genomic loci that are experimentally validated forebrain enhancers, active in early embryonic development. We hypothesized that genetic variation within these enhancers may affect the development and ultimately the structure of subcortical brain regions in adults. We tested whether variants in forebrain enhancer regions showed an overall enrichment of association with volumetric variation in subcortical structures of >13,000 healthy adults. We observed significant enrichment of genomic loci that affect the volume of the hippocampus within forebrain enhancers (empirical P = 0.0015), a finding which robustly passed the adjusted threshold for testing of multiple brain phenotypes (cutoff of P < 0.0083 at an alpha of 0.05). In analyses of individual single nucleotide polymorphisms (SNPs), we identified an association upstream of the ID2 gene with rs7588305 and variation in hippocampal volume. This SNP-based association survived multiple-testing correction for the number of SNPs analyzed but not for the number of subcortical structures. Targeting known regulatory regions offers a way to understand the underlying biology that connects genotypes to phenotypes, particularly in the context of neuroimaging genetics. This biology-driven approach generates testable hypotheses regarding the functional biology of identified associations. Hum Brain Mapp 37:1788-1800, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Use of biotin targeted methotrexate–human serum albumin conjugated nanoparticles to enhance methotrexate antitumor efficacy

PubMed Central

Taheri, Azade; Dinarvand, Rassoul; Nouri, Faranak Salman; Khorramizadeh, Mohammad Reza; Borougeni, Atefeh Taheri; Mansoori, Pooria; Atyabi, Fatemeh

2011-01-01

Biotin molecules could be used as suitable targeting moieties in targeted drug delivery systems against tumors. To develop a biotin targeted drug delivery system, we employed human serum albumin (HSA) as a carrier. Methotrexate (MTX) molecules were conjugated to HSA. MTX-HSA nanoparticles (MTX-HSA NPs) were prepared from these conjugates by cross-linking the HSA molecules. Biotin molecules were then conjugated on the surface of MTX-HSA NPs. The anticancer efficacy of biotin targeted MTX-HSA NPs was evaluated in mice bearing 4T1 breast carcinoma. A single dose of biotin targeted MTX-HSA NPs showed stronger in vivo antitumor activity than non-targeted MTX-HSA NPs and free MTX. By 7 days after treatment, average tumor volume in the biotin targeted MTX-HSA NPs-treated group decreased to 17.6% of the initial tumor volume when the number of attached biotin molecules on MTX-HSA-NPs was the highest. Average tumor volume in non-targeted MTX-HSA NPs-treated mice grew rapidly and reached 250.7% of the initial tumor volume. Biotin targeted MTX-HSA NPs increased the survival of tumor-bearing mice to 47.5 ± 0.71 days and increased their life span up to 216.7%. Mice treated with biotin targeted MTX-HSA NPs showed slight body weight loss (8%) 21 days after treatment, whereas non-targeted MTX-HSA NPs treatment at the same dose caused a body weight loss of 27.05% ± 3.1%. PMID:21931482

Comparative planning evaluation of intensity-modulated radiotherapy techniques for complex lung cancer cases.

PubMed

Yartsev, Slav; Chen, Jeff; Yu, Edward; Kron, Tomas; Rodrigues, George; Coad, Terry; Trenka, Kristina; Wong, Eugene; Bauman, Glenn; Dyk, Jake Van

2006-02-01

Lung cancer treatment can be one of the most challenging fields in radiotherapy. The aim of the present study was to compare different modalities of radiation delivery based on a balanced scoring scheme for target coverage and normal tissue avoidance. Treatment plans were developed for 15 patients with stage III inoperable non-small cell lung cancer using 3D conformal technique and intensity-modulated radiotherapy (IMRT). Elective nodal irradiation was included for all cases to create the most challenging scenarios with large target volumes. A 2 cm margin was used around the gross tumour volume (GTV) to generate PTV2 and 1cm margin around elective nodes for PTV1 resulting in PTV1 volumes larger than 1000 cm(3) in 13 of the 15 patients. 3D conformal and IMRT plans were generated on a commercial treatment planning system (TheraPlan Plus, Nucletron) with various combinations of beam energies and gantry angles. A 'dose quality factor' (DQF) was introduced to correlate the plan quality with patient specific parameters. A good correlation was found between the quality of the plans and the overlap between PTV1 and lungs. The patient feature factor (PFF), which is a product of several pertinent characteristics, was introduced to facilitate the choice of a particular technique for a particular patient. This approach may allow the evaluation of different treatment options prior to actual planning, subject to validation in larger prospective data sets.

4D computed tomography scans for conformal thoracic treatment planning: is a single scan sufficient to capture thoracic tumor motion?

NASA Astrophysics Data System (ADS)

Tseng, Yolanda D.; Wootton, Landon; Nyflot, Matthew; Apisarnthanarax, Smith; Rengan, Ramesh; Bloch, Charles; Sandison, George; St. James, Sara

2018-01-01

Four dimensional computed tomography (4DCT) scans are routinely used in radiation therapy to determine the internal treatment volume for targets that are moving (e.g. lung tumors). The use of these studies has allowed clinicians to create target volumes based upon the motion of the tumor during the imaging study. The purpose of this work is to determine if a target volume based on a single 4DCT scan at simulation is sufficient to capture thoracic motion. Phantom studies were performed to determine expected differences between volumes contoured on 4DCT scans and those on the evaluation CT scans (slow scans). Evaluation CT scans acquired during treatment of 11 patients were compared to the 4DCT scans used for treatment planning. The images were assessed to determine if the target remained within the target volume determined during the first 4DCT scan. A total of 55 slow scans were compared to the 11 planning 4DCT scans. Small differences were observed in phantom between the 4DCT volumes and the slow scan volumes, with a maximum of 2.9%, that can be attributed to minor differences in contouring and the ability of the 4DCT scan to adequately capture motion at the apex and base of the motion trajectory. Larger differences were observed in the patients studied, up to a maximum volume difference of 33.4%. These results demonstrate that a single 4DCT scan is not adequate to capture all thoracic motion throughout treatment.

In vivo acoustic and photoacoustic focusing of circulating cells

NASA Astrophysics Data System (ADS)

Galanzha, Ekaterina I.; Viegas, Mark G.; Malinsky, Taras I.; Melerzanov, Alexander V.; Juratli, Mazen A.; Sarimollaoglu, Mustafa; Nedosekin, Dmitry A.; Zharov, Vladimir P.

2016-03-01

In vivo flow cytometry using vessels as natural tubes with native cell flows has revolutionized the study of rare circulating tumor cells in a complex blood background. However, the presence of many blood cells in the detection volume makes it difficult to count each cell in this volume. We introduce method for manipulation of circulating cells in vivo with the use of gradient acoustic forces induced by ultrasound and photoacoustic waves. In a murine model, we demonstrated cell trapping, redirecting and focusing in blood and lymph flow into a tight stream, noninvasive wall-free transportation of blood, and the potential for photoacoustic detection of sickle cells without labeling and of leukocytes targeted by functionalized nanoparticles. Integration of cell focusing with intravital imaging methods may provide a versatile biological tool for single-cell analysis in circulation, with a focus on in vivo needleless blood tests, and preclinical studies of human diseases in animal models.

In vivo acoustic and photoacoustic focusing of circulating cells

PubMed Central

Galanzha, Ekaterina I.; Viegas, Mark G.; Malinsky, Taras I.; Melerzanov, Alexander V.; Juratli, Mazen A.; Sarimollaoglu, Mustafa; Nedosekin, Dmitry A.; Zharov, Vladimir P.

2016-01-01

In vivo flow cytometry using vessels as natural tubes with native cell flows has revolutionized the study of rare circulating tumor cells in a complex blood background. However, the presence of many blood cells in the detection volume makes it difficult to count each cell in this volume. We introduce method for manipulation of circulating cells in vivo with the use of gradient acoustic forces induced by ultrasound and photoacoustic waves. In a murine model, we demonstrated cell trapping, redirecting and focusing in blood and lymph flow into a tight stream, noninvasive wall-free transportation of blood, and the potential for photoacoustic detection of sickle cells without labeling and of leukocytes targeted by functionalized nanoparticles. Integration of cell focusing with intravital imaging methods may provide a versatile biological tool for single-cell analysis in circulation, with a focus on in vivo needleless blood tests, and preclinical studies of human diseases in animal models. PMID:26979811

Investigation of Procedures for Automatic Resonance Extraction from Noisy Transient Electromagnetics Data. Volume III. Translation of Prony’s Original Paper and Bibliography of Prony’s Method

DTIC Science & Technology

1981-08-17

Van Blaricum, "On the Source of Parameter Bias in Prony’s Method," 1980 NEM Conference, Disneyland Hotel, August 1980. Auton, J.R., "An Unbiased...Method for the Estimation of the SEM Parameters of an Electromagnetic System," 1980 NEM Conference, Disneyland Hotel, August 1980. Auton, J.R. and M.L...34 1980 NEM Conference, Disneyland Hotel, August 5-7, 1980. Chuang, C.W. and D.L. Moffatt, "Complex Natural Responances of Radar Targets via Prony’s

Impact of Node Negative Target Volume Delineation on Contralateral Parotid Gland Dose Sparing Using IMRT in Head and Neck Cancer.

PubMed

Magnuson, William J; Urban, Erich; Bayliss, R Adam; Harari, Paul M

2015-06-01

There is considerable practice variation in treatment of the node negative (N0) contralateral neck in patients with head and neck cancer. In this study, we examined the impact of N0 neck target delineation volume on radiation dose to the contralateral parotid gland. Following institutional review board approval, 12 patients with head and neck cancer were studied. All had indications for treatment of the N0 neck, such as midline base of tongue or soft palate extension or advanced ipsilateral nodal disease. The N0 neck volumes were created using the Radiation Therapy Oncology Group head and neck contouring atlas. The physician-drawn N0 neck clinical target volume (CTV) was expanded by 25% to 200% to generate volume variation, followed by a 3-mm planning target volume (PTV) expansion. Surrounding organs at risk were contoured and complete intensity-modulated radiation therapy plans were generated for each N0 volume expansion. The median N0 target volume drawn by the radiation oncologist measured 93 cm(3) (range 71-145). Volumetric expansion of the N0 CTV by 25% to 200% increased the resultant mean dose to the contralateral parotid gland by 1.4 to 8.5 Gray (Gy). For example, a 4.1-mm increase in the N0 neck CTV translated to a 2.0-Gy dose increase to the parotid, 7.4 mm to a 4.5 Gy dose increase, and 12.5 mm to an 8.5 Gy dose increase, respectively. The treatment volume designated for the N0 neck has profound impact on resultant dose to the contralateral parotid gland. Variations of up to 15 mm are routine across physicians in target contouring, reflecting individual preference and training expertise. Depending on the availability of immobilization and image guidance techniques, experts commonly recommend 3 to 10 mm margin expansions to generate the PTV. Careful attention to the original volume of the N0 neck CTV, as well as expansion margins, is important in achieving effective contralateral gland sparing to reduce the resultant xerostomia and dysguesia that may ensue after radiotherapy. © The Author(s) 2014.

Clinical applications of 3-dimensional printing in radiation therapy.

PubMed

Zhao, Yizhou; Moran, Kathryn; Yewondwossen, Mammo; Allan, James; Clarke, Scott; Rajaraman, Murali; Wilke, Derek; Joseph, Paul; Robar, James L

2017-01-01

Three-dimensional (3D) printing is suitable for the fabrication of complex radiotherapy bolus. Although investigated from dosimetric and feasibility standpoints, there are few reports to date of its use for actual patient treatment. This study illustrates the versatile applications of 3D printing in clinical radiation oncology through a selection of patient cases, namely, to create bolus for photon and modulated electron radiotherapy (MERT), as well as applicators for surface high-dose rate (HDR) brachytherapy. Photon boluses were 3D-printed to treat a recurrent squamous cell carcinoma (SCC) of the nasal septum and a basal cell carcinoma (BCC) of the posterior pinna. For a patient with a mycosis fungoides involving the upper face, a 3D-printed MERT bolus was used. To treat an SCC of the nose, a 3D-printed applicator for surface brachytherapy was made. The structures' fit to the anatomy and the radiotherapy treatment plans were assessed. Based on the treatment planning computed tomography (CT), the size of the largest air gap at the interface of the 3D-printed structure was 3 mm for the SCC of the nasal septum, 3 mm for the BCC of the pinna, 2 mm for the mycosis fungoides of the face, and 2 mm for the SCC of the nose. Acceptable treatment plans were obtained for the SCC of the nasal septum (95% isodose to 99.8% of planning target volume [PTV]), the BCC of the pinna (95% isodose to 97.7% of PTV), and the mycosis fungoides of the face (90% isodose to 92.5% of PTV). For the latter, compared with a plan with a uniform thickness bolus, the one featuring the MERT bolus achieved relative sparing of all the organs at risk (OARs) distal to the target volume, while maintaining similar target volume coverage. The surface brachytherapy plan for the SCC of the nose had adequate coverage (95% isodose to 95.6% of clinical target volume [CTV]), but a relatively high dose to the left eye, owing to its proximity to the tumor. 3D printing can be implemented effectively in the clinical setting to create highly conformal bolus for photon and MERT, as well as applicators for surface brachytherapy. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Dosimetric Comparison between Three-Dimensional Magnetic Resonance Imaging-Guided and Conventional Two-Dimensional Point A-Based Intracavitary Brachytherapy Planning for Cervical Cancer

PubMed Central

Ren, Juan; Yuan, Wei; Wang, Ruihua; Wang, Qiuping; Li, Yi; Xue, Chaofan; Yan, Yanli; Ma, Xiaowei; Tan, Li; Liu, Zi

2016-01-01

Objective The purpose of this study was to comprehensively compare the 3-dimensional (3D) magnetic resonance imaging (MRI)-guided and conventional 2-dimensional (2D) point A-based intracavitary brachytherapy (BT) planning for cervical cancer with regard to target dose coverage and dosages to adjacent organs-at risk (OARs). Methods A total of 79 patients with cervical cancer were enrolled to receive 2D point A-based BT planning and then immediately to receive 3D planning between October 2011 and April 2013 at the First Hospital Affiliated to Xi’an Jiao Tong University (Xi’an, China). The dose-volume histogram (DVH) parameters for gross tumor volume (GTV), high-risk clinical target volume (HR-CTV), intermediate-risk clinical target volume (IR-CTV) and OARs were compared between the 2D and 3D planning. Results In small tumors, there was no significant difference in most of the DVHs between 2D and 3D planning (all p>0.05). While in big tumors, 3D BT planning significantly increased the DVHs for most of the GTV, HR-CTV and IR-CTV, and some OARs compared with 2D planning (all P<0.05). In 3D planning, DVHs for GTV, HR-CTV, IR-CTV and some OARs were significantly higher in big tumors than in small tumors (all p<0.05). In contrast, in 2D planning, DVHs for almost all of the HR-CTV and IR-CTV were significantly lower in big tumors (all p<0.05). In eccentric tumors, 3D planning significantly increased dose coverage but decreased dosages to OARs compared with 2D planning (p<0.05). In tumors invading adjacent tissues, the target dose coverage in 3D planning was generally significantly higher than in 2D planning (P<0.05); the dosages to the adjacent rectum and bladder were significantly higher but those to sigmoid colon were lower in 3D planning (all P<0.05). Conclusions 3D MRI image-guided BT planning exhibits advantages over 2D planning in a complex way, generally showing advantages for the treatment of cervical cancer except small tumors. PMID:27611853

Use of volume-targeted non-invasive bilevel positive airway pressure ventilation in a patient with amyotrophic lateral sclerosis*,**

PubMed Central

Diaz-Abad, Montserrat; Brown, John Edward

2014-01-01

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease in which most patients die of respiratory failure. Although volume-targeted non-invasive bilevel positive airway pressure (BPAP) ventilation has been studied in patients with chronic respiratory failure of various etiologies, its use in ALS has not been reported. We present the case of a 66-year-old woman with ALS and respiratory failure treated with volume-targeted BPAP ventilation for 15 weeks. Weekly data downloads showed that disease progression was associated with increased respiratory muscle weakness, decreased spontaneous breathing, and increased use of non-invasive positive pressure ventilation, whereas tidal volume and minute ventilation remained relatively constant. PMID:25210968

Combining transrectal ultrasound and CT for image-guided adaptive brachytherapy of cervical cancer: Proof of concept.

PubMed

Nesvacil, Nicole; Schmid, Maximilian P; Pötter, Richard; Kronreif, Gernot; Kirisits, Christian

To investigate the feasibility of a treatment planning workflow for three-dimensional image-guided cervix cancer brachytherapy, combining volumetric transrectal ultrasound (TRUS) for target definition with CT for dose optimization to organs at risk (OARs), for settings with no access to MRI. A workflow for TRUS/CT-based volumetric treatment planning was developed, based on a customized system including ultrasound probe, stepper unit, and software for image volume acquisition. A full TRUS/CT-based workflow was simulated in a clinical case and compared with MR- or CT-only delineation. High-risk clinical target volume was delineated on TRUS, and OARs were delineated on CT. Manually defined tandem/ring applicator positions on TRUS and CT were used as a reference for rigid registration of the image volumes. Treatment plan optimization for TRUS target and CT organ volumes was performed and compared to MRI and CT target contours. TRUS/CT-based contouring, applicator reconstruction, image fusion, and treatment planning were feasible, and the full workflow could be successfully demonstrated. The TRUS/CT plan fulfilled all clinical planning aims. Dose-volume histogram evaluation of the TRUS/CT-optimized plan (high-risk clinical target volume D 90 , OARs D 2cm³ for) on different image modalities showed good agreement between dose values reported for TRUS/CT and MRI-only reference contours and large deviations for CT-only target parameters. A TRUS/CT-based workflow for full three-dimensional image-guided cervix brachytherapy treatment planning seems feasible and may be clinically comparable to MRI-based treatment planning. Further development to solve challenges with applicator definition in the TRUS volume is required before systematic applicability of this workflow. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

On the performances of different IMRT Treatment Planning Systems for selected paediatric cases.

PubMed

Fogliata, Antonella; Nicolini, Giorgia; Alber, Markus; Asell, Mats; Clivio, Alessandro; Dobler, Barbara; Larsson, Malin; Lohr, Frank; Lorenz, Friedlieb; Muzik, Jan; Polednik, Martin; Vanetti, Eugenio; Wolff, Dirk; Wyttenbach, Rolf; Cozzi, Luca

2007-02-15

To evaluate the performance of seven different TPS (Treatment Planning Systems: Corvus, Eclipse, Hyperion, KonRad, Oncentra Masterplan, Pinnacle and PrecisePLAN) when intensity modulated (IMRT) plans are designed for paediatric tumours. Datasets (CT images and volumes of interest) of four patients were used to design IMRT plans. The tumour types were: one extraosseous, intrathoracic Ewing Sarcoma; one mediastinal Rhabdomyosarcoma; one metastatic Rhabdomyosarcoma of the anus; one Wilm's tumour of the left kidney with multiple liver metastases. Prescribed doses ranged from 18 to 54.4 Gy. To minimise variability, the same beam geometry and clinical goals were imposed on all systems for every patient. Results were analysed in terms of dose distributions and dose volume histograms. For all patients, IMRT plans lead to acceptable treatments in terms of conformal avoidance since most of the dose objectives for Organs At Risk (OARs) were met, and the Conformity Index (averaged over all TPS and patients) ranged from 1.14 to 1.58 on primary target volumes and from 1.07 to 1.37 on boost volumes. The healthy tissue involvement was measured in terms of several parameters, and the average mean dose ranged from 4.6 to 13.7 Gy. A global scoring method was developed to evaluate plans according to their degree of success in meeting dose objectives (lower scores are better than higher ones). For OARs the range of scores was between 0.75 +/- 0.15 (Eclipse) to 0.92 +/- 0.18 (Pinnacle(3) with physical optimisation). For target volumes, the score ranged from 0.05 +/- 0.05 (Pinnacle(3) with physical optimisation) to 0.16 +/- 0.07 (Corvus). A set of complex paediatric cases presented a variety of individual treatment planning challenges. Despite the large spread of results, inverse planning systems offer promising results for IMRT delivery, hence widening the treatment strategies for this very sensitive class of patients.

On the performances of different IMRT treatment planning systems for selected paediatric cases

PubMed Central

Fogliata, Antonella; Nicolini, Giorgia; Alber, Markus; Åsell, Mats; Clivio, Alessandro; Dobler, Barbara; Larsson, Malin; Lohr, Frank; Lorenz, Friedlieb; Muzik, Jan; Polednik, Martin; Vanetti, Eugenio; Wolff, Dirk; Wyttenbach, Rolf; Cozzi, Luca

2007-01-01

Background To evaluate the performance of seven different TPS (Treatment Planning Systems: Corvus, Eclipse, Hyperion, KonRad, Oncentra Masterplan, Pinnacle and PrecisePLAN) when intensity modulated (IMRT) plans are designed for paediatric tumours. Methods Datasets (CT images and volumes of interest) of four patients were used to design IMRT plans. The tumour types were: one extraosseous, intrathoracic Ewing Sarcoma; one mediastinal Rhabdomyosarcoma; one metastatic Rhabdomyosarcoma of the anus; one Wilm's tumour of the left kidney with multiple liver metastases. Prescribed doses ranged from 18 to 54.4 Gy. To minimise variability, the same beam geometry and clinical goals were imposed on all systems for every patient. Results were analysed in terms of dose distributions and dose volume histograms. Results For all patients, IMRT plans lead to acceptable treatments in terms of conformal avoidance since most of the dose objectives for Organs At Risk (OARs) were met, and the Conformity Index (averaged over all TPS and patients) ranged from 1.14 to 1.58 on primary target volumes and from 1.07 to 1.37 on boost volumes. The healthy tissue involvement was measured in terms of several parameters, and the average mean dose ranged from 4.6 to 13.7 Gy. A global scoring method was developed to evaluate plans according to their degree of success in meeting dose objectives (lower scores are better than higher ones). For OARs the range of scores was between 0.75 ± 0.15 (Eclipse) to 0.92 ± 0.18 (Pinnacle3 with physical optimisation). For target volumes, the score ranged from 0.05 ± 0.05 (Pinnacle3 with physical optimisation) to 0.16 ± 0.07 (Corvus). Conclusion A set of complex paediatric cases presented a variety of individual treatment planning challenges. Despite the large spread of results, inverse planning systems offer promising results for IMRT delivery, hence widening the treatment strategies for this very sensitive class of patients. PMID:17302972

Focal CA3 hippocampal subfield atrophy following LGI1 VGKC-complex antibody limbic encephalitis

PubMed Central

Miller, Thomas D.; Chong, Trevor T.-J.; Aimola Davies, Anne M.; Ng, Tammy W.C.; Johnson, Michael R.; Irani, Sarosh R.; Vincent, Angela; Husain, Masud; Jacob, Saiju; Maddison, Paul; Kennard, Christopher; Gowland, Penny A.

2017-01-01

Magnetic resonance imaging has linked chronic voltage-gated potassium channel (VGKC) complex antibody-mediated limbic encephalitis with generalized hippocampal atrophy. However, autoantibodies bind to specific rodent hippocampal subfields. Here, human hippocampal subfield (subiculum, cornu ammonis 1-3, and dentate gyrus) targets of immunomodulation-treated LGI1 VGKC-complex antibody-mediated limbic encephalitis were investigated using in vivo ultra-high resolution (0.39 × 0.39 × 1.0 mm3) 7.0 T magnetic resonance imaging [n = 18 patients, 17 patients (94%) positive for LGI1 antibody and one patient negative for LGI1/CASPR2 but positive for VGKC-complex antibodies, mean age: 64.0 ± 2.55 years, median 4 years post-limbic encephalitis onset; n = 18 controls]. First, hippocampal subfield quantitative morphometry indicated significant volume loss confined to bilateral CA3 [F(1,34) = 16.87, P < 0.0001], despite hyperintense signal evident in 5 of 18 patients on presentation. Second, early and later intervention (<3 versus >3 months from symptom onset) were associated with CA3 atrophy. Third, whole-brain voxel-by-voxel morphometry revealed no significant grey matter loss. Fourth, CA3 subfield atrophy was associated with severe episodic but not semantic amnesia for postmorbid autobiographical events that was predicted by variability in CA3 volume. The results raise important questions about the links with histopathology, the impact of the observed focal atrophy on other CA3-mediated reconstructive and episodic mechanisms, and the role of potential antibody-mediated pathogenicity as part of the pathophysiology cascade in humans. PMID:28369215

Numerical Modeling of Complex Targets for High-Energy- Density Experiments with Ion Beams and other Drivers

DOE PAGES

Koniges, Alice; Liu, Wangyi; Lidia, Steven; ...

2016-04-01

We explore the simulation challenges and requirements for experiments planned on facilities such as the NDCX-II ion accelerator at LBNL, currently undergoing commissioning. Hydrodynamic modeling of NDCX-II experiments include certain lower temperature effects, e.g., surface tension and target fragmentation, that are not generally present in extreme high-energy laser facility experiments, where targets are completely vaporized in an extremely short period of time. Target designs proposed for NDCX-II range from metal foils of order one micron thick (thin targets) to metallic foam targets several tens of microns thick (thick targets). These high-energy-density experiments allow for the study of fracture as wellmore » as the process of bubble and droplet formation. We incorporate these physics effects into a code called ALE-AMR that uses a combination of Arbitrary Lagrangian Eulerian hydrodynamics and Adaptive Mesh Refinement. Inclusion of certain effects becomes tricky as we must deal with non-orthogonal meshes of various levels of refinement in three dimensions. A surface tension model used for droplet dynamics is implemented in ALE-AMR using curvature calculated from volume fractions. Thick foam target experiments provide information on how ion beam induced shock waves couple into kinetic energy of fluid flow. Although NDCX-II is not fully commissioned, experiments are being conducted that explore material defect production and dynamics.« less

Laser program annual report, 1980

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coleman, L.W.; Krupke, W.F.; Strack, J.R.

1981-06-01

Volume 2 contains five sections that cover the areas of target design, target fabrication, diagnostics, and fusion experiments. Section 3 reports on target design activities, plasma theory and simulation, code development, and atomic theory. Section 4 presents the accomplishments of the Target Fabrication Group, Section 5 contains the results of our diagnostics development, and Section 6 describes advances made in the management and analysis of experimental data. Finally, Section 7 in Volume 2 reports the results of laser target experiments conducted during the year.

CT-Guided Interventions Using a Free-Hand, Optical Tracking System: Initial Clinical Experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schubert, Tilman, E-mail: TSchubert@uhbs.ch; Jacob, Augustinus L.; Pansini, Michele

2013-08-01

PurposeThe present study was designed to evaluate the geometrical accuracy and clinical applicability of a new, free-hand, CT-guided, optical navigation system.MethodsFifteen procedures in 14 consecutive patients were retrospectively analyzed. The navigation system was applied for interventional procedures on small target lesions, in cases with long needle paths, narrow access windows, or when an out-of-plane access was expected. Mean lesion volume was 27.9 ml, and mean distance to target measured was 107.5 mm. Eleven of 15 needle trajectories were planned as out-of-plane approaches regarding the axial CT plane.ResultsNinety-one percent of the biopsies were diagnostic. All therapeutic interventions were technically successful. Targetingmore » precision was high with a mean distance of the needle tip from planned target of 1.98 mm. Mean intervention time was 1:12 h. A statistically significant correlation between angular needle deviation and intervention time (p = 0.007), respiratory movement of the target (p = 0.008), and body mass index (p = 0.02) was detected. None of the evaluated parameters correlated significantly with the distance from the needle tip to the planned target.ConclusionsThe application of a navigation system for complex CT-guided procedures provided safe and effective targeting within a reasonable intervention time in our series.« less

Focusing analytes from 50 μL into 500 pL: On-chip focusing from large sample volumes using isotachophoresis.

PubMed

van Kooten, Xander F; Truman-Rosentsvit, Marianna; Kaigala, Govind V; Bercovici, Moran

2017-09-05

The use of on-chip isotachophoresis assays for diagnostic applications is often limited by the small volumes of standard microfluidic channels. Overcoming this limitation is particularly important for detection of 'discrete' biological targets (such as bacteria) at low concentrations, where the volume of processed liquid in a standard microchannel might not contain any targets. We present a novel microfluidic chip that enables ITP focusing of target analytes from initial sample volumes of 50 μL into a concentrated zone with a volume of 500 pL, corresponding to a 100,000-fold increase in mean concentration, and a 300,000-fold increase in peak concentration. We present design considerations for limiting sample dispersion in such large-volume focusing (LVF) chips and discuss the trade-off between assay time and Joule heating, which ultimately governs the scalability of LVF designs. Finally, we demonstrate a 100-fold improvement of ITP focusing performance in the LVF chip as compared to conventional microchannels, and apply this enhancement to achieve highly sensitive detection of both molecular targets (DNA, down to 10 fM) and whole bacteria (down to 100 cfu/mL).

SU-F-J-45: Sparing Normal Tissue with Ultra-High Dose Rate in Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feng, Y

Purpose: To spare normal tissue by reducing the location uncertainty of a moving target, we proposed an ultra-high dose rate system and evaluated. Methods: High energy electrons generated with a linear accelerator were injected into a storage ring to be accumulated. The number of the electrons in the ring was determined based on the prescribed radiation dose. The dose was delivered within a millisecond, when an online imaging system found that the target was in the position that was consistent with that in a treatment plan. In such a short time period, the displacement of the target was negligible. Themore » margin added to the clinical target volume (CTV) could be reduced that was evaluated by comparing of volumes between CTV and ITV in 14 cases of lung stereotactic body radiation therapy (SBRT) treatments. A design of the ultra-high dose rate system was evaluated based clinical needs and the recent developments of low energy (a few MeV) electron storage ring. Results: This design of ultra-high dose rate system was feasible based on the techniques currently available. The reduction of a target volume was significant by reducing the margin that accounted the motion of the target. ∼50% volume reduction of the internal target volume (ITV) could be achieved in lung SBRT treatments. Conclusion: With this innovation of ultra-high dose rate system, the margin of target is able to be significantly reduced. It will reduce treatment time of gating and allow precisely specified gating window to improve the accuracy of dose delivering.« less

Predictors of pneumothorax following endoscopic valve therapy in patients with severe emphysema.

PubMed

Gompelmann, Daniela; Lim, Hyun-Ju; Eberhardt, Ralf; Gerovasili, Vasiliki; Herth, Felix Jf; Heussel, Claus Peter; Eichinger, Monika

2016-01-01

Endoscopic valve implantation is an effective treatment for patients with advanced emphysema. Despite the minimally invasive procedure, valve placement is associated with risks, the most common of which is pneumothorax. This study was designed to identify predictors of pneumothorax following endoscopic valve implantation. Preinterventional clinical measures (vital capacity, forced expiratory volume in 1 second, residual volume, total lung capacity, 6-minute walk test), qualitative computed tomography (CT) parameters (fissure integrity, blebs/bulla, subpleural nodules, pleural adhesions, partial atelectasis, fibrotic bands, emphysema type) and quantitative CT parameters (volume and low attenuation volume of the target lobe and the ipsilateral untreated lobe, target air trapping, ipsilateral lobe volume/hemithorax volume, collapsibility of the target lobe and the ipsilateral untreated lobe) were retrospectively evaluated in patients who underwent endoscopic valve placement (n=129). Regression analysis was performed to compare those who developed pneumothorax following valve therapy (n=46) with those who developed target lobe volume reduction without pneumothorax (n=83). Low attenuation volume% of ipsilateral untreated lobe (odds ratio [OR] =1.08, P=0.001), ipsilateral untreated lobe volume/hemithorax volume (OR =0.93, P=0.017), emphysema type (OR =0.26, P=0.018), pleural adhesions (OR =0.33, P=0.012) and residual volume (OR =1.58, P=0.012) were found to be significant predictors of pneumothorax. Fissure integrity (OR =1.16, P=0.075) and 6-minute walk test (OR =1.05, P=0.077) were also indicative of pneumothorax. The model including the aforementioned parameters predicted whether a patient would experience a pneumothorax 84% of the time (area under the curve =0.84). Clinical and CT parameters provide a promising tool to effectively identify patients at high risk of pneumothorax following endoscopic valve therapy.

Predictors of pneumothorax following endoscopic valve therapy in patients with severe emphysema

PubMed Central

Gompelmann, Daniela; Lim, Hyun-ju; Eberhardt, Ralf; Gerovasili, Vasiliki; Herth, Felix JF; Heussel, Claus Peter; Eichinger, Monika

2016-01-01

Background Endoscopic valve implantation is an effective treatment for patients with advanced emphysema. Despite the minimally invasive procedure, valve placement is associated with risks, the most common of which is pneumothorax. This study was designed to identify predictors of pneumothorax following endoscopic valve implantation. Methods Preinterventional clinical measures (vital capacity, forced expiratory volume in 1 second, residual volume, total lung capacity, 6-minute walk test), qualitative computed tomography (CT) parameters (fissure integrity, blebs/bulla, subpleural nodules, pleural adhesions, partial atelectasis, fibrotic bands, emphysema type) and quantitative CT parameters (volume and low attenuation volume of the target lobe and the ipsilateral untreated lobe, target air trapping, ipsilateral lobe volume/hemithorax volume, collapsibility of the target lobe and the ipsilateral untreated lobe) were retrospectively evaluated in patients who underwent endoscopic valve placement (n=129). Regression analysis was performed to compare those who developed pneumothorax following valve therapy (n=46) with those who developed target lobe volume reduction without pneumothorax (n=83). Finding Low attenuation volume% of ipsilateral untreated lobe (odds ratio [OR] =1.08, P=0.001), ipsilateral untreated lobe volume/hemithorax volume (OR =0.93, P=0.017), emphysema type (OR =0.26, P=0.018), pleural adhesions (OR =0.33, P=0.012) and residual volume (OR =1.58, P=0.012) were found to be significant predictors of pneumothorax. Fissure integrity (OR =1.16, P=0.075) and 6-minute walk test (OR =1.05, P=0.077) were also indicative of pneumothorax. The model including the aforementioned parameters predicted whether a patient would experience a pneumothorax 84% of the time (area under the curve =0.84). Interpretation Clinical and CT parameters provide a promising tool to effectively identify patients at high risk of pneumothorax following endoscopic valve therapy. PMID:27536088

Consequences of anorectal cancer atlas implementation in the cooperative group setting: radiobiologic analysis of a prospective randomized in silico target delineation study.

PubMed

Mavroidis, Panayiotis; Giantsoudis, Drosoula; Awan, Musaddiq J; Nijkamp, Jasper; Rasch, Coen R N; Duppen, Joop C; Thomas, Charles R; Okunieff, Paul; Jones, William E; Kachnic, Lisa A; Papanikolaou, Niko; Fuller, Clifton D

2014-09-01

The aim of this study is to ascertain the subsequent radiobiological impact of using a consensus guideline target volume delineation atlas. Using a representative case and target volume delineation instructions derived from a proposed IMRT rectal cancer clinical trial, gross tumor volume (GTV) and clinical/planning target volumes (CTV/PTV) were contoured by 13 physician observers (Phase 1). The observers were then randomly assigned to follow (atlas) or not-follow (control) a consensus guideline/atlas for anorectal cancers, and instructed to re-contour the same case (Phase 2). The atlas group was found to have increased tumor control probability (TCP) after the atlas intervention for both the CTV (p<0.0001) and PTV1 (p=0.0011) with decreasing normal tissue complication probability (NTCP) for small intestine, while the control group did not. Additionally, the atlas group had reduced variance in TCP for all target volumes and reduced variance in NTCP for the bowel. In Phase 2, the atlas group had increased TCP relative to the control for CTV (p=0.03). Visual atlas and consensus treatment guideline usage in the development of rectal cancer IMRT treatment plans reduced the inter-observer radiobiological variation, with clinically relevant TCP alteration for CTV and PTV volumes. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Radiation therapy for breast cancer: Literature review

DOE Office of Scientific and Technical Information (OSTI.GOV)

Balaji, Karunakaran, E-mail: karthik.balaji85@gmail.com; School of Advanced Sciences, VIT University, Vellore; Subramanian, Balaji

Concave shape with variable size target volume makes treatment planning for the breast/chest wall a challenge. Conventional techniques used for the breast/chest wall cancer treatment provided better sparing of organs at risk (OARs), with poor conformity and uniformity to the target volume. Advanced technologies such as intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) improve the target coverage at the cost of higher low dose volumes to OARs. Novel hybrid techniques present promising results in breast/chest wall irradiation in terms of target coverage as well as OARs sparing. Several published data compared these technologies for the benefit ofmore » the breast/chest wall with or without nodal volumes. The aim of this article is to review relevant data and identify the scope for further research in developing optimal treatment plan for breast/chest wall cancer treatment.« less

Mobilization of Cd from human serum albumin by small molecular weight thiols.

PubMed

Morris, Thomas T; Keir, Jennifer L A; Boshart, Steven J; Lobanov, Victor P; Ruhland, Anthony M A; Bahl, Nishita; Gailer, Jürgen

2014-05-01

Although the toxic metal Cd is an established human nephrotoxin, little is known about the role that interactions with plasma constitutents play in determining its mammalian target organs. To gain insight, a Cd-human serum albumin (HSA) complex was analyzed on a system consisting of size exclusion chromatography (SEC) coupled on-line to a flame atomic absorption spectrometer (FAAS). Using phosphate buffered saline (pH 7.4) as the mobile phase, we investigated the effect of 1-10mM oxidized glutathione (GSSG), l-cysteine (Cys), l-glutathione (GSH), or N-acetyl-l-cysteine (NAC) on the elution of Cd. As expected, GSSG did not mobilize Cd from the Cd-HSA complex up to a concentration of 4mM. With 1.0mM NAC, ∼30% of the injected Cd-HSA complex eluted as such, while the mobilized Cd was lost on the column. With 1.0mM of Cys or GSH, no parent Cd-HSA complex was detected and 88% and 82% of the protein bound Cd eluted close to the elution volume, likely in form of Cd(Cys)2 and a Cd-GSH 1:1 complex. Interestingly, with GSH and NAC concentrations >4.0mM, a Cd double peak was detected, which was rationalized in terms of the elution of a polynuclear Cd complex baseline-separated from a mononuclear Cd complex. In contrast, mobile phases which contained Cys concentrations ≥2mM resulted in the detection of only a single Cd peak, probably Cd(Cys)4. Our results establish SEC-FAAS as a viable tool to probe the mobilization of Cd from binding sites on plasma proteins at near physiological conditions. The detected complexes between Cd and Cys or GSH may be involved in the translocation of Cd to mammalian target organs. Copyright © 2014 Elsevier B.V. All rights reserved.

Maximal volume behind horizons without curvature singularity

NASA Astrophysics Data System (ADS)

Wang, Shao-Jun; Guo, Xin-Xuan; Wang, Towe

2018-01-01

The black hole information paradox is related to the area of event horizon, and potentially to the volume and singularity behind it. One example is the complexity/volume duality conjectured by Stanford and Susskind. Accepting the proposal of Christodoulou and Rovelli, we calculate the maximal volume inside regular black holes, which are free of curvature singularity, in asymptotically flat and anti-de Sitter spacetimes respectively. The complexity/volume duality is then applied to anti-de Sitter regular black holes. We also present an analytical expression for the maximal volume outside the de Sitter horizon.

[Cone-beam CT evaluation of nasomaxillary complex and upper airway following rapid maxillary expansion].

PubMed

Li, Lei; Qi, Suqing; Wang, Hongwei; Ren, Sufeng; Ban, Jiandong

2015-07-01

To evaluate the naso-maxillary complex width and pharyngeal airway volume changes after rapid maxillary expansion (RME). Thirty-five patients were selected (18 males, 17 females, mean age, 12.1 ± 1.1 years). All patients underwent orthodontic treatment with Hyrax palatal expanders. Cone-beam CT (CBCT) scan was taken before treatment (T0), 16 days (T1) and three months (T3) after RME. Naso-maxillary complex width and pharyngeal airway volume were measured. After treatment the width of piriform aperture and maxillary width were significantly increased compared with that before treatment (P < 0.05). Three months after RME, no statistical difference was found in maxillary width compared with that before treatment. The nasopharyngeal volume significantly increased by 29.9% compared with that before treatment (P < 0.05), and the volume remained relatively stable after three months. RME resulted in a significant increase in the naso-maxillary complex width and nasopharyngeal volume.

Prospective feasibility trial of radiotherapy target definition for head and neck cancer using 3-dimensional PET and CT imaging.

PubMed

Scarfone, Christopher; Lavely, William C; Cmelak, Anthony J; Delbeke, Dominique; Martin, William H; Billheimer, Dean; Hallahan, Dennis E

2004-04-01

The aim of this investigation was to evaluate the influence and accuracy of (18)F-FDG PET in target volume definition as a complementary modality to CT for patients with head and neck cancer (HNC) using dedicated PET and CT scanners. Six HNC patients were custom fitted with head and neck and upper body immobilization devices, and conventional radiotherapy CT simulation was performed together with (18)F-FDG PET imaging. Gross target volume (GTV) and pathologic nodal volumes were first defined in the conventional manner based on CT. A segmentation and surface-rendering registration technique was then used to coregister the (18)F-FDG PET and CT planning image datasets. (18)F-FDG PET GTVs were determined and displayed simultaneously with the CT contours. CT GTVs were then modified based on the PET data to form final PET/CT treatment volumes. Five-field intensity-modulated radiation therapy (IMRT) was then used to demonstrate dose targeting to the CT GTV or the PET/CT GTV. One patient was PET-negative after induction chemotherapy. The CT GTV was modified in all remaining patients based on (18)F-FDG PET data. The resulting PET/CT GTV was larger than the original CT volume by an average of 15%. In 5 cases, (18)F-FDG PET identified active lymph nodes that corresponded to lymph nodes contoured on CT. The pathologically enlarged CT lymph nodes were modified to create final lymph node volumes in 3 of 5 cases. In 1 of 6 patients, (18)F-FDG-avid lymph nodes were not identified as pathologic on CT. In 2 of 6 patients, registration of the independently acquired PET and CT data using segmentation and surface rendering resulted in a suboptimal alignment and, therefore, had to be repeated. Radiotherapy planning using IMRT demonstrated the capability of this technique to target anatomic or anatomic/physiologic target volumes. In this manner, metabolically active sites can be intensified to greater daily doses. Inclusion of (18)F-FDG PET data resulted in modified target volumes in radiotherapy planning for HNC. PET and CT data acquired on separate, dedicated scanners may be coregistered for therapy planning; however, dual-acquisition PET/CT systems may be considered to reduce the need for reregistrations. It is possible to use IMRT to target dose to metabolically active sites based on coregistered PET/CT data.

Visual search and segregation as a function of display complexity.

PubMed

Scharroo, J; Stalmeier, P F; Boselie, F

1994-01-01

Complexity is proposed as an important psychological factor in search and segregation tasks. Displays were presented with target and nontarget areas that were each built up of one type of randomly rotated micropatterns. We manipulated experimentally (a) the complexity of the target elements, as measured by Garner's (1970) invariance criterion; (b) the complexity of the target region; (c) the complexity of the nontargets; and (d) the number of elements within a target region. The main result is that detectability increases when the within-region complexity of the target and the nontarget regions decreases. Furthermore, interactions between the target and nontarget areas affect detectability too: We found that search asymmetry is produced by the asymmetrical effect of complexity when target and nontarget areas are interchanged.

Mitochondrial impairment contributes to cocaine-induced cardiac dysfunction: Prevention by the targeted antioxidant MitoQ.

PubMed

Vergeade, Aurélia; Mulder, Paul; Vendeville-Dehaudt, Cathy; Estour, François; Fortin, Dominique; Ventura-Clapier, Renée; Thuillez, Christian; Monteil, Christelle

2010-09-01

The goal of this study was to assess mitochondrial function and ROS production in an experimental model of cocaine-induced cardiac dysfunction. We hypothesized that cocaine abuse may lead to altered mitochondrial function that in turn may cause left ventricular dysfunction. Seven days of cocaine administration to rats led to an increased oxygen consumption detected in cardiac fibers, specifically through complex I and complex III. ROS levels were increased, specifically in interfibrillar mitochondria. In parallel there was a decrease in ATP synthesis, whereas no difference was observed in subsarcolemmal mitochondria. This uncoupling effect on oxidative phosphorylation was not detectable after short-term exposure to cocaine, suggesting that these mitochondrial abnormalities were a late rather than a primary event in the pathological response to cocaine. MitoQ, a mitochondrial-targeted antioxidant, was shown to completely prevent these mitochondrial abnormalities as well as cardiac dysfunction characterized here by a diastolic dysfunction studied with a conductance catheter to obtain pressure-volume data. Taken together, these results extend previous studies and demonstrate that cocaine-induced cardiac dysfunction may be due to a mitochondrial defect. Copyright 2010 Elsevier Inc. All rights reserved.

Intracranial stereotactic radiosurgery with an adapted linear accelerator vs. robotic radiosurgery: Comparison of dosimetric treatment plan quality.

PubMed

Treuer, Harald; Hoevels, Moritz; Luyken, Klaus; Visser-Vandewalle, Veerle; Wirths, Jochen; Kocher, Martin; Ruge, Maximilian

2015-06-01

Stereotactic radiosurgery with an adapted linear accelerator (linac-SRS) is an established therapy option for brain metastases, benign brain tumors, and arteriovenous malformations. We intended to investigate whether the dosimetric quality of treatment plans achieved with a CyberKnife (CK) is at least equivalent to that for linac-SRS with circular or micromultileaf collimators (microMLC). A random sample of 16 patients with 23 target volumes, previously treated with linac-SRS, was replanned with CK. Planning constraints were identical dose prescription and clinical applicability. In all cases uniform optimization scripts and inverse planning objectives were used. Plans were compared with respect to coverage, minimal dose within target volume, conformity index, and volume of brain tissue irradiated with ≥ 10 Gy. Generating the CK plan was unproblematic with simple optimization scripts in all cases. With the CK plans, coverage, minimal target volume dosage, and conformity index were significantly better, while no significant improvement could be shown regarding the 10 Gy volume. Multiobjective comparison for the irradiated target volumes was superior in the CK plan in 20 out of 23 cases and equivalent in 3 out of 23 cases. Multiobjective comparison for the treated patients was superior in the CK plan in all 16 cases. The results clearly demonstrate the superiority of the irradiation plan for CK compared to classical linac-SRS with circular collimators and microMLC. In particular, the average minimal target volume dose per patient, increased by 1.9 Gy, and at the same time a 14% better conformation index seems to be an improvement with clinical relevance.

Melt production in large-scale impact events: Implications and observations at terrestrial craters

NASA Technical Reports Server (NTRS)

Grieve, Richard A. F.; Cintala, Mark J.

1992-01-01

The volume of impact melt relative to the volume of the transient cavity increases with the size of the impact event. Here, we use the impact of chondrite into granite at 15, 25, and 50 km s(sup -1) to model impact-melt volumes at terrestrial craters in crystalline targets and explore the implications for terrestrial craters. Figures are presented that illustrate the relationships between melt volume and final crater diameter D(sub R) for observed terrestrial craters in crystalline targets; also included are model curves for the three different impact velocities. One implication of the increase in melt volumes with increasing crater size is that the depth of melting will also increase. This requires that shock effects occurring at the base of the cavity in simple craters and in the uplifted peaks of central structures at complex craters record progressively higher pressures with increasing crater size, up to a maximum of partial melting (approx. 45 GPa). Higher pressures cannot be recorded in the parautochthonous rocks of the cavity floor as they will be represented by impact melt, which will not remain in place. We have estimated maximum recorded pressures from a review of the literature, using such observations as planar features in quartz and feldspar, diaplectic glasses of feldspar and quartz, and partial fusion and vesiculation, as calibrated with estimates of the pressures required for their formation. Erosion complicates the picture by removing the surficial (most highly shocked) rocks in uplifted structures, thereby reducing the maximum shock pressures observed. In addition, the range of pressures that can be recorded is limited. Nevertheless, the data define a trend to higher recorded pressures with crater diameter, which is consistent with the implications of the model. A second implication is that, as the limit of melting intersects the base of the cavity, central topographic peaks will be modified in appearance and ultimately will not occur. That is, the peak will first develop a central depression, due to the flow of low-strength melted materials, when the melt volume begins to intersect the transient-cavity base.

Hippocampal volume and sensitivity to maternal aggressive behavior: a prospective study of adolescent depressive symptoms.

PubMed

Whittle, Sarah; Yap, Marie B H; Sheeber, Lisa; Dudgeon, Paul; Yücel, Murat; Pantelis, Christos; Simmons, Julian G; Allen, Nicholas B

2011-02-01

It has been suggested that biological factors confer increased sensitivity to environmental influences on depressive symptoms during adolescence, a crucial time for the onset of depressive disorders. Given the critical role of the hippocampus in sensitivity to stress and processing of contextual aspects of the environment, investigation of its role in determining sensitivity to environmental context seems warranted. This study prospectively examined hippocampal volume as a measure of sensitivity to the influence of aggressive maternal behavior on change in depressive symptoms from early to midadolescence. The interaction between aggressive maternal behavior and hippocampal volume was found to predict change in depressive symptoms. Significant sex differences also emerged, whereby only for girls were larger bilateral hippocampal volumes more sensitive to the effects of maternal aggressive behavior, particularly with respect to experiencing the protective effects of low levels of maternal aggressiveness. These findings help elucidate the complex relationships between brain structure, environmental factors such as maternal parenting style, and sensitivity to (i.e., risk for, and protection from) the emergence of depression during this life stage. Given that family context risk factors are modifiable, our findings suggest the potential utility of targeted parenting interventions for the prevention and treatment of adolescent depressive disorder.

SU-F-P-64: The Impact of Plan Complexity Parameters On the Plan Quality and Deliverability of Volumetric Modulated Arc Therapy with Canonical Correlation Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jin, X; Yi, J; Xie, C

Purpose: To evaluate the impact of complexity indices on the plan quality and deliverability of volumetric modulated arc therapy (VMAT), and to determine the most significant parameters in the generation of an ideal VMAT plan. Methods: A multi-dimensional exploratory statistical method, canonical correlation analysis (CCA) was adopted to study the correlations between VMAT parameters of complexity, quality and deliverability, as well as their contribution weights with 32 two-arc VMAT nasopharyngeal cancer (NPC) patients and 31 one-arc VMAT prostate cancer patients. Results: The MU per arc (MU/Arc) and MU per control point (MU/CP) of NPC were 337.8±25.2 and 3.7±0.3, respectively, whichmore » were significantly lower than those of prostate cancer patients (MU/Arc : 506.9±95.4, MU/CP : 5.6±1.1). The plan complexity indices indicated that two-arc VMAT plans were more complex than one-arc VMAT plans. Plan quality comparison confirmed that one-arc VMAT plans had a high quality than two-arc VMAT plans. CCA results implied that plan complexity parameters were highly correlated with plan quality with the first two canonical correlations of 0.96, 0.88 (both p<0.001) and significantly correlated with deliverability with the first canonical correlation of 0.79 (p<0.001), plan quality and deliverability was also correlated with the first canonical correlation of 0.71 (p=0.02). Complexity parameters of MU/CP, segment area (SA) per CP, percent of MU/CP less 3 and planning target volume (PTV) were weighted heavily in correlation with plan quality and deliveability . Similar results obtained from individual NPC and prostate CCA analysis. Conclusion: Relationship between complexity, quality, and deliverability parameters were investigated with CCA. MU, SA related parameters and PTV volume were found to have strong effect on the plan quality and deliverability. The presented correlation among different quantified parameters could be used to improve the plan quality and the efficiency of the radiotherapy process when creating a complex VMAT plan.« less

Functional Requirements of a Target Description System for Vulnerability Analysis

DTIC Science & Technology

1979-11-01

called GIFT .1,2 Together the COMGEOM description model and GIFT codes make up the BRL’s target description system. The significance of a target...and modifying target descriptions are described. 1 Lawrence W. Bain, Jr. and Mathew J. Reisinger, "The GIFT Code User Manual; Volume 1...34The GIFT Code User Manual; Volume II, The Output Options," unpublished draft of BRL report. II. UNDERLYING PHILOSOPHY The BRL has a computer

Generation of Parametric Equivalent-Area Targets for Design of Low-Boom Supersonic Concepts

NASA Technical Reports Server (NTRS)

Li, Wu; Shields, Elwood

2011-01-01

A tool with an Excel visual interface is developed to generate equivalent-area (A(sub e)) targets that satisfy the volume constraints for a low-boom supersonic configuration. The new parametric Ae target explorer allows users to interactively study the tradeoffs between the aircraft volume constraints and the low-boom characteristics (e.g., loudness) of the ground signature. Moreover, numerical optimization can be used to generate the optimal A(sub e) target for given A(sub e) volume constraints. A case study is used to demonstrate how a generated low-boom Ae target can be matched by a supersonic configuration that includes a fuselage, wing, nacelle, pylon, aft pod, horizontal tail, and vertical tail. The low-boom configuration is verified by sonic-boom analysis with an off-body pressure distribution at three body lengths below the configuration

3D flexible alignment using 2D maximum common substructure: dependence of prediction accuracy on target-reference chemical similarity.

PubMed

Kawabata, Takeshi; Nakamura, Haruki

2014-07-28

A protein-bound conformation of a target molecule can be predicted by aligning the target molecule on the reference molecule obtained from the 3D structure of the compound-protein complex. This strategy is called "similarity-based docking". For this purpose, we develop the flexible alignment program fkcombu, which aligns the target molecule based on atomic correspondences with the reference molecule. The correspondences are obtained by the maximum common substructure (MCS) of 2D chemical structures, using our program kcombu. The prediction performance was evaluated using many target-reference pairs of superimposed ligand 3D structures on the same protein in the PDB, with different ranges of chemical similarity. The details of atomic correspondence largely affected the prediction success. We found that topologically constrained disconnected MCS (TD-MCS) with the simple element-based atomic classification provides the best prediction. The crashing potential energy with the receptor protein improved the performance. We also found that the RMSD between the predicted and correct target conformations significantly correlates with the chemical similarities between target-reference molecules. Generally speaking, if the reference and target compounds have more than 70% chemical similarity, then the average RMSD of 3D conformations is <2.0 Å. We compared the performance with a rigid-body molecular alignment program based on volume-overlap scores (ShaEP). Our MCS-based flexible alignment program performed better than the rigid-body alignment program, especially when the target and reference molecules were sufficiently similar.

Analysis of radiation exposure for naval units of Operation Crossroads. Volume 2. (Appendix A) target ships. Technical report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weitz, R.; Thomas, C.; Klemm, J.

1982-03-03

External radiation doses are reconstructed for crews of support and target ships of Joint Task Force One at Operation CROSSROADS, 1946. Volume I describes the reconstruction methodology, which consists of modeling the radiation environment, to include the radioactivity of lagoon water, target ships, and support ship contamination; retracing ship paths through this environment; and calculating the doses to shipboard personnel. The USS RECLAIMER, a support ship, is selected as a representative ship to demonstrate this methodology. Doses for all other ships are summarized. Volume II (Appendix A) details the results for target ship personnel. Volume III (Appendix B) details themore » results for support ship personnel. Calculated doses for more than 36,000 personnel aboard support ships while at Bikini range from zero to 1.7 rem. Of those, approximately 34,000 are less than 0.5 rem. From the models provided, doses due to target ship reboarding and doses accrued after departure from Bikini can be calculated, based on the individual circumstances of exposure.« less

Pretreatment Predictors of Adverse Radiation Effects After Radiosurgery for Arteriovenous Malformation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hayhurst, Caroline; Monsalves, Eric; Prooijen, Monique van

Purpose: To identify vascular and dosimetric predictors of symptomatic T2 signal change and adverse radiation effects after radiosurgery for arteriovenous malformation, in order to define and validate preexisting risk models. Methods and Materials: A total of 125 patients with arteriovenous malformations (AVM) were treated at our institution between 2005 and 2009. Eighty-five patients have at least 12 months of clinical and radiological follow-up. Any new-onset headaches, new or worsening seizures, or neurological deficit were considered adverse events. Follow-up magnetic resonance images were assessed for new onset T2 signal change and the volume calculated. Pretreatment characteristics and dosimetric variables were analyzedmore » to identify predictors of adverse radiation effects. Results: There were 19 children and 66 adults in the study cohort, with a mean age of 34 (range 6-74). Twenty-three (27%) patients suffered adverse radiation effects (ARE), 9 patients with permanent neurological deficit (10.6%). Of these, 5 developed fixed visual field deficits. Target volume and 12 Gy volume were the most significant predictors of adverse radiation effects on univariate analysis (p < 0.001). Location and cortical eloquence were not significantly associated with the development of adverse events (p = 0.12). No additional vascular parameters were identified as predictive of ARE. There was a significant target volume threshold of 4 cm{sup 3}, above which the rate of ARE increased dramatically. Multivariate analysis target volume and the absence of prior hemorrhage are the only significant predictors of ARE. The volume of T2 signal change correlates to ARE, but only target volume is predictive of a higher volume of T2 signal change. Conclusions: Target volume and the absence of prior hemorrhage is the most accurate predictor of adverse radiation effects and complications after radiosurgery for AVMs. A high percentage of permanent visual field defects in this series suggest the optic radiation is a critical radiosensitive structure.« less

Regional Differences in Brain Volume Predict the Acquisition of Skill in a Complex Real-Time Strategy Videogame

PubMed Central

Basak, Chandramallika; Voss, Michelle W.; Erickson, Kirk I.; Boot, Walter R.; Kramer, Arthur F.

2015-01-01

Previous studies have found that differences in brain volume among older adults predict performance in laboratory tasks of executive control, memory, and motor learning. In the present study we asked whether regional differences in brain volume as assessed by the application of a voxel-based morphometry technique on high resolution MRI would also be useful in predicting the acquisition of skill in complex tasks, such as strategy-based video games. Twenty older adults were trained for over 20 hours to play Rise of Nations, a complex real-time strategy game. These adults showed substantial improvements over the training period in game performance. MRI scans obtained prior to training revealed that the volume of a number of brain regions, which have been previously associated with subsets of the trained skills, predicted a substantial amount of variance in learning on the complex game. Thus, regional differences in brain volume can predict learning in complex tasks that entail the use of a variety of perceptual, cognitive and motor processes. PMID:21546146

Regional differences in brain volume predict the acquisition of skill in a complex real-time strategy videogame.

PubMed

Basak, Chandramallika; Voss, Michelle W; Erickson, Kirk I; Boot, Walter R; Kramer, Arthur F

2011-08-01

Previous studies have found that differences in brain volume among older adults predict performance in laboratory tasks of executive control, memory, and motor learning. In the present study we asked whether regional differences in brain volume as assessed by the application of a voxel-based morphometry technique on high resolution MRI would also be useful in predicting the acquisition of skill in complex tasks, such as strategy-based video games. Twenty older adults were trained for over 20 h to play Rise of Nations, a complex real-time strategy game. These adults showed substantial improvements over the training period in game performance. MRI scans obtained prior to training revealed that the volume of a number of brain regions, which have been previously associated with subsets of the trained skills, predicted a substantial amount of variance in learning on the complex game. Thus, regional differences in brain volume can predict learning in complex tasks that entail the use of a variety of perceptual, cognitive and motor processes. Copyright © 2011 Elsevier Inc. All rights reserved.

Gpu Implementation of a Viscous Flow Solver on Unstructured Grids

NASA Astrophysics Data System (ADS)

Xu, Tianhao; Chen, Long

2016-06-01

Graphics processing units have gained popularities in scientific computing over past several years due to their outstanding parallel computing capability. Computational fluid dynamics applications involve large amounts of calculations, therefore a latest GPU card is preferable of which the peak computing performance and memory bandwidth are much better than a contemporary high-end CPU. We herein focus on the detailed implementation of our GPU targeting Reynolds-averaged Navier-Stokes equations solver based on finite-volume method. The solver employs a vertex-centered scheme on unstructured grids for the sake of being capable of handling complex topologies. Multiple optimizations are carried out to improve the memory accessing performance and kernel utilization. Both steady and unsteady flow simulation cases are carried out using explicit Runge-Kutta scheme. The solver with GPU acceleration in this paper is demonstrated to have competitive advantages over the CPU targeting one.

IFSA: a microfluidic chip-platform for frit-based immunoassay protocols

NASA Astrophysics Data System (ADS)

Hlawatsch, Nadine; Bangert, Michael; Miethe, Peter; Becker, Holger; Gärtner, Claudia

2013-03-01

Point-of-care diagnostics (POC) is one of the key application fields for lab-on-a-chip devices. While in recent years much of the work has concentrated on integrating complex molecular diagnostic assays onto a microfluidic device, there is a need to also put comparatively simple immunoassay-type protocols on a microfluidic platform. In this paper, we present the development of a microfluidic cartridge using an immunofiltration approach. In this method, the sandwich immunoassay takes place in a porous frit on which the antibodies have immobilized. The device is designed to be able to handle three samples in parallel and up to four analytical targets per sample. In order to meet the critical cost targets for the diagnostic market, the microfluidic chip has been designed and manufactured using high-volume manufacturing technologies in mind. Validation experiments show comparable sensitivities in comparison with conventional immunofiltration kits.

Beyond Extreme Ultra Violet (BEUV) Radiation from Spherically symmetrical High-Z plasmas

NASA Astrophysics Data System (ADS)

Yoshida, Kensuke; Fujioka, Shinsuke; Higashiguchi, Takeshi; Ugomori, Teruyuki; Tanaka, Nozomi; Kawasaki, Masato; Suzuki, Yuhei; Suzuki, Chihiro; Tomita, Kentaro; Hirose, Ryouichi; Eshima, Takeo; Ohashi, Hayato; Nishikino, Masaharu; Scally, Enda; Nshimura, Hiroaki; Azechi, Hiroshi; O'Sullivan, Gerard

2016-03-01

Photo-lithography is a key technology for volume manufacture of high performance and compact semiconductor devices. Smaller and more complex structures can be fabricated by using shorter wavelength light in the photolithography. One of the most critical issues in development of the next generation photo-lithography is to increase energy conversion efficiency (CE) from laser to shorter wavelength light. Experimental database of beyond extreme ultraviolet (BEUV) radiation was obtained by using spherically symmetrical high-Z plasmas generated with spherically allocated laser beams. Absolute energy and spectra of BEUV light emitted from Tb, Gd, and Mo plasmas were measured with a absolutely calibrated BEUV calorimeter and a transmission grating spectrometer. 1.0 x 1012 W/cm2 is the optimal laser intensity to produced efficient BEUV light source plasmas with Tb and Gd targets. Maximum CE is achieved at 0.8% that is two times higher than the published CEs obtained with planar targets.

Single gene-based distinction of individual microbial genomes from a mixed population of microbial cells.

PubMed

Tamminen, Manu V; Virta, Marko P J

2015-01-01

Recent progress in environmental microbiology has revealed vast populations of microbes in any given habitat that cannot be detected by conventional culturing strategies. The use of sensitive genetic detection methods such as CARD-FISH and in situ PCR have been limited by the cell wall permeabilization requirement that cannot be performed similarly on all cell types without lysing some and leaving some nonpermeabilized. Furthermore, the detection of low copy targets such as genes present in single copies in the microbial genomes, has remained problematic. We describe an emulsion-based procedure to trap individual microbial cells into picoliter-volume polyacrylamide droplets that provide a rigid support for genetic material and therefore allow complete degradation of cellular material to expose the individual genomes. The polyacrylamide droplets are subsequently converted into picoliter-scale reactors for genome amplification. The amplified genomes are labeled based on the presence of a target gene and differentiated from those that do not contain the gene by flow cytometry. Using the Escherichia coli strains XL1 and MC1061, which differ with respect to the presence (XL1), or absence (MC1061) of a single copy of a tetracycline resistance gene per genome, we demonstrate that XL1 genomes present at 0.1% of MC1061 genomes can be differentiated using this method. Using a spiked sediment microbial sample, we demonstrate that the method is applicable to highly complex environmental microbial communities as a target gene-based screen for individual microbes. The method provides a novel tool for enumerating functional cell populations in complex microbial communities. We envision that the method could be optimized for fluorescence-activated cell sorting to enrich genetic material of interest from complex environmental samples.

Quantitative analysis of treatment process time and throughput capacity for spot scanning proton therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suzuki, Kazumichi, E-mail: kazumichisuzuki@gmail.c

Purpose: To determine the patient throughput and the overall efficiency of the spot scanning system by analyzing treatment time, equipment availability, and maximum daily capacity for the current spot scanning port at Proton Therapy Center Houston and to assess the daily throughput capacity for a hypothetical spot scanning proton therapy center. Methods: At their proton therapy center, the authors have been recording in an electronic medical record system all treatment data, including disease site, number of fields, number of fractions, delivered dose, energy, range, number of spots, and number of layers for every treatment field. The authors analyzed delivery systemmore » downtimes that had been recorded for every equipment failure and associated incidents. These data were used to evaluate the patient census, patient distribution as a function of the number of fields and total target volume, and equipment clinical availability. The duration of each treatment session from patient walk-in to patient walk-out of the spot scanning treatment room was measured for 64 patients with head and neck, central nervous system, thoracic, and genitourinary cancers. The authors retrieved data for total target volume and the numbers of layers and spots for all fields from treatment plans for a total of 271 patients (including the above 64 patients). A sensitivity analysis of daily throughput capacity was performed by varying seven parameters in a throughput capacity model. Results: The mean monthly equipment clinical availability for the spot scanning port in April 2012–March 2015 was 98.5%. Approximately 1500 patients had received spot scanning proton therapy as of March 2015. The major disease sites treated in September 2012–August 2014 were the genitourinary system (34%), head and neck (30%), central nervous system (21%), and thorax (14%), with other sites accounting for the remaining 1%. Spot scanning beam delivery time increased with total target volume and accounted for approximately 30%–40% of total treatment time for the total target volumes exceeding 200 cm{sup 3}, which was the case for more than 80% of the patients in this study. When total treatment time was modeled as a function of the number of fields and total target volume, the model overestimated total treatment time by 12% on average, with a standard deviation of 32%. A sensitivity analysis of throughput capacity for a hypothetical four-room spot scanning proton therapy center identified several priority items for improvements in throughput capacity, including operation time, beam delivery time, and patient immobilization and setup time. Conclusions: The spot scanning port at our proton therapy center has operated at a high performance level and has been used to treat a large number of complex cases. Further improvements in efficiency may be feasible in the areas of facility operation, beam delivery, patient immobilization and setup, and optimization of treatment scheduling.« less

Radiotherapy treatment planning: benefits of CT-MR image registration and fusion in tumor volume delineation.

PubMed

Djan, Igor; Petrović, Borislava; Erak, Marko; Nikolić, Ivan; Lucić, Silvija

2013-08-01

Development of imaging techniques, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET), made great impact on radiotherapy treatment planning by improving the localization of target volumes. Improved localization allows better local control of tumor volumes, but also minimizes geographical misses. Mutual information is obtained by registration and fusion of images achieved manually or automatically. The aim of this study was to validate the CT-MRI image fusion method and compare delineation obtained by CT versus CT-MRI image fusion. The image fusion software (XIO CMS 4.50.0) was applied to delineate 16 patients. The patients were scanned on CT and MRI in the treatment position within an immobilization device before the initial treatment. The gross tumor volume (GTV) and clinical target volume (CTV) were delineated on CT alone and on CT+MRI images consecutively and image fusion was obtained. Image fusion showed that CTV delineated on a CT image study set is mainly inadequate for treatment planning, in comparison with CTV delineated on CT-MRI fused image study set. Fusion of different modalities enables the most accurate target volume delineation. This study shows that registration and image fusion allows precise target localization in terms of GTV and CTV and local disease control.

Current concepts in targeting chronic obstructive pulmonary disease pharmacotherapy: making progress towards personalised management.

PubMed

Woodruff, Prescott G; Agusti, Alvar; Roche, Nicolas; Singh, Dave; Martinez, Fernando J

2015-05-02

Chronic obstructive pulmonary disease (COPD) is a common, complex, and heterogeneous disorder that is responsible for substantial and growing morbidity, mortality, and health-care expense worldwide. Of imperative importance to decipher the complexity of COPD is to identify groups of patients with similar clinical characteristics, prognosis, or therapeutic needs, the so-called clinical phenotypes. This strategy is logical for research but might be of little clinical value because clinical phenotypes can overlap in the same patient and the same clinical phenotype could result from different biological mechanisms. With the goal to match assessment with treatment choices, the latest iteration of guidelines from the Global Initiative for Chronic Obstructive Lung Disease reorganised treatment objectives into two categories: to improve symptoms (ie, dyspnoea and health status) and to decrease future risk (as predicted by forced expiratory volume in 1 s level and exacerbations history). This change thus moves treatment closer to individualised medicine with available bronchodilators and anti-inflammatory drugs. Yet, future treatment options are likely to include targeting endotypes that represent subtypes of patients defined by a distinct pathophysiological mechanism. Specific biomarkers of these endotypes would be particularly useful in clinical practice, especially in patients in which clinical phenotype alone is insufficient to identify the underlying endotype. A few series of potential COPD endotypes and biomarkers have been suggested. Empirical knowledge will be gained from proof-of-concept trials in COPD with emerging drugs that target specific inflammatory pathways. In every instance, specific endotype and biomarker efforts will probably be needed for the success of these trials, because the pathways are likely to be operative in only a subset of patients. Network analysis of human diseases offers the possibility to improve understanding of disease pathobiological complexity and to help with the development of new treatment alternatives and, importantly, a reclassification of complex diseases. All these developments should pave the way towards personalised treatment of patients with COPD in the clinic. Copyright © 2015 Elsevier Ltd. All rights reserved.

Treatment planning for heavy ion radiotherapy: clinical implementation and application.

PubMed

Jäkel, O; Krämer, M; Karger, C P; Debus, J

2001-04-01

The clinical implementation and application of a novel treatment planning system (TPS) for scanned ion beams is described, which is in clinical use for carbon ion treatments at the German heavy ion facility (GSI). All treatment plans are evaluated on the basis of biologically effective dose distributions. For therapy control, in-beam positron emission tomography (PET) and an online monitoring system for the beam intensity and position are used. The absence of a gantry restricts the treatment plans to horizontal beams. Most of the treatment plans consist of two nearly opposing lateral fields or sometimes orthogonal fields. In only a very few cases a single beam was used. For patients with very complex target volumes lateral and even distal field patching techniques were applied. Additional improvements can be achieved when the patient's head is fixed in a tilted position, in order to achieve sparing of the organs at risk. In order to test the stability of dose distributions in the case of patient misalignments we routinely simulate the effects of misalignments for patients with critical structures next to the target volume. The uncertainties in the range calculation are taken into account by a margin around the target volume of typically 2-3 mm, which can, however, be extended if the simulation demonstrates larger deviations. The novel TPS developed for scanned ion beams was introduced into clinical routine in December 1997 and was used for the treatment planning of 63 patients with head and neck tumours until July 2000. Planning strategies and methods were developed for this tumour location that facilitate the treatment of a larger number of patients with the scanned heavy ion beam in a clinical setting. Further developments aim towards a simultaneous optimization of the treatment field intensities and more effective procedures for the patient set-up. The results demonstrate that ion beams can be integrated into a clinical environment for treatment planning and delivery.

Dosimetric comparison of four different external beams for breast irradiation

NASA Astrophysics Data System (ADS)

Lee, Yoon Hee; Chung, Weon Kuu; Kim, Dong Wook; Kwon, Oh Young

2017-02-01

An intensity-modulated radiation-therapy (IMRT)-based technique, blocked single iso-centric IMRT (IMRT), is compared to multi-center IMRT (MIRT) and other conventional techniques such as three dimensional conformal radiation therapy (3D-CRT) and volumetric modulated arc therapy (VMAT) for the treatment of breast cancer patients. Four different plans were devised and compared for 15 breast cancer patients, all of whom had early stage disease and had undergone breast conserving surgery. A total dose of 50.4 Gy in 28 fractions was prescribed as the planning target volume in all treatment plans. The doses to the ipsilateral lung, heart, and opposite breast were compared using a dose-volume histogram. The conformity index (CI), homogeneity index (HI), and coverage index (CoVI) were evaluated and compared among the four treatment techniques. The lifetime attributable risk (LAR) associated with each of the four techniques from age at exposure of 30 to 100 years was measured for the organs at risk. We found that MIRT had a better CoVI (1.02 ± 0.13 and 1.01 ± 0.04, respectively) and IMRT had a better CI (0.88 ± 0.04, and 0.87 ± 0.02, respectively) compared to the other three modalities. All four techniques had similar HIs. Moreover, we found that IMRT and MIRT were less likely to cause radiation induced-pneumonitis, 3D-CRT had the lowest LAR, IMRT and MIRT had similar LARs and VMAT had the highest LAR. In study we found that compared to the VMAT, MIRT and IMRT provided adequate the planning target volume (PTV) coverage and reduced the risk of secondary cancers in most of the organs at risk (OARs), while 3D-CRT had the lowest secondary-cancer risks. Therefore, 3D-CRT is still a reasonable choice for whole breast RT except for patients with complex PTV shapes, in which cases IMRT and MIRT may provide better target coverage.

Feasibility and Initial Dosimetric Findings for a Randomized Trial Using Dose-Painted Multiparametric Magnetic Resonance Imaging–Defined Targets in Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bossart, Elizabeth L., E-mail: EBossart@med.miami.edu; Stoyanova, Radka; Sandler, Kiri

2016-06-01

Purpose: To compare dosimetric characteristics with multiparametric magnetic resonance imaging–identified imaging tumor volume (gross tumor volume, GTV), prostate clinical target volume and planning target volume, and organs at risk (OARs) for 2 treatment techniques representing 2 arms of an institutional phase 3 randomized trial of hypofractionated external beam image guided highly targeted radiation therapy. Methods and Materials: Group 1 (n=20) patients were treated before the trial inception with the standard dose prescription. Each patient had an additional treatment plan generated per the experimental arm. A total of 40 treatment plans were compared (20 plans for each technique). Group 2 (n=15)more » consists of patients currently accrued to the hypofractionated external beam image guided highly targeted radiation therapy trial. Plans were created as per the treatment arm, with additional plans for 5 of the group 2 experimental arm with a 3-mm expansion in the imaging GTV. Results: For all plans in both patient groups, planning target volume coverage ranged from 95% to 100%; GTV coverage of 89.3 Gy for the experimental treatment plans ranged from 95.2% to 99.8%. For both groups 1 and 2, the percent volumes of rectum/anus and bladder receiving 40 Gy, 65 Gy, and 80 Gy were smaller in the experimental plans than in the standard plans. The percent volume at 1 Gy per fraction and 1.625 Gy per fraction were compared between the standard and the experimental arms, and these were found to be equivalent. Conclusions: The dose per fraction to the OARs can be made equal even when giving a large simultaneous integrated boost to the GTV. The data suggest that a GTV margin may be added without significant dose effects on the OARs.« less

Comparison of plan quality and delivery time between volumetric arc therapy (RapidArc) and Gamma Knife radiosurgery for multiple cranial metastases.

PubMed

Thomas, Evan M; Popple, Richard A; Wu, Xingen; Clark, Grant M; Markert, James M; Guthrie, Barton L; Yuan, Yu; Dobelbower, Michael C; Spencer, Sharon A; Fiveash, John B

2014-10-01

Volumetric modulated arc therapy (VMAT) has been shown to be feasible for radiosurgical treatment of multiple cranial lesions with a single isocenter. To investigate whether equivalent radiosurgical plan quality and reduced delivery time could be achieved in VMAT for patients with multiple intracranial targets previously treated with Gamma Knife (GK) radiosurgery. We identified 28 GK treatments of multiple metastases. These were replanned for multiarc and single-arc, single-isocenter VMAT (RapidArc) in Eclipse. The prescription for all targets was standardized to 18 Gy. Each plan was normalized for 100% prescription dose to 99% to 100% of target volume. Plan quality was analyzed by target conformity (Radiation Therapy Oncology Group and Paddick conformity indices [CIs]), dose falloff (area under the dose-volume histogram curve), as well as the V4.5, V9, V12, and V18 isodose volumes. Other end points included beam-on and treatment time. Compared with GK, multiarc VMAT improved median plan conformity (CIVMAT = 1.14, CIGK = 1.65; P < .001) with no significant difference in median dose falloff (P = .269), 12 Gy isodose volume (P = .500), or low isodose spill (P = .49). Multiarc VMAT plans were associated with markedly reduced treatment time. A predictive model of the 12 Gy isodose volume as a function of tumor number and volume was also developed. For multiple target stereotactic radiosurgery, 4-arc VMAT produced clinically equivalent conformity, dose falloff, 12 Gy isodose volume, and low isodose spill, and reduced treatment time compared with GK. Because of its similar plan quality and increased delivery efficiency, single-isocenter VMAT radiosurgery may constitute an attractive alternative to multi-isocenter radiosurgery for some patients.

Atlas-Based Segmentation Improves Consistency and Decreases Time Required for Contouring Postoperative Endometrial Cancer Nodal Volumes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Young, Amy V.; Department of Radiation Oncology, St. Luke's-Roosevelt Hospital, New York, NY; Wortham, Angela

2011-03-01

Purpose: Accurate target delineation of the nodal volumes is essential for three-dimensional conformal and intensity-modulated radiotherapy planning for endometrial cancer adjuvant therapy. We hypothesized that atlas-based segmentation ('autocontouring') would lead to time savings and more consistent contours among physicians. Methods and Materials: A reference anatomy atlas was constructed using the data from 15 postoperative endometrial cancer patients by contouring the pelvic nodal clinical target volume on the simulation computed tomography scan according to the Radiation Therapy Oncology Group 0418 trial using commercially available software. On the simulation computed tomography scans from 10 additional endometrial cancer patients, the nodal clinical targetmore » volume autocontours were generated. Three radiation oncologists corrected the autocontours and delineated the manual nodal contours under timed conditions while unaware of the other contours. The time difference was determined, and the overlap of the contours was calculated using Dice's coefficient. Results: For all physicians, manual contouring of the pelvic nodal target volumes and editing the autocontours required a mean {+-} standard deviation of 32 {+-} 9 vs. 23 {+-} 7 minutes, respectively (p = .000001), a 26% time savings. For each physician, the time required to delineate the manual contours vs. correcting the autocontours was 30 {+-} 3 vs. 21 {+-} 5 min (p = .003), 39 {+-} 12 vs. 30 {+-} 5 min (p = .055), and 29 {+-} 5 vs. 20 {+-} 5 min (p = .0002). The mean overlap increased from manual contouring (0.77) to correcting the autocontours (0.79; p = .038). Conclusion: The results of our study have shown that autocontouring leads to increased consistency and time savings when contouring the nodal target volumes for adjuvant treatment of endometrial cancer, although the autocontours still required careful editing to ensure that the lymph nodes at risk of recurrence are properly included in the target volume.« less

Coverage-based constraints for IMRT optimization

NASA Astrophysics Data System (ADS)

Mescher, H.; Ulrich, S.; Bangert, M.

2017-09-01

Radiation therapy treatment planning requires an incorporation of uncertainties in order to guarantee an adequate irradiation of the tumor volumes. In current clinical practice, uncertainties are accounted for implicitly with an expansion of the target volume according to generic margin recipes. Alternatively, it is possible to account for uncertainties by explicit minimization of objectives that describe worst-case treatment scenarios, the expectation value of the treatment or the coverage probability of the target volumes during treatment planning. In this note we show that approaches relying on objectives to induce a specific coverage of the clinical target volumes are inevitably sensitive to variation of the relative weighting of the objectives. To address this issue, we introduce coverage-based constraints for intensity-modulated radiation therapy (IMRT) treatment planning. Our implementation follows the concept of coverage-optimized planning that considers explicit error scenarios to calculate and optimize patient-specific probabilities q(\\hat{d}, \\hat{v}) of covering a specific target volume fraction \\hat{v} with a certain dose \\hat{d} . Using a constraint-based reformulation of coverage-based objectives we eliminate the trade-off between coverage and competing objectives during treatment planning. In-depth convergence tests including 324 treatment plan optimizations demonstrate the reliability of coverage-based constraints for varying levels of probability, dose and volume. General clinical applicability of coverage-based constraints is demonstrated for two cases. A sensitivity analysis regarding penalty variations within this planing study based on IMRT treatment planning using (1) coverage-based constraints, (2) coverage-based objectives, (3) probabilistic optimization, (4) robust optimization and (5) conventional margins illustrates the potential benefit of coverage-based constraints that do not require tedious adjustment of target volume objectives.

The accomplishments of lithium target and test facility validation activities in the IFMIF/EVEDA phase

NASA Astrophysics Data System (ADS)

Arbeiter, Frederik; Baluc, Nadine; Favuzza, Paolo; Gröschel, Friedrich; Heidinger, Roland; Ibarra, Angel; Knaster, Juan; Kanemura, Takuji; Kondo, Hiroo; Massaut, Vincent; Saverio Nitti, Francesco; Miccichè, Gioacchino; O'hira, Shigeru; Rapisarda, David; Sugimoto, Masayoshi; Wakai, Eiichi; Yokomine, Takehiko

2018-01-01

As part of the engineering validation and engineering design activities (EVEDA) phase for the international fusion materials irradiation facility IFMIF, major elements of a lithium target facility and the test facility were designed, prototyped and validated. For the lithium target facility, the EVEDA lithium test loop was built at JAEA and used to test the stability (waves and long term) of the lithium flow in the target, work out the startup procedures, and test lithium purification and analysis. It was confirmed by experiments in the Lifus 6 plant at ENEA that lithium corrosion on ferritic martensitic steels is acceptably low. Furthermore, complex remote handling procedures for the remote maintenance of the target in the test cell environment were successfully practiced. For the test facility, two variants of a high flux test module were prototyped and tested in helium loops, demonstrating their good capabilities of maintaining the material specimens at the desired temperature with a low temperature spread. Irradiation tests were performed for heated specimen capsules and irradiation instrumentation in the BR2 reactor at SCK-CEN. The small specimen test technique, essential for obtaining material test results with limited irradiation volume, was advanced by evaluating specimen shape and test technique influences.

Targeting TORC1/2 enhances sensitivity to EGFR inhibitors in head and neck cancer preclinical models.

PubMed

Cassell, Andre; Freilino, Maria L; Lee, Jessica; Barr, Sharon; Wang, Lin; Panahandeh, Mary C; Thomas, Sufi M; Grandis, Jennifer R

2012-11-01

Head and neck squamous cell carcinoma (HNSCC) is characterized by overexpression of the epidermal growth factor receptor (EGFR) where treatments targeting EGFR have met with limited clinical success. Elucidation of the key downstream-pathways that remain activated in the setting of EGFR blockade may reveal new therapeutic targets. The present study was undertaken to test the hypothesis that inhibition of the mammalian target of rapamycin (mTOR) complex would enhance the effects of EGFR blockade in HNSCC preclinical models. Treatment of HNSCC cell lines with the newly developed TORC1/TORC2 inhibitor OSI-027/ASP4876 resulted in dose-dependent inhibition of proliferation with abrogation of phosphorylation of known downstream targets including phospho-AKT (Ser473), phospho-4E-BP1, phospho-p70s6K, and phospho-PRAS40. Furthermore, combined treatment with OSI-027 and erlotinib resulted in enhanced biochemical effects and synergistic growth inhibition in vitro. Treatment of mice bearing HNSCC xenografts with a combination of the Food and Drug Administration (FDA)-approved EGFR inhibitor cetuximab and OSI-027 demonstrated a significant reduction of tumor volumes compared with either treatment alone. These findings suggest that TORC1/TORC2 inhibition in conjunction with EGFR blockade represents a plausible therapeutic strategy for HNSCC.

Targeting TORC1/2 Enhances Sensitivity to EGFR Inhibitors in Head and Neck Cancer Preclinical Models1

PubMed Central

Cassell, Andre; Freilino, Maria L; Lee, Jessica; Barr, Sharon; Wang, Lin; Panahandeh, Mary C; Thomas, Sufi M; Grandis, Jennifer R

2012-01-01

Head and neck squamous cell carcinoma (HNSCC) is characterized by overexpression of the epidermal growth factor receptor (EGFR) where treatments targeting EGFR have met with limited clinical success. Elucidation of the key downstream-pathways that remain activated in the setting of EGFR blockade may reveal new therapeutic targets. The present study was undertaken to test the hypothesis that inhibition of the mammalian target of rapamycin (mTOR) complex would enhance the effects of EGFR blockade in HNSCC preclinical models. Treatment of HNSCC cell lines with the newly developed TORC1/TORC2 inhibitor OSI-027/ASP4876 resulted in dose-dependent inhibition of proliferation with abrogation of phosphorylation of known downstream targets including phospho-AKT (Ser473), phospho-4E-BP1, phospho-p70s6K, and phospho-PRAS40. Furthermore, combined treatment with OSI-027 and erlotinib resulted in enhanced biochemical effects and synergistic growth inhibition in vitro. Treatment of mice bearing HNSCC xenografts with a combination of the Food and Drug Administration (FDA)-approved EGFR inhibitor cetuximab and OSI-027 demonstrated a significant reduction of tumor volumes compared with either treatment alone. These findings suggest that TORC1/TORC2 inhibition in conjunction with EGFR blockade represents a plausible therapeutic strategy for HNSCC. PMID:23226094

Functionalized active-nucleus complex sensor

DOEpatents

Pines, Alexander; Wemmer, David E.; Spence, Megan; Rubin, Seth

2003-11-25

A functionalized active-nucleus complex sensor that selectively associates with one or more target species, and a method for assaying and screening for one or a plurality of target species utilizing one or a plurality of functionalized active-nucleus complexes with at least two of the functionalized active-nucleus complexes having an attraction affinity to different corresponding target species. The functionalized active-nucleus complex has an active-nucleus and a targeting carrier. The method involves functionalizing an active-nucleus, for each functionalized active-nucleus complex, by incorporating the active-nucleus into a macromolucular or molecular complex that is capable of binding one of the target species and then bringing the macromolecular or molecular complexes into contact with the target species and detecting the occurrence of or change in a nuclear magnetic resonance signal from each of the active-nuclei in each of the functionalized active-nucleus complexes.

Age-related differences in the structural complexity of subcortical and ventricular structures.

PubMed

Madan, Christopher R; Kensinger, Elizabeth A

2017-02-01

It has been well established that the volume of several subcortical structures decreases in relation to age. Different metrics of cortical structure (e.g., volume, thickness, surface area, and gyrification) have been shown to index distinct characteristics of interindividual differences; thus, it is important to consider the relation of age to multiple structural measures. Here, we compare age-related differences in subcortical and ventricular volume to those differences revealed with a measure of structural complexity, quantified as fractal dimensionality. Across 3 large data sets, totaling nearly 900 individuals across the adult lifespan (aged 18-94 years), we found greater age-related differences in complexity than volume for the subcortical structures, particularly in the caudate and thalamus. The structural complexity of ventricular structures was not more strongly related to age than volume. These results demonstrate that considering shape-related characteristics improves sensitivity to detect age-related differences in subcortical structures. Copyright © 2016 Elsevier Inc. All rights reserved.

Definition of the key target volume in radiosurgical management of arteriovenous malformations: a new dynamic concept based on angiographic circulation time.

PubMed

Valle, Ramiro Del; Zenteno, Marco; Jaramillo, José; Lee, Angel; De Anda, Salvador

2008-12-01

The cumulative experience worldwide indicates complete radiosurgical obliteration rates of brain arteriovenous malformations (AVMs) ranging from 35 to 90%. The purpose of this study was to propose a strategy to increase the obliteration rate for AVMs through the dynamic definition of the key target volume (KTV). A prospective series of patients harboring an AVM was assessed using digital subtraction angiography in which a digital counter was used to measure the several stages of the frame-by-frame circulation time. All the patients were analyzed using dynamic measurement planning to define the KTV, corresponding to the volume of the shunt with the least vascular resistance and the earliest venous drainage. All patients underwent catheter-based angiography, a subgroup was additionally assessed by means of a superselective catheterization, and among these a further subgroup received embolization. The shunts were also categorized according to their angioarchitectural type: fistulous, plexiform, or mixed. The authors applied the radiosurgery-based grading system (RBGS) as well to find a correlation with the obliteration rate. This series includes 44 patients treated by radiosurgery; global angiography was performed for all patients, including dynamic measurement planning. Eighty-four percent of them underwent superselective catheterization, and 50% of the total population underwent embolization. In the embolized arm of the study, the pretreatment volume was up to 120 ml. In patients with a single treatment, the mean volume was 8.5 ml, and the median volume was 6.95 +/- 4.56 ml (mean +/- standard deviation), with a KTV of up to 15 ml. For prospectively staged radiosurgery, the mean KTV was 28 ml. The marginal radiation dose was 18-22 Gy, with a mean of dose 20 Gy. The mean RBGS score was 1.70. The overall obliteration rate was 91%, including the repeated radiosurgery group (4 patients), in which 100% showed complete obliteration. The overall permanent deficit was 2 of 44 patients, 1 in each group. Dynamic definition of the KTV might increase the obliteration rate, even in complex AVMs, allowing the treatment of smaller volumes off the recruitment vessels (pseudonidus). By using this technique, the authors avoided double-blind treatment, where the neurosurgeon does not know precisely which type of lesion he or she is irradiating and the interventionalist does not know why and what he or she is embolizing.

Standardizing Naming Conventions in Radiation Oncology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Santanam, Lakshmi; Hurkmans, Coen; Mutic, Sasa

2012-07-15

Purpose: The aim of this study was to report on the development of a standardized target and organ-at-risk naming convention for use in radiation therapy and to present the nomenclature for structure naming for interinstitutional data sharing, clinical trial repositories, integrated multi-institutional collaborative databases, and quality control centers. This taxonomy should also enable improved plan benchmarking between clinical institutions and vendors and facilitation of automated treatment plan quality control. Materials and Methods: The Advanced Technology Consortium, Washington University in St. Louis, Radiation Therapy Oncology Group, Dutch Radiation Oncology Society, and the Clinical Trials RT QA Harmonization Group collaborated in creatingmore » this new naming convention. The International Commission on Radiation Units and Measurements guidelines have been used to create standardized nomenclature for target volumes (clinical target volume, internal target volume, planning target volume, etc.), organs at risk, and planning organ-at-risk volumes in radiation therapy. The nomenclature also includes rules for specifying laterality and margins for various structures. The naming rules distinguish tumor and nodal planning target volumes, with correspondence to their respective tumor/nodal clinical target volumes. It also provides rules for basic structure naming, as well as an option for more detailed names. Names of nonstandard structures used mainly for plan optimization or evaluation (rings, islands of dose avoidance, islands where additional dose is needed [dose painting]) are identified separately. Results: In addition to its use in 16 ongoing Radiation Therapy Oncology Group advanced technology clinical trial protocols and several new European Organization for Research and Treatment of Cancer protocols, a pilot version of this naming convention has been evaluated using patient data sets with varying treatment sites. All structures in these data sets were satisfactorily identified using this nomenclature. Conclusions: Use of standardized naming conventions is important to facilitate comparison of dosimetry across patient datasets. The guidelines presented here will facilitate international acceptance across a wide range of efforts, including groups organizing clinical trials, Radiation Oncology Institute, Dutch Radiation Oncology Society, Integrating the Healthcare Enterprise, Radiation Oncology domain (IHE-RO), and Digital Imaging and Communication in Medicine (DICOM).« less

Focal CA3 hippocampal subfield atrophy following LGI1 VGKC-complex antibody limbic encephalitis.

PubMed

Miller, Thomas D; Chong, Trevor T-J; Aimola Davies, Anne M; Ng, Tammy W C; Johnson, Michael R; Irani, Sarosh R; Vincent, Angela; Husain, Masud; Jacob, Saiju; Maddison, Paul; Kennard, Christopher; Gowland, Penny A; Rosenthal, Clive R

2017-05-01

Magnetic resonance imaging has linked chronic voltage-gated potassium channel (VGKC) complex antibody-mediated limbic encephalitis with generalized hippocampal atrophy. However, autoantibodies bind to specific rodent hippocampal subfields. Here, human hippocampal subfield (subiculum, cornu ammonis 1-3, and dentate gyrus) targets of immunomodulation-treated LGI1 VGKC-complex antibody-mediated limbic encephalitis were investigated using in vivo ultra-high resolution (0.39 × 0.39 × 1.0 mm3) 7.0 T magnetic resonance imaging [n = 18 patients, 17 patients (94%) positive for LGI1 antibody and one patient negative for LGI1/CASPR2 but positive for VGKC-complex antibodies, mean age: 64.0 ± 2.55 years, median 4 years post-limbic encephalitis onset; n = 18 controls]. First, hippocampal subfield quantitative morphometry indicated significant volume loss confined to bilateral CA3 [F(1,34) = 16.87, P < 0.0001], despite hyperintense signal evident in 5 of 18 patients on presentation. Second, early and later intervention (<3 versus >3 months from symptom onset) were associated with CA3 atrophy. Third, whole-brain voxel-by-voxel morphometry revealed no significant grey matter loss. Fourth, CA3 subfield atrophy was associated with severe episodic but not semantic amnesia for postmorbid autobiographical events that was predicted by variability in CA3 volume. The results raise important questions about the links with histopathology, the impact of the observed focal atrophy on other CA3-mediated reconstructive and episodic mechanisms, and the role of potential antibody-mediated pathogenicity as part of the pathophysiology cascade in humans. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

Optimization of Craniospinal Irradiation for Pediatric Medulloblastoma Using VMAT and IMRT.

PubMed

Al-Wassia, Rolina K; Ghassal, Noor M; Naga, Adly; Awad, Nesreen A; Bahadur, Yasir A; Constantinescu, Camelia

2015-10-01

Intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) provide highly conformal target radiation doses, but also expose large volumes of healthy tissue to low-dose radiation. With improving survival, more children with medulloblastoma (MB) are at risk of late adverse effects of radiotherapy, including secondary cancers. We evaluated the characteristics of IMRT and VMAT craniospinal irradiation treatment plans in children with standard-risk MB to compare radiation dose delivery to target organs and organs at risk (OAR). Each of 10 children with standard-risk MB underwent both IMRT and VMAT treatment planning. Dose calculations used inverse planning optimization with a craniospinal dose of 23.4 Gy followed by a posterior fossa boost to 55.8 Gy. Clinical and planning target volumes were demarcated on axial computed tomography images. Dose distributions to target organs and OAR for each planning technique were measured and compared with published dose-volume toxicity data for pediatric patients. All patients completed treatment planning for both techniques. Analyses and comparisons of dose distributions and dose-volume histograms for the planned target volumes, and dose delivery to the OAR for each technique demonstrated the following: (1) VMAT had a modest, but significantly better, planning target volume-dose coverage and homogeneity compared with IMRT; (2) there were different OAR dose-sparing profiles for IMRT versus VMAT; and (3) neither IMRT nor VMAT demonstrated dose reductions to the published pediatric dose limits for the eyes, the lens, the cochlea, the pituitary, and the brain. The use of both IMRT and VMAT provides good target tissue coverage and sparing of the adjacent tissue for MB. Both techniques resulted in OAR dose delivery within published pediatric dose guidelines, except those mentioned above. Pediatric patients with standard-risk MB remain at risk for late endocrinologic, sensory (auditory and visual), and brain functional impairments.

[Effect of image fusion technology of radioactive particles implantation before and after the planning target and dosimetry].

PubMed

Jiang, Y L; Yu, J P; Sun, H T; Guo, F X; Ji, Z; Fan, J H; Zhang, L J; Li, X; Wang, J J

2017-08-01

Objective: To compare the post-implant target volumes and dosimetric evaluation with pre-plan, the gross tumor volume(GTV) by CT image fusion-based and the manual delineation of target volume in CT guided radioactive seeds implantation. Methods: A total of 10 patients treated under CT-guidance (125)I seed implantation during March 2016 to April 2016 were analyzed in Peking University Third Hospital.All patients underwent pre-operative CT simulation, pre-operative planning, implantation seeds, CT scanning after seed implantation and dosimetric evaluation of GTV.In every patient, post-implant target volumes were delineated by both two methods, and were divided into two groups. Group 1: image fusion pre-implantation simulation and post-operative CT image, then the contours of GTV were automatically performed by brachytherapy treatment planning system; Group 2: the contouring of the GTV on post-operative CT image were performed manually by three senior radiation oncologists independently. The average of three data was sets. Statistical analyses were performed using SPSS software, version 3.2.0. The paired t -test was used to compare the target volumes and D(90) parameters in two modality. Results: In Group 1, average volume of GTV in post-operation group was 12-167(73±56) cm(3). D(90) was 101-153 (142±19)Gy. In Group 2, they were 14-186(80±58)cm(3) and 96-146(122±16) Gy respectively. In both target volumes and D(90), there was no statistical difference between pre-operation and post-operation in Group 1.The D(90) was slightly lower than that of pre-plan group, but there was no statistical difference ( P =0.142); in Group 2, between pre-operation and post-operation group, there was a significant statistical difference in the GTV ( P =0.002). The difference of D(90) was similarly ( P <0.01). Conclusion: The method of delineation of post-implant GTV through fusion pre-implantation simulation and post-operative CT scan images, the contours of GTV are automatically performed by brachytherapy treatment planning system appears to have improved more accuracy, reproducibility and convenience than manual delineation of target volume by maximum reduce the interference from artificial factor and metal artifacts. Further work and more cases are required in the future.

DOE Office of Scientific and Technical Information (OSTI.GOV)

MacFadden, Derek; Zhang Beibei; Brock, Kristy K.

Purpose: Increasing the magnetic resonance imaging (MRI) field strength can improve image resolution and quality, but concerns remain regarding the influence on geometric fidelity. The objectives of the present study were to spatially investigate the effect of 3-Tesla (3T) MRI on clinical target localization for stereotactic radiosurgery. Methods and Materials: A total of 39 patients were enrolled in a research ethics board-approved prospective clinical trial. Imaging (1.5T and 3T MRI and computed tomography) was performed after stereotactic frame placement. Stereotactic target localization at 1.5T vs. 3T was retrospectively analyzed in a representative cohort of patients with tumor (n = 4)more » and functional (n = 5) radiosurgical targets. The spatial congruency of the tumor gross target volumes was determined by the mean discrepancy between the average gross target volume surfaces at 1.5T and 3T. Reproducibility was assessed by the displacement from an averaged surface and volume congruency. Spatial congruency and the reproducibility of functional radiosurgical targets was determined by comparing the mean and standard deviation of the isocenter coordinates. Results: Overall, the mean absolute discrepancy across all patients was 0.67 mm (95% confidence interval, 0.51-0.83), significantly <1 mm (p < .010). No differences were found in the overall interuser target volume congruence (mean, 84% for 1.5T vs. 84% for 3T, p > .4), and the gross target volume surface mean displacements were similar within and between users. The overall average isocenter coordinate discrepancy for the functional targets at 1.5T and 3T was 0.33 mm (95% confidence interval, 0.20-0.48), with no patient-specific differences between the mean values (p >.2) or standard deviations (p >.1). Conclusion: Our results have provided clinically relevant evidence supporting the spatial validity of 3T MRI for use in stereotactic radiosurgery under the imaging conditions used.« less

SU-E-T-480: Radiobiological Dose Comparison of Single Fraction SRS, Multi-Fraction SRT and Multi-Stage SRS of Large Target Volumes Using the Linear-Quadratic Formula

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ding, C; Hrycushko, B; Jiang, S

2014-06-01

Purpose: To compare the radiobiological effect on large tumors and surrounding normal tissues from single fraction SRS, multi-fractionated SRT, and multi-staged SRS treatment. Methods: An anthropomorphic head phantom with a centrally located large volume target (18.2 cm{sup 3}) was scanned using a 16 slice large bore CT simulator. Scans were imported to the Multiplan treatment planning system where a total prescription dose of 20Gy was used for a single, three staged and three fractionated treatment. Cyber Knife treatment plans were inversely optimized for the target volume to achieve at least 95% coverage of the prescription dose. For the multistage plan,more » the target was segmented into three subtargets having similar volume and shape. Staged plans for individual subtargets were generated based on a planning technique where the beam MUs of the original plan on the total target volume are changed by weighting the MUs based on projected beam lengths within each subtarget. Dose matrices for each plan were export in DICOM format and used to calculate equivalent dose distributions in 2Gy fractions using an alpha beta ratio of 10 for the target and 3 for normal tissue. Results: Singe fraction SRS, multi-stage plan and multi-fractionated SRT plans had an average 2Gy dose equivalent to the target of 62.89Gy, 37.91Gy and 33.68Gy, respectively. The normal tissue within 12Gy physical dose region had an average 2Gy dose equivalent of 29.55Gy, 16.08Gy and 13.93Gy, respectively. Conclusion: The single fraction SRS plan had the largest predicted biological effect for the target and the surrounding normal tissue. The multi-stage treatment provided for a more potent biologically effect on target compared to the multi-fraction SRT treatments with less biological normal tissue than single-fraction SRS treatment.« less

Optimized programming algorithm for cylindrical and directional deep brain stimulation electrodes.

PubMed

Anderson, Daria Nesterovich; Osting, Braxton; Vorwerk, Johannes; Dorval, Alan D; Butson, Christopher R

2018-04-01

Deep brain stimulation (DBS) is a growing treatment option for movement and psychiatric disorders. As DBS technology moves toward directional leads with increased numbers of smaller electrode contacts, trial-and-error methods of manual DBS programming are becoming too time-consuming for clinical feasibility. We propose an algorithm to automate DBS programming in near real-time for a wide range of DBS lead designs. Magnetic resonance imaging and diffusion tensor imaging are used to build finite element models that include anisotropic conductivity. The algorithm maximizes activation of target tissue and utilizes the Hessian matrix of the electric potential to approximate activation of neurons in all directions. We demonstrate our algorithm's ability in an example programming case that targets the subthalamic nucleus (STN) for the treatment of Parkinson's disease for three lead designs: the Medtronic 3389 (four cylindrical contacts), the direct STNAcute (two cylindrical contacts, six directional contacts), and the Medtronic-Sapiens lead (40 directional contacts). The optimization algorithm returns patient-specific contact configurations in near real-time-less than 10 s for even the most complex leads. When the lead was placed centrally in the target STN, the directional leads were able to activate over 50% of the region, whereas the Medtronic 3389 could activate only 40%. When the lead was placed 2 mm lateral to the target, the directional leads performed as well as they did in the central position, but the Medtronic 3389 activated only 2.9% of the STN. This DBS programming algorithm can be applied to cylindrical electrodes as well as novel directional leads that are too complex with modern technology to be manually programmed. This algorithm may reduce clinical programming time and encourage the use of directional leads, since they activate a larger volume of the target area than cylindrical electrodes in central and off-target lead placements.

SU-G-JeP3-09: Tumor Location Prediction Using Natural Respiratory Volume for Respiratory Gated Radiation Therapy (RGRT): System Verification Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, M; Jung, J; Yoon, D

Purpose: Respiratory gated radiation therapy (RGRT) gives accurate results when a patient’s breathing is stable and regular. Thus, the patient should be fully aware during respiratory pattern training before undergoing the RGRT treatment. In order to bypass the process of respiratory pattern training, we propose a target location prediction system for RGRT that uses only natural respiratory volume, and confirm its application. Methods: In order to verify the proposed target location prediction system, an in-house phantom set was used. This set involves a chest phantom including target, external markers, and motion generator. Natural respiratory volume signals were generated using themore » random function in MATLAB code. In the chest phantom, the target takes a linear motion based on the respiratory signal. After a four-dimensional computed tomography (4DCT) scan of the in-house phantom, the motion trajectory was derived as a linear equation. The accuracy of the linear equation was compared with that of the motion algorithm used by the operating motion generator. In addition, we attempted target location prediction using random respiratory volume values. Results: The correspondence rate of the linear equation derived from the 4DCT images with the motion algorithm of the motion generator was 99.41%. In addition, the average error rate of target location prediction was 1.23% for 26 cases. Conclusion: We confirmed the applicability of our proposed target location prediction system for RGRT using natural respiratory volume. If additional clinical studies can be conducted, a more accurate prediction system can be realized without requiring respiratory pattern training.« less

Equivalent uniform dose concept evaluated by theoretical dose volume histograms for thoracic irradiation.

PubMed

Dumas, J L; Lorchel, F; Perrot, Y; Aletti, P; Noel, A; Wolf, D; Courvoisier, P; Bosset, J F

2007-03-01

The goal of our study was to quantify the limits of the EUD models for use in score functions in inverse planning software, and for clinical application. We focused on oesophagus cancer irradiation. Our evaluation was based on theoretical dose volume histograms (DVH), and we analyzed them using volumetric and linear quadratic EUD models, average and maximum dose concepts, the linear quadratic model and the differential area between each DVH. We evaluated our models using theoretical and more complex DVHs for the above regions of interest. We studied three types of DVH for the target volume: the first followed the ICRU dose homogeneity recommendations; the second was built out of the first requirements and the same average dose was built in for all cases; the third was truncated by a small dose hole. We also built theoretical DVHs for the organs at risk, in order to evaluate the limits of, and the ways to use both EUD(1) and EUD/LQ models, comparing them to the traditional ways of scoring a treatment plan. For each volume of interest we built theoretical treatment plans with differences in the fractionation. We concluded that both volumetric and linear quadratic EUDs should be used. Volumetric EUD(1) takes into account neither hot-cold spot compensation nor the differences in fractionation, but it is more sensitive to the increase of the irradiated volume. With linear quadratic EUD/LQ, a volumetric analysis of fractionation variation effort can be performed.

Cul3-mediated Nrf2 ubiquitination and antioxidant response element (ARE) activation are dependent on the partial molar volume at position 151 of Keap1.

PubMed

Eggler, Aimee L; Small, Evan; Hannink, Mark; Mesecar, Andrew D

2009-07-29

Nrf2 (nuclear factor erythroid 2-related factor 2) is a transcription factor that activates transcription of a battery of cytoprotective genes by binding to the ARE (antioxidant response element). Nrf2 is repressed by the cysteine-rich Keap1 (kelch-like ECH-associated protein 1) protein, which targets Nrf2 for ubiquitination and subsequent degradation by a Cul3 (cullin 3)-mediated ubiquitination complex. We find that modification of Cys(151) of human Keap1, by mutation to a tryptophan, relieves the repression by Keap1 and allows activation of the ARE by Nrf2. The Keap1 C151W substitution has a decreased affinity for Cul3, and can no longer serve to target Nrf2 for ubiquitination, though it retains its affinity for Nrf2. A series of 12 mutant Keap1 proteins, each containing a different residue at position 151, was constructed to explore the chemistry required for this effect. The series reveals that the extent to which Keap1 loses the ability to target Nrf2 for degradation, and hence the ability to repress ARE activation, correlates well with the partial molar volume of the residue. Other physico-chemical properties do not appear to contribute significantly to the effect. Based on this finding, a structural model is proposed whereby large residues at position 151 cause steric clashes that lead to alteration of the Keap1-Cul3 interaction. This model has significant implications for how electrophiles which modify Cys(151), disrupt the repressive function of Keap1.

Automated linking of suspicious findings between automated 3D breast ultrasound volumes

NASA Astrophysics Data System (ADS)

Gubern-Mérida, Albert; Tan, Tao; van Zelst, Jan; Mann, Ritse M.; Karssemeijer, Nico

2016-03-01

Automated breast ultrasound (ABUS) is a 3D imaging technique which is rapidly emerging as a safe and relatively inexpensive modality for screening of women with dense breasts. However, reading ABUS examinations is very time consuming task since radiologists need to manually identify suspicious findings in all the different ABUS volumes available for each patient. Image analysis techniques to automatically link findings across volumes are required to speed up clinical workflow and make ABUS screening more efficient. In this study, we propose an automated system to, given the location in the ABUS volume being inspected (source), find the corresponding location in a target volume. The target volume can be a different view of the same study or the same view from a prior examination. The algorithm was evaluated using 118 linkages between suspicious abnormalities annotated in a dataset of ABUS images of 27 patients participating in a high risk screening program. The distance between the predicted location and the center of the annotated lesion in the target volume was computed for evaluation. The mean ± stdev and median distance error achieved by the presented algorithm for linkages between volumes of the same study was 7.75±6.71 mm and 5.16 mm, respectively. The performance was 9.54±7.87 and 8.00 mm (mean ± stdev and median) for linkages between volumes from current and prior examinations. The proposed approach has the potential to minimize user interaction for finding correspondences among ABUS volumes.

Fluctuating residual limb volume accommodated with an adjustable, modular socket design: A novel case report.

PubMed

Mitton, Kay; Kulkarni, Jai; Dunn, Kenneth William; Ung, Anthony Hoang

2017-10-01

This novel case report describes the problems of prescribing a prosthetic socket in a left transfemoral amputee secondary to chronic patellofemoral instability compounded by complex regional pain syndrome. Case Description and Methods: Following the amputation, complex regional pain syndrome symptoms recurred in the residual limb, presenting mainly with oedema. Due to extreme daily volume fluctuations of the residual limb, a conventional, laminated thermoplastic socket fitting was not feasible. Findings and Outcomes: An adjustable, modular socket design was trialled. The residual limb volume fluctuations were accommodated within the socket. Amputee rehabilitation could be continued, and the rehabilitation goals were achieved. The patient was able to wear the prosthesis for 8 h daily and to walk unaided indoors and outdoors. An adjustable, modular socket design accommodated the daily residual limb volume fluctuations and provided a successful outcome in this case. It demonstrates the complexities of socket fitting and design with volume fluctuations. Clinical relevance Ongoing complex regional pain syndrome symptoms within the residual limb can lead to fitting difficulties in a conventional, laminated thermoplastic socket due to volume fluctuations. An adjustable, modular socket design can accommodate this and provide a successful outcome.

Nanodosimetric track structure in homogeneous extended beams.

PubMed

Conte, V; Moro, D; Colautti, P; Grosswendt, B

2015-09-01

Physical aspects of particle track structure are important in determining the induction of clustered damage in relevant subcellular structures like the DNA and higher-order genomic structures. The direct measurement of track-structure properties of ionising radiation is feasible today by counting the number of ionisations produced inside a small gas volume. In particular, the so-called track-nanodosimeter, installed at the TANDEM-ALPI accelerator complex of LNL, measures ionisation cluster-size distributions in a simulated subcellular structure of dimensions 20 nm, corresponding approximately to the diameter of the chromatin fibre. The target volume is irradiated by pencil beams of primary particles passing at specified impact parameter. To directly relate these measured track-structure data to radiobiological measurements performed in broad homogeneous particle beams, these data can be integrated over the impact parameter. This procedure was successfully applied to 240 MeV carbon ions and compared with Monte Carlo simulations for extended fields. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Analyte quantification with comprehensive two-dimensional gas chromatography: assessment of methods for baseline correction, peak delineation, and matrix effect elimination for real samples.

PubMed

Samanipour, Saer; Dimitriou-Christidis, Petros; Gros, Jonas; Grange, Aureline; Samuel Arey, J

2015-01-02

Comprehensive two-dimensional gas chromatography (GC×GC) is used widely to separate and measure organic chemicals in complex mixtures. However, approaches to quantify analytes in real, complex samples have not been critically assessed. We quantified 7 PAHs in a certified diesel fuel using GC×GC coupled to flame ionization detector (FID), and we quantified 11 target chlorinated hydrocarbons in a lake water extract using GC×GC with electron capture detector (μECD), further confirmed qualitatively by GC×GC with electron capture negative chemical ionization time-of-flight mass spectrometer (ENCI-TOFMS). Target analyte peak volumes were determined using several existing baseline correction algorithms and peak delineation algorithms. Analyte quantifications were conducted using external standards and also using standard additions, enabling us to diagnose matrix effects. We then applied several chemometric tests to these data. We find that the choice of baseline correction algorithm and peak delineation algorithm strongly influence the reproducibility of analyte signal, error of the calibration offset, proportionality of integrated signal response, and accuracy of quantifications. Additionally, the choice of baseline correction and the peak delineation algorithm are essential for correctly discriminating analyte signal from unresolved complex mixture signal, and this is the chief consideration for controlling matrix effects during quantification. The diagnostic approaches presented here provide guidance for analyte quantification using GC×GC. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

SU-C-BRA-02: Gradient Based Method of Target Delineation On PET/MR Image of Head and Neck Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dance, M; Chera, B; Falchook, A

2015-06-15

Purpose: Validate the consistency of a gradient-based segmentation tool to facilitate accurate delineation of PET/CT-based GTVs in head and neck cancers by comparing against hybrid PET/MR-derived GTV contours. Materials and Methods: A total of 18 head and neck target volumes (10 primary and 8 nodal) were retrospectively contoured using a gradient-based segmentation tool by two observers. Each observer independently contoured each target five times. Inter-observer variability was evaluated via absolute percent differences. Intra-observer variability was examined by percentage uncertainty. All target volumes were also contoured using the SUV percent threshold method. The thresholds were explored case by case so itsmore » derived volume matched with the gradient-based volume. Dice similarity coefficients (DSC) were calculated to determine overlap of PET/CT GTVs and PET/MR GTVs. Results: The Levene’s test showed there was no statistically significant difference of the variances between the observer’s gradient-derived contours. However, the absolute difference between the observer’s volumes was 10.83%, with a range from 0.39% up to 42.89%. PET-avid regions with qualitatively non-uniform shapes and intensity levels had a higher absolute percent difference near 25%, while regions with uniform shapes and intensity levels had an absolute percent difference of 2% between observers. The average percentage uncertainty between observers was 4.83% and 7%. As the volume of the gradient-derived contours increased, the SUV threshold percent needed to match the volume decreased. Dice coefficients showed good agreement of the PET/CT and PET/MR GTVs with an average DSC value across all volumes at 0.69. Conclusion: Gradient-based segmentation of PET volume showed good consistency in general but can vary considerably for non-uniform target shapes and intensity levels. PET/CT-derived GTV contours stemming from the gradient-based tool show good agreement with the anatomically and metabolically more accurate PET/MR-derived GTV contours, but tumor delineation accuracy can be further improved with the use PET/MR.« less

Bar coded retroreflective target

DOEpatents

Vann, Charles S.

2000-01-01

This small, inexpensive, non-contact laser sensor can detect the location of a retroreflective target in a relatively large volume and up to six degrees of position. The tracker's laser beam is formed into a plane of light which is swept across the space of interest. When the beam illuminates the retroreflector, some of the light returns to the tracker. The intensity, angle, and time of the return beam is measured to calculate the three dimensional location of the target. With three retroreflectors on the target, the locations of three points on the target are measured, enabling the calculation of all six degrees of target position. Until now, devices for three-dimensional tracking of objects in a large volume have been heavy, large, and very expensive. Because of the simplicity and unique characteristics of this tracker, it is capable of three-dimensional tracking of one to several objects in a large volume, yet it is compact, light-weight, and relatively inexpensive. Alternatively, a tracker produces a diverging laser beam which is directed towards a fixed position, and senses when a retroreflective target enters the fixed field of view. An optically bar coded target can be read by the tracker to provide information about the target. The target can be formed of a ball lens with a bar code on one end. As the target moves through the field, the ball lens causes the laser beam to scan across the bar code.

SU-E-T-287: Dose Verification On the Variation of Target Volume and Organ at Risk in Preradiation Chemotherapy IMRT for Nasopharyngeal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, X; Kong, L; Wang, J

2015-06-15

Purpose: To quantify the target volume and organ at risk of nasopharyngeal carcinoma (NPC) patients with preradiation chemotherapy based on CT scanned during intensity-modulated radiotherapy (IMRT), and recalculate the dose distribution. Methods: Seven patients with NPC and preradiation chemotherapy, treated with IMRT (35 to 37 fractions) were reviewed. Repeat CT scanning was required to all of the patients during the radiotherapy, and the number of repeat CTs varies from 2 to 6. The plan CT and repeat CT were generated by different CT scanner. To ensure crespectively on the same IMPT plan. The real dose distribution was calculated by deformablemore » registration and weighted method in Raystation (v 4.5.1). The fraction of each dose is based on radiotherapy record. The volumetric and dose differences among these images were calculated for nascIpharyngeal tumor and retro-pharyngeal lymph nodes (GTV-NX), neck lymph nodes(GTV-ND), and parotid glands. Results: The volume variation in GTV-NX from CT1 to CT2 was 1.15±3.79%, and in GTV-LN −0.23±4.93%. The volume variation in left parotid from CT1 to CT2 was −6.79±11.91%, and in right parotid −3.92±8.80%. In patient 2, the left parotid volume were decreased remarkably, as a Result, the V30 and V40 of it were increased as well. Conclusion: The target volume of patients with NPC varied lightly during IMRT. It shows that preradiation chemotherapy can control the target volume variation and perform a good dose repeatability. Also, the decreasing volume of parotid in some patient might increase the dose of it, which might course potential complications.« less

The application of positron emission tomography/computed tomography in radiation treatment planning: effect on gross target volume definition and treatment management.

PubMed

Iğdem, S; Alço, G; Ercan, T; Unalan, B; Kara, B; Geceer, G; Akman, C; Zengin, F O; Atilla, S; Okkan, S

2010-04-01

To analyse the effect of the use of molecular imaging on gross target volume (GTV) definition and treatment management. Fifty patients with various solid tumours who underwent positron emission tomography (PET)/computed tomography (CT) simulation for radiotherapy planning from 2006 to 2008 were enrolled in this study. First, F-18 fluorodeoxyglucose (FDG)-PET and CT scans of the treatment site in the treatment position and then a whole body scan were carried out with a dedicated PET/CT scanner and fused thereafter. FDG-avid primary tumour and lymph nodes were included into the GTV. A multidisciplinary team defined the target volume, and contouring was carried out by a radiation oncologist using visual methods. To compare the PET/CT-based volumes with CT-based volumes, contours were drawn on CT-only data with the help of site-specific radiologists who were blind to the PET/CT results after a median time of 7 months. In general, our PET/CT volumes were larger than our CT-based volumes. This difference was significant in patients with head and neck cancers. Major changes (> or =25%) in GTV delineation were observed in 44% of patients. In 16% of cases, PET/CT detected incidental second primaries and metastatic disease, changing the treatment strategy from curative to palliative. Integrating functional imaging with FDG-PET/CT into the radiotherapy planning process resulted in major changes in a significant proportion of our patients. An interdisciplinary approach between imaging and radiation oncology departments is essential in defining the target volumes. Copyright 2010 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Ultra-low field nuclear magnetic resonance and magnetic resonance imaging to discriminate and identify materials

DOEpatents

Kraus, Robert H.; Matlashov, Andrei N.; Espy, Michelle A.; Volegov, Petr L.

2010-03-30

An ultra-low magnetic field NMR system can non-invasively examine containers. Database matching techniques can then identify hazardous materials within the containers. Ultra-low field NMR systems are ideal for this purpose because they do not require large powerful magnets and because they can examine materials enclosed in conductive shells such as lead shells. The NMR examination technique can be combined with ultra-low field NMR imaging, where an NMR image is obtained and analyzed to identify target volumes. Spatial sensitivity encoding can also be used to identify target volumes. After the target volumes are identified the NMR measurement technique can be used to identify their contents.

Aging dynamics in the polymer glass of poly(2-chlorostyrene): Dielectric susceptibility and volume

NASA Astrophysics Data System (ADS)

Fukao, Koji; Tahara, Daisuke

2009-11-01

Aging dynamics was investigated in the glassy states of poly(2-chlorostyrene) by measuring the complex electrical capacitance during aging below the glass transition temperature. The variations with time and temperature of the ac dielectric susceptibility and volume could be determined by simply measuring the variation in the complex electrical capacitance. Isothermal aging at a given temperature for several hours after an intermittent stop in constant-rate cooling is stored in the deviations of both the real and imaginary parts of the complex ac dielectric susceptibility and volume. During cooling after isothermal aging, the deviation of the ac dielectric susceptibility from the reference value decreases and almost vanishes at room temperature. By contrast, the deviation in volume induced during isothermal aging remains almost constant during cooling. The simultaneous measurement of ac dielectric susceptibility and volume clearly revealed that the ac dielectric susceptibility exhibits a full rejuvenation effect, whereas the volume does not show any rejuvenation effects. We discuss a plausible model that can reproduce the present experimental results.

Lunar crater volumes - Interpretation by models of impact cratering and upper crustal structure

NASA Technical Reports Server (NTRS)

Croft, S. K.

1978-01-01

Lunar crater volumes can be divided by size into two general classes with distinctly different functional dependence on diameter. Craters smaller than approximately 12 km in diameter are morphologically simple and increase in volume as the cube of the diameter, while craters larger than about 20 km are complex and increase in volume at a significantly lower rate implying shallowing. Ejecta and interior volumes are not identical and their ratio, Schroeters Ratio (SR), increases from about 0.5 for simple craters to about 1.5 for complex craters. The excess of ejecta volume causing the increase, can be accounted for by a discontinuity in lunar crust porosity at 1.5-2 km depth. The diameter range of significant increase in SR corresponds with the diameter range of transition from simple to complex crater morphology. This observation, combined with theoretical rebound calculation, indicates control of the transition diameter by the porosity structure of the upper crust.

Predictors of clinical outcome in emphysema patients with atelectasis following endoscopic valve therapy: A retrospective study.

PubMed

Gompelmann, Daniela; Hofbauer, Tobias; Gerovasili, Vasiliki; Eberhardt, Ralf; Lim, Hyun-Ju; Herth, Felix; Heussel, Claus-Peter

2016-10-01

The aim of endoscopic valve therapy in patients with emphysema is complete lobar atelectasis of the most emphysematous lobe. However, even after the radiological advent of atelectasis, great variability in clinical outcomes can be observed. The baseline clinical measures (vital capacity (VC), forced expiratory flow in 1 s (FEV1 ), residual volume (RV) and 6-min walk test (6-MWT)) and computed tomography variables (low attenuation volume (LAV) of the target lobe, LAV% of the target and the ipsilateral untreated lobe and LAV of the target lobe to LAV of the target lung and to LAV of the total lung) of 77 patients with complete atelectasis following valve therapy were retrospectively examined to determine their impact on patient´s outcome (changes in VC, FEV1 , RV and 6-MWT from baseline to the time of atelectasis). Low attenuation volume of the target lobe to LAV of the target lung predicts a significant FEV1 improvement in patients with complete lobar atelectasis following valve therapy. A 10% difference in that computed tomography predictor was associated with a 82-mL improvement in FEV1 (P = 0.006). Lower 6-MWT scores, low VC and high RV at baseline were significantly associated with greater improvement in the respective parameter (all P < 0.001). Low attenuation volume of the target lobe to LAV of the target lung and baseline clinical measures seem to significantly predict clinical outcomes in patients with complete lobar atelectasis following valve treatment. © 2016 Asian Pacific Society of Respirology.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lamichhane, N; Johnson, P; Chinea, F

Purpose: To evaluate the correlation between image features and the accuracy of manually drawn target contours on synthetic PET images Methods: A digital PET phantom was used in combination with Monte Carlo simulation to create a set of 26 simulated PET images featuring a variety of tumor shapes and activity heterogeneity. These tumor volumes were used as a gold standard in comparisons with manual contours delineated by 10 radiation oncologist on the simulated PET images. Metrics used to evaluate segmentation accuracy included the dice coefficient, false positive dice, false negative dice, symmetric mean absolute surface distance, and absolute volumetric difference.more » Image features extracted from the simulated tumors consisted of volume, shape complexity, mean curvature, and intensity contrast along with five texture features derived from the gray-level neighborhood difference matrices including contrast, coarseness, busyness, strength, and complexity. Correlation between these features and contouring accuracy were examined. Results: Contour accuracy was reasonably well correlated with a variety of image features. Dice coefficient ranged from 0.7 to 0.90 and was correlated closely with contrast (r=0.43, p=0.02) and complexity (r=0.5, p<0.001). False negative dice ranged from 0.10 to 0.50 and was correlated closely with contrast (r=0.68, p<0.001) and complexity (r=0.66, p<0.001). Absolute volumetric difference ranged from 0.0002 to 0.67 and was correlated closely with coarseness (r=0.46, p=0.02) and complexity (r=0.49, p=0.008). Symmetric mean absolute difference ranged from 0.02 to 1 and was correlated closely with mean curvature (r=0.57, p=0.02) and contrast (r=0.6, p=0.001). Conclusion: The long term goal of this study is to assess whether contouring variability can be reduced by providing feedback to the practitioner based on image feature analysis. The results are encouraging and will be used to develop a statistical model which will enable a prediction of contour accuracy based purely on image feature analysis.« less

Effect of spatial nonuniformity of heating on compression and burning of a thermonuclear target under direct multibeam irradiation by a megajoule laser pulse

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bel’kov, S. A.; Bondarenko, S. V.; Vergunova, G. A.

Direct-drive fusion targets are considered at present as an alternative to targets of indirect compression at a laser energy level of about 2 MJ. In this approach, the symmetry of compression and ignition of thermonuclear fuel play the major role. We report on the results of theoretical investigation of compression and burning of spherical direct-drive targets in the conditions of spatial nonuniformity of heating associated with a shift of the target from the beam center of focusing and possible laser radiation energy disbalance in the beams. The investigation involves numerous calculations based on a complex of 1D and 2D codesmore » RAPID, SEND (for determining the target illumination and the dynamics of absorption), DIANA, and NUT (1D and multidimensional hydrodynamics of compression and burning of targets). The target under investigation had the form of a two-layer shell (ablator made of inertial material CH and DT ice) filled with DT gas. We have determined the range of admissible variation of compression and combustion parameters of the target depending on the variation of the spatial nonuniformity of its heating by a multibeam laser system. It has been shown that low-mode (long-wavelength) perturbations deteriorate the characteristics of the central region due to less effective conversion of the kinetic energy of the target shell into the internal energy of the center. Local initiation of burning is also observed in off-center regions of the target in the case of substantial asymmetry of irradiation. In this case, burning is not spread over the entire volume of the DT fuel as a rule, which considerably reduces the thermonuclear yield as compared to that in the case of spherical symmetry and central ignition.« less

Intravesical markers for delineation of target volume during external focal irradiation of bladder carcinomas.

PubMed

Hulshof, Maarten C C M; van Andel, George; Bel, Arjen; Gangel, Pieter; van de Kamer, Jeroen B

2007-07-01

A clip forceps was developed which can insert markers at the border of a bladder tumour through a rigid cystoscope. This technique proved to be simple and safe and is of help for delineation of the target volume during CT simulation for focal boost irradiation of bladder cancer.

Intra-fraction motion of larynx radiotherapy

NASA Astrophysics Data System (ADS)

Durmus, Ismail Faruk; Tas, Bora

2018-02-01

In early stage laryngeal radiotherapy, movement is an important factor. Thyroid cartilage can move from swallowing, breathing, sound and reflexes. The effects of this motion on the target volume (PTV) during treatment were examined. In our study, the target volume movement during the treatment for this purpose was examined. Thus, setup margins are re-evaluated and patient-based PTV margins are determined. Intrafraction CBCT was scanned in 246 fractions for 14 patients. During the treatment, the amount of deviation which could be lateral, vertical and longitudinal axis was determined. ≤ ± 0.1cm deviation; 237 fractions in the lateral direction, 202 fractions in the longitudinal direction, 185 fractions in the vertical direction. The maximum deviation values were found in the longitudinal direction. Intrafraction guide in laryngeal radiotherapy; we are sure of the correctness of the treatment, the target volume is to adjust the margin and dose more precisely, we control the maximum deviation of the target volume for each fraction. Although the image quality of intrafraction-CBCT scans was lower than the image quality of planning CT, they showed sufficient contrast for this work.

Using injectable hydrogel markers to assess resimulation for boost target volume definition in a patient undergoing whole-breast radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patel, Henal; Goyal, Sharad; Kim, Leonard, E-mail: kimlh@rutgers.edu

Several publications have recommended that patients undergoing whole-breast radiotherapy be resimulated for boost planning. The rationale for this is that the seroma may be smaller when compared with the initial simulation. However, the decision remains whether to use the earlier or later images to define an appropriate boost target volume. A patient undergoing whole-breast radiotherapy had new, injectable, temporary hydrogel fiducial markers placed 1 to 3 cm from the seroma at the time of initial simulation. The patient was resimulated 4.5 weeks later for conformal photon boost planning. Computed tomography (CT) scans acquired at the beginning and the end ofmore » whole-breast radiotherapy showed that shrinkage of the lumpectomy cavity was not matched by a corresponding reduction in the surrounding tissue volume, as demarcated by hydrogel markers. This observation called into question the usual interpretation of cavity shrinkage for boost target definition. For this patient, it was decided to define the boost target volume on the initial planning CT instead of the new CT.« less

Analysis of radiation exposure for naval units of Operation Crossroads. Volume 3. (Appendix B) support ships. Technical report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weitz, R.; Thomas, C.; Klemm, J.

1982-03-03

External radiation doses are reconstructed for crews of support and target ships of Joint Task Force One at Operation CROSSROADS, 1946. Volume I describes the reconstruction methodology, which consists of modeling the radiation environment, to include the radioactivity of lagoon water, target ships, and support ship contamination; retracing ship paths through this environment; and calculating the doses to shipboard personnel. The USS RECLAIMER, a support ship, is selected as a representative ship to demonstrate this methodology. Doses for all other ships are summarized. Volume II (Appendix A) details the results for target ship personnel. Volume III (Appendix B) details themore » results for support ship personnel. Calculated doses for more than 36,000 personnel aboard support ships while at Bikini range from zero to 1.7 rem. Of those approximately 34,000 are less than 0.5 rem. From the models provided, doses due to target ship reboarding and doses accrued after departure from Bikini can be calculated, based on the individual circumstances of exposure.« less

The role of PET in target localization for radiotherapy treatment planning.

PubMed

Rembielak, Agata; Price, Pat

2008-02-01

Positron emission tomography (PET) is currently accepted as an important tool in oncology, mostly for diagnosis, staging and restaging purposes. It provides a new type of information in radiotherapy, functional rather than anatomical. PET imaging can also be used for target volume definition in radiotherapy treatment planning. The need for very precise target volume delineation has arisen with the increasing use of sophisticated three-dimensional conformal radiotherapy techniques and intensity modulated radiation therapy. It is expected that better delineation of the target volume may lead to a significant reduction in the irradiated volume, thus lowering the risk of treatment complications (smaller safety margins). Better tumour visualisation also allows a higher dose of radiation to be applied to the tumour, which may lead to better tumour control. The aim of this article is to review the possible use of PET imaging in the radiotherapy of various cancers. We focus mainly on non-small cell lung cancer, lymphoma and oesophageal cancer, but also include current opinion on the use of PET-based planning in other tumours including brain, uterine cervix, rectum and prostate.

High-resolution 3D laser imaging based on tunable fiber array link

NASA Astrophysics Data System (ADS)

Zhao, Sisi; Ruan, Ningjuan; Yang, Song

2017-10-01

Airborne photoelectric reconnaissance system with the bore sight down to the ground is an important battlefield situational awareness system, which can be used for reconnaissance and surveillance of complex ground scene. Airborne 3D imaging Lidar system is recognized as the most potential candidates for target detection under the complex background, and is progressing in the directions of high resolution, long distance detection, high sensitivity, low power consumption, high reliability, eye safe and multi-functional. However, the traditional 3D laser imaging system has the disadvantages of lower imaging resolutions because of the small size of the existing detector, and large volume. This paper proposes a high resolution laser 3D imaging technology based on the tunable optical fiber array link. The echo signal is modulated by a tunable optical fiber array link and then transmitted to the focal plane detector. The detector converts the optical signal into electrical signals which is given to the computer. Then, the computer accomplishes the signal calculation and image restoration based on modulation information, and then reconstructs the target image. This paper establishes the mathematical model of tunable optical fiber array signal receiving link, and proposes the simulation and analysis of the affect factors on high density multidimensional point cloud reconstruction.

LLE Review Quarterly Report (October - December 2007). Volume 113

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zuegel, Jonathan D.

2007-12-01

This volume of the LLE Review, covering October–December 2007, features “High-Intensity Laser–Plasma Interactions in the Refluxing Limit,” by P. M. Nilson, W. Theobald, J. Myatt, C. Stoeckl, M. Storm, O. V. Gotchev, J. D. Zuegel, R. Betti, D. D. Meyerhofer, and T. C. Sangster. In this article (p. 1), the authors report on target experiments using the Multi-Terawatt (MTW) Laser Facility to study isochoric heating of solid-density targets by fast electrons produced from intense, short-pulse laser irradiation. Electron refluxing occurs due to target-sheath field effects and contains most of the fast electrons within the target volume. This efficiently heats themore » solid-density plasma through collisions. X-ray spectroscopic measurements of absolute K α (x-radiation) photon yields and variations of the K β/K α b emission ratio both indicate that laser energy couples to fast electrons with a conversion efficiency of approximately 20%. Bulk electron temperatures of at least 200 eV are inferred for the smallest mass targets.« less

Changes in Search Path Complexity and Length During Learning of a Virtual Water Maze: Age Differences and Differential Associations with Hippocampal Subfield Volumes

PubMed Central

Daugherty, Ana M.; Bender, Andrew R.; Yuan, Peng; Raz, Naftali

2016-01-01

Impairment of hippocampus-dependent cognitive processes has been proposed to underlie age-related deficits in navigation. Animal studies suggest a differential role of hippocampal subfields in various aspects of navigation, but that hypothesis has not been tested in humans. In this study, we examined the association between volume of hippocampal subfields and age differences in virtual spatial navigation. In a sample of 65 healthy adults (age 19–75 years), advanced age was associated with a slower rate of improvement operationalized as shortening of the search path over 25 learning trials on a virtual Morris water maze task. The deficits were partially explained by greater complexity of older adults' search paths. Larger subiculum and entorhinal cortex volumes were associated with a faster decrease in search path complexity, which in turn explained faster shortening of search distance. Larger Cornu Ammonis (CA)1–2 volume was associated with faster distance shortening, but not in path complexity reduction. Age differences in regional volumes collectively accounted for 23% of the age-related variance in navigation learning. Independent of subfield volumes, advanced age was associated with poorer performance across all trials, even after reaching the asymptote. Thus, subiculum and CA1–2 volumes were associated with speed of acquisition, but not magnitude of gains in virtual maze navigation. PMID:25838036

Doses to organs and tissues from concomitant imaging in radiotherapy: a suggested framework for clinical justification.

PubMed

Harrison, R M

2008-12-01

The increasing use of imaging for localization and verification in radiotherapy has raised issues concerning the justifiable doses to critical organs and tissues from concomitant exposures, particularly when extensive image-guided radiotherapy is indicated. Doses at positions remote from the target volume include components from high-energy leakage and scatter, as well as from concomitant imaging. In this paper, simulated prostate, breast and larynx treatments are used to compare doses from both high-energy and concomitant exposures as a function of distance from the target volume. It is suggested that the fraction, R, of the total dose at any point within the patient that is attributable to concomitant exposures may be a useful aid in their justification. R is small within the target volume and at large distances from it. However, there is a critical region immediately adjacent to the planning target volume where the dose from concomitant imaging combines with leakage and scatter to give values of R that approach 0.5 in the examples given here. This is noteworthy because the regions just outside the target volume will receive total doses in the order of 1 Gy, where commensurately high risk factors may not be substantially reduced because of cell kill. Other studies have identified these regions as sites of second cancers. The justification of an imaging regimen might therefore usefully take into account the maximum value of R encountered from the combination of imaging and radiotherapy for particular treatment sites.

Effects of online cone-beam computed tomography with active breath control in determining planning target volume during accelerated partial breast irradiation.

PubMed

Li, Y; Zhong, R; Wang, X; Ai, P; Henderson, F; Chen, N; Luo, F

2017-04-01

To test if active breath control during cone-beam computed tomography (CBCT) could improve planning target volume during accelerated partial breast radiotherapy for breast cancer. Patients who were more than 40 years old, underwent breast-conserving dissection and planned for accelerated partial breast irradiation, and with postoperative staging limited to T1-2 N0 M0, or postoperative staging T2 lesion no larger than 3cm with a negative surgical margin greater than 2mm were enrolled. Patients with lobular carcinoma or extensive ductal carcinoma in situ were excluded. CBCT images were obtained pre-correction, post-correction and post-treatment. Set-up errors were recorded at left-right, anterior-posterior and superior-inferior directions. The differences between these CBCT images, as well as calculated radiation doses, were compared between patients with active breath control or free breathing. Forty patients were enrolled, among them 25 had active breath control. A total of 836 CBCT images were obtained for analysis. CBCT significantly reduced planning target volume. However, active breath control did not show significant benefit in decreasing planning target volume margin and the doses of organ-at-risk when compared to free breathing. CBCT, but not active breath control, could reduce planning target volume during accelerated partial breast irradiation. Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Utilization of cone-beam CT for offline evaluation of target volume coverage during prostate image-guided radiotherapy based on bony anatomy alignment.

PubMed

Paluska, Petr; Hanus, Josef; Sefrova, Jana; Rouskova, Lucie; Grepl, Jakub; Jansa, Jan; Kasaova, Linda; Hodek, Miroslav; Zouhar, Milan; Vosmik, Milan; Petera, Jiri

2012-01-01

To assess target volume coverage during prostate image-guided radiotherapy based on bony anatomy alignment and to assess possibility of safety margin reduction. Implementation of IGRT should influence safety margins. Utilization of cone-beam CT provides current 3D anatomic information directly in irradiation position. Such information enables reconstruction of the actual dose distribution. Seventeen prostate patients were treated with daily bony anatomy image-guidance. Cone-beam CT (CBCT) scans were acquired once a week immediately after bony anatomy alignment. After the prostate, seminal vesicles, rectum and bladder were contoured, the delivered dose distribution was reconstructed. Target dose coverage was evaluated by the proportion of the CTV encompassed by the 95% isodose. Original plans employed a 1 cm safety margin. Alternative plans assuming a smaller 7 mm margin between CTV and PTV were evaluated in the same way. Rectal and bladder volumes were compared with the initial ones. Rectal and bladder volumes irradiated with doses higher than 75 Gy, 70 Gy, 60 Gy, 50 Gy and 40 Gy were analyzed. In 12% of reconstructed plans the prostate coverage was not sufficient. The prostate underdosage was observed in 5 patients. Coverage of seminal vesicles was not satisfactory in 3% of plans. Most of the target underdosage corresponded to excessive rectal or bladder filling. Evaluation of alternative plans assuming a smaller 7 mm margin revealed 22% and 11% of plans where prostate and seminal vesicles coverage, respectively, was compromised. These were distributed over 8 and 7 patients, respectively. Sufficient dose coverage of target volumes was not achieved for all patients. Reducing of safety margin is not acceptable. Initial rectal and bladder volumes cannot be considered representative for subsequent treatment.

Miniature Laser Tracker

DOEpatents

Vann, Charles S.

2003-09-09

This small, inexpensive, non-contact laser sensor can detect the location of a retroreflective target in a relatively large volume and up to six degrees of position. The tracker's laser beam is formed into a plane of light which is swept across the space of interest. When the beam illuminates the retroreflector, some of the light returns to the tracker. The intensity, angle, and time of the return beam is measured to calculate the three dimensional location of the target. With three retroreflectors on the target, the locations of three points on the target are measured, enabling the calculation of all six degrees of target position. Until now, devices for three-dimensional tracking of objects in a large volume have been heavy, large, and very expensive. Because of the simplicity and unique characteristics of this tracker, it is capable of three-dimensional tracking of one to several objects in a large volume, yet it is compact, light-weight, and relatively inexpensive. Alternatively, a tracker produces a diverging laser beam which is directed towards a fixed position, and senses when a retroreflective target enters the fixed field of view. An optically bar coded target can be read by the tracker to provide information about the target. The target can be formed of a ball lens with a bar code on one end. As the target moves through the field, the ball lens causes the laser beam to scan across the bar code.

ON THE BENEFITS AND RISKS OF PROTON THERAPY IN PEDIATRIC CRANIOPHARYNGIOMA

PubMed Central

Beltran, Chris; Roca, Monica; Merchant, Thomas E.

2013-01-01

Purpose Craniopharyngioma is a pediatric brain tumor whose volume is prone to change during radiation therapy. We compared photon- and proton-based irradiation methods to determine the effect of tumor volume change on target coverage and normal tissue irradiation in these patients. Methods and Materials For this retrospective study, we acquired imaging and treatment-planning data from 14 children with craniopharyngioma (mean age, 5.1 years) irradiated with photons (54 Gy) and monitored by weekly magnetic resonance imaging (MRI) examinations during radiation therapy. Photon intensity-modulated radiation therapy (IMRT), double-scatter proton (DSP) therapy, and intensity-modulated proton therapy (IMPT) plans were created for each patient based on his or her pre-irradiation MRI. Target volumes were contoured on each weekly MRI scan for adaptive modeling. The measured differences in conformity index (CI) and normal tissue doses, including functional sub-volumes of the brain, were compared across the planning methods, as was target coverage based on changes in target volumes during treatment. Results CI and normal tissue dose values of IMPT plans were significantly better than those of the IMRT and DSP plans (p < 0.01). Although IMRT plans had a higher CI and lower optic nerve doses (p < 0.01) than did DSP plans, DSP plans had lower cochlear, optic chiasm, brain, and scanned body doses (p < 0.01). The mean planning target volume (PTV) at baseline was 54.8 cm3, and the mean increase in PTV was 11.3% over the course of treatment. The dose to 95% of the PTV was correlated with a change in the PTV; the R2 values for all models, 0.73 (IMRT), 0.38 (DSP), and 0.62 (IMPT), were significant (p < 0.01). Conclusions Compared with photon IMRT, proton therapy has the potential to significantly reduce whole-brain and -body irradiation in pediatric patients with craniopharyngioma. IMPT is the most conformal method and spares the most normal tissue; however, it is highly sensitive to target volume changes, whereas the DSP method is not. PMID:21570209

Interobserver delineation uncertainty in involved-node radiation therapy (INRT) for early-stage Hodgkin lymphoma: on behalf of the Radiotherapy Committee of the EORTC lymphoma group.

PubMed

Aznar, Marianne C; Girinsky, Theodore; Berthelsen, Anne Kiil; Aleman, Berthe; Beijert, Max; Hutchings, Martin; Lievens, Yolande; Meijnders, Paul; Meidahl Petersen, Peter; Schut, Deborah; Maraldo, Maja V; van der Maazen, Richard; Specht, Lena

2017-04-01

In early-stage classical Hodgkin lymphoma (HL) the target volume nowadays consists of the volume of the originally involved nodes. Delineation of this volume on a post-chemotherapy CT-scan is challenging. We report on the interobserver variability in target volume definition and its impact on resulting treatment plans. Two representative cases were selected (1: male, stage IB, localization: left axilla; 2: female, stage IIB, localizations: mediastinum and bilateral neck). Eight experienced observers individually defined the clinical target volume (CTV) using involved-node radiotherapy (INRT) as defined by the EORTC-GELA guidelines for the H10 trial. A consensus contour was generated and the standard deviation computed. We investigated the overlap between observer and consensus contour [Sørensen-Dice coefficient (DSC)] and the magnitude of gross deviations between the surfaces of the observer and consensus contour (Hausdorff distance). 3D-conformal (3D-CRT) and intensity-modulated radiotherapy (IMRT) plans were calculated for each contour in order to investigate the impact of interobserver variability on each treatment modality. Similar target coverage was enforced for all plans. The median CTV was 120 cm 3 (IQR: 95-173 cm 3 ) for Case 1, and 255 cm 3 (IQR: 183-293 cm 3 ) for Case 2. DSC values were generally high (>0.7), and Hausdorff distances were about 30 mm. The SDs between all observer contours, providing an estimate of the systematic error associated with delineation uncertainty, ranged from 1.9 to 3.8 mm (median: 3.2 mm). Variations in mean dose resulting from different observer contours were small and were not higher in IMRT plans than in 3D-CRT plans. We observed considerable differences in target volume delineation, but the systematic delineation uncertainty of around 3 mm is comparable to that reported in other tumour sites. This report is a first step towards calculating an evidence-based planning target volume margin for INRT in HL.

[Management of locally advanced anal canal carcinoma with modulated arctherapy and concurrent chemotherapy].

PubMed

Troussier, I; Huguet, F; Servagi-Vernat, S; Benahim, C; Khalifa, J; Darmon, I; Ortholan, C; Krebs, L; Dejean, C; Fenoglietto, P; Vieillot, S; Bensadoun, R-J; Thariat, J

2015-04-01

The standard treatment of locally advanced (stage II and III) squamous cell carcinoma of the anal canal consists of concurrent chemoradiotherapy (two cycles of 5-fluoro-uracil, mitomycin C, on a 28-day cycle), with a dose of 45 Gy in 1.8 Gy per fraction in the prophylactic planning target volume and additional 14 to 20 Gy in the boost planning target volume (5 days per week) with a possibility of 15 days gap period between the two sequences. While conformal irradiation may only yield suboptimal tumor coverage using complex photon/electron field junctions (especially on nodal areas), intensity modulated radiation therapy techniques (segmented static, dynamic, volumetric modulated arc therapy and helical tomotherapy) allow better tumour coverage while sparing organs at risk from intermediate/high doses (small intestine, perineum/genitalia, bladder, pelvic bone, etc.). Such dosimetric advantages result in fewer severe acute toxicities and better potential to avoid a prolonged treatment break that increases risk of local failure. These techniques also allow a reduction in late gastrointestinal and skin toxicities of grade 3 or above, as well as better functional conservation of anorectal sphincter. The technical achievements (simulation, contouring, prescription dose, treatment planning, control quality) of volumetric modulated arctherapy are discussed. Copyright © 2015 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Geometric modeling of subcellular structures, organelles, and multiprotein complexes

PubMed Central

Feng, Xin; Xia, Kelin; Tong, Yiying; Wei, Guo-Wei

2013-01-01

SUMMARY Recently, the structure, function, stability, and dynamics of subcellular structures, organelles, and multi-protein complexes have emerged as a leading interest in structural biology. Geometric modeling not only provides visualizations of shapes for large biomolecular complexes but also fills the gap between structural information and theoretical modeling, and enables the understanding of function, stability, and dynamics. This paper introduces a suite of computational tools for volumetric data processing, information extraction, surface mesh rendering, geometric measurement, and curvature estimation of biomolecular complexes. Particular emphasis is given to the modeling of cryo-electron microscopy data. Lagrangian-triangle meshes are employed for the surface presentation. On the basis of this representation, algorithms are developed for surface area and surface-enclosed volume calculation, and curvature estimation. Methods for volumetric meshing have also been presented. Because the technological development in computer science and mathematics has led to multiple choices at each stage of the geometric modeling, we discuss the rationales in the design and selection of various algorithms. Analytical models are designed to test the computational accuracy and convergence of proposed algorithms. Finally, we select a set of six cryo-electron microscopy data representing typical subcellular complexes to demonstrate the efficacy of the proposed algorithms in handling biomolecular surfaces and explore their capability of geometric characterization of binding targets. This paper offers a comprehensive protocol for the geometric modeling of subcellular structures, organelles, and multiprotein complexes. PMID:23212797

Quality assurance for high dose rate brachytherapy treatment planning optimization: using a simple optimization to verify a complex optimization

NASA Astrophysics Data System (ADS)

Deufel, Christopher L.; Furutani, Keith M.

2014-02-01

As dose optimization for high dose rate brachytherapy becomes more complex, it becomes increasingly important to have a means of verifying that optimization results are reasonable. A method is presented for using a simple optimization as quality assurance for the more complex optimization algorithms typically found in commercial brachytherapy treatment planning systems. Quality assurance tests may be performed during commissioning, at regular intervals, and/or on a patient specific basis. A simple optimization method is provided that optimizes conformal target coverage using an exact, variance-based, algebraic approach. Metrics such as dose volume histogram, conformality index, and total reference air kerma agree closely between simple and complex optimizations for breast, cervix, prostate, and planar applicators. The simple optimization is shown to be a sensitive measure for identifying failures in a commercial treatment planning system that are possibly due to operator error or weaknesses in planning system optimization algorithms. Results from the simple optimization are surprisingly similar to the results from a more complex, commercial optimization for several clinical applications. This suggests that there are only modest gains to be made from making brachytherapy optimization more complex. The improvements expected from sophisticated linear optimizations, such as PARETO methods, will largely be in making systems more user friendly and efficient, rather than in finding dramatically better source strength distributions.

Generation of WNK1 knockout cell lines by CRISPR/Cas-mediated genome editing.

PubMed

Roy, Ankita; Goodman, Joshua H; Begum, Gulnaz; Donnelly, Bridget F; Pittman, Gabrielle; Weinman, Edward J; Sun, Dandan; Subramanya, Arohan R

2015-02-15

Sodium-coupled SLC12 cation chloride cotransporters play important roles in cell volume and chloride homeostasis, epithelial fluid secretion, and renal tubular salt reabsorption. These cotransporters are phosphorylated and activated indirectly by With-No-Lysine (WNK) kinases through their downstream effector kinases, Ste20- and SPS1-related proline alanine-rich kinase (SPAK) and oxidative stress-responsive kinase 1 (OSR1). Multiple WNK kinases can coexist within a single cell type, although their relative contributions to SPAK/OSR1 activation and salt transport remain incompletely understood. Deletion of specific WNKs from cells that natively express a functional WNK-SPAK/OSR1 network will help resolve these knowledge gaps. Here, we outline a simple method to selectively knock out full-length WNK1 expression from mammalian cells using RNA-guided clustered regularly interspaced short palindromic repeats/Cas9 endonucleases. Two clonal cell lines were generated by using a single-guide RNA (sgRNA) targeting exon 1 of the WNK1 gene, which produced indels that abolished WNK1 protein expression. Both cell lines exhibited reduced endogenous WNK4 protein abundance, indicating that WNK1 is required for WNK4 stability. Consistent with an on-target effect, the reduced WNK4 abundance was associated with increased expression of the KLHL3/cullin-3 E3 ubiquitin ligase complex and was rescued by exogenous WNK1 overexpression. Although the morphology of the knockout cells was indistinguishable from control, they exhibited low baseline SPAK/OSR1 activity and failed to trigger regulatory volume increase after hypertonic stress, confirming an essential role for WNK1 in cell volume regulation. Collectively, our data show how this new, powerful, and accessible gene-editing technology can be used to dissect and analyze WNK signaling networks.

Treatment planning and dose analysis for interstitial photodynamic therapy of prostate cancer

NASA Astrophysics Data System (ADS)

Davidson, Sean R. H.; Weersink, Robert A.; Haider, Masoom A.; Gertner, Mark R.; Bogaards, Arjen; Giewercer, David; Scherz, Avigdor; Sherar, Michael D.; Elhilali, Mostafa; Chin, Joseph L.; Trachtenberg, John; Wilson, Brian C.

2009-04-01

With the development of new photosensitizers that are activated by light at longer wavelengths, interstitial photodynamic therapy (PDT) is emerging as a feasible alternative for the treatment of larger volumes of tissue. Described here is the application of PDT treatment planning software developed by our group to ensure complete coverage of larger, geometrically complex target volumes such as the prostate. In a phase II clinical trial of TOOKAD vascular targeted photodynamic therapy (VTP) for prostate cancer in patients who failed prior radiotherapy, the software was used to generate patient-specific treatment prescriptions for the number of treatment fibres, their lengths, their positions and the energy each delivered. The core of the software is a finite element solution to the light diffusion equation. Validation against in vivo light measurements indicated that the software could predict the location of an iso-fluence contour to within approximately ±2 mm. The same software was used to reconstruct the treatments that were actually delivered, thereby providing an analysis of the threshold light dose required for TOOKAD-VTP of the post-irradiated prostate. The threshold light dose for VTP-induced prostate damage, as measured one week post-treatment using contrast-enhanced MRI, was found to be highly heterogeneous, both within and between patients. The minimum light dose received by 90% of the prostate, D90, was determined from each patient's dose-volume histogram and compared to six-month sextant biopsy results. No patient with a D90 less than 23 J cm-2 had complete biopsy response, while 8/13 (62%) of patients with a D90 greater than 23 J cm-2 had negative biopsies at six months. The doses received by the urethra and the rectal wall were also investigated.

Pancreatic cancer planning: Complex conformal vs modulated therapies.

PubMed

Chapman, Katherine L; Witek, Matthew E; Chen, Hongyu; Showalter, Timothy N; Bar-Ad, Voichita; Harrison, Amy S

2016-01-01

To compare the roles of intensity-modulated radiation therapy (IMRT) and volumetric- modulated arc therapy (VMAT) therapy as compared to simple and complex 3-dimensional chemoradiotherpy (3DCRT) planning for resectable and borderline resectable pancreatic cancer. In all, 12 patients who received postoperative radiotherapy (8) or neoadjuvant concurrent chemoradiotherapy (4) were evaluated retrospectively. Radiotherapy planning was performed for 4 treatment techniques: simple 4-field box, complex 5-field 3DCRT, 5 to 6-field IMRT, and single-arc VMAT. All volumes were approved by a single observer in accordance with Radiation Therapy Oncology Group (RTOG) Pancreas Contouring Atlas. Plans included tumor/tumor bed and regional lymph nodes to 45Gy; with tumor/tumor bed boosted to 50.4Gy, at least 95% of planning target volume (PTV) received the prescription dose. Dose-volume histograms (DVH) for multiple end points, treatment planning, and delivery time were assessed. Complex 3DCRT, IMRT, and VMAT plans significantly (p < 0.05) decreased mean kidney dose, mean liver dose, liver (V30, V35), stomach (D10%), stomach (V45), mean right kidney dose, and right kidney (V15) as compared with the simple 4-field plans that are most commonly reported in the literature. IMRT plans resulted in decreased mean liver dose, liver (V35), and left kidney (V15, V18, V20). VMAT plans decreased small bowel (D10%, D15%), small bowel (V35, V45), stomach (D10%, D15%), stomach (V35, V45), mean liver dose, liver (V35), left kidney (V15, V18, V20), and right kidney (V18, V20). VMAT plans significantly decreased small bowel (D10%, D15%), left kidney (V20), and stomach (V45) as compared with IMRT plans. Treatment planning and delivery times were most efficient for simple 4-field box and VMAT. Excluding patient setup and imaging, average treatment delivery was within 10minutes for simple and complex 3DCRT, IMRT, and VMAT treatments. This article shows significant improvements in 3D plan performance with complex planning over the more frequently compared 3- or 4-field simple 3D planning techniques. VMAT plans continue to demonstrate potential for the most organ sparing. However, further studies are required to identify if dosimetric benefits associated with inverse optimized planning can be translated into clinical benefits and if these treatment techniques are value-added therapies for this group of patients with cancer. Published by Elsevier Inc.

Detection of E. coli O157:H7 in complex matrices under varying flow parameters with a robotic fluorometric assay system

NASA Astrophysics Data System (ADS)

Leskinen, Stephaney D.; Schlemmer, Sarah M.; Kearns, Elizabeth A.; Lim, Daniel V.

2009-02-01

The development of rapid assays for detection of microbial pathogens in complex matrices is needed to protect public health due to continued outbreaks of disease from contaminated foods and water. An Escherichia coli O157:H7 detection assay was designed using a robotic, fluorometric assay system. The system integrates optics, fluidics, robotics and software for the detection of foodborne pathogens or toxins in as many as four samples simultaneously. It utilizes disposable fiber optic waveguides coated with biotinylated antibodies for capture of target analytes from complex sample matrices. Computer-controlled rotation of sample cups allows complete contact between the sample and the waveguide. Detection occurs via binding of a fluorophore-labeled antibody to the captured target, which leads to an increase in the fluorescence signal. Assays are completed within twenty-five minutes. Sample matrices included buffer, retentate (material recovered from the filter of the Automated Concentration System (ACS) following hollow fiber ultrafiltration), spinach wash and ground beef. The matrices were spiked with E. coli O157:H7 (103-105 cells/ml) and the limits of detection were determined. The effect of sample rotation on assay sensitivity was also examined. Rotation parameters for each sample matrix included 10 ml with rotation, 5 ml with rotation and 0.1 ml without rotation. Detection occurred at 104 cells/ml in buffer and spinach wash and at 105 cells/ml in retentate and ground beef. Detection was greater for rotated samples in each matrix except ground beef. Enhanced detection of E. coli from large, rotated volumes of complex matrices was confirmed.

Analysis of FET-PET imaging for target volume definition in patients with gliomas treated with conformal radiotherapy.

PubMed

Rieken, Stefan; Habermehl, Daniel; Giesel, Frederik L; Hoffmann, Christoph; Burger, Ute; Rief, Harald; Welzel, Thomas; Haberkorn, Uwe; Debus, Jürgen; Combs, Stephanie E

2013-12-01

Modern radiotherapy (RT) techniques such as stereotactic RT, intensity-modulated RT, or particle irradiation allow local dose escalation with simultaneous sparing of critical organs. Several trials are currently investigating their benefit in glioma reirradiation and boost irradiation. Target volume definition is of critical importance especially when steep dose gradient techniques are employed. In this manuscript we investigate the impact of O-(2-(F-18)fluoroethyl)-l-tyrosine-positron emission tomography/computer tomography (FET-PET/CT) on target volume definition in low and high grade glioma patients undergoing either first or re-irradiation with particles. We investigated volumetric size and uniformity of magnetic resonance imaging (MRI)- vs. FET-PET/CT-derived gross tumor volumes (GTVs) and planning target volumes (PTVs) of 41 glioma patients. Clinical cases are presented to demonstrate potential benefits of integrating FET-PET/CT-planning into daily routine. Integrating FET-uptake into the delineation of GTVs yields larger volumes. Combined modality-derived PTVs are significantly enlarged in high grade glioma patients and in case of primary RT. The congruence of MRI and FET signals for the identification of glioma GTVs is poor with mean uniformity indices of 0.39. MRI-based PTVs miss 17% of FET-PET/CT-based GTVs. Non significant alterations were detected in low grade glioma patients and in those undergoing reirradiation. Target volume definition for malignant gliomas during initial RT may yield significantly differing results depending upon the imaging modality, which the contouring process is based upon. The integration of both MRI and FET-PET/CT may help to improve GTV coverage by avoiding larger incongruences between physical and biological imaging techniques. In low grade gliomas and in cases of reirradiation, more studies are needed in order to investigate a potential benefit of FET-PET/CT for planning of RT. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Dosimetric and radiobiological characterizations of prostate intensity-modulated radiotherapy and volumetric-modulated arc therapy: A single-institution review of ninety cases

PubMed Central

Khan, Muhammad Isa; Jiang, Runqing; Kiciak, Alexander; ur Rehman, Jalil; Afzal, Muhammad; Chow, James C. L.

2016-01-01

This study reviewed prostate volumetric-modulated arc therapy (VMAT) plans with intensity-modulated radiotherapy (IMRT) plans after prostate IMRT technique was replaced by VMAT in an institution. Characterizations of dosimetry and radiobiological variation in prostate were determined based on treatment plans of 40 prostate IMRT patients (planning target volume = 77.8–335 cm3) and 50 VMAT patients (planning target volume = 120–351 cm3) treated before and after 2013, respectively. Both IMRT and VMAT plans used the same dose-volume criteria in the inverse planning optimization. Dose-volume histogram, mean doses of target and normal tissues (rectum, bladder and femoral heads), dose-volume points (D99% of planning target volume; D30%, D50%, V30 Gy and V35 Gy of rectum and bladder; D5%, V14 Gy, V22 Gy of femoral heads), conformity index (CI), homogeneity index (HI), gradient index (GI), prostate tumor control probability (TCP), and rectal normal tissue complication probability (NTCP) based on the Lyman-Burman-Kutcher algorithm were calculated for each IMRT and VMAT plan. From our results, VMAT plan was found better due to its higher (1.05%) CI, lower (0.83%) HI and (0.75%) GI than IMRT. Comparing doses in normal tissues between IMRT and VMAT, it was found that IMRT mostly delivered higher doses of about 1.05% to the normal tissues than VMAT. Prostate TCP and rectal NTCP were found increased (1%) for VMAT than IMRT. It is seen that VMAT technique can decrease the dose-volume evaluation criteria for the normal tissues. Based on our dosimetric and radiobiological results in treatment plans, it is concluded that our VMAT implementation could produce comparable or slightly better target coverage and normal tissue sparing with a faster treatment time in prostate radiotherapy. PMID:27651562

Radar cross sections of standard and complex shape targets

NASA Technical Reports Server (NTRS)

Sohel, M. S.

1974-01-01

The theoretical, analytical, and experimental results are described for radar cross sections (RCS) of different-shaped targets. Various techniques for predicting RCS are given, and RCS of finite standard targets are presented. Techniques used to predict the RCS of complex targets are made, and the RCS complex shapes are provided.

ESTRO ACROP guidelines for target volume definition in the treatment of locally advanced non-small cell lung cancer.

PubMed

Nestle, Ursula; De Ruysscher, Dirk; Ricardi, Umberto; Geets, Xavier; Belderbos, Jose; Pöttgen, Christoph; Dziadiuszko, Rafal; Peeters, Stephanie; Lievens, Yolande; Hurkmans, Coen; Slotman, Ben; Ramella, Sara; Faivre-Finn, Corinne; McDonald, Fiona; Manapov, Farkhad; Putora, Paul Martin; LePéchoux, Cécile; Van Houtte, Paul

2018-04-01

Radiotherapy (RT) plays a major role in the curative treatment of locally advanced non-small cell lung cancer (NSCLC). Therefore, the ACROP committee was asked by the ESTRO to provide recommendations on target volume delineation for standard clinical scenarios in definitive (chemo)radiotherapy (RT) and adjuvant RT for locally advanced NSCLC. The guidelines given here are a result of the evaluation of a structured questionnaire followed by a consensus discussion, voting and writing procedure within the committee. Hence, we provide advice for methods and time-points of diagnostics and imaging before the start of treatment planning and for the mandatory and optional imaging to be used for planning itself. Concerning target volumes, recommendations are given for GTV delineation of primary tumour and lymph nodes followed by issues related to the delineation of CTVs for definitive and adjuvant radiotherapy. In the context of PTV delineation, recommendations about the management of geometric uncertainties and target motion are given. We further provide our opinions on normal tissue delineation and organisational and responsibility questions in the process of target volume delineation. This guideline intends to contribute to the standardisation and optimisation of the process of RT treatment planning for clinical practice and prospective studies. Copyright © 2018 Elsevier B.V. All rights reserved.

Clinical implementation of stereotaxic brain implant optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rosenow, U.F.; Wojcicka, J.B.

1991-03-01

This optimization method for stereotaxic brain implants is based on seed/strand configurations of the basic type developed for the National Cancer Institute (NCI) atlas of regular brain implants. Irregular target volume shapes are determined from delineation in a stack of contrast enhanced computed tomography scans. The neurosurgeon may then select up to ten directions, or entry points, of surgical approach of which the program finds the optimal one under the criterion of smallest target volume diameter. Target volume cross sections are then reconstructed in 5-mm-spaced planes perpendicular to the implantation direction defined by the entry point and the target volumemore » center. This information is used to define a closed line in an implant cross section along which peripheral seed strands are positioned and which has now an irregular shape. Optimization points are defined opposite peripheral seeds on the target volume surface to which the treatment dose rate is prescribed. Three different optimization algorithms are available: linear least-squares programming, quadratic programming with constraints, and a simplex method. The optimization routine is implemented into a commercial treatment planning system. It generates coordinate and source strength information of the optimized seed configurations for further dose rate distribution calculation with the treatment planning system, and also the coordinate settings for the stereotaxic Brown-Roberts-Wells (BRW) implantation device.« less

Target coverage in image-guided stereotactic body radiotherapy of liver tumors.

PubMed

Wunderink, Wouter; Méndez Romero, Alejandra; Vásquez Osorio, Eliana M; de Boer, Hans C J; Brandwijk, René P; Levendag, Peter C; Heijmen, Ben J M

2007-05-01

To determine the effect of image-guided procedures (with computed tomography [CT] and electronic portal images before each treatment fraction) on target coverage in stereotactic body radiotherapy for liver patients using a stereotactic body frame (SBF) and abdominal compression. CT guidance was used to correct for day-to-day variations in the tumor's mean position in the SBF. By retrospectively evaluating 57 treatment sessions, tumor coverage, as obtained with the clinically applied CT-guided protocol, was compared with that of alternative procedures. The internal target volume-plus (ITV(+)) was introduced to explicitly include uncertainties in tumor delineations resulting from CT-imaging artifacts caused by residual respiratory motion. Tumor coverage was defined as the volume overlap of the ITV(+), derived from a tumor delineated in a treatment CT scan, and the planning target volume. Patient stability in the SBF, after acquisition of the treatment CT scan, was evaluated by measuring the displacement of the bony anatomy in the electronic portal images relative to CT. Application of our clinical protocol (with setup corrections following from manual measurements of the distances between the contours of the planning target volume and the daily clinical target volume in three orthogonal planes, multiple two-dimensional) increased the frequency of nearly full (> or = 99%) ITV(+) coverage to 77% compared with 63% without setup correction. An automated three-dimensional method further improved the frequency to 96%. Patient displacements in the SBF were generally small (< or = 2 mm, 1 standard deviation), but large craniocaudal displacements (maximal 7.2 mm) were occasionally observed. Daily, CT-assisted patient setup may substantially improve tumor coverage, especially with the automated three-dimensional procedure. In the present treatment design, patient stability in the SBF should be verified with portal imaging.

Preoperative single fraction partial breast radiotherapy for early-stage breast cancer.

PubMed

Palta, Manisha; Yoo, Sua; Adamson, Justus D; Prosnitz, Leonard R; Horton, Janet K

2012-01-01

Several recent series evaluating external beam accelerated partial breast irradiation (PBI) have reported adverse cosmetic outcomes, possibly related to large volumes of normal tissue receiving near-prescription doses. We hypothesized that delivery of external beam PBI in a single fraction to the preoperative tumor volume would be feasible and result in a decreased dose to the uninvolved breast compared with institutional postoperative PBI historical controls. A total of 17 patients with unifocal Stage T1 breast cancer were identified. Contrast-enhanced subtraction magnetic resonance images were loaded into an Eclipse treatment planning system and used to define the target volumes. A "virtual plan" was created using four photon beams in a noncoplanar beam arrangement and optimized to deliver 15 Gy to the planning target volume. The median breast volume was 1,713 cm(3) (range: 1,014-2,140), and the median clinical target volume was 44 cm(3) (range: 26-73). In all cases, 100% of the prescription dose covered 95% of the clinical target volume. The median conformity index was 0.86 (range: 0.70-1.12). The median percentage of the ipsilateral breast volume receiving 100% and 50% of the prescribed dose was 3.8% (range: 2.2-6.9) and 13.3% (range: 7.5-20.8) compared with 18% (range: 3-42) and 53% (range: 24-65) in the institutional historical controls treated with postoperative external beam PBI (p = .002). The median maximum skin dose was 9 Gy. The median dose to 1 and 10 cm(3) of skin was 6.7 and 4.9 Gy. The doses to the heart and ipsilateral lung were negligible. Preoperative PBI resulted in a substantial reduction in ipsilateral breast tissue dose compared with postoperative PBI. The skin dose appeared reasonable, given the small volumes. A prospective Phase I trial evaluating this technique is ongoing. Copyright © 2012 Elsevier Inc. All rights reserved.

Individualized Nonadaptive and Online-Adaptive Intensity-Modulated Radiotherapy Treatment Strategies for Cervical Cancer Patients Based on Pretreatment Acquired Variable Bladder Filling Computed Tomography Scans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bondar, M.L., E-mail: m.bondar@erasmusmc.nl; Hoogeman, M.S.; Mens, J.W.

2012-08-01

Purpose: To design and evaluate individualized nonadaptive and online-adaptive strategies based on a pretreatment established motion model for the highly deformable target volume in cervical cancer patients. Methods and Materials: For 14 patients, nine to ten variable bladder filling computed tomography (CT) scans were acquired at pretreatment and after 40 Gy. Individualized model-based internal target volumes (mbITVs) accounting for the cervix and uterus motion due to bladder volume changes were generated by using a motion-model constructed from two pretreatment CT scans (full and empty bladder). Two individualized strategies were designed: a nonadaptive strategy, using an mbITV accounting for the full-rangemore » of bladder volume changes throughout the treatment; and an online-adaptive strategy, using mbITVs of bladder volume subranges to construct a library of plans. The latter adapts the treatment online by selecting the plan-of-the-day from the library based on the measured bladder volume. The individualized strategies were evaluated by the seven to eight CT scans not used for mbITVs construction, and compared with a population-based approach. Geometric uniform margins around planning cervix-uterus and mbITVs were determined to ensure adequate coverage. For each strategy, the percentage of the cervix-uterus, bladder, and rectum volumes inside the planning target volume (PTV), and the clinical target volume (CTV)-to-PTV volume (volume difference between PTV and CTV) were calculated. Results: The margin for the population-based approach was 38 mm and for the individualized strategies was 7 to 10 mm. Compared with the population-based approach, the individualized nonadaptive strategy decreased the CTV-to-PTV volume by 48% {+-} 6% and the percentage of bladder and rectum inside the PTV by 5% to 45% and 26% to 74% (p < 0.001), respectively. Replacing the individualized nonadaptive strategy by an online-adaptive, two-plan library further decreased the percentage of bladder and rectum inside the PTV (0% to 10% and -1% to 9%; p < 0.004) and the CTV-to-PTV volume (4-96 ml). Conclusions: Compared with population-based margins, an individualized PTV results in better organ-at-risk sparing. Online-adaptive radiotherapy further improves organ-at-risk sparing.« less

Concentration and purification of HIV-1 virions by microfluidic separation of superparamagnetic nanoparticles

PubMed Central

Chen, Grace Dongqing; Alberts, Catharina Johanna

2009-01-01

The low concentration and complex sample matrix of many clinical and environmental viral samples presents a significant challenge in the development of low cost, point-of-care viral assays. To address this problem, we investigated the use of a microfluidic passive magnetic separator combined with on-chip mixer to both purify and concentrate whole particle HIV-1 virions. Virus-containing plasma samples are first mixed to allow specific binding of the viral particles with antibody-conjugated superparamagnetic nanoparticles, and several passive mixer geometries were assessed for their mixing efficiencies. The virus-nanoparticle complexes are then separated from the plasma in a novel magnetic separation chamber, where packed micron-sized ferromagnetic particles serve as high magnetic gradient concentrators for an externally applied magnetic field. Thereafter, a viral lysis buffer was flowed through the chip and the released HIV proteins were assayed off-chip. Viral protein extraction efficiencies of 62% and 45% were achieved at 10uL/min and 30uL/min throughputs respectively. More importantly, an 80-fold concentration was observed for an initial sample volume of 1mL, and a 44-fold concentration for an initial sample volume of 0.5mL. The system is broadly applicable to microscale sample preparation of any viral sample and can be used for nucleic acid extraction as well as 40–80 fold enrichment of target viruses. PMID:19954210

Magnetic resonance imaging in dissociated strabismus complex demonstrates generalized hypertrophy of rectus extraocular muscles.

PubMed

Rajab, Ghada Z; Suh, Soh Youn; Demer, Joseph L

2017-06-01

Dissociated strabismus complex (DSC) is an enigmatic form of strabismus that includes dissociated vertical deviation (DVD) and dissociated horizontal deviation (DHD). We employed magnetic resonance imaging (MRI) to evaluate the extraocular muscles in DSC. We studied 5 patients with DSC and mean age of 25 years (range, 12-42 years), and 15 age-matched, orthotropic control subjects. All patients had DVD; 4 also had DHD. We employed high-resolution, surface coil MRI with thin, 2 mm slices and central target fixation. Volumes of the rectus and superior oblique muscles in the region 12 mm posterior to 4 mm anterior to the globe-optic nerve junction were measured in quasi-coronal planes in central gaze. Patients with DSC had no structural abnormalities of rectus muscles or rectus pulleys or the superior oblique muscle but exhibited modest, statistically significant increased volume of all rectus muscles ranging from 20% for medial rectus to 9% for lateral rectus (P < 0.05). DSC includes various combinations of sursumduction, excycloduction, and abduction not conforming to Hering's law. We have found modest generalized enlargement of all rectus muscles. DSC is associated with generalized rectus extraocular muscle hypertrophy in the absence of other orbital abnormalities. Copyright © 2017 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

Dosimetric evaluation of IMRT plan for homogenous and inhomogeneous medium using AAPM TG-119 protocol

NASA Astrophysics Data System (ADS)

Fatimah, L. A. N.; Wibowo, W. E.; Pawiro, S. A.

2017-05-01

The American Association of Physicists in Medicine (AAPM) TG-119 protocol has been applied for dose verification in IMRT technique. However, some criteria in the protocol need to be verified for inhomogeneous medium and small volume targets. Hence, the purpose of this study was to verify the assessment criteria of dose verification in AAPM TG-119 for inhomogeneous medium and small volume targets. The work has been conducted by dose verification for homogeneous (phantom A) and inhomogeneous phantoms (phantom B and C) on two geometrical targets: C-shape and circular targets. The targets were simulated using 7 static dMLC IMRT fields at two different depths of 5 g/cm2 and 10 g/cm2. The dose optimisation and calculation were done by using Pinnacle3 for 6 MV photons beam. The planning objectives were set according to AAPM TG-119 parameters. The plan analysis was conducted by Conformity Index and Homogeneity Index. The point dose measurements were conducted with Exradin A16, Semiflex 0.125cc, and Gafchromic EBT3. The plan results show that CI for C-shape target is in the range of 0.710-0.999 at 10 g/cm2 depth and 0.691-1.613 at 5 g/cm2. In addition, HI for C-shape and circular were in the range of 6.3%-58.7% and 5.4%-87.1% for 10 g/cm2 depth. The measurement results show that the dose measurement at inhomogeneous medium and small volume targets are much lower than the criteria in AAPM TG-119. In conclusion, the criteria in the AAPM TG-119 cannot be fully implemented for inhomogeneous medium and small volume targets.

MO-F-CAMPUS-T-02: Optimizing Orientations of Hundreds of Intensity-Modulated Beams to Treat Multiple Brain Targets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, L; Dong, P; Larson, D

Purpose: To investigate a new modulated beam orientation optimization (MBOO) approach maximizing treatment planning quality for the state-of-the-art flattening filter free (FFF) beam that has enabled rapid treatments of multiple brain targets. Methods: MBOO selects and optimizes a large number of intensity-modulated beams (400 or more) from all accessible beam angles surrounding a patient’s skull. The optimization algorithm was implemented on a standalone system that interfaced with the 3D Dicom images and structure sets. A standard published data set that consisted of 1 to 12 metastatic brain tumor combinations was selected for MBOO planning. The planning results from various coplanarmore » and non-coplanar configurations via MBOO were then compared with the results obtained from a clinical volume modulated arc therapy (VMAT) delivery system (Truebeam RapidArc, Varian Oncology). Results: When planning a few number of targets (n<4), MBOO produced results equivalent to non-coplanar multi-arc VMAT planning in terms of target volume coverage and normal tissue sparing. For example, the 12-Gy and 4-Gy normal brain volumes for the 3-target plans differed by less than 1 mL ( 3.0 mLvs 3.8 mL; and 35.2 mL vs 36.3 mL, respectively) for MBOO versus VMAT. However, when planning a larger number of targets (n≥4), MBOO significantly reduced the dose to the normal brain as compared to VMAT, though the target volume coverage was equivalent. For example, the 12-Gy and 4-Gy normal brain volumes for the 12-target plans were 10.8 mL vs. 18.0 mL and 217.9 mL vs. 390.0 mL, respectively for the non-coplanar MBOO versus the non-coplanar VMAT treatment plans, yielding a reduction in volume of more than 60% for the case. Conclusion: MBOO is a unique approach for maximizing normal tissue sparing when treating a large number (n≥4) of brain tumors with FFF linear accelerators. Dr Ma and Dr Sahgal are currently on the board of international society of stereotactic radiosurgery. Dr Sahgal has received support for educational presentations from Elekta company.« less

Complex dynamics of our economic life on different scales: insights from search engine query data.

PubMed

Preis, Tobias; Reith, Daniel; Stanley, H Eugene

2010-12-28

Search engine query data deliver insight into the behaviour of individuals who are the smallest possible scale of our economic life. Individuals are submitting several hundred million search engine queries around the world each day. We study weekly search volume data for various search terms from 2004 to 2010 that are offered by the search engine Google for scientific use, providing information about our economic life on an aggregated collective level. We ask the question whether there is a link between search volume data and financial market fluctuations on a weekly time scale. Both collective 'swarm intelligence' of Internet users and the group of financial market participants can be regarded as a complex system of many interacting subunits that react quickly to external changes. We find clear evidence that weekly transaction volumes of S&P 500 companies are correlated with weekly search volume of corresponding company names. Furthermore, we apply a recently introduced method for quantifying complex correlations in time series with which we find a clear tendency that search volume time series and transaction volume time series show recurring patterns.

A ballistic performance study on multiphase particulate systems impacted by various projectiles

NASA Astrophysics Data System (ADS)

Comtois-Arnaldo, Christian; Petel, Oren

2017-06-01

The present study investigates the complex multiscale dynamic response of particulate composites, in an effort to link the bulk material behavior to strain-rate activated microstructures. These investigations involve multiphase systems containing micron-sized ceramic particles integrated into a siloxane elastomer to create flexible nanocomposites with varying inclusion properties. In particular, the effects of varying particle morphology, strength, volume fraction, and density are under investigation. The experimental focus of the study concerns the ballistic penetration of the nanocomposite targets. The targets are impacted by fragment simulating steel projectiles of constant mass and varying nose shapes (i.e., flat, ogive, and chisel-nose) to identify variations in the penetration mechanics. The projectiles are accelerated in a single-stage gas gun to velocities ranging from 200 m/s to 900 m/s prior to impact. The results for each projectile type are compared to analytical penetration models in order to shed light on the dominant penetration mechanisms and their relationship to the microstructure of the nanocomposites.

Dynamic magnetic resonance imaging assessment of vascular targeting agent effects in rat intracerebral tumor models

PubMed Central

Muldoon, Leslie L.; Gahramanov, Seymur; Li, Xin; Marshall, Deborah J.; Kraemer, Dale F.; Neuwelt, Edward A.

2011-01-01

We used dynamic MRI to evaluate the effects of monoclonal antibodies targeting brain tumor vasculature. Female athymic rats with intracerebral human tumor xenografts were untreated or treated with intetumumab, targeting αV-integrins, or bevacizumab, targeting vascular endothelial growth factor (n = 4–6 per group). Prior to treatment and at 1, 3, and 7 days after treatment, we performed standard MRI to assess tumor volume, dynamic susceptibility-contrast MRI with the blood-pool iron oxide nanoparticle ferumoxytol to evaluate relative cerebral blood volume (rCBV), and dynamic contrast-enhanced MRI to assess tumor vascular permeability. Tumor rCBV increased by 27 ± 13% over 7 days in untreated rats; intetumumab increased tumor rCBV by 65 ± 10%, whereas bevacizumab reduced tumor rCBV by 31 ± 10% at 7 days (P < .001 for group and day). Similarly, intetumumab increased brain tumor vascular permeability compared with controls at 3 and 7 days after treatment, whereas bevacizumab decreased tumor permeability within 24 hours (P = .0004 for group, P = .0081 for day). All tumors grew over the 7-day assessment period, but bevacizumab slowed the increase in tumor volume on MRI. We conclude that the vascular targeting agents intetumumab and bevacizumab had diametrically opposite effects on dynamic MRI of tumor vasculature in rat brain tumor models. Targeting αV-integrins increased tumor vascular permeability and blood volume, whereas bevacizumab decreased both measures. These findings have implications for chemotherapy delivery and antitumor efficacy. PMID:21123368

Changes in Search Path Complexity and Length During Learning of a Virtual Water Maze: Age Differences and Differential Associations with Hippocampal Subfield Volumes.

PubMed

Daugherty, Ana M; Bender, Andrew R; Yuan, Peng; Raz, Naftali

2016-06-01

Impairment of hippocampus-dependent cognitive processes has been proposed to underlie age-related deficits in navigation. Animal studies suggest a differential role of hippocampal subfields in various aspects of navigation, but that hypothesis has not been tested in humans. In this study, we examined the association between volume of hippocampal subfields and age differences in virtual spatial navigation. In a sample of 65 healthy adults (age 19-75 years), advanced age was associated with a slower rate of improvement operationalized as shortening of the search path over 25 learning trials on a virtual Morris water maze task. The deficits were partially explained by greater complexity of older adults' search paths. Larger subiculum and entorhinal cortex volumes were associated with a faster decrease in search path complexity, which in turn explained faster shortening of search distance. Larger Cornu Ammonis (CA)1-2 volume was associated with faster distance shortening, but not in path complexity reduction. Age differences in regional volumes collectively accounted for 23% of the age-related variance in navigation learning. Independent of subfield volumes, advanced age was associated with poorer performance across all trials, even after reaching the asymptote. Thus, subiculum and CA1-2 volumes were associated with speed of acquisition, but not magnitude of gains in virtual maze navigation. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

[Definition of nodal volumes in breast cancer treatment and segmentation guidelines].

PubMed

Kirova, Y M; Castro Pena, P; Dendale, R; Campana, F; Bollet, M A; Fournier-Bidoz, N; Fourquet, A

2009-06-01

To assist in the determination of breast and nodal volumes in the setting of radiotherapy for breast cancer and establish segmentation guidelines. Materials and methods. Contrast metarial enhanced CT examinations were obtained in the treatment position in 25 patients to clearly define the target volumes. The clinical target volume (CTV) including the breast, internal mammary nodes, supraclavicular and subclavicular regions and axxilary region were segmented along with the brachial plexus and interpectoral nodes. The following critical organs were also segmented: heart, lungs, contralateral breast, thyroid, esophagus and humeral head. A correlation between clinical and imaging findings and meeting between radiation oncologists and breast specialists resulted in a better definition of irradiation volumes for breast and nodes with establishement of segmentation guidelines and creation of an anatomical atlas. A practical approach, based on anatomical criteria, is proposed to assist in the segmentation of breast and node volumes in the setting of breast cancer treatment along with a definition of irradiation volumes.

Maxillary sinus volume in patients with impacted canines.

PubMed

Oz, Aslihan Zeynep; Oz, Abdullah Alper; El, Hakan; Palomo, Juan Martin

2017-01-01

To evaluate the maxillary sinus volumes in unilaterally impacted canine patients and to compare the volumetric changes that occur after the eruption of canines to the dental arch using cone beam computed tomography (CBCT). Pre- (T0) and posttreatment (T1) CBCT records of 30 patients were used to calculate maxillary sinus volumes between the impacted and erupted canine sides. The InVivoDental 5.0 program was used to measure the volume of the maxillary sinuses. The distance from impacted canine cusp tip to the target point on the palatal plane was also measured. Right maxillary sinus volume was statistically significantly smaller compared to that of the left maxillary sinus when the canine was impacted on the right side at T0. According to the T1 measurements there was no significant difference between the mean volumes of the impaction side and the contralateral side. The distance from the canine tip to its target point on the palatal plane were 17.17 mm, and the distance from the tip to the target point was 15.14 mm for the left- and right-side impacted canines, respectively, and there was a significant difference between the mean amount of change of both sides of maxillary sinuses after treatment of impacted canines. Orthodontic treatment of impacted canines created a significant increase in maxillary sinus volume when the impacted canines were closer with respect to the maxillary sinus.

SU-E-T-621: Planning Methodologies for Cancer of the Anal Canal: Comparing IMRT, Rapid Arc, and Pencil Beam Scanning Proton Beam

DOE Office of Scientific and Technical Information (OSTI.GOV)

McGlade, J; Kassaee, A

2015-06-15

Purpose: To evaluate planning methods for anal canal cancer and compare the results of 9-field Intensity Modulated Radiotherapy (IMRT), Volumetric Modulated Arc Therapy (Varian, RapidArc), and Proton Pencil Beam Scanning (PBS). Methods: We generated plans with IMRT, RapidArc (RA) and PBS for twenty patients for both initial phase including nodes and cone down phase of treatment using Eclipe (Varian). We evaluated the advantage of each technique for each phase. RA plans used 2 to 4 arcs and various collimator orientations. PBS used two posterior oblique fields. We evaluated the plans comparing dose volume histogram (DVH), locations of hot spots, andmore » PTV dose conformity. Results: Due to complex shape of target, for RA plans, multiple arcs (>2) are required to achieve optimal PTV conformity. When the PTV exceeds 15 cm in the superior-inferior direction, limitations of deliverability start to dominate. The PTV should be divided into a superior and an inferior structure. The optimization is performed with fixed jaws for each structure and collimator set to 90 degrees for the inferior PTV. Proton PBS plans show little advantage in small bowel sparing when treating the nodes. However, PBS plan reduces volumetric dose to the bladder at the cost of higher doses to the perineal skin. IMRT plans provide good target conformity, but they generate hot spots outside of the target volume. Conclusion: When using one planning technique for entire course of treatment, Multiple arc (>2) RA plans are better as compared to IMRT and PBS plans. When combining techniques, RA for the initial phase in combination with PBS for the cone down phase results in the most optimal plans.« less

Accuracy of MRI-compatible contrast media injectors.

PubMed

Saake, M; Wuest, W; Becker, S; Uder, M; Janka, R

2014-03-01

To analyze the exactness of MRI-compatible contrast media (CM) injectors in an experimental setup and clinical use. Ejected fluid volumes and amounts of CM were quantified for single and double piston injections. The focus was on small volumes, as used in pediatric examination and test-bolus measurements. Samples were collected before and after clinical MRI scans and amounts of CM were measured. For single piston injections the volume differences were minimal (mean difference 0.01  ml). For double piston injections the volume of the first injection was decreased (mean 20.74  ml, target 21.00  ml, p < 0.01). After a position change of the Y-piece of the injection system, the amount of CM differed significantly from the target value (mean 1.23  mmol and 0.83  mmol at 1  ml/s flow rate, target 1.00  mmol, p < 0.01), independently of the wait time. The clinical samples confirmed these findings. The pistons of modern CM injectors work exactly. However, for small CM volumes the injected amount of CM can differ significantly from the target value in both directions. Influence factors are an incomplete elimination of air and exchange processes between the CM and saline chaser in the injection system. • In MRI examinations of children and test-bolus measurements, small amounts of CM are used. • The accuracy of single piston injections is high. • In double piston injections the injected amount of CM can differ significantly from the target value. © Georg Thieme Verlag KG Stuttgart · New York.

Dose gradient curve: A new tool for evaluating dose gradient.

PubMed

Sung, KiHoon; Choi, Young Eun

2018-01-01

Stereotactic radiotherapy, which delivers an ablative high radiation dose to a target volume for maximum local tumor control, requires a rapid dose fall-off outside the target volume to prevent extensive damage to nearby normal tissue. Currently, there is no tool to comprehensively evaluate the dose gradient near the target volume. We propose the dose gradient curve (DGC) as a new tool to evaluate the quality of a treatment plan with respect to the dose fall-off characteristics. The average distance between two isodose surfaces was represented by the dose gradient index (DGI) estimated by a simple equation using the volume and surface area of isodose levels. The surface area was calculated by mesh generation and surface triangulation. The DGC was defined as a plot of the DGI of each dose interval as a function of the dose. Two types of DGCs, differential and cumulative, were generated. The performance of the DGC was evaluated using stereotactic radiosurgery plans for virtual targets. Over the range of dose distributions, the dose gradient of each dose interval was well-characterized by the DGC in an easily understandable graph format. Significant changes in the DGC were observed reflecting the differences in planning situations and various prescription doses. The DGC is a rational method for visualizing the dose gradient as the average distance between two isodose surfaces; the shorter the distance, the steeper the dose gradient. By combining the DGC with the dose-volume histogram (DVH) in a single plot, the DGC can be utilized to evaluate not only the dose gradient but also the target coverage in routine clinical practice.

Patterns of recurrence after surgery alone versus preoperative chemoradiotherapy and surgery in the CROSS trials.

PubMed

Oppedijk, Vera; van der Gaast, Ate; van Lanschot, Jan J B; van Hagen, Pieter; van Os, Rob; van Rij, Caroline M; van der Sangen, Maurice J; Beukema, Jannet C; Rütten, Heidi; Spruit, Patty H; Reinders, Janny G; Richel, Dick J; van Berge Henegouwen, Mark I; Hulshof, Maarten C C M

2014-02-10

To analyze recurrence patterns in patients with cancer of the esophagus or gastroesophageal junction treated with either preoperative chemoradiotherapy (CRT) plus surgery or surgery alone. Recurrence pattern was analyzed in patients from the previously published CROSS I and II trials in relation to radiation target volumes. CRT consisted of five weekly courses of paclitaxel and carboplatin combined with a concurrent radiation dose of 41.4 Gy in 1.8-Gy fractions to the tumor and pathologic lymph nodes with margin. Of the 422 patients included from 2001 to 2008, 418 were available for analysis. Histology was mostly adenocarcinoma (75%). Of the 374 patients who underwent resection, 86% were allocated to surgery and 92% to CRT plus surgery. On January 1, 2011, after a minimum follow-up of 24 months (median, 45 months), the overall recurrence rate in the surgery arm was 58% versus 35% in the CRT plus surgery arm. Preoperative CRT reduced locoregional recurrence (LRR) from 34% to 14% (P < .001) and peritoneal carcinomatosis from 14% to 4% (P < .001). There was a small but significant effect on hematogenous dissemination in favor of the CRT group (35% v 29%; P = .025). LRR occurred in 5% within the target volume, in 2% in the margins, and in 6% outside the radiation target volume. In 1%, the exact site in relation to the target volume was unclear. Only 1% had an isolated infield recurrence after CRT plus surgery. Preoperative CRT in patients with esophageal cancer reduced LRR and peritoneal carcinomatosis. Recurrence within the radiation target volume occurred in only 5%, mostly combined with outfield failures.

Variability in target delineation of cervical carcinoma: A Korean radiation oncology group study (KROG 15-06)

PubMed Central

Joo, Ji Hyeon; Cho, Byung Chul; Jeong, Chi Young; Park, Won; Kim, Hak Jae; Yoon, Won Sup; Yoon, Mee Sun; Kim, Ji-Yoon; Choi, Jin Hwa; Choi, Youngmin; Kim, Joo-Young

2017-01-01

Purpose To determine inter-observer variability in target volume definition of cervical cancer in radical and adjuvant radiotherapy (RT) settings. Methods Eight physicians contoured CTVs of 2 patients underwent definitive and postoperative RT. Each volume was analyzed using the individual/median volume ratio and generalized conformity index (CIgen). And center of mass (COM) of each contour was calculated. Expert agreement was quantified using an expectation maximization algorithm for Simultaneous Truth and Performance Level Estimation (STAPLE). Results For definitive RT, the individual/median volume ratio ranged from 0.51 to 1.41, and CIgen was 0.531. Mean 3-dimensional distances of average to each COM were 7.8 mm. For postoperative RT setting, corresponding values were 0.65–1.38, 0.563, and 5.3 mm. Kappa value of expert agreement was 0.65 and 0.67, respectively. STAPLE estimates of the sensitivity, specificity, and kappa measures of inter-physician agreement were 0.73, 0.98, and 0.65 for the definitive and 0.75, 0.98, and 0.67 for the adjuvant radiotherapy setting. The largest difference was observed in the superior-inferior direction, particularly in the upper vagina and the common iliac area. Conclusion As there was still some variability in target delineation, more detailed guidelines for target volume delineation and continuing education would help to reduce this uncertainty. PMID:28301492

Surgical volume-to-outcome relationship and monitoring of technical performance in pediatric cardiac surgery.

PubMed

Kalfa, David; Chai, Paul; Bacha, Emile

2014-08-01

A significant inverse relationship of surgical institutional and surgeon volumes to outcome has been demonstrated in many high-stakes surgical specialties. By and large, the same results were found in pediatric cardiac surgery, for which a more thorough analysis has shown that this relationship depends on case complexity and type of surgical procedures. Lower-volume programs tend to underperform larger-volume programs as case complexity increases. High-volume pediatric cardiac surgeons also tend to have better results than low-volume surgeons, especially at the more complex end of the surgery spectrum (e.g., the Norwood procedure). Nevertheless, this trend for lower mortality rates at larger centers is not universal. All larger programs do not perform better than all smaller programs. Moreover, surgical volume seems to account for only a small proportion of the overall between-center variation in outcome. Intraoperative technical performance is one of the most important parts, if not the most important part, of the therapeutic process and a critical component of postoperative outcome. Thus, the use of center-specific, risk-adjusted outcome as a tool for quality assessment together with monitoring of technical performance using a specific score may be more reliable than relying on volume alone. However, the relationship between surgical volume and outcome in pediatric cardiac surgery is strong enough that it ought to support adapted and well-balanced health care strategies that take advantage of the positive influence that higher center and surgeon volumes have on outcome.

Brain architecture and social complexity in modern and ancient birds.

PubMed

Burish, Mark J; Kueh, Hao Yuan; Wang, Samuel S-H

2004-01-01

Vertebrate brains vary tremendously in size, but differences in form are more subtle. To bring out functional contrasts that are independent of absolute size, we have normalized brain component sizes to whole brain volume. The set of such volume fractions is the cerebrotype of a species. Using this approach in mammals we previously identified specific associations between cerebrotype and behavioral specializations. Among primates, cerebrotypes are linked principally to enlargement of the cerebral cortex and are associated with increases in the complexity of social structure. Here we extend this analysis to include a second major vertebrate group, the birds. In birds the telencephalic volume fraction is strongly correlated with social complexity. This correlation accounts for almost half of the observed variation in telencephalic size, more than any other behavioral specialization examined, including the ability to learn song. A prominent exception to this pattern is owls, which are not social but still have very large forebrains. Interpolating the overall correlation for Archaeopteryx, an ancient bird, suggests that its social complexity was likely to have been on a par with modern domesticated chickens. Telencephalic volume fraction outperforms residuals-based measures of brain size at separating birds by social structure. Telencephalic volume fraction may be an anatomical substrate for social complexity, and perhaps cognitive ability, that can be generalized across a range of vertebrate brains, including dinosaurs. Copyright 2004 S. Karger AG, Basel

Preclinical evaluation of multistep targeting of diasialoganglioside GD2 using a IgG-scFv bispecific antibody with high affinity for GD2 and DOTA metal complex

PubMed Central

Cheal, Sarah M.; Xu, Hong; Guo, Hong-fen; Zanzonico, Pat B.; Larson, Steven M.; Cheung, Nai-Kong

2014-01-01

Bispecific antibodies (BsAb) have proven to be useful targeting vectors for pretargeted radioimmunotherapy (PRIT). We sought to overcome key PRIT limitations such as high renal radiation exposure and immunogenicity (e.g. of streptavidin-antibody fusions), to advance clinical translation of this PRIT strategy for diasialoganglioside GD2-positive (GD2(+)) tumors. For this purpose, a IgG-scFv BsAb was engineered using the sequences for the anti-GD2 humanized monoclonal antibody hu3F8 (1) and C825, a murine scFv antibody with high affinity for the chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) complexed with beta-particle emitting radiometals such as 177Lu and 90Y (2, 3). A three-step regimen including hu3F8-C825, a dextran-based clearing agent, and p-aminobenzyl-DOTA radiolabeled with 177Lu (as 177Lu-DOTA-Bn; t1/2 = 6.71 days (d)) was optimized in immunocompromised mice carrying subcutaneous (s.c.) human GD2(+) neuroblastoma (NB) xenografts. Absorbed doses for tumor and normal tissues were ∼85 cGy/MBq and ≤3.7 cGy/MBq, respectively, with therapeutic indicies (TI) of 142 for blood and 23 for kidney. A therapy study (n = 5 per group; tumor volume: 240 ± 160 mm3) with three successive PRIT cycles (total 177Lu: ∼33 MBq; tumor dose ∼3400 cGy), revealed complete tumor response in 5/5 animals, with no recurrence up to 28 d post-treatment. Tumor ablation was confirmed histologically in 4/5 mice, and normal organs showed minimal overall toxicities. All non-treated mice required sacrifice within 12 d (>1.0 cm3 tumor volume). We conclude that this novel anti-GD2 PRIT approach has sufficient TI to successfully ablate s.c. GD2(+)–NB in mice while sparing kidney and bone marrow. PMID:24944121

Microstructure refinement and mechanical properties improvement by developing IAF on inclusions in Ti–Al complex deoxidized HSLA steel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, M., E-mail: jiangmin@ustb.edu.cn; Wang, X.H.; Hu, Z.Y.

2015-10-15

The present study focused on microstructure refinement in Ti–Al complex deoxidized low alloy structural steel by developing IAF on inclusions. The goal was to establish more determined relation between Ti, Al in steel and the produced microstructures. In steel sample with Ti and Al contents of 0.0035% and 0.0004%, respectively, IAF was well developed by inclusions characterized by TiO{sub x}–MnO oxide cores enwrapped by (MnO–SiO{sub 2}–Al{sub 2}O{sub 3})–MnS or (MnO–SiO{sub 2})–MnS surface layers. With the rise of Ti and Al contents, IAF volume decreased greatly because of different inclusion chemistry, TiO{sub x} + MnS, TiO{sub x}–Al{sub 2}O{sub 3} or Al{submore » 2}O{sub 3}, which inhibit the formation of IAF. Thermodynamic calculations were carried out for optimal Ti and Al contents in steel to target inclusions with proper chemistry for nucleating IAF. These laboratorial findings were successfully applied and reproducibly observed in pilot trials. It was indicated that low temperature impact toughness at 0 °C and − 20 °C of the produced medium plate was effectively improved despite lower Ti contents than common process, which was very meaningful in saving the cost of high Ti content steels. - Highlights: • IAF volume showed close relationship to Ti or Al contents. • To target IAF, there is no need to add too many titanium alloys. • Optimal Ti and Al were about 0.0020–0.0060% and 0.0005–0.0020%, respectively. • Impact toughness of steel plate at 0 °C and − 20 °C was successfully improved.« less

An estimation of vehicle kilometer traveled and on-road emissions using the traffic volume and travel speed on road links in Incheon City.

PubMed

Jung, Sungwoon; Kim, Jounghwa; Kim, Jeongsoo; Hong, Dahee; Park, Dongjoo

2017-04-01

The objective of this study is to estimate the vehicle kilometer traveled (VKT) and on-road emissions using the traffic volume in urban. We estimated two VKT; one is based on registered vehicles and the other is based on traffic volumes. VKT for registered vehicles was 2.11 times greater than that of the applied traffic volumes because each VKT estimation method is different. Therefore, we had to define the inner VKT is moved VKT inner in urban to compare two values. Also, we focused on freight modes because these are discharged much air pollutant emissions. From analysis results, we found middle and large trucks registered in other regions traveled to target city in order to carry freight, target city has included many industrial and logistics areas. Freight is transferred through the harbors, large logistics centers, or via locations before being moved to the final destination. During this process, most freight is moved by middle and large trucks, and trailers rather than small trucks for freight import and export. Therefore, these trucks from other areas are inflow more than registered vehicles. Most emissions from diesel trucks had been overestimated in comparison to VKT from applied traffic volumes in target city. From these findings, VKT is essential based on traffic volume and travel speed on road links in order to estimate accurately the emissions of diesel trucks in target city. Our findings support the estimation of the effect of on-road emissions on urban air quality in Korea. Copyright © 2016. Published by Elsevier B.V.

Host specificity of microsporidia pathogenic to the gypsy moth, Lymantria dispar (L.): field studies in Slovakia.

PubMed

Solter, Leellen F; Pilarska, Daniela K; McManus, Michael L; Zúbrik, Milan; Patocka, Jan; Huang, Wei-Fone; Novotný, Julius

2010-09-01

Several species of microsporidia are important chronic pathogens of Lymantria dispar in Europe but have never been recovered from North American gypsy moth populations. The major issue for their introduction into North American L. dispar populations is concern about their safety to native non-target insects. In this study, we evaluated the susceptibility of sympatric non-target Lepidoptera to two species of microsporidia, Nosema lymantriae and Vairimorpha disparis, isolated from European populations of L. dispar and applied in field plots in Slovakia. Application of ultra low volume sprays of the microsporidia maximized coverage of infective spores in a complex natural environment and, thus, exposure of non-target species to the pathogens. Of 653 non-target larvae collected from plots treated with V. disparis in 2002, 18 individual larvae representing nine species in four families were infected. These plots were monitored for two subsequent seasons and V. disparis was not recovered from non-target species. Of 2571 non-target larvae collected in N. lymantriae-treated sites, one larva was found to be infected. Both species of microsporidia, particularly N. lymantriae, appear to have a very narrow host range in the field, even when an inundative technique is used for their introduction. V. disparis infections in L. dispar exceeded 40% of recovered larvae in the treated study sites; infection rates were lower in sites sprayed with N. lymantriae. Several naturally-occurring pathogens were recorded from the non-target species. The most common pathogen, isolated from 21 species in eight families, was a microsporidium in the genus Cystosporogenes. Copyright 2010 Elsevier Inc. All rights reserved.

[Clinical target volume delineation for radiotherapy of the esophagus].

PubMed

Lazarescu, I; Thureau, S; Nkhali, L; Pradier, O; Dubray, B

2013-10-01

The dense lymphatic network of the esophagus facilitates tumour spreading along the cephalo-caudal axis and to locoregional lymph nodes. A better understanding of microscopic invasion by tumour cells, based on histological analysis of surgical specimens and analysis of recurrence sites, has justified a reduction in radiotherapy target volumes. The delineation of the clinical target volume (CTV) depends on tumour characteristics (site, histology) and on its spread as assessed on endoscopic ultrasonography and ((18)F)-fluorodeoxyglucose positron-emission tomography (FDG-PET). We propose that positive and negative predictive values for FDG-PET should be used to adapt the CTV according to the risk of nodal involvement. Copyright © 2013 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Prioritized System Science Targets for Heliophysics

NASA Astrophysics Data System (ADS)

Spann, J. F.; Christensen, A. B.; St Cyr, O. C.; Posner, A.; Giles, B. L.

2009-12-01

Heliophysics is a discipline that investigates the science at work from the interface of Earth and space, to the core of the Sun, and to the outer edge of our solar system. This solar-interplanetary-planetary system is vast and inherently coupled on many spatial, temporal and energy scales. The Sun’s explosive energy output creates complicated field and plasma structures that when coupled with our terrestrial magnetized space, generates an extraordinary complex environment that has practical implications for humanity as we are becoming increasingly dependent on space-based assets. This immense volume of our cosmic neighborhood is the domain of heliophysics. Understanding this domain and the dominant mechanisms that control the transfer of mass and energy requires a system approach that addresses all aspects and regions of the system. The 2009 NASA Heliophysics Roadmap presents a science-focused strategic approach to advance the goal of heliophysics: why does the Sun vary; how do the Earth and heliosphere respond; and what are the impacts on humanity? This talk will present the top 6 prioritized science targets to understand the coupled heliophysics system as presented in the 2009 NASA Heliophysics Roadmap. An exposition of each science target and how it addresses outstanding questions in heliophysics will be discussed.

Future System Science Mission Targets for Heliophysics

NASA Technical Reports Server (NTRS)

Spann, James; Christensen, Andrew B.; SaintCyr, O. C.; Giles, Barbara I.; Posner, Arik

2009-01-01

Heliophysics is a discipline that investigates the science at work from the interface of Earth and space, to the core of the Sun, and to the outer edge of our solar system. This solar-interplanetary-planetary system is vast and inherently coupled on many spatial, temporal and energy scales. The Sun's explosive energy output creates complicated field and plasma structures that when coupled without terrestrial magnetized space, generates an extraordinary complex environment that has practical implications for humanity as we are becoming increasingly dependent on space-based assets. The immense volume of our cosmic neighborhood is the domain of heliophysics. Understanding this domain and the dominant mechanisms that control the transfer of mass and energy requires a system approach that addresses all aspects and regions of the system. The 2009 NASA Heliophysics Roadmap presents a science-focused strategic approach to advance the goal of heliophysics: why does the Sun vary; how do the Earth and heliosphere respond; and what are the impacts on humanity? This talk will present the top 6 prioritized science targets to understand the coupled heliophysics system as presented in the 2009 NASA Heliophysics Roadmap. An exposition of each science target and how it addresses outstanding questions in heliophysics will be discussed.

Prioritized System Science Targets for Heliophysics

NASA Technical Reports Server (NTRS)

Spann, James Frederick; Christensen, Andrew B.; SaintCyr, Orville Chris; Posner, Arik; Giles, Barbara L.

2009-01-01

Heliophysics is a discipline that investigates the science at work from the interface of Earth and space, to the core of the Sun, and to the outer edge of our solar system. This solar-interplanetary-planetary system is vast and inherently coupled on many spatial, temporal and energy scales. The Sun's explosive energy output creates complicated field and plasma structures that when coupled with our terrestrial magnetized space, generates an extraordinary complex environment that has practical implications for humanity as we are becoming increasingly dependent on space-based assets. This immense volume of our cosmic neighborhood is the domain of heliophysics. Understanding this domain and the dominant mechanisms that control the transfer of mass and energy requires a system approach that addresses all aspects and regions of the system. The 2009 NASA Heliophysics Roadmap presents a science-focused strategic approach to advance the goal of heliophysics: why does the Sun vary; how do the Earth and heliosphere respond; and what are the impacts on humanity? This talk will present the top 6 prioritized science targets to understand the coupled heliophysics system as presented in the 2009 NASA Heliophysics Roadmap. An exposition of each science target and how it addresses outstanding questions in heliophysics will be discussed.

Influence of multiple brain metastases’ size and number on the quality of SRS - VMAT dose delivery

NASA Astrophysics Data System (ADS)

Prentou, G.; Koutsouveli, E.; Pantelis, E.; Papagiannis, P.; Georgiou, E.; Karaiskos, P.

2017-11-01

Stereotactic radiosurgery with volumetric modulated arc therapy (SRS-VMAT) has recently been introduced for treatment of multiple brain metastases with a single isocenter. The technique’s high efficiency is nevertheless dependent of metastatic tumors’ characteristics such as size and number. In this work the impact of the metastases’ size and number on the plan quality indices clinically used for plan evaluation and acceptance is investigated. Fifteen targets with a diameter of 1 cm and average volume of 0.7 cm3 and ten targets with a diameter of 2 cm and average volume of 6.5 cm3 were contoured on an anonymized patient CT dataset, in Monaco (Elekta) treatment planning system. VMAT plans for different target volumes (1 and 2 cm in diameter) and various target numbers (1-15) were generated using four non-coplanar arcs and the Agility (Elekta) linear accelerator (5 mm MLC width) using a Monte Carlo dose calculation algorithm and 1mm dose calculation grid resolution. Conformity index (CI), gradient index (GI) and heterogeneity index (HI) were determined for each target. High quality plans were created for both 1 cm and 2 cm in diameter targets for limited (<6) number of targets per plan. For increased number of irradiated targets (>6) both CI and GI, clinically used for plan evaluation and acceptance, were found to deteriorate.

Strategies for the Integration of Cough and Swallow to Maintain Airway Protection in Humans.

PubMed

Huff, Alyssa; Reed, Mitchell D; Smith, Barbara K; Brown, Edward H; Ovechkin, Alexander V; Pitts, Teresa

2018-06-20

Airway protective behaviors, like cough and swallow, deteriorate in many populations suffering from neurologic disorders. While coordination of these behaviors has been investigated in an animal model, it has not been tested in humans. We used a novel protocol, adapted from previous work in the cat, to assess cough and swallow independently and their coordination strategies in seven healthy males (26 ± 6 years). Surface electromyograms of the submental complex and external oblique complex, spirometry, and thoracic and abdominal wall kinematics, were used to evaluate the timing of swallow, cough, and breathing as well as lung volume (LV) during these behaviors. Unlike the cat, there was significant variability in the cough-swallow phase preference; however, there was a targeted LV range in which swallow occurred. These results give insight into the differences between the cat and human models in airway protective strategies related to the coordination of cough and swallow behaviors, allowing for better understanding of dystussia and dysphagia.

PAM-Dependent Target DNA Recognition and Cleavage by C2c1 CRISPR-Cas Endonuclease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Hui; Gao, Pu; Rajashankar, Kanagalaghatta R.

C2c1 is a newly identified guide RNA-mediated type V-B CRISPR-Cas endonuclease that site-specifically targets and cleaves both strands of target DNA. We have determined crystal structures of Alicyclobacillus acidoterrestris C2c1 (AacC2c1) bound to sgRNA as a binary complex and to target DNAs as ternary complexes, thereby capturing catalytically competent conformations of AacC2c1 with both target and non-target DNA strands independently positioned within a single RuvC catalytic pocket. Moreover, C2c1-mediated cleavage results in a staggered seven-nucleotide break of target DNA. crRNA adopts a pre-ordered five-nucleotide A-form seed sequence in the binary complex, with release of an inserted tryptophan, facilitating zippering upmore » of 20-bp guide RNA:target DNA heteroduplex on ternary complex formation. Notably, the PAM-interacting cleft adopts a “locked” conformation on ternary complex formation. Structural comparison of C2c1 ternary complexes with their Cas9 and Cpf1 counterparts highlights the diverse mechanisms adopted by these distinct CRISPR-Cas systems, thereby broadening and enhancing their applicability as genome editing tools.« less

Complex conductivity response to silver nanoparticles in ...

EPA Pesticide Factsheets

The increase in the use of nanoscale materials in consumer products has resulted in a growing concern of their potential hazard to ecosystems and public health from their accidental or intentional introduction to the environment. Key environmental, health, and safety research needs include knowledge and methods for their detection, characterization, fate, and transport. Specifically, techniques available for the direct detection and quantification of their fate and transport in the environment are limited. Their small size, high surface area to volume ratio, interfacial, and electrical properties make metallic nanoparticles, such as silver nanoparticles, good targets for detection using electrical geophysical techniques. Here we measured the complex conductivity response to silver nanoparticles in sand columns under varying moisture conditions (0–30%), nanoparticle concentrations (0–10 mg/g), lithology (presence of clay), pore water salinity (0.0275 and 0.1000 S/m), and particle size (35, 90–210 and 1500–2500 nm). Based on the Cole-Cole relaxation models we obtained the chargeability and the time constant. We demonstrate that complex conductivity can detect silver nanoparticles in porous media with the response enhanced by higher concentrations of silver nanoparticles, moisture content, ionic strength, clay content and particle diameter. Quantification of the volumetric silver nanoparticles content in the porous media can also be obtained from complex co

TRIM.FaTE Evaluation Report

EPA Pesticide Factsheets

The TRIM.FaTE Evaluation Report is composed of three volumes. Volume I presents conceptual, mechanistic, and structural complexity evaluations of various aspects of the model. Volumes II and III present performance evaluation.

Efficiency gains for spinal radiosurgery using multicriteria optimization intensity modulated radiation therapy guided volumetric modulated arc therapy planning.

PubMed

Chen, Huixiao; Winey, Brian A; Daartz, Juliane; Oh, Kevin S; Shin, John H; Gierga, David P

2015-01-01

To evaluate plan quality and delivery efficiency gains of volumetric modulated arc therapy (VMAT) versus a multicriteria optimization-based intensity modulated radiation therapy (MCO-IMRT) for stereotactic radiosurgery of spinal metastases. MCO-IMRT plans (RayStation V2.5; RaySearch Laboratories, Stockholm, Sweden) of 10 spinal radiosurgery cases using 7-9 beams were developed for clinical delivery, and patients were replanned using VMAT with partial arcs. The prescribed dose was 18 Gy, and target coverage was maximized such that the maximum dose to the planning organ-at-risk volume (PRV) of the spinal cord was 10 or 12 Gy. Dose-volume histogram (DVH) constraints from the clinically acceptable MCO-IMRT plans were utilized for VMAT optimization. Plan quality and delivery efficiency with and without collimator rotation for MCO-IMRT and VMAT were compared and analyzed based upon DVH, planning target volume coverage, homogeneity index, conformity number, cord PRV sparing, total monitor units (MU), and delivery time. The VMAT plans were capable of matching most DVH constraints from the MCO-IMRT plans. The ranges of MU were 4808-7193 for MCO-IMRT without collimator rotation, 3509-5907 for MCO-IMRT with collimator rotation, 4444-7309 for VMAT without collimator rotation, and 3277-5643 for VMAT with collimator of 90 degrees. The MU for the VMAT plans were similar to their corresponding MCO-IMRT plans, depending upon the complexity of the target and PRV geometries, but had a larger range. The delivery times of the MCO-IMRT and VMAT plans, both with collimator rotation, were 18.3 ± 2.5 minutes and 14.2 ± 2.0 minutes, respectively (P < .05). The MCO-IMRT and VMAT can create clinically acceptable plans for spinal radiosurgery. The MU for MCO-IMRT and VMAT can be reduced significantly by utilizing a collimator rotation following the orientation of the spinal cord. Plan quality for VMAT is similar to MCO-IMRT, with similar MU for both modalities. Delivery times can be reduced by nominally 25% with VMAT. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Cryo-EM Structures Reveal Mechanism and Inhibition of DNA Targeting by a CRISPR-Cas Surveillance Complex.

PubMed

Guo, Tai Wei; Bartesaghi, Alberto; Yang, Hui; Falconieri, Veronica; Rao, Prashant; Merk, Alan; Eng, Edward T; Raczkowski, Ashleigh M; Fox, Tara; Earl, Lesley A; Patel, Dinshaw J; Subramaniam, Sriram

2017-10-05

Prokaryotic cells possess CRISPR-mediated adaptive immune systems that protect them from foreign genetic elements, such as invading viruses. A central element of this immune system is an RNA-guided surveillance complex capable of targeting non-self DNA or RNA for degradation in a sequence- and site-specific manner analogous to RNA interference. Although the complexes display considerable diversity in their composition and architecture, many basic mechanisms underlying target recognition and cleavage are highly conserved. Using cryoelectron microscopy (cryo-EM), we show that the binding of target double-stranded DNA (dsDNA) to a type I-F CRISPR system yersinia (Csy) surveillance complex leads to large quaternary and tertiary structural changes in the complex that are likely necessary in the pathway leading to target dsDNA degradation by a trans-acting helicase-nuclease. Comparison of the structure of the surveillance complex before and after dsDNA binding, or in complex with three virally encoded anti-CRISPR suppressors that inhibit dsDNA binding, reveals mechanistic details underlying target recognition and inhibition. Published by Elsevier Inc.

Complex matrix multiplication operations with data pre-conditioning in a high performance computing architecture

DOEpatents

Eichenberger, Alexandre E; Gschwind, Michael K; Gunnels, John A

2014-02-11

Mechanisms for performing a complex matrix multiplication operation are provided. A vector load operation is performed to load a first vector operand of the complex matrix multiplication operation to a first target vector register. The first vector operand comprises a real and imaginary part of a first complex vector value. A complex load and splat operation is performed to load a second complex vector value of a second vector operand and replicate the second complex vector value within a second target vector register. The second complex vector value has a real and imaginary part. A cross multiply add operation is performed on elements of the first target vector register and elements of the second target vector register to generate a partial product of the complex matrix multiplication operation. The partial product is accumulated with other partial products and a resulting accumulated partial product is stored in a result vector register.

Detection and isolation of nucleic acid sequences using competitive hybridization probes

DOEpatents

Lucas, Joe N.; Straume, Tore; Bogen, Kenneth T.

1997-01-01

A method for detecting a target nucleic acid sequence in a sample is provided using hybridization probes which competitively hybridize to a target nucleic acid. According to the method, a target nucleic acid sequence is hybridized to first and second hybridization probes which are complementary to overlapping portions of the target nucleic acid sequence, the first hybridization probe including a first complexing agent capable of forming a binding pair with a second complexing agent and the second hybridization probe including a detectable marker. The first complexing agent attached to the first hybridization probe is contacted with a second complexing agent, the second complexing agent being attached to a solid support such that when the first and second complexing agents are attached, target nucleic acid sequences hybridized to the first hybridization probe become immobilized on to the solid support. The immobilized target nucleic acids are then separated and detected by detecting the detectable marker attached to the second hybridization probe. A kit for performing the method is also provided.

Detection and isolation of nucleic acid sequences using competitive hybridization probes

DOEpatents

Lucas, J.N.; Straume, T.; Bogen, K.T.

1997-04-01

A method for detecting a target nucleic acid sequence in a sample is provided using hybridization probes which competitively hybridize to a target nucleic acid. According to the method, a target nucleic acid sequence is hybridized to first and second hybridization probes which are complementary to overlapping portions of the target nucleic acid sequence, the first hybridization probe including a first complexing agent capable of forming a binding pair with a second complexing agent and the second hybridization probe including a detectable marker. The first complexing agent attached to the first hybridization probe is contacted with a second complexing agent, the second complexing agent being attached to a solid support such that when the first and second complexing agents are attached, target nucleic acid sequences hybridized to the first hybridization probe become immobilized on to the solid support. The immobilized target nucleic acids are then separated and detected by detecting the detectable marker attached to the second hybridization probe. A kit for performing the method is also provided. 7 figs.

Remote volume rendering pipeline for mHealth applications

NASA Astrophysics Data System (ADS)

Gutenko, Ievgeniia; Petkov, Kaloian; Papadopoulos, Charilaos; Zhao, Xin; Park, Ji Hwan; Kaufman, Arie; Cha, Ronald

2014-03-01

We introduce a novel remote volume rendering pipeline for medical visualization targeted for mHealth (mobile health) applications. The necessity of such a pipeline stems from the large size of the medical imaging data produced by current CT and MRI scanners with respect to the complexity of the volumetric rendering algorithms. For example, the resolution of typical CT Angiography (CTA) data easily reaches 512^3 voxels and can exceed 6 gigabytes in size by spanning over the time domain while capturing a beating heart. This explosion in data size makes data transfers to mobile devices challenging, and even when the transfer problem is resolved the rendering performance of the device still remains a bottleneck. To deal with this issue, we propose a thin-client architecture, where the entirety of the data resides on a remote server where the image is rendered and then streamed to the client mobile device. We utilize the display and interaction capabilities of the mobile device, while performing interactive volume rendering on a server capable of handling large datasets. Specifically, upon user interaction the volume is rendered on the server and encoded into an H.264 video stream. H.264 is ubiquitously hardware accelerated, resulting in faster compression and lower power requirements. The choice of low-latency CPU- and GPU-based encoders is particularly important in enabling the interactive nature of our system. We demonstrate a prototype of our framework using various medical datasets on commodity tablet devices.

Target Capture during Mos1 Transposition*

PubMed Central

Pflieger, Aude; Jaillet, Jerôme; Petit, Agnès; Augé-Gouillou, Corinne; Renault, Sylvaine

2014-01-01

DNA transposition contributes to genomic plasticity. Target capture is a key step in the transposition process, because it contributes to the selection of new insertion sites. Nothing or little is known about how eukaryotic mariner DNA transposons trigger this step. In the case of Mos1, biochemistry and crystallography have deciphered several inverted terminal repeat-transposase complexes that are intermediates during transposition. However, the target capture complex is still unknown. Here, we show that the preintegration complex (i.e., the excised transposon) is the only complex able to capture a target DNA. Mos1 transposase does not support target commitment, which has been proposed to explain Mos1 random genomic integrations within host genomes. We demonstrate that the TA dinucleotide used as the target is crucial both to target recognition and in the chemistry of the strand transfer reaction. Bent DNA molecules are better targets for the capture when the target DNA is nicked two nucleotides apart from the TA. They improve strand transfer when the target DNA contains a mismatch near the TA dinucleotide. PMID:24269942

Target capture during Mos1 transposition.

PubMed

Pflieger, Aude; Jaillet, Jerôme; Petit, Agnès; Augé-Gouillou, Corinne; Renault, Sylvaine

2014-01-03

DNA transposition contributes to genomic plasticity. Target capture is a key step in the transposition process, because it contributes to the selection of new insertion sites. Nothing or little is known about how eukaryotic mariner DNA transposons trigger this step. In the case of Mos1, biochemistry and crystallography have deciphered several inverted terminal repeat-transposase complexes that are intermediates during transposition. However, the target capture complex is still unknown. Here, we show that the preintegration complex (i.e., the excised transposon) is the only complex able to capture a target DNA. Mos1 transposase does not support target commitment, which has been proposed to explain Mos1 random genomic integrations within host genomes. We demonstrate that the TA dinucleotide used as the target is crucial both to target recognition and in the chemistry of the strand transfer reaction. Bent DNA molecules are better targets for the capture when the target DNA is nicked two nucleotides apart from the TA. They improve strand transfer when the target DNA contains a mismatch near the TA dinucleotide.

Performance of Leak Compensation in All-Age ICU Ventilators During Volume-Targeted Neonatal Ventilation: A Lung Model Study.

PubMed

Itagaki, Taiga; Bennett, Desmond J; Chenelle, Christopher T; Fisher, Daniel F; Kacmarek, Robert M

2017-01-01

Volume-targeted ventilation is increasingly used in low birthweight infants because of the potential for reducing volutrauma and avoiding hypocapnea. However, it is not known what level of air leak is acceptable during neonatal volume-targeted ventilation when leak compensation is activated concurrently. Four ICU ventilators (Servo-i, PB980, V500, and Avea) were compared in available invasive volume-targeted ventilation modes (pressure control continuous spontaneous ventilation [PC-CSV] and pressure control continuous mandatory ventilation [PC-CMV]). The Servo-i and PB980 were tested with (+) and without (-) their proximal flow sensor. The V500 and Avea were tested with their proximal flow sensor as indicated by their manufacturers. An ASL 5000 lung model was used to simulate 4 neonatal scenarios (body weight 0.5, 1, 2, and 4 kg). The ASL 5000 was ventilated via an endotracheal tube with 3 different leaks. Two minutes of data were collected after each change in leak level, and the asynchrony index was calculated. Tidal volume (V T ) before and after the change in leak was assessed. The differences in delivered V T between before and after the change in leak were within ±5% in all scenarios with the PB980 (-/+) and V500. With the Servo-i (-/+), baseline V T was ≥10% greater than set V T during PC-CSV, and delivered V T markedly changed with leak. The Avea demonstrated persistent high V T in all leak scenarios. Across all ventilators, the median asynchrony index was 1% (interquartile range 0-27%) in PC-CSV and 1.8% (0-45%) in PC-CMV. The median asynchrony index was significantly higher in the Servo-i (-/+) than in the PB980 (-/+) and V500 in 1 and 2 kg scenarios during PC-CSV and PC-CMV. The PB980 and V500 were the only ventilators to acclimate to all leak scenarios and achieve targeted V T . Further clinical investigation is needed to validate the use of leak compensation during neonatal volume-targeted ventilation. Copyright © 2017 by Daedalus Enterprises.

Scalable, cGMP-compatible purification of extracellular vesicles carrying bioactive human heterodimeric IL-15/lactadherin complexes

PubMed Central

Watson, Dionysios C.; Yung, Bryant C.; Bergamaschi, Cristina; Chowdhury, Bhabadeb; Bear, Jenifer; Stellas, Dimitris; Morales-Kastresana, Aizea; Jones, Jennifer C.; Felber, Barbara K.; Chen, Xiaoyuan; Pavlakis, George N.

2018-01-01

ABSTRACT The development of extracellular vesicles (EV) for therapeutic applications is contingent upon the establishment of reproducible, scalable, and high-throughput methods for the production and purification of clinical grade EV. Methods including ultracentrifugation (U/C), ultrafiltration, immunoprecipitation, and size-exclusion chromatography (SEC) have been employed to isolate EV, each facing limitations such as efficiency, particle purity, lengthy processing time, and/or sample volume. We developed a cGMP-compatible method for the scalable production, concentration, and isolation of EV through a strategy involving bioreactor culture, tangential flow filtration (TFF), and preparative SEC. We applied this purification method for the isolation of engineered EV carrying multiple complexes of a novel human immunostimulatory cytokine-fusion protein, heterodimeric IL-15 (hetIL-15)/lactadherin. HEK293 cells stably expressing the fusion cytokine were cultured in a hollow-fibre bioreactor. Conditioned medium was collected and EV were isolated comparing three procedures: U/C, SEC, or TFF + SEC. SEC demonstrated comparable particle recovery, size distribution, and hetIL-15 density as U/C purification. Relative to U/C, SEC preparations achieved a 100-fold reduction in ferritin concentration, a major protein-complex contaminant. Comparative proteomics suggested that SEC additionally decreased the abundance of cytoplasmic proteins not associated with EV. Combination of TFF and SEC allowed for bulk processing of large starting volumes, and resulted in bioactive EV, without significant loss in particle yield or changes in size, morphology, and hetIL-15/lactadherin density. Taken together, the combination of bioreactor culture with TFF + SEC comprises a scalable, efficient method for the production of highly purified, bioactive EV carrying hetIL-15/lactadherin, which may be useful in targeted cancer immunotherapy approaches. PMID:29535850

Cytosolic proteins can exploit membrane localization to trigger functional assembly

PubMed Central

2018-01-01

Cell division, endocytosis, and viral budding would not function without the localization and assembly of protein complexes on membranes. What is poorly appreciated, however, is that by localizing to membranes, proteins search in a reduced space that effectively drives up concentration. Here we derive an accurate and practical analytical theory to quantify the significance of this dimensionality reduction in regulating protein assembly on membranes. We define a simple metric, an effective equilibrium constant, that allows for quantitative comparison of protein-protein interactions with and without membrane present. To test the importance of membrane localization for driving protein assembly, we collected the protein-protein and protein-lipid affinities, protein and lipid concentrations, and volume-to-surface-area ratios for 46 interactions between 37 membrane-targeting proteins in human and yeast cells. We find that many of the protein-protein interactions between pairs of proteins involved in clathrin-mediated endocytosis in human and yeast cells can experience enormous increases in effective protein-protein affinity (10–1000 fold) due to membrane localization. Localization of binding partners thus triggers robust protein complexation, suggesting that it can play an important role in controlling the timing of endocytic protein coat formation. Our analysis shows that several other proteins involved in membrane remodeling at various organelles have similar potential to exploit localization. The theory highlights the master role of phosphoinositide lipid concentration, the volume-to-surface-area ratio, and the ratio of 3D to 2D equilibrium constants in triggering (or preventing) constitutive assembly on membranes. Our simple model provides a novel quantitative framework for interpreting or designing in vitro experiments of protein complexation influenced by membrane binding. PMID:29505559

Under conditions of large geometric miss, tumor control probability can be higher for static gantry intensity-modulated radiation therapy compared to volume-modulated arc therapy for prostate cancer.

PubMed

Balderson, Michael; Brown, Derek; Johnson, Patricia; Kirkby, Charles

2016-01-01

The purpose of this work was to compare static gantry intensity-modulated radiation therapy (IMRT) with volume-modulated arc therapy (VMAT) in terms of tumor control probability (TCP) under scenarios involving large geometric misses, i.e., those beyond what are accounted for when margin expansion is determined. Using a planning approach typical for these treatments, a linear-quadratic-based model for TCP was used to compare mean TCP values for a population of patients who experiences a geometric miss (i.e., systematic and random shifts of the clinical target volume within the planning target dose distribution). A Monte Carlo approach was used to account for the different biological sensitivities of a population of patients. Interestingly, for errors consisting of coplanar systematic target volume offsets and three-dimensional random offsets, static gantry IMRT appears to offer an advantage over VMAT in that larger shift errors are tolerated for the same mean TCP. For example, under the conditions simulated, erroneous systematic shifts of 15mm directly between or directly into static gantry IMRT fields result in mean TCP values between 96% and 98%, whereas the same errors on VMAT plans result in mean TCP values between 45% and 74%. Random geometric shifts of the target volume were characterized using normal distributions in each Cartesian dimension. When the standard deviations were doubled from those values assumed in the derivation of the treatment margins, our model showed a 7% drop in mean TCP for the static gantry IMRT plans but a 20% drop in TCP for the VMAT plans. Although adding a margin for error to a clinical target volume is perhaps the best approach to account for expected geometric misses, this work suggests that static gantry IMRT may offer a treatment that is more tolerant to geometric miss errors than VMAT. Copyright © 2016 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Explaining Racial/Ethnic Disparities in Use of High-Volume Hospitals

PubMed Central

Gray, Bradford H.; Schlesinger, Mark

2014-01-01

Racial/ethnic minorities are less likely to use higher-quality hospitals than whites. We propose that a higher level of information-related complexity in their local hospital environments compounds the effects of discrimination and more limited access to services, contributing to racial/ethnic disparities in hospital use. While minorities live closer than whites to high-volume hospitals, minorities also face greater choice complexity and live in neighborhoods with lower levels of medical experience. Our empirical results reveal that it is generally the overall context associated with proximity, choice complexity, and local experience, rather than differential sensitivity to these factors, that provides a partial explanation of the disparity gap in high-volume hospital use. PMID:25316717

Target volume motion during anal cancer image guided radiotherapy using cone-beam computed tomography.

PubMed

Brooks, Corrinne J; Bernier, Laurence; Hansen, Vibeke N; Tait, Diana M

2018-05-01

Literature regarding image-guidance and interfractional motion of the anal canal (AC) during anal cancer radiotherapy is sparse. This study investigates interfractional AC motion during anal cancer radiotherapy. Bone matched cone beam CT (CBCT) images were acquired for 20 patients receiving anal cancer radiotherapy allowing population systematic and random error calculations. 12 were selected to investigate interfractional AC motion. Primary anal gross tumour volume and clinical target volume (CTVa) were contoured on each CBCT. CBCT CTVa volumes were compared to planning CTVa. CBCT CTVa volumes were combined into a CBCT-CTVa envelope for each patient. Maximum distortion between each orthogonal border of the planning CTVa and CBCT-CTVa envelope was measured. Frequency, volume and location of CBCT-CTVa envelope beyond the planning target volume (PTVa) was analysed. Population systematic and random errors were 1 and 3 mm respectively. 112 CBCTs were analysed in the interfractional motion study. CTVa varied between each imaging session particularly T location patients of anorectal origin. CTVa border expansions ≥ 1 cm were seen inferiorly, anteriorly, posteriorly and left direction. The CBCT-CTVa envelope fell beyond the PTVa ≥ 50% imaging sessions (n = 5). Of these CBCT CTVa distortions beyond PTVa, 44% and 32% were in the upper and lower thirds of PTVa respectively. The AC is susceptible to volume changes and shape deformations. Care must be taken when calculating or considering reducing the PTV margin to the anus. Advances in knowledge: Within a limited field of research, this study provides further knowledge of how the AC deforms during anal cancer radiotherapy.

[Comparison of planning quality and delivery efficiency between volumetric modulated arc therapy and dynamic intensity modulated radiation therapy for nasopharyngeal carcinoma with more than 4 prescribed dose levels].

PubMed

Jia, Pengfei; Xu, Jun; Zhou, Xiaoxi; Chen, Jian; Tang, Lemin

2017-12-01

The aim of this study is to compare the planning quality and delivery efficiency between dynamic intensity modulated radiation therapy (d-IMRT) and dual arc volumetric modulated arc therapy (VMAT) systematically for nasopharyngeal carcinoma (NPC) patients with multi-prescribed dose levels, and to analyze the correlations between target volumes and plan qualities. A total of 20 patients of NPC with 4-5 prescribed dose levels to achieve simultaneous integrated boost (SIB) treated by sliding window d-IMRT in our department from 2014 to 2015 were re-planned with dual arc VMAT. All optimization objectives for each VMAT plan were as the same as the corresponding d-IMRT plan. The dose parameters for targets and organ at risk (OAR), the delivery time and monitor units (MU) in two sets of plans were compared respectively. The treatment accuracy was tested by three dimensional dose validation system. Finally, the correlations between the difference of planning quality and the volume of targets were discussed. The conform indexes (CIs) of planning target volumes (PTVs) in VMAT plans were obviously high than those in d-IMRT plans ( P < 0.05), but no significant correlations between the difference of CIs and the volume of targets were discovered ( P > 0.05). The target coverage and heterogeneity indexes (HIs) of PTV 1 and PGTV nd and PTV 3 in two sets of plans were consistent. The doses of PTV 2 decreased and HIs were worse in VMAT plans. VMAT could provide better spinal cord and brainstem sparing, but increase mean dose of parotids. The average number of MUs and delivery time for d-IMRT were 3.32 and 2.19 times of that for VMAT. The γ-index (3 mm, 3%) analysis for each plans was more than 97% in COMPASS ® measurement for quality assurance (QA). The results show that target dose coverages in d-IMRT and VMAT plans are similar for NPC with multi-prescribed dose levels. VMAT could improve the the CIs of targets, but reduce the dose to the target volume in neck except for PGTV nd . The biggest advantages of VMAT over d-IMRT are delivery efficiency and QA.

[Radiotherapy volume delineation based on (18F)-fluorodeoxyglucose positron emission tomography for locally advanced or inoperable oesophageal cancer].

PubMed

Encaoua, J; Abgral, R; Leleu, C; El Kabbaj, O; Caradec, P; Bourhis, D; Pradier, O; Schick, U

2017-06-01

To study the impact on radiotherapy planning of an automatically segmented target volume delineation based on ( 18 F)-fluorodeoxy-D-glucose (FDG)-hybrid positron emission tomography-computed tomography (PET-CT) compared to a manually delineation based on computed tomography (CT) in oesophageal carcinoma patients. Fifty-eight patients diagnosed with oesophageal cancer between September 2009 and November 2014 were included. The majority had squamous cell carcinoma (84.5 %), and advanced stage (37.9 % were stade IIIA) and 44.8 % had middle oesophageal lesion. Gross tumour volumes were retrospectively defined based either manually on CT or automatically on coregistered PET/CT images using three different threshold methods: standard-uptake value (SUV) of 2.5, 40 % of maximum intensity and signal-to-background ratio. Target volumes were compared in length, volume and using the index of conformality. Radiotherapy plans to the dose of 50Gy and 66Gy using intensity-modulated radiotherapy were generated and compared for both data sets. Planification target volume coverage and doses delivered to organs at risk (heart, lung and spinal cord) were compared. The gross tumour volume based manually on CT was significantly longer than that automatically based on signal-to-background ratio (6.4cm versus 5.3cm; P<0.008). Doses to the lungs (V20, D mean ), heart (V40), and spinal cord (D max ) were significantly lower on plans using the PTV SBR . The PTV SBR coverage was statistically better than the PTV CT coverage on both plans. (50Gy: P<0.0004 and 66Gy: P<0.0006). The automatic PET segmentation algorithm based on the signal-to-background ratio method for the delineation of oesophageal tumours is interesting, and results in better target volume coverage and decreased dose to organs at risk. This may allow dose escalation up to 66Gy to the gross tumour volume. Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Locoregional control after intensity-modulated radiotherapy for nasopharyngeal carcinoma with an anatomy-based target definition.

PubMed

Kawashima, Mitsuhiko; Ariji, Takaki; Kameoka, Satoru; Ueda, Takashi; Kohno, Ryosuke; Nishio, Teiji; Arahira, Satoko; Motegi, Atsushi; Zenda, Sadamoto; Akimoto, Tetsuo; Tahara, Makoto; Hayashi, Ryuichi

2013-12-01

The objective of the study was to evaluate locoregional control after intensity-modulated radiotherapy for nasopharyngeal cancer using a target definition along with anatomical boundaries. Forty patients with biopsy-proven squamous cell or non-keratinizing carcinoma of the nasopharynx who underwent intensity-modulated radiotherapy between April 2006 and November 2009 were reviewed. There were 10 females and 30 males with a median age of 48 years (range, 17-74 years). More than half of the patients had T3/4 (n = 21) and/or N2/3 (n = 24) disease. Intensity-modulated radiotherapy was administered as 70 Gy/33 fractions with or without concomitant chemotherapy. The clinical target volume was contoured along with muscular fascia or periosteum, and the prescribed radiotherapy dose was determined for each anatomical compartment and lymph node level in the head and neck. One local recurrence was observed at Meckel's cave on the periphery of the high-risk clinical target volume receiving a total dose of <63 Gy. Otherwise, six locoregional failures were observed within irradiated volume receiving 70 Gy. Local and nodal control rates at 3 years were 91 and 89%, respectively. Adverse events were acceptable, and 25 (81%) of 31 patients who were alive without recurrence at 2 years had xerostomia of ≤Grade 1. The overall survival rate at 3 years was 87%. Target definition along with anatomically defined boundaries was feasible without compromise of the therapeutic ratio. It is worth testing this method further to minimize the unnecessary irradiated volume and to standardize the target definition in intensity-modulated radiotherapy for nasopharyngeal cancer.

Australasian Gastrointestinal Trials Group (AGITG) Contouring Atlas and Planning Guidelines for Intensity-Modulated Radiotherapy in Anal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ng, Michael, E-mail: mng@radoncvic.com.au; Leong, Trevor; University of Melbourne

2012-08-01

Purpose: To develop a high-resolution target volume atlas with intensity-modulated radiotherapy (IMRT) planning guidelines for the conformal treatment of anal cancer. Methods and Materials: A draft contouring atlas and planning guidelines for anal cancer IMRT were prepared at the Australasian Gastrointestinal Trials Group (AGITG) annual meeting in September 2010. An expert panel of radiation oncologists contoured an anal cancer case to generate discussion on recommendations regarding target definition for gross disease, elective nodal volumes, and organs at risk (OARs). Clinical target volume (CTV) and planning target volume (PTV) margins, dose fractionation, and other IMRT-specific issues were also addressed. A steeringmore » committee produced the final consensus guidelines. Results: Detailed contouring and planning guidelines and a high-resolution atlas are provided. Gross tumor and elective target volumes are described and pictorially depicted. All elective regions should be routinely contoured for all disease stages, with the possible exception of the inguinal and high pelvic nodes for select, early-stage T1N0. A 20-mm CTV margin for the primary, 10- to 20-mm CTV margin for involved nodes and a 7-mm CTV margin for the elective pelvic nodal groups are recommended, while respecting anatomical boundaries. A 5- to 10-mm PTV margin is suggested. When using a simultaneous integrated boost technique, a dose of 54 Gy in 30 fractions to gross disease and 45 Gy to elective nodes with chemotherapy is appropriate. Guidelines are provided for OAR delineation. Conclusion: These consensus planning guidelines and high-resolution atlas complement the existing Radiation Therapy Oncology Group (RTOG) elective nodal ano-rectal atlas and provide additional anatomic, clinical, and technical instructions to guide radiation oncologists in the planning and delivery of IMRT for anal cancer.« less

A New Suggestion for the Radiation Target Volume After a Subtotal Gastrectomy in Patients With Stomach Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nam, Heerim; Lim, Do Hoon; Kim, Sung

2008-06-01

Purpose: To compare treatment results between the use of two different radiation fields including and excluding remnant stomach and suggest new target volumes excluding remnant stomach after subtotal gastrectomy (STG) in patients with stomach cancer. Methods and Materials: We retrospectively analyzed 291 patients treated with adjuvant chemoradiotherapy after STG and D2 dissection at the Samsung Medical Center, Seoul, South Korea. Eighty-three patients registered from 1995 to 1997 underwent irradiation according to the INT 0116 protocol that recommended the inclusion of remnant stomach within the target volume (Group A). After this period, we excluded remnant stomach from the target volume formore » 208 patients (Group B). Median follow-up was 67 months. Results: Treatment failure developed in 93 patients (32.0%). Local and regional recurrence rates for Group A vs. Group B were 10.8% vs. 5.3% (p = not significant) and 9.6% vs. 6.3% (p = not significant), and recurrence rates for remnant stomach were 7.2% vs. 1.4% (p = 0.018), respectively. Overall and disease-free survival rates were not different between the two groups. Grade 3 or 4 vomiting and diarrhea developed more frequently in Group A than Group B (4.8% vs. 1.4% and 6.0% vs. 1.9%, respectively; p = 0.012; p < 0.001). Conclusion: Exclusion of remnant stomach from the radiation field had no effect on failure rates or survival, and a low complication rate occurred in patients treated excluding remnant stomach. We suggest that remnant stomach be excluded from the radiation target volume for patients with stomach cancer who undergo STG and D2 dissection.« less

Dose gradient curve: A new tool for evaluating dose gradient

PubMed Central

Choi, Young Eun

2018-01-01

Purpose Stereotactic radiotherapy, which delivers an ablative high radiation dose to a target volume for maximum local tumor control, requires a rapid dose fall-off outside the target volume to prevent extensive damage to nearby normal tissue. Currently, there is no tool to comprehensively evaluate the dose gradient near the target volume. We propose the dose gradient curve (DGC) as a new tool to evaluate the quality of a treatment plan with respect to the dose fall-off characteristics. Methods The average distance between two isodose surfaces was represented by the dose gradient index (DGI) estimated by a simple equation using the volume and surface area of isodose levels. The surface area was calculated by mesh generation and surface triangulation. The DGC was defined as a plot of the DGI of each dose interval as a function of the dose. Two types of DGCs, differential and cumulative, were generated. The performance of the DGC was evaluated using stereotactic radiosurgery plans for virtual targets. Results Over the range of dose distributions, the dose gradient of each dose interval was well-characterized by the DGC in an easily understandable graph format. Significant changes in the DGC were observed reflecting the differences in planning situations and various prescription doses. Conclusions The DGC is a rational method for visualizing the dose gradient as the average distance between two isodose surfaces; the shorter the distance, the steeper the dose gradient. By combining the DGC with the dose-volume histogram (DVH) in a single plot, the DGC can be utilized to evaluate not only the dose gradient but also the target coverage in routine clinical practice. PMID:29698471

DOE Office of Scientific and Technical Information (OSTI.GOV)

Balderson, Michael, E-mail: michael.balderson@rmp.uhn.ca; Brown, Derek; Johnson, Patricia

The purpose of this work was to compare static gantry intensity-modulated radiation therapy (IMRT) with volume-modulated arc therapy (VMAT) in terms of tumor control probability (TCP) under scenarios involving large geometric misses, i.e., those beyond what are accounted for when margin expansion is determined. Using a planning approach typical for these treatments, a linear-quadratic–based model for TCP was used to compare mean TCP values for a population of patients who experiences a geometric miss (i.e., systematic and random shifts of the clinical target volume within the planning target dose distribution). A Monte Carlo approach was used to account for themore » different biological sensitivities of a population of patients. Interestingly, for errors consisting of coplanar systematic target volume offsets and three-dimensional random offsets, static gantry IMRT appears to offer an advantage over VMAT in that larger shift errors are tolerated for the same mean TCP. For example, under the conditions simulated, erroneous systematic shifts of 15 mm directly between or directly into static gantry IMRT fields result in mean TCP values between 96% and 98%, whereas the same errors on VMAT plans result in mean TCP values between 45% and 74%. Random geometric shifts of the target volume were characterized using normal distributions in each Cartesian dimension. When the standard deviations were doubled from those values assumed in the derivation of the treatment margins, our model showed a 7% drop in mean TCP for the static gantry IMRT plans but a 20% drop in TCP for the VMAT plans. Although adding a margin for error to a clinical target volume is perhaps the best approach to account for expected geometric misses, this work suggests that static gantry IMRT may offer a treatment that is more tolerant to geometric miss errors than VMAT.« less

Potential dosimetric benefits of adaptive tumor tracking over the internal target volume concept for stereotactic body radiation therapy of pancreatic cancer.

PubMed

Karava, Konstantina; Ehrbar, Stefanie; Riesterer, Oliver; Roesch, Johannes; Glatz, Stefan; Klöck, Stephan; Guckenberger, Matthias; Tanadini-Lang, Stephanie

2017-11-09

Radiotherapy for pancreatic cancer has two major challenges: (I) the tumor is adjacent to several critical organs and, (II) the mobility of both, the tumor and its surrounding organs at risk (OARs). A treatment planning study simulating stereotactic body radiation therapy (SBRT) for pancreatic tumors with both the internal target volume (ITV) concept and the tumor tracking approach was performed. The two respiratory motion-management techniques were compared in terms of doses to the target volume and organs at risk. Two volumetric-modulated arc therapy (VMAT) treatment plans (5 × 5 Gy) were created for each of the 12 previously treated pancreatic cancer patients, one using the ITV concept and one the tumor tracking approach. To better evaluate the overall dose delivered to the moving tumor volume, 4D dose calculations were performed on four-dimensional computed tomography (4DCT) scans. The resulting planning target volume (PTV) size for each technique was analyzed. Target and OAR dose parameters were reported and analyzed for both 3D and 4D dose calculation. Tumor motion ranged from 1.3 to 11.2 mm. Tracking led to a reduction of PTV size (max. 39.2%) accompanied with significant better tumor coverage (p<0.05, paired Wilcoxon signed rank test) both in 3D and 4D dose calculations and improved organ at risk sparing. Especially for duodenum, stomach and liver, the mean dose was significantly reduced (p<0.05) with tracking for 3D and 4D dose calculations. By using an adaptive tumor tracking approach for respiratory-induced pancreatic motion management, a significant reduction in PTV size can be achieved, which subsequently facilitates treatment planning, and improves organ dose sparing. The dosimetric benefit of tumor tracking is organ and patient-specific.

Postoperative radiation in esophageal squamous cell carcinoma and target volume delineation

PubMed Central

Zhu, Yingming; Li, Minghuan; Kong, Li; Yu, Jinming

2016-01-01

Esophageal cancer is the sixth leading cause of cancer death worldwide, and patients who are treated with surgery alone, without neoadjuvant therapies, experience frequent relapses. Whether postoperative therapies could reduce the recurrence or improve overall survival is still controversial for these patients. The purpose of our review is to figure out the value of postoperative adjuvant therapy and address the disputes about target volume delineation according to published data. Based on the evidence of increased morbidity and disadvantages on patient survival caused by postoperative chemotherapy or radiotherapy (RT) alone provided by studies in the early 1990s, the use of postoperative adjuvant therapies in cases of esophageal squamous cell carcinoma has diminished substantially and has been replaced gradually by neoadjuvant chemoradiation. With advances in surgery and RT, accumulating evidence has recently rekindled interest in the delivery of postoperative RT or chemoradiotherapy in patients with stage T3/T4 or N1 (lymph node positive) carcinomas after radical surgery. However, due to complications with the standard radiation field, a nonconforming modified field has been adopted in most studies. Therefore, we analyze different field applications and provide suggestions on the optimization of the radiation field based on the major sites of relapse and the surgical non-clearance area. For upper and middle thoracic esophageal carcinomas, the bilateral supraclavicular and superior mediastinal areas remain common sites of recurrence and should be encompassed within the clinical target volume. In contrast, a consensus has yet to be reached regarding lower thoracic esophageal carcinomas; the “standard” clinical target volume is still recommended. Further studies of larger sample sizes should focus on different recurrence patterns, categorized by tumor locations, refined classifications, and differing molecular biology, to provide more information on the delineation of target volumes. PMID:27471393

Poster — Thur Eve — 32: Stereotactic Body Radiation Therapy for Peripheral Lung Lesion: Treatment Planning and Quality Assurance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wan, Shuying; Oliver, Michael; Wang, Xiaofang

2014-08-15

Stereotactic body radiation therapy (SBRT), due to its high precision for target localizing, has become widely used to treat tumours at various locations, including the lungs. Lung SBRT program was started at our institution a year ago. Eighteen patients with peripheral lesions up to 3 cm diameter have been treated with 48 Gy in 4 fractions. Based on four-dimensional computed tomography (4DCT) simulation, internal target volume (ITV) was delineated to encompass the respiratory motion of the lesion. A margin of 5 mm was then added to create the planning target volume (PTV) for setup uncertainties. There was no expansion frommore » gross tumour volume (GTV) to clinical target volume (CTV). Pinnacle 9.6 was used as the primary treatment planning system. Volumetric modulated arc therapy (VMAT) technique, with one or two coplanar arcs, generally worked well. For quality assurance (QA), each plan was exported to Eclipse 10 and dose calculation was repeated. Dose volume histograms (DVHs) of the targets and organs at risk (OARs) were then compared between the two treatment planning systems. Winston-Lutz tests were carried out as routine machine QA. Patient-specific QA included ArcCheck measurement with an insert, where an ionization chamber was placed at the centre to measure dose at the isocenter. For the first several patients, and subsequently for the plans with extremely strong modulation, Gafchromic film dosimetry was also employed. For each patient, a mock setup was scheduled prior to treatments. Daily pre- and post-CBCT were acquired for setup and assessment of intra-fractional motion, respectively.« less

Impact of FDG-PET on radiation therapy volume delineation in non-small-cell lung cancer.

PubMed

Bradley, Jeffrey; Thorstad, Wade L; Mutic, Sasa; Miller, Tom R; Dehdashti, Farrokh; Siegel, Barry A; Bosch, Walter; Bertrand, Rudi J

2004-05-01

Locoregional failure remains a significant problem for patients receiving definitive radiation therapy alone or combined with chemotherapy for non-small-cell lung cancer (NSCLC). Positron emission tomography (PET) with [(18)F]fluoro-2-deoxy-d-glucose (FDG) has proven to be a valuable diagnostic and staging tool for NSCLC. This prospective study was performed to determine the impact of treatment simulation with FDG-PET and CT on radiation therapy target volume definition and toxicity profiles by comparison to simulation with computed tomography (CT) scanning alone. Twenty-six patients with Stages I-III NSCLC were studied. Each patient underwent sequential CT and FDG-PET simulation on the same day. Immobilization devices used for both simulations included an alpha cradle, a flat tabletop, 6 external fiducial markers, and a laser positioning system. A radiation therapist participated in both simulations to reproduce the treatment setup. Both the CT and fused PET/CT image data sets were transferred to the radiation treatment planning workstation for contouring. Each FDG-PET study was reviewed with the interpreting nuclear radiologist before tumor volumes were contoured. The fused PET/CT images were used to develop the three-dimensional conformal radiation therapy (3DCRT) plan. A second physician, blinded to the results of PET, contoured the gross tumor volumes (GTV) and planning target volumes (PTV) from the CT data sets, and these volumes were used to generate mock 3DCRT plans. The PTV was defined by a 10-mm margin around the GTV. The two 3DCRT plans for each patient were compared with respect to the GTV, PTV, mean lung dose, volume of normal lung receiving > or =20 Gy (V20), and mean esophageal dose. The FDG-PET findings altered the AJCC TNM stage in 8 of 26 (31%) patients; 2 patients were diagnosed with metastatic disease based on FDG-PET and received palliative radiation therapy. Of the 24 patients who were planned with 3DCRT, PET clearly altered the radiation therapy volume in 14 (58%), as follows. PET helped to distinguish tumor from atelectasis in all 3 patients with atelectasis. Unsuspected nodal disease was detected by PET in 10 patients, and 1 patient had a separate tumor focus detected within the same lobe of the lung. Increases in the target volumes led to increases in the mean lung dose, V20, and mean esophageal dose. Decreases in the target volumes in the patients with atelectasis led to decreases in these normal-tissue toxicity parameters. Radiation targeting with fused FDG-PET and CT images resulted in alterations in radiation therapy planning in over 50% of patients by comparison with CT targeting. The increasing availability of integrated PET/CT units will facilitate the use of this technology for radiation treatment planning. A confirmatory multicenter, cooperative group trial is planned within the Radiation Therapy Oncology Group.

A study of unsteady physiological magneto-fluid flow and heat transfer through a finite length channel by peristaltic pumping.

PubMed

Tripathi, Dharmendra; Bég, O Anwar

2012-08-01

Magnetohydrodynamic peristaltic flows arise in controlled magnetic drug targeting, hybrid haemodynamic pumps and biomagnetic phenomena interacting with the human digestive system. Motivated by the objective of improving an understanding of the complex fluid dynamics in such flows, we consider in the present article the transient magneto-fluid flow and heat transfer through a finite length channel by peristaltic pumping. Reynolds number is small enough and the wavelength to diameter ratio is large enough to negate inertial effects. Analytical solutions for temperature field, axial velocity, transverse velocity, pressure gradient, local wall shear stress, volume flowrate and averaged volume flowrate are obtained. The effects of the transverse magnetic field, Grashof number and thermal conductivity on the flow patterns induced by peristaltic waves (sinusoidal propagation along the length of channel) are studied using graphical plots. The present study identifies that greater pressure is required to propel the magneto-fluid by peristaltic pumping in comparison to a non-conducting Newtonian fluid, whereas, a lower pressure is required if heat transfer is effective. The analytical solutions further provide an important benchmark for future numerical simulations.

Microextraction by packed sorbent: an emerging, selective and high-throughput extraction technique in bioanalysis.

PubMed

Pereira, Jorge; Câmara, José S; Colmsjö, Anders; Abdel-Rehim, Mohamed

2014-06-01

Sample preparation is an important analytical step regarding the isolation and concentration of desired components from complex matrices and greatly influences their reliable and accurate analysis and data quality. It is the most labor-intensive and error-prone process in analytical methodology and, therefore, may influence the analytical performance of the target analytes quantification. Many conventional sample preparation methods are relatively complicated, involving time-consuming procedures and requiring large volumes of organic solvents. Recent trends in sample preparation include miniaturization, automation, high-throughput performance, on-line coupling with analytical instruments and low-cost operation through extremely low volume or no solvent consumption. Micro-extraction techniques, such as micro-extraction by packed sorbent (MEPS), have these advantages over the traditional techniques. This paper gives an overview of MEPS technique, including the role of sample preparation in bioanalysis, the MEPS description namely MEPS formats (on- and off-line), sorbents, experimental and protocols, factors that affect the MEPS performance, and the major advantages and limitations of MEPS compared with other sample preparation techniques. We also summarize MEPS recent applications in bioanalysis. Copyright © 2014 John Wiley & Sons, Ltd.

@neurIST: infrastructure for advanced disease management through integration of heterogeneous data, computing, and complex processing services.

PubMed

Benkner, Siegfried; Arbona, Antonio; Berti, Guntram; Chiarini, Alessandro; Dunlop, Robert; Engelbrecht, Gerhard; Frangi, Alejandro F; Friedrich, Christoph M; Hanser, Susanne; Hasselmeyer, Peer; Hose, Rod D; Iavindrasana, Jimison; Köhler, Martin; Iacono, Luigi Lo; Lonsdale, Guy; Meyer, Rodolphe; Moore, Bob; Rajasekaran, Hariharan; Summers, Paul E; Wöhrer, Alexander; Wood, Steven

2010-11-01

The increasing volume of data describing human disease processes and the growing complexity of understanding, managing, and sharing such data presents a huge challenge for clinicians and medical researchers. This paper presents the @neurIST system, which provides an infrastructure for biomedical research while aiding clinical care, by bringing together heterogeneous data and complex processing and computing services. Although @neurIST targets the investigation and treatment of cerebral aneurysms, the system's architecture is generic enough that it could be adapted to the treatment of other diseases. Innovations in @neurIST include confining the patient data pertaining to aneurysms inside a single environment that offers clinicians the tools to analyze and interpret patient data and make use of knowledge-based guidance in planning their treatment. Medical researchers gain access to a critical mass of aneurysm related data due to the system's ability to federate distributed information sources. A semantically mediated grid infrastructure ensures that both clinicians and researchers are able to seamlessly access and work on data that is distributed across multiple sites in a secure way in addition to providing computing resources on demand for performing computationally intensive simulations for treatment planning and research.

Enantioselective column coupled electrophoresis employing large bore capillaries hyphenated with tandem mass spectrometry for ultra-trace determination of chiral compounds in complex real samples.

PubMed

Piešťanský, Juraj; Maráková, Katarína; Kovaľ, Marián; Havránek, Emil; Mikuš, Peter

2015-12-01

A new multidimensional analytical approach for the ultra-trace determination of target chiral compounds in unpretreated complex real samples was developed in this work. The proposed analytical system provided high orthogonality due to on-line combination of three different methods (separation mechanisms), i.e. (1) isotachophoresis (ITP), (2) chiral capillary zone electrophoresis (chiral CZE), and (3) triple quadrupole mass spectrometry (QqQ MS). The ITP step, performed in a large bore capillary (800 μm), was utilized for the effective sample pretreatment (preconcentration and matrix clean-up) in a large injection volume (1-10 μL) enabling to obtain as low as ca. 80 pg/mL limits of detection for the target enantiomers in urine matrices. In the chiral CZE step, the different chiral selectors (neutral, ionizable, and permanently charged cyclodextrins) and buffer systems were tested in terms of enantioselectivity and influence on the MS detection response. The performance parameters of the optimized ITP - chiral CZE-QqQ MS method were evaluated according to the FDA guidance for bioanalytical method validation. Successful validation and application (enantioselective monitoring of renally eliminated pheniramine and its metabolite in human urine) highlighted great potential of this chiral approach in advanced enantioselective biomedical applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

High-Frequency Jet Ventilation for Complete Target Immobilization and Reduction of Planning Target Volume in Stereotactic High Single-Dose Irradiation of Stage I Non-Small Cell Lung Cancer and Lung Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fritz, Peter, E-mail: p.h.fritz@t-online.d; Kraus, Hans-Joerg; Muehlnickel, Werner

2010-09-01

Purpose: To demonstrate the feasibility of complete target immobilization by means of high-frequency jet ventilation (HFJV); and to show that the saving of planning target volume (PTV) on the stereotactic body radiation therapy (SBRT) under HFJV, compared with SBRT with respiratory motion, can be predicted with reliable accuracy by computed tomography (CT) scans at peak inspiration phase. Methods and Materials: A comparison regarding different methods for defining the PTV was carried out in 22 patients with tumors that clearly moved with respiration. A movement span of the gross tumor volume (GTV) was defined by fusing respiration-correlated CT scans. The PTVmore » enclosed the GTV positions with a safety margin throughout the breathing cycle. To create a PTV from CT scans acquired under HFJV, the same margins were drawn around the immobilized target. In addition, peak inspiration phase CT images (PIP-CTs) were used to approximate a target immobilized by HFJV. Results: The resulting HFJV-PTVs were between 11.6% and 45.4% smaller than the baseline values calculated as respiration-correlated CT-PTVs (median volume reduction, 25.4%). Tentative planning by means of PIP-CT PTVs predicted that in 19 of 22 patients, use of HFJV would lead to a reduction in volume of {>=}20%. Using this threshold yielded a positive predictive value of 0.89, as well as a sensitivity of 0.94 and a specificity of 0.5. Conclusions: In all patients, SBRT under HFJV provided a reliable immobilization of the GTVs and achieved a reduction in PTVs, regardless of patient compliance. Tentative planning facilitated the selection of patients who could better undergo radiation in respiratory standstill, both with greater accuracy and lung protection.« less

Simultaneous integrated vs. sequential boost in VMAT radiotherapy of high-grade gliomas.

PubMed

Farzin, Mostafa; Molls, Michael; Astner, Sabrina; Rondak, Ina-Christine; Oechsner, Markus

2015-12-01

In 20 patients with high-grade gliomas, we compared two methods of planning for volumetric-modulated arc therapy (VMAT): simultaneous integrated boost (SIB) vs. sequential boost (SEB). The investigation focused on the analysis of dose distributions in the target volumes and the organs at risk (OARs). After contouring the target volumes [planning target volumes (PTVs) and boost volumes (BVs)] and OARs, SIB planning and SEB planning were performed. The SEB method consisted of two plans: in the first plan the PTV received 50 Gy in 25 fractions with a 2-Gy dose per fraction. In the second plan the BV received 10 Gy in 5 fractions with a dose per fraction of 2 Gy. The doses of both plans were summed up to show the total doses delivered. In the SIB method the PTV received 54 Gy in 30 fractions with a dose per fraction of 1.8 Gy, while the BV received 60 Gy in the same fraction number but with a dose per fraction of 2 Gy. All of the OARs showed higher doses (Dmax and Dmean) in the SEB method when compared with the SIB technique. The differences between the two methods were statistically significant in almost all of the OARs. Analysing the total doses of the target volumes we found dose distributions with similar homogeneities and comparable total doses. Our analysis shows that the SIB method offers advantages over the SEB method in terms of sparing OARs.

Conformal Radiotherapy in the Treatment of Advanced Juvenile Nasopharyngeal Angiofibroma With Intracranial Extension: An Institutional Experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chakraborty, Santam, E-mail: drsantam@gmail.com; Ghoshal, Sushmita; Patil, Vijay Maruti

2011-08-01

Purpose: To describe the results of conformal radiotherapy in advanced juvenile nasopharyngeal angiofibroma in a tertiary care institution. Methods and Materials: Retrospective chart review was conducted for 8 patients treated with conformal radiotherapy between 2006 and 2009. The median follow-up was 17 months. All patients had Stage IIIB disease with intracranial extension. Radiotherapy was considered as treatment because patients were deemed inoperable owing to extensive intracranial/intraorbital extension or proximity to optic nerve. All but 1 patient were treated with intensity-modulated radiotherapy using seven coplanar fields. Median (range) dose prescribed was 39.6 (30-46) Gy. Actuarial analysis of local control and descriptivemore » analysis of toxicity profile was conducted. Results: Despite the large and complex target volume (median planning target volume, 292 cm{sup 3}), intensity-modulated radiotherapy achieved conformal dose distributions (median van't Reit index, 0.66). Significant sparing of the surrounding organs at risk was obtained. No significant Grade 3/4 toxicities were experienced during or after treatment. Actual local control at 2 years was 87.5%. One patient died 1 month after radiotherapy secondary to massive epistaxis. The remaining 7 patients had progressive resolution of disease and were symptom-free at last follow-up. Persistent rhinitis was the only significant toxicity, seen in 1 patient. Conclusions: Conformal radiotherapy results in good local control with minimal acute and late side effects in juvenile nasopharyngeal angiofibromas, even in the presence of advanced disease.« less

Assessment of Drug Binding Potential of Pockets in the NS2B/NS3 Dengue Virus Protein

NASA Astrophysics Data System (ADS)

Amelia, F.; Iryani; Sari, P. Y.; Parikesit, A. A.; Bakri, R.; Toepak, E. P.; Tambunan, U. S. F.

2018-04-01

Every year an endemic dengue fever estimated to affect over 390 million cases in over 128 countries occurs. However, the antigen types which stimulate the human immune response are variable, as a result, neither effective vaccines nor antiviral treatments have been successfully developed for this disease. The NS2B/NS3 protease of the dengue virus (DENV) responsible for viral replication is a potential drug target. The ligand-enzyme binding site determination is a key role in the success of virtual screening of new inhibitors. The NS2B/NS3 protease of DENV (PDB ID: 2FOM) has two pockets consisting of 37 (Pocket 1) and 27 (Pocket 2) amino acid residues in each pocket. In this research, we characterized the amino acid residues for binding sites in NS3/NS2B based on the hydrophobicity, the percentage of charged residues, volume, depth, ΔGbinding, hydrogen bonding and bond length. The hydrophobic percentages of both pockets are high, 59 % (Pocket 1) and 41% (Pocket 2) and the percentage of charged residues in Pocket 1 and 2 are 22% and 48%, and the pocket volume is less than 700 Å3. An interaction analysis using molecular docking showed that interaction between the ligand complex and protein in Pocket 1 is more negative than Pocket 2. As a result, Pocket 1 is the better potential target for a ligand to inhibit the action of NS2B/NS3 DENV.

Novel Platform for MRI-Guided Convection-Enhanced Delivery of Therapeutics: Preclinical Validation in Nonhuman Primate Brain

PubMed Central

Richardson, R. Mark; Kells, Adrian P.; Martin, Alastair J.; Larson, Paul S.; Starr, Philip A.; Piferi, Peter G.; Bates, Geoffrey; Tansey, Lisa; Rosenbluth, Kathryn H.; Bringas, John R.; Berger, Mitchel S.; Bankiewicz, Krystof S.

2011-01-01

Background/Aims A skull-mounted aiming device and integrated software platform has been developed for MRI-guided neurological interventions. In anticipation of upcoming gene therapy clinical trials, we adapted this device for real-time convection-enhanced delivery of therapeutics via a custom-designed infusion cannula. The targeting accuracy of this delivery system and the performance of the infusion cannula were validated in nonhuman primates. Methods Infusions of gadoteridol were delivered to multiple brain targets and the targeting error was determined for each cannula placement. Cannula performance was assessed by analyzing gadoteridol distributions and by histological analysis of tissue damage. Results The average targeting error for all targets (n = 11) was 0.8 mm (95% CI = 0.14). For clinically relevant volumes, the distribution volume of gadoteridol increased as a linear function (R2 = 0.97) of the infusion volume (average slope = 3.30, 95% CI = 0.2). No infusions in any target produced occlusion, cannula reflux or leakage from adjacent tracts, and no signs of unexpected tissue damage were observed. Conclusions This integrated delivery platform allows real-time convection-enhanced delivery to be performed with a high level of precision, predictability and safety. This approach may improve the success rate for clinical trials involving intracerebral drug delivery by direct infusion. PMID:21494065

Implementation of three dimensional conformal radiation therapy: prospects, opportunities, and challenges.

PubMed

Vijayakumar, S; Chen, G T

1995-12-01

To briefly review scientific rationale of 3D conformal radiation therapy (3DCRT) and discuss the prospects, opportunities, and challenges in the implementation of 3DCRT. Some of these ideas were discussed during a workshop on "Implementation of Three-Dimensional Conformal Radiation Therapy" in April 1994 at Bethesda, MD, and others have been discussed elsewhere in the literature. Local-regional control of cancer is an important component in the overall treatment strategy in any patient with cancer. It has been shown that failure to achieve local-regional control can lead to (a) an increase in chances of distant metastases, and (b) a decrease in the survival. In many disease sites, the doses delivered currently are inadequate to achieve satisfactory local tumor control rates; this is because in many sites, only limited doses of radiotherapy can be delivered due to the proximity of cancer to radiosensitive normal tissues. By conforming the radiotherapy beams to the tumor, doses to the tumors can be enhanced and doses to the normal tissues can be reduced. With the advances in 3DCRT, such conformation is possible now and is the rationale for using 3DCRT. However, a number of questions do remain that are not limited to the following: (a) What are the implications in terms of target volume definitions when implementing 3DCRT? (b) Are there some sites where research efforts can be focused to document the efficacy and cost effectiveness of 3DCRT? (c) How do we implement day-to-day 3DCRT treatment efficiently? (d) How do we transfer the technology from the university centers to the community without compromising quality? (e) What are all the quality assurance/quality improvement questions that need to be addressed and how do we ascertain quality assurance of 3DCRT? (f) Have we looked at cost-benefit ratios and quality of life (QOL) issues closely? There is a need for defining multiple target volumes: gross tumor volume, clinical target volume(s), and planning target volume(s). Such definitions should make implementation of 3DCRT more complex, yet will make high-dose delivery a possibility. There are many sites in which single and multiinstitutional studies are ongoing that include prostate, lung, head and neck, and brain. In other areas, cooperative group trials are required because of the inability of single institutions to accrue enough patients to answer clinically relevant questions with statistical validity. Although implementation of 3DCRT will require multiple steps, these multiple steps can be brought into clinical practice gradually and one does not have to wait until all steps required for implementation of 3DCRT are available. In this respect, "3DCRT" should be used in a very broad sense, from beam's eye view blocking, use of multibeam dose distribution, use of dose-volume histograms in choosing alternative plans, noncoplanar beam arrangements, intensity modulation, inverse planning, to totally automated implementation of 3DCRT. To transfer the 3DCRT capabilities to the community from the University Centers, there is a necessity to develop quality assurance programs. RTOG and the Three-Dimensional Oncology Group are spearheading these efforts. Three-dimensional conformal radiation therapy has potential not only to improve local control and decrease toxicity, but also to improve the cost benefit ratio in the use of radiotherapy as well as in improving quality of life in patients with cancer. Achieving many potential benefits of 3DCRT (improvement in local control, decreasing toxicity, organs-function preservation, improvement in cost effectiveness) will require further physics-related and clinical research in carefully conceived and successfully completed future clinical trials.

The dependence of crowding on flanker complexity and target-flanker similarity

PubMed Central

Bernard, Jean-Baptiste; Chung, Susana T.L.

2013-01-01

We examined the effects of the spatial complexity of flankers and target-flanker similarity on the performance of identifying crowded letters. On each trial, observers identified the middle character of random strings of three characters (“trigrams”) briefly presented at 10° below fixation. We tested the 26 lowercase letters of the Times-Roman and Courier fonts, a set of 79 characters (letters and non-letters) of the Times-Roman font, and the uppercase letters of two highly complex ornamental fonts, Edwardian and Aristocrat. Spatial complexity of characters was quantified by the length of the morphological skeleton of each character, and target-flanker similarity was defined based on a psychometric similarity matrix. Our results showed that (1) letter identification error rate increases with flanker complexity up to a certain value, beyond which error rate becomes independent of flanker complexity; (2) the increase of error rate is slower for high-complexity target letters; (3) error rate increases with target-flanker similarity; and (4) mislocation error rate increases with target-flanker similarity. These findings, combined with the current understanding of the faulty feature integration account of crowding, provide some constraints of how the feature integration process could cause perceptual errors. PMID:21730225

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahmed, Raef S.; Shen, Sui; Ove, Roger

We wanted to describe a technique for the implementation of intensity-modulated radiotherapy (IMRT) with a real-time position monitor (RPM) respiratory gating system for the treatment of pleural space with intact lung. The technique is illustrated by a case of pediatric osteosarcoma, metastatic to the pleura of the right lung. The patient was simulated in the supine position where a breathing tracer and computed tomography (CT) scans synchronized at end expiration were acquired using the RPM system. The gated CT images were used to define target volumes and critical structures. Right pleural gated IMRT delivered at end expiration was prescribed tomore » a dose of 44 Gy, with 55 Gy delivered to areas of higher risk via simultaneous integrated boost (SIB) technique. IMRT was necessary to avoid exceeding the tolerance of intact lung. Although very good coverage of the target volume was achieved with a shell-shaped dose distribution, dose over the targets was relatively inhomogeneous. Portions of target volumes necessarily intruded into the right lung, the liver, and right kidney, limiting the degree of normal tissue sparing that could be achieved. The radiation doses to critical structures were acceptable and well tolerated. With intact lung, delivering a relatively high dose to the pleura with acceptable doses to surrounding normal tissues using respiratory gated pleural IMRT is feasible. Treatment delivery during a limited part of the respiratory cycle allows for reduced CT target volume motion errors, with reduction in the portion of the planning margin that accounts for respiratory motion, and subsequent increase in the therapeutic ratio.« less

Recurrent eruption and subsidence at the Platoro caldera complex, southeastern San Juan volcanic field, Colorado: New tales from old tuffs

USGS Publications Warehouse

Lipman, P.W.; Dungan, M.A.; Brown, L.L.; Deino, A.

1996-01-01

Reinterpretation of a voluminous regional ash-flow sheet (Masonic Park Tuff) as two separate tuff sheets of similar phenocryst-rich dacite erupted from separate source calderas has important implications for evolution of the multicyclic Platoro caldera complex and for caldera-forming processes generally. Masonic Park Tuff in central parts of the San Juan field, including the type area, was erupted from a concealed source at 28.6 Ma, but widespread tuff previously mapped as Masonic Park Tuff in the southeastern San Juan Mountains is the product of the youngest large-volume eruption of the Platoro caldera complex at 28.4 Ma. This large unit, newly named the "Chiquito Peak Tuff," is the last-erupted tuff of the Treasure Mountain Group, which consists of at least 20 separate ash-flow sheets of dacite to low-silica rhyolite erupted from the Platoro complex during a 1 m.y. interval (29.5-28.4 Ma). Two Treasure Mountain tuff sheets have volumes in excess of 1000 km3 each, and five more have volumes of 50-150 km3. The total volume of ash-flow tuff exceeds 2500 km3, and caldera-related lavas of dominantly andesitic composition make up 250-500 km3 more. A much greater volume of intermediate-composition magma must have solidified in subcaldera magma chambers. Most preserved features of the Platoro complex - including postcollapse asymmetrical trap-door resurgent uplift of the ponded intracaldera tuff and concurrent infilling by andesitic lava flows - postdate eruption of the Chiquito Peak Tuff. The numerous large-volume pre-Chiquito Peak ash-flow tuffs document multiple eruptions accompanied by recurrent subsidence; early-formed caldera walls nearly coincide with margins of the later Chiquito Peak collapse. Repeated syneruptive collapse at the Platoro complex requires cumulative subsidence of at least 10 km. The rapid regeneration of silicic magmas requires the sustained presence of an andesitic subcaldera magma reservoir, or its rapid replenishment, during the 1 m.y. life span of the Platoro complex. Either case implies large-scale stoping and assimilative recycling of the Tertiary section, including intracaldera tuffs.

Pancreatic cancer planning: Complex conformal vs modulated therapies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chapman, Katherine L.; Witek, Matthew E.; Chen, Hongyu

To compare the roles of intensity-modulated radiation therapy (IMRT) and volumetric- modulated arc therapy (VMAT) therapy as compared to simple and complex 3-dimensional chemoradiotherpy (3DCRT) planning for resectable and borderline resectable pancreatic cancer. In all, 12 patients who received postoperative radiotherapy (8) or neoadjuvant concurrent chemoradiotherapy (4) were evaluated retrospectively. Radiotherapy planning was performed for 4 treatment techniques: simple 4-field box, complex 5-field 3DCRT, 5 to 6-field IMRT, and single-arc VMAT. All volumes were approved by a single observer in accordance with Radiation Therapy Oncology Group (RTOG) Pancreas Contouring Atlas. Plans included tumor/tumor bed and regional lymph nodes to 45more » Gy; with tumor/tumor bed boosted to 50.4 Gy, at least 95% of planning target volume (PTV) received the prescription dose. Dose-volume histograms (DVH) for multiple end points, treatment planning, and delivery time were assessed. Complex 3DCRT, IMRT, and VMAT plans significantly (p < 0.05) decreased mean kidney dose, mean liver dose, liver (V{sub 30}, V{sub 35}), stomach (D{sub 10}%), stomach (V{sub 45}), mean right kidney dose, and right kidney (V{sub 15}) as compared with the simple 4-field plans that are most commonly reported in the literature. IMRT plans resulted in decreased mean liver dose, liver (V{sub 35}), and left kidney (V{sub 15}, V{sub 18}, V{sub 20}). VMAT plans decreased small bowel (D{sub 10}%, D{sub 15}%), small bowel (V{sub 35}, V{sub 45}), stomach (D{sub 10}%, D{sub 15}%), stomach (V{sub 35}, V{sub 45}), mean liver dose, liver (V{sub 35}), left kidney (V{sub 15}, V{sub 18}, V{sub 20}), and right kidney (V{sub 18}, V{sub 20}). VMAT plans significantly decreased small bowel (D{sub 10}%, D{sub 15}%), left kidney (V{sub 20}), and stomach (V{sub 45}) as compared with IMRT plans. Treatment planning and delivery times were most efficient for simple 4-field box and VMAT. Excluding patient setup and imaging, average treatment delivery was within 10 minutes for simple and complex 3DCRT, IMRT, and VMAT treatments. This article shows significant improvements in 3D plan performance with complex planning over the more frequently compared 3- or 4-field simple 3D planning techniques. VMAT plans continue to demonstrate potential for the most organ sparing. However, further studies are required to identify if dosimetric benefits associated with inverse optimized planning can be translated into clinical benefits and if these treatment techniques are value-added therapies for this group of patients with cancer.« less

Diffusion and perfusion weighted magnetic resonance imaging for tumor volume definition in radiotherapy of brain tumors.

PubMed

Guo, Lu; Wang, Gang; Feng, Yuanming; Yu, Tonggang; Guo, Yu; Bai, Xu; Ye, Zhaoxiang

2016-09-21

Accurate target volume delineation is crucial for the radiotherapy of tumors. Diffusion and perfusion magnetic resonance imaging (MRI) can provide functional information about brain tumors, and they are able to detect tumor volume and physiological changes beyond the lesions shown on conventional MRI. This review examines recent studies that utilized diffusion and perfusion MRI for tumor volume definition in radiotherapy of brain tumors, and it presents the opportunities and challenges in the integration of multimodal functional MRI into clinical practice. The results indicate that specialized and robust post-processing algorithms and tools are needed for the precise alignment of targets on the images, and comprehensive validations with more clinical data are important for the improvement of the correlation between histopathologic results and MRI parameter images.

Predicting Nonauditory Adverse Radiation Effects Following Radiosurgery for Vestibular Schwannoma: A Volume and Dosimetric Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hayhurst, Caroline; Monsalves, Eric; Bernstein, Mark

2012-04-01

Purpose: To define clinical and dosimetric predictors of nonauditory adverse radiation effects after radiosurgery for vestibular schwannoma treated with a 12 Gy prescription dose. Methods: We retrospectively reviewed our experience of vestibular schwannoma patients treated between September 2005 and December 2009. Two hundred patients were treated at a 12 Gy prescription dose; 80 had complete clinical and radiological follow-up for at least 24 months (median, 28.5 months). All treatment plans were reviewed for target volume and dosimetry characteristics; gradient index; homogeneity index, defined as the maximum dose in the treatment volume divided by the prescription dose; conformity index; brainstem; andmore » trigeminal nerve dose. All adverse radiation effects (ARE) were recorded. Because the intent of our study was to focus on the nonauditory adverse effects, hearing outcome was not evaluated in this study. Results: Twenty-seven (33.8%) patients developed ARE, 5 (6%) developed hydrocephalus, 10 (12.5%) reported new ataxia, 17 (21%) developed trigeminal dysfunction, 3 (3.75%) had facial weakness, and 1 patient developed hemifacial spasm. The development of edema within the pons was significantly associated with ARE (p = 0.001). On multivariate analysis, only target volume is a significant predictor of ARE (p = 0.001). There is a target volume threshold of 5 cm3, above which ARE are more likely. The treatment plan dosimetric characteristics are not associated with ARE, although the maximum dose to the 5th nerve is a significant predictor of trigeminal dysfunction, with a threshold of 9 Gy. The overall 2-year tumor control rate was 96%. Conclusions: Target volume is the most important predictor of adverse radiation effects, and we identified the significant treatment volume threshold to be 5 cm3. We also established through our series that the maximum tolerable dose to the 5th nerve is 9 Gy.« less

Characterization and Cytotoxic Assessment of Ballistic Aerosol Particulates for Tungsten Alloy Penetrators into Steel Target Plates

PubMed Central

Machado, Brenda I.; Murr, Lawrence E.; Suro, Raquel M.; Gaytan, Sara M.; Ramirez, Diana A.; Garza, Kristine M.; Schuster, Brian E.

2010-01-01

The nature and constituents of ballistic aerosol created by kinetic energy penetrator rods of tungsten heavy alloys (W-Fe-Ni and W-Fe-Co) perforating steel target plates was characterized by scanning and transmission electron microscopy. These aerosol regimes, which can occur in closed, armored military vehicle penetration, are of concern for potential health effects, especially as a consequence of being inhaled. In a controlled volume containing 10 equispaced steel target plates, particulates were systematically collected onto special filters. Filter collections were examined by scanning and transmission electron microscopy (SEM and TEM) which included energy-dispersive (X-ray) spectrometry (EDS). Dark-field TEM identified a significant nanoparticle concentration while EDS in the SEM identified the propensity of mass fraction particulates to consist of Fe and FeO, representing target erosion and formation of an accumulating debris field. Direct exposure of human epithelial cells (A549), a model for lung tissue, to particulates (especially nanoparticulates) collected on individual filters demonstrated induction of rapid and global cell death to the extent that production of inflammatory cytokines was entirely inhibited. These observations along with comparisons of a wide range of other nanoparticulate species exhibiting cell death in A549 culture may suggest severe human toxicity potential for inhaled ballistic aerosol, but the complexity of the aerosol (particulate) mix has not yet allowed any particular chemical composition to be identified. PMID:20948926

Neurotechnology for intelligence analysts

NASA Astrophysics Data System (ADS)

Kruse, Amy A.; Boyd, Karen C.; Schulman, Joshua J.

2006-05-01

Geospatial Intelligence Analysts are currently faced with an enormous volume of imagery, only a fraction of which can be processed or reviewed in a timely operational manner. Computer-based target detection efforts have failed to yield the speed, flexibility and accuracy of the human visual system. Rather than focus solely on artificial systems, we hypothesize that the human visual system is still the best target detection apparatus currently in use, and with the addition of neuroscience-based measurement capabilities it can surpass the throughput of the unaided human severalfold. Using electroencephalography (EEG), Thorpe et al1 described a fast signal in the brain associated with the early detection of targets in static imagery using a Rapid Serial Visual Presentation (RSVP) paradigm. This finding suggests that it may be possible to extract target detection signals from complex imagery in real time utilizing non-invasive neurophysiological assessment tools. To transform this phenomenon into a capability for defense applications, the Defense Advanced Research Projects Agency (DARPA) currently is sponsoring an effort titled Neurotechnology for Intelligence Analysts (NIA). The vision of the NIA program is to revolutionize the way that analysts handle intelligence imagery, increasing both the throughput of imagery to the analyst and overall accuracy of the assessments. Successful development of a neurobiologically-based image triage system will enable image analysts to train more effectively and process imagery with greater speed and precision.

Characterization and cytotoxic assessment of ballistic aerosol particulates for tungsten alloy penetrators into steel target plates.

PubMed

Machado, Brenda I; Murr, Lawrence E; Suro, Raquel M; Gaytan, Sara M; Ramirez, Diana A; Garza, Kristine M; Schuster, Brian E

2010-09-01

The nature and constituents of ballistic aerosol created by kinetic energy penetrator rods of tungsten heavy alloys (W-Fe-Ni and W-Fe-Co) perforating steel target plates was characterized by scanning and transmission electron microscopy. These aerosol regimes, which can occur in closed, armored military vehicle penetration, are of concern for potential health effects, especially as a consequence of being inhaled. In a controlled volume containing 10 equispaced steel target plates, particulates were systematically collected onto special filters. Filter collections were examined by scanning and transmission electron microscopy (SEM and TEM) which included energy-dispersive (X-ray) spectrometry (EDS). Dark-field TEM identified a significant nanoparticle concentration while EDS in the SEM identified the propensity of mass fraction particulates to consist of Fe and FeO, representing target erosion and formation of an accumulating debris field. Direct exposure of human epithelial cells (A549), a model for lung tissue, to particulates (especially nanoparticulates) collected on individual filters demonstrated induction of rapid and global cell death to the extent that production of inflammatory cytokines was entirely inhibited. These observations along with comparisons of a wide range of other nanoparticulate species exhibiting cell death in A549 culture may suggest severe human toxicity potential for inhaled ballistic aerosol, but the complexity of the aerosol (particulate) mix has not yet allowed any particular chemical composition to be identified.

The mammalian toxicological hazards of petroleum-derived substances: an overview of the petroleum industry response to the high production volume challenge program.

PubMed

McKee, Richard H; White, Russell

2014-01-01

Petroleum-derived substances are complex and composed of aliphatic (normal-, iso-, and cycloparaffins), olefinic, and/or aromatic constituents. Approximately 400 of these complex substances were evaluated as part of the US Environmental Protection Agency voluntary High Production Volume (HPV) Challenge program. The substances were separated into 13 groups (categories), and all available data were assessed. Toxicology testing was conducted as necessary to fully address the end points encompassed by the HPV initiative. In a broad sense, volatile hydrocarbons may cause acute central nervous system effects, and those that are liquids at room temperature pose aspiration hazards if taken into the lungs as liquids and may also cause skin irritation. Higher boiling substances may contain polycyclic aromatic constituents (PACs) that can be mutagenic and carcinogenic and may also cause developmental effects. Substances containing PACs can also cause target organ and developmental effects. The effects of aliphatic constituents include liver enlargement and/or renal effects in male rats via an α-2u-globulin-mediated process and, in some cases, small but statistically significant reductions in hematological parameters. Crude oils may contain other constituents, particularly sulfur- and nitrogen-containing compounds, which are removed during refining. Aside from these more generic considerations, some specific petroleum substances may contain unusually toxic constituents including benzene, 1,3-butadiene, and/or n-hexane, which should also be taken into account if present at toxicologically relevant levels.

PET/CT aids the staging of and radiotherapy planning for early-stage extranodal natural killer/T-cell lymphoma, nasal type: A case series

PubMed Central

2011-01-01

Extranodal natural killer/T-cell lymphoma (ENKTL), nasal type, is a rare form of non-Hodgkin lymphoma. Treatment of ENKTL primarily relies on radiation; thus, proper delineation of target volumes is critical. Currently, the ideal modalities for delineation of gross tumor volume for ENKTL are unknown. We describe three consecutive cases of localized ENKTL that presented to the Nova Scotia Cancer Centre in Halifax, Nova Scotia. All patients had a planning CT and MRI as well as a planning FDG-PET/CT in the radiotherapy treatment position, wearing immobilization masks. All patients received radiation alone. In two patients, PET/CT changed not only the stage, but also the target volume requiring treatment. The third patient was unable to tolerate an MRI, but was able to undergo PET/CT, which improved the accuracy of the target volume. PET/CT aided the staging of and radiotherapy planning for our patients and appears to be a promising tool in the treatment of ENKTL. PMID:22208903

Real-Time Measurement of Host Bioenergetics During Mycobacterium Tuberculosis Infection

DTIC Science & Technology

2015-05-01

antimycobacterial drugs on Mtb bioenergetics. We focused on Clofazimine (CFZ, targets Complex I), Bedaquiline (BDQ/TMC207, targets Complex V) and Q203 (targets... Complex III). Firstly we investigated the effect of CFZ and BDQ on the OCR profiles of Mtb mc2 6230 (Figure 3). These experiments were done in...addition with of CFZ. The decrease in OCR is consistent with ETC complex inhibition. BDQ caused a very surprising concentration-depended increase

Accuracy of implementing principles of fusion imaging in the follow up and surveillance of complex aneurysm repair.

PubMed

Martin-Gonzalez, Teresa; Penney, Graeme; Chong, Debra; Davis, Meryl; Mastracci, Tara M

2018-05-01

Fusion imaging is standard for the endovascular treatment of complex aortic aneurysms, but its role in follow up has not been explored. A critical issue is renal function deterioration over time. Renal volume has been used as a marker of renal impairment; however, it is not reproducible and remains a complex and resource-intensive procedure. The aim of this study is to determine the accuracy of a fusion-based software to automatically calculate the renal volume changes during follow up. In this study, computerized tomography (CT) scans of 16 patients who underwent complex aortic endovascular repair were analysed. Preoperative, 1-month and 1-year follow-up CT scans have been analysed using a conventional approach of semi-automatic segmentation, and a second approach with automatic segmentation. For each kidney and at each time point the percentage of change in renal volume was calculated using both techniques. After review, volume assessment was feasible for all CT scans. For the left kidney, the intraclass correlation coefficient (ICC) was 0.794 and 0.877 at 1 month and 1 year, respectively. For the right side, the ICC was 0.817 at 1 month and 0.966 at 1 year. The automated technique reliably detected a decrease in renal volume for the eight patients with occluded renal arteries during follow up. This is the first report of a fusion-based algorithm to detect changes in renal volume during postoperative surveillance using an automated process. Using this technique, the standardized assessment of renal volume could be implemented with greater ease and reproducibility and serve as a warning of potential renal impairment.

Comparison of five segmentation tools for 18F-fluoro-deoxy-glucose-positron emission tomography-based target volume definition in head and neck cancer.

PubMed

Schinagl, Dominic A X; Vogel, Wouter V; Hoffmann, Aswin L; van Dalen, Jorn A; Oyen, Wim J; Kaanders, Johannes H A M

2007-11-15

Target-volume delineation for radiation treatment to the head and neck area traditionally is based on physical examination, computed tomography (CT), and magnetic resonance imaging. Additional molecular imaging with (18)F-fluoro-deoxy-glucose (FDG)-positron emission tomography (PET) may improve definition of the gross tumor volume (GTV). In this study, five methods for tumor delineation on FDG-PET are compared with CT-based delineation. Seventy-eight patients with Stages II-IV squamous cell carcinoma of the head and neck area underwent coregistered CT and FDG-PET. The primary tumor was delineated on CT, and five PET-based GTVs were obtained: visual interpretation, applying an isocontour of a standardized uptake value of 2.5, using a fixed threshold of 40% and 50% of the maximum signal intensity, and applying an adaptive threshold based on the signal-to-background ratio. Absolute GTV volumes were compared, and overlap analyses were performed. The GTV method of applying an isocontour of a standardized uptake value of 2.5 failed to provide successful delineation in 45% of cases. For the other PET delineation methods, volume and shape of the GTV were influenced heavily by the choice of segmentation tool. On average, all threshold-based PET-GTVs were smaller than on CT. Nevertheless, PET frequently detected significant tumor extension outside the GTV delineated on CT (15-34% of PET volume). The choice of segmentation tool for target-volume definition of head and neck cancer based on FDG-PET images is not trivial because it influences both volume and shape of the resulting GTV. With adequate delineation, PET may add significantly to CT- and physical examination-based GTV definition.

The Dependency of Penetration on the Momentum Per Unit Area of the Impacting Projectile and the Resistance of Materials to Penetration

NASA Technical Reports Server (NTRS)

Collins, Rufus D., Jr.; Kinard, William H.

1960-01-01

The results of this investigation indicate that the penetration of projectiles into quasi-infinite targets can be correlated as a function of the maximum momentum per unit area possessed by the projectiles. The penetration of projectiles into aluminum, copper, and steel targets was found to be a linear function while the penetration into lead targets was a nonlinear function of the momentum per unit area of the impacting projectiles. Penetration varied inversely as the projectile density and the elastic modulus of the target material for a given projectile momentum per unit area. Crater volumes were found to be a linear function of the kinetic energy of the projectile, the greater volumes being obtained in the target materials which had the lowest yield strength and the lowest speed of sound.

Youth Attitude Tracking Study. Volume 1. Spring 1980.

DTIC Science & Technology

1980-08-01

JobICharacteristics 11 Active Duty Positive Propensity Respondents Target Market Profile 13 Advertising Awareness 14 ’LIAttitudes Toward Enlistment Incentives...service advertising awareness. The fact that target market men value job characteristics that pertain to improving oneself suggests that this change in copy...W,0-R143 ii4 YOUTH ATTITUDE TRACKING STUDY VOLUME i SPRING i988(U) 1/3 MARKET FACTS INC CHICAGO IL PUBLIC SECTOR RESEARCH CORP J T HEISLER AUG 80

Speed-up of the volumetric method of moments for the approximate RCS of large arbitrary-shaped dielectric targets

NASA Astrophysics Data System (ADS)

Moreno, Javier; Somolinos, Álvaro; Romero, Gustavo; González, Iván; Cátedra, Felipe

2017-08-01

A method for the rigorous computation of the electromagnetic scattering of large dielectric volumes is presented. One goal is to simplify the analysis of large dielectric targets with translational symmetries taken advantage of their Toeplitz symmetry. Then, the matrix-fill stage of the Method of Moments is efficiently obtained because the number of coupling terms to compute is reduced. The Multilevel Fast Multipole Method is applied to solve the problem. Structured meshes are obtained efficiently to approximate the dielectric volumes. The regular mesh grid is achieved by using parallelepipeds whose centres have been identified as internal to the target. The ray casting algorithm is used to classify the parallelepiped centres. It may become a bottleneck when too many points are evaluated in volumes defined by parametric surfaces, so a hierarchical algorithm is proposed to minimize the number of evaluations. Measurements and analytical results are included for validation purposes.

Conformal and intensity modulated irradiation of head and neck cancer: the potential for improved target irradiation, salivary gland function, and quality of life.

PubMed

Eisbruch, A; Dawson, L A; Kim, H M; Bradford, C R; Terrell, J E; Chepeha, D B; Teknos, T N; Anzai, Y; Marsh, L H; Martel, M K; Ten Haken, R K; Wolf, G T; Ship, J A

1999-01-01

To develop techniques which facilitate sparing of the major salivary glands while adequately treating the targets in patients requiring comprehensive bilateral neck irradiation (RT). Conformal and static, multisegmental intensity modulated (IMRT) techniques have been developed. The salivary flow rates before and periodically after RT have been measured selectively from each major salivary gland and the residual flows correlated with glands' dose volume histograms. Subjective xerostomia questionnaires have been developed and validated. The pattern of local-regional recurrences has been examined using CT scans at the time of recurrence, transferring the recurrence volumes to the planning CT scans and regenerating the dose distributions at the recurrence sites. Target coverage and dose homogeneity in IMRT treatment plans were found to be significantly better than standard RT plans. Significant parotid gland sparing was achieved. The relationships among dose, irradiated volume and saliva flow rates from the parotid glands were characterized by dose and volume thresholds. A mean dose of 26 Gy was found to be the threshold for stimulated saliva. Subjective xerostomia was significantly reduced in patients irradiated with parotid sparing techniques, compared to patients with similar tumors treated with standard RT. The large majority of recurrences occurred inside high-risk targets. Tangible gains in salivary gland sparing and target coverage are being achieved and an improvement in some measures of quality of life is suggested by our findings. A mean parotid gland dose of < or = 26 Gy should be a planning objective if significant parotid function preservation is desired. The pattern of recurrence suggests that careful escalation of the dose to targets judged to be at highest risk may improve tumor control.

Bipartite recognition of target RNAs activates DNA cleavage by the Type III-B CRISPR–Cas system

PubMed Central

Elmore, Joshua R.; Sheppard, Nolan F.; Ramia, Nancy; Deighan, Trace; Li, Hong; Terns, Rebecca M.; Terns, Michael P.

2016-01-01

CRISPR–Cas systems eliminate nucleic acid invaders in bacteria and archaea. The effector complex of the Type III-B Cmr system cleaves invader RNAs recognized by the CRISPR RNA (crRNA ) of the complex. Here we show that invader RNAs also activate the Cmr complex to cleave DNA. As has been observed for other Type III systems, Cmr eliminates plasmid invaders in Pyrococcus furiosus by a mechanism that depends on transcription of the crRNA target sequence within the plasmid. Notably, we found that the target RNA per se induces DNA cleavage by the Cmr complex in vitro. DNA cleavage activity does not depend on cleavage of the target RNA but notably does require the presence of a short sequence adjacent to the target sequence within the activating target RNA (rPAM [RNA protospacer-adjacent motif]). The activated complex does not require a target sequence (or a PAM) in the DNA substrate. Plasmid elimination by the P. furiosus Cmr system also does not require the Csx1 (CRISPR-associated Rossman fold [CARF] superfamily) protein. Plasmid silencing depends on the HD nuclease and Palm domains of the Cmr2 (Cas10 superfamily) protein. The results establish the Cmr complex as a novel DNA nuclease activated by invader RNAs containing a crRNA target sequence and a rPAM. PMID:26848045

Traditional surgical planning of liver surgery is modified by 3D interactive quantitative surgical planning approach: a single-center experience with 305 patients.

PubMed

Wang, Xue-Dong; Wang, Hong-Guang; Shi, Jun; Duan, Wei-Dong; Luo, Ying; Ji, Wen-Bin; Zhang, Ning; Dong, Jia-Hong

2017-06-01

Decision making and surgical planning are to achieve the precise balance of maximal removal of target lesion, maximal sparing of functional liver remnant volume, and minimal surgical invasiveness and therefore, crucial in liver surgery. The aim of this prospective study was to validate the accuracy and predictability of 3D interactive quantitative surgical planning approach (IQSP), and to evaluate the impact of IQSP on traditional surgical plans based on 2D images. A total of 305 consecutive patients undergoing hepatectomy were included in this study. Surgical plans were created by traditional 2D approach using picture archiving and communication system (PACS) and 3D approach using IQSP respectively by two groups of physicians who did not know the surgical plans of the other group. The two surgical plans were submitted to the chief surgeon for selection before operation. The specimens were weighed. The two surgical plans were compared and analyzed retrospectively based on the operation results. The two surgical plans were successfully developed in all 305 patients and all the 3D IQSP surgical plans were selected as the final decision. Total 278 patients successfully underwent surgery, including 147 uncomplex hepatectomy and 131 complex hepatectomy. Twenty-seven patients were withdrawn from hepatectomy. In the uncomplex group, the two surgical plans were the same in all 147 patients and no statistically significant difference was found among 2D calculated resection volume (2D-RV), 3D IQSP calculated resection volume (IQSP-RV) and the specimen volume. In the complex group, the two surgical plans were different in 49 patients (49/131, 37.4%). According to the significance of differences, the 49 different patients were classified into three grades. No statistically significant difference was found between IQSP-RV and specimen volume. The coincidence rate of territory analysis of IQSP with operation was 92.1% (93/101) for 101 patients of anatomic hepatectomy. The accuracy and predictability of 3D IQSP were validated. Compared with traditional surgical planning, 3D IQSP can provide more quantitative information of anatomic structure. With the assistance of 3D IQSP, traditional surgical plans were modified to be more radical and safe.

Measurement of complex joint trajectories using slice-to-volume 2D/3D registration and cine MR

NASA Astrophysics Data System (ADS)

Bloch, C.; Figl, M.; Gendrin, C.; Weber, C.; Unger, E.; Aldrian, S.; Birkfellner, W.

2010-02-01

A method for studying the in vivo kinematics of complex joints is presented. It is based on automatic fusion of single slice cine MR images capturing the dynamics and a static MR volume. With the joint at rest the 3D scan is taken. In the data the anatomical compartments are identified and segmented resulting in a 3D volume of each individual part. In each of the cine MR images the joint parts are segmented and their pose and position are derived using a 2D/3D slice-to-volume registration to the volumes. The method is tested on the carpal joint because of its complexity and the small but complex motion of its compartments. For a first study a human cadaver hand was scanned and the method was evaluated with artificially generated slice images. Starting from random initial positions of about 5 mm translational and 12° rotational deviation, 70 to 90 % of the registrations converged successfully to a deviation better than 0.5 mm and 5°. First evaluations using real data from a cine MR were promising. The feasibility of the method was demonstrated. However we experienced difficulties with the segmentation of the cine MR images. We therefore plan to examine different parameters for the image acquisition in future studies.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang Hua; Department of Radiation Oncology, Cancer Hospital of Jiangxi Province, Jiangxi Province; Li Yexiong, E-mail: yexiong@yahoo.com

Purpose: The value of intensity-modulated radiotherapy (IMRT) for early-stage nasal NK/T-cell lymphoma has not been previously reported. The aim of the present study was to assess the dosimetric parameters, toxicity, and treatment outcomes of patients with nasal NK/T-cell lymphoma. Methods and Materials: Between 2003 and 2008, 42 patients with early-stage nasal NK/T-cell lymphoma underwent definitive high-dose and extended involved-field IMRT with or without combination chemotherapy. The median radiation dose to the primary tumor was 50 Gy. The dose-volume histograms of the target volume and critical normal structures were evaluated in all patients. The locoregional control, overall survival, and progression-free survivalmore » were calculated using the Kaplan-Meier method. Results: The average mean dose delivered to the planning target volume was 55.5 Gy. Only 1.3% and 2.5% of the planning target volume received <90% and 95% of the prescribed dose, respectively, indicating excellent planning target volume coverage. The mean dose and average dose to the parotid glands was 15 Gy and 14 Gy, respectively. With a median follow-up time of 27 months, the 2-year locoregional control, overall survival, and progression-free survivalrate was 93%, 78%, and 74%, respectively. No Grade 4 or 5 acute or late toxicity was reported. Conclusions: High-dose and extended involved-field IMRT for patients with early-stage nasal NK/T-cell lymphoma showed favorable locoregional control, overall survival, and progression-free survival, with mild toxicity. The dose constraints of IMRT for the parotid glands can be limited to <20 Gy in these patients.« less

Set-up uncertainties: online correction with X-ray volume imaging.

PubMed

Kataria, Tejinder; Abhishek, Ashu; Chadha, Pranav; Nandigam, Janardhan

2011-01-01

To determine interfractional three-dimensional set-up errors using X-ray volumetric imaging (XVI). Between December 2007 and August 2009, 125 patients were taken up for image-guided radiotherapy using online XVI. After matching of reference and acquired volume view images, set-up errors in three translation directions were recorded and corrected online before treatment each day. Mean displacements, population systematic (Σ), and random (σ) errors were calculated and analyzed using SPSS (v16) software. Optimum clinical target volume (CTV) to planning target volume (PTV) margin was calculated using Van Herk's (2.5Σ + 0.7 σ) and Stroom's (2Σ + 0.7 σ) formula. Patients were grouped in 4 cohorts, namely brain, head and neck, thorax, and abdomen-pelvis. The mean vector displacement recorded were 0.18 cm, 0.15 cm, 0.36 cm, and 0.35 cm for brain, head and neck, thorax, and abdomen-pelvis, respectively. Analysis of individual mean set-up errors revealed good agreement with the proposed 0.3 cm isotropic margins for brain and 0.5 cm isotropic margins for head-neck. Similarly, 0.5 cm circumferential and 1 cm craniocaudal proposed margins were in agreement with thorax and abdomen-pelvic cases. The calculated mean displacements were well within CTV-PTV margin estimates of Van Herk (90% population coverage to minimum 95% prescribed dose) and Stroom (99% target volume coverage by 95% prescribed dose). Employing these individualized margins in a particular cohort ensure comparable target coverage as described in literature, which is further improved if XVI-aided set-up error detection and correction is used before treatment.

Retinal Prosthetics, Optogenetics, and Chemical Photoswitches

PubMed Central

2015-01-01

Three technologies have emerged as therapies to restore light sensing to profoundly blind patients suffering from late-stage retinal degenerations: (1) retinal prosthetics, (2) optogenetics, and (3) chemical photoswitches. Prosthetics are the most mature and the only approach in clinical practice. Prosthetic implants require complex surgical intervention and provide only limited visual resolution but can potentially restore navigational ability to many blind patients. Optogenetics uses viral delivery of type 1 opsin genes from prokaryotes or eukaryote algae to restore light responses in survivor neurons. Targeting and expression remain major problems, but are potentially soluble. Importantly, optogenetics could provide the ultimate in high-resolution vision due to the long persistence of gene expression achieved in animal models. Nevertheless, optogenetics remains challenging to implement in human eyes with large volumes, complex disease progression, and physical barriers to viral penetration. Now, a new generation of photochromic ligands or chemical photoswitches (azobenzene-quaternary ammonium derivatives) can be injected into a degenerated mouse eye and, in minutes to hours, activate light responses in neurons. These photoswitches offer the potential for rapidly and reversibly screening the vision restoration expected in an individual patient. Chemical photoswitch variants that persist in the cell membrane could make them a simple therapy of choice, with resolution and sensitivity equivalent to optogenetics approaches. A major complexity in treating retinal degenerations is retinal remodeling: pathologic network rewiring, molecular reprogramming, and cell death that compromise signaling in the surviving retina. Remodeling forces a choice between upstream and downstream targeting, each engaging different benefits and defects. Prosthetics and optogenetics can be implemented in either mode, but the use of chemical photoswitches is currently limited to downstream implementations. Even so, given the high density of human foveal ganglion cells, the ultimate chemical photoswitch treatment could deliver cost-effective, high-resolution vision for the blind. PMID:25089879

Calculation of the Frequency Distribution of the Energy Deposition in DNA Volumes by Heavy Ions

NASA Technical Reports Server (NTRS)

Plante, Ianik; Cicinotta, Francis A.

2012-01-01

Radiation quality effects are largely determined by energy deposition in small volumes of characteristic sizes less than 10 nm representative of short-segments of DNA, the DNA nucleosome, or molecules initiating oxidative stress in the nucleus, mitochondria, or extra-cellular matrix. On this scale, qualitatively distinct types of molecular damage are possible for high linear energy transfer (LET) radiation such as heavy ions compared to low LET radiation. Unique types of DNA lesions or oxidative damages are the likely outcome of the energy deposition. The frequency distribution for energy imparted to 1-20 nm targets per unit dose or particle fluence is a useful descriptor and can be evaluated as a function of impact parameter from an ions track. In this work, the simulation of 1-Gy irradiation of a cubic volume of 5 micron by: 1) 450 (1)H(+) ions, 300 MeV; 2) 10 (12)C(6+) ions, 290 MeV/amu and 3) (56)Fe(26+) ions, 1000 MeV/amu was done with the Monte-Carlo simulation code RITRACKS. Cylindrical targets are generated in the irradiated volume, with random orientation. The frequency distribution curves of the energy deposited in the targets is obtained. For small targets (i.e. <25 nm size), the probability of an ion to hit a target is very small; therefore a large number of tracks and targets as well as a large number of histories are necessary to obtain statistically significant results. This simulation is very time-consuming and is difficult to perform by using the original version of RITRACKS. Consequently, the code RITRACKS was adapted to use multiple CPU on a workstation or on a computer cluster. To validate the simulation results, similar calculations were performed using targets with fixed position and orientation, for which experimental data are available [5]. Since the probability of single- and double-strand breaks in DNA as function of energy deposited is well know, the results that were obtained can be used to estimate the yield of DSB, and can be extended to include other targeted or non-target effects.

Comparison of pencil beam–based homogeneous vs inhomogeneous target dose planning for stereotactic body radiotherapy of peripheral lung tumors through Monte Carlo–based recalculation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ohtakara, Kazuhiro, E-mail: ohtakara@murakami.asahi-u.ac.jp; Hoshi, Hiroaki

2015-10-01

This study was conducted to ascertain whether homogeneous target dose planning is suitable for stereotactic body radiotherapy (SBRT) of peripheral lung cancer under appropriate breath-holding. For 20 peripheral lung tumors, paired dynamic conformal arc plans were generated by only adjusting the leaf margin to the planning target volume (PTV) edge for fulfilling the conditions such that the prescription isodose surface (IDS) encompassing exactly 95% of the PTV (PTV D{sub 95}) corresponds to 95% and 80% IDS, normalized to 100% at the PTV isocenter under a pencil beam (PB) algorithm with radiologic path length correction. These plans were recalculated using themore » x-ray voxel Monte Carlo (XVMC) algorithm under otherwise identical conditions, and then compared. Lesions abutting the parietal pleura or not were defined as edge or island tumors, respectively, and the influences of the target volume and its location relative to the chest wall on the target dose were examined. The median (range) leaf margin required for the 95% and 80% plans was 3.9 mm (1.3 to 5.0) and −1.2 mm (−1.8 to 0.1), respectively. Notably, the latter was significantly correlated negatively with PTV. In the 80% plans, the PTV D{sub 95} was slightly higher under XVMC, whereas the PTV D{sub 98} was significantly lower, irrespective of the dose calculation algorithm used. Other PTV and all gross tumor volume doses were significantly higher, while the lung doses outside the PTV were slightly lower. The target doses increased as a function of PTV and were significantly lower for island tumors than for edge tumors. In conclusion, inhomogeneous target dose planning using smaller leaf margin for a larger tumor volume was deemed suitable in ensuring more sufficient target dose while slightly reducing lung dose. In addition, more inhomogeneous target dose planning using <80% IDS (e.g., 70%) for PTV covering would be preferable for island tumors.« less

Cross-modal links among vision, audition, and touch in complex environments.

PubMed

Ferris, Thomas K; Sarter, Nadine B

2008-02-01

This study sought to determine whether performance effects of cross-modal spatial links that were observed in earlier laboratory studies scale to more complex environments and need to be considered in multimodal interface design. It also revisits the unresolved issue of cross-modal cuing asymmetries. Previous laboratory studies employing simple cues, tasks, and/or targets have demonstrated that the efficiency of processing visual, auditory, and tactile stimuli is affected by the modality, lateralization, and timing of surrounding cues. Very few studies have investigated these cross-modal constraints in the context of more complex environments to determine whether they scale and how complexity affects the nature of cross-modal cuing asymmetries. Amicroworld simulation of battlefield operations with a complex task set and meaningful visual, auditory, and tactile stimuli was used to investigate cuing effects for all cross-modal pairings. Significant asymmetric performance effects of cross-modal spatial links were observed. Auditory cues shortened response latencies for collocated visual targets but visual cues did not do the same for collocated auditory targets. Responses to contralateral (rather than ipsilateral) targets were faster for tactually cued auditory targets and each visual-tactile cue-target combination, suggesting an inhibition-of-return effect. The spatial relationships between multimodal cues and targets significantly affect target response times in complex environments. The performance effects of cross-modal links and the observed cross-modal cuing asymmetries need to be examined in more detail and considered in future interface design. The findings from this study have implications for the design of multimodal and adaptive interfaces and for supporting attention management in complex, data-rich domains.

Microfluidic impact printer with interchangeable cartridges for versatile non-contact multiplexed micropatterning

PubMed Central

Ding, Yuzhe; Huang, Eric; Lam, Kit S.; Pan, Tingrui

2015-01-01

Biopatterning has been increasingly used for well-defined cellular microenvironment, patterned surface topology, and guided biological cues; however, it meets additional challenges on biocompatibility, temperature and chemical sensitivity and limited reagent volume. In this paper, we target at combining the desired features from the non-contact inkjet printing and the dot-matrix impact printing to establish a versatile multiplexed micropatterning platform, referred to as Microfluidic Impact Printer (MI-Printer), for emerging biomedical applications. Using this platform, we can achieve the distinct features of no cross-contamination, minute volume manipulation with minimal dead volume, high-throughput and biocompatible printing process, multiplexed patterning with automatic alignment, printing availability for complex medium (cell suspension or colloidal solutions), interchangeable/disposable microfluidic cartridge design with out-of-cleanroom microfabrication, simple printing system assembly and configuration, all highly desirable towards biological applications. Specifically, the printing resolution of the MI-printer platform has been experimentally characterized and theoretically analyzed. Printed droplets with 80µm in diameter have been repeatedly obtained. Furthermore, two unique features of MI-printer platform, multiplexed printing and self-alignment printing, have been successfully experimentally demonstrated (less than 10µm misalignment). In addition, combinatorial patterning and biological patterning, which utilizes the multiplexed and self-alignment printing nature of the MI-printer, have been devised to demonstrate the applicability of this robust printing technique for emerging biomedical applications. PMID:23525299

Consequence of preterm birth in early adolescence: the role of language on auditory short-term memory.

PubMed

Fraello, David; Maller-Kesselman, Jill; Vohr, Betty; Katz, Karol H; Kesler, Shelli; Schneider, Karen; Reiss, Allan; Ment, Laura; Spann, Marisa N

2011-06-01

This study tested the hypothesis that preterm early adolescents' short-term memory is compromised when presented with increasingly complex verbal information and that associated neuroanatomical volumes would differ between preterm and term groups. Forty-nine preterm and 20 term subjects were evaluated at age 12 years with neuropsychological measures and magnetic resonance imaging (MRI). There were no differences between groups in simple short-term and working memory. Preterm subjects performed lower on learning and short-term memory tests that included increased verbal complexity. They had reduced right parietal, left temporal, and right temporal white matter volumes and greater bilateral frontal gray and right frontal white matter volumes. There was a positive association between complex working memory and the left hippocampus and frontal white matter in term subjects. While not correlated, memory scores and volumes of cortical regions known to subserve language and memory were reduced in preterm subjects. This study provides evidence of possible mechanisms for learning problems in former preterm infants.

Laser program annual report, 1979

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coleman, L.W.; Strack, J.R.

1980-03-01

This volume contains four sections that covers the areas of target design, target fabrication, diagnostics, and experiments. Section 3 reports on target design activities, plasma theory and simulation, code development, and atomic theory. Section 4 presents the accomplishments of the target fabrication group, and Section 5 presents results of diagnostic developments and applications for the year. The results of laser-target experiments are presented. (MOW)

Impact of 4D image quality on the accuracy of target definition.

PubMed

Nielsen, Tine Bjørn; Hansen, Christian Rønn; Westberg, Jonas; Hansen, Olfred; Brink, Carsten

2016-03-01

Delineation accuracy of target shape and position depends on the image quality. This study investigates whether the image quality on standard 4D systems has an influence comparable to the overall delineation uncertainty. A moving lung target was imaged using a dynamic thorax phantom on three different 4D computed tomography (CT) systems and a 4D cone beam CT (CBCT) system using pre-defined clinical scanning protocols. Peak-to-peak motion and target volume were registered using rigid registration and automatic delineation, respectively. A spatial distribution of the imaging uncertainty was calculated as the distance deviation between the imaged target and the true target shape. The measured motions were smaller than actual motions. There were volume differences of the imaged target between respiration phases. Imaging uncertainties of >0.4 cm were measured in the motion direction which showed that there was a large distortion of the imaged target shape. Imaging uncertainties of standard 4D systems are of similar size as typical GTV-CTV expansions (0.5-1 cm) and contribute considerably to the target definition uncertainty. Optimising and validating 4D systems is recommended in order to obtain the most optimal imaged target shape.

Beyond mean pharyngeal constrictor dose for beam path toxicity in non-target swallowing muscles: dose-volume correlates of chronic radiation-associated dysphagia (RAD) after oropharyngeal intensity modulated radiotherapy

PubMed Central

2016-01-01

Purpose/Objective(s) We sought to identify swallowing muscle dose-response thresholds associated with chronic radiation-associated dysphagia (RAD) after IMRT for oropharyngeal cancer. Materials/Methods T1-4 N0-3 M0 oropharyngeal cancer patients who received definitive IMRT and systemic therapy were examined. Chronic RAD was coded as any of the following ≥ 12 months post-IMRT: videofluoroscopy/endoscopy detected aspiration or stricture, gastrostomy tube and/or aspiration pneumonia. DICOM-RT plan data were autosegmented using a custom region-of-interest (ROI) library and included inferior, middle and superior constrictors (IPC, MPC, and SPC), medial and lateral pterygoids (MPM, LPM), anterior and posterior digastrics (ADM, PDM), intrinsic tongue muscles (ITM), mylo/geniohyoid complex (MHM), genioglossus (GGM), ), masseter (MM), Buccinator (BM), palatoglossus (PGM), and cricopharyngeus (CPM), with ROI dose-volume histograms (DVHs) calculated. Recursive partitioning analysis (RPA) was used to identify dose-volume effects associated with chronic-RAD, for use in a multivariate (MV) model. Results Of 300 patients, 34 (11%) had chronic-RAD. RPA showed DVH-derived MHM V69 (i.e. the volume receiving ≥69Gy), GGM V35, ADM V60, MPC V49, and SPC V70 were associated with chronic-RAD. A model including age in addition to MHM V69 as continuous variables was optimal among tested MV models (AUC 0.835). Conclusion In addition to SPCs, dose to MHM should be monitored and constrained, especially in older patients (>62-years), when feasible. PMID:26897515

Beyond mean pharyngeal constrictor dose for beam path toxicity in non-target swallowing muscles: Dose-volume correlates of chronic radiation-associated dysphagia (RAD) after oropharyngeal intensity modulated radiotherapy.

PubMed

2016-02-01

We sought to identify swallowing muscle dose-response thresholds associated with chronic radiation-associated dysphagia (RAD) after IMRT for oropharyngeal cancer. T1-4 N0-3 M0 oropharyngeal cancer patients who received definitive IMRT and systemic therapy were examined. Chronic RAD was coded as any of the following ⩾12months post-IMRT: videofluoroscopy/endoscopy detected aspiration or stricture, gastrostomy tube and/or aspiration pneumonia. DICOM-RT plan data were autosegmented using a custom region-of-interest (ROI) library and included inferior, middle and superior constrictors (IPC, MPC, and SPC), medial and lateral pterygoids (MPM, LPM), anterior and posterior digastrics (ADM, PDM), intrinsic tongue muscles (ITM), mylo/geniohyoid complex (MHM), genioglossus (GGM), masseter (MM), buccinator (BM), palatoglossus (PGM), and cricopharyngeus (CPM), with ROI dose-volume histograms (DVHs) calculated. Recursive partitioning analysis (RPA) was used to identify dose-volume effects associated with chronic-RAD, for use in a multivariate (MV) model. Of 300 patients, 34 (11%) had chronic-RAD. RPA showed DVH-derived MHM V69 (i.e. the volume receiving⩾69Gy), GGM V35, ADM V60, MPC V49, and SPC V70 were associated with chronic-RAD. A model including age in addition to MHM V69 as continuous variables was optimal among tested MV models (AUC 0.835). In addition to SPCs, dose to MHM should be monitored and constrained, especially in older patients (>62-years), when feasible. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The separation of flavonoids from Pongamia pinnata using combination columns in high-speed counter-current chromatography with a three-phase solvent system.

PubMed

Yin, Hao; Zhang, Si; Long, Lijuan; Yin, Hang; Tian, Xinpeng; Luo, Xiongming; Nan, Haihan; He, Sha

2013-11-08

The mangrove plant Pongamia pinnata (Leguminosae) is well known as a plant pesticide. Previous studies have indicated that the flavonoids are responsible of the biological activities of the plant. A new high-speed counter-current chromatography (HSCCC) method for the separation of three flavonoids, karanjin (1), pinnatin (2), and pongaflavone (3), from P. pinnata was developed in the present study. The lower and intermediate phase (LP and IP) of a new three-phase solvent system, n-hexane-acetonitrile-dichloromethane-water, at a volume ratio of 5:5:1:5, were used as the stationary phases, while the upper phase (UP) was used as the mobile phase, and the volume ratio between the stationary phases in the CCC column could be tuned by varying the initial pumped volume ratio of the stationary phases. The CCC columns containing all three phases of the solvent system were considered combination columns. According to the theories of combination column, it is possible to optimize the retention time of the target compounds by varying the volume ratio of the stationary phases in the HSCCC combination columns, as well as the suitable volume ratios of the stationary phases for the separation of the target compounds were predicted from the partition coefficients of the compounds in the three-phase solvent system. Then, three HSCCC separations using the combination columns with initial pumped LP:IP volume ratios of 1:0, 0.9:0.1, and 0.7:0.3 were performed separately based on the prediction. Three target compounds were prepared with high purity when the initial pumped volume ratio of the stationary phases was 0.9:0.1. The baseline separation of compounds 2 and 3 was achieved on the combination column with an initial pumped volume ratio of 0.7:0.3. Furthermore, the three experiments clearly demonstrated that the retentions and resolutions of the target compounds increased with an increasing volume ratio of IP, which is consistent with the prediction for the retention times for the solutes on combination columns. The method proposed here reduces the need for solvent selection compared with the conventional method and may have broad potential applicability in the preparation of natural products. Copyright © 2013 Elsevier B.V. All rights reserved.

FDG-PET/CT imaging for tumor staging and definition of tumor volumes in radiation treatment planning in non-small cell lung cancer.

PubMed

Zheng, Yuanda; Sun, Xiaojiang; Wang, Jian; Zhang, Lingnan; DI, Xiaoyun; Xu, Yaping

2014-04-01

18 F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) has the potential to improve the staging and radiation treatment (RT) planning of various tumor sites. However, from a clinical standpoint, questions remain with regard to what extent PET/CT changes the target volume and whether PET/CT reduces interobserver variability in target volume delineation. The present study analyzed the use of FDG-PET/CT images for staging and evaluated the impact of FDG-PET/CT on the radiotherapy volume delineation compared with CT in patients with non-small cell lung cancer (NSCLC) who were candidates for radiotherapy. Intraobserver variation in delineating tumor volumes was also observed. In total, 23 patients with stage I-III NSCLC were enrolled and treated with fractionated RT-based therapy with or without chemotherapy. FDG-PET/CT scans were acquired within two weeks prior to RT. PET and CT data sets were sent to the treatment planning system, Pinnacle, through compact discs. The CT and PET images were subsequently fused by means of a dedicated RT planning system. Gross tumor volume (GTV) was contoured by four radiation oncologists on CT (GTV-CT) and PET/CT images (GTV-PET/CT). The resulting volumes were analyzed and compared. For the first phase, two radiation oncologists outlined the contours together, achieving a final consensus. Based on PET/CT, changes in tumor-node-metastasis categories occurred in 8/23 cases (35%). Radiation targeting with fused FDG-PET and CT images resulted in alterations in radiation therapy planning in 12/20 patients (60%) in comparison with CT targeting. The most prominent changes in GTV were observed in cases with atelectasis. For the second phase, the variation in delineating tumor volumes was assessed by four observers. The mean ratio of largest to smallest CT-based GTV was 2.31 (range, 1.01-5.96). The addition of the PET results reduced the mean ratio to 1.46 (range, 1.02-2.27). PET/CT fusion images may have a potential impact on tumor staging and treatment planning. Implementing matched PET/CT results reduced observer variation in delineating tumor volumes significantly with respect to CT only.

Complex conductivity response to silver nanoparticles in partially saturated sand columns

NASA Astrophysics Data System (ADS)

Abdel Aal, Gamal; Atekwana, Estella A.; Werkema, D. Dale

2017-02-01

The increase in the use of nanoscale materials in consumer products has resulted in a growing concern of their potential hazard to ecosystems and public health from their accidental or intentional introduction to the environment. Key environmental, health, and safety research needs include knowledge and methods for their detection, characterization, fate, and transport. Specifically, techniques available for the direct detection and quantification of their fate and transport in the environment are limited. Their small size, high surface area to volume ratio, interfacial, and electrical properties make metallic nanoparticles, such as silver nanoparticles, good targets for detection using electrical geophysical techniques. Here we measured the complex conductivity response to silver nanoparticles in sand columns under varying moisture conditions (0-30%), nanoparticle concentrations (0-10 mg/g), lithology (presence of clay), pore water salinity (0.0275 and 0.1000 S/m), and particle size (35, 90-210 and 1500-2500 nm). Based on the Cole-Cole relaxation models we obtained the chargeability and the time constant. We demonstrate that complex conductivity can detect silver nanoparticles in porous media with the response enhanced by higher concentrations of silver nanoparticles, moisture content, ionic strength, clay content and particle diameter. Quantification of the volumetric silver nanoparticles content in the porous media can also be obtained from complex conductivity parameters based on the strong power law relationships.

Tandem Mass Spectrometry on a Miniaturized Laser Desorption Time-of-Flight Mass Spectrometer

NASA Technical Reports Server (NTRS)

Li, Xiang; Cornish, Timothy; Getty, Stephanie A.; Brinckerhoff, William B.

2016-01-01

Tandem mass spectrometry (MSMS) is a powerful and widely-used technique for identifying the molecular structure of organic constituents of a complex sample. Application of MSMS to the study of unknown planetary samples on a remote space mission would contribute to our understanding of the origin, evolution, and distribution of extraterrestrial organics in our solar system. Here we report on the realization of MSMS on a miniaturized laser desorption time-of-flight mass spectrometer (LD-TOF-MS), which is one of the most promising instrument types for future planetary missions. This achievement relies on two critical components: a curved-field reflectron and a pulsed-pin ion gate. These enable use of the complementary post-source decay (PSD) and laser-assisted collision induced dissociation (L-CID) MSMS methods on diverse measurement targets with only modest investment in instrument resources such as volume and weight. MSMS spectra of selected molecular targets in various organic standards exhibit excellent agreement when compared with results from a commercial, laboratory-scale TOF instrument, demonstrating the potential of this powerful technique in space and planetary environments.

Dendrimers in drug delivery and targeting: Drug-dendrimer interactions and toxicity issues

PubMed Central

Madaan, Kanika; Kumar, Sandeep; Poonia, Neelam; Lather, Viney; Pandita, Deepti

2014-01-01

Dendrimers are the emerging polymeric architectures that are known for their defined structures, versatility in drug delivery and high functionality whose properties resemble with biomolecules. These nanostructured macromolecules have shown their potential abilities in entrapping and/or conjugating the high molecular weight hydrophilic/hydrophobic entities by host-guest interactions and covalent bonding (prodrug approach) respectively. Moreover, high ratio of surface groups to molecular volume has made them a promising synthetic vector for gene delivery. Owing to these properties dendrimers have fascinated the researchers in the development of new drug carriers and they have been implicated in many therapeutic and biomedical applications. Despite of their extensive applications, their use in biological systems is limited due to toxicity issues associated with them. Considering this, the present review has focused on the different strategies of their synthesis, drug delivery and targeting, gene delivery and other biomedical applications, interactions involved in formation of drug-dendrimer complex along with characterization techniques employed for their evaluation, toxicity problems and associated approaches to alleviate their inherent toxicity. PMID:25035633

SU-F-T-648: Sharpening Dose Fall-Off Via Beam Number Enhancements For Stereotactic Brain Radiosurgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chiu, J; Braunstein, S; McDermott, M

Purpose: Sharp dose fall-off is the hallmark of brain radiosurgery to deliver a high dose of radiation to the target while minimizing dose to normal brain tissue. In this study, we developed a technique for the purpose of enhancing the peripheral dose gradient by magnifying the total number of beams focused toward each isocenter via patient head tilt and simultaneous beam intensity modulations. Methods: Computer scripting for the proposed beam number enhancement (BNE) technique was developed. The technique was tested and then implemented on a clinical treatment planning system for a dedicated brain radiosurgical system (GK Perfexion, Elekta Oncology). Tomore » study technical feasibility and dosimetric advantages of the technique, we compared treatment planning quality and delivery efficiency for 20 radiosurgical cases previously treated at our institution. These cases included relatively complex treatments such as acoustic schwannoma, meningioma, brain metastasis and mesial temporal lobe epilepsy. Results: The BNE treatment plans were found to produce nearly identical target volume coverage (absolute value < 0.5%, P > 0.2) and dose conformity (BNE CI= 1.41±0.15 versus 1.41±0.20, P>0.9) as the original treatment plans. The total beam-on time for theBNE treatment plans were comparable (within 1.0 min or 1.8%) with those of the original treatment plans for all the cases. However, BNE treatment plans significantly improved the mean gradient index (BNE GI = 2.9±0.3 versus original GI =3.0±0.3 p<0.0001) and low-level isodose volumes, e.g. 20-50% prescribed isodose volumes, by 2.0% to 5.0% (p<0.02). Furthermore, with 4 to 5-fold increase in the total number of beams, the GI decreased by as much as 20% or 0.5 in absolute values. Conclusion: BNE via head tilt and simultaneous beam intensity modulation is an effective and efficient technique that physically sharpens the peripheral dose gradient for brain radiosurgery.« less

Target location after deep cerebral biopsies using low-volume air injection in 75 patients. Results and technical note.

PubMed

Poca, Maria A; Martínez-Ricarte, Francisco-Ramon; Gándara, Dario F; Coscojuela, Pilar; Martínez-Sáez, Elena; Sahuquillo, Juan

2017-10-01

Stereotactic biopsy is a minimally invasive technique that allows brain tissue samples to be obtained with low risk. Classically, different techniques have been used to identify the biopsy site after surgery. To describe a technique to identify the precise location of the target in the postoperative CT scan using the injection of a low volume of air into the biopsy cannula. Seventy-five biopsies were performed in 65 adults and 10 children (40 males and 35 females, median age 51 years). Frame-based biopsy was performed in 46 patients, while frameless biopsy was performed in the remaining 29 patients. In both systems, after brain specimens had been collected and with the biopsy needle tip in the center of the target, a small volume of air (median 0.7 cm 3 ) was injected into the site. A follow-up CT scan was performed in all patients. Intracranial air in the selected target was present in 69 patients (92%). No air was observed in two patients (air volume administered in these 2 cases was below 0.7 cm 3 ), while in the remaining four patients blood content was observed in the target. The diagnostic yield in this series was 97.3%. No complications were found to be associated with intracranial air injection in any of the 75 patients who underwent this procedure. The air-injection maneuver proposed for use in stereotactic biopsies of intracranial mass lesions is a safe and reliable technique that allows the exact biopsy site to be located without any related complications.

Breaking through the uncertainty ceiling in LA-ICP-MS U-Pb geochronology

NASA Astrophysics Data System (ADS)

Horstwood, M.

2016-12-01

Sources of systematic uncertainty associated with session-to-session bias are the dominant contributor to the 2% (2s) uncertainty ceiling that currently limits the accuracy of LA-ICP-MS U-Pb geochronology. Sources include differential downhole fractionation (LIEF), `matrix effects' and ablation volume differences, which result in irreproducibility of the same reference material across sessions. Current mitigation methods include correcting for LIEF mathematically, using matrix-matched reference materials, annealing material to reduce or eliminate radiation damage effects and tuning for robust plasma conditions. Reducing the depth and volume of ablation can also mitigate these problems and should contribute to the reduction of the uncertainty ceiling. Reducing analysed volume leads to increased detection efficiency, reduced matrix-effects, eliminates LIEF, obviates ablation rate differences and reduces the likelihood of intercepting complex growth zones with depth, thereby apparently improving material homogeneity. High detection efficiencies (% level) and low sampling volumes (20um box, 1-2um deep) can now be achieved using MC-ICP-MS such that low volume ablations should be considered part of the toolbox of methods targeted at improving the reproducibility of LA-ICP-MS U-Pb geochronology. In combination with other strategies these improvements should be feasible on any ICP platform. However, reducing the volume of analysis reduces detected counts and requires a change of analytical approach in order to mitigate this. Appropriate strategies may include the use of high efficiency cell and torch technologies and the optimisation of acquisition protocols and data handling techniques such as condensing signal peaks, using log ratios and total signal integration. The tools required to break the 2% (2s) uncertainty ceiling in LA-ICP-MS U-Pb geochronology are likely now known but require a coherent strategy and change of approach to combine their implementation and realise this goal. This study will highlight these changes and efforts towards reducing the uncertainty contribution for LA-ICP-MS U-Pb geochronology.

Oklahoma's induced seismicity strongly linked to wastewater injection depth

NASA Astrophysics Data System (ADS)

Hincks, Thea; Aspinall, Willy; Cooke, Roger; Gernon, Thomas

2018-03-01

The sharp rise in Oklahoma seismicity since 2009 is due to wastewater injection. The role of injection depth is an open, complex issue, yet critical for hazard assessment and regulation. We developed an advanced Bayesian network to model joint conditional dependencies between spatial, operational, and seismicity parameters. We found that injection depth relative to crystalline basement most strongly correlates with seismic moment release. The joint effects of depth and volume are critical, as injection rate becomes more influential near the basement interface. Restricting injection depths to 200 to 500 meters above basement could reduce annual seismic moment release by a factor of 1.4 to 2.8. Our approach enables identification of subregions where targeted regulation may mitigate effects of induced earthquakes, aiding operators and regulators in wastewater disposal regions.

Data Acquisition and Linguistic Resources

NASA Astrophysics Data System (ADS)

Strassel, Stephanie; Christianson, Caitlin; McCary, John; Staderman, William; Olive, Joseph

All human language technology demands substantial quantities of data for system training and development, plus stable benchmark data to measure ongoing progress. While creation of high quality linguistic resources is both costly and time consuming, such data has the potential to profoundly impact not just a single evaluation program but language technology research in general. GALE's challenging performance targets demand linguistic data on a scale and complexity never before encountered. Resources cover multiple languages (Arabic, Chinese, and English) and multiple genres -- both structured (newswire and broadcast news) and unstructured (web text, including blogs and newsgroups, and broadcast conversation). These resources include significant volumes of monolingual text and speech, parallel text, and transcribed audio combined with multiple layers of linguistic annotation, ranging from word aligned parallel text and Treebanks to rich semantic annotation.

In vivo potency revisited - Keep the target in sight.

PubMed

Gabrielsson, Johan; Peletier, Lambertus A; Hjorth, Stephan

2018-04-01

Potency is a central parameter in pharmacological and biochemical sciences, as well as in drug discovery and development endeavors. It is however typically defined in terms only of ligand to target binding affinity also in in vivo experimentation, thus in a manner analogous to in in vitro studies. As in vivo potency is in fact a conglomerate of events involving ligand, target, and target-ligand complex processes, overlooking some of the fundamental differences between in vivo and in vitro may result in serious mispredictions of in vivo efficacious dose and exposure. The analysis presented in this paper compares potency measures derived from three model situations. Model A represents the closed in vitro system, defining target binding of a ligand when total target and ligand concentrations remain static and constant. Model B describes an open in vivo system with ligand input and clearance (Cl (L) ), adding in parallel to the turnover (k syn , k deg ) of the target. Model C further adds to the open in vivo system in Model B also the elimination of the target-ligand complex (k e(RL) ) via a first-order process. We formulate corresponding equations of the equilibrium (steady-state) relationships between target and ligand, and complex and ligand for each of the three model systems and graphically illustrate the resulting simulations. These equilibrium relationships demonstrate the relative impact of target and target-ligand complex turnover, and are easier to interpret than the more commonly used ligand-, target- and complex concentration-time courses. A new potency expression, labeled L 50 , is then derived. L 50 is the ligand concentration at half-maximal target and complex concentrations and is an amalgamation of target turnover, target-ligand binding and complex elimination parameters estimated from concentration-time data. L 50 is then compared to the dissociation constant K d (target-ligand binding affinity), the conventional Black & Leff potency estimate EC 50 , and the derived Michaelis-Menten parameter K m (target-ligand binding and complex removal) across a set of literature data. It is evident from a comparison between parameters derived from in vitro vs. in vivo experiments that L 50 can be either numerically greater or smaller than the K d (or K m ) parameter, primarily depending on the ratio of k deg -to-k e(RL) . Contrasting the limit values of target R and target-ligand complex RL for ligand concentrations approaching infinity demonstrates that the outcome of the three models differs to a great extent. Based on the analysis we propose that a better understanding of in vivo pharmacological potency requires simultaneous assessment of the impact of its underlying determinants in the open system setting. We propose that L 50 will be a useful parameter guiding predictions of the effective concentration range, for translational purposes, and assessment of in vivo target occupancy/suppression by ligand, since it also encompasses target turnover - in turn also subject to influence by pathophysiology and drug treatment. Different compounds may have similar binding affinity for a target in vitro (same K d ), but vastly different potencies in vivo. L 50 points to what parameters need to be taken into account, and particularly that closed-system (in vitro) parameters should not be first choice when ranking compounds in vivo (open system). Copyright © 2017 Elsevier Inc. All rights reserved.

Using airborne laser altimetry to estimate Sabellaria alveolata (Polychaeta: Sabellariidae) reefs volume in tidal flat environments

NASA Astrophysics Data System (ADS)

Noernberg, Mauricio Almeida; Fournier, Jérôme; Dubois, Stanislas; Populus, Jacques

2010-12-01

This study has exploited aerial photographs and LiDAR digital elevation model to quantify intertidal complex landforms volume. A first volume estimation of the main sabellariid polychaete reef complex of the Bay of Mont-Saint-Michel - France is presented. The Sabellaria alveolata is an engineering species that heavily modifies its environment. This gregarious tube-building annelid forms dense and solid reefs of bioclastic coarse sand which can reach several km 2. Since 1970 a very strong decline of reefs has been observed. The authorities have curbed fishing activities without any noticeable changes in reef health status. The S. alveolata reef volume is estimated to be 132 048 m 3 (96 301 m 3 for Sainte-Anne reef and 35 747 m 3 for Champeaux reef). Further LiDAR data surveys will be needed to be able to understand and quantify the accretion/erosion processes in play in the reef dynamic. Because of the internal variability of topographic complexity of the reef, characterized by crevices, cracks, and holes rather than whole blocks, further studies are needed to calculate more accurately the volume of the reef.

Multispectral imaging probe

DOEpatents

Sandison, David R.; Platzbecker, Mark R.; Descour, Michael R.; Armour, David L.; Craig, Marcus J.; Richards-Kortum, Rebecca

1999-01-01

A multispectral imaging probe delivers a range of wavelengths of excitation light to a target and collects a range of expressed light wavelengths. The multispectral imaging probe is adapted for mobile use and use in confined spaces, and is sealed against the effects of hostile environments. The multispectral imaging probe comprises a housing that defines a sealed volume that is substantially sealed from the surrounding environment. A beam splitting device mounts within the sealed volume. Excitation light is directed to the beam splitting device, which directs the excitation light to a target. Expressed light from the target reaches the beam splitting device along a path coaxial with the path traveled by the excitation light from the beam splitting device to the target. The beam splitting device directs expressed light to a collection subsystem for delivery to a detector.

Multispectral imaging probe

DOEpatents

Sandison, D.R.; Platzbecker, M.R.; Descour, M.R.; Armour, D.L.; Craig, M.J.; Richards-Kortum, R.

1999-07-27

A multispectral imaging probe delivers a range of wavelengths of excitation light to a target and collects a range of expressed light wavelengths. The multispectral imaging probe is adapted for mobile use and use in confined spaces, and is sealed against the effects of hostile environments. The multispectral imaging probe comprises a housing that defines a sealed volume that is substantially sealed from the surrounding environment. A beam splitting device mounts within the sealed volume. Excitation light is directed to the beam splitting device, which directs the excitation light to a target. Expressed light from the target reaches the beam splitting device along a path coaxial with the path traveled by the excitation light from the beam splitting device to the target. The beam splitting device directs expressed light to a collection subsystem for delivery to a detector. 8 figs.

A pilot prospective feasibility study of organ-at-risk definition using Target Contour Testing/Instructional Computer Software (TaCTICS), a training and evaluation platform for radiotherapy target delineation.

PubMed

Kalpathy-Cramer, Jayashree; Bedrick, Steven D; Boccia, Kelly; Fuller, Clifton D

2011-01-01

Target volume delineation is a critical, but time-consuming step in the creation of radiation therapy plans used in the treatment of many types of cancer. However, variability in target volume definitions can introduce substantial differences in resulting doses to tumors and critical structures. We developed TaCTICS, a web-based educational training software application targeted towards non-expert users. We report on a small, prospective study to evaluate the utility of this online tool in improving conformance of regions-of-interest (ROIs) with a reference set. Eight residents contoured a set of structures for a head-and-neck cancer case. Subsequently, they were provided access to TaCTICS as well as contouring atlases to allow evaluation of their contours in reference to other users as well as reference ROIs. The residents then contoured a second case using these resources. Volume overlap metrics between the users showed a substantial improvement following the intervention. Additionally, 66% of users reported that they found TaCTICS to be a useful educational tool and all participants reported they would like to use TaCTICS to track their contouring skills over the course of their residency.

Dosimetric comparison between conventional and conformal radiotherapy for carcinoma cervix: Are we treating the right volumes?

PubMed Central

Goswami, Jyotirup; Patra, Niladri B.; Sarkar, Biplab; Basu, Ayan; Pal, Santanu

2013-01-01

Background and Purpose: Conventional portals, based on bony anatomy, for external beam radiotherapy for cervical cancer have been repeatedly demonstrated as inadequate. Conversely, with image-based conformal radiotherapy, better target coverage may be offset by the greater toxicities and poorer compliance associated with treating larger volumes. This study was meant to dosimetrically compare conformal and conventional radiotherapy. Materials and Methods: Five patients of carcinoma cervix underwent planning CT scan with IV contrast and targets, and organs at risk (OAR) were contoured. Two sets of plans-conventional and conformal were generated for each patient. Field sizes were recorded, and dose volume histograms of both sets of plans were generated and compared on the basis of target coverage and OAR sparing. Results: Target coverage was significantly improved with conformal plans though field sizes required were significantly larger. On the other hand, dose homogeneity was not significantly improved. Doses to the OARs (rectum, urinary bladder, and small bowel) were not significantly different across the 2 arms. Conclusion: Three-dimensional conformal radiotherapy gives significantly better target coverage, which may translate into better local control and survival. On the other hand, it also requires significantly larger field sizes though doses to the OARs are not significantly increased. PMID:24455584

Inhibition of atherosclerosis-promoting microRNAs via targeted polyelectrolyte complex micelles

PubMed Central

Kuo, Cheng-Hsiang; Leon, Lorraine; Chung, Eun Ji; Huang, Ru-Ting; Sontag, Timothy J.; Reardon, Catherine A.; Getz, Godfrey S.; Tirrell, Matthew; Fang, Yun

2015-01-01

Polyelectrolyte complex micelles have great potential as gene delivery vehicles because of their ability to encapsulate charged nucleic acids forming a core by neutralizing their charge, while simultaneously protecting the nucleic acids from non-specific interactions and enzymatic degradation. Furthermore, to enhance specificity and transfection efficiency, polyelectrolyte complex micelles can be modified to include targeting capabilities. Here, we describe the design of targeted polyelectrolyte complex micelles containing inhibitors against dys-regulated microRNAs (miRNAs) that promote atherosclerosis, a leading cause of human mortality and morbidity. Inhibition of dys-regulated miRNAs in diseased cells associated with atherosclerosis has resulted in therapeutic efficacy in animal models and has been proposed to treat human diseases. However, the non-specific targeting of microRNA inhibitors via systemic delivery has remained an issue that may cause unwanted side effects. For this reason, we incorporated two different peptide sequences to our miRNA inhibitor containing polyelectrolyte complex micelles. One of the peptides (Arginine-Glutamic Acid-Lysine-Alanine or REKA) was used in another micellar system that demonstrated lesion-specific targeting in a mouse model of atherosclerosis. The other peptide (Valine-Histidine-Proline-Lysine-Glutamine-Histidine-Arginine or VHPKQHR) was identified via phage display and targets vascular endothelial cells through the vascular cell adhesion molecule-1 (VCAM-1). In this study we have tested the in vitro efficacy and efficiency of lesion- and cell-specific delivery of microRNA inhibitors to the cells associated with atherosclerotic lesions via peptide-targeted polyelectrolyte complex micelles. Our results show that REKA-containing micelles (fibrin-targeting) and VHPKQHR-containing micelles (VCAM-1 targeting) can be used to carry and deliver microRNA inhibitors into macrophages and human endothelial cells, respectively. Additionally, the functionality of miRNA inhibitors in cells was demonstrated by analyzing miRNA expression as well as the expression or the biological function of its downstream target protein. Our study provides the first demonstration of targeting dys-regulated miRNAs in atherosclerosis using targeted polyelectrolyte complex micelles and holds promising potential for translational applications. PMID:25685357

Facilitated Protein Association via Engineered Target Search Pathways Visualized by Paramagnetic NMR Spectroscopy.

PubMed

An, So Young; Kim, Eun-Hee; Suh, Jeong-Yong

2018-06-05

Proteins assemble to form functional complexes via the progressive evolution of nonspecific complexes formed by transient encounters. This target search process generally involves multiple routes that lead the initial encounters to the final complex. In this study, we have employed NMR paramagnetic relaxation enhancement to visualize the encounter complexes between histidine-containing phosphocarrier protein and the N-terminal domain of enzyme I and demonstrate that protein association can be significantly enhanced by engineering on-pathways. Specifically, mutations in surface charges away from the binding interface can elicit new on-pathway encounter complexes, increasing their binding affinity by an order of magnitude. The structure of these encounter complexes indicates that such on-pathways extend the built-in target search process of the native protein complex. Furthermore, blocking on-pathways by countering mutations reverts their binding affinity. Our study thus illustrates that protein interactions can be engineered by rewiring the target search process. Copyright © 2018 Elsevier Ltd. All rights reserved.

Double targeting and aptamer-assisted controlled release delivery of epirubicin to cancer cells by aptamers-based dendrimer in vitro and in vivo.

PubMed

Taghdisi, Seyed Mohammad; Danesh, Noor Mohammad; Ramezani, Mohammad; Lavaee, Parirokh; Jalalian, Seyed Hamid; Robati, Rezvan Yazdian; Abnous, Khalil

2016-05-01

Clinical use of epirubicin (Epi) in the treatment of cancer has been limited, due to its cardiotoxicity. Targeted delivery of chemotherapeutic agents could increase their efficacy and reduce their off-target effects. High drug loading and excellent stability of DNA dendrimers make these DNA nanostructures unique candidates for biological applications. In this study a modified and promoted dendrimer using three kinds of aptamers (MUC1, AS1411 and ATP aptamers) was designed for targeted delivery of Epi and its efficacy was evaluated in target cells including MCF-7 cells (breast cancer cell) and C26 cells (murine colon carcinoma cell). Aptamers (Apts)-Dendrimer-Epi complex formation was analyzed by fluorometric analysis and gel retardation assay. Release profiles of Epi from the designed complex were assessed at pHs 5.4 and 7.4. For MTT assay (cytotoxic study) MCF-7 and C26 cells (target cells) and CHO cells (Chinese hamster ovary cell, nontarget) were treated with Epi, Apts-Dendrimer-Epi complex and Apts-Dendrimer conjugate. Internalization was evaluated using flow cytometry analysis. Finally, the developed complex was used for inhibition of tumor growth in vivo. 25μM Epi was efficiently intercalated to 1μM dendrimer. Epi was released from the Apts-Dendrimer-Epi complex in a pH-sensitive manner (more release at pH 5.5). The results of flow cytometry analysis indicated that the designed complex was efficiently internalized into target cells, but not into control cells. The internalization data were confirmed by the results of MTT assay. Apts-Dendrimer-Epi complex had less cytotoxicity in CHO cells compared to Epi alone. The complex had more cytotoxicity in C26 and MCF-7 cells compared to Epi alone. Moreover, the Apts-Dendrimer-Epi complex could efficiently prohibit tumor growth in vivo. In conclusion, the designed targeted drug delivery system inherited characteristics of pH-dependent drug release, high drug loading and tumor targeting in vitro and in vivo. Copyright © 2016 Elsevier B.V. All rights reserved.

Science information systems: Visualization

NASA Technical Reports Server (NTRS)

Wall, Ray J.

1991-01-01

Future programs in earth science, planetary science, and astrophysics will involve complex instruments that produce data at unprecedented rates and volumes. Current methods for data display, exploration, and discovery are inadequate. Visualization technology offers a means for the user to comprehend, explore, and examine complex data sets. The goal of this program is to increase the effectiveness and efficiency of scientists in extracting scientific information from large volumes of instrument data.

Comparative evaluation of two-dimensional radiography and three dimensional computed tomography based dose-volume parameters for high-dose-rate intracavitary brachytherapy of cervical cancer: a prospective study.

PubMed

Madan, Renu; Pathy, Sushmita; Subramani, Vellaiyan; Sharma, Seema; Mohanti, Bidhu Kalyan; Chander, Subhash; Thulkar, Sanjay; Kumar, Lalit; Dadhwal, Vatsla

2014-01-01

Dosimetric comparison of two dimensional (2D) radiography and three-dimensional computed tomography (3D-CT) based dose distributions with high-dose-rate (HDR) intracavitry radiotherapy (ICRT) for carcinoma cervix, in terms of target coverage and doses to bladder and rectum. Sixty four sessions of HDR ICRT were performed in 22 patients. External beam radiotherapy to pelvis at a dose of 50 Gray in 27 fractions followed by HDR ICRT, 21 Grays to point A in 3 sessions, one week apart was planned . All patients underwent 2D-orthogonal and 3D-CT simulation for each session. Treatment plans were generated using 2D-orthogonal images and dose prescription was made at point A. 3D plans were generated using 3D-CT images after delineating target volume and organs at risk. Comparative evaluation of 2D and 3D treatment planning was made for each session in terms of target coverage (dose received by 90%, 95% and 100% of the target volume: D90, D95 and D100 respectively) and doses to bladder and rectum: ICRU-38 bladder and rectum point dose in 2D planning and dose to 0.1cc, 1cc, 2cc, 5cc, and 10cc of bladder and rectum in 3D planning. Mean doses received by 100% and 90% of the target volume were 4.24 ± 0.63 and 4.9 ± 0.56 Gy respectively. Doses received by 0.1cc, 1cc and 2cc volume of bladder were 2.88 ± 0.72, 2.5 ± 0.65 and 2.2 ± 0.57 times more than the ICRU bladder reference point. Similarly, doses received by 0.1cc, 1cc and 2cc of rectum were 1.80 ± 0.5, 1.48 ± 0.41 and 1.35 ± 0.37 times higher than ICRU rectal reference point. Dosimetric comparative evaluation of 2D and 3D CT based treatment planning for the same brachytherapy session demonstrates underestimation of OAR doses and overestimation of target coverage in 2D treatment planning.

Intensity-Modulated Radiotherapy for Craniospinal Irradiation: Target Volume Considerations, Dose Constraints, and Competing Risks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parker, William; Filion, Edith; Roberge, David

2007-09-01

Purpose: To report the results of an analysis of dose received to tissues and organs outside the target volume, in the setting of spinal axis irradiation for the treatment of medulloblastoma, using three treatment techniques. Methods and Materials: Treatment plans (total dose, 23.4 Gy) for a standard two-dimensional (2D) technique, a three-dimensional (3D) technique using a 3D imaging-based target volume, and an intensity-modulated radiotherapy (IMRT) technique, were compared for 3 patients in terms of dose-volume statistics for target coverage, as well as organ at risk (OAR) and overall tissue sparing. Results: Planning target volume coverage and dose homogeneity was superiormore » for the IMRT plans for V{sub 95%} (IMRT, 100%; 3D, 96%; 2D, 98%) and V{sub 107%} (IMRT, 3%; 3D, 38%; 2D, 37%). In terms of OAR sparing, the IMRT plan was better for all organs and whole-body contour when comparing V{sub 10Gy}, V{sub 15Gy}, and V{sub 20Gy}. The 3D plan was superior for V{sub 5Gy} and below. For the heart and liver in particular, the IMRT plans provided considerable sparing in terms of V{sub 10Gy} and above. In terms of the integral dose, the IMRT plans were superior for liver (IMRT, 21.9 J; 3D, 28.6 J; 2D, 38.6 J) and heart (IMRT, 9 J; 3D, 14.1J; 2D, 19.4 J), the 3D plan for the body contour (IMRT, 349 J; 3D, 337 J; 2D, 555 J). Conclusions: Intensity-modulated radiotherapy is a valid treatment option for spinal axis irradiation. We have shown that IMRT results in sparing of organs at risk without a significant increase in integral dose.« less

A new functional method to choose the target lobe for lung volume reduction in emphysema - comparison with the conventional densitometric method.

PubMed

Hetzel, Juergen; Boeckeler, Michael; Horger, Marius; Ehab, Ahmed; Kloth, Christopher; Wagner, Robert; Freitag, Lutz; Slebos, Dirk-Jan; Lewis, Richard Alexander; Haentschel, Maik

2017-01-01

Lung volume reduction (LVR) improves breathing mechanics by reducing hyperinflation. Lobar selection usually focuses on choosing the most destroyed emphysematous lobes as seen on an inspiratory CT scan. However, it has never been shown to what extent these densitometric CT parameters predict the least deflation of an individual lobe during expiration. The addition of expiratory CT analysis allows measurement of the extent of lobar air trapping and could therefore provide additional functional information for choice of potential treatment targets. To determine lobar vital capacity/lobar total capacity (LVC/LTC) as a functional parameter for lobar air trapping using on an inspiratory and expiratory CT scan. To compare lobar selection by LVC/LTC with the established morphological CT density parameters. 36 patients referred for endoscopic LVR were studied. LVC/LTC, defined as delta volume over maximum volume of a lobe, was calculated using inspiratory and expiratory CT scans. The CT morphological parameters of mean lung density (MLD), low attenuation volume (LAV), and 15th percentile of Hounsfield units (15%P) were determined on an inspiratory CT scan for each lobe. We compared and correlated LVC/LTC with MLD, LAV, and 15%P. There was a weak correlation between the functional parameter LVC/LTC and all inspiratory densitometric parameters. Target lobe selection using lowest lobar deflation (lowest LVC/LTC) correlated with target lobe selection based on lowest MLD in 18 patients (50.0%), with the highest LAV in 13 patients (36.1%), and with the lowest 15%P in 12 patients (33.3%). CT-based measurement of deflation (LVC/LTC) as a functional parameter correlates weakly with all densitometric CT parameters on a lobar level. Therefore, morphological criteria based on inspiratory CT densitometry partially reflect the deflation of particular lung lobes, and may be of limited value as a sole predictor for target lobe selection in LVR.

Electrostatically assembled dendrimer complex with a high-affinity protein binder for targeted gene delivery.

PubMed

Kim, Jong-Won; Lee, Joong-Jae; Choi, Joon Sig; Kim, Hak-Sung

2018-06-10

Although a variety of non-viral gene delivery systems have been developed, they still suffer from low efficiency and specificity. Herein, we present the assembly of a dendrimer complex comprising a DNA cargo and a targeting moiety as a new format for targeted gene delivery. A PAMAM dendrimer modified with histidine and arginine (HR-dendrimer) was used to enhance the endosomal escape and transfection efficiency. An EGFR-specific repebody, composed of leucine-rich repeat (LRR) modules, was employed as a targeting moiety. A polyanionic peptide was genetically fused to the repebody, followed by incubation with an HR-dendrimer and a DNA cargo to assemble the dendrimer complex through an electrostatic interaction. The resulting dendrimer complex was shown to deliver a DNA cargo with high efficiency in a receptor-specific manner. An analysis using a confocal microscope confirmed the internalization of the dendrimer complex and subsequent dissociation of a DNA cargo from the complex. The present approach can be broadly used in a targeted gene delivery in many areas. Copyright © 2018 Elsevier B.V. All rights reserved.

Volume comparison of radiofrequency ablation at 3- and 5-cm target volumes for four different radiofrequency generators: MR volumetry in an open 1-T MRI system versus macroscopic measurement.

PubMed

Rathke, Hendrik; Hamm, Bernd; Guettler, Felix; Lohneis, Philipp; Stroux, Andrea; Suttmeyer, Britta; Jonczyk, Martin; Teichgräber, Ulf; de Bucourt, Maximilian

2015-12-01

In a patient, it is usually not macroscopically possible to estimate the non-viable volume induced by radiofrequency ablation (RFA) after the procedure. The purpose of this study was to use an ex vivo bovine liver model to perform magnetic resonance (MR) volumetry of the visible tissue signal change induced by RFA and to correlate the MR measurement with the actual macroscopic volume measured in the dissected specimens. Sixty-four liver specimens cut from 16 bovine livers were ablated under constant simulated, close physiological conditions with target volumes set to 14.14 ml (3-cm lesion) and 65.45 ml (5-cm lesion). Four commercially available radiofrequency (RF) systems were tested (n=16 for each system; n=8 for 3 cm and n=8 for 5 cm). A T1-weighted turbo spin echo (TSE) sequence with inversion recovery and a proton-density (PD)-weighted TSE sequence were acquired in a 1.0-T open magnetic resonance imaging (MRI) system. After manual dissection, actual macroscopic ablation diameters were measured and volumes calculated. MR volumetry was performed using a semiautomatic software tool. To validate the correctness and feasibility of the volume formula in macroscopic measurements, MR multiplanar reformation diameter measurements with subsequent volume calculation and semiautomatic MR volumes were correlated. Semiautomatic MR volumetry yielded smaller volumes than manual measurement after dissection, irrespective of RF system used, target lesion size, and MR sequence. For the 3-cm lesion, only 43.3% (T1) and 41.5% (PD) of the entire necrosis are detectable. For the 5-cm lesion, only 40.8% (T1) and 37.2% (PD) are visualized in MRI directly after intervention. The correlation between semiautomatic MR volumes and calculated MR volumes was 0.888 for the T1-weighted sequence and 0.875 for the PD sequence. After correlation of semiautomatic MR volumes and calculated MR volumes, it seems reasonable to use the respective volume formula for macroscopic volume calculation. Hyperacute MRI after ex vivo intervention may result in the underestimation of the real expansion of the produced necrosis zone. This must be kept in mind when using MRI for validating ablation success directly after RFA. One reason for the discrepancy between macroscopic and MRI appearance immediately after RFA may be that the transitional zone shows no or only partially visible MR signal change.

Impact of introduction of endoscopic ultrasound on volume, success, and complexity of endoscopic retrograde cholangiopancreatography in a tertiary referral center.

PubMed

Yandrapu, Harathi; Elhanafi, Sherif; Chowdhury, Farhanaz; Liu, Jiayang; Onate, Eduardo J; Dwivedi, Alok; Othman, Mohamed O

2017-01-01

Endoscopic ultrasound (EUS) is commonly used to examine pancreaticobiliary disorders. We hypothesize that the introduction of EUS service may change the pattern and the complexity of endoscopic retrograde cholangiopancreatographies (ERCPs) performed. The aim of this study is to assess the impact of introducing EUS on the volume, success, and complexity of ERCP. This is a single-center retrospective data review of ERCP procedures done "before" and "after" the introduction of EUS (before EUS and after EUS). Patients' demographics, ERCP indications, types of sedation, therapeutic interventions, outcomes, complications, and complexity of ERCP were collected. The categorical and continuous variables were compared using Fisher's exact test and the unpaired t-test, respectively. Multivariable logistic regression analysis was used to compare ERCP outcomes. A total of 945 ERCPs performed over a 3-year period between January 2010 and January 2013 (411 and 534 in the "before EUS" and "after EUS" time periods, respectively) were included in this study. There was a 30% relative increase in the volume of ERCPs after the introduction of EUS. ERCP success rate was higher after the introduction of EUS, even after adjusting the complexity grade [odds ratio (OR) = 4.54, P = 0.001]. Significant increase in the complexity of ERCP was observed after the introduction of EUS service. The OR of performing grade 4 ERCP was 4.44 (P = 0.0005) after the introduction of EUS. The introduction of a new EUS service in our tertiary referral university medical center is associated with an increase in the volume, success, and complexity of ERCP procedures. EUS expertise may be valuable for better ERCP outcomes.

Pharmacokinetic Steady-States Highlight Interesting Target-Mediated Disposition Properties.

PubMed

Gabrielsson, Johan; Peletier, Lambertus A

2017-05-01

In this paper, we derive explicit expressions for the concentrations of ligand L, target R and ligand-target complex RL at steady state for the classical model describing target-mediated drug disposition, in the presence of a constant-rate infusion of ligand. We demonstrate that graphing the steady-state values of ligand, target and ligand-target complex, we obtain striking and often singular patterns, which yield a great deal of insight and understanding about the underlying processes. Deriving explicit expressions for the dependence of L, R and RL on the infusion rate, and displaying graphs of the relations between L, R and RL, we give qualitative and quantitive information for the experimentalist about the processes involved. Understanding target turnover is pivotal for optimising these processes when target-mediated drug disposition (TMDD) prevails. By a combination of mathematical analysis and simulations, we also show that the evolution of the three concentration profiles towards their respective steady-states can be quite complex, especially for lower infusion rates. We also show how parameter estimates obtained from iv bolus studies can be used to derive steady-state concentrations of ligand, target and complex. The latter may serve as a template for future experimental designs.

Modern Radiation Therapy for Hodgkin Lymphoma: Field and Dose Guidelines From the International Lymphoma Radiation Oncology Group (ILROG)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Specht, Lena, E-mail: lena.specht@regionh.dk; Yahalom, Joachim; Illidge, Tim

2014-07-15

Radiation therapy (RT) is the most effective single modality for local control of Hodgkin lymphoma (HL) and an important component of therapy for many patients. These guidelines have been developed to address the use of RT in HL in the modern era of combined modality treatment. The role of reduced volumes and doses is addressed, integrating modern imaging with 3-dimensional (3D) planning and advanced techniques of treatment delivery. The previously applied extended field (EF) and original involved field (IF) techniques, which treated larger volumes based on nodal stations, have now been replaced by the use of limited volumes, based solelymore » on detectable nodal (and extranodal extension) involvement at presentation, using contrast-enhanced computed tomography, positron emission tomography/computed tomography, magnetic resonance imaging, or a combination of these techniques. The International Commission on Radiation Units and Measurements concepts of gross tumor volume, clinical target volume, internal target volume, and planning target volume are used for defining the targeted volumes. Newer treatment techniques, including intensity modulated radiation therapy, breath-hold, image guided radiation therapy, and 4-dimensional imaging, should be implemented when their use is expected to decrease significantly the risk for normal tissue damage while still achieving the primary goal of local tumor control. The highly conformal involved node radiation therapy (INRT), recently introduced for patients for whom optimal imaging is available, is explained. A new concept, involved site radiation therapy (ISRT), is introduced as the standard conformal therapy for the scenario, commonly encountered, wherein optimal imaging is not available. There is increasing evidence that RT doses used in the past are higher than necessary for disease control in this era of combined modality therapy. The use of INRT and of lower doses in early-stage HL is supported by available data. Although the use of ISRT has not yet been validated in a formal study, it is more conservative than INRT, accounting for suboptimal information and appropriately designed for safe local disease control. The goal of modern smaller field radiation therapy is to reduce both treatment volume and treatment dose while maintaining efficacy and minimizing acute and late sequelae. This review is a consensus of the International Lymphoma Radiation Oncology Group (ILROG) Steering Committee regarding the modern approach to RT in the treatment of HL, outlining a new concept of ISRT in which reduced treatment volumes are planned for the effective control of involved sites of HL. Nodal and extranodal non-Hodgkin lymphomas (NHL) are covered separately by ILROG guidelines.« less

Modern radiation therapy for Hodgkin lymphoma: field and dose guidelines from the international lymphoma radiation oncology group (ILROG).

PubMed

Specht, Lena; Yahalom, Joachim; Illidge, Tim; Berthelsen, Anne Kiil; Constine, Louis S; Eich, Hans Theodor; Girinsky, Theodore; Hoppe, Richard T; Mauch, Peter; Mikhaeel, N George; Ng, Andrea

2014-07-15

Radiation therapy (RT) is the most effective single modality for local control of Hodgkin lymphoma (HL) and an important component of therapy for many patients. These guidelines have been developed to address the use of RT in HL in the modern era of combined modality treatment. The role of reduced volumes and doses is addressed, integrating modern imaging with 3-dimensional (3D) planning and advanced techniques of treatment delivery. The previously applied extended field (EF) and original involved field (IF) techniques, which treated larger volumes based on nodal stations, have now been replaced by the use of limited volumes, based solely on detectable nodal (and extranodal extension) involvement at presentation, using contrast-enhanced computed tomography, positron emission tomography/computed tomography, magnetic resonance imaging, or a combination of these techniques. The International Commission on Radiation Units and Measurements concepts of gross tumor volume, clinical target volume, internal target volume, and planning target volume are used for defining the targeted volumes. Newer treatment techniques, including intensity modulated radiation therapy, breath-hold, image guided radiation therapy, and 4-dimensional imaging, should be implemented when their use is expected to decrease significantly the risk for normal tissue damage while still achieving the primary goal of local tumor control. The highly conformal involved node radiation therapy (INRT), recently introduced for patients for whom optimal imaging is available, is explained. A new concept, involved site radiation therapy (ISRT), is introduced as the standard conformal therapy for the scenario, commonly encountered, wherein optimal imaging is not available. There is increasing evidence that RT doses used in the past are higher than necessary for disease control in this era of combined modality therapy. The use of INRT and of lower doses in early-stage HL is supported by available data. Although the use of ISRT has not yet been validated in a formal study, it is more conservative than INRT, accounting for suboptimal information and appropriately designed for safe local disease control. The goal of modern smaller field radiation therapy is to reduce both treatment volume and treatment dose while maintaining efficacy and minimizing acute and late sequelae. This review is a consensus of the International Lymphoma Radiation Oncology Group (ILROG) Steering Committee regarding the modern approach to RT in the treatment of HL, outlining a new concept of ISRT in which reduced treatment volumes are planned for the effective control of involved sites of HL. Nodal and extranodal non-Hodgkin lymphomas (NHL) are covered separately by ILROG guidelines. Copyright © 2014 Elsevier Inc. All rights reserved.

Volumetric Modulated Arc (Radio) Therapy in Pets Treatment: The “La Cittadina Fondazione” Experience

PubMed Central

Dolera, Mario; Malfassi, Luca; Carrara, Nancy; Finesso, Sara; Marcarini, Silvia; Mazza, Giovanni; Pavesi, Simone; Sala, Massimo; Urso, Gaetano

2018-01-01

Volumetric Modulated Arc Therapy (VMAT) is a modern technique, widely used in human radiotherapy, which allows a high dose to be delivered to tumor volumes and low doses to the surrounding organs at risk (OAR). Veterinary clinics takes advantage of this feature due to the small target volumes and distances between the target and the OAR. Sparing the OAR permits dose escalation, and hypofractionation regimens reduce the number of treatment sessions with a simpler manageability in the veterinary field. Multimodal volumes definition is mandatory for the small volumes involved and a positioning device precisely reproducible with a setup confirmation is needed before each session for avoiding missing the target. Additionally, the elaborate treatment plan must pursue hard constraints and objectives, and its feasibility must be evaluated with a per patient quality control. The aim of this work is to report results with regard to brain meningiomas and gliomas, trigeminal nerve tumors, brachial plexus tumors, adrenal tumors with vascular invasion and rabbit thymomas, in comparison with literature to determine if VMAT is a safe and viable alternative to surgery or chemotherapy alone, or as an adjuvant therapy in pets. PMID:29364837

SU-E-T-397: Evaluation of Planned Dose Distributions by Monte Carlo (0.5%) and Ray Tracing Algorithm for the Spinal Tumors with CyberKnife

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cho, H; Brindle, J; Hepel, J

2015-06-15

Purpose: To analyze and evaluate dose distribution between Ray Tracing (RT) and Monte Carlo (MC) algorithms of 0.5% uncertainty on a critical structure of spinal cord and gross target volume and planning target volume. Methods: Twenty four spinal tumor patients were treated with stereotactic body radiotherapy (SBRT) by CyberKnife in 2013 and 2014. The MC algorithm with 0.5% of uncertainty is used to recalculate the dose distribution for the treatment plan of the patients using the same beams, beam directions, and monitor units (MUs). Results: The prescription doses are uniformly larger for MC plans than RT except one case. Upmore » to a factor of 1.19 for 0.25cc threshold volume and 1.14 for 1.2cc threshold volume of dose differences are observed for the spinal cord. Conclusion: The MC recalculated dose distributions are larger than the original MC calculations for the spinal tumor cases. Based on the accuracy of the MC calculations, more radiation dose might be delivered to the tumor targets and spinal cords with the increase prescription dose.« less

Antibody Protein Array Analysis of the Tear Film Cytokines

PubMed Central

Li, Shimin; Sack, Robert; Vijmasi, Trinka; Sathe, Sonal; Beaton, Ann; Quigley, David; Gallup, Marianne; McNamara, Nancy A.

2013-01-01

Purpose Many bioactive proteins including cytokines are reported to increase in dry eye disease although the specific profile and concentration of inflammatory mediators varies considerably from study to study. In part this variability results from inherent difficulties in quantifying low abundance proteins in a limited sample volume using relatively low sensitivity dot ELISA methods. Additional complexity comes with the use of pooled samples collected using a variety of techniques and intrinsic variation in the diurnal pattern of individual tear proteins. The current study describes a recent advance in the area of proteomics that has allowed the identification of dozens of low abundance proteins in human tear samples. Methods Commercially available stationary phase antibody protein arrays were adapted to improve suitability for use in small volume biological fluid analysis with particular emphasis on tear film proteomics. Arrays were adapted to allow simultaneous screening for a panel of inflammatory cytokines in low volume tear samples collected from individual eyes. Results A preliminary study comparing tear array results in a small population of Sjögren’s syndrome patients was conducted. The multiplex microplate array assays of cytokines in tear fluid present an unanticipated challenge due to the unique nature of tear fluid. The presence of factors that exhibit an affinity for plastic, capture antibodies and IgG and create a complex series of matrix effects profoundly impacting the reliability of dot ELISA, including with elevated levels of background reactivity and reduction in capacity to bind targeted protein. Conclusions Preliminary results using tears collected from patients with Sjögren’s syndrome reveal methodological advantages of protein array technology and support the concept that autoimmune-mediated dry eye disease has an inflammatory component. They also emphasize the inherent difficulties one can face when interpreting the results of micro-well arrays that result from blooming effects, matrix effects, image saturation and cross-talk between capture and probe antibodies that can greatly reduce signal-to-noise and limit the ability to obtain meaningful results. PMID:18677223

Will weight loss cause significant dosimetric changes of target volumes and organs at risk in nasopharyngeal carcinoma treated with intensity-modulated radiation therapy?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Chuanben; Fei, Zhaodong; Chen, Lisha

This study aimed to quantify dosimetric effects of weight loss for nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). Overall, 25 patients with NPC treated with IMRT were enrolled. We simulated weight loss during IMRT on the computer. Weight loss model was based on the planning computed tomography (CT) images. The original external contour of head and neck was labeled plan 0, and its volume was regarded as pretreatment normal weight. We shrank the external contour with different margins (2, 3, and 5 mm) and generated new external contours of head and neck. The volumes of reconstructed external contoursmore » were regarded as weight during radiotherapy. After recontouring outlines, the initial treatment plan was mapped to the redefined CT scans with the same beam configurations, yielding new plans. The computer model represented a theoretical proportional weight loss of 3.4% to 13.7% during the course of IMRT. The dose delivered to the planning target volume (PTV) of primary gross tumor volume and clinical target volume significantly increased by 1.9% to 2.9% and 1.8% to 2.9% because of weight loss, respectively. The dose to the PTV of gross tumor volume of lymph nodes fluctuated from −2.0% to 1.0%. The dose to the brain stem and the spinal cord was increased (p < 0.001), whereas the dose to the parotid gland was decreased (p < 0.001). Weight loss may lead to significant dosimetric change during IMRT. Repeated scanning and replanning for patients with NPC with an obvious weight loss may be necessary.« less

77 FR 59234 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing of Proposed Rule Change To Amend...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-26

... as the product of (i) the Founding Firm aggregate target market share for such measurement period... exceeded its ``Individual Target'' during the measurement period. A Founding Firm's Individual Target is its pro rata portion of an aggregate Founding Firm target contribution to the annual volume of the...

Assessment of Prospectively Assigned Likert Scores for Targeted Magnetic Resonance Imaging-Transrectal Ultrasound Fusion Biopsies in Patients with Suspected Prostate Cancer.

PubMed

Costa, Daniel N; Lotan, Yair; Rofsky, Neil M; Roehrborn, Claus; Liu, Alexander; Hornberger, Brad; Xi, Yin; Francis, Franto; Pedrosa, Ivan

2016-01-01

We assess the performance of prospectively assigned magnetic resonance imaging based Likert scale scores for the detection of clinically significant prostate cancer, and analyze the pre-biopsy imaging variables associated with increased cancer detection using targeted magnetic resonance imaging-transrectal ultrasound fusion biopsy. In this retrospective review of prospectively generated data including men with abnormal multiparametric prostate magnetic resonance imaging (at least 1 Likert score 3 or greater lesion) who underwent subsequent targeted magnetic resonance imaging-transrectal ultrasound fusion biopsy, we determined the association between different imaging variables (Likert score, lesion size, lesion location, prostate volume, radiologist experience) and targeted biopsy positivity rate. We also compared the detection of clinically significant cancer according to Likert scale scores. Tumors with high volume (50% or more of any core) Gleason score 3+4 or any tumor with greater Gleason score were considered clinically significant. Each lesion served as the elementary unit for analysis. We used logistic regression for univariate and multivariate (stepwise selection) analysis to assess for an association between targeted biopsy positivity rate and each tested variable. The relationship between Likert scale and Gleason score was evaluated using the Spearman correlation coefficient. A total of 161 men with 244 lesions met the study eligibility criteria. Targeted biopsies diagnosed cancer in 41% (66 of 161) of the men and 41% (99 of 244) of the lesions. The Likert score was the strongest predictor of targeted biopsy positivity (OR 3.7, p <0.0001). Other imaging findings associated with a higher targeted biopsy positivity rate included smaller prostate volume (OR 0.7, p <0.01), larger lesion size (OR 2.2, p <0.001) and anterior location (OR 2.0, p=0.01). On multiple logistic regression analysis Likert score, lesion size and prostate volume were significant predictors of targeted biopsy positivity. Higher Likert scores were also associated with increased detection of clinically significant tumors (p <0.0001). The Likert scale score used to convey the degree of suspicion on multiparametric magnetic resonance imaging is the strongest predictor of targeted biopsy positivity and of the presence of clinically significant tumor. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Modeling protein complexes with BiGGER.

PubMed

Krippahl, Ludwig; Moura, José J; Palma, P Nuno

2003-07-01

This article describes the method and results of our participation in the Critical Assessment of PRediction of Interactions (CAPRI) experiment, using the protein docking program BiGGER (Bimolecular complex Generation with Global Evaluation and Ranking) (Palma et al., Proteins 2000;39:372-384). Of five target complexes (CAPRI targets 2, 4, 5, 6, and 7), only one was successfully predicted (target 6), but BiGGER generated reasonable models for targets 4, 5, and 7, which could have been identified if additional biochemical information had been available. Copyright 2003 Wiley-Liss, Inc.

Policy options for alcohol price regulation: the importance of modelling population heterogeneity.

PubMed

Meier, Petra Sylvia; Purshouse, Robin; Brennan, Alan

2010-03-01

Context and aims Internationally, the repertoire of alcohol pricing policies has expanded to include targeted taxation, inflation-linked taxation, taxation based on alcohol-by-volume (ABV), minimum pricing policies (general or targeted), bans of below-cost selling and restricting price-based promotions. Policy makers clearly need to consider how options compare in reducing harms at the population level, but are also required to demonstrate proportionality of their actions, which necessitates a detailed understanding of policy effects on different population subgroups. This paper presents selected findings from a policy appraisal for the UK government and discusses the importance of accounting for population heterogeneity in such analyses. Method We have built a causal, deterministic, epidemiological model which takes account of differential preferences by population subgroups defined by age, gender and level of drinking (moderate, hazardous, harmful). We consider purchasing preferences in terms of the types and volumes of alcoholic beverages, prices paid and the balance between bars, clubs and restaurants as opposed to supermarkets and off-licenses. Results Age, sex and level of drinking fundamentally affect beverage preferences, drinking location, prices paid, price sensitivity and tendency to substitute for other beverage types. Pricing policies vary in their impact on different product types, price points and venues, thus having distinctly different effects on subgroups. Because population subgroups also have substantially different risk profiles for harms, policies are differentially effective in reducing health, crime, work-place absence and unemployment harms. Conclusion Policy appraisals must account for population heterogeneity and complexity if resulting interventions are to be well considered, proportionate, effective and cost-effective.

Cardiomyocyte mitochondrial oxidative stress and cytoskeletal breakdown in the heart with a primary volume overload.

PubMed

Yancey, Danielle M; Guichard, Jason L; Ahmed, Mustafa I; Zhou, Lufang; Murphy, Michael P; Johnson, Michelle S; Benavides, Gloria A; Collawn, James; Darley-Usmar, Victor; Dell'Italia, Louis J

2015-03-15

Left ventricular (LV) volume overload (VO) results in cardiomyocyte oxidative stress and mitochondrial dysfunction. Because mitochondria are both a source and target of ROS, we hypothesized that the mitochondrially targeted antioxidant mitoubiquinone (MitoQ) will improve cardiomyocyte damage and LV dysfunction in VO. Isolated cardiomyocytes from Sprague-Dawley rats were exposed to stretch in vitro and VO of aortocaval fistula (ACF) in vivo. ACF rats were treated with and without MitoQ. Isolated cardiomyocytes were analyzed after 3 h of cyclical stretch or 8 wk of ACF with MitoSox red or 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate to measure ROS and with tetramethylrhodamine to measure mitochondrial membrane potential. Transmission electron microscopy and immunohistochemistry were used for cardiomyocyte structural assessment. In vitro cyclical stretch and 8-wk ACF resulted in increased cardiomyocyte mitochondrial ROS production and decreased mitochondrial membrane potential, which were significantly improved by MitoQ. ACF had extensive loss of desmin and β₂-tubulin that was paralleled by mitochondrial disorganization, loss of cristae, swelling, and clustering identified by mitochondria complex IV staining and transmission electron microscopy. MitoQ improved mitochondrial structural damage and attenuated desmin loss/degradation evidenced by immunohistochemistry and protein expression. However, LV dilatation and fractional shortening were unaffected by MitoQ treatment in 8-wk ACF. In conclusion, although MitoQ did not affect LV dilatation or function in ACF, these experiments suggest a connection of cardiomyocyte mitochondria-derived ROS production with cytoskeletal disruption and mitochondrial damage in the VO of ACF.

Cardiomyocyte mitochondrial oxidative stress and cytoskeletal breakdown in the heart with a primary volume overload

PubMed Central

Yancey, Danielle M.; Guichard, Jason L.; Ahmed, Mustafa I.; Zhou, Lufang; Murphy, Michael P.; Johnson, Michelle S.; Benavides, Gloria A.; Collawn, James; Darley-Usmar, Victor

2015-01-01

Left ventricular (LV) volume overload (VO) results in cardiomyocyte oxidative stress and mitochondrial dysfunction. Because mitochondria are both a source and target of ROS, we hypothesized that the mitochondrially targeted antioxidant mitoubiquinone (MitoQ) will improve cardiomyocyte damage and LV dysfunction in VO. Isolated cardiomyocytes from Sprague-Dawley rats were exposed to stretch in vitro and VO of aortocaval fistula (ACF) in vivo. ACF rats were treated with and without MitoQ. Isolated cardiomyocytes were analyzed after 3 h of cyclical stretch or 8 wk of ACF with MitoSox red or 5-(and-6)-chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate to measure ROS and with tetramethylrhodamine to measure mitochondrial membrane potential. Transmission electron microscopy and immunohistochemistry were used for cardiomyocyte structural assessment. In vitro cyclical stretch and 8-wk ACF resulted in increased cardiomyocyte mitochondrial ROS production and decreased mitochondrial membrane potential, which were significantly improved by MitoQ. ACF had extensive loss of desmin and β2-tubulin that was paralleled by mitochondrial disorganization, loss of cristae, swelling, and clustering identified by mitochondria complex IV staining and transmission electron microscopy. MitoQ improved mitochondrial structural damage and attenuated desmin loss/degradation evidenced by immunohistochemistry and protein expression. However, LV dilatation and fractional shortening were unaffected by MitoQ treatment in 8-wk ACF. In conclusion, although MitoQ did not affect LV dilatation or function in ACF, these experiments suggest a connection of cardiomyocyte mitochondria-derived ROS production with cytoskeletal disruption and mitochondrial damage in the VO of ACF. PMID:25599572

The RDE-10/RDE-11 complex triggers RNAi-induced mRNA degradation by association with target mRNA in C. elegans

PubMed Central

Yang, Huan; Zhang, Ying; Vallandingham, Jim; Li, Hau; Florens, Laurence; Mak, Ho Yi

2012-01-01

The molecular mechanisms for target mRNA degradation in Caenorhabditis elegans undergoing RNAi are not fully understood. Using a combination of genetic, proteomic, and biochemical approaches, we report a divergent RDE-10/RDE-11 complex that is required for RNAi in C. elegans. Genetic analysis indicates that the RDE-10/RDE-11 complex acts in parallel to nuclear RNAi. Association of the complex with target mRNA is dependent on RDE-1 but not RRF-1, suggesting that target mRNA recognition depends on primary but not secondary siRNA. Furthermore, RDE-11 is required for mRNA degradation subsequent to target engagement. Deep sequencing reveals a fivefold decrease in secondary siRNA abundance in rde-10 and rde-11 mutant animals, while primary siRNA and microRNA biogenesis is normal. Therefore, the RDE-10/RDE-11 complex is critical for amplifying the exogenous RNAi response. Our work uncovers an essential output of the RNAi pathway in C. elegans. PMID:22508728

The RDE-10/RDE-11 complex triggers RNAi-induced mRNA degradation by association with target mRNA in C. elegans.

PubMed

Yang, Huan; Zhang, Ying; Vallandingham, Jim; Li, Hua; Li, Hau; Florens, Laurence; Mak, Ho Yi

2012-04-15

The molecular mechanisms for target mRNA degradation in Caenorhabditis elegans undergoing RNAi are not fully understood. Using a combination of genetic, proteomic, and biochemical approaches, we report a divergent RDE-10/RDE-11 complex that is required for RNAi in C. elegans. Genetic analysis indicates that the RDE-10/RDE-11 complex acts in parallel to nuclear RNAi. Association of the complex with target mRNA is dependent on RDE-1 but not RRF-1, suggesting that target mRNA recognition depends on primary but not secondary siRNA. Furthermore, RDE-11 is required for mRNA degradation subsequent to target engagement. Deep sequencing reveals a fivefold decrease in secondary siRNA abundance in rde-10 and rde-11 mutant animals, while primary siRNA and microRNA biogenesis is normal. Therefore, the RDE-10/RDE-11 complex is critical for amplifying the exogenous RNAi response. Our work uncovers an essential output of the RNAi pathway in C. elegans.

SU-G-JeP4-05: Effects of Irregular Respiratory Motion On the Positioning Accuracy of Moving Target with Free Breathing Cone-Beam Computerized Tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, X; Xiong, W; Gewanter, R

Purpose: Average or maximum intensity projection (AIP or MIP) images derived from 4DCT images are often used as a reference image for target alignment when free breathing Cone-beam CT (FBCBCT) is used for positioning a moving target at treatment. This method can be highly accurate if the patient has stable respiratory motion. However, a patient’s breathing pattern often varies irregularly. The purpose of this study is to investigate the effect of irregular respiration on the positioning accuracy of a moving target with FBCBCT. Methods: Eight patients’ respiratory motion curves were selected to drive a Quasar phantom with embedded cubic andmore » spherical targets. A 4DCT of the moving phantom was acquired on a CT scanner (Philips Brilliance 16) equipped with a Varian RPM system. The phase binned 4DCT images and the corresponding MIP and AIP images were transferred into Eclipse for analysis. CBCTs of the phantom driven by the same breathing curves were acquired on a Varian TrueBeam and fused such that the zero positions of moving targets are the same on both CBCT and AIP images. The sphere and cube volumes and centrioid differences (alignment error) determined by MIP, AIP and FBCBCT images were compared. Results: Compared to the volume determined by FBCBCT, the volumes of cube and sphere in MIP images were 22.4%±8.8% and 34.2%±6.2% larger while the volumes in AIP images were 7.1%±6.2% and 2.7%±15.3% larger, respectively. The alignment errors for the cube and sphere with center-center matches between MIP and FBCBCT were 3.5±3.1mm and 3.2±2.3mm, and the alignment errors between AIP and FBCBCT were 2.1±2.6mm and 2.1±1.7mm, respectively. Conclusion: AIP images appear to be superior reference images than MIP images. However, irregular respiratory motions could compromise the positioning accuracy of a moving target if the target center-center match is used to align FBCBCT and AIP images.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sakanaka, Katsuyuki; Mizowaki, Takashi, E-mail: mizo@kuhp.kyoto-u.ac.jp; Hiraoka, Masahiro

Purpose: To investigate the dosimetric advantage of intensity-modulated radiotherapy (IMRT) for whole ventricles (WV) in patients with a localized intracranial germinoma receiving induction chemotherapy. Methods and Materials: Data from 12 consecutive patients with localized intracranial germinomas who received induction chemotherapy and radiotherapy were used. Four-field coplanar three-dimensional conformal radiotherapy (3D-CRT) and seven-field coplanar IMRT plans were created. In both plans, 24 Gy was prescribed in 12 fractions for the planning target volume (PTV) involving WV and tumor bed. In IMRT planning, optimization was conducted to reduce the doses to the organs at risk (OARs) as much as possible, keeping themore » minimum dose equivalent to that of 3D-CRT. The 3D-CRT and IMRT plans were compared in terms of the dose-volume statistics for target coverage and the OARs. Results: IMRT significantly increased the percentage volume of the PTV receiving 24 Gy compared with 3D-CRT (93.5% vs. 84.8%; p = 0.007), while keeping target homogeneity equivalent to 3D-CRT (p = 0.869). The absolute percentage reduction in the irradiated volume of the normal brain receiving 100%, 75%, 50%, and 25% of 24 Gy ranged from 0.7% to 16.0% in IMRT compared with 3D-CRT (p < 0.001). No significant difference was observed in the volume of the normal brain receiving 10% and 5% of 24 Gy between IMRT and 3D-CRT. Conformation number was significantly improved in IMRT (p < 0.001). For other OARs, the mean dose to the cochlea was reduced significantly in IMRT by 22.3% of 24 Gy compared with 3D-CRT (p < 0.001). Conclusions: Compared with 3D-CRT, IMRT for WV improved the target coverage and reduced the irradiated volume of the normal brain in patients with intracranial germinomas receiving induction chemotherapy. IMRT for WV with induction chemotherapy could reduce the late side effects from cranial irradiation without compromising control of the tumor.« less

TU-AB-202-03: Prediction of PET Transfer Uncertainty by DIR Error Estimating Software, AUTODIRECT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, H; Chen, J; Phillips, J

2016-06-15

Purpose: Deformable image registration (DIR) is a powerful tool, but DIR errors can adversely affect its clinical applications. To estimate voxel-specific DIR uncertainty, a software tool, called AUTODIRECT (automated DIR evaluation of confidence tool), has been developed and validated. This work tests the ability of this software to predict uncertainty for the transfer of standard uptake values (SUV) from positron-emission tomography (PET) with DIR. Methods: Virtual phantoms are used for this study. Each phantom has a planning computed tomography (CT) image and a diagnostic PET-CT image set. A deformation was digitally applied to the diagnostic CT to create the planningmore » CT image and establish a known deformation between the images. One lung and three rectum patient datasets were employed to create the virtual phantoms. Both of these sites have difficult deformation scenarios associated with them, which can affect DIR accuracy (lung tissue sliding and changes in rectal filling). The virtual phantoms were created to simulate these scenarios by introducing discontinuities in the deformation field at the lung rectum border. The DIR algorithm from Plastimatch software was applied to these phantoms. The SUV mapping errors from the DIR were then compared to that predicted by AUTODIRECT. Results: The SUV error distributions closely followed the AUTODIRECT predicted error distribution for the 4 test cases. The minimum and maximum PET SUVs were produced from AUTODIRECT at 95% confidence interval before applying gradient-based SUV segmentation for each of these volumes. Notably, 93.5% of the target volume warped by the true deformation was included within the AUTODIRECT-predicted maximum SUV volume after the segmentation, while 78.9% of the target volume was within the target volume warped by Plastimatch. Conclusion: The AUTODIRECT framework is able to predict PET transfer uncertainty caused by DIR, which enables an understanding of the associated target volume uncertainty.« less

A novel concept for tumour targeting with radiation: Inverse dose-painting or targeting the "Low Drug Uptake Volume".

PubMed

Yaromina, Ala; Granzier, Marlies; Biemans, Rianne; Lieuwes, Natasja; van Elmpt, Wouter; Shakirin, Georgy; Dubois, Ludwig; Lambin, Philippe

2017-09-01

We tested a novel treatment approach combining (1) targeting radioresistant hypoxic tumour cells with the hypoxia-activated prodrug TH-302 and (2) inverse radiation dose-painting to boost selectively non-hypoxic tumour sub-volumes having no/low drug uptake. 18 F-HX4 hypoxia tracer uptake measured with a clinical PET/CT scanner was used as a surrogate of TH-302 activity in rhabdomyosarcomas growing in immunocompetent rats. Low or high drug uptake volume (LDUV/HDUV) was defined as 40% of the GTV with the lowest or highest 18 F-HX4 uptake, respectively. Two hours post TH-302/saline administration, animals received either single dose radiotherapy (RT) uniformly (15 or 18.5Gy) or a dose-painted non-uniform radiation (15Gy) with 50% higher dose to LDUV or HDUV (18.5Gy). Treatment plans were created using Eclipse treatment planning system and radiation was delivered using VMAT. Tumour response was quantified as time to reach 3 times starting tumour volume. Non-uniform RT boosting tumour sub-volume with low TH-302 uptake (LDUV) was superior to the same dose escalation to HDUV (p<0.0001) and uniform RT with the same mean dose 15Gy (p=0.0077). Noteworthy, dose escalation to LDUV required on average 3.5Gy lower dose to the GTV to achieve similar tumour response as uniform dose escalation. The results support targeted dose escalation to non-hypoxic tumour sub-volume with no/low activity of hypoxia-activated prodrugs. This strategy applies on average a lower radiation dose and is as effective as uniform dose escalation to the entire tumour. It could be applied to other type of drugs provided that their distribution can be imaged. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Defining the "Hostile Pelvis" for Intensity Modulated Radiation Therapy: The Impact of Anatomic Variations in Pelvic Dimensions on Dose Delivered to Target Volumes and Organs at Risk in Patients With High-Risk Prostate Cancer Treated With Whole Pelvic Radiation Therapy.

PubMed

Yirmibeşoğlu Erkal, Eda; Karabey, Sinan; Karabey, Ayşegül; Hayran, Mutlu; Erkal, Haldun Şükrü

2015-07-15

The aim of this study was to evaluate the impact of variations in pelvic dimensions on the dose delivered to the target volumes and the organs at risk (OARs) in patients with high-risk prostate cancer (PCa) to be treated with whole pelvic radiation therapy (WPRT) in an attempt to define the hostile pelvis in terms of intensity modulated radiation therapy (IMRT). In 45 men with high-risk PCa to be treated with WPRT, the target volumes and the OARs were delineated, the dose constraints for the OARs were defined, and treatment plans were generated according to the Radiation Therapy Oncology Group 0924 protocol. Six dimensions to reflect the depth, width, and height of the bony pelvis were measured, and 2 indexes were calculated from the planning computed tomographic scans. The minimum dose (Dmin), maximum dose (Dmax), and mean dose (Dmean) for the target volumes and OARs and the partial volumes of each of these structures receiving a specified dose (VD) were calculated from the dose-volume histograms (DVHs). The data from the DVHs were correlated with the pelvic dimensions and indexes. According to an overall hostility score (OHS) calculation, 25 patients were grouped as having a hospitable pelvis and 20 as having a hostile pelvis. Regarding the OHS grouping, the DVHs for the bladder, bowel bag, left femoral head, and right femoral head differed in favor of the hospitable pelvis group, and the DVHs for the rectum differed for a range of lower doses in favor of the hospitable pelvis group. Pelvimetry might be used as a guide to define the challenging anatomy or the hostile pelvis in terms of treatment planning for IMRT in patients with high-risk PCa to be treated with WPRT. Copyright © 2015 Elsevier Inc. All rights reserved.

Radioiodine therapy in Graves' disease based on tissue-absorbed dose calculations: effect of pre-treatment thyroid volume on clinical outcome.

PubMed

Reinhardt, Michael J; Brink, Ingo; Joe, Alexius Y; Von Mallek, Dirk; Ezziddin, Samer; Palmedo, Holger; Krause, Thomas M

2002-09-01

This study was performed with three aims. The first was to analyse the effectiveness of radioiodine therapy in Graves' disease patients with and without goitres under conditions of mild iodine deficiency using several tissue-absorbed doses. The second aim was to detect further parameters which might be predictive for treatment outcome. Finally, we wished to determine the deviation of the therapeutically achieved dose from that intended. Activities of 185-2,220 MBq radioiodine were calculated by means of Marinelli's formula to deliver doses of 150, 200 or 300 Gy to the thyroids of 224 patients with Graves' disease and goitres up to 130 ml in volume. Control of hyperthyroidism, change in thyroid volume and thyrotropin-receptor antibodies were evaluated 15+/-9 months after treatment for each dose. The results were further evaluated with respect to pre-treatment parameters which might be predictive for therapy outcome. Thyroidal radioiodine uptake was measured every day during therapy to determine the therapeutically achieved target dose and its coefficient of variation. There was a significant dose dependency in therapeutic outcome: frequency of hypothyroidism increased from 27.4% after 150 Gy to 67.7% after 300 Gy, while the frequency of persistent hyperthyroidism decreased from 27.4% after 150 Gy to 8.1% after 300 Gy. Patients who became hypothyroid had a maximum thyroid volume of 42 ml and received a target dose of 256+/-80 Gy. The coefficient of variation for the achieved target dose ranged between 27.7% for 150 Gy and 17.8% for 300 Gy. When analysing further factors which might influence therapeutic outcome, only pre-treatment thyroid volume showed a significant relationship to the result of treatment. It is concluded that a target dose of 250 Gy is essential to achieve hypothyroidism within 1 year after radioiodine therapy in Graves' disease patients with goitres up to 40 ml in volume. Patients with larger goitres might need higher doses.

Comparative studies on mitochondrial electron transport chain complexes of Sitophilus zeamais treated with allyl isothiocyanate and calcium phosphide.

PubMed

Zhang, Chao; Wu, Hua; Zhao, Yuan; Ma, Zhiqing; Zhang, Xing

2016-01-01

With Sitophilus zeamais as the target organism, the present study for the first time attempted to elucidate the comparative effects between allyl isothiocyanate (AITC) and calcium phosphide (Ca3P2), exposure on mitochondrial electron transport chain (ETC.) complex I & IV and their downstream effects on enzymes relevant to reactive oxygen species (ROS). In vivo, both AITC and Ca3P2 inhibited complex I and IV with similar downstream effects. In contrast with Ca3P2, the inhibition of complex I caused by AITC was dependent on time and dose. In vitro, AITC inhibited complex IV more significantly than complex I. These results indicate that mitochondrial complex IV is the primary target of AITC, and that complex I is another potential target. Copyright © 2015 Elsevier B.V. All rights reserved.

Breaking into the epithelial apical–junctional complex — news from pathogen hackers

PubMed Central

Vogelmann, Roger; Amieva, Manuel R; Falkow, Stanley; Nelson, W James

2012-01-01

The epithelial apical–junctional complex is a key regulator of cellular functions. In addition, it is an important target for microbial pathogens that manipulate the cell to survive, proliferate and sometimes persist within a host. Out of a myriad of potential molecular targets, some bacterial and viral pathogens have selected a subset of protein targets at the apical–junctional complex of epithelial cells. Studying how microbes use these targets also teaches us about the inherent physiological properties of host molecules in the context of normal junctional structure and function. Thus, we have learned that three recently uncovered components of the apical–junctional complex of the Ig superfamily — junctional adhesion molecule, Nectin and the coxsackievirus and adenovirus receptor — are important regulators of junction structure and function and represent critical targets of microbial virulence gene products. PMID:15037310

Breaking into the epithelial apical-junctional complex--news from pathogen hackers.

PubMed

Vogelmann, Roger; Amieva, Manuel R; Falkow, Stanley; Nelson, W James

2004-02-01

The epithelial apical-junctional complex is a key regulator of cellular functions. In addition, it is an important target for microbial pathogens that manipulate the cell to survive, proliferate and sometimes persist within a host. Out of a myriad of potential molecular targets, some bacterial and viral pathogens have selected a subset of protein targets at the apical-junctional complex of epithelial cells. Studying how microbes use these targets also teaches us about the inherent physiological properties of host molecules in the context of normal junctional structure and function. Thus, we have learned that three recently uncovered components of the apical-junctional complex of the Ig superfamily--junctional adhesion molecule, Nectin and the coxsackievirus and adenovirus receptor--are important regulators of junction structure and function and represent critical targets of microbial virulence gene products.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krayenbuehl, Jerome Dipl.Phys. E.T.H.; Oertel, Susanne; Davis, J. Bernard

Purpose: The optimal technique for postoperative radiotherapy (RT) after extrapleural pleuropneumonectomy (EPP) of malignant pleural mesothelioma (MPM) remains debated. Methods and Materials: The data from 8 right-sided and 9 left-sided consecutive cases of MPM treated with RT after radical EPP were reviewed. Of the 17 patients, 8 had been treated with three-dimensional (3D) conformal RT (3D-CRT) and 9 with intensity-modulated RT (IMRT) with 6-MV photons. The clinical outcome and adverse events were assessed. For comparative planning, each case was replanned with 3D-CRT using photons and electrons or with IMRT. Homogeneity, doses to the organs at risk, and target volume coveragemore » were analyzed. Results: Both techniques yielded acceptable plans. The dose coverage and homogeneity of IMRT increased by 7.7% for the first planning target volume and 9.7% for the second planning target volume, ensuring {>=}95% of the prescribed dose compared with 3D-CRT (p < 0.01). Compared with 3D-CRT, IMRT increased the dose to the contralateral lung, with an increase in the mean lung dose of 7.8 Gy and an increase in the volume receiving 13 Gy and 20 Gy by 20.5% and 7.2%, respectively (p < 0.01). A negligible dose increase to the contralateral kidney and liver was observed. No differences were seen for the spinal cord and ipsilateral kidney. Two adverse events of clinical relevant lung toxicity were observed with IMRT. Conclusion: Intensity-modulated RT and 3D-CRT are both suitable for adjuvant RT. IMRT improves the planning target volume coverage but delivered greater doses to the organs at risk. Rigid dose constraints for the lung should be respected.« less

Efficacy of patient-specific bolus created using three-dimensional printing technique in photon radiotherapy.

PubMed

Fujimoto, Koya; Shiinoki, Takehiro; Yuasa, Yuki; Hanazawa, Hideki; Shibuya, Keiko

2017-06-01

A commercially available bolus ("commercial-bolus") does not make complete contact with the irregularly shaped patient skin. This study aims to customise a patient-specific three-dimensional (3D) bolus using a 3D printing technique ("3D-bolus") and to evaluate its clinical feasibility for photon radiotherapy. The 3D-bolus was designed using a treatment planning system (TPS) in Digital Imaging and Communications in Medicine-Radiotherapy (DICOM-RT) format, and converted to stereolithographic format for printing. To evaluate its physical characteristics, treatment plans were created for water-equivalent phantoms that were bolus-free, or had a flat-form printed 3D-bolus, a TPS-designed bolus ("virtual-bolus"), or a commercial-bolus. These plans were compared based on the percentage depth dose (PDD) and target-volume dose volume histogram (DVH) measurements. To evaluate the clinical feasibility, treatment plans were created for head phantoms that were bolus-free or had a 3D-bolus, a virtual-bolus, or a commercial-bolus. These plans were compared based on the target volume DVH. In the physical evaluation, the 3D-bolus provided effective dose coverage in the build-up region, which was equivalent to the commercial-bolus. With regard to the clinical feasibility, the air gaps were lesser with the 3D-bolus when compared to the commercial-bolus. Furthermore, the prescription dose could be delivered appropriately to the target volume. The 3D-bolus has potential use for air-gap reduction compared to the commercial-bolus and facilitates target-volume dose coverage and homogeneity improvement. A 3D-bolus produced using a 3D printing technique is comparable to a commercial-bolus applied to an irregular-shaped skin surface. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Evaluation of dose coverage to target volume and normal tissue sparing in the adjuvant radiotherapy of gastric cancers: 3D-CRT compared with dynamic IMRT.

PubMed

Murthy, Kk; Shukeili, Ka; Kumar, Ss; Davis, Ca; Chandran, Rr; Namrata, S

2010-01-01

To assess the potential advantage of intensity-modulated radiotherapy (IMRT) over 3D-conformal radiotherapy (3D-CRT) planning in postoperative adjuvant radiotherapy for patients with gastric carcinoma. In a retrospective study, for plan comparison, dose distribution was recalculated in 15 patients treated with 3D-CRT on the contoured structures of same CT images using an IMRT technique. 3D-conformal plans with three fields and four-fields were compared with seven-field dynamic IMRT plans. The different plans were compared by analyzing the dose coverage of planning target volume using TV(95), D(mean), uniformity index, conformity index and homogeneity index parameters. To assess critical organ sparing, D(mean), D(max), dose to one-third and two-third volumes of the OARs and percentage of volumes receiving more than their tolerance doses were compared. The average dose coverage values of PTV with 3F-CRT and 4F-CRT plans were comparable, where as IMRT plans achieved better target coverage(p<0.001) with higher conformity index value of 0.81±0.07 compared to both the 3D-CRT plans. The doses to the liver and bowel reduced significantly (p<0.001) with IMRT plans compared to other 3D-CRT plans. For all OARs the percentage of volumes receiving more than their tolerance doses were reduced with the IMRT plans. This study showed that a better target coverage and significant dose reduction to OARs could be achieved with the IMRT plans. The IMRT can be preferred with caution for organ motion. The authors are currently studying organ motion in the upper abdomen to use IMRT for patient treatment.

Impact of 4D-(18)FDG-PET/CT imaging on target volume delineation in SBRT patients with central versus peripheral lung tumors. Multi-reader comparative study.

PubMed

Chirindel, Alin; Adebahr, Sonja; Schuster, Daniel; Schimek-Jasch, Tanja; Schanne, Daniel H; Nemer, Ursula; Mix, Michael; Meyer, Philipp; Grosu, Anca-Ligia; Brunner, Thomas; Nestle, Ursula

2015-06-01

Evaluation of the effect of co-registered 4D-(18)FDG-PET/CT for SBRT target delineation in patients with central versus peripheral lung tumors. Analysis of internal target volume (ITV) delineation of central and peripheral lung lesions in 21 SBRT-patients. Manual delineation was performed by 4 observers in 2 contouring phases: on respiratory gated 4DCT with diagnostic 3DPET available aside (CT-ITV) and on co-registered 4DPET/CT (PET/CT-ITV). Comparative analysis of volumes and inter-reader agreement. 11 cases of peripheral and 10 central lesions were evaluated. In peripheral lesions, average CT-ITV was 6.2 cm(3) and PET/CT-ITV 8.6 cm(3), resembling a mean change in hypothetical radius of 2 mm. For both CT-ITVs and PET/CT-ITVs inter reader agreement was good and unchanged (0.733 and 0.716; p=0.58). All PET/CT-ITVs stayed within the PTVs derived from CT-ITVs. In central lesions, average CT-ITVs were 42.1 cm(3), PET/CT-ITVs 44.2 cm(3), without significant overall volume changes. Inter-reader agreement improved significantly (0.665 and 0.750; p<0.05). 2/10 PET/CT-ITVs exceeded the PTVs derived from CT-ITVs by >1 ml in average for all observers. The addition of co-registered 4DPET data to 4DCT based target volume delineation for SBRT of centrally located lung tumors increases the inter-observer agreement and may help to avoid geographic misses. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Decreasing Temporal Lobe Dose With Five-Field Intensity-Modulated Radiotherapy for Treatment of Pituitary Macroadenomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parhar, Preeti K.; Duckworth, Tamara; Shah, Parinda

2010-10-01

Purpose: To compare temporal lobe dose delivered by three pituitary macroadenoma irradiation techniques: three-field three-dimensional conformal radiotherapy (3D-CRT), three-field intensity-modulated radiotherapy (3F IMRT), and a proposed novel alternative of five-field IMRT (5F IMRT). Methods and Materials: Computed tomography-based external beam radiotherapy planning was performed for 15 pituitary macroadenoma patients treated at New York University between 2002 and 2007 using: 3D-CRT (two lateral, one midline superior anterior oblique [SAO] beams), 3F IMRT (same beam angles), and 5F IMRT (same beam angles with additional right SAO and left SAO beams). Prescription dose was 45 Gy. Target volumes were: gross tumor volume (GTV)more » = macroadenoma, clinical target volume (CTV) = GTV, and planning target volume = CTV + 0.5 cm. Structure contouring was performed by two radiation oncologists guided by an expert neuroradiologist. Results: Five-field IMRT yielded significantly decreased temporal lobe dose delivery compared with 3D-CRT and 3F IMRT. Temporal lobe sparing with 5F IMRT was most pronounced at intermediate doses: mean V25Gy (% of total temporal lobe volume receiving {>=}25 Gy) of 13% vs. 28% vs. 29% for right temporal lobe and 14% vs. 29% vs. 30% for left temporal lobe for 5F IMRT, 3D-CRT, and 3F IMRT, respectively (p < 10{sup -7} for 5F IMRT vs. 3D-CRT and 5F IMRT vs. 3F IMRT). Five-field IMRT plans did not compromise target coverage, exceed normal tissue dose constraints, or increase estimated brain integral dose. Conclusions: Five-field IMRT irradiation technique results in a statistically significant decrease in the dose to the temporal lobes and may thus help prevent neurocognitive sequelae in irradiated pituitary macroadenoma patients.« less

Simple, Inexpensive Model Spirometer for Understanding Ventilation Volumes

ERIC Educational Resources Information Center

Giuliodori, Mauricio J.; DiCarlo, Stephen E.

2004-01-01

Spirometers are useful for enhancing students' understanding of normal lung volumes, capacities, and flow rates. Spirometers are also excellent for understanding how lung diseases alter ventilation volumes. However, spirometers are expensive, complex, and not appropriate for programs with limited space and budgets. Therefore, we developed a…

Water-soluble polymers for recovery of metal ions from aqueous streams

DOEpatents

Smith, Barbara F.; Robison, Thomas W.

1998-01-01

A process of selectively separating a target metal contained in an aqueous solution by contacting the aqueous solution containing a target metal with an aqueous solution including a water-soluble polymer capable of binding with the target metal for sufficient time whereby a water-soluble polymer-target metal complex is formed, and, separating the solution including the water-soluble polymer-target metal complex from the solution is disclosed.

Evaluation of target coverage and margins adequacy during CyberKnife Lung Optimized Treatment.

PubMed

Ricotti, Rosalinda; Seregni, Matteo; Ciardo, Delia; Vigorito, Sabrina; Rondi, Elena; Piperno, Gaia; Ferrari, Annamaria; Zerella, Maria Alessia; Arculeo, Simona; Francia, Claudia Maria; Sibio, Daniela; Cattani, Federica; De Marinis, Filippo; Spaggiari, Lorenzo; Orecchia, Roberto; Riboldi, Marco; Baroni, Guido; Jereczek-Fossa, Barbara Alicja

2018-04-01

Evaluation of target coverage and verification of safety margins, in motion management strategies implemented by Lung Optimized Treatment (LOT) module in CyberKnife system. Three fiducial-less motion management strategies provided by LOT can be selected according to tumor visibility in the X ray images acquired during treatment. In 2-view modality the tumor is visible in both X ray images and full motion tracking is performed. In 1-view modality the tumor is visible in a single X ray image, therefore, motion tracking is combined with an internal target volume (ITV)-based margin expansion. In 0-view modality the lesion is not visible, consequently the treatment relies entirely on an ITV-based approach. Data from 30 patients treated in 2-view modality were selected providing information on the three-dimensional tumor motion in correspondence to each X ray image. Treatments in 1-view and 0-view modalities were simulated by processing log files and planning volumes. Planning target volume (PTV) margins were defined according to the tracking modality: end-exhale clinical target volume (CTV) + 3 mm in 2-view and ITV + 5 mm in 0-view. In the 1-view scenario, the ITV encompasses only tumor motion along the non-visible direction. Then, non-uniform ITV to PTV margins were applied: 3 mm and 5 mm in the visible and non-visible direction, respectively. We defined the coverage of each voxel of the CTV as the percentage of X ray images where such voxel was included in the PTV. In 2-view modality coverage was calculated as the intersection between the CTV centred on the imaged target position and the PTV centred on the predicted target position, as recorded in log files. In 1-view modality, coverage was calculated as the intersection between the CTV centred on the imaged target position and the PTV centred on the projected predictor data. In 0-view modality coverage was calculated as the intersection between the CTV centred on the imaged target position and the non-moving PTV. Similar to dose-volume histogram, CTV coverage-volume histograms (defined as CVH) were derived for each patient and treatment modality. The geometric coverages of the 90% and 95% of CTV volume (C90, C95, respectively) were evaluated. Patient-specific optimal margins (ensuring C95 ≥ 95%) were computed retrospectively. The median ± interquartile-rage of C90 and C95 for upper lobe lesions was 99.1 ± 0.6% and 99.0 ± 3.1%, whereas they were 98.9 ± 4.2% and 97.8 ± 7.5% for lower and middle lobe tumors. In 2-view, 1-view and 0-view modality, adopted margins ensured C95 ≥ 95% in 70%, 85% and 63% of cases and C95 ≥ 90% in 90%, 88% and 83% of cases, respectively. In 2-view, 1-view and 0-view a reduction in margins still ensured C95 ≥ 95% in 33%, 78% and 59% of cases, respectively. CTV coverage analysis provided an a-posteriori evaluation of the treatment geometric accuracy and allowed a quantitative verification of the adequacy of the PTV margins applied in CyberKnife LOT treatments offering guidance in the selection of CTV margins. © 2018 American Association of Physicists in Medicine.

Enterobacteria identification and detection of diarrheagenic Escherichia coli in a Port Complex

PubMed Central

Costa, Clarissa Frota Macatrão; Neto, Valério Monteiro; Santos, Bruno Rafael de Carvalho; Costa, Bruno Rafael Rabelo; Azevedo, Alexandre; Serra, Josilene Lima; Mendes, Hermínio Benítez Rabello; Nascimento, Adenilde Ribeiro; Mendes, Mariana Bonfim Pinto; Kuppinger, Oliver

2014-01-01

The Port Complex of Maranhão (PCM) is the second largest port complex in Brazil, receiving ships with large volumes of ballast water. To evaluate the microbiological quality of its waters, physicochemical parameters (pH and salinity), the number of coliforms (thermotolerants and totals), and the presence of enterobacterias and diarrheagenic Escherichia coli strains were analyzed. In order to identify the presence of E. coli virulence genes target regions of the stx, elt, est, aggR, CVD432, ipaH and eae nucleotide sequences were studied. The presence of totals and thermotolerants coliforms were positive. Analyzing the salinity parameter, a significant increase in total coliforms was observed during the rainy season. We identified the species Escherichia coli, Proteus mirabilis, Citrobacter freundii, Proteus vulgaris, Klebsiella pneumoniae, Klebsiella ozaenae, Morganella morganii, Enterobacter cloacae and Edwardsiella tarda. Out of the 51 E. coli isolated, two were positive for the elt gene and one was positive for the CVD432 sequence, features of enterotoxigenic and enteroaggregative strains, respectively. This study reveals that the PCM is contaminated by enterobacteria and diarrheagenic E.coli thus providing evidence regarding the risk of these bacteria being carried by ships to other countries, and draws attention to the input of fecal bacteria brought by ships in the port waters of Maranhão. PMID:25477930

Digital Transplantation Pathology: Combining Whole Slide Imaging, Multiplex Staining, and Automated Image Analysis

PubMed Central

Isse, Kumiko; Lesniak, Andrew; Grama, Kedar; Roysam, Badrinath; Minervini, Martha I.; Demetris, Anthony J

2013-01-01

Conventional histopathology is the gold standard for allograft monitoring, but its value proposition is increasingly questioned. “-Omics” analysis of tissues, peripheral blood and fluids and targeted serologic studies provide mechanistic insights into allograft injury not currently provided by conventional histology. Microscopic biopsy analysis, however, provides valuable and unique information: a) spatial-temporal relationships; b) rare events/cells; c) complex structural context; and d) integration into a “systems” model. Nevertheless, except for immunostaining, no transformative advancements have “modernized” routine microscopy in over 100 years. Pathologists now team with hardware and software engineers to exploit remarkable developments in digital imaging, nanoparticle multiplex staining, and computational image analysis software to bridge the traditional histology - global “–omic” analyses gap. Included are side-by-side comparisons, objective biopsy finding quantification, multiplexing, automated image analysis, and electronic data and resource sharing. Current utilization for teaching, quality assurance, conferencing, consultations, research and clinical trials is evolving toward implementation for low-volume, high-complexity clinical services like transplantation pathology. Cost, complexities of implementation, fluid/evolving standards, and unsettled medical/legal and regulatory issues remain as challenges. Regardless, challenges will be overcome and these technologies will enable transplant pathologists to increase information extraction from tissue specimens and contribute to cross-platform biomarker discovery for improved outcomes. PMID:22053785

Toward an in-situ analytics and diagnostics framework for earth system models

NASA Astrophysics Data System (ADS)

Anantharaj, Valentine; Wolf, Matthew; Rasch, Philip; Klasky, Scott; Williams, Dean; Jacob, Rob; Ma, Po-Lun; Kuo, Kwo-Sen

2017-04-01

The development roadmaps for many earth system models (ESM) aim for a globally cloud-resolving model targeting the pre-exascale and exascale systems of the future. The ESMs will also incorporate more complex physics, chemistry and biology - thereby vastly increasing the fidelity of the information content simulated by the model. We will then be faced with an unprecedented volume of simulation output that would need to be processed and analyzed concurrently in order to derive the valuable scientific results. We are already at this threshold with our current generation of ESMs at higher resolution simulations. Currently, the nominal I/O throughput in the Community Earth System Model (CESM) via Parallel IO (PIO) library is around 100 MB/s. If we look at the high frequency I/O requirements, it would require an additional 1 GB / simulated hour, translating to roughly 4 mins wallclock / simulated-day => 24.33 wallclock hours / simulated-model-year => 1,752,000 core-hours of charge per simulated-model-year on the Titan supercomputer at the Oak Ridge Leadership Computing Facility. There is also a pending need for 3X more volume of simulation output . Meanwhile, many ESMs use instrument simulators to run forward models to compare model simulations against satellite and ground-based instruments, such as radars and radiometers. The CFMIP Observation Simulator Package (COSP) is used in CESM as well as the Accelerated Climate Model for Energy (ACME), one of the ESMs specifically targeting current and emerging leadership-class computing platforms These simulators can be computationally expensive, accounting for as much as 30% of the computational cost. Hence the data are often written to output files that are then used for offline calculations. Again, the I/O bottleneck becomes a limitation. Detection and attribution studies also use large volume of data for pattern recognition and feature extraction to analyze weather and climate phenomenon such as tropical cyclones, atmospheric rivers, blizzards, etc. It is evident that ESMs need an in-situ framework to decouple the diagnostics and analytics from the prognostics and physics computations of the models so that the diagnostic computations could be performed concurrently without limiting model throughput. We are designing a science-driven online analytics framework for earth system models. Our approach is to adopt several data workflow technologies, such as the Adaptable IO System (ADIOS), being developed under the U.S. Exascale Computing Project (ECP) and integrate these to allow for extreme performance IO, in situ workflow integration, science-driven analytics and visualization all in a easy to use computational framework. This will allow science teams to write data 100-1000 times faster and seamlessly move from post processing the output for validation and verification purposes to performing these calculations in situ. We can easily and knowledgeably envision a near-term future where earth system models like ACME and CESM will have to address not only the challenges of the volume of data but also need to consider the velocity of the data. The earth system model of the future in the exascale era, as they incorporate more complex physics at higher resolutions, will be able to analyze more simulation content without having to compromise targeted model throughput.

Three-dimensional conformal versus non-graphic radiation treatment planning for apocrine gland adenocarcinoma of the anal sac in 18 dogs (2002-2007).

PubMed

Keyerleber, M A; Gieger, T L; Erb, H N; Thompson, M S; McEntee, M C

2012-12-01

Differences in dose homogeneity and irradiated volumes of target and surrounding normal tissues between 3D conformal radiation treatment planning and simulated non-graphic manual treatment planning were evaluated in 18 dogs with apocrine gland adenocarcinoma of the anal sac. Overall, 3D conformal treatment planning resulted in more homogenous dose distribution to target tissues with lower hot spots and dose ranges. Dose homogeneity and guarantee of not under-dosing target tissues with 3D conformal planning came at the cost, however, of delivering greater mean doses of radiation and of irradiating greater volumes of surrounding normal tissue structures. © 2011 Blackwell Publishing Ltd.

Agronomic performance of Populus deltoides trees engineered for biofuel production

DOE PAGES

Macaya-Sanz, David; Chen, Jin?Gui; Kalluri, Udaya C.; ...

2017-11-30

Background: One of the major barriers to the development of lignocellulosic feedstocks is the recalcitrance of plant cell walls to deconstruction and saccharification. Recalcitrance can be reduced by targeting genes involved in cell wall biosynthesis, but this can have unintended consequences that compromise the agronomic performance of the trees under field conditions. Here we report the results of a field trial of fourteen distinct transgenic Populus deltoides lines that had previously demonstrated reduced recalcitrance without yield penalties under greenhouse conditions.Results: Survival and productivity of the trial were excellent in the first year, and there was little evidence for reduced performancemore » of the transgenic lines with modified target gene expression. Surprisingly, the most striking phenotypic effects in this trial were for two empty-vector control lines that had modified bud set and bud flush. This is most likely due to somaclonal variation or insertional mutagenesis. Traits related to yield, crown architecture, herbivory, pathogen response, and frost damage showed few significant differences between target gene transgenics and empty vector controls. However, there were a few interesting exceptions. Lines overexpressing the DUF231 gene, a putative O-acetyltransferase, showed early bud flush and marginally increased height growth. Lines overexpressing the DUF266 gene, a putative glycosyltransferase, had significantly decreased stem internode length and slightly higher volume index. Finally, lines overexpressing the PFD2 gene, a putative member of the prefoldin complex, had a slightly reduced volume index.Conclusions: This field trial demonstrates that these cell wall modifications, which decreased cell wall recalcitrance under laboratory conditions, did not seriously compromise first-year performance in the field, despite substantial challenges, including an outbreak of a stem boring insect (Gypsonoma haimbachiana), attack by a leaf rust pathogen (Melampsora spp.), and a late frost event. This bodes well for the potential utility of these lines as advanced biofuels feedstocks.« less

Agronomic performance of Populus deltoides trees engineered for biofuel production

DOE Office of Scientific and Technical Information (OSTI.GOV)

Macaya-Sanz, David; Chen, Jin?Gui; Kalluri, Udaya C.

Background: One of the major barriers to the development of lignocellulosic feedstocks is the recalcitrance of plant cell walls to deconstruction and saccharification. Recalcitrance can be reduced by targeting genes involved in cell wall biosynthesis, but this can have unintended consequences that compromise the agronomic performance of the trees under field conditions. Here we report the results of a field trial of fourteen distinct transgenic Populus deltoides lines that had previously demonstrated reduced recalcitrance without yield penalties under greenhouse conditions.Results: Survival and productivity of the trial were excellent in the first year, and there was little evidence for reduced performancemore » of the transgenic lines with modified target gene expression. Surprisingly, the most striking phenotypic effects in this trial were for two empty-vector control lines that had modified bud set and bud flush. This is most likely due to somaclonal variation or insertional mutagenesis. Traits related to yield, crown architecture, herbivory, pathogen response, and frost damage showed few significant differences between target gene transgenics and empty vector controls. However, there were a few interesting exceptions. Lines overexpressing the DUF231 gene, a putative O-acetyltransferase, showed early bud flush and marginally increased height growth. Lines overexpressing the DUF266 gene, a putative glycosyltransferase, had significantly decreased stem internode length and slightly higher volume index. Finally, lines overexpressing the PFD2 gene, a putative member of the prefoldin complex, had a slightly reduced volume index.Conclusions: This field trial demonstrates that these cell wall modifications, which decreased cell wall recalcitrance under laboratory conditions, did not seriously compromise first-year performance in the field, despite substantial challenges, including an outbreak of a stem boring insect (Gypsonoma haimbachiana), attack by a leaf rust pathogen (Melampsora spp.), and a late frost event. This bodes well for the potential utility of these lines as advanced biofuels feedstocks.« less

Transorbital target localization in the porcine model

NASA Astrophysics Data System (ADS)

DeLisi, Michael P.; Mawn, Louise A.; Galloway, Robert L.

2013-03-01

Current pharmacological therapies for the treatment of chronic optic neuropathies such as glaucoma are often inadequate due to their inability to directly affect the optic nerve and prevent neuron death. While drugs that target the neurons have been developed, existing methods of administration are not capable of delivering an effective dose of medication along the entire length of the nerve. We have developed an image-guided system that utilizes a magnetically tracked flexible endoscope to navigate to the back of the eye and administer therapy directly to the optic nerve. We demonstrate the capabilities of this system with a series of targeted surgical interventions in the orbits of live pigs. Target objects consisted of NMR microspherical bulbs with a volume of 18 μL filled with either water or diluted gadolinium-based contrast, and prepared with either the presence or absence of a visible coloring agent. A total of 6 pigs were placed under general anesthesia and two microspheres of differing color and contrast content were blindly implanted in the fat tissue of each orbit. The pigs were scanned with T1-weighted MRI, image volumes were registered, and the microsphere containing gadolinium contrast was designated as the target. The surgeon was required to navigate the flexible endoscope to the target and identify it by color. For the last three pigs, a 2D/3D registration was performed such that the target's coordinates in the image volume was noted and its location on the video stream was displayed with a crosshair to aid in navigation. The surgeon was able to correctly identify the target by color, with an average intervention time of 20 minutes for the first three pigs and 3 minutes for the last three.

The potential advantages of (18)FDG PET/CT-based target volume delineation in radiotherapy planning of head and neck cancer.

PubMed

Moule, Russell N; Kayani, Irfan; Moinuddin, Syed A; Meer, Khalda; Lemon, Catherine; Goodchild, Kathleen; Saunders, Michele I

2010-11-01

This study investigated two fixed threshold methods to delineate the target volume using (18)FDG PET/CT before and during a course of radical radiotherapy in locally advanced squamous cell carcinoma of the head and neck. Patients were enrolled into the study between March 2006 and May 2008. (18)FDG PET/CT scans were carried out 72h prior to the start of radiotherapy and then at 10, 44 and 66Gy. Functional volumes were delineated according to the SUV Cut Off (SUVCO) (2.5, 3.0, 3.5, and 4.0bwg/ml) and percentage of the SUVmax (30%, 35%, 40%, 45%, and 50%) thresholds. The background (18)FDG uptake and the SUVmax within the volumes were also assessed. Primary and lymph node volumes for the eight patients significantly reduced with each increase in the delineation threshold (for example 2.5-3.0bwg/ml SUVCO) compared to the baseline threshold at each imaging point. There was a significant reduction in the volume (p⩽0.0001-0.01) after 36Gy compared to the 0Gy by the SUVCO method. There was a negative correlation between the SUVmax within the primary and lymph node volumes and delivered radiation dose (p⩽0.0001-0.011) but no difference in the SUV within the background reference region. The volumes delineated by the PTSUVmax method increased with the increase in the delivered radiation dose after 36Gy because the SUVmax within the region of interest used to define the edge of the volume was equal or less than the background (18)FDG uptake and the software was unable to effectively differentiate between tumour and background uptake. The changes in the target volumes delineated by the SUVCO method were less susceptible to background (18)FDG uptake compared to those delineated by the PTSUVmax and may be more helpful in radiotherapy planning. The best method and threshold have still to be determined within institutions, both nationally and internationally. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Operating rules for multireservoir systems

NASA Astrophysics Data System (ADS)

Oliveira, Rodrigo; Loucks, Daniel P.

1997-04-01

Multireservoir operating policies are usually defined by rules that specify either individual reservoir desired (target) storage volumes or desired (target) releases based on the time of year and the existing total storage volume in all reservoirs. This paper focuses on the use of genetic search algorithms to derive these multireservoir operating policies. The genetic algorithms use real-valued vectors containing information needed to define both system release and individual reservoir storage volume targets as functions of total storage in each of multiple within-year periods. Elitism, arithmetic crossover, mutation, and "en bloc" replacement are used in the algorithms to generate successive sets of possible operating policies. Each policy is then evaluated using simulation to compute a performance index for a given flow series. The better performing policies are then used as a basis for generating new sets of possible policies. The process of improved policy generation and evaluation is repeated until no further improvement in performance is obtained. The proposed algorithm is applied to example reservoir systems used for water supply and hydropower.

Impact of gastric filling on radiation dose delivered to gastroesophageal junction tumors.

PubMed

Bouchard, Myriam; McAleer, Mary Frances; Starkschall, George

2010-05-01

This study examined the impact of gastric filling variation on target coverage of gastroesophageal junction (GEJ) tumors in three-dimensional conformal radiation therapy (3DCRT), intensity-modulated radiation therapy (IMRT), or IMRT with simultaneous integrated boost (IMRT-SIB) plans. Eight patients previously receiving radiation therapy for esophageal cancer had computed tomography (CT) datasets acquired with full stomach (FS) and empty stomach (ES). We generated treatment plans for 3DCRT, IMRT, or IMRT-SIB for each patient on the ES-CT and on the FS-CT datasets. The 3DCRT and IMRT plans were planned to 50.4 Gy to the clinical target volume (CTV), and the same for IMRT-SIB plus 63.0 Gy to the gross tumor volume (GTV). Target coverage was evaluated using dose-volume histogram data for patient treatments simulated with ES-CT sets, assuming treatment on an FS for the entire course, and vice versa. FS volumes were a mean of 3.3 (range, 1.7-7.5) times greater than ES volumes. The volume of the GTV receiving >or=50.4 Gy (V(50.4Gy)) was 100% in all situations. The planning GTV V(63Gy) became suboptimal when gastric filling varied, regardless of whether simulation was done on the ES-CT or the FS-CT set. Stomach filling has a negligible impact on prescribed dose delivered to the GEJ GTV, using either 3DCRT or IMRT planning. Thus, local relapses are not likely to be related to variations in gastric filling. Dose escalation for GEJ tumors with IMRT-SIB may require gastric filling monitoring.

Space Station Facility government estimating

NASA Technical Reports Server (NTRS)

Brown, Joseph A.

1993-01-01

This new, unique Cost Engineering Report introduces the 800-page, C-100 government estimate for the Space Station Processing Facility (SSPF) and Volume IV Aerospace Construction Price Book. At the January 23, 1991, bid opening for the SSPF, the government cost estimate was right on target. Metric, Inc., Prime Contractor, low bid was 1.2 percent below the government estimate. This project contains many different and complex systems. Volume IV is a summary of the cost associated with construction, activation and Ground Support Equipment (GSE) design, estimating, fabrication, installation, testing, termination, and verification of this project. Included are 13 reasons the government estimate was so accurate; abstract of bids, for 8 bidders and government estimate with additive alternates, special labor and materials, budget comparison and system summaries; and comments on the energy credit from local electrical utility. This report adds another project to our continuing study of 'How Does the Low Bidder Get Low and Make Money?' which was started in 1967, and first published in the 1973 AACE Transaction with 18 ways the low bidders get low. The accuracy of this estimate proves the benefits of our Kennedy Space Center (KSC) teamwork efforts and KSC Cost Engineer Tools which are contributing toward our goals of the Space Station.

Monitoring of In-Situ Remediation By Time Lapse 3D Geo-Electric Measurements

NASA Astrophysics Data System (ADS)

Kanli, A. I.; Tildy, P.; Neducza, B.; Nagy, P.; Hegymegi, C.

2017-12-01

Injection of chemical oxidant solution to degrade the subsurface contaminants can be used for hydrocarbon contamination remediation. In this study, we developed a non-destructive measurement strategy to monitor oxidative in-situ remediation processes. The difficulties of the presented study originate from the small volume of conductive solution that can be used due to environmental considerations. Due to the effect of conductive groundwater and the high clay content of the targeted layer and the small volume of conductive solution that can be used due to environmental considerations, a site specific synthetic modelling is necessary for measurement design involving the results of preliminary 2D ERT measurements, electrical conductivity measurements of different active agents and expected resistivity changes calculated by soil resistivity modelling. Because of chemical biodegradation, the results of soil resistivity modelling have suggested that the reagent have complex effects on contaminated soils. As a result the plume of resistivity changes caused by the injected agent was determined showing strong fracturing effect because of the high pressure of injection. 3D time-lapse geo-electric measurements were proven to provide a usable monitoring tool for in-situ remediation as a result of our sophisticated tests and synthetic modelling.

Monte Carlo evaluation of Acuros XB dose calculation Algorithm for intensity modulated radiation therapy of nasopharyngeal carcinoma

NASA Astrophysics Data System (ADS)

Yeh, Peter C. Y.; Lee, C. C.; Chao, T. C.; Tung, C. J.

2017-11-01

Intensity-modulated radiation therapy is an effective treatment modality for the nasopharyngeal carcinoma. One important aspect of this cancer treatment is the need to have an accurate dose algorithm dealing with the complex air/bone/tissue interface in the head-neck region to achieve the cure without radiation-induced toxicities. The Acuros XB algorithm explicitly solves the linear Boltzmann transport equation in voxelized volumes to account for the tissue heterogeneities such as lungs, bone, air, and soft tissues in the treatment field receiving radiotherapy. With the single beam setup in phantoms, this algorithm has already been demonstrated to achieve the comparable accuracy with Monte Carlo simulations. In the present study, five nasopharyngeal carcinoma patients treated with the intensity-modulated radiation therapy were examined for their dose distributions calculated using the Acuros XB in the planning target volume and the organ-at-risk. Corresponding results of Monte Carlo simulations were computed from the electronic portal image data and the BEAMnrc/DOSXYZnrc code. Analysis of dose distributions in terms of the clinical indices indicated that the Acuros XB was in comparable accuracy with Monte Carlo simulations and better than the anisotropic analytical algorithm for dose calculations in real patients.

Dose escalation to high-risk sub-volumes based on non-invasive imaging of hypoxia and glycolytic activity in canine solid tumors: a feasibility study

PubMed Central

2013-01-01

Introduction Glycolytic activity and hypoxia are associated with poor prognosis and radiation resistance. Including both the tumor uptake of 2-deoxy-2-[18 F]-fluorodeoxyglucose (FDG) and the proposed hypoxia tracer copper(II)diacetyl-bis(N4)-methylsemithio-carbazone (Cu-ATSM) in targeted therapy planning may therefore lead to improved tumor control. In this study we analyzed the overlap between sub-volumes of FDG and hypoxia assessed by the uptake of 64Cu-ATSM in canine solid tumors, and evaluated the possibilities for dose redistribution within the gross tumor volume (GTV). Materials and methods Positron emission tomography/computed tomography (PET/CT) scans of five spontaneous canine solid tumors were included. FDG-PET/CT was obtained at day 1, 64Cu-ATSM at day 2 and 3 (3 and 24 h pi.). GTV was delineated and CT images were co-registered. Sub-volumes for 3 h and 24 h 64Cu-ATSM (Cu3 and Cu24) were defined by a threshold based method. FDG sub-volumes were delineated at 40% (FDG40) and 50% (FDG50) of SUVmax. The size of sub-volumes, intersection and biological target volume (BTV) were measured in a treatment planning software. By varying the average dose prescription to the tumor from 66 to 85 Gy, the possible dose boost (D B ) was calculated for the three scenarios that the optimal target for the boost was one, the union or the intersection of the FDG and 64Cu-ATSM sub-volumes. Results The potential boost volumes represented a fairly large fraction of the total GTV: Cu3 49.8% (26.8-72.5%), Cu24 28.1% (2.4-54.3%), FDG40 45.2% (10.1-75.2%), and FDG50 32.5% (2.6-68.1%). A BTV including the union (∪) of Cu3 and FDG would involve boosting to a larger fraction of the GTV, in the case of Cu3∪FDG40 63.5% (51.8-83.8) and Cu3∪FDG50 48.1% (43.7-80.8). The union allowed only a very limited D B whereas the intersection allowed a substantial dose escalation. Conclusions FDG and 64Cu-ATSM sub-volumes were only partly overlapping, suggesting that the tracers offer complementing information on tumor physiology. Targeting the combined PET positive volume (BTV) for dose escalation within the GTV results in a limited D B . This suggests a more refined dose redistribution based on a weighted combination of the PET tracers in order to obtain an improved tumor control. PMID:24199939

Small Intracranial Aneurysm Treatment Using Target (®) Ultrasoft (™) Coils.

PubMed

Jindal, Gaurav; Miller, Timothy; Iyohe, Moronke; Shivashankar, Ravi; Prasad, Vikram; Gandhi, Dheeraj

2016-06-01

The introduction of small, soft, complex-shaped microcoils has helped facilitate the endovascular treatment of small intracranial aneurysms (IAs) over the last several years. Here, we evaluate the initial safety and efficacy of treating small IAs using only Target(®) Ultrasoft(™) coils. A retrospective review of a prospectively maintained clinical database at a single, high volume, teaching hospital was performed from September 2011 to May 2015. IAs smaller than or equal to 5.0 mm in maximal dimension treated with only Target(®) Ultrasoft(™) coils were included. A total of 50 patients with 50 intracranial aneurysms were included. Subarachnoid hemorrhage from index aneurysm rupture was the indication for treatment in 23 of 50 (46%) cases, and prior subarachnoid hemorrhage (SAH) from another aneurysm was the indication for treatment in eight of 50 (16%) cases. The complete aneurysm occlusion rate was 70% (35/50), the minimal residual aneurysm rate was 14% (7/50), and residual aneurysm rate was 16% (8/50). One intraoperative aneurysm rupture occurred. Three patients died during hospitalization from clinical sequelae of subarachnoid hemorrhage. Follow-up at a mean of 13.6 months demonstrated complete aneurysm occlusion in 75% (30/40) of cases, near complete occlusion in 15% (6/40) of cases, and residual aneurysm in 10% (4/40) of cases, all four of which were retreated. Our initial results using only Target(®) Ultrasoft(™) coils for the endovascular treatment of small intracranial aneurysms demonstrate initial excellent safety and efficacy profiles.

Carbon Capture Multidisciplinary Simulation Center Trilab Support Team (TST) Fall Meeting 2016 Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Draeger, Erik W.

The theme of this year’s meeting was “Predictivity: Now and in the Future”. After welcoming remarks, Erik Draeger gave a talk on the NNSA Labs’ history of predictive simulation and the new challenges faced by upcoming architecture changes. He described an example where the volume of analysis data produced by a set of inertial confinement fusion (ICF) simulations on the Trinity machine was too large to store or transfer, and the steps needed to reduce it to a manageable size. He also described the software re-engineering plan for LLNL’s suite of multiphysics codes and physics packages with a new pushmore » toward common components, making collaboration with teams like the CCMSC who already have experience trying to architect complex multiphysics code infrastructure on next-generation architectures all the more important. Phil Smith then gave an overview outlining the goals of the project, namely to accelerate development of new technology in the form of high efficiency carbon capture pulverized coal power generation as well as further optimize existing state of the art designs. He then presented a summary of the Center’s top-down uncertainty quantification approach, in which ultimate target predictivity informs uncertainty targets for lower-level components, and gave data on how close all the different components currently are to their targets. Most components still need an approximately two-fold reduction in uncertainty to hit the ultimate predictivity target, but the current accuracy is already rather impressive.« less

Compiler writing system detail design specification. Volume 1: Language specification

NASA Technical Reports Server (NTRS)

Arthur, W. J.

1974-01-01

Construction within the Meta language for both language and target machine specification is reported. The elements of the function language as a meaning and syntax are presented, and the structure of the target language is described which represents the target dependent object text representation of applications programs.

SINGLE INSTITUTION VARIABILITY IN INTENSITY MODULATED RADIATION TARGET DELINEATION FOR CANINE NASAL NEOPLASIA.

PubMed

Christensen, Neil I; Forrest, Lisa J; White, Pamela J; Henzler, Margaret; Turek, Michelle M

2016-11-01

Contouring variability is a significant barrier to the accurate delivery and reporting of radiation therapy. The aim of this descriptive study was to determine the variation in contouring radiation targets and organs at risk by participants within our institution. Further, we also aimed to determine if all individuals contoured the same normal tissues. Two canine nasal tumor datasets were selected and contoured by two ACVR-certified radiation oncologists and two radiation oncology residents from the same institution. Eight structures were consistently contoured including the right and left eye, the right and left lens, brain, the gross tumor volume (GTV), clinical target volume (CTV), and planning target volume (PTV). Spinal cord, hard and soft palate, and bulla were contoured on 50% of datasets. Variation in contouring occurred in both targets and normal tissues at risk and was particularly significant for the GTV, CTV, and PTV. The mean metric score and dice similarity coefficient were below the threshold criteria in 37.5-50% and 12.5-50% of structures, respectively, quantitatively indicating contouring variation. This study refutes our hypothesis that minimal variation in target and normal tissue delineation occurs. The variation in contouring may contribute to different tumor response and toxicity for any given patient. Our results also highlight the difficulty associated with replication of published radiation protocols or treatments, as even with replete contouring description the outcome of treatment is still fundamentally influenced by the individual contouring the patient. © 2016 American College of Veterinary Radiology.

Dosimetric comparison of IMRT rectal and anal canal plans generated using an anterior dose avoidance structure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leicher, Brian, E-mail: bleicher@wpahs.org; Day, Ellen; Colonias, Athanasios

2014-10-01

To describe a dosimetric method using an anterior dose avoidance structure (ADAS) during the treatment planning process for intensity-modulated radiation therapy (IMRT) for patients with anal canal and rectal carcinomas. A total of 20 patients were planned on the Elekta/CMS XiO treatment planning system, version 4.5.1 (Maryland Heights MO) with a superposition algorithm. For each patient, 2 plans were created: one employing an ADAS (ADAS plan) and the other replanned without an ADAS (non-ADAS plan). The ADAS was defined to occupy the volume between the inguinal nodes and primary target providing a single organ at risk that is completely outsidemore » of the target volume. Each plan used the same beam parameters and was analyzed by comparing target coverage, overall plan dose conformity using a conformity number (CN) equation, bowel dose-volume histograms, and the number of segments, daily treatment duration, and global maximum dose. The ADAS and non-ADAS plans were equivalent in target coverage, mean global maximum dose, and sparing of small bowel in low-dose regions (5, 10, 15, and 20 Gy). The mean difference between the CN value for the non-ADAS plans and ADAS plans was 0.04 ± 0.03 (p < 0.001). The mean difference in the number of segments was 15.7 ± 12.7 (p < 0.001) in favor of ADAS plans. The ADAS plan delivery time was shorter by 2.0 ± 1.5 minutes (p < 0.001) than the non-ADAS one. The ADAS has proven to be a powerful tool when planning rectal and anal canal IMRT cases with critical structures partially contained inside the target volume.« less

Impact of pelvic nodal irradiation with intensity-modulated radiotherapy on treatment of prostate cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Price, Robert A.; Hannoun-Levi, Jean-Michel; Horwitz, Eric

2006-10-01

Purpose: The aim of this study was to evaluate the feasibility of treating the pelvic lymphatic regions during prostate intensity-modulated radiotherapy (IMRT) with respect to our routine acceptance criteria. Methods and Materials: A series of 10 previously treated prostate patients were randomly selected and the pelvic lymphatic regions delineated on the fused magnetic resonance/computed tomography data sets. A targeting progression was formed from the prostate and proximal seminal vesicles only to the inclusion of all pelvic lymphatic regions and presacral region resulting in 5 planning scenarios of increasing geometric difficulty. IMRT plans were generated for each stage for two acceleratormore » manufacturers. Dose volume histogram data were analyzed with respect to dose to the planning target volumes, rectum, bladder, bowel, and normal tissue. Analysis was performed for the number of segments required, monitor units, 'hot spots,' and treatment time. Results: Both rectal endpoints were met for all targets. Bladder endpoints were not met and the bowel endpoint was met in 40% of cases with the inclusion of the extended and presacral lymphatics. A significant difference was found in the number of segments and monitor units with targeting progression and between accelerators, with the smaller beamlets yielding poorer results. Treatment times between the 2 linacs did not exhibit a clinically significant difference when compared. Conclusions: Many issues should be considered with pelvic lymphatic irradiation during IMRT delivery for prostate cancer including dose per fraction, normal structure dose/volume limits, planning target volumes generation, localization, treatment time, and increased radiation leakage. We would suggest that, at a minimum, the endpoints used in this work be evaluated before beginning IMRT pelvic nodal irradiation.« less

Estimation of Error in Maximal Intensity Projection-Based Internal Target Volume of Lung Tumors: A Simulation and Comparison Study Using Dynamic Magnetic Resonance Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cai Jing; Read, Paul W.; Baisden, Joseph M.

Purpose: To evaluate the error in four-dimensional computed tomography (4D-CT) maximal intensity projection (MIP)-based lung tumor internal target volume determination using a simulation method based on dynamic magnetic resonance imaging (dMRI). Methods and Materials: Eight healthy volunteers and six lung tumor patients underwent a 5-min MRI scan in the sagittal plane to acquire dynamic images of lung motion. A MATLAB program was written to generate re-sorted dMRI using 4D-CT acquisition methods (RedCAM) by segmenting and rebinning the MRI scans. The maximal intensity projection images were generated from RedCAM and dMRI, and the errors in the MIP-based internal target area (ITA)more » from RedCAM ({epsilon}), compared with those from dMRI, were determined and correlated with the subjects' respiratory variability ({nu}). Results: Maximal intensity projection-based ITAs from RedCAM were comparatively smaller than those from dMRI in both phantom studies ({epsilon} = -21.64% {+-} 8.23%) and lung tumor patient studies ({epsilon} = -20.31% {+-} 11.36%). The errors in MIP-based ITA from RedCAM correlated linearly ({epsilon} = -5.13{nu} - 6.71, r{sup 2} = 0.76) with the subjects' respiratory variability. Conclusions: Because of the low temporal resolution and retrospective re-sorting, 4D-CT might not accurately depict the excursion of a moving tumor. Using a 4D-CT MIP image to define the internal target volume might therefore cause underdosing and an increased risk of subsequent treatment failure. Patient-specific respiratory variability might also be a useful predictor of the 4D-CT-induced error in MIP-based internal target volume determination.« less

Estimation of error in maximal intensity projection-based internal target volume of lung tumors: a simulation and comparison study using dynamic magnetic resonance imaging.

PubMed

Cai, Jing; Read, Paul W; Baisden, Joseph M; Larner, James M; Benedict, Stanley H; Sheng, Ke

2007-11-01

To evaluate the error in four-dimensional computed tomography (4D-CT) maximal intensity projection (MIP)-based lung tumor internal target volume determination using a simulation method based on dynamic magnetic resonance imaging (dMRI). Eight healthy volunteers and six lung tumor patients underwent a 5-min MRI scan in the sagittal plane to acquire dynamic images of lung motion. A MATLAB program was written to generate re-sorted dMRI using 4D-CT acquisition methods (RedCAM) by segmenting and rebinning the MRI scans. The maximal intensity projection images were generated from RedCAM and dMRI, and the errors in the MIP-based internal target area (ITA) from RedCAM (epsilon), compared with those from dMRI, were determined and correlated with the subjects' respiratory variability (nu). Maximal intensity projection-based ITAs from RedCAM were comparatively smaller than those from dMRI in both phantom studies (epsilon = -21.64% +/- 8.23%) and lung tumor patient studies (epsilon = -20.31% +/- 11.36%). The errors in MIP-based ITA from RedCAM correlated linearly (epsilon = -5.13nu - 6.71, r(2) = 0.76) with the subjects' respiratory variability. Because of the low temporal resolution and retrospective re-sorting, 4D-CT might not accurately depict the excursion of a moving tumor. Using a 4D-CT MIP image to define the internal target volume might therefore cause underdosing and an increased risk of subsequent treatment failure. Patient-specific respiratory variability might also be a useful predictor of the 4D-CT-induced error in MIP-based internal target volume determination.

Treatment plan comparison between Tri-Co-60 magnetic-resonance image-guided radiation therapy and volumetric modulated arc therapy for prostate cancer

PubMed Central

Park, Jong Min; Park, So-Yeon; Choi, Chang Heon; Chun, Minsoo; Kim, Jin Ho; Kim, Jung-In

2017-01-01

To investigate the plan quality of tri-Co-60 intensity-modulated radiation therapy (IMRT) with magnetic-resonance image-guided radiation therapy compared with volumetric-modulated arc therapy (VMAT) for prostate cancer. Twenty patients with intermediate-risk prostate cancer, who received radical VMAT were selected. Additional tri-Co-60 IMRT plans were generated for each patient. Both primary and boost plans were generated with tri-Co-60 IMRT and VMAT techniques. The prescription doses of the primary and boost plans were 50.4 Gy and 30.6 Gy, respectively. The primary and boost planning target volumes (PTVs) of the tri-Co-60 IMRT were generated with 3 mm margins from the primary clinical target volume (CTV, prostate + seminal vesicle) and a boost CTV (prostate), respectively. VMAT had a primary planning target volume (primary CTV + 1 cm or 2 cm margins) and a boost PTV (boost CTV + 0.7 cm margins), respectively. For both tri-Co-60 IMRT and VMAT, all the primary and boost plans were generated that 95% of the target volumes would be covered by the 100% of the prescription doses. Sum plans were generated by summation of primary and boost plans. In sum plans, the average values of V70 Gy of the bladder of tri-Co-60 IMRT vs. VMAT were 4.0% ± 3.1% vs. 10.9% ± 6.7%, (p < 0.001). Average values of V70 Gy of the rectum of tri-Co-60 IMRT vs. VMAT were 5.2% ± 1.8% vs. 19.1% ± 4.0% (p < 0.001). The doses of tri-Co-60 IMRT delivered to the bladder and rectum were smaller than those of VMAT while maintaining identical target coverage in both plans. PMID:29207634

Validation of a 4D-PET Maximum Intensity Projection for Delineation of an Internal Target Volume

DOE Office of Scientific and Technical Information (OSTI.GOV)

Callahan, Jason, E-mail: jason.callahan@petermac.org; Kron, Tomas; Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne

2013-07-15

Purpose: The delineation of internal target volumes (ITVs) in radiation therapy of lung tumors is currently performed by use of either free-breathing (FB) {sup 18}F-fluorodeoxyglucose-positron emission tomography-computed tomography (FDG-PET/CT) or 4-dimensional (4D)-CT maximum intensity projection (MIP). In this report we validate the use of 4D-PET-MIP for the delineation of target volumes in both a phantom and in patients. Methods and Materials: A phantom with 3 hollow spheres was prepared surrounded by air then water. The spheres and water background were filled with a mixture of {sup 18}F and radiographic contrast medium. A 4D-PET/CT scan was performed of the phantom whilemore » moving in 4 different breathing patterns using a programmable motion device. Nine patients with an FDG-avid lung tumor who underwent FB and 4D-PET/CT and >5 mm of tumor motion were included for analysis. The 3 spheres and patient lesions were contoured by 2 contouring methods (40% of maximum and PET edge) on the FB-PET, FB-CT, 4D-PET, 4D-PET-MIP, and 4D-CT-MIP. The concordance between the different contoured volumes was calculated using a Dice coefficient (DC). The difference in lung tumor volumes between FB-PET and 4D-PET volumes was also measured. Results: The average DC in the phantom using 40% and PET edge, respectively, was lowest for FB-PET/CT (DCAir = 0.72/0.67, DCBackground 0.63/0.62) and highest for 4D-PET/CT-MIP (DCAir = 0.84/0.83, DCBackground = 0.78/0.73). The average DC in the 9 patients using 40% and PET edge, respectively, was also lowest for FB-PET/CT (DC = 0.45/0.44) and highest for 4D-PET/CT-MIP (DC = 0.72/0.73). In the 9 lesions, the target volumes of the FB-PET using 40% and PET edge, respectively, were on average 40% and 45% smaller than the 4D-PET-MIP. Conclusion: A 4D-PET-MIP produces volumes with the highest concordance with 4D-CT-MIP across multiple breathing patterns and lesion sizes in both a phantom and among patients. Freebreathing PET/CT consistently underestimates ITV when compared with 4D PET/CT for a lesion affected by respiration.« less

Evaluation of the Dosimetric Feasibility of Hippocampal Sparing Intensity-Modulated Radiotherapy in Patients with Locally Advanced Nasopharyngeal Carcinoma

PubMed Central

Gan, Hua; Denniston, Kyle A.; Li, Sicong; Tan, Wenyong; Wang, Zhaohua

2014-01-01

Purpose The objective of this study was to evaluate the dosimetric feasibility of using hippocampus (HPC) sparing intensity-modulated radiotherapy (IMRT) in patients with locally advanced nasopharyngeal carcinoma (NPC). Materials/Methods Eight cases of either T3 or T4 NPC were selected for this study. Standard IMRT treatment plans were constructed using the volume and dose constraints for the targets and organs at risk (OAR) per Radiation Therapy Oncology Group (RTOG) 0615 protocol. Experimental plans were constructed using the same criteria, with the addition of the HPC as an OAR. The two dose-volume histograms for each case were compared for the targets and OARs. Results All plans achieved the protocol dose criteria. The homogeneity index, conformity index, and coverage index for the planning target volumes (PTVs) were not significantly compromised by the avoidance of the HPC. The doses to all OARs, excluding the HPC, were similar. Both the dose (Dmax, D2%, D40%, Dmean, Dmedian, D98% and Dmin) and volume (V5, V10, V15, V20, V30, V40 and V50) parameters for the HPC were significantly lower in the HPC sparing plans (p<0.05), except for Dmin (P = 0.06) and V5 (P = 0.12). Conclusions IMRT for patients with locally advanced NPC exposes the HPC to a significant radiation dose. HPC sparing IMRT planning significantly decreases this dose, with minimal impact on the therapeutic targets and other OARs. PMID:24587184

A new approach to delineating lymph node target volumes for post-operative radiotherapy in gastric cancer: A phase II trial.

PubMed

Haijun, Yu; Qiuji, Wu; Zhenming, Fu; Yong, Huang; Zhengkai, Liao; Conghua, Xie; Yunfeng, Zhou; Yahua, Zhong

2015-08-01

In the context of gastric cancer, lymph node target volume delineation for post-operative radiotherapy is currently built on the traditional system of dividing the stomach and 2-D treatment methods. Here, we have proposed a new delineation approach with irradiation indications for lymph node stations. Its safety and efficacy were evaluated in a phase II clinical trial. Fifty-four gastric cancer patients with D2 lymph node dissection received 2 cycles of FOLFOX4. They subsequently received concurrent chemoradiotherapy (45 Gy at 1.8 Gy per fraction, 5 fractions per week for 5 weeks) with a 5-fluorouracil/leucovorin regimen, followed by 4 additional FOLFOX4 cycles. The target volume included the remnant stomach, anastomosis site, tumor bed, and regional lymph nodes selected through our new approach by taking gastric arteries as references. The most common grade 3-4 adverse event was neutropenia (14.8%). Neutropenia, anemia, and nausea were common grade 1-2 toxicities. No treatment-related deaths occurred during treatment. The 3-year overall, disease-free, and locoregional recurrence-free survival rates were 81.6%, 70.2%, and 91.1%, respectively. Eight patients developed peritoneal or distant metastases. Using our new approach and irradiation indications, delineation of the target volume of post-operative lymph node stations was feasible and well tolerated after D2 resection in patients with gastric cancer. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Neuropsychological Investigation of Motor Impairments in Autism

PubMed Central

Duffield, Tyler; Trontel, Haley; Bigler, Erin D.; Froehlich, Alyson; Prigge, Molly B.; Travers, Brittany; Green, Ryan R.; Cariello, Annahir N.; Cooperrider, Jason; Nielsen, Jared; Alexander, Andrew; Anderson, Jeffrey; Fletcher, P. Thomas; Lange, Nicholas; Zielinski, Brandon; Lainhart, Janet

2013-01-01

It is unclear how standardized neuropsychological measures of motor function relate to brain volumes of motor regions in autism spectrum disorder (ASD). An all male sample composed of 59 ASD and 30 controls (ages 5–33 years) completed three measures of motor function: strength of grip (SOG), finger tapping test (FTT), and grooved peg-board test (GPT). Likewise, all participants underwent magnetic resonance imaging with region of interest (ROI) volumes obtained to include the following regions: motor cortex (pre-central gyrus), somatosensory cortex (post-central gyrus), thalamus, basal ganglia, cerebellum and caudal middle frontal gyrus. These traditional neuropsychological measures of motor function are assumed to differ in motor complexity with GPT requiring the most followed by FTT and SOG. Performance by ASD participants on the GPT and FTT differed significantly from controls, with the largest effect size differences observed on the more complex GPT task. Differences on the SOG task between the two groups were non-significant. Since more complex motor tasks tap more complex networks, poorer GPT performance by those with ASD may reflect less efficient motor networks. There was no gross pathology observed in classic motor areas of the brain in ASD, as region of interest (ROI) volumes did not differ, but FTT was negatively related to motor cortex volume in ASD. The results suggest a hierarchical motor disruption in ASD, with difficulties evident only in more complex tasks as well as a potential anomalous size-function relation in motor cortex in ASD. PMID:23985036

Dosimetric Comparison of Bone Marrow-Sparing Intensity-Modulated Radiotherapy Versus Conventional Techniques for Treatment of Cervical Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mell, Loren K.; Tiryaki, Hanifi; Ahn, Kang-Hyun

2008-08-01

Purpose: To compare bone marrow-sparing intensity-modulated pelvic radiotherapy (BMS-IMRT) with conventional (four-field box and anteroposterior-posteroanterior [AP-PA]) techniques in the treatment of cervical cancer. Methods and Materials: The data from 7 cervical cancer patients treated with concurrent chemotherapy and IMRT without BMS were analyzed and compared with data using four-field box and AP-PA techniques. All plans were normalized to cover the planning target volume with the 99% isodose line. The clinical target volume consisted of the pelvic and presacral lymph nodes, uterus and cervix, upper vagina, and parametrial tissue. Normal tissues included bowel, bladder, and pelvic bone marrow (PBM), which comprisedmore » the lumbosacral spine and ilium and the ischium, pubis, and proximal femora (lower pelvis bone marrow). Dose-volume histograms for the planning target volume and normal tissues were compared for BMS-IMRT vs. four-field box and AP-PA plans. Results: BMS-IMRT was superior to the four-field box technique in reducing the dose to the PBM, small bowel, rectum, and bladder. Compared with AP-PA plans, BMS-IMRT reduced the PBM volume receiving a dose >16.4 Gy. BMS-IMRT reduced the volume of ilium, lower pelvis bone marrow, and bowel receiving a dose >27.7, >18.7, and >21.1 Gy, respectively, but increased dose below these thresholds compared with the AP-PA plans. BMS-IMRT reduced the volume of lumbosacral spine bone marrow, rectum, small bowel, and bladder at all dose levels in all 7 patients. Conclusion: BMS-IMRT reduced irradiation of PBM compared with the four-field box technique. Compared with the AP-PA technique, BMS-IMRT reduced lumbosacral spine bone marrow irradiation and reduced the volume of PBM irradiated to high doses. Therefore BMS-IMRT might reduce acute hematologic toxicity compared with conventional techniques.« less

MRI to delineate the gross tumor volume of nasopharyngeal cancers: which sequences and planes should be used?

PubMed

Popovtzer, Aron; Ibrahim, Mohannad; Tatro, Daniel; Feng, Felix Y; Ten Haken, Randall K; Eisbruch, Avraham

2014-09-01

Magnetic resonance imaging (MRI) has been found to be better than computed tomography for defining the extent of primary gross tumor volume (GTV) in advanced nasopharyngeal cancer. It is routinely applied for target delineation in planning radiotherapy. However, the specific MRI sequences/planes that should be used are unknown. Twelve patients with nasopharyngeal cancer underwent primary GTV evaluation with gadolinium-enhanced axial T1 weighted image (T1) and T2 weighted image (T2), coronal T1, and sagittal T1 sequences. Each sequence was registered with the planning computed tomography scans. Planning target volumes (PTVs) were derived by uniform expansions of the GTVs. The volumes encompassed by the various sequences/planes, and the volumes common to all sequences/planes, were compared quantitatively and anatomically to the volume delineated by the commonly used axial T1-based dataset. Addition of the axial T2 sequence increased the axial T1-based GTV by 12% on average (p = 0.004), and composite evaluations that included the coronal T1 and sagittal T1 planes increased the axial T1-based GTVs by 30% on average (p = 0.003). The axial T1-based PTVs were increased by 20% by the additional sequences (p = 0.04). Each sequence/plane added unique volume extensions. The GTVs common to all the T1 planes accounted for 38% of the total volumes of all the T1 planes. Anatomically, addition of the coronal and sagittal-based GTVs extended the axial T1-based GTV caudally and cranially, notably to the base of the skull. Adding MRI planes and sequences to the traditional axial T1 sequence yields significant quantitative and anatomically important extensions of the GTVs and PTVs. For accurate target delineation in nasopharyngeal cancer, we recommend that GTVs be outlined in all MRI sequences/planes and registered with the planning computed tomography scans.

Proposed Site Treatment Plan (PSTP). Volumes 1 and 2 and Reference Document

DOE Office of Scientific and Technical Information (OSTI.GOV)

Helmich, E.; Noller, D.K.; Wierzbicki, K.S.

1994-12-22

The Compliance Plan Volume provides overall schedules with target dates for achieving compliance with the land disposal restrictions (LDR) and contains procedures to establish milestones to be enforced under the Order. Information regarding the technical evaluation of treatment options for SRS mixed wastes is contained in the Background Volume and is provided for informational purposes only.

Draft Site Treatment Plan (DSTP), Volumes I and II

DOE Office of Scientific and Technical Information (OSTI.GOV)

D`Amelio, J.

1994-08-30

Site Treatment Plans (STP) are required for facilities at which the DOE generates or stores mixed waste. This Draft Site Treatment Plan (DSTP) the second step in a three-phase process, identifies the currently preferred options for treating mixed waste at the Savannah River Site (SRS) or for developing treatment technologies where technologies do not exist or need modification. The DSTP reflects site-specific preferred options, developed with the state`s input and based on existing available information. To the extent possible, the DSTP identifies specific treatment facilities for treating the mixed waste and proposes schedules. Where the selection of specific treatment facilitiesmore » is not possible, schedules for alternative activities such as waste characterization and technology assessment are provided. All schedule and cost information presented is preliminary and is subject to change. The DSTP is comprised of two volumes: this Compliance Plan Volume and the Background Volume. This Compliance Plan Volume proposes overall schedules with target dates for achieving compliance with the land disposal restrictions (LDR) of RCRA and procedures for converting the target dates into milestones to be enforced under the Order. The more detailed discussion of the options contained in the Background Volume is provided for informational purposes only.« less

Optical Imaging of Targeted β-Galactosidase in Brain Tumors to Detect EGFR Levels

PubMed Central

Broome, Ann-Marie; Ramamurthy, Gopal; Lavik, Kari; Liggett, Alexander; Kinstlinger, Ian; Basilion, James

2015-01-01

A current limitation in molecular imaging is that it often requires genetic manipulation of cancer cells for noninvasive imaging. Other methods to detect tumor cells in vivo using exogenously delivered and functionally active reporters, such as β-gal, are required. We report the development of a platform system for linking β-gal to any number of different ligands or antibodies for in vivo targeting to tissue or cells, without the requirement for genetic engineering of the target cells prior to imaging. Our studies demonstrate significant uptake in vitro and in vivo of an EGFR-targeted β-gal complex. We were then able to image orthotopic brain tumor accumulation and localization of the targeted enzyme when a fluorophore was added to the complex, as well as validate the internalization of the intravenously administered β-gal reporter complex ex vivo. After fluorescence imaging localized the β-gal complexes to the brain tumor, we topically applied a bioluminescent β-gal substrate to serial sections of the brain to evaluate the delivery and integrity of the enzyme. Finally, robust bioluminescence of the EGFR-targeted β-gal complex was captured within the tumor during noninvasive in vivo imaging. PMID:25775241

Optical imaging of targeted β-galactosidase in brain tumors to detect EGFR levels.

PubMed

Broome, Ann-Marie; Ramamurthy, Gopal; Lavik, Kari; Liggett, Alexander; Kinstlinger, Ian; Basilion, James

2015-04-15

A current limitation in molecular imaging is that it often requires genetic manipulation of cancer cells for noninvasive imaging. Other methods to detect tumor cells in vivo using exogenously delivered and functionally active reporters, such as β-gal, are required. We report the development of a platform system for linking β-gal to any number of different ligands or antibodies for in vivo targeting to tissue or cells, without the requirement for genetic engineering of the target cells prior to imaging. Our studies demonstrate significant uptake in vitro and in vivo of an EGFR-targeted β-gal complex. We were then able to image orthotopic brain tumor accumulation and localization of the targeted enzyme when a fluorophore was added to the complex, as well as validate the internalization of the intravenously administered β-gal reporter complex ex vivo. After fluorescence imaging localized the β-gal complexes to the brain tumor, we topically applied a bioluminescent β-gal substrate to serial sections of the brain to evaluate the delivery and integrity of the enzyme. Finally, robust bioluminescence of the EGFR-targeted β-gal complex was captured within the tumor during noninvasive in vivo imaging.

Discovery of functional monoclonal antibodies targeting G-protein-coupled receptors and ion channels.

PubMed

Wilkinson, Trevor C I

2016-06-15

The development of recombinant antibody therapeutics is a significant area of growth in the pharmaceutical industry with almost 50 approved monoclonal antibodies on the market in the US and Europe. Despite this growth, however, certain classes of important molecular targets have remained intractable to therapeutic antibodies due to complexity of the target molecules. These complex target molecules include G-protein-coupled receptors and ion channels which represent a large potential target class for therapeutic intervention with monoclonal antibodies. Although these targets have typically been addressed by small molecule approaches, the exquisite specificity of antibodies provides a significant opportunity to provide selective modulation of these target proteins. Given this opportunity, substantial effort has been applied to address the technical challenges of targeting these complex membrane proteins with monoclonal antibodies. In this review recent progress made in the strategies for discovery of functional monoclonal antibodies for these challenging membrane protein targets is addressed. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Anomalous Putamen Volume in Children with Complex Motor Stereotypies

PubMed Central

Mahone, E. Mark; Crocetti, Deana; Tochen, Laura; Kline, Tina; Mostofsky, Stewart H.; Singer, Harvey S.

2016-01-01

Introduction Complex motor stereotypies in children are repetitive, rhythmic movements that have a predictable pattern and location, seem purposeful, but serve no obvious function, tend to be prolonged, and stop with distraction, e.g., arm/hand flapping, waving. They occur in both “primary” (otherwise typically developing) and secondary conditions. These movements are best defined as habitual behaviors and therefore pathophysiologically hypothesized to reside in premotor to posterior putamen circuits. This study sought to clarify the underlying neurobiological abnormality in children with primary complex motor stereotypies using structural neuroimaging, emphasizing brain regions hypothesized to underlie these atypical behaviors. Methods High-resolution anatomical MRI images, acquired at 3.0T, were analyzed in children ages 8–12 years (20 with primary complex motor stereotypies, 20 typically developing). Frontal lobe sub-regions and striatal structures were delineated for analysis. Results Significant reductions (p=0.045) in the stereotypies group were identified in total putamen volume, but not caudate, nucleus accumbens or frontal sub-regions. There were no group differences in total cerebral volume. Conclusion Findings of a smaller putamen provide preliminary evidence suggesting the potential involvement of the habitual pathway as the underlying anatomical site in primary complex motor stereotypies. PMID:27751663

Abnormal sudomotor function in the hypomelanotic macules of tuberous sclerosis complex.

PubMed

Chudnow, R S; Wolfe, G I; Sparagana, S P; Delgado, M R; Batchelor, L; Roach, E S

2000-08-01

To investigate the integrity of sympathetic innervation in the hypomelanotic macules of tuberous sclerosis complex, we studied sudomotor function in nine patients with tuberous sclerosis complex. Postganglionic sudomotor function was assessed using the Silastic imprint test in nine patients with tuberous sclerosis complex who have at least one hypomelanotic macule greater than 2 cm in diameter. Sweating was induced by iontophoresis with 0.5% pilocarpine nitrate and sweat droplets were counted under a microscope using a 1 x 1 cm grid. Silastic imprint testing of an analogous skin area contralateral to the hypomelanotic macule was measured as a control. Sweat volume quantitation using sweat collectors was performed in five of the subjects. The sweat volume collected from the hypomelanotic macule was reduced compared to the control skin in four of the five subjects. Sweat droplet counts from the hypomelanotic macule were significantly reduced in only one of nine subjects. These data suggest that, although there is no difference in the number of functioning sweat glands in most hypomelanotic macules, the sweat glands produce less sweat (ie, decreased sweat volume) than in normal skin. We hypothesize that focal abnormalities of sympathetic innervation might be responsible for the hypomelanotic macules of tuberous sclerosis complex.

SU-E-J-44: A Novel Approach to Quantify Patient Setup and Target Motion for Real-Time Image-Guided Radiotherapy (IGRT)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, S; Charpentier, P; Sayler, E

2015-06-15

Purpose Isocenter shifts and rotations to correct patient setup errors and organ motion cannot remedy some shape changes of large targets. We are investigating new methods in quantification of target deformation for realtime IGRT of breast and chest wall cancer. Methods Ninety-five patients of breast or chest wall cancer were accrued in an IRB-approved clinical trial of IGRT using 3D surface images acquired at daily setup and beam-on time via an in-room camera. Shifts and rotations relating to the planned reference surface were determined using iterative-closest-point alignment. Local surface displacements and target deformation are measured via a ray-surface intersection andmore » principal component analysis (PCA) of external surface, respectively. Isocenter shift, upper-abdominal displacement, and vectors of the surface projected onto the two principal components, PC1 and PC2, were evaluated for sensitivity and accuracy in detection of target deformation. Setup errors for some deformed targets were estimated by superlatively registering target volume, inner surface, or external surface in weekly CBCT or these outlines on weekly EPI. Results Setup difference according to the inner-surface, external surface, or target volume could be 1.5 cm. Video surface-guided setup agreed with EPI results to within < 0.5 cm while CBCT results were sometimes (∼20%) different from that of EPI (>0.5 cm) due to target deformation for some large breasts and some chest walls undergoing deep-breath-hold irradiation. Square root of PC1 and PC2 is very sensitive to external surface deformation and irregular breathing. Conclusion PCA of external surfaces is quick and simple way to detect target deformation in IGRT of breast and chest wall cancer. Setup corrections based on the target volume, inner surface, and external surface could be significant different. Thus, checking of target shape changes is essential for accurate image-guided patient setup and motion tracking of large deformable targets. NIH grant for the first author as cionsultant and the last author as the PI.« less

Scan-based volume animation driven by locally adaptive articulated registrations.

PubMed

Rhee, Taehyun; Lewis, J P; Neumann, Ulrich; Nayak, Krishna S

2011-03-01

This paper describes a complete system to create anatomically accurate example-based volume deformation and animation of articulated body regions, starting from multiple in vivo volume scans of a specific individual. In order to solve the correspondence problem across volume scans, a template volume is registered to each sample. The wide range of pose variations is first approximated by volume blend deformation (VBD), providing proper initialization of the articulated subject in different poses. A novel registration method is presented to efficiently reduce the computation cost while avoiding strong local minima inherent in complex articulated body volume registration. The algorithm highly constrains the degrees of freedom and search space involved in the nonlinear optimization, using hierarchical volume structures and locally constrained deformation based on the biharmonic clamped spline. Our registration step establishes a correspondence across scans, allowing a data-driven deformation approach in the volume domain. The results provide an occlusion-free person-specific 3D human body model, asymptotically accurate inner tissue deformations, and realistic volume animation of articulated movements driven by standard joint control estimated from the actual skeleton. Our approach also addresses the practical issues arising in using scans from living subjects. The robustness of our algorithms is tested by their applications on the hand, probably the most complex articulated region in the body, and the knee, a frequent subject area for medical imaging due to injuries. © 2011 IEEE

Dosimetric comparison of deep inspiration breath hold and free breathing technique in stereotactic body radiotherapy for localized lung tumor using Flattening Filter Free beam

NASA Astrophysics Data System (ADS)

Mani, Karthick Raj; Bhuiyan, Md. Anisuzzaman; Alam, Md. Mahbub; Ahmed, Sharif; Sumon, Mostafa Aziz; Sengupta, Ashim Kumar; Rahman, Md. Shakilur; Azharul Islam, Md. S. M.

2018-03-01

Aim: To compare the dosimetric advantage of stereotactic body radiotherapy (SBRT) for localized lung tumor between deep inspiration breath hold technique and free breathing technique. Materials and methods: We retrospectively included ten previously treated lung tumor patients in this dosimetric study. All the ten patients underwent CT simulation using 4D-CT free breathing (FB) and deep inspiration breath hold (DIBH) techniques. Plans were created using three coplanar full modulated arc using 6 MV flattening filter free (FFF) bream with a dose rate of 1400 MU/min. Same dose constraints for the target and the critical structures for a particular patient were used during the plan optimization process in DIBH and FB datasets. We intend to deliver 50 Gy in 5 fractions for all the patients. For standardization, all the plans were normalized at target mean of the planning target volume (PTV). Doses to the critical structures and targets were recorded from the dose volume histogram for evaluation. Results: The mean right and left lung volumes were inflated by 1.55 and 1.60 times in DIBH scans compared to the FB scans. The mean internal target volume (ITV) increased in the FB datasets by 1.45 times compared to the DIBH data sets. The mean dose followed by standard deviation (x¯ ± σx¯) of ipsilateral lung for DIBH-SBRT and FB-SBRT plans were 7.48 ± 3.57 (Gy) and 10.23 ± 4.58 (Gy) respectively, with a mean reduction of 36.84% in DIBH-SBRT plans. Ipsilateral lung were reduced to 36.84% in DIBH plans compared to FB plans. Conclusion: Significant dose reduction in ipsilateral lung due to the lung inflation and target motion restriction in DIBH-SBRT plans were observed compare to FB-SBRT. DIBH-SBRT plans demonstrate superior dose reduction to the normal tissues and other critical structures.

Elasticity-based three dimensional ultrasound real-time volume rendering

NASA Astrophysics Data System (ADS)

Boctor, Emad M.; Matinfar, Mohammad; Ahmad, Omar; Rivaz, Hassan; Choti, Michael; Taylor, Russell H.

2009-02-01

Volumetric ultrasound imaging has not gained wide recognition, despite the availability of real-time 3D ultrasound scanners and the anticipated potential of 3D ultrasound imaging in diagnostic and interventional radiology. Their use, however, has been hindered by the lack of real-time visualization methods that are capable of producing high quality 3D rendering of the target/surface of interest. Volume rendering is a known visualization method, which can display clear surfaces out of the acquired volumetric data, and has an increasing number of applications utilizing CT and MRI data. The key element of any volume rendering pipeline is the ability to classify the target/surface of interest by setting an appropriate opacity function. Practical and successful real-time 3D ultrasound volume rendering can be achieved in Obstetrics and Angio applications where setting these opacity functions can be done rapidly, and reliably. Unfortunately, 3D ultrasound volume rendering of soft tissues is a challenging task due to the presence of significant amount of noise and speckle. Recently, several research groups have shown the feasibility of producing 3D elasticity volume from two consecutive 3D ultrasound scans. This report describes a novel volume rendering pipeline utilizing elasticity information. The basic idea is to compute B-mode voxel opacity from the rapidly calculated strain values, which can also be mixed with conventional gradient based opacity function. We have implemented the volume renderer using GPU unit, which gives an update rate of 40 volume/sec.

Development of Sorbents for Extraction and Stabilization of Nucleic Acids

DTIC Science & Technology

2016-09-13

traditional stabilization compounds. The materials were further shown to provide capture and subsequent stabilization of targets from a complex ...22 CAPTURE FROM COMPLEX SOLUTIONS...stabilization compounds (sugars and BSA). The materials were further shown to provide capture and subsequent stabilization of targets from a complex

A new chemotherapy agent-free theranostic system composed of graphene oxide nano-complex and aptamers for treatment of cancer cells.

PubMed

Bahreyni, Amirhossein; Yazdian-Robati, Rezvan; Hashemitabar, Shirin; Ramezani, Mohammad; Ramezani, Pouria; Abnous, Khalil; Taghdisi, Seyed Mohammad

2017-06-30

The common cancer treatment strategies like chemotherapy and radiotherapy are nonspecific and can trigger severe side effects by damaging normal cells. So, targeted cancer therapies, such as apoptosis induction, have attracted great attention in recent years. In this project, two nano-complexes, MUC1 aptamer-NAS-24 aptamer-Graphene oxide (GO) and MUC1 aptamer-Cytochrome C aptamer-GO, were designed to induce cell programmed death in MDA-MB-231 and MCF-7 cells (breast cancer cell lines) and to verify the level of apoptosis in both cell lines. MUC1 aptamer was a molecular recognition probe that led the internalization of two nano-complexes into MDA-MB-231 and MCF-7 cells (MUC1 positive cells) but not into HepG2 cell (liver cancer cell line, MUC1 negative cells). The apoptosis induction relied on binding of NAS-24 aptamer to its target, vimentin, in MDA-MB-231 and MCF-7 (target cells) with different levels of vimentin content. The function of first nano-complex was confirmed by binding of FAM-labeled cytochrome C aptamer to its target (cytochrome C) which was released from mitochondria, based on the function of the first nano-complex. Fluorometric analysis and gel retardation assay proved the formation of nano-complexes. The results of flow cytometry and fluorescence microscopy indicated efficient apoptosis induction just in target cells (MDA-MB-231 and MCF-7 cells) but not in non-target cells (HepG2 cell). The results of MTT assay also confirmed cell death process. Overall, our results proved excellent targeted apoptosis in breast cancer cells by designed nano-complexes which can be applied as an efficient cancer therapy method. Copyright © 2017 Elsevier B.V. All rights reserved.

Robotic liquid handling and automation in epigenetics.

PubMed

Gaisford, Wendy

2012-10-01

Automated liquid-handling robots and high-throughput screening (HTS) are widely used in the pharmaceutical industry for the screening of large compound libraries, small molecules for activity against disease-relevant target pathways, or proteins. HTS robots capable of low-volume dispensing reduce assay setup times and provide highly accurate and reproducible dispensing, minimizing variation between sample replicates and eliminating the potential for manual error. Low-volume automated nanoliter dispensers ensure accuracy of pipetting within volume ranges that are difficult to achieve manually. In addition, they have the ability to potentially expand the range of screening conditions from often limited amounts of valuable sample, as well as reduce the usage of expensive reagents. The ability to accurately dispense lower volumes provides the potential to achieve a greater amount of information than could be otherwise achieved using manual dispensing technology. With the emergence of the field of epigenetics, an increasing number of drug discovery companies are beginning to screen compound libraries against a range of epigenetic targets. This review discusses the potential for the use of low-volume liquid handling robots, for molecular biological applications such as quantitative PCR and epigenetics.

Component extraction on CT volumes of assembled products using geometric template matching

NASA Astrophysics Data System (ADS)

Muramatsu, Katsutoshi; Ohtake, Yutaka; Suzuki, Hiromasa; Nagai, Yukie

2017-03-01

As a method of non-destructive internal inspection, X-ray computed tomography (CT) is used not only in medical applications but also for product inspection. Some assembled products can be divided into separate components based on density, which is known to be approximately proportional to CT values. However, components whose densities are similar cannot be distinguished using the CT value driven approach. In this study, we proposed a new component extraction algorithm from the CT volume, using a set of voxels with an assigned CT value with the surface mesh as the template rather than the density. The method has two main stages: rough matching and fine matching. At the rough matching stage, the position of candidate targets is identified roughly from the CT volume, using the template of the target component. At the fine matching stage, these candidates are precisely matched with the templates, allowing the correct position of the components to be detected from the CT volume. The results of two computational experiments showed that the proposed algorithm is able to extract components with similar density within the assembled products on CT volumes.

The effect of structural complexity, prey density, and "predator-free space" on prey survivorship at created oyster reef mesocosms

USGS Publications Warehouse

Humphries, Austin T.; La Peyre, Megan K.; Decossas, Gary A.

2011-01-01

Interactions between predators and their prey are influenced by the habitat they occupy. Using created oyster (Crassostrea virginica) reef mesocosms, we conducted a series of laboratory experiments that created structure and manipulated complexity as well as prey density and “predator-free space” to examine the relationship between structural complexity and prey survivorship. Specifically, volume and spatial arrangement of oysters as well as prey density were manipulated, and the survivorship of prey (grass shrimp, Palaemonetes pugio) in the presence of a predator (wild red drum, Sciaenops ocellatus) was quantified. We found that the presence of structure increased prey survivorship, and that increasing complexity of this structure further increased survivorship, but only to a point. This agrees with the theory that structural complexity may influence predator-prey dynamics, but that a threshold exists with diminishing returns. These results held true even when prey density was scaled to structural complexity, or the amount of “predator-free space” was manipulated within our created reef mesocosms. The presence of structure and its complexity (oyster shell volume) were more important in facilitating prey survivorship than perceived refugia or density-dependent prey effects. A more accurate indicator of refugia might require “predator-free space” measures that also account for the available area within the structure itself (i.e., volume) and not just on the surface of a structure. Creating experiments that better mimic natural conditions and test a wider range of “predator-free space” are suggested to better understand the role of structural complexity in oyster reefs and other complex habitats.

Method of detecting luminescent target ions with modified magnetic microspheres

DOEpatents

Shkrob, Ilya A; Kaminski, Michael D

2014-05-13

This invention provides methods of using modified magnetic microspheres to extract target ions from a sample in order to detect their presence in a microfluidic environment. In one or more embodiments, the microspheres are modified with molecules on the surface that allow the target ions in the sample to form complexes with specific ligand molecules on the microsphere surface. In one or more embodiments, the microspheres are modified with molecules that sequester the target ions from the sample, but specific ligand molecules in solution subsequently re-extract the target ions from the microspheres into the solution, where the complexes form independent of the microsphere surface. Once the complexes form, they are exposed to an excitation wavelength light source suitable for exciting the target ion to emit a luminescent signal pattern. Detection of the luminescent signal pattern allows for determination of the presence of the target ions in the sample.

A high pressure study of calmodulin-ligand interactions using small-angle X-ray and elastic incoherent neutron scattering.

PubMed

Cinar, Süleyman; Al-Ayoubi, Samy; Sternemann, Christian; Peters, Judith; Winter, Roland; Czeslik, Claus

2018-01-31

Calmodulin (CaM) is a Ca 2+ sensor and mediates Ca 2+ signaling through binding of numerous target ligands. The binding of ligands by Ca 2+ -saturated CaM (holo-CaM) is governed by attractive hydrophobic and electrostatic interactions that are weakened under high pressure in aqueous solutions. Moreover, the potential formation of void volumes upon ligand binding creates a further source of pressure sensitivity. Hence, high pressure is a suitable thermodynamic variable to probe protein-ligand interactions. In this study, we compare the binding of two different ligands to holo-CaM as a function of pressure by using X-ray and neutron scattering techniques. The two ligands are the farnesylated hypervariable region (HVR) of the K-Ras4B protein, which is a natural binding partner of holo-CaM, and the antagonist trifluoperazine (TFP), which is known to inhibit holo-CaM activity. From small-angle X-ray scattering experiments performed up to 3000 bar, we observe a pressure-induced partial unfolding of the free holo-CaM in the absence of ligands, where the two lobes of the dumbbell-shaped protein are slightly swelled. In contrast, upon binding TFP, holo-CaM forms a closed globular conformation, which is pressure stable at least up to 3000 bar. The HVR of K-Ras4B shows a different binding behavior, and the data suggest the dissociation of the holo-CaM/HVR complex under high pressure, probably due to a less dense protein contact of the HVR as compared to TFP. The elastic incoherent neutron scattering experiments corroborate these findings. Below 2000 bar, pressure induces enhanced atomic fluctuations in both holo-CaM/ligand complexes, but those of the holo-CaM/HVR complex seem to be larger. Thus, the inhibition of holo-CaM by TFP is supported by a low-volume ligand binding, albeit this is not associated with a rigidification of the complex structure on the sub-ns Å-scale.

Target motion tracking in MRI-guided transrectal robotic prostate biopsy.

PubMed

Tadayyon, Hadi; Lasso, Andras; Kaushal, Aradhana; Guion, Peter; Fichtinger, Gabor

2011-11-01

MRI-guided prostate needle biopsy requires compensation for organ motion between target planning and needle placement. Two questions are studied and answered in this paper: 1) is rigid registration sufficient in tracking the targets with an error smaller than the clinically significant size of prostate cancer and 2) what is the effect of the number of intraoperative slices on registration accuracy and speed? we propose multislice-to-volume registration algorithms for tracking the biopsy targets within the prostate. Three orthogonal plus additional transverse intraoperative slices are acquired in the approximate center of the prostate and registered with a high-resolution target planning volume. Both rigid and deformable scenarios were implemented. Both simulated and clinical MRI-guided robotic prostate biopsy data were used to assess tracking accuracy. average registration errors in clinical patient data were 2.6 mm for the rigid algorithm and 2.1 mm for the deformable algorithm. rigid tracking appears to be promising. Three tracking slices yield significantly high registration speed with an affordable error.

Modifications of highway air pollution models for complex geometries, volume II : wind tunnel test program.

DOT National Transportation Integrated Search

2002-09-01

This is volume I1 of a two-volume report of a study to increase the scope and clarity of air pollution models for : depressed highway and street canyon sites. It presents the atmospheric wind tunnel program conducted to increase the : data base and i...

Modern Written Arabic, Volume II.

ERIC Educational Resources Information Center

Naja, A. Nashat; Snow, James A.

This second volume of Modern Written Arabic builds on the previous volume and is the second step designed to teach members of the Foreign Service to read the modern Arabic press. The student will gain recognitional mastery of an extensive set of vocabulary items and will be more intensively exposed to wider and more complex morphological and…

Feasibility of a semi-automated contrast-oriented algorithm for tumor segmentation in retrospectively gated PET images: phantom and clinical validation.

PubMed

Carles, Montserrat; Fechter, Tobias; Nemer, Ursula; Nanko, Norbert; Mix, Michael; Nestle, Ursula; Schaefer, Andrea

2015-12-21

PET/CT plays an important role in radiotherapy planning for lung tumors. Several segmentation algorithms have been proposed for PET tumor segmentation. However, most of them do not take into account respiratory motion and are not well validated. The aim of this work was to evaluate a semi-automated contrast-oriented algorithm (COA) for PET tumor segmentation adapted to retrospectively gated (4D) images. The evaluation involved a wide set of 4D-PET/CT acquisitions of dynamic experimental phantoms and lung cancer patients. In addition, segmentation accuracy of 4D-COA was compared with four other state-of-the-art algorithms. In phantom evaluation, the physical properties of the objects defined the gold standard. In clinical evaluation, the ground truth was estimated by the STAPLE (Simultaneous Truth and Performance Level Estimation) consensus of three manual PET contours by experts. Algorithm evaluation with phantoms resulted in: (i) no statistically significant diameter differences for different targets and movements (Δφ = 0.3 ± 1.6 mm); (ii) reproducibility for heterogeneous and irregular targets independent of user initial interaction and (iii) good segmentation agreement for irregular targets compared to manual CT delineation in terms of Dice Similarity Coefficient (DSC = 0.66 ± 0.04), Positive Predictive Value (PPV  = 0.81 ± 0.06) and Sensitivity (Sen. = 0.49 ± 0.05). In clinical evaluation, the segmented volume was in reasonable agreement with the consensus volume (difference in volume (%Vol) = 40 ± 30, DSC = 0.71 ± 0.07 and PPV = 0.90 ± 0.13). High accuracy in target tracking position (ΔME) was obtained for experimental and clinical data (ΔME(exp) = 0 ± 3 mm; ΔME(clin) 0.3 ± 1.4 mm). In the comparison with other lung segmentation methods, 4D-COA has shown the highest volume accuracy in both experimental and clinical data. In conclusion, the accuracy in volume delineation, position tracking and its robustness on highly irregular target movements, make this algorithm a useful tool for 4D-PET based volume definition for radiotherapy planning of lung cancer and may help to improve the reproducibility in PET quantification for therapy response assessment and prognosis.

Feasibility of a semi-automated contrast-oriented algorithm for tumor segmentation in retrospectively gated PET images: phantom and clinical validation

NASA Astrophysics Data System (ADS)

Carles, Montserrat; Fechter, Tobias; Nemer, Ursula; Nanko, Norbert; Mix, Michael; Nestle, Ursula; Schaefer, Andrea

2015-12-01

PET/CT plays an important role in radiotherapy planning for lung tumors. Several segmentation algorithms have been proposed for PET tumor segmentation. However, most of them do not take into account respiratory motion and are not well validated. The aim of this work was to evaluate a semi-automated contrast-oriented algorithm (COA) for PET tumor segmentation adapted to retrospectively gated (4D) images. The evaluation involved a wide set of 4D-PET/CT acquisitions of dynamic experimental phantoms and lung cancer patients. In addition, segmentation accuracy of 4D-COA was compared with four other state-of-the-art algorithms. In phantom evaluation, the physical properties of the objects defined the gold standard. In clinical evaluation, the ground truth was estimated by the STAPLE (Simultaneous Truth and Performance Level Estimation) consensus of three manual PET contours by experts. Algorithm evaluation with phantoms resulted in: (i) no statistically significant diameter differences for different targets and movements (Δ φ =0.3+/- 1.6 mm); (ii) reproducibility for heterogeneous and irregular targets independent of user initial interaction and (iii) good segmentation agreement for irregular targets compared to manual CT delineation in terms of Dice Similarity Coefficient (DSC  =  0.66+/- 0.04 ), Positive Predictive Value (PPV  =  0.81+/- 0.06 ) and Sensitivity (Sen.  =  0.49+/- 0.05 ). In clinical evaluation, the segmented volume was in reasonable agreement with the consensus volume (difference in volume (%Vol)  =  40+/- 30 , DSC  =  0.71+/- 0.07 and PPV  =  0.90+/- 0.13 ). High accuracy in target tracking position (Δ ME) was obtained for experimental and clinical data (Δ ME{{}\\text{exp}}=0+/- 3 mm; Δ ME{{}\\text{clin}}=0.3+/- 1.4 mm). In the comparison with other lung segmentation methods, 4D-COA has shown the highest volume accuracy in both experimental and clinical data. In conclusion, the accuracy in volume delineation, position tracking and its robustness on highly irregular target movements, make this algorithm a useful tool for 4D-PET based volume definition for radiotherapy planning of lung cancer and may help to improve the reproducibility in PET quantification for therapy response assessment and prognosis.

Biotin-tagged platinum(iv) complexes as targeted cytostatic agents against breast cancer cells.

PubMed

Muhammad, Nafees; Sadia, Nasreen; Zhu, Chengcheng; Luo, Cheng; Guo, Zijian; Wang, Xiaoyong

2017-09-05

A biotin-guided platinum IV complex is highly cytotoxic against breast cancer cells but hypotoxic against mammary epithelial cells. The mono-biotinylated Pt IV complex is superior to the di-biotinylated one and hence a promising drug candidate for the targeted therapy of breast cancer.

Underestimation of Low-Dose Radiation in Treatment Planning of Intensity-Modulated Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jang, Si Young; Liu, H. Helen; Mohan, Radhe

2008-08-01

Purpose: To investigate potential dose calculation errors in the low-dose regions and identify causes of such errors for intensity-modulated radiotherapy (IMRT). Methods and Materials: The IMRT treatment plans of 23 patients with lung cancer and mesothelioma were reviewed. Of these patients, 15 had severe pulmonary complications after radiotherapy. Two commercial treatment-planning systems (TPSs) and a Monte Carlo system were used to calculate and compare dose distributions and dose-volume parameters of the target volumes and critical structures. The effect of tissue heterogeneity, multileaf collimator (MLC) modeling, beam modeling, and other factors that could contribute to the differences in IMRT dose calculationsmore » were analyzed. Results: In the commercial TPS-generated IMRT plans, dose calculation errors primarily occurred in the low-dose regions of IMRT plans (<50% of the radiation dose prescribed for the tumor). Although errors in the dose-volume histograms of the normal lung were small (<5%) above 10 Gy, underestimation of dose <10 Gy was found to be up to 25% in patients with mesothelioma or large target volumes. These errors were found to be caused by inadequate modeling of MLC transmission and leaf scatter in commercial TPSs. The degree of low-dose errors depends on the target volumes and the degree of intensity modulation. Conclusions: Secondary radiation from MLCs contributes a significant portion of low dose in IMRT plans. Dose underestimation could occur in conventional IMRT dose calculations if such low-dose radiation is not properly accounted for.« less

Wrapping with a splash: High-speed encapsulation with ultrathin sheets

NASA Astrophysics Data System (ADS)

Kumar, Deepak; Paulsen, Joseph D.; Russell, Thomas P.; Menon, Narayanan

2018-02-01

Many complex fluids rely on surfactants to contain, protect, or isolate liquid drops in an immiscible continuous phase. Thin elastic sheets can wrap liquid drops in a spontaneous process driven by capillary forces. For encapsulation by sheets to be practically viable, a rapid, continuous, and scalable process is essential. We exploit the fast dynamics of droplet impact to achieve wrapping of oil droplets by ultrathin polymer films in a water phase. Despite the violence of splashing events, the process robustly yields wrappings that are optimally shaped to maximize the enclosed fluid volume and have near-perfect seams. We achieve wrappings of targeted three-dimensional (3D) shapes by tailoring the 2D boundary of the films and show the generality of the technique by producing both oil-in-water and water-in-oil wrappings.

Mechanisms for cytoplasmic organization: an overview.

PubMed

Pagliaro, L

2000-01-01

One of the basic characteristics of life is the intrinsic organization of cytoplasm, yet we know surprisingly little about the manner in which cytoplasmic macromolecules are arranged. It is clear that cytoplasm is not the homogeneous "soup" it was once envisioned to be, but a comprehensive model for cytoplasmic organization is not available in modern cell biology. The premise of this volume is that phase separation in cytoplasm may play a role in organization at the subcellular level. Other mechanisms for non-membrane-bounded intracellular organization have previously been proposed. Some of these will be reviewed in this chapter. Multiple mechanisms, involving phase separation, specific intracellular targeting, formation of macromolecular complexes, and channeling, all could well contribute to cytoplasmic organization. Temporal and spatial organization, as well as composition, are likely to be important in defining the characteristics of cytoplasm.

Linear Approximation SAR Azimuth Processing Study

NASA Technical Reports Server (NTRS)

Lindquist, R. B.; Masnaghetti, R. K.; Belland, E.; Hance, H. V.; Weis, W. G.

1979-01-01

A segmented linear approximation of the quadratic phase function that is used to focus the synthetic antenna of a SAR was studied. Ideal focusing, using a quadratic varying phase focusing function during the time radar target histories are gathered, requires a large number of complex multiplications. These can be largely eliminated by using linear approximation techniques. The result is a reduced processor size and chip count relative to ideally focussed processing and a correspondingly increased feasibility for spaceworthy implementation. A preliminary design and sizing for a spaceworthy linear approximation SAR azimuth processor meeting requirements similar to those of the SEASAT-A SAR was developed. The study resulted in a design with approximately 1500 IC's, 1.2 cubic feet of volume, and 350 watts of power for a single look, 4000 range cell azimuth processor with 25 meters resolution.

Effect of lung and target density on small-field dose coverage and PTV definition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Higgins, Patrick D., E-mail: higgi010@umn.edu; Ehler, Eric D.; Cho, Lawrence C.

We have studied the effect of target and lung density on block margin for small stereotactic body radiotherapy (SBRT) targets. A phantom (50 × 50 × 50 cm{sup 3}) was created in the Pinnacle (V9.2) planning system with a 23-cm diameter lung region of interest insert. Diameter targets of 1.6, 2.0, 3.0, and 4.0 cm were placed in the lung region of interest and centered at a physical depth of 15 cm. Target densities evaluated were 0.1 to 1.0 g/cm{sup 3}, whereas the surrounding lung density was varied between 0.05 and 0.6 g/cm{sup 3}. A dose of 100 cGy wasmore » delivered to the isocenter via a single 6-MV field, and the ratio of the average dose to points defining the lateral edges of the target to the isocenter dose was recorded for each combination. Field margins were varied from none to 1.5 cm in 0.25-cm steps. Data obtained in the phantom study were used to predict planning treatment volume (PTV) margins that would match the clinical PTV and isodose prescription for a clinical set of 39 SBRT cases. The average internal target volume (ITV) density was 0.73 ± 0.17, average local lung density was 0.33 ± 0.16, and average ITV diameter was 2.16 ± 0.8 cm. The phantom results initially underpredicted PTV margins by 0.35 cm. With this offset included in the model, the ratio of predicted-to-clinical PTVs was 1.05 ± 0.32. For a given target and lung density, it was found that treatment margin was insensitive to target diameter, except for the smallest (1.6-cm diameter) target, for which the treatment margin was more sensitive to density changes than the larger targets. We have developed a graphical relationship for block margin as a function of target and lung density, which should save time in the planning phase by shortening the design of PTV margins that can satisfy Radiation Therapy Oncology Group mandated treatment volume ratios.« less

Mathematical modelling of tumour volume dynamics in response to stereotactic ablative radiotherapy for non-small cell lung cancer

NASA Astrophysics Data System (ADS)

Tariq, Imran; Humbert-Vidan, Laia; Chen, Tao; South, Christopher P.; Ezhil, Veni; Kirkby, Norman F.; Jena, Rajesh; Nisbet, Andrew

2015-05-01

This paper reports a modelling study of tumour volume dynamics in response to stereotactic ablative radiotherapy (SABR). The main objective was to develop a model that is adequate to describe tumour volume change measured during SABR, and at the same time is not excessively complex as lacking support from clinical data. To this end, various modelling options were explored, and a rigorous statistical method, the Akaike information criterion, was used to help determine a trade-off between model accuracy and complexity. The models were calibrated to the data from 11 non-small cell lung cancer patients treated with SABR. The results showed that it is feasible to model the tumour volume dynamics during SABR, opening up the potential for using such models in a clinical environment in the future.

Factors affecting choice between ureterostomy, ileal conduit and continent reservoir after radical cystectomy: Japanese series.

PubMed

Sugihara, Toru; Yasunaga, Hideo; Horiguchi, Hiromasa; Fujimura, Tetsuya; Fushimi, Kiyohide; Yu, Changhong; Kattan, Michael W; Homma, Yukio

2014-12-01

Little is known about the disparity of choices between three urinary diversions after radical cystectomy, focusing on patient and institutional factors. We identified urothelial carcinoma patients who received radical cystectomy with cutaneous ureterostomy, ileal conduit or continent reservoir using the Japanese Diagnosis Procedure Combination database from 2007 to 2012. Data comprised age, sex, comorbidities (converted into the Charlson index), TNM classification (converted into oncological stage), hospitals' academic status, hospital volume, bed volume and geographical region. Multivariate ordinal logistic regression analyses fitted with the proportional odds model were performed to analyze factors affecting urinary diversion choices. For dependent variables, the three diversions were converted into an ordinal variable in order of complexity: cutaneous ureterostomy (reference), ileal conduit and continent reservoir. Geographical variations were also examined by multivariate logistic regression models. A total of 4790 patients (1131 cutaneous ureterostomies [23.6 %], 2970 ileal conduits [62.0 %] and 689 continent reservoirs [14.4 %]) were included. Ordinal logistic regression analyses showed that male sex, lower age, lower Charlson index, early tumor stage, higher hospital volume (≥3.4 cases/year) and larger bed volume (≥450 beds) were significantly associated with the preference of more complex urinary diversion. Significant geographical disparity was also found. Good patient condition and early oncological status, as well as institutional factors, including high hospital volume, large bed volume and specific geographical regions, are independently related to the likelihood of choosing complex diversions. Recognizing this disparity would help reinforce the need for clinical practice uniformity.

Optimal volume of injectate for fluoroscopy-guided cervical interlaminar epidural injection in patients with neck and upper extremity pain

PubMed Central

Park, Jun Young; Kim, Doo Hwan; Lee, Kunhee; Choi, Seong-Soo; Leem, Jeong-Gil

2016-01-01

Abstract There is no study of optimal volume of contrast medium to use in cervical interlaminar epidural injections (CIEIs) for appropriate spread to target lesions. To determine optimal volume of contrast medium to use in CIEIs. We analyzed the records of 80 patients who had undergone CIEIs. Patients were divided into 3 groups according to the amount of contrast: 3, 4.5, and 6 mL. The spread of medium to the target level was analyzed. Numerical rating scale data were also analyzed. The dye had spread to a point above the target level in 15 (78.9%), 22 (84.6%), and 32 (91.4%) patients in groups 1 to 3, respectively. The dye reached both sides in 14 (73.7%), 18 (69.2%), and 23 (65.7%) patients, and reached the ventral epidural space in 15 (78.9%), 22 (84.6%), and 30 (85.7%) patients, respectively. There were no significant differences of contrast spread among the groups. There were no significant differences in the numerical rating scale scores among the groups during the 3 months. When performing CIEIs, 3 mL medication is sufficient volume for the treatment of neck and upper-extremity pain induced by lower cervical degenerative disease. PMID:27787378

Optimal volume of injectate for fluoroscopy-guided cervical interlaminar epidural injection in patients with neck and upper extremity pain.

PubMed

Park, Jun Young; Kim, Doo Hwan; Lee, Kunhee; Choi, Seong-Soo; Leem, Jeong-Gil

2016-10-01

There is no study of optimal volume of contrast medium to use in cervical interlaminar epidural injections (CIEIs) for appropriate spread to target lesions. To determine optimal volume of contrast medium to use in CIEIs. We analyzed the records of 80 patients who had undergone CIEIs. Patients were divided into 3 groups according to the amount of contrast: 3, 4.5, and 6 mL. The spread of medium to the target level was analyzed. Numerical rating scale data were also analyzed. The dye had spread to a point above the target level in 15 (78.9%), 22 (84.6%), and 32 (91.4%) patients in groups 1 to 3, respectively. The dye reached both sides in 14 (73.7%), 18 (69.2%), and 23 (65.7%) patients, and reached the ventral epidural space in 15 (78.9%), 22 (84.6%), and 30 (85.7%) patients, respectively. There were no significant differences of contrast spread among the groups. There were no significant differences in the numerical rating scale scores among the groups during the 3 months. When performing CIEIs, 3 mL medication is sufficient volume for the treatment of neck and upper-extremity pain induced by lower cervical degenerative disease.

Physiological and biochemical principles underlying volume-targeted therapy--the "Lund concept".

PubMed

Nordström, Carl-Henrik

2005-01-01

The optimal therapy of sustained increase in intracranial pressure (ICP) remains controversial. The volume-targeted therapy ("Lund concept") discussed in this article focuses on the physiological volume regulation of the intracranial compartments. The balance between effective transcapillary hydrostatic and osmotic pressures constitutes the driving force for transcapillary fluid exchange. The low permeability for sodium and chloride combined with the high crystalloid osmotic pressure (approximately 5700 mmHg) on both sides of the blood-brain barrier (BBB) counteracts fluid exchange across the intact BBB. Additionally, variations in systemic blood pressure generally are not transmitted to these capillaries because cerebral intracapillary hydrostatic pressure (and blood flow) is physio-logically tightly autoregulated. Under pathophysiological conditions, the BBB may be partially disrupted. Transcapillary water exchange is then determined by the differences in hydrostatic and colloid osmotic pressure between the intra- and extracapillary compartments. Pressure autoregulation of cerebral blood flow is likely to be impaired in these conditions. A high cerebral perfusion pressure accordingly increases intracapillary hydrostatic pressure and leads to increased intracerebral water content and an increase in ICP. The volume-targeted "Lund concept" has been evaluated in experimental and clinical studies to examine the physiological and biochemical (utilizing intracerebral microdialysis) effects, and the clinical experiences have been favorable.

TASK-2: a K2P K+ channel with complex regulation and diverse physiological functions

PubMed Central

Cid, L. Pablo; Roa-Rojas, Hugo A.; Niemeyer, María I.; González, Wendy; Araki, Masatake; Araki, Kimi; Sepúlveda, Francisco V.

2013-01-01

TASK-2 (K2P5.1) is a two-pore domain K+ channel belonging to the TALK subgroup of the K2P family of proteins. TASK-2 has been shown to be activated by extra- and intracellular alkalinization. Extra- and intracellular pH-sensors reside at arginine 224 and lysine 245 and might affect separate selectivity filter and inner gates respectively. TASK-2 is modulated by changes in cell volume and a regulation by direct G-protein interaction has also been proposed. Activation by extracellular alkalinization has been associated with a role of TASK-2 in kidney proximal tubule bicarbonate reabsorption, whilst intracellular pH-sensitivity might be the mechanism for its participation in central chemosensitive neurons. In addition to these functions TASK-2 has been proposed to play a part in apoptotic volume decrease in kidney cells and in volume regulation of glial cells and T-lymphocytes. TASK-2 is present in chondrocytes of hyaline cartilage, where it is proposed to play a central role in stabilizing the membrane potential. Additional sites of expression are dorsal root ganglion neurons, endocrine and exocrine pancreas and intestinal smooth muscle cells. TASK-2 has been associated with the regulation of proliferation of breast cancer cells and could become target for breast cancer therapeutics. Further work in native tissues and cells together with genetic modification will no doubt reveal the details of TASK-2 functions that we are only starting to suspect. PMID:23908634

Proof of Principle of Ocular sparing in dogs with sinonasal tumors treated with intensity-modulated radiation therapy

PubMed Central

Lawrence, Jessica A.; Forrest, Lisa J.; Turek, Michelle M.; Miller, Paul E.; Mackie, T. Rockwell; Jaradat, Hazim A.; Vail, David M.; Dubielzig, Richard R.; Chappell, Richard; Mehta, Minesh P.

2010-01-01

Intensity modulated radiation therapy (IMRT) allows optimization of radiation dose delivery to complex tumor volumes with rapid dose drop-off to surrounding normal tissues. A prospective study was performed to evaluate the concept of conformal avoidance using IMRT in canine sinonasal cancer. The potential of IMRT to improve clinical outcome with respect to acute and late ocular toxicity was evaluated. Thirty-one dogs with sinonasal cancer were treated definitively with IMRT using helical tomotherapy and/or dynamic multileaf collimator (DMLC) delivery. Ocular toxicity was evaluated prospectively and compared to a comparable group of historical controls treated with conventional two-dimensional radiotherapy (2D-RT) techniques. Treatment plans were devised for each dog using helical tomotherapy and DMLC that achieved the target dose to the planning treatment volume and limited critical normal tissues to the prescribed dose-volume constraints. Overall acute and late toxicities were limited and minor, detectable by an experienced observer. This was in contrast to the profound ocular morbidity observed in the historical control group treated with 2D-RT. Overall median survival for IMRT treated and 2D treated dogs was 420 days and 411 days, respectively. Compared with conventional techniques, IMRT reduced dose delivered to eyes and resulted in bilateral ocular sparing in the dogs reported herein. These data provide proof-of-principle that conformal avoidance radiotherapy can be delivered through high conformity IMRT, resulting in decreased normal tissue toxicity as compared to historical controls treated with 2D-RT. PMID:20973393

Technology transfer from NASA to targeted industries, volume 2

NASA Technical Reports Server (NTRS)

Mccain, Wayne; Schroer, Bernard J.; Souder, William E.; Spann, Mary S.; Watters, Harry; Ziemke, M. Carl

1993-01-01

This volume contains the following materials to support Volume 1: (1) Survey of Metal Fabrication Industry in Alabama; (2) Survey of Electronics Manufacturing/Assembly Industry in Alabama; (3) Apparel Modular Manufacturing Simulators; (4) Synopsis of a Stereolithography Project; (5) Transferring Modular Manufacturing Technology to an Apparel Firm; (6) Letters of Support; (7) Fact Sheets; (8) Publications; and (9) One Stop Access to NASA Technology Brochure.

Allometry, nitrogen status, and carbon stable isotope composition of Pinus ponderosa seedlings in two growing media with contrasting nursery irrigation regimes

Treesearch

R. Kasten Dumroese; Deborah S. Page-Dumroese; Robert E. Brown

2011-01-01

Nursery irrigation regimes that recharged container capacity when target volumetric water content reached 72%, 58%, and 44% (by volume) influenced Pinus ponderosa Douglas ex Lawson & C. Lawson growth more than either a 1:1 (by volume) Sphagnum peat - vermiculite (PV) or a 7:3 (by volume) Sphagnum peat - sawdust (PS) medium. Exponential fertilization avoided...

Mechanism of host-guest complexation by cucurbituril.

PubMed

Márquez, César; Hudgins, Robert R; Nau, Werner M

2004-05-12

The factors affecting host-guest complexation between the molecular container compound cucurbit[6]uril (CB6) and various guests in aqueous solution are studied, and a detailed complexation mechanism in the presence of cations is derived. The formation of the supramolecular complex is studied in detail for cyclohexylmethylammonium ion as guest. The kinetics and thermodynamics of complexation is monitored by NMR as a function of temperature, salt concentration, and cation size. The binding constants and the ingression rate constants decrease with increasing salt concentration and cation-binding constant, in agreement with a competitive binding of the ammonium site of the guest and the metal cation with the ureido carbonyl portals of CB6. Studies as a function of guest size indicate that the effective container volume of the CB6 cavity is approximately 105 A(3). It is suggested that larger guests are excluded for two reasons: a high activation barrier for ingression imposed by the tight CB6 portals and a destabilization of the complex due to steric repulsion inside. For example, in the case of the nearly spherical azoalkane homologues 2,3-diazabicyclo[2.2.1]hept-2-ene (DBH, volume ca. 96 A(3)) and 2,3-diazabicyclo[2.2.2]oct-2-ene (DBO, volume ca. 110 A(3)), the former forms the CB6 complex promptly with a sizable binding constant (1300 M(-1)), while the latter does not form a complex even after several months at optimized complexation conditions. Molecular mechanics calculations are performed for several CB6/guest complexes. A qualitative agreement is found between experimental and calculated activation energies for ingression as a function of both guest size and state of protonation. The potential role of constrictive binding by CB6 is discussed.

Deformable 3D-2D registration for CT and its application to low dose tomographic fluoroscopy

NASA Astrophysics Data System (ADS)

Flach, Barbara; Brehm, Marcus; Sawall, Stefan; Kachelrieß, Marc

2014-12-01

Many applications in medical imaging include image registration for matching of images from the same or different modalities. In the case of full data sampling, the respective reconstructed images are usually of such a good image quality that standard deformable volume-to-volume (3D-3D) registration approaches can be applied. But research in temporal-correlated image reconstruction and dose reductions increases the number of cases where rawdata are available from only few projection angles. Here, deteriorated image quality leads to non-acceptable deformable volume-to-volume registration results. Therefore a registration approach is required that is robust against a decreasing number of projections defining the target position. We propose a deformable volume-to-rawdata (3D-2D) registration method that aims at finding a displacement vector field maximizing the alignment of a CT volume and the acquired rawdata based on the sum of squared differences in rawdata domain. The registration is constrained by a regularization term in accordance with a fluid-based diffusion. Both cost function components, the rawdata fidelity and the regularization term, are optimized in an alternating manner. The matching criterion is optimized by a conjugate gradient descent for nonlinear functions, while the regularization is realized by convolution of the vector fields with Gaussian kernels. We validate the proposed method and compare it to the demons algorithm, a well-known 3D-3D registration method. The comparison is done for a range of 4-60 target projections using datasets from low dose tomographic fluoroscopy as an application example. The results show a high correlation to the ground truth target position without introducing artifacts even in the case of very few projections. In particular the matching in the rawdata domain is improved compared to the 3D-3D registration for the investigated range. The proposed volume-to-rawdata registration increases the robustness regarding sparse rawdata and provides more stable results than volume-to-volume approaches. By applying the proposed registration approach to low dose tomographic fluoroscopy it is possible to improve the temporal resolution and thus to increase the robustness of low dose tomographic fluoroscopy.

SU-F-T-253: Volumetric Comparison Between 4D CT Amplitude and Phase Binning Mode

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, G; Ma, R; Reyngold, M

2016-06-15

Purpose: Motion artifact in 4DCT images can affect radiation treatment quality. To identify the most robust and accurate binning method, we compare the volume difference between targets delineated on amplitude and phase binned 4DCT scans. Methods: Varian RPM system and CT scanner were used to acquire 4DCTs of a Quasar phantom with embedded cubic and spherical objects having superior-inferior motion. Eight patients’ respiration waveforms were used to drive the phantom. The 4DCT scan was reconstructed into 10 phase and 10 amplitude bins (2 mm slices). A scan of the static phantom was also acquired. For each waveform, sphere and cubemore » volumes were generated automatically on each phase using HU thresholding. Phase (amplitude) ITVs were the union of object volumes over all phase (amplitude) binned images. The sphere and cube volumes measured in the static phantom scan were V{sub sphere}=4.19cc and V{sub cube}=27.0cc. Volume difference (VD) and dice similarity coefficient (DSC) of the ITVs, and mean volume error (MVE) defined as the average target volume percentage difference between each phase image and the static image, were used to evaluate the performance of amplitude and phase binning. Results: Averaged over the eight breathing traces, the VD and DSC of the internal target volume (ITV) between amplitude and phase binning were 3.4%±3.2% (mean ± std) and 95.9%±2.1% for sphere; 2.1%±3.3% and 98.0% ±1.5% for cube, respectively.For all waveforms, the average sphere MVE of amplitude and phase binning was 6.5% ± 5.0% and 8.2%±6.3%, respectively; and the average cube MVE of amplitude and phase binning was 5.7%±3.5%and 12.9%±8.9%, respectively. Conclusion: ITV volume and spatial overlap as assessed by VD and DSC are similar between amplitude and phase binning. Compared to phase binning, amplitude binning results in lower MVE suggesting it is less susceptible to motion artifact.« less

Volumetric Image Guidance Using Carina vs Spine as Registration Landmarks for Conventionally Fractionated Lung Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lavoie, Caroline; Higgins, Jane; Bissonnette, Jean-Pierre

2012-12-01

Purpose: To compare the relative accuracy of 2 image guided radiation therapy methods using carina vs spine as landmarks and then to identify which landmark is superior relative to tumor coverage. Methods and Materials: For 98 lung patients, 2596 daily image-guidance cone-beam computed tomography scans were analyzed. Tattoos were used for initial patient alignment; then, spine and carina registrations were performed independently. A separate analysis assessed the adequacy of gross tumor volume, internal target volume, and planning target volume coverage on cone-beam computed tomography using the initial, middle, and final fractions of radiation therapy. Coverage was recorded for primary tumormore » (T), nodes (N), and combined target (T+N). Three scenarios were compared: tattoos alignment, spine registration, and carina registration. Results: Spine and carina registrations identified setup errors {>=}5 mm in 35% and 46% of fractions, respectively. The mean vector difference between spine and carina matching had a magnitude of 3.3 mm. Spine and carina improved combined target coverage, compared with tattoos, in 50% and 34% (spine) to 54% and 46% (carina) of the first and final fractions, respectively. Carina matching showed greater combined target coverage in 17% and 23% of fractions for the first and final fractions, respectively; with spine matching, this was only observed in 4% (first) and 6% (final) of fractions. Carina matching provided superior nodes coverage at the end of radiation compared with spine matching (P=.0006), without compromising primary tumor coverage. Conclusion: Frequent patient setup errors occur in locally advanced lung cancer patients. Spine and carina registrations improved combined target coverage throughout the treatment course, but carina matching provided superior combined target coverage.« less

Calibration and evaluation of a magnetically tracked ICE probe for guidance of left atrial ablation therapy

NASA Astrophysics Data System (ADS)

Linte, Cristian A.; Rettmann, Maryam E.; Dilger, Ben; Gunawan, Mia S.; Arunachalam, Shivaram P.; Holmes, David R., III; Packer, Douglas L.; Robb, Richard A.

2012-02-01

The novel prototype system for advanced visualization for image-guided left atrial ablation therapy developed in our laboratory permits ready integration of multiple imaging modalities, surgical instrument tracking, interventional devices and electro-physiologic data. This technology allows subject-specific procedure planning and guidance using 3D dynamic, patient-specific models of the patient's heart, augmented with real-time intracardiac echocardiography (ICE). In order for the 2D ICE images to provide intuitive visualization for accurate catheter to surgical target navigation, the transducer must be tracked, so that the acquired images can be appropriately presented with respect to the patient-specific anatomy. Here we present the implementation of a previously developed ultrasound calibration technique for a magnetically tracked ICE transducer, along with a series of evaluation methods to ensure accurate imaging and faithful representation of the imaged structures. Using an engineering-designed phantom, target localization accuracy is assessed by comparing known target locations with their transformed locations inferred from the tracked US images. In addition, the 3D volume reconstruction accuracy is also estimated by comparing a truth volume to that reconstructed from sequential 2D US images. Clinically emulating validation studies are conducted using a patient-specific left atrial phantom. Target localization error of clinically-relevant surgical targets represented by nylon fiducials implanted within the endocardial wall of the phantom was assessed. Our studies have demonstrated 2.4 +/- 0.8 mm target localization error in the engineering-designed evaluation phantoms, 94.8 +/- 4.6 % volume reconstruction accuracy, and 3.1 +/- 1.2 mm target localization error in the left atrial-mimicking phantom. These results are consistent with those disseminated in the literature and also with the accuracy constraints imposed by the employed technology and the clinical application.

PROCOS: computational analysis of protein-protein complexes.

PubMed

Fink, Florian; Hochrein, Jochen; Wolowski, Vincent; Merkl, Rainer; Gronwald, Wolfram

2011-09-01

One of the main challenges in protein-protein docking is a meaningful evaluation of the many putative solutions. Here we present a program (PROCOS) that calculates a probability-like measure to be native for a given complex. In contrast to scores often used for analyzing complex structures, the calculated probabilities offer the advantage of providing a fixed range of expected values. This will allow, in principle, the comparison of models corresponding to different targets that were solved with the same algorithm. Judgments are based on distributions of properties derived from a large database of native and false complexes. For complex analysis PROCOS uses these property distributions of native and false complexes together with a support vector machine (SVM). PROCOS was compared to the established scoring schemes of ZRANK and DFIRE. Employing a set of experimentally solved native complexes, high probability values above 50% were obtained for 90% of these structures. Next, the performance of PROCOS was tested on the 40 binary targets of the Dockground decoy set, on 14 targets of the RosettaDock decoy set and on 9 targets that participated in the CAPRI scoring evaluation. Again the advantage of using a probability-based scoring system becomes apparent and a reasonable number of near native complexes was found within the top ranked complexes. In conclusion, a novel fully automated method is presented that allows the reliable evaluation of protein-protein complexes. Copyright © 2011 Wiley Periodicals, Inc.

Targeting Common but Complex Proteoglycans on Breast Cancer Cells and Stem Cells Using Evolutionary Refined Malaria Proteins

DTIC Science & Technology

2015-11-01

AWARD NUMBER: W81XWH-13-1-0139 TITLE: Targeting Common but Complex Proteoglycans on Breast Cancer Cells and Stem Cells Using Evolutionary Refined...DATES COVERED 15Aug2013 - 14Aug2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-13-1-0139 Targeting Common but Complex Proteoglycans on...outbreaks in epidemic regions of the world. Prior to this application we discovered that human breast cancer cells express this same carbohydrate

Implant strategies for endocervical and interstitial ultrasound hyperthermia adjunct to HDR brachytherapy for the treatment of cervical cancer

NASA Astrophysics Data System (ADS)

Wootton, Jeffery H.; Prakash, Punit; Hsu, I.-Chow Joe; Diederich, Chris J.

2011-07-01

Catheter-based ultrasound devices provide a method to deliver 3D conformable heating integrated with HDR brachytherapy delivery. Theoretical characterization of heating patterns was performed to identify implant strategies for these devices which can best be used to apply hyperthermia to cervical cancer. A constrained optimization-based hyperthermia treatment planning platform was used for the analysis. The proportion of tissue >=41 °C in a hyperthermia treatment volume was maximized with constraints Tmax <= 47 °C, Trectum <= 41.5 °C, and Tbladder <= 42.5 °C. Hyperthermia treatment was modeled for generalized implant configurations and complex configurations from a database of patients (n = 14) treated with HDR brachytherapy. Various combinations of endocervical (360° or 2 × 180° output; 6 mm OD) and interstitial (180°, 270°, or 360° output; 2.4 mm OD) applicators within catheter locations from brachytherapy implants were modeled, with perfusion constant (1 or 3 kg m-3 s-1) or varying with location or temperature. Device positioning, sectoring, active length and aiming were empirically optimized to maximize thermal coverage. Conformable heating of appreciable volumes (>200 cm3) is possible using multiple sectored interstitial and endocervical ultrasound devices. The endocervical device can heat >41 °C to 4.6 cm diameter compared to 3.6 cm for the interstitial. Sectored applicators afford tight control of heating that is robust to perfusion changes in most regularly spaced configurations. T90 in example patient cases was 40.5-42.7 °C (1.9-39.6 EM43 °C) at 1 kg m-3 s-1 with 10/14 patients >=41 °C. Guidelines are presented for positioning of implant catheters during the initial surgery, selection of ultrasound applicator configurations, and tailored power schemes for achieving T90 >= 41 °C in clinically practical implant configurations. Catheter-based ultrasound devices, when adhering to the guidelines, show potential to generate conformal therapeutic heating ranging from a single endocervical device targeting small volumes local to the cervix (<2 cm radial) to a combination of a 2 × 180° endocervical and directional interstitial applicators in the lateral periphery to target much larger volumes (6 cm radial), while preferentially limiting heating of the bladder and rectum.

High-order graph matching based feature selection for Alzheimer's disease identification.

PubMed

Liu, Feng; Suk, Heung-Il; Wee, Chong-Yaw; Chen, Huafu; Shen, Dinggang

2013-01-01

One of the main limitations of l1-norm feature selection is that it focuses on estimating the target vector for each sample individually without considering relations with other samples. However, it's believed that the geometrical relation among target vectors in the training set may provide useful information, and it would be natural to expect that the predicted vectors have similar geometric relations as the target vectors. To overcome these limitations, we formulate this as a graph-matching feature selection problem between a predicted graph and a target graph. In the predicted graph a node is represented by predicted vector that may describe regional gray matter volume or cortical thickness features, and in the target graph a node is represented by target vector that include class label and clinical scores. In particular, we devise new regularization terms in sparse representation to impose high-order graph matching between the target vectors and the predicted ones. Finally, the selected regional gray matter volume and cortical thickness features are fused in kernel space for classification. Using the ADNI dataset, we evaluate the effectiveness of the proposed method and obtain the accuracies of 92.17% and 81.57% in AD and MCI classification, respectively.

Computerized optimization of multiple isocentres in stereotactic convergent beam irradiation

NASA Astrophysics Data System (ADS)

Treuer, U.; Treuer, H.; Hoevels, M.; Müller, R. P.; Sturm, V.

1998-01-01

A method for the fully computerized determination and optimization of positions of target points and collimator sizes in convergent beam irradiation is presented. In conventional interactive trial and error methods, which are very time consuming, the treatment parameters are chosen according to the operator's experience and improved successively. This time is reduced significantly by the use of a computerized procedure. After the definition of target volume and organs at risk in the CT or MR scans, an initial configuration is created automatically. In the next step the target point positions and collimator diameters are optimized by the program. The aim of the optimization is to find a configuration for which a prescribed dose at the target surface is approximated as close as possible. At the same time dose peaks inside the target volume are minimized and organs at risk and tissue surrounding the target are spared. To enhance the speed of the optimization a fast method for approximate dose calculation in convergent beam irradiation is used. A possible application of the method for calculating the leaf positions when irradiating with a micromultileaf collimator is briefly discussed. The success of the procedure has been demonstrated for several clinical cases with up to six target points.

More Accurate Definition of Clinical Target Volume Based on the Measurement of Microscopic Extensions of the Primary Tumor Toward the Uterus Body in International Federation of Gynecology and Obstetrics Ib-IIa Squamous Cell Carcinoma of the Cervix

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xie, Wen-Jia; Wu, Xiao; Xue, Ren-Liang

Purpose: To more accurately define clinical target volume for cervical cancer radiation treatment planning by evaluating tumor microscopic extension toward the uterus body (METU) in International Federation of Gynecology and Obstetrics stage Ib-IIa squamous cell carcinoma of the cervix (SCCC). Patients and Methods: In this multicenter study, surgical resection specimens from 318 cases of stage Ib-IIa SCCC that underwent radical hysterectomy were included. Patients who had undergone preoperative chemotherapy, radiation, or both were excluded from this study. Microscopic extension of primary tumor toward the uterus body was measured. The association between other pathologic factors and METU was analyzed. Results: Microscopicmore » extension toward the uterus body was not common, with only 12.3% of patients (39 of 318) demonstrating METU. The mean (±SD) distance of METU was 0.32 ± 1.079 mm (range, 0-10 mm). Lymphovascular space invasion was associated with METU distance and occurrence rate. A margin of 5 mm added to gross tumor would adequately cover 99.4% and 99% of the METU in the whole group and in patients with lymphovascular space invasion, respectively. Conclusion: According to our analysis of 318 SCCC specimens for METU, using a 5-mm gross tumor volume to clinical target volume margin in the direction of the uterus should be adequate for International Federation of Gynecology and Obstetrics stage Ib-IIa SCCC. Considering the discrepancy between imaging and pathologic methods in determining gross tumor volume extent, we recommend a safer 10-mm margin in the uterine direction as the standard for clinical practice when using MRI for contouring tumor volume.« less

Influence of gestational age on dead space and alveolar ventilation in preterm infants ventilated with volume guarantee.

PubMed

Neumann, Roland P; Pillow, Jane J; Thamrin, Cindy; Larcombe, Alexander N; Hall, Graham L; Schulzke, Sven M

2015-01-01

Ventilated preterm infant lungs are vulnerable to overdistension and underinflation. The optimal ventilator-delivered tidal volume (VT) in these infants is unknown and may depend on the extent of alveolarisation at birth. We aimed to calculate respiratory dead space (VD) from the molar mass (MM) signal of an ultrasonic flowmeter (VD,MM) in very preterm infants on volume-targeted ventilation (VT target, 4-5 ml/kg) and to study the association between gestational age (GA) and VD,MM-to-VT ratio (VD,MM/VT), alveolar tidal volume (VA) and alveolar minute volume (AMV). This was a single-centre, prospective, observational, cohort study in a neonatal intensive care unit. Tidal breathing analysis was performed in ventilated very preterm infants (GA range 23-32 weeks) on day 1 of life. Valid measurements were obtained in 43/51 (87%) infants. Tidal breathing variables were analysed using multivariable linear regression. VD,MM/VT was negatively associated with GA after adjusting for birth weight Z score (p < 0.001, R(2) = 0.26). This association was primarily influenced by the appliance dead space. Despite similar VT/kg and VA/kg across all studied infants, respiratory rate and AMV/kg increased with GA. VD,app rather than anatomical VD is the major factor influencing increased VD,MM/VT at a younger GA. A volume guarantee setting of 4-5 ml/kg in the Dräger Babylog® 8000 plus ventilator may be inappropriate as a universal target across the GA range of 23-32 weeks. Differences between measured and set VT and the dependence of this difference on GA require further investigation. © 2014 S. Karger AG, Basel.

Dosimetric and Clinical Analysis of Spatial Distribution of the Radiation Dose in Gamma Knife Radiosurgery for Vestibular Schwannoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Massager, Nicolas, E-mail: nmassage@ulb.ac.be; Neurosurgery-Department, Hospital Erasme, Brussels; Lonneville, Sarah

2011-11-15

Objectives: We investigated variations in the distribution of radiation dose inside (dose inhomogeneity) and outside (dose falloff) the target volume during Gamma Knife (GK) irradiation of vestibular schwannoma (VS). We analyzed the relationship between some parameters of dose distribution and the clinical and radiological outcome of patients. Methods and Materials: Data from dose plans of 203 patients treated for a vestibular schwannoma by GK C using same prescription dose (12 Gy at the 50% isodose) were collected. Four different dosimetric indexes were defined and calculated retrospectively in all plannings on the basis of dose-volume histograms: Paddick conformity index (PI), gradientmore » index (GI), homogeneity index (HI), and unit isocenter (UI). The different measures related to distribution of the radiation dose were compared with hearing and tumor outcome of 203 patients with clinical and radiological follow-up of minimum 2 years. Results: Mean, median, SD, and ranges of the four indexes of dose distribution analyzed were calculated; large variations were found between dose plans. We found a high correlation between the target volume and PI, GI, and UI. No significant association was found between the indexes of dose distribution calculated in this study and tumor control, tumor volume shrinkage, hearing worsening, loss of functional hearing, or complete hearing loss at last follow-up. Conclusions: Parameters of distribution of the radiation dose during GK radiosurgery for VS can be highly variable between dose plans. The tumor and hearing outcome of patients treated is not significantly related to these global indexes of dose distribution inside and around target volume. In GK radiosurgery for VS, the outcome seems more to be influenced by local radiation dose delivered to specific structures or volumes than by global dose gradients.« less

Bronchoscopic Thermal Vapor Ablation: Best Practice Recommendations from an Expert Panel on Endoscopic Lung Volume Reduction.

PubMed

Gompelmann, Daniela; Shah, Pallav L; Valipour, Arschang; Herth, Felix J F

2018-06-12

Bronchoscopic thermal vapor ablation (BTVA) represents one of the endoscopic lung volume reduction (ELVR) techniques that aims at hyperinflation reduction in patients with advanced emphysema to improve respiratory mechanics. By targeted segmental vapor ablation, an inflammatory response leads to tissue and volume reduction of the most diseased emphysematous segments. So far, BTVA has been demonstrated in several single-arm trials and 1 multinational randomized controlled trial to improve lung function, exercise capacity, and quality of life in patients with upper lobe-predominant emphysema irrespective of the collateral ventilation. In this review, we emphasize the practical aspects of this ELVR method. Patients with upper lobe-predominant emphysema, forced expiratory volume in 1 second (FEV1) between 20 and 45% of predicted, residual volume (RV) > 175% of predicted, and carbon monoxide diffusing capacity (DLCO) ≥20% of predicted can be considered for BTVA treatment. Prior to the procedure, a special software assists in identifying the target segments with the highest emphysema index, volume and the highest heterogeneity index to the untreated ipsilateral lung lobes. The procedure may be performed under deep sedation or preferably under general anesthesia. After positioning of the BTVA catheter and occlusion of the target segment by the occlusion balloon, heated water vapor is delivered in a predetermined specified time according to the vapor dose. After the procedure, patients should be strictly monitored to proactively detect symptoms of localized inflammatory reaction that may temporarily worsen the clinical status of the patient and to detect complications. As the data are still very limited, BTVA should be performed within clinical trials or comprehensive registries where the product is commercially available. © 2018 S. Karger AG, Basel.

SU-F-T-498: A Comparative Evaluation of 6MV Flatten Beam and Flattening Filter Free Photon Beam in Carcinoma Breast

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tamilarasu, Suresh; Saminathan, Madeswaran

Purpose: Aim of the current study is to look plan quality, treatment beam ON time for IMRT using 6MV FB (Flatten Beam) and FFFB (Flattening Filter Free Beam) in left breast cancer cases. Methods: Ten left breast cancer patients treated with breast conserving surgical (BCS) procedure approach and adjuvant radiotherapy were selected from the department database. Simultaneous Integrated boost (SIB) technique was used to irradiate the total left breast (PTV) to a dose of 50.40Gy with concomitant enhance to the lumpectomy cavity known as gross tumour volume (GTV) to a dose of 59.40Gy in 28 fractions. Plans 6MV FB IMRTmore » and 6MV FFFB IMRT had been generated to achieve dose to 95% target volume (TV) and spare Organ at risks (OAR’s). Homogeneity index (HI), conformity index (CI), treatment monitor unit (MU),normal tissues integral dose (NTID) and low dose volume of normal tissue were compared. Results: There was no statistically huge difference among the plans with respect to target volume coverage, CI HI, Ipsilateral Lung and Breast. But statistically significant difference (p< 0.05) as observed in Heart, V5Gy of Contralateral Lung, MU’s NTID and low dose volume of normal tissue. Conclusion: 6MV FB and FFF beam produce almost equivalent plans in IMRT modality with admire to target volume coverage, HI, CI. Beam on time and NTID was determined to be much less in 6MV FFFB IMRT. FFF beam leads to a time saving treatment delivery and fewer NTID in cancer of left breast cases.« less

Stereotactic ultrasound for target volume definition in a patient with prostate cancer and bilateral total hip replacement.

PubMed

Boda-Heggemann, Judit; Haneder, Stefan; Ehmann, Michael; Sihono, Dwi Seno Kuncoro; Wertz, Hansjörg; Mai, Sabine; Kegel, Stefan; Heitmann, Sigrun; von Swietochowski, Sandra; Lohr, Frank; Wenz, Frederik

2015-01-01

Target-volume definition for prostate cancer in patients with bilateral metal total hip replacements (THRs) is a challenge because of metal artifacts in the planning computed tomography (CT) scans. Magnetic resonance imaging (MRI) can be used for matching and prostate delineation; however, at a spatial and temporal distance from the planning CT, identical rectal and vesical filling is difficult to achieve. In addition, MRI may also be impaired by metal artifacts, even resulting in spatial image distortion. Here, we present a method to define prostate target volumes based on ultrasound images acquired during CT simulation and online-matched to the CT data set directly at the planning CT. A 78-year-old patient with cT2cNxM0 prostate cancer with bilateral metal THRs was referred to external beam radiation therapy. T2-weighted MRI was performed on the day of the planning CT with preparation according to a protocol for reproducible bladder and rectal filling. The planning CT was obtained with the immediate acquisition of a 3-dimensional ultrasound data set with a dedicated stereotactic ultrasound system for online intermodality image matching referenced to the isocenter by ceiling-mounted infrared cameras. MRI (offline) and ultrasound images (online) were thus both matched to the CT images for planning. Daily image guided radiation therapy (IGRT) was performed with transabdominal ultrasound and compared with cone beam CT. Because of variations in bladder and rectal filling and metal-induced image distortion in MRI, soft-tissue-based matching of the MRI to CT was not sufficient for unequivocal prostate target definition. Ultrasound-based images could be matched, and prostate, seminal vesicles, and target volumes were reliably defined. Daily IGRT could be successfully completed with transabdominal ultrasound with good accordance between cone beam CT and ultrasound. For prostate cancer patients with bilateral THRs causing artifacts in planning CTs, ultrasound referenced to the isocenter of the CT simulator and acquired with intermodal online coregistration directly at the planning CT is a fast and easy method to reliably delineate the prostate and target volumes and for daily IGRT. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

The CRISPR RNA-guided surveillance complex in Escherichia coli accommodates extended RNA spacers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luo, Michelle L.; Jackson, Ryan N.; Denny, Steven R.

Bacteria and archaea acquire resistance to foreign genetic elements by integrating fragments of foreign DNA into CRISPR (clustered regularly interspaced short palindromic repeats) loci. In Escherichia coli, CRISPR-derived RNAs (crRNAs) assemble with Cas proteins into a multi-subunit surveillance complex called Cascade (CRISPR-associated complex for antiviral defense). Cascade recognizes DNA targets via protein-mediated recognition of a protospacer adjacent motif and complementary base pairing between the crRNA spacer and the DNA target. Previously determined structures of Cascade showed that the crRNA is stretched along an oligomeric protein assembly, leading us to ask how crRNA length impacts the assembly and function of thismore » complex. We found that extending the spacer portion of the crRNA resulted in larger Cascade complexes with altered stoichiometry and preserved in vitro binding affinity for target DNA. Longer spacers also preserved the in vivo ability of Cascade to repress target gene expression and to recruit the Cas3 endonuclease for target degradation. Lastly, longer spacers exhibited enhanced silencing at particular target locations and were sensitive to mismatches within the extended region. These findings demonstrate the flexibility of the Type I-E CRISPR machinery and suggest that spacer length can be modified to fine-tune Cascade activity.« less

The CRISPR RNA-guided surveillance complex in Escherichia coli accommodates extended RNA spacers

DOE PAGES

Luo, Michelle L.; Jackson, Ryan N.; Denny, Steven R.; ...

2016-05-12

Bacteria and archaea acquire resistance to foreign genetic elements by integrating fragments of foreign DNA into CRISPR (clustered regularly interspaced short palindromic repeats) loci. In Escherichia coli, CRISPR-derived RNAs (crRNAs) assemble with Cas proteins into a multi-subunit surveillance complex called Cascade (CRISPR-associated complex for antiviral defense). Cascade recognizes DNA targets via protein-mediated recognition of a protospacer adjacent motif and complementary base pairing between the crRNA spacer and the DNA target. Previously determined structures of Cascade showed that the crRNA is stretched along an oligomeric protein assembly, leading us to ask how crRNA length impacts the assembly and function of thismore » complex. We found that extending the spacer portion of the crRNA resulted in larger Cascade complexes with altered stoichiometry and preserved in vitro binding affinity for target DNA. Longer spacers also preserved the in vivo ability of Cascade to repress target gene expression and to recruit the Cas3 endonuclease for target degradation. Lastly, longer spacers exhibited enhanced silencing at particular target locations and were sensitive to mismatches within the extended region. These findings demonstrate the flexibility of the Type I-E CRISPR machinery and suggest that spacer length can be modified to fine-tune Cascade activity.« less

Target specific proteochemometric model development for BACE1 - protein flexibility and structural water are critical in virtual screening.

PubMed

Manoharan, Prabu; Chennoju, Kiranmai; Ghoshal, Nanda

2015-07-01

BACE1 is an attractive target in Alzheimer's disease (AD) treatment. A rational drug design effort for the inhibition of BACE1 is actively pursued by researchers in both academic and pharmaceutical industries. This continued effort led to the steady accumulation of BACE1 crystal structures, co-complexed with different classes of inhibitors. This wealth of information is used in this study to develop target specific proteochemometric models and these models are exploited for predicting the prospective BACE1 inhibitors. The models developed in this study have performed excellently in predicting the computationally generated poses, separately obtained from single and ensemble docking approaches. The simple protein-ligand contact (SPLC) model outperforms other sophisticated high end models, in virtual screening performance, developed during this study. In an attempt to account for BACE1 protein active site flexibility information in predictive models, we included the change in the area of solvent accessible surface and the change in the volume of solvent accessible surface in our models. The ensemble and single receptor docking results obtained from this study indicate that the structural water mediated interactions improve the virtual screening results. Also, these waters are essential for recapitulating bioactive conformation during docking study. The proteochemometric models developed in this study can be used for the prediction of BACE1 inhibitors, during the early stage of AD drug discovery.

Poster - 36: Effect of Planning Target Volume Coverage on the Dose Delivered in Lung Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dekker, Chris; Wierzbicki, Marcin

2016-08-15

Purpose: In lung radiotherapy, breathing motion may be encompassed by contouring the internal target volume (ITV). Remaining uncertainties are included in a geometrical expansion to the planning target volume (PTV). In IMRT, the treatment is then optimized until a desired PTV fraction is covered by the appropriate dose. The resulting beams often carry high fluence in the PTV margin to overcome low lung density and to generate steep dose gradients. During treatment, the high density tumour can enter the PTV margin, potentially increasing target dose. Thus, planning lung IMRT with a reduced PTV dose may still achieve the desired ITVmore » dose during treatment. Methods: A retrospective analysis was carried out with 25 IMRT plans prescribed to 63 Gy in 30 fractions. The plans were re-normalized to cover various fractions of the PTV by different isodose lines. For each case, the isocentre was moved using 125 shifts derived from all 3D combinations of 0 mm, (PTV margin - 1 mm), and PTV margin. After each shift, the dose was recomputed to approximate the delivered dose. Results and Conclusion: Our plans typically cover 95% of the PTV by 95% of the dose. Reducing the PTV covered to 94% did not significantly reduce the delivered ITV doses for (PTV margin - 1 mm) shifts. Target doses were reduced significantly for all other shifts and planning goals studied. Thus, a reduced planning goal will likely deliver the desired target dose as long as the ITV rarely enters the last mm of the PTV margin.« less

SU-E-J-35: Using CBCT as the Alternative Method of Assessing ITV Volume

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liao, Y; Turian, J; Templeton, A

2015-06-15

Purpose To study the accuracy of Internal Target Volumes (ITVs) created on cone beam CT (CBCT) by comparing the visible target volume on CBCT to volumes (GTV, ITV, and PTV) outlined on free breathing (FB) CT and 4DCT. Methods A Quasar Cylindrical Motion Phantom with a 3cm diameter ball (14.14 cc) embedded within a cork insert was set up to simulate respiratory motion with a period of 4 seconds and amplitude of 2cm superioinferiorly and 1cm anterioposteriorly. FBCT and 4DCT images were acquired. A PTV-4D was created on the 4DCT by applying a uniform margin of 5mm to the ITV-CT.more » PTV-FB was created by applying a margin of the motion range plus 5mm, i.e. total of 1.5cm laterally and 2.5cm superioinferiorly to the GTV outlined on the FBCT. A dynamic conformal arc was planned to treat the PTV-FB with 1mm margin. A CBCT was acquired before the treatment, on which the target was delineated. During the treatment, the position of the target was monitored using the EPID in cine mode. Results ITV-CBCT and ITV-CT were measured to be 56.6 and 62.7cc, respectively, with a Dice Coefficient (DC) of 0.94 and disagreement in center of mass (COM) of 0.59 mm. On the other hand, GTV-FB was 11.47cc, 19% less than the known volume of the ball. PTV-FB and PTV-4D were 149 and 116 cc, with a DC of 0.71. Part of the ITV-CT was not enclosed by the PTV-FB despite the large margin. The cine EPID images have confirmed geometrical misses of the target. Similar under-coverage was observed in one clinical case and captured by the CBCT, where the implanted fiducials moved outside PTV-FB. Conclusion ITV-CBCT is in good agreement with ITV-CT. When 4DCT was not available, CBCT can be an effective alternative in determining and verifying the PTV margin.« less

SU-E-T-572: Normal Lung Tissue Sparing in Radiation Therapy for Locally Advanced Non-Small Cell Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hong, C; Ju, S; Ahn, Y

2015-06-15

Purpose: To compare normal lung-sparing capabilities of three advanced radiation therapy techniques for locally advanced non-small cell lung cancer (LA-NSCLC). Methods: Four-dimensional computed tomography (4DCT) was performed in 10 patients with stage IIIb LA-NSCLC. The internal target volume (ITV); planning target volume (PTV); and organs at risks (OARs) such as spinal cord, total normal lung, heart, and esophagus were delineated for each CT data set. Intensity-modulated radiation therapy (IMRT), Tomohelical-IMRT (TH-IMRT), and TomoDirect-IMRT (TD-IMRT) plans were generated (total prescribed dose, 66 Gy in 33 fractions to the PTV) for each patient. To reduce the normal lung dose, complete and directionalmore » block function was applied outside the normal lung far from the target for both TH-IMRT and TD-IMRT, while pseudo- OAR was set in the same region for IMRT. Dosimetric characteristics of the three plans were compared in terms of target coverage, the sparing capability for the OAR, and the normal tissue complication probability (NTCP). Beam delivery efficiency was also compared. Results: TH-IMRT and TD-IMRT provided better target coverage than IMRT plans. Lung volume receiving ≥–30 Gy, mean dose, and NTCP were significant with TH-IMRT than with IMRT (p=0.006), and volume receiving ≥20–30 Gy was lower in TD-IMRT than in IMRT (p<0.05). Compared with IMRT, TH-IMRT had better sparing effect on the spinal cord (Dmax, NTCP) and heart (V45) (p<0.05). NTCP for the spinal cord, V45 and V60 for the heart, and Dmax for the esophagus were significantly lower in TD-IMRT than in IMRT. The monitor units per fraction were clearly smaller for IMRT than for TH-IMRT and TD-IMRT (p=0.006). Conclusion: In LA-NSCLC, TH-IMRT gave superior PTV coverage and OAR sparing compared to IMRT. TH-IMRT provided better control of the lung volume receiving ≥5–30 Gy. The delivery time and monitor units were lower in TD-IMRT than in TH-IMRT.« less

Exploratory Study of 4D Versus 3D Robust Optimization in Intensity-Modulated Proton Therapy for Lung Cancer

PubMed Central

Liu, Wei; Schild, Steven E.; Chang, Joe Y.; Liao, Zhongxing; Chang, Yu-Hui; Wen, Zhifei; Shen, Jiajian; Stoker, Joshua B.; Ding, Xiaoning; Hu, Yanle; Sahoo, Narayan; Herman, Michael G.; Vargas, Carlos; Keole, Sameer; Wong, William; Bues, Martin

2015-01-01

Background To compare the impact of uncertainties and interplay effect on 3D and 4D robustly optimized intensity-modulated proton therapy (IMPT) plans for lung cancer in an exploratory methodology study. Methods IMPT plans were created for 11 non-randomly selected non-small-cell lung cancer (NSCLC) cases: 3D robustly optimized plans on average CTs with internal gross tumor volume density overridden to irradiate internal target volume, and 4D robustly optimized plans on 4D CTs to irradiate clinical target volume (CTV). Regular fractionation (66 Gy[RBE] in 33 fractions) were considered. In 4D optimization, the CTV of individual phases received non-uniform doses to achieve a uniform cumulative dose. The root-mean-square-dose volume histograms (RVH) measured the sensitivity of the dose to uncertainties, and the areas under the RVH curve (AUCs) were used to evaluate plan robustness. Dose evaluation software modeled time-dependent spot delivery to incorporate interplay effect with randomized starting phases of each field per fraction. Dose-volume histogram indices comparing CTV coverage, homogeneity, and normal tissue sparing were evaluated using Wilcoxon signed-rank test. Results 4D robust optimization plans led to smaller AUC for CTV (14.26 vs. 18.61 (p=0.001), better CTV coverage (Gy[RBE]) [D95% CTV: 60.6 vs 55.2 (p=0.001)], and better CTV homogeneity [D5%–D95% CTV: 10.3 vs 17.7 (p=0.002)] in the face of uncertainties. With interplay effect considered, 4D robust optimization produced plans with better target coverage [D95% CTV: 64.5 vs 63.8 (p=0.0068)], comparable target homogeneity, and comparable normal tissue protection. The benefits from 4D robust optimization were most obvious for the 2 typical stage III lung cancer patients. Conclusions Our exploratory methodology study showed that, compared to 3D robust optimization, 4D robust optimization produced significantly more robust and interplay-effect-resistant plans for targets with comparable dose distributions for normal tissues. A further study with a larger and more realistic patient population is warranted to generalize the conclusions. PMID:26725727

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heijkoop, Sabrina T., E-mail: s.heijkoop@erasmusmc.nl; Langerak, Thomas R.; Quint, Sandra

Purpose: To evaluate the clinical implementation of an online adaptive plan-of-the-day protocol for nonrigid target motion management in locally advanced cervical cancer intensity modulated radiation therapy (IMRT). Methods and Materials: Each of the 64 patients had four markers implanted in the vaginal fornix to verify the position of the cervix during treatment. Full and empty bladder computed tomography (CT) scans were acquired prior to treatment to build a bladder volume-dependent cervix-uterus motion model for establishment of the plan library. In the first phase of clinical implementation, the library consisted of one IMRT plan based on a single model-predicted internal targetmore » volume (mpITV), covering the target for the whole pretreatment observed bladder volume range, and a 3D conformal radiation therapy (3DCRT) motion-robust backup plan based on the same mpITV. The planning target volume (PTV) combined the ITV and nodal clinical target volume (CTV), expanded with a 1-cm margin. In the second phase, for patients showing >2.5-cm bladder-induced cervix-uterus motion during planning, two IMRT plans were constructed, based on mpITVs for empty-to-half-full and half-full-to-full bladder. In both phases, a daily cone beam CT (CBCT) scan was acquired to first position the patient based on bony anatomy and nodal targets and then select the appropriate plan. Daily post-treatment CBCT was used to verify plan selection. Results: Twenty-four and 40 patients were included in the first and second phase, respectively. In the second phase, 11 patients had two IMRT plans. Overall, an IMRT plan was used in 82.4% of fractions. The main reasons for selecting the motion-robust backup plan were uterus outside the PTV (27.5%) and markers outside their margin (21.3%). In patients with two IMRT plans, the half-full-to-full bladder plan was selected on average in 45% of the first 12 fractions, which was reduced to 35% in the last treatment fractions. Conclusions: The implemented online adaptive plan-of-the-day protocol for locally advanced cervical cancer enables (almost) daily tissue-sparing IMRT.« less

Disease Control After Reduced Volume Conformal and Intensity Modulated Radiation Therapy for Childhood Craniopharyngioma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Merchant, Thomas E., E-mail: thomas.merchant@stjude.org; Kun, Larry E.; Hua, Chia-Ho

2013-03-15

Purpose: To estimate the rate of disease control after conformal radiation therapy using reduced clinical target volume (CTV) margins and to determine factors that predict for tumor progression. Methods and Materials: Eighty-eight children (median age, 8.5 years; range, 3.2-17.6 years) received conformal or intensity modulated radiation therapy between 1998 and 2009. The study group included those prospectively treated from 1998 to 2003, using a 10-mm CTV, defined as the margin surrounding the solid and cystic tumor targeted to receive the prescription dose of 54 Gy. The CTV margin was subsequently reduced after 2003, yielding 2 groups of patients: those treatedmore » with a CTV margin greater than 5 mm (n=26) and those treated with a CTV margin less than or equal to 5 mm (n=62). Disease progression was estimated on the basis of additional variables including sex, race, extent of resection, tumor interventions, target volume margins, and frequency of weekly surveillance magnetic resonance (MR) imaging during radiation therapy. Median follow-up was 5 years. Results: There was no difference between progression-free survival rates based on CTV margins (>5 mm vs ≤5 mm) at 5 years (88.1% ± 6.3% vs 96.2% ± 4.4% [P=.6386]). There were no differences based on planning target volume (PTV) margins (or combined CTV plus PTV margins). The PTV was systematically reduced from 5 to 3 mm during the time period of the study. Factors predictive of superior progression-free survival included Caucasian race (P=.0175), no requirement for cerebrospinal fluid shunting (P=.0066), and number of surveillance imaging studies during treatment (P=.0216). Patients whose treatment protocol included a higher number of weekly surveillance MR imaging evaluations had a lower rate of tumor progression. Conclusions: These results suggest that targeted volume reductions for radiation therapy using smaller margins are feasible and safe but require careful monitoring. We are currently investigating the differences in outcome based on host factors to explain the results.« less

Liquid Metering Centrifuge Sticks (LMCS): A Centrifugal Approach to Metering Known Sample Volumes for Colorimetric Solid Phase Extraction (C-SPE)

NASA Technical Reports Server (NTRS)

Gazda, Daniel B.; Schultz, John R.; Clarke, Mark S.

2007-01-01

Phase separation is one of the most significant obstacles encountered during the development of analytical methods for water quality monitoring in spacecraft environments. Removing air bubbles from water samples prior to analysis is a routine task on earth; however, in the absence of gravity, this routine task becomes extremely difficult. This paper details the development and initial ground testing of liquid metering centrifuge sticks (LMCS), devices designed to collect and meter a known volume of bubble-free water in microgravity. The LMCS uses centrifugal force to eliminate entrapped air and reproducibly meter liquid sample volumes for analysis with Colorimetric Solid Phase Extraction (C-SPE). C-SPE is a sorption-spectrophotometric platform that is being developed as a potential spacecraft water quality monitoring system. C-SPE utilizes solid phase extraction membranes impregnated with analyte-specific colorimetric reagents to concentrate and complex target analytes in spacecraft water samples. The mass of analyte extracted from the water sample is determined using diffuse reflectance (DR) data collected from the membrane surface and an analyte-specific calibration curve. The analyte concentration can then be calculated from the mass of extracted analyte and the volume of the sample analyzed. Previous flight experiments conducted in microgravity conditions aboard the NASA KC-135 aircraft demonstrated that the inability to collect and meter a known volume of water using a syringe was a limiting factor in the accuracy of C-SPE measurements. Herein, results obtained from ground based C-SPE experiments using ionic silver as a test analyte and either the LMCS or syringes for sample metering are compared to evaluate the performance of the LMCS. These results indicate very good agreement between the two sample metering methods and clearly illustrate the potential of utilizing centrifugal forces to achieve phase separation and metering of water samples in microgravity.

Folate-conjugated boron nitride nanospheres for targeted delivery of anticancer drugs.

PubMed

Feng, Shini; Zhang, Huijie; Yan, Ting; Huang, Dandi; Zhi, Chunyi; Nakanishi, Hideki; Gao, Xiao-Dong

With its unique physical and chemical properties and structural similarity to carbon, boron nitride (BN) has attracted considerable attention and found many applications. Biomedical applications of BN have recently started to emerge, raising great hopes in drug and gene delivery. Here, we developed a targeted anticancer drug delivery system based on folate-conjugated BN nanospheres (BNNS) with receptor-mediated targeting. Folic acid (FA) was successfully grafted onto BNNS via esterification reaction. In vitro cytotoxicity assay showed that BNNS-FA complexes were non-toxic to HeLa cells up to a concentration of 100 μg/mL. Then, doxorubicin hydrochloride (DOX), a commonly used anticancer drug, was loaded onto BNNS-FA complexes. BNNS-FA/DOX complexes were stable at pH 7.4 but effectively released DOX at pH 5.0, which exhibited a pH sensitive and sustained release pattern. BNNS-FA/DOX complexes could be recognized and specifically internalized by HeLa cells via FA receptor-mediated endocytosis. BNNS-FA/DOX complexes exhibited greater cytotoxicity to HeLa cells than free DOX and BNNS/DOX complexes due to the increased cellular uptake of DOX mediated by the FA receptor. Therefore, BNNS-FA complexes had strong potential for targeted cancer therapy.

Pragmatics & Language Learning. Volume 12

ERIC Educational Resources Information Center

Kasper, Gabriele, Ed.; Nguyen, Hanh thi, Ed.; Yoshimi, Dina Rudolph, Ed.; Yoshioka, Jim K., Ed.

2010-01-01

This volume examines the organization of second language and multilingual speakers' talk and pragmatic knowledge across a range of naturalistic and experimental activities. Based on data collected on Danish, English, Hawai'i Creole, Indonesian, and Japanese as target languages, the contributions explore the nexus of pragmatic knowledge,…

Communications strategies on alcohol and highway safety. Volume 2, High school youth

DOT National Transportation Integrated Search

1975-02-01

The study is in two volumes, the first dealing with adults aged 18-55, the second with high school youth. Both identify target populations and communications strategies for encouraging personal action steps to prevent drunk driving. One fourth of hig...

Communications strategies on alcohol and highway safety. Volume 1, Adults 18-55

DOT National Transportation Integrated Search

1975-02-01

The study is in two volumes, the first dealing with adults aged 18-55, the second with high school youth. Both identify target populations and communications strategies for encouraging personal action steps to prevent drunk driving. Fully 54% of adul...

Capturing microRNA targets using an RNA-induced silencing complex (RISC)-trap approach

PubMed Central

Cambronne, Xiaolu A.; Shen, Rongkun; Auer, Paul L.; Goodman, Richard H.

2012-01-01

Identifying targets is critical for understanding the biological effects of microRNA (miRNA) expression. The challenge lies in characterizing the cohort of targets for a specific miRNA, especially when targets are being actively down-regulated in miRNA– RNA-induced silencing complex (RISC)–messengerRNA (mRNA) complexes. We have developed a robust and versatile strategy called RISCtrap to stabilize and purify targets from this transient interaction. Its utility was demonstrated by determining specific high-confidence target datasets for miR-124, miR-132, and miR-181 that contained known and previously unknown transcripts. Two previously unknown miR-132 targets identified with RISCtrap, adaptor protein CT10 regulator of kinase 1 (CRK1) and tight junction-associated protein 1 (TJAP1), were shown to be endogenously regulated by miR-132 in adult mouse forebrain. The datasets, moreover, differed in the number of targets and in the types and frequency of microRNA recognition element (MRE) motifs, thus revealing a previously underappreciated level of specificity in the target sets regulated by individual miRNAs. PMID:23184980

Capturing microRNA targets using an RNA-induced silencing complex (RISC)-trap approach.

PubMed

Cambronne, Xiaolu A; Shen, Rongkun; Auer, Paul L; Goodman, Richard H

2012-12-11

Identifying targets is critical for understanding the biological effects of microRNA (miRNA) expression. The challenge lies in characterizing the cohort of targets for a specific miRNA, especially when targets are being actively down-regulated in miRNA- RNA-induced silencing complex (RISC)-messengerRNA (mRNA) complexes. We have developed a robust and versatile strategy called RISCtrap to stabilize and purify targets from this transient interaction. Its utility was demonstrated by determining specific high-confidence target datasets for miR-124, miR-132, and miR-181 that contained known and previously unknown transcripts. Two previously unknown miR-132 targets identified with RISCtrap, adaptor protein CT10 regulator of kinase 1 (CRK1) and tight junction-associated protein 1 (TJAP1), were shown to be endogenously regulated by miR-132 in adult mouse forebrain. The datasets, moreover, differed in the number of targets and in the types and frequency of microRNA recognition element (MRE) motifs, thus revealing a previously underappreciated level of specificity in the target sets regulated by individual miRNAs.

The SET1 Complex Selects Actively Transcribed Target Genes via Multivalent Interaction with CpG Island Chromatin.

PubMed

Brown, David A; Di Cerbo, Vincenzo; Feldmann, Angelika; Ahn, Jaewoo; Ito, Shinsuke; Blackledge, Neil P; Nakayama, Manabu; McClellan, Michael; Dimitrova, Emilia; Turberfield, Anne H; Long, Hannah K; King, Hamish W; Kriaucionis, Skirmantas; Schermelleh, Lothar; Kutateladze, Tatiana G; Koseki, Haruhiko; Klose, Robert J

2017-09-05

Chromatin modifications and the promoter-associated epigenome are important for the regulation of gene expression. However, the mechanisms by which chromatin-modifying complexes are targeted to the appropriate gene promoters in vertebrates and how they influence gene expression have remained poorly defined. Here, using a combination of live-cell imaging and functional genomics, we discover that the vertebrate SET1 complex is targeted to actively transcribed gene promoters through CFP1, which engages in a form of multivalent chromatin reading that involves recognition of non-methylated DNA and histone H3 lysine 4 trimethylation (H3K4me3). CFP1 defines SET1 complex occupancy on chromatin, and its multivalent interactions are required for the SET1 complex to place H3K4me3. In the absence of CFP1, gene expression is perturbed, suggesting that normal targeting and function of the SET1 complex are central to creating an appropriately functioning vertebrate promoter-associated epigenome. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

RNA editing of microRNA prevents RNA-induced silencing complex recognition of target mRNA

PubMed Central

Cui, Yalei; Huang, Tianzhi; Zhang, Xiaobo

2015-01-01

MicroRNAs (miRNAs) integrate with Argonaut (Ago) to create the RNA-induced silencing complex, and regulate gene expression by silencing target mRNAs. RNA editing of miRNA may affect miRNA processing, assembly of the Ago complex and target mRNA binding. However, the function of edited miRNA, assembled within the Ago complex, has not been extensively investigated. In this study, sequence analysis of the Ago complex of Marsupenaeus japonicus shrimp infected with white spot syndrome virus (WSSV) revealed that host ADAR (adenosine deaminase acting on RNA) catalysed A-to-I RNA editing of a viral miRNA (WSSV-miR-N12) at the +16 site. This editing of the non-seed sequence did not affect association of the edited miRNA with the Ago protein, but inhibited interaction between the miRNA and its target gene (wsv399). The WSSV early gene wsv399 inhibited WSSV infection. As a result, the RNA editing of miRNA caused virus latency. Our results highlight a novel example of miRNA editing in the miRNA-induced silencing complex. PMID:26674414

The Lateral Decubitus Breast Boost: Description, Rationale, and Efficacy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ludwig, Michelle S., E-mail: mludwig@mdanderson.or; McNeese, Marsha D.; Buchholz, Thomas A.

2010-01-15

Purpose: To describe and evaluate the modified lateral decubitus boost, a breast irradiation technique. Patients are repositioned and resimulated for electron boost to minimize the necessary depth for the electron beam and optimize target volume coverage. Methods and Materials: A total of 2,606 patients were treated with post-lumpectomy radiation at our institution between January 1, 2000, and February 1, 2008. Of these, 231 patients underwent resimulation in the lateral decubitus position with electron boost. Distance from skin to the maximal depth of target volume was measured in both the original and boost plans. Age, body mass index (BMI), boost electronmore » energy, and skin reaction were evaluated. Results: Resimulation in the lateral decubitus position reduced the distance from skin to maximal target volume depth in all patients. Average depth reduction by repositioning was 2.12 cm, allowing for an average electron energy reduction of approximately 7 MeV. Mean skin entrance dose was reduced from about 90% to about 85% (p < 0.001). Only 14 patients (6%) experienced moist desquamation in the boost field at the end of treatment. Average BMI of these patients was 30.4 (range, 17.8-50.7). BMI greater than 30 was associated with more depth reduction by repositioning and increased risk of moist desquamation. Conclusions: The lateral decubitus position allows for a decrease in the distance from the skin to the target volume depth, improving electron coverage of the tumor bed while reducing skin entrance dose. This is a well-tolerated regimen for a patient population with a high BMI or deep tumor location.« less

Planning magnetic resonance imaging for prostate cancer intensity-modulated radiation therapy: Impact on target volumes, radiotherapy dose and androgen deprivation administration.

PubMed

Horsley, Patrick J; Aherne, Noel J; Edwards, Grace V; Benjamin, Linus C; Wilcox, Shea W; McLachlan, Craig S; Assareh, Hassan; Welshman, Richard; McKay, Michael J; Shakespeare, Thomas P

2015-03-01

Magnetic resonance imaging (MRI) scans are increasingly utilized for radiotherapy planning to contour the primary tumors of patients undergoing intensity-modulated radiation therapy (IMRT). These scans may also demonstrate cancer extent and may affect the treatment plan. We assessed the impact of planning MRI detection of extracapsular extension, seminal vesicle invasion, or adjacent organ invasion on the staging, target volume delineation, doses, and hormonal therapy of patients with prostate cancer undergoing IMRT. The records of 509 consecutive patients with planning MRI scans being treated with IMRT for prostate cancer between January 2010 and July 2012 were retrospectively reviewed. Tumor staging and treatment plans before and after MRI were compared. Of the 509 patients, 103 (20%) were upstaged and 44 (9%) were migrated to a higher risk category as a result of findings at MRI. In 94 of 509 patients (18%), the MRI findings altered management. Ninety-four of 509 patients (18%) had a change to their clinical target volume (CTV) or treatment technique, and in 41 of 509 patients (8%) the duration of hormone therapy was changed because of MRI findings. The use of radiotherapy planning MRI altered CTV design, dose and/or duration of androgen deprivation in 18% of patients in this large, single institution series of men planned for dose-escalated prostate IMRT. This has substantial implications for radiotherapy target volumes and doses, as well as duration of androgen deprivation. Further research is required to investigate whether newer MRI techniques can simultaneously fulfill staging and radiotherapy contouring roles. © 2014 Wiley Publishing Asia Pty Ltd.

[State of the art in fluid and volume therapy : A user-friendly staged concept].

PubMed

Rehm, M; Hulde, N; Kammerer, T; Meidert, A S; Hofmann-Kiefer, K

2017-03-01

Adequate fluid therapy is highly important for the perioperative outcome of our patients. Both, hypovolemia and hypervolemia can lead to an increase in perioperative complications and can impair the outcome. Therefore, perioperative infusion therapy should be target-oriented. The main target is to maintain the patient's preoperative normovolemia by using a sophisticated, rational infusion strategy.Perioperative fluid losses should be discriminated from volume losses (surgical blood loss or interstitial volume losses containing protein). Fluid losses as urine or perspiratio insensibilis (0.5-1.0 ml/kg/h) should be replaced by balanced crystalloids in a ratio of 1:1. Volume therapy step 1: Blood loss up to a maximum value of 20% of the patient's blood volume should be replaced by balanced crystalloids in a ratio of 4(-5):1. Volume therapy step 2: Higher blood losses should be treated by using iso-oncotic, preferential balanced colloids in a ratio of 1:1. For this purpose hydroxyethyl starch can also be used perioperatively if there is no respective contraindication, such as sepsis, burn injuries, critically ill patients, renal impairment or renal replacement therapy, and severe coagulopathy. Volume therapy step 3: If there is an indication for red cell concentrates or coagulation factors, a differentiated application of blood and blood products should be performed.

Ambient temperature and volume of perihematomal edema in acute intracerebral haemorrhage: the INTERACT1 study.

PubMed

Zheng, Danni; Arima, Hisatomi; Heeley, Emma; Karpin, Anne; Yang, Jie; Chalmers, John; Anderson, Craig S

2015-01-01

As no human data exist, we aimed to determine the relation between ambient temperature and volume of perihematomal 'cerebral' edema in acute spontaneous intracerebral haemorrhage (ICH) among Chinese participants of the pilot phase, Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT1). INTERACT1 was a multicenter, open, blind outcome assessed, randomized controlled trial of intensive (systolic target <140 mmHg) vs. guideline-recommended (systolic target <180 mmHg) blood pressure (BP) lowering in 404 patients with acute ICH. Data on ambient temperature (mean, minimum, maximum, and range) on the day of each participant's ICH obtained from China Meteorological Data Sharing Service System were linked to other data including edema volumes. Multivariable regression analyses were performed to evaluate association between ambient temperature and edema volumes. A generalized linear regression model with a generalized estimating equations approach (GEE) was used to assess any association of ambient temperature and change in edema volume over 72 h. A total of 250 of all 384 Chinese participants had complete data that showed positive associations between ambient temperature (mean and minimum temperatures) and edema volumes at each time point over 72 h after hospital admission (all P < 0·05). All temperature parameters except diurnal temperature range were positively associated with edema volume after adjustment for confounding variables (all P < 0·02). An apparent positive association exists between ambient temperature and perihematomal edema volume in acute spontaneous ICH. © 2014 World Stroke Organization.

A method for deriving a 4D-interpolated balanced planning target for mobile tumor radiotherapy.

PubMed

Roland, Teboh; Hales, Russell; McNutt, Todd; Wong, John; Simari, Patricio; Tryggestad, Erik

2012-01-01

Tumor control and normal tissue toxicity are strongly correlated to the tumor and normal tissue volumes receiving high prescribed dose levels in the course of radiotherapy. Planning target definition is, therefore, crucial to ensure favorable clinical outcomes. This is especially important for stereotactic body radiation therapy of lung cancers, characterized by high fractional doses and steep dose gradients. The shift in recent years from population-based to patient-specific treatment margins, as facilitated by the emergence of 4D medical imaging capabilities, is a major improvement. The commonly used motion-encompassing, or internal-target volume (ITV), target definition approach provides a high likelihood of coverage for the mobile tumor but inevitably exposes healthy tissue to high prescribed dose levels. The goal of this work was to generate an interpolated balanced planning target that takes into account both tumor coverage and normal tissue sparing from high prescribed dose levels, thereby improving on the ITV approach. For each 4DCT dataset, 4D deformable image registration was used to derive two bounding targets, namely, a 4D-intersection and a 4D-composite target which minimized normal tissue exposure to high prescribed dose levels and maximized tumor coverage, respectively. Through definition of an "effective overlap volume histogram" the authors derived an "interpolated balanced planning target" intended to balance normal tissue sparing from prescribed doses with tumor coverage. To demonstrate the dosimetric efficacy of the interpolated balanced planning target, the authors performed 4D treatment planning based on deformable image registration of 4D-CT data for five previously treated lung cancer patients. Two 4D plans were generated per patient, one based on the interpolated balanced planning target and the other based on the conventional ITV target. Plans were compared for tumor coverage and the degree of normal tissue sparing resulting from the new approach was quantified. Analysis of the 4D dose distributions from all five patients showed that while achieving tumor coverage comparable to the ITV approach, the new planning target definition resulted in reductions of lung V(10), V(20), and V(30) of 6.3% ± 1.7%, 10.6% ± 3.9%, and 12.9% ± 5.5%, respectively, as well as reductions in mean lung dose, mean dose to the GTV-ring and mean heart dose of 8.8% ± 2.5%, 7.2% ± 2.5%, and 10.6% ± 3.6%, respectively. The authors have developed a simple and systematic approach to generate a 4D-interpolated balanced planning target volume that implicitly incorporates the dynamics of respiratory-organ motion without requiring 4D-dose computation or optimization. Preliminary results based on 4D-CT data of five previously treated lung patients showed that this new planning target approach may improve normal tissue sparing without sacrificing tumor coverage.

78 FR 3934 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-17

... Symbols, 2) increase the maker fee for complex orders that trade against Priority Customer complex orders... provides volume-based tiered rebates for Priority Customer complex orders in the Select Symbols (excluding... orders trade with non-Priority Customer orders in the complex order book. In the Select Symbols, the...

Current Scientific Approaches to Decision Making in Complex Systems. 3. Volume 2. Conference Position Papers

DTIC Science & Technology

1980-01-01

Search: Traffic on a Multi- dimensional Structure R. i. Atkin, University of Essex, England b. Annex. Volume 3: Decision: Foundation and Practice Brian R...Gaines, University of Essex, England Volume 4: Competing Modes of Cognition and Communication in Simulated and Self-Reflective Systems Stein Braten... University of Oslo, Norway Volume 5: On the Spontaneous Emergence of Decision Making Constraints in Communicating Hierarchical Structure John S

Does linear separability really matter? Complex visual search is explained by simple search

PubMed Central

Vighneshvel, T.; Arun, S. P.

2013-01-01

Visual search in real life involves complex displays with a target among multiple types of distracters, but in the laboratory, it is often tested using simple displays with identical distracters. Can complex search be understood in terms of simple searches? This link may not be straightforward if complex search has emergent properties. One such property is linear separability, whereby search is hard when a target cannot be separated from its distracters using a single linear boundary. However, evidence in favor of linear separability is based on testing stimulus configurations in an external parametric space that need not be related to their true perceptual representation. We therefore set out to assess whether linear separability influences complex search at all. Our null hypothesis was that complex search performance depends only on classical factors such as target-distracter similarity and distracter homogeneity, which we measured using simple searches. Across three experiments involving a variety of artificial and natural objects, differences between linearly separable and nonseparable searches were explained using target-distracter similarity and distracter heterogeneity. Further, simple searches accurately predicted complex search regardless of linear separability (r = 0.91). Our results show that complex search is explained by simple search, refuting the widely held belief that linear separability influences visual search. PMID:24029822

Trans-acting RNAs as molecular probes for monitoring time-dependent structural change of an RNA complex adapting two structures.

PubMed

Maeda, Yuri; Furuta, Hiroyuki; Ikawa, Yoshiya

2011-03-01

As dynamic structural changes are pivotal for the functions of some classes of RNA molecule, it is important to develop methods to monitor structural changes in RNA in a time-dependent manner without chemical modification. Based on previous reports that trans-acting RNAs can be used as probes for analysis and control of 3D structures of target RNAs, we applied this method to monitor time-dependent structural changes in RNA. We designed and performed a proof-of-principle study using a simple model RNA complex that adopts two different structures as a target. The time-dependent structural changes in the target RNA were successfully monitored using two trans-acting RNAs, which stably form a ternary complex with the bimolecular target RNA and act as a catalyst to join two RNA fragments of the target complex, respectively. Copyright © 2010 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Investigation of effective decision criteria for multiobjective optimization in IMRT.

PubMed

Holdsworth, Clay; Stewart, Robert D; Kim, Minsun; Liao, Jay; Phillips, Mark H

2011-06-01

To investigate how using different sets of decision criteria impacts the quality of intensity modulated radiation therapy (IMRT) plans obtained by multiobjective optimization. A multiobjective optimization evolutionary algorithm (MOEA) was used to produce sets of IMRT plans. The MOEA consisted of two interacting algorithms: (i) a deterministic inverse planning optimization of beamlet intensities that minimizes a weighted sum of quadratic penalty objectives to generate IMRT plans and (ii) an evolutionary algorithm that selects the superior IMRT plans using decision criteria and uses those plans to determine the new weights and penalty objectives of each new plan. Plans resulting from the deterministic algorithm were evaluated by the evolutionary algorithm using a set of decision criteria for both targets and organs at risk (OARs). Decision criteria used included variation in the target dose distribution, mean dose, maximum dose, generalized equivalent uniform dose (gEUD), an equivalent uniform dose (EUD(alpha,beta) formula derived from the linear-quadratic survival model, and points on dose volume histograms (DVHs). In order to quantatively compare results from trials using different decision criteria, a neutral set of comparison metrics was used. For each set of decision criteria investigated, IMRT plans were calculated for four different cases: two simple prostate cases, one complex prostate Case, and one complex head and neck Case. When smaller numbers of decision criteria, more descriptive decision criteria, or less anti-correlated decision criteria were used to characterize plan quality during multiobjective optimization, dose to OARs and target dose variation were reduced in the final population of plans. Mean OAR dose and gEUD (a = 4) decision criteria were comparable. Using maximum dose decision criteria for OARs near targets resulted in inferior populations that focused solely on low target variance at the expense of high OAR dose. Target dose range, (D(max) - D(min)), decision criteria were found to be most effective for keeping targets uniform. Using target gEUD decision criteria resulted in much lower OAR doses but much higher target dose variation. EUD(alpha,beta) based decision criteria focused on a region of plan space that was a compromise between target and OAR objectives. None of these target decision criteria dominated plans using other criteria, but only focused on approaching a different area of the Pareto front. The choice of decision criteria implemented in the MOEA had a significant impact on the region explored and the rate of convergence toward the Pareto front. When more decision criteria, anticorrelated decision criteria, or decision criteria with insufficient information were implemented, inferior populations are resulted. When more informative decision criteria were used, such as gEUD, EUD(alpha,beta), target dose range, and mean dose, MOEA optimizations focused on approaching different regions of the Pareto front, but did not dominate each other. Using simple OAR decision criteria and target EUD(alpha,beta) decision criteria demonstrated the potential to generate IMRT plans that significantly reduce dose to OARs while achieving the same or better tumor control when clinical requirements on target dose variance can be met or relaxed.

Crystal Structure of a CRISPR RNA-guided Surveillance Complex Bound to a ssDNA Target

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mulepati, Sabin; Heroux, Annie; Bailey, Scott

In prokaryotes, RNA derived from type I and type III CRISPR loci direct large ribonucleoprotein complexes to destroy invading bacteriophage and plasmids. In Escherichia coli, this 405-kilodalton complex is called Cascade. We report the crystal structure of Cascade bound to a single-stranded DNA (ssDNA) target at a resolution of 3.03 angstroms. The structure reveals that the CRISPR RNA and target strands do not form a double helix but instead adopt an underwound ribbon-like structure. This noncanonical structure is facilitated by rotation of every sixth nucleotide out of the RNA-DNA hybrid and is stabilized by the highly interlocked organization of proteinmore » subunits. These studies provide insight into both the assembly and the activity of this complex and suggest a mechanism to enforce fidelity of target binding.« less

Crystal structure of a CRISPR RNA-guided surveillance complex bound to a ssDNA target

PubMed Central

Mulepati, Sabin; Héroux, Annie; Bailey, Scott

2015-01-01

In prokaryotes, RNA derived from type I and type III CRISPR loci direct large ribonucleoprotein complexes to destroy invading bacteriophage and plasmids. In Escherichia coli, this 405-kDa complex is called Cascade. Here we report the 3.03Å crystal structure of Cascade bound to a single-stranded DNA target. The structure reveals that the CRISPR RNA and target strands do not form a double helix but instead adopt an underwound ribbon-like structure. This non-canonical structure is facilitated by rotation of every sixth nucleotide out of the RNA-DNA hybrid and is stabilized by the highly interlocked organization of protein subunits. These studies provide insight into both the assembly and the activity of this complex and suggest a mechanism to enforce fidelity of target binding. PMID:25123481

Essential Requirements for Robust Signaling in Hfq Dependent Small RNA Networks

PubMed Central

Adamson, David N.; Lim, Han N.

2011-01-01

Bacteria possess networks of small RNAs (sRNAs) that are important for modulating gene expression. At the center of many of these sRNA networks is the Hfq protein. Hfq's role is to quickly match cognate sRNAs and target mRNAs from among a large number of possible combinations and anneal them to form duplexes. Here we show using a kinetic model that Hfq can efficiently and robustly achieve this difficult task by minimizing the sequestration of sRNAs and target mRNAs in Hfq complexes. This sequestration can be reduced by two non-mutually exclusive kinetic mechanisms. The first mechanism involves heterotropic cooperativity (where sRNA and target mRNA binding to Hfq is influenced by other RNAs bound to Hfq); this cooperativity can selectively decrease singly-bound Hfq complexes and ternary complexes with non-cognate sRNA-target mRNA pairs while increasing cognate ternary complexes. The second mechanism relies on frequent RNA dissociation enabling the rapid cycling of sRNAs and target mRNAs among different Hfq complexes; this increases the probability the cognate ternary complex forms before the sRNAs and target mRNAs degrade. We further demonstrate that the performance of sRNAs in isolation is not predictive of their performance within a network. These findings highlight the importance of experimentally characterizing duplex formation in physiologically relevant contexts with multiple RNAs competing for Hfq. The model will provide a valuable framework for guiding and interpreting these experiments. PMID:21876666

SU-E-T-578: On Definition of Minimum and Maximum Dose for Target Volume

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gong, Y; Yu, J; Xiao, Y

Purpose: This study aims to investigate the impact of different minimum and maximum dose definitions in radiotherapy treatment plan quality evaluation criteria by using tumor control probability (TCP) models. Methods: Dosimetric criteria used in RTOG 1308 protocol are used in the investigation. RTOG 1308 is a phase III randomized trial comparing overall survival after photon versus proton chemoradiotherapy for inoperable stage II-IIIB NSCLC. The prescription dose for planning target volume (PTV) is 70Gy. Maximum dose (Dmax) should not exceed 84Gy and minimum dose (Dmin) should not go below 59.5Gy in order for the plan to be “per protocol” (satisfactory).A mathematicalmore » model that simulates the characteristics of PTV dose volume histogram (DVH) curve with normalized volume is built. The Dmax and Dmin are noted as percentage volumes Dη% and D(100-δ)%, with η and d ranging from 0 to 3.5. The model includes three straight line sections and goes through four points: D95%= 70Gy, Dη%= 84Gy, D(100-δ)%= 59.5 Gy, and D100%= 0Gy. For each set of η and δ, the TCP value is calculated using the inhomogeneously irradiated tumor logistic model with D50= 74.5Gy and γ50=3.52. Results: TCP varies within 0.9% with η; and δ values between 0 and 1. With η and η varies between 0 and 2, TCP change was up to 2.4%. With η and δ variations from 0 to 3.5, maximum of 8.3% TCP difference is seen. Conclusion: When defined maximum and minimum volume varied more than 2%, significant TCP variations were seen. It is recommended less than 2% volume used in definition of Dmax or Dmin for target dosimetric evaluation criteria. This project was supported by NIH grants U10CA180868, U10CA180822, U24CA180803, U24CA12014 and PA CURE Grant.« less

Optimal application of the Contura multilumen balloon breast brachytherapy catheter vacuum port to deliver accelerated partial breast irradiation.

PubMed

Tokita, Kenneth M; Cuttino, Laurie W; Vicini, Frank A; Arthur, Douglas W; Todor, Dorin A; Julian, Thomas B; Lyden, Maureen R

2011-01-01

The impact of using the Contura multilumen balloon (MLB) (SenoRx, Inc., Irvine, CA) breast brachytherapy catheter's vacuum port in patients treated with accelerated partial breast irradiation (APBI) was analyzed. Data from 32 patients at two sites were reviewed. Variables analyzed included the seroma fluid (SF):air volume around the MLB before and after vacuum port use and on its ability to improve (1) the eligibility of patients for APBI and (2) dose coverage of the planning target volume for evaluation (PTV_EVAL) in eligible patients. The median SF/air volume before vacuum removal was 6.8 cc vs. 0.8 cc after vacuum removal (median reduction in SF/air volume was 90.5%). Before vacuum port use, the median SF/air volume expressed as percentage of the PTV_EVAL was 7.8% (range, 1.9-26.6) in all patients. After application of the vacuum, this was reduced to 1.2%. Before vacuum port use, 10 (31.3%) patients were not considered acceptable candidates for APBI because the SF/air volume:PTV_EVAL ratio (SF:PTV) was greater than 10% (range, 10.1-26.6%; median, 15.2%). After vacuum port use, the median SF:PTV ratio was 1.6% for a median reduction of 91.5%. In addition, the percentage of the prescribed dose covering greater than or equal to 90% of the PTV_EVAL proportionally increased a median of 8% (range, 3-10%) in eligible patients. Use of the Contura MLB vacuum port significantly improved the conformity of the target tissue to the balloon surface, leading to reproducible dose delivery and increased target volume coverage. In addition, application of the vacuum allowed the safe treatment of unacceptable patients with APBI. Copyright © 2011 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Clinical target volume delineation in glioblastomas: pre-operative versus post-operative/pre-radiotherapy MRI

PubMed Central

Farace, P; Giri, M G; Meliadò, G; Amelio, D; Widesott, L; Ricciardi, G K; Dall'Oglio, S; Rizzotti, A; Sbarbati, A; Beltramello, A; Maluta, S; Amichetti, M

2011-01-01

Objectives Delineation of clinical target volume (CTV) is still controversial in glioblastomas. In order to assess the differences in volume and shape of the radiotherapy target, the use of pre-operative vs post-operative/pre-radiotherapy T1 and T2 weighted MRI was compared. Methods 4 CTVs were delineated in 24 patients pre-operatively and post-operatively using T1 contrast-enhanced (T1PRECTV and T1POSTCTV) and T2 weighted images (T2PRECTV and T2POSTCTV). Pre-operative MRI examinations were performed the day before surgery, whereas post-operative examinations were acquired 1 month after surgery and before chemoradiation. A concordance index (CI) was defined as the ratio between the overlapping and composite volumes. Results The volumes of T1PRECTV and T1POSTCTV were not statistically different (248 ± 88 vs 254 ± 101), although volume differences >100 cm3 were observed in 6 out of 24 patients. A marked increase due to tumour progression was shown in three patients. Three patients showed a decrease because of a reduced mass effect. A significant reduction occurred between pre-operative and post-operative T2 volumes (139 ± 68 vs 78 ± 59). Lack of concordance was observed between T1PRECTV and T1POSTCTV (CI = 0.67 ± 0.09), T2PRECTV and T2POSTCTV (CI = 0.39 ± 0.20) and comparing the portion of the T1PRECTV and T1POSTCTV not covered by that defined on T2PRECTV images (CI = 0.45 ± 0.16 and 0.44 ± 0.17, respectively). Conclusion Using T2 MRI, huge variations can be observed in peritumoural oedema, which are probably due to steroid treatment. Using T1 MRI, brain shifts after surgery and possible progressive enhancing lesions produce substantial differences in CTVs. Our data support the use of post-operative/pre-radiotherapy T1 weighted MRI for planning purposes. PMID:21045069

Dosimetric benefits of automation in the treatment of lower thoracic esophageal cancer: Is manual planning still an alternative option?

PubMed

Li, Xiadong; Wang, Lu; Wang, Jiahao; Han, Xu; Xia, Bing; Wu, Shixiu; Hu, Weigang

2017-01-01

This study aimed to design automated volumetric-modulated arc therapy (VMAT) plans in Pinnacle auto-planning and compare it with manual plans for patients with lower thoracic esophageal cancer (EC). Thirty patients with lower thoracic EC were randomly selected for replanning VMAT plans using auto-planning in Pinnacle treatment planning system (TPS) version 9.10. Historical plans of these patients were then compared. Dose-volume histogram (DVH) statistics, dose uniformity, and dose homogeneity were analyzed to evaluate treatment plans. Auto-planning was superior in terms of conformity index (CI) and homogeneity index (HI) for planning target volume (PTV), significantly improving 8.2% (p = 0.013) and 25% (p = 0.007) compared with manual planning, respectively, and decreasing dose of heart and liver irradiated by 20 to 40 Gy and 5 to 30 Gy, respectively (p < 0.05). Meanwhile, auto-planning further reduced the maximum dose (D max ) of spinal cord by 6.9 Gy compared with manual planning (p = 0.000). Additionally, manual planning showed the significantly lower low-dose volume (V 5 ) for the lung (p = 0.005). For auto-planning, the V 5 of the lung was significantly associated with the relative volume index (the volume ratio of PTV to the lung), and the correlation coefficient (R) and p-value were 0.994 and 0.000. Pinnacle auto-planning achieved superior target conformity and homogeneity and similar target coverage compared with historical manual planning. Most of organs at risk (OARs) sparing was significantly improved by auto-planning except for the V 5 of the lung, and the low dose distribution was highly associated with PTV volume and lung volume in auto-planning. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Post-adolescent developmental changes in cortical complexity.

PubMed

Sandu, Anca-Larisa; Izard, Edouard; Specht, Karsten; Beneventi, Harald; Lundervold, Arvid; Ystad, Martin

2014-11-27

Post-adolescence is known to be a period of general maturation and development in the human brain. In brain imaging, volumetric and morphologic cortical grey-matter changes can easily be assessed, but the analysis of cortical complexity seems to have been broadly neglected for this age interval. Magnetic resonance imaging (MRI) was used to acquire structural brain images. The study involved 17 adolescents (mean age 14.1 ± 0.27, 11 girls) who were compared with 14 young adults (mean age 24.24 ± 2.76, 7 women) for measures of brain complexity (fractal dimension--FD), grey matter (GM) volume and surface-area of cortical ribbon. FD was calculated using box-counting and Minkowski-Bouligand methods; FD and GM volume were measured for the whole brain, each hemisphere and lobes: frontal, occipital, parietal and temporal. The results show that the adults have a lower cortical complexity than the adolescents, which was significant for whole brain, left and right hemisphere, frontal and parietal lobes for both genders; and only for males in left temporal lobe. The GM volume was smaller in men than in boys for almost all measurements, and smaller in women than in girls just for right parietal lobe. A significant Pearson correlation was found between FD and GM volume for whole brain and each hemisphere in both genders. The decrease of the GM surface-area was significant in post-adolescence for males, not for females. During post-adolescence there are common changes in cortical complexity in the same regions for both genders, but there are also gender specific changes in some cortical areas. The sex differences from different cortical measurements (FD, GM volume and surface-area of cortical ribbon) could suggest a maturation delay in specific brain regions for each gender in relation to the other and might be explained through the functional role of the corresponding regions reflected in gender difference of developed abilities.

Improving throughput for temporal target nomination using existing infrastructure

NASA Astrophysics Data System (ADS)

Raeth, Peter G.

2007-04-01

Earlier, we reported on predictive anomaly detection (PAD) for nominating targets within data streams generated by persistent sensing and surveillance. This technique is purely temporal and does not directly depend on the physics attendant on the sensed environment. Since PAD adapts to evolving data streams, there are no determinacy assumptions. We showed PAD to be general across sensor types, demonstrating it using synthetic chaotic data and in audio, visual, and infrared applications. Defense-oriented demonstrations included explosions, muzzle flashes, and missile and aircraft detection. Experiments were ground-based and air-to-air. As new sensors come on line, PAD offers immediate data filtering and target nomination. Its results can be taken individually, pixel by pixel, for spectral analysis and material detection/identification. They can also be grouped for shape analysis, target identification, and track development. PAD analyses reduce data volume by around 95%, depending on target number and size, while still retaining all target indicators. While PAD's code is simple when compared to physics codes, PAD tends to build a huge model. A PAD model for 512 x 640 frames may contain 19,660,800 Gaussian basis functions. (PAD models grow linearly with the number of pixels and the frequency content, in the FFT sense, of the sensed scenario's background data). PAD's complexity in terms of computational and data intensity is an example of what one sees in new algorithms now in the R&D pipeline, especially as DoD seeks capability that runs fully automatic, with little to no human interaction. Work is needed to improve algorithms' throughput while employing existing infrastructure, yet allowing for growth in the types of hardware employed. In this present paper, we discuss a generic cluster interface for legacy codes that can be partitioned at the data level. The discussion's foundation is the growth of PAD models to accommodate a particular scenario and the need to reduce false alarms while preserving all targets. The discussion closes with a view of future software and hardware opportunities.

A novel algorithm for finding optimal driver nodes to target control complex networks and its applications for drug targets identification.

PubMed

Guo, Wei-Feng; Zhang, Shao-Wu; Shi, Qian-Qian; Zhang, Cheng-Ming; Zeng, Tao; Chen, Luonan

2018-01-19

The advances in target control of complex networks not only can offer new insights into the general control dynamics of complex systems, but also be useful for the practical application in systems biology, such as discovering new therapeutic targets for disease intervention. In many cases, e.g. drug target identification in biological networks, we usually require a target control on a subset of nodes (i.e., disease-associated genes) with minimum cost, and we further expect that more driver nodes consistent with a certain well-selected network nodes (i.e., prior-known drug-target genes). Therefore, motivated by this fact, we pose and address a new and practical problem called as target control problem with objectives-guided optimization (TCO): how could we control the interested variables (or targets) of a system with the optional driver nodes by minimizing the total quantity of drivers and meantime maximizing the quantity of constrained nodes among those drivers. Here, we design an efficient algorithm (TCOA) to find the optional driver nodes for controlling targets in complex networks. We apply our TCOA to several real-world networks, and the results support that our TCOA can identify more precise driver nodes than the existing control-fucus approaches. Furthermore, we have applied TCOA to two bimolecular expert-curate networks. Source code for our TCOA is freely available from http://sysbio.sibcb.ac.cn/cb/chenlab/software.htm or https://github.com/WilfongGuo/guoweifeng . In the previous theoretical research for the full control, there exists an observation and conclusion that the driver nodes tend to be low-degree nodes. However, for target control the biological networks, we find interestingly that the driver nodes tend to be high-degree nodes, which is more consistent with the biological experimental observations. Furthermore, our results supply the novel insights into how we can efficiently target control a complex system, and especially many evidences on the practical strategic utility of TCOA to incorporate prior drug information into potential drug-target forecasts. Thus applicably, our method paves a novel and efficient way to identify the drug targets for leading the phenotype transitions of underlying biological networks.

The treatment of extensive scalp lesions combining electrons with intensity-modulated photons.

PubMed

Chan, Maria F; Song, Yulin; Burman, Chandra; Chui, Chen S; Schupak, Karen

2006-01-01

This study was to investigate the feasibility and potential benefits of combining electrons with intensity modulated photons (IMRT+e) for patients with extensive scalp lesions. A case of a patient with an extensive scalp lesion, in which the target volume covered the entire front half of the scalp, is presented. This approach incorporated the electron dose into the inverse treatment planning optimization. The resulting doses to the planning target volume (PTV) and relevant critical structures were compared. Thermoluminescent dosimeters (TLD), diodes, and GAFCHROMIC EBT films were used to verify the accuracy of the techniques. The IMRT+e plan produced a superior dose distribution to the patient as compared to the IMRT plan in terms of reduction of the dose to the brain with the same dose conformity and homogeneity in the target volumes. This study showed that IMRT+e is a viable treatment modality for extensive scalp lesions patients. It provides a feasible alternative to existing treatment techniques, resulting in improved homogeneity of dose to the PTV compared to conventional electron techniques and a decrease in dose to the brain compared to photon IMRT alone.

Genetically targeted 3D visualisation of Drosophila neurons under Electron Microscopy and X-Ray Microscopy using miniSOG

PubMed Central

Ng, Julian; Browning, Alyssa; Lechner, Lorenz; Terada, Masako; Howard, Gillian; Jefferis, Gregory S. X. E.

2016-01-01

Large dimension, high-resolution imaging is important for neural circuit visualisation as neurons have both long- and short-range patterns: from axons and dendrites to the numerous synapses at terminal endings. Electron Microscopy (EM) is the favoured approach for synaptic resolution imaging but how such structures can be segmented from high-density images within large volume datasets remains challenging. Fluorescent probes are widely used to localise synapses, identify cell-types and in tracing studies. The equivalent EM approach would benefit visualising such labelled structures from within sub-cellular, cellular, tissue and neuroanatomical contexts. Here we developed genetically-encoded, electron-dense markers using miniSOG. We demonstrate their ability in 1) labelling cellular sub-compartments of genetically-targeted neurons, 2) generating contrast under different EM modalities, and 3) segmenting labelled structures from EM volumes using computer-assisted strategies. We also tested non-destructive X-ray imaging on whole Drosophila brains to evaluate contrast staining. This enabled us to target specific regions for EM volume acquisition. PMID:27958322

New Language and Old Problems in Breast Cancer Radiotherapy.

PubMed

Chiricuţă, Ion Christian

2017-01-01

New developments in breast cancer radiotherapy make possible new standards in treatment recommandations based on international guidelines. Developments in radiotherapy irradiation techniques from 2D to 3D-Conformal RT and to IMRT (Intensity Modulated Arc Therapy) make possible to reduce the usual side effects on the organs at risk as: skin, lung, miocard, bone, esophagus and brahial plexus. Dispite of all these progresses acute and late side effects are present. Side effects are as old as the radiotherapy was used. New solutions are available now by improving irradiation techniques. New techniques as sentinel node procedure (SNP) or partial breast irradiation (PBRT) and immediate breast reconstruction with silicon implants (IBRIS) make necessary new considerations regarding the target volume delineations. A new language for definition of gross tumor volume (GTV), clinical target volume (CTV) based on the new diagnostic methods as PET/CT,nonaparticle MRI will have real impact on target delineation and irradiation techniques. "The new common language in breast cancer therapy" would be the first step to improve the endresults and finally the quality of life of the patients. Celsius.

Proton therapy may allow for comprehensive elective nodal coverage for patients receiving neoadjuvant radiotherapy for localized pancreatic head cancers.

PubMed

Lee, Richard Y; Nichols, Romaine C; Huh, Soon N; Ho, Meng W; Li, Zuofeng; Zaiden, Robert; Awad, Ziad T; Ahmed, Bestoun; Hoppe, Bradfors S

2013-12-01

Neoadjuvant radiotherapy has the potential to improve local disease control for patients with localized pancreatic cancers. Concern about an increased risk of surgical complications due to small bowel and gastric exposure, however, has limited enthusiasm for this approach. Dosimetric studies have demonstrated the potential for proton therapy to reduce intestinal exposure compared with X-ray-based therapy. We sought to determine if neoadjuvant proton therapy allowed for field expansions to cover high-risk nodal stations in addition to the primary tumor. Twelve consecutive patients with nonmetastatic cancers of the pancreatic head underwent proton-based planning for neoadjuvant radiotherapy. Gross tumor volume was contoured using diagnostic computed tomography (CT) scans with oral and intravenous contrast. Four-dimensional planning scans were utilized to define an internal clinical target volume (ICTV). Five-mm planning target volume (PTV) expansions on the ICTV were generated to establish an initial PTV (PTV1). A second PTV was created using the initial PTV but was expanded to include the high-risk nodal targets as defined by the RTOG contouring atlas (PTV2). Optimized proton plans were generated for both PTVs for each patient. All PTVs received a dose of 50.4 cobalt gray equivalent (CGE). Normal-tissue exposures to the small bowel space, stomach, right kidney, left kidney and liver were recorded. Point spinal cord dose was limited to 45 CGE. Median PTV1 volume was 308.75 cm(3) (range, 133.33-495.61 cm(3)). Median PTV2 volume was 541.75 cm(3) (range, 399.44-691.14 cm(3)). In spite of the substantial enlargement of the PTV when high-risk lymph nodes were included in the treatment volume, normal-tissue exposures (stomach, bowel space, liver, and kidneys) were only minimally increased relative to the exposures seen when only the gross tumor target was treated. Proton therapy appears to allow for field expansions to cover high-risk lymph nodes without significantly increasing critical normal-tissue exposure in the neoadjuvant setting.

Feasibility study on image guided patient positioning for stereotactic body radiation therapy of liver malignancies guided by liver motion.

PubMed

Heinz, Christian; Gerum, Sabine; Freislederer, Philipp; Ganswindt, Ute; Roeder, Falk; Corradini, Stefanie; Belka, Claus; Niyazi, Maximilian

2016-06-27

Fiducial markers are the superior method to compensate for interfractional motion in liver SBRT. However this method is invasive and thereby limits its application range. In this retrospective study, the compensation method for the interfractional motion using fiducial markers (gold standard) was compared to a new non-invasive approach, which does rely on the organ motion of the liver and the relative tumor position within this volume. We analyzed six patients (3 m, 3f) treated with SBRT in 2014. After fiducial marker implantation, all patients received a treatment CT (free breathing, without abdominal compression) and a 4D-CT (consisting of 10 respiratory phases). For all patients the gross tumor volumes (GTVs), internal target volume (ITV), planning target volume (PTV), internal marker target volumes (IMTVs) and the internal liver target volume (ILTV) were delineated based on the CT and 4D-CT images. CBCT imaging was used for the standard treatment setup based on the fiducial markers. According to the patient coordinates the 3 translational compensation values (t x , t y , t z ) for the interfractional motion were calculated by matching the blurred fiducial markers with the corresponding IMTV structures. 4 observers were requested to recalculate the translational compensation values for each CBCT (31) based on the ILTV structures. The differences of the translational compensation values between the IMTV and ILTV approach were analyzed. The magnitude of the mean absolute 3D registration error with regard to the gold standard overall patients and observers was 0.50 cm ± 0.28 cm. Individual registration errors up to 1.3 cm were observed. There was no significant overall linear correlation between the respiratory motion and the registration error of the ILTV approach. Two different methods to calculate the translational compensation values for interfractional motion in stereotactic liver therapy were evaluated. The registration accuracy of the ILTV approach is mainly limited by the non-rigid behavior of the liver and the individual registration experience of the observer. The ILTV approach lacks the accuracy that would be desired for stereotactic radiotherapy of the liver.

Dosimetric comparison of moderate deep inspiration breath-hold and free-breathing intensity-modulated radiotherapy for left-sided breast cancer.

PubMed

Chi, F; Wu, S; Zhou, J; Li, F; Sun, J; Lin, Q; Lin, H; Guan, X; He, Z

2015-05-01

This study determined the dosimetric comparison of moderate deep inspiration breath-hold using active breathing control and free-breathing intensity-modulated radiotherapy (IMRT) after breast-conserving surgery for left-sided breast cancer. Thirty-one patients were enrolled. One free breathe and two moderate deep inspiration breath-hold images were obtained. A field-in-field-IMRT free-breathing plan and two field-in-field-IMRT moderate deep inspiration breath-holding plans were compared in the dosimetry to target volume coverage of the glandular breast tissue and organs at risks for each patient. The breath-holding time under moderate deep inspiration extended significantly after breathing training (P<0.05). There was no significant difference between the free-breathing and moderate deep inspiration breath-holding in the target volume coverage. The volume of the ipsilateral lung in the free-breathing technique were significantly smaller than the moderate deep inspiration breath-holding techniques (P<0.05); however, there was no significant difference between the two moderate deep inspiration breath-holding plans. There were no significant differences in target volume coverage between the three plans for the field-in-field-IMRT (all P>0.05). The dose to ipsilateral lung, coronary artery and heart in the field-in-field-IMRT were significantly lower for the free-breathing plan than for the two moderate deep inspiration breath-holding plans (all P<0.05); however, there was no significant difference between the two moderate deep inspiration breath-holding plans. The whole-breast field-in-field-IMRT under moderate deep inspiration breath-hold with active breathing control after breast-conserving surgery in left-sided breast cancer can reduce the irradiation volume and dose to organs at risks. There are no significant differences between various moderate deep inspiration breath-holding states in the dosimetry of irradiation to the field-in-field-IMRT target volume coverage and organs at risks. Copyright © 2015 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Variations of target volume definition and daily target volume localization in stereotactic body radiotherapy for early-stage non-small cell lung cancer patients under abdominal compression.

PubMed

Han, Chunhui; Sampath, Sagus; Schultheisss, Timothy E; Wong, Jeffrey Y C

2017-01-01

We aimed to compare gross tumor volumes (GTV) in 3-dimensional computed tomography (3DCT) simulation and daily cone beam CT (CBCT) with the internal target volume (ITV) in 4-dimensional CT (4DCT) simulation in stereotactic body radiotherapy (SBRT) treatment of patients with early-stage non-small cell lung cancer (NSCLC) under abdominal compression. We retrospectively selected 10 patients with NSCLC who received image-guided SBRT treatments under abdominal compression with daily CBCT imaging. GTVs were contoured as visible gross tumor on the planning 3DCT and daily CBCT, and ITVs were contoured using maximum intensity projection (MIP) images of the planning 4DCT. Daily CBCTs were registered with 3DCT and MIP images by matching of bony landmarks in the thoracic region to evaluate interfractional GTV position variations. Relative to MIP-based ITVs, the average 3DCT-based GTV volume was 66.3 ± 17.1% (range: 37.5% to 92.0%) (p < 0.01 in paired t-test), and the average CBCT-based GTV volume was 90.0 ± 6.7% (daily range: 75.7% to 107.1%) (p = 0.02). Based on bony anatomy matching, the center-of-mass coordinates for CBCT-based GTVs had maximum absolute shift of 2.4 mm (left-right), 7.0 mm (anterior-posterior [AP]), and 5.2 mm (superior-inferior [SI]) relative to the MIP-based ITV. CBCT-based GTVs had average overlapping ratio of 81.3 ± 11.2% (range: 45.1% to 98.9%) with the MIP-based ITV, and 57.7 ± 13.7% (range: 35.1% to 83.2%) with the 3DCT-based GTV. Even with abdominal compression, both 3DCT simulations and daily CBCT scans significantly underestimated the full range of tumor motion. In daily image-guided patient setup corrections, automatic bony anatomy-based image registration could lead to target misalignment. Soft tissue-based image registration should be performed for accurate treatment delivery. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.