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Sample records for accurate dose delivery

  1. Production of pure quasi-monochromatic 11C beams for accurate radiation therapy and dose delivery verification

    NASA Astrophysics Data System (ADS)

    Lazzeroni, Marta; Brahme, Anders

    2015-09-01

    In the present study we develop a new technique for the production of clean quasi-monochromatic 11C positron emitter beams for accurate radiation therapy and PET-CT dose delivery imaging and treatment verification. The 11C ion beam is produced by projectile fragmentation using a primary 12C ion beam. The practical elimination of the energy spread of the secondary 11C fragments and other beam contaminating fragments is described. Monte Carlo calculation with the SHIELD-HIT10+ code and analytical methods for the transport of the ions in matter are used in the analysis. Production yields, as well as energy, velocity and magnetic rigidity distributions of the fragments generated in a cylindrical target are scored as a function of the depth within 1 cm thick slices for an optimal target consisting of a fixed 20 cm section of liquid hydrogen followed by a variable thickness section of polyethylene. The wide energy and magnetic rigidity spread of the 11C ion beam can be reduced to values around 1% by using a variable monochromatizing wedge-shaped degrader in the beam line. Finally, magnetic rigidity and particle species selection, as well as discrimination of the particle velocity through a combined Time of Flight and Radio Frequency-driven Velocity filter purify the beam from similar magnetic rigidity contaminating fragments (mainly 7Be and 3He fragments). A beam purity of about 99% is expected by the combined method.

  2. Gantries and dose delivery systems

    NASA Astrophysics Data System (ADS)

    Meer, David; Psoroulas, Serena

    2015-04-01

    Particle therapy is a field in remarkable development, with the goal of increasing the number of indications which could benefit from such treatments and the access to the therapy. The therapeutic usage of a particle beam defines the technical requirements of all the elements of the therapy chain: we summarize the main characteristics of accelerators, the beam line, the treatment room, the integrated therapy and imaging systems used in particle therapy. Aiming at a higher flexibility in the choice of treatments, an increasing number of centers around the world have chosen to equip their treatment rooms with gantries, rotating beam line structures that allow a complete flexibility in the choice of the treatment angle. We review the current designs. A particle therapy gantry though is a quite expensive structure, and future development will increasingly consider reducing the cost and the footprint. Increasing the number of indications also means development in the delivery techniques and solving some of the issues which traditionally affected particle therapy, for example the precision of the delivery in presence of motion and the large penumbras for low depths. We show the current strategies in these fields, focusing on pencil beam scanning (PBS), and give some hints about future developments.

  3. Delivery verification and dose reconstruction in tomotherapy

    NASA Astrophysics Data System (ADS)

    Kapatoes, Jeffrey Michael

    2000-11-01

    It has long been a desire in photon-beam radiation therapy to make use of the significant fraction of the beam exiting the patient to infer how much of the beam energy was actually deposited in the patient. With a linear accelerator and corresponding exit detector mounted on the same ring gantry, tomotherapy provides a unique opportunity to accomplish this. Dose reconstruction describes the process in which the full three-dimensional dose actually deposited in a patient is computed. Dose reconstruction requires two inputs: an image of the patient at the time of treatment and the actual energy fluence delivered. Dose is reconstructed by computing the dose in the CT with the verified energy fluence using any model-based algorithm such as convolution/superposition or Monte Carlo. In tomotherapy, the CT at the time of treatment is obtained by megavoltage CT, the merits of which have been studied and proven. The actual energy fluence delivered to the patient is computed in a process called delivery verification. Methods for delivery verification and dose reconstruction in tomotherapy were investigated in this work. It is shown that delivery verification can be realized by a linear model of the tornotherapy system. However, due to the measurements required with this initial approach, clinical implementation would be difficult. Therefore, a clinically viable method for delivery verification was established, the details of which are discussed. With the verified energy fluence from delivery verification, an assessment of the accuracy and usefulness of dose reconstruction is performed. The latter two topics are presented in the context of a generalized dose comparison tool developed for intensity modulated radiation therapy. Finally, the importance of having a CT from the time of treatment for reconstructing the dose is shown. This is currently a point of contention in modern clinical radiotherapy and it is proven that using the incorrect CT for dose reconstruction can lead

  4. Accurate skin dose measurements using radiochromic film in clinical applications

    SciTech Connect

    Devic, S.; Seuntjens, J.; Abdel-Rahman, W.; Evans, M.; Olivares, M.; Podgorsak, E.B.; Vuong, Te; Soares, Christopher G.

    2006-04-15

    Megavoltage x-ray beams exhibit the well-known phenomena of dose buildup within the first few millimeters of the incident phantom surface, or the skin. Results of the surface dose measurements, however, depend vastly on the measurement technique employed. Our goal in this study was to determine a correction procedure in order to obtain an accurate skin dose estimate at the clinically relevant depth based on radiochromic film measurements. To illustrate this correction, we have used as a reference point a depth of 70 {mu}. We used the new GAFCHROMIC[reg] dosimetry films (HS, XR-T, and EBT) that have effective points of measurement at depths slightly larger than 70 {mu}. In addition to films, we also used an Attix parallel-plate chamber and a home-built extrapolation chamber to cover tissue-equivalent depths in the range from 4 {mu} to 1 mm of water-equivalent depth. Our measurements suggest that within the first millimeter of the skin region, the PDD for a 6 MV photon beam and field size of 10x10 cm{sup 2} increases from 14% to 43%. For the three GAFCHROMIC[reg] dosimetry film models, the 6 MV beam entrance skin dose measurement corrections due to their effective point of measurement are as follows: 15% for the EBT, 15% for the HS, and 16% for the XR-T model GAFCHROMIC[reg] films. The correction factors for the exit skin dose due to the build-down region are negligible. There is a small field size dependence for the entrance skin dose correction factor when using the EBT GAFCHROMIC[reg] film model. Finally, a procedure that uses EBT model GAFCHROMIC[reg] film for an accurate measurement of the skin dose in a parallel-opposed pair 6 MV photon beam arrangement is described.

  5. Commissioning a passive-scattering proton therapy nozzle for accurate SOBP delivery

    PubMed Central

    Engelsman, M.; Lu, H.-M.; Herrup, D.; Bussiere, M.; Kooy, H. M.

    2009-01-01

    Proton radiotherapy centers that currently use passively scattered proton beams do field specific calibrations for a non-negligible fraction of treatment fields, which is time and resource consuming. Our improved understanding of the passive scattering mode of the IBA universal nozzle, especially of the current modulation function, allowed us to re-commission our treatment control system for accurate delivery of SOBPs of any range and modulation, and to predict the output for each of these fields. We moved away from individual field calibrations to a state where continued quality assurance of SOBP field delivery is ensured by limited system-wide measurements that only require one hour per week. This manuscript reports on a protocol for generation of desired SOBPs and prediction of dose output. PMID:19610306

  6. How accurately can the peak skin dose in fluoroscopy be determined using indirect dose metrics?

    SciTech Connect

    Jones, A. Kyle; Ensor, Joe E.; Pasciak, Alexander S.

    2014-07-15

    Purpose: Skin dosimetry is important for fluoroscopically-guided interventions, as peak skin doses (PSD) that result in skin reactions can be reached during these procedures. There is no consensus as to whether or not indirect skin dosimetry is sufficiently accurate for fluoroscopically-guided interventions. However, measuring PSD with film is difficult and the decision to do so must be madea priori. The purpose of this study was to assess the accuracy of different types of indirect dose estimates and to determine if PSD can be calculated within ±50% using indirect dose metrics for embolization procedures. Methods: PSD were measured directly using radiochromic film for 41 consecutive embolization procedures at two sites. Indirect dose metrics from the procedures were collected, including reference air kerma. Four different estimates of PSD were calculated from the indirect dose metrics and compared along with reference air kerma to the measured PSD for each case. The four indirect estimates included a standard calculation method, the use of detailed information from the radiation dose structured report, and two simplified calculation methods based on the standard method. Indirect dosimetry results were compared with direct measurements, including an analysis of uncertainty associated with film dosimetry. Factors affecting the accuracy of the different indirect estimates were examined. Results: When using the standard calculation method, calculated PSD were within ±35% for all 41 procedures studied. Calculated PSD were within ±50% for a simplified method using a single source-to-patient distance for all calculations. Reference air kerma was within ±50% for all but one procedure. Cases for which reference air kerma or calculated PSD exhibited large (±35%) differences from the measured PSD were analyzed, and two main causative factors were identified: unusually small or large source-to-patient distances and large contributions to reference air kerma from cone

  7. Rotational IMRT delivery using a digital linear accelerator in very high dose rate 'burst mode'.

    PubMed

    Salter, Bill J; Sarkar, Vikren; Wang, Brian; Shukla, Himanshu; Szegedi, Martin; Rassiah-Szegedi, Prema

    2011-04-01

    Recently, there has been a resurgence of interest in arc-based IMRT, through the use of 'conventional' multileaf collimator (MLC) systems that can treat large tumor volumes in a single, or very few pass(es) of the gantry. Here we present a novel 'burst mode' modulated arc delivery approach, wherein 2000 monitor units per minute (MU min(-1)) high dose rate bursts of dose are facilitated by a flattening-filter-free treatment beam on a Siemens Artiste (Oncology Care Systems, Siemens Medical Solutions, Concord, CA, USA) digital linear accelerator in a non-clinical configuration. Burst mode delivery differs from continuous mode delivery, used by Elekta's VMAT (Elekta Ltd, Crawley, UK) and Varian's RapidArc (Varian Medical Systems, Palo Alto, CA, USA) implementations, in that dose is not delivered while MLC leaves are moving. Instead, dose is delivered in bursts over very short arc angles and only after an MLC segment shape has been completely formed and verified by the controller. The new system was confirmed to be capable of delivering a wide array of clinically relevant treatment plans, without machine fault or other delivery anomalies. Dosimetric accuracy of the modulated arc platform, as well as the Prowess (Prowess Inc., Concord, CA, USA) prototype treatment planning version utilized here, was quantified and confirmed, and delivery times were measured as significantly brief, even with large hypofractionated doses. The burst mode modulated arc approach evaluated here appears to represent a capable, accurate and efficient delivery approach. PMID:21364260

  8. Dose error analysis for a scanned proton beam delivery system

    NASA Astrophysics Data System (ADS)

    Coutrakon, G.; Wang, N.; Miller, D. W.; Yang, Y.

    2010-12-01

    All particle beam scanning systems are subject to dose delivery errors due to errors in position, energy and intensity of the delivered beam. In addition, finite scan speeds, beam spill non-uniformities, and delays in detector, detector electronics and magnet responses will all contribute errors in delivery. In this paper, we present dose errors for an 8 × 10 × 8 cm3 target of uniform water equivalent density with 8 cm spread out Bragg peak and a prescribed dose of 2 Gy. Lower doses are also analyzed and presented later in the paper. Beam energy errors and errors due to limitations of scanning system hardware have been included in the analysis. By using Gaussian shaped pencil beams derived from measurements in the research room of the James M Slater Proton Treatment and Research Center at Loma Linda, CA and executing treatment simulations multiple times, statistical dose errors have been calculated in each 2.5 mm cubic voxel in the target. These errors were calculated by delivering multiple treatments to the same volume and calculating the rms variation in delivered dose at each voxel in the target. The variations in dose were the result of random beam delivery errors such as proton energy, spot position and intensity fluctuations. The results show that with reasonable assumptions of random beam delivery errors, the spot scanning technique yielded an rms dose error in each voxel less than 2% or 3% of the 2 Gy prescribed dose. These calculated errors are within acceptable clinical limits for radiation therapy.

  9. Dose error analysis for a scanned proton beam delivery system.

    PubMed

    Coutrakon, G; Wang, N; Miller, D W; Yang, Y

    2010-12-01

    All particle beam scanning systems are subject to dose delivery errors due to errors in position, energy and intensity of the delivered beam. In addition, finite scan speeds, beam spill non-uniformities, and delays in detector, detector electronics and magnet responses will all contribute errors in delivery. In this paper, we present dose errors for an 8 × 10 × 8 cm(3) target of uniform water equivalent density with 8 cm spread out Bragg peak and a prescribed dose of 2 Gy. Lower doses are also analyzed and presented later in the paper. Beam energy errors and errors due to limitations of scanning system hardware have been included in the analysis. By using Gaussian shaped pencil beams derived from measurements in the research room of the James M Slater Proton Treatment and Research Center at Loma Linda, CA and executing treatment simulations multiple times, statistical dose errors have been calculated in each 2.5 mm cubic voxel in the target. These errors were calculated by delivering multiple treatments to the same volume and calculating the rms variation in delivered dose at each voxel in the target. The variations in dose were the result of random beam delivery errors such as proton energy, spot position and intensity fluctuations. The results show that with reasonable assumptions of random beam delivery errors, the spot scanning technique yielded an rms dose error in each voxel less than 2% or 3% of the 2 Gy prescribed dose. These calculated errors are within acceptable clinical limits for radiation therapy. PMID:21076200

  10. Modulation of photodynamic activity with Photofrin: effect of dose, time interval, fluence, and delivery system

    NASA Astrophysics Data System (ADS)

    Garbo, Greta M.; Ballard, Jonathan R.; Harrison, Linda T.; Kik, Peter K.; Wieman, T. J.; Fingar, Victor H.

    2005-04-01

    A goal of our laboratory is to accurately define the parameters of light dose and drug dose that contribute to tissue destruction after Photodynamic therapy (PDT). Using Photofrin as sensitizer, we examined a range of drug doses, various intervals between injection and light treatment, and various fluence rates. The effect of Photofrin photosensitizer encapsulated in liposomal delivery vehicle was also studied. Three liposome delivery vehicles were chosen to deliver the photosensitizer in vivo: DPPC/cholesterol, DMPC/HPC and stealth liposomes. Tumor response and microvessel behaviour were examined in tumor and surrounding skin in a mouse model. Under these conditions, better selectivity of tissue damage was seen using some of the treatment. These data might be used to design better clinical protocols for patient care. In memory of Dr. Victor Fingar (Supported by R01 CA51771).

  11. Tomotherapy – a different way of dose delivery in radiotherapy

    PubMed Central

    Skórska, Małgorzata; Jodda, Agata; Ryczkowski, Adam; Kaźmierska, Joanna; Adamska, Krystyna; Karczewska-Dzionk, Aldona; Żmijewska-Tomczak, Małgorzata; Włodarczyk, Hanna

    2012-01-01

    Aim of the study Helical tomotherapy is one of the methods of radiotherapy. This method enables treatment implementation for a wide spectrum of clinical cases. The vast array of therapeutic uses of helical tomotherapy results directly from the method of dose delivery, which is significantly different from the classic method developed for conventional linear accelerators. The paper discusses the method of dose delivery by a tomotherapy machine. Moreover, an analysis and presentation of treatment plans was performed in order to show the therapeutic possibilities of the applied technology. Dose distributions were obtained for anaplastic medulloblastoma, multifocal metastases to brain, vulva cancer, tongue cancer, metastases to bones, and advanced skin cancer. Tomotherapy treatment plans were compared with conventional linear accelerator plans. Results Following the comparative analysis of tomotherapy and conventional linear accelerator plans, in each case we obtained the increase in dose distribution conformity manifested in greater homogeneity of doses in the radiation target area for anaplastic medulloblastoma, multifocal metastases to brain, vulva cancer, metastases to bones, and advanced skin cancer, and the reduction of doses in organs at risk (OAR) for anaplastic medulloblastoma, vulva cancer, tongue cancer, and advanced skin cancer. The time of treatment delivery in the case of a tomotherapy machine is comparable to the implementation of the plan prepared in intensity-modulated radiotherapy (IMRT) technique for a conventional linear accelerator. In the case of tomotherapy the application of a fractional dose was carried out in each case during one working period of the machine. For a conventional linear accelerator the total value of the fractional dose in the case of anaplastic medulloblastoma and metastases to bones was delivered using several treatment plans, for which a change of set-up was necessary during a fraction. Conclusion The obtained results

  12. Quality Control of High-Dose-Rate Brachytherapy: Treatment Delivery Analysis Using Statistical Process Control

    SciTech Connect

    Able, Charles M.; Bright, Megan; Frizzell, Bart

    2013-03-01

    Purpose: Statistical process control (SPC) is a quality control method used to ensure that a process is well controlled and operates with little variation. This study determined whether SPC was a viable technique for evaluating the proper operation of a high-dose-rate (HDR) brachytherapy treatment delivery system. Methods and Materials: A surrogate prostate patient was developed using Vyse ordnance gelatin. A total of 10 metal oxide semiconductor field-effect transistors (MOSFETs) were placed from prostate base to apex. Computed tomography guidance was used to accurately position the first detector in each train at the base. The plan consisted of 12 needles with 129 dwell positions delivering a prescribed peripheral dose of 200 cGy. Sixteen accurate treatment trials were delivered as planned. Subsequently, a number of treatments were delivered with errors introduced, including wrong patient, wrong source calibration, wrong connection sequence, single needle displaced inferiorly 5 mm, and entire implant displaced 2 mm and 4 mm inferiorly. Two process behavior charts (PBC), an individual and a moving range chart, were developed for each dosimeter location. Results: There were 4 false positives resulting from 160 measurements from 16 accurately delivered treatments. For the inaccurately delivered treatments, the PBC indicated that measurements made at the periphery and apex (regions of high-dose gradient) were much more sensitive to treatment delivery errors. All errors introduced were correctly identified by either the individual or the moving range PBC in the apex region. Measurements at the urethra and base were less sensitive to errors. Conclusions: SPC is a viable method for assessing the quality of HDR treatment delivery. Further development is necessary to determine the most effective dose sampling, to ensure reproducible evaluation of treatment delivery accuracy.

  13. Impact of Surface Curvature on Dose Delivery in Intraoperative High-Dose-Rate Brachytherapy

    SciTech Connect

    Oh, Moonseong Wang Zhou; Malhotra, Harish K.; Jaggernauth, Wainwright; Podgorsak, Matthew B.

    2009-04-01

    In intraoperative high-dose-rate (IOHDR) brachytherapy, a 2-dimensional (2D) geometry is typically used for treatment planning. The assumption of planar geometry may cause serious errors in dose delivery for target surfaces that are, in reality, curved. A study to evaluate the magnitude of these errors in clinical practice was undertaken. Cylindrical phantoms with 6 radii (range: 1.35-12.5 cm) were used to simulate curved treatment geometries. Treatment plans were developed for various planar geometries and were delivered to the cylindrical phantoms using catheters inserted into Freiburg applicators of varying dimension. Dose distributions were measured using radiographic film. In comparison to the treatment plan (for a planar geometry), the doses delivered to prescription points were higher on the concave side of the geometry, up to 15% for the phantom with the smallest radius. On the convex side of the applicator, delivered doses were up to 10% lower for small treated areas ({<=} 5 catheters) but, interestingly, the dose error was negligible for large treated areas (>5 catheters). Our measurements have shown inaccuracy in dose delivery when the original planar treatment plan is delivered with a curved applicator. Dose delivery errors arising from the use of planar treatment plans with curved applicators may be significant.

  14. DICOM organ dose does not accurately represent calculated dose in mammography

    NASA Astrophysics Data System (ADS)

    Suleiman, Moayyad E.; Brennan, Patrick C.; McEntee, Mark F.

    2016-03-01

    This study aims to analyze the agreement between the mean glandular dose estimated by the mammography unit (organ dose) and mean glandular dose calculated using Dance et al published method (calculated dose). Anonymised digital mammograms from 50 BreastScreen NSW centers were downloaded and exposure information required for the calculation of dose was extracted from the DICOM header along with the organ dose estimated by the system. Data from quality assurance annual tests for the included centers were collected and used to calculate the mean glandular dose for each mammogram. Bland-Altman analysis and a two-tailed paired t-test were used to study the agreement between calculated and organ dose and the significance of any differences. A total of 27,869 dose points from 40 centers were included in the study, mean calculated dose and mean organ dose (+/- standard deviation) were 1.47 (+/-0.66) and 1.38 (+/-0.56) mGy respectively. A statistically significant 0.09 mGy bias (t = 69.25; p<0.0001) with 95% limits of agreement between calculated and organ doses ranging from -0.34 and 0.52 were shown by Bland-Altman analysis, which indicates a small yet highly significant difference between the two means. The use of organ dose for dose audits is done at the risk of over or underestimating the calculated dose, hence, further work is needed to identify the causal agents for differences between organ and calculated doses and to generate a correction factor for organ dose.

  15. Can radiation therapy treatment planning system accurately predict surface doses in postmastectomy radiation therapy patients?

    SciTech Connect

    Wong, Sharon; Back, Michael; Tan, Poh Wee; Lee, Khai Mun; Baggarley, Shaun; Lu, Jaide Jay

    2012-07-01

    Skin doses have been an important factor in the dose prescription for breast radiotherapy. Recent advances in radiotherapy treatment techniques, such as intensity-modulated radiation therapy (IMRT) and new treatment schemes such as hypofractionated breast therapy have made the precise determination of the surface dose necessary. Detailed information of the dose at various depths of the skin is also critical in designing new treatment strategies. The purpose of this work was to assess the accuracy of surface dose calculation by a clinically used treatment planning system and those measured by thermoluminescence dosimeters (TLDs) in a customized chest wall phantom. This study involved the construction of a chest wall phantom for skin dose assessment. Seven TLDs were distributed throughout each right chest wall phantom to give adequate representation of measured radiation doses. Point doses from the CMS Xio Registered-Sign treatment planning system (TPS) were calculated for each relevant TLD positions and results correlated. There were no significant difference between measured absorbed dose by TLD and calculated doses by the TPS (p > 0.05 (1-tailed). Dose accuracy of up to 2.21% was found. The deviations from the calculated absorbed doses were overall larger (3.4%) when wedges and bolus were used. 3D radiotherapy TPS is a useful and accurate tool to assess the accuracy of surface dose. Our studies have shown that radiation treatment accuracy expressed as a comparison between calculated doses (by TPS) and measured doses (by TLD dosimetry) can be accurately predicted for tangential treatment of the chest wall after mastectomy.

  16. A real time dose monitoring and dose reconstruction tool for patient specific VMAT QA and delivery

    SciTech Connect

    Tyagi, Neelam; Yang Kai; Gersten, David; Yan Di

    2012-12-15

    Purpose: To develop a real time dose monitoring and dose reconstruction tool to identify and quantify sources of errors during patient specific volumetric modulated arc therapy (VMAT) delivery and quality assurance. Methods: The authors develop a VMAT delivery monitor tool called linac data monitor that connects to the linac in clinical mode and records, displays, and compares real time machine parameters with the planned parameters. A new measure, called integral error, keeps a running total of leaf overshoot and undershoot errors in each leaf pair, multiplied by leaf width, and the amount of time during which the error exists in monitor unit delivery. Another tool reconstructs Pinnacle{sup 3} Trade-Mark-Sign format delivered plan based on the saved machine logfile and recalculates actual delivered dose in patient anatomy. Delivery characteristics of various standard fractionation and stereotactic body radiation therapy (SBRT) VMAT plans delivered on Elekta Axesse and Synergy linacs were quantified. Results: The MLC and gantry errors for all the treatment sites were 0.00 {+-} 0.59 mm and 0.05 {+-} 0.31 Degree-Sign , indicating a good MLC gain calibration. Standard fractionation plans had a larger gantry error than SBRT plans due to frequent dose rate changes. On average, the MLC errors were negligible but larger errors of up to 6 mm and 2.5 Degree-Sign were seen when dose rate varied frequently. Large gantry errors occurred during the acceleration and deceleration process, and correlated well with MLC errors (r= 0.858, p= 0.0004). PTV mean, minimum, and maximum dose discrepancies were 0.87 {+-} 0.21%, 0.99 {+-} 0.59%, and 1.18 {+-} 0.52%, respectively. The organs at risk (OAR) doses were within 2.5%, except some OARs that showed up to 5.6% discrepancy in maximum dose. Real time displayed normalized total positive integral error (normalized to the total monitor units) correlated linearly with MLC (r= 0.9279, p < 0.001) and gantry errors (r= 0.742, p= 0.005). There

  17. Is internal target volume accurate for dose evaluation in lung cancer stereotactic body radiotherapy?

    PubMed Central

    Peng, Jiayuan; Zhang, Zhen; Wang, Jiazhou; Xie, Jiang; Hu, Weigang

    2016-01-01

    Purpose 4DCT delineated internal target volume (ITV) was applied to determine the tumor motion and used as planning target in treatment planning in lung cancer stereotactic body radiotherapy (SBRT). This work is to study the accuracy of using ITV to predict the real target dose in lung cancer SBRT. Materials and methods Both for phantom and patient cases, the ITV and gross tumor volumes (GTVs) were contoured on the maximum intensity projection (MIP) CT and ten CT phases, respectively. A SBRT plan was designed using ITV as the planning target on average projection (AVG) CT. This plan was copied to each CT phase and the dose distribution was recalculated. The GTV_4D dose was acquired through accumulating the GTV doses over all ten phases and regarded as the real target dose. To analyze the ITV dose error, the ITV dose was compared to the real target dose by endpoints of D99, D95, D1 (doses received by the 99%, 95% and 1% of the target volume), and dose coverage endpoint of V100(relative volume receiving at least the prescription dose). Results The phantom study shows that the ITV underestimates the real target dose by 9.47%∼19.8% in D99, 4.43%∼15.99% in D95, and underestimates the dose coverage by 5% in V100. The patient cases show that the ITV underestimates the real target dose and dose coverage by 3.8%∼10.7% in D99, 4.7%∼7.2% in D95, and 3.96%∼6.59% in V100 in motion target cases. Conclusions Cautions should be taken that ITV is not accurate enough to predict the real target dose in lung cancer SBRT with large tumor motions. Restricting the target motion or reducing the target dose heterogeneity could reduce the ITV dose underestimation effect in lung SBRT. PMID:26968812

  18. Radiation dose delivery verification in the treatment of carcinoma-cervix

    SciTech Connect

    Shrotriya, D. Srivastava, R. N. L.; Kumar, S.

    2015-06-24

    The accurate dose delivery to the clinical target volume in radiotherapy can be affected by various pelvic tissues heterogeneities. An in-house heterogeneous woman pelvic phantom was designed and used to verify the consistency and computational capability of treatment planning system of radiation dose delivery in the treatment of cancer cervix. Oncentra 3D-TPS with collapsed cone convolution (CCC) dose calculation algorithm was used to generate AP/PA and box field technique plan. the radiation dose was delivered by Primus Linac (Siemens make) employing high energy 15 MV photon beam by isocenter technique. A PTW make, 0.125cc ionization chamber was used for direct measurements at various reference points in cervix, bladder and rectum. The study revealed that maximum variation between computed and measured dose at cervix reference point was 1% in both the techniques and 3% and 4% variation in AP/PA field and 5% and 4.5% in box technique at bladder and rectum points respectively.

  19. Monte Carlo calculation of helical tomotherapy dose delivery

    SciTech Connect

    Zhao Yingli; Mackenzie, M.; Kirkby, C.; Fallone, B. G.

    2008-08-15

    Helical tomotherapy delivers intensity modulated radiation therapy using a binary multileaf collimator (MLC) to modulate a fan beam of radiation. This delivery occurs while the linac gantry and treatment couch are both in constant motion, so the beam describes, from a patient/phantom perspective, a spiral or helix of dose. The planning system models this continuous delivery as a large number (51) of discrete gantry positions per rotation, and given the small jaw/fan width setting typically used (1 or 2.5 cm) and the number of overlapping rotations used to cover the target (pitch often <0.5), the treatment planning system (TPS) potentially employs a very large number of static beam directions and leaf opening configurations to model the modulated fields. All dose calculations performed by the system employ a convolution/superposition model. In this work the authors perform a full Monte Carlo (MC) dose calculation of tomotherapy deliveries to phantom computed tomography (CT) data sets to verify the TPS calculations. All MC calculations are performed with the EGSnrc-based MC simulation codes, BEAMnrc and DOSXYZnrc. Simulations are performed by taking the sinogram (leaf opening versus time) of the treatment plan and decomposing it into 51 different projections per rotation, as does the TPS, each of which is segmented further into multiple MLC opening configurations, each with different weights that correspond to leaf opening times. Then the projection is simulated by the summing of all of the opening configurations, and the overall rotational treatment is simulated by the summing of all of the projection simulations. Commissioning of the source model was verified by comparing measured and simulated values for the percent depth dose and beam profiles shapes for various jaw settings. The accuracy of the MLC leaf width and tongue and groove spacing were verified by comparing measured and simulated values for the MLC leakage and a picket fence pattern. The validated source

  20. More accurate fitting of {sup 125}I and {sup 103}Pd radial dose functions

    SciTech Connect

    Taylor, R. E. P.; Rogers, D. W. O.

    2008-09-15

    In this study an improved functional form for fitting the radial dose functions, g(r), of {sup 125}I and {sup 103}Pd brachytherapy seeds is presented. The new function is capable of accurately fitting radial dose functions over ranges as large as 0.05 cm{<=}r{<=}10 cm for {sup 125}I seeds and 0.10 cm{<=}r{<=}10 cm for {sup 103}Pd seeds. The average discrepancies between fit and calculated data are less than 0.5% over the full range of fit and maximum discrepancies are 2% or less. The fitting function is also capable of accounting for the sharp increase in g(r) (upturn) seen for some sources for r<0.1 cm. This upturn has previously been attributed to the breakdown of the approximation of the sources as a line, however, in this study we demonstrate that another contributing factor is the 4.5 keV characteristic x-rays emitted from the Ti seed casing. Radial dose functions are calculated for 18 {sup 125}I seeds and 9 {sup 103}Pd seeds using the EGSnrc Monte Carlo user-code BrachyDose. Fitting coefficients of the new function are tabulated for all 27 seeds. Extrapolation characteristics of the function are also investigated. The new functional form is an improvement over currently used fitting functions with its main strength being the ability to accurately fit the rapidly varying radial dose function at small distances. The new function is an excellent candidate for fitting the radial dose function of all {sup 103}Pd and {sup 125}I brachytherapy seeds and will increase the accuracy of dose distributions calculated around brachytherapy seeds using the TG-43 protocol over a wider range of data. More accurate values of g(r) for r<0.5 cm may be particularly important in the treatment of ocular melanoma.

  1. The CNAO dose delivery system for modulated scanning ion beam radiotherapy

    SciTech Connect

    Giordanengo, S.; Marchetto, F.; Garella, M. A.; Donetti, M.; Bourhaleb, F.; Monaco, V.; Hosseini, M. A.; Peroni, C.; Sacchi, R.; Cirio, R.; Ciocca, M.; Mirandola, A.

    2015-01-15

    Purpose: This paper describes the system for the dose delivery currently used at the Centro Nazionale di Adroterapia Oncologica (CNAO) for ion beam modulated scanning radiotherapy. Methods: CNAO Foundation, Istituto Nazionale di Fisica Nucleare and University of Torino have designed, built, and commissioned a dose delivery system (DDS) to monitor and guide ion beams accelerated by a dedicated synchrotron and to distribute the dose with a full 3D scanning technique. Protons and carbon ions are provided for a wide range of energies in order to cover a sizable span of treatment depths. The target volume, segmented in several layers orthogonally to the beam direction, is irradiated by thousands of pencil beams which must be steered and held to the prescribed positions until the prescribed number of particles has been delivered. For the CNAO beam lines, these operations are performed by the DDS. The main components of this system are two independent beam monitoring detectors, called BOX1 and BOX2, interfaced with two control systems performing the tasks of real-time fast and slow control, and connected to the scanning magnets and the beam chopper. As a reaction to any condition leading to a potential hazard, a DDS interlock signal is sent to the patient interlock system which immediately stops the irradiation. The essential tasks and operations performed by the DDS are described following the data flow from the treatment planning system through the end of the treatment delivery. Results: The ability of the DDS to guarantee a safe and accurate treatment was validated during the commissioning phase by means of checks of the charge collection efficiency, gain uniformity of the chambers, and 2D dose distribution homogeneity and stability. A high level of reliability and robustness has been proven by three years of system activity needing rarely more than regular maintenance and working with 100% uptime. Four identical and independent DDS devices have been tested showing

  2. A simplified approach to characterizing a kilovoltage source spectrum for accurate dose computation

    SciTech Connect

    Poirier, Yannick; Kouznetsov, Alexei; Tambasco, Mauro

    2012-06-15

    % for the homogeneous and heterogeneous block phantoms, and agreement for the transverse dose profiles was within 6%. Conclusions: The HVL and kVp are sufficient for characterizing a kV x-ray source spectrum for accurate dose computation. As these parameters can be easily and accurately measured, they provide for a clinically feasible approach to characterizing a kV energy spectrum to be used for patient specific x-ray dose computations. Furthermore, these results provide experimental validation of our novel hybrid dose computation algorithm.

  3. IMRT dose delivery effects in radiotherapy treatment planning using Monte Carlo methods

    NASA Astrophysics Data System (ADS)

    Tyagi, Neelam

    Inter- and intra-leaf transmission and head scatter can play significant roles in Intensity Modulated Radiation Therapy (IMRT)-based treatment deliveries. In order to accurately calculate the dose in the IMRT planning process, it is therefore important that the detailed geometry of the multi-leaf collimator (MLC), in addition to other components in the accelerator treatment head be accurately modeled. In this thesis Monte Carlo (MC) methods have been used to model the treatment head of a Varian linear accelerator. A comprehensive model of the Varian 120-leaf MLC has been developed within the DPM MC code and has been verified against measurements in homogeneous and heterogeneous phantom geometries under different IMRT delivery circumstances. Accuracy of the MLC model in simulating details in the leaf geometry has been established over a range of arbitrarily shaped fields and IMRT fields. A sensitivity analysis of the effect of the electron-on-target parameters and the structure of the flattening filter on the accuracy of calculated dose distributions has been conducted. Adjustment of the electron-on-target parameters resulting in optimal agreement with measurements was an iterative process, with the final parameters representing a tradeoff between small (3x3 cm2) and large (40x40 cm2) field sizes. A novel method based on adaptive kernel density estimation, in the phase space simulation process is also presented as an alternative to particle recycling. Using this model dosimetric differences between MLC-based static (SMLC) and dynamic (DMLC) deliveries have been investigated. Differences between SMLC and DMLC, possibly related to fluence and/or spectral changes, appear to vary systematically with the density of the medium. The effect of fluence modulation due to leaf sequencing shows differences, up to 10% between plans developed with 1% and 10% fluence intervals for both SMLC and DMLC-delivered sequences. Dose differences between planned and delivered leaf sequences

  4. A live weight-heart girth relationship for accurate dosing of east African shorthorn zebu cattle.

    PubMed

    Lesosky, Maia; Dumas, Sarah; Conradie, Ilana; Handel, Ian Graham; Jennings, Amy; Thumbi, Samuel; Toye, Phillip; Bronsvoort, Barend Mark de Clare

    2013-01-01

    The accurate estimation of livestock weights is important for many aspects of livestock management including nutrition, production and appropriate dosing of pharmaceuticals. Subtherapeutic dosing has been shown to accelerate pathogen resistance which can have subsequent widespread impacts. There are a number of published models for the prediction of live weight from morphometric measurements of cattle, but many of these models use measurements difficult to gather and include complicated age, size and gender stratification. In this paper, we use data from the Infectious Diseases of East Africa calf cohort study and additional data collected at local markets in western Kenya to develop a simple model based on heart girth circumference to predict live weight of east African shorthorn zebu (SHZ) cattle. SHZ cattle are widespread throughout eastern and southern Africa and are economically important multipurpose animals. We demonstrate model accuracy by splitting the data into training and validation subsets and comparing fitted and predicted values. The final model is weight(0.262) = 0.95 + 0.022 × girth which has an R (2) value of 0.98 and 95 % prediction intervals that fall within the ± 20 % body weight error band regarded as acceptable when dosing livestock. This model provides a highly reliable and accurate method for predicting weights of SHZ cattle using a single heart girth measurement which can be easily obtained with a tape measure in the field setting. PMID:22923040

  5. Oxymetazoline Metered Dose Spray: Factors Affecting Delivery Volume

    PubMed Central

    Walia, Hina; Rafiq, Mahmood; Grannell, Timothy; Cartabuke, Richard S.; Tobias, Joseph D.

    2016-01-01

    OBJECTIVES: The current study compared the amount of oxymetazoline delivered by various anesthesia providers when holding the bottle in the upright and inverted position. Additionally, the amount delivered from a full bottle and a half-full bottle was also investigated. METHODS: Using an analytical balance that was calibrated to zero, we evaluated the impact the position of the bottle and the volume of oxymetazoline in the bottle had on the amount being delivered by both anesthesia staff and trainees. RESULTS: When using both filled and half-filled bottles, the amount delivered increased significantly when comparing the upright versus inverted position. With a full bottle, the amount delivered when the bottle was inverted increased almost 10-fold from 62 ± 80 to 606 ± 366 μL (p < 0.0001). Similarly, even with a half-filled bottle, the amount delivered increased in the inverted positions from 41 ± 48 to 645 ± 393 μL. Regardless of the scenario, we also noted significant variation from provider to provider. CONCLUSIONS: Our results demonstrate that several factors may affect the amount of oxymetazoline delivered for metered dose bottles. Given the potential for severe end-organ effects with excessive dosage, alternative means of delivery are needed for its perioperative use. PMID:27453703

  6. An in vivo dose verification method for SBRT–VMAT delivery using the EPID

    SciTech Connect

    McCowan, P. M.; Van Uytven, E.; Van Beek, T.; Asuni, G.; McCurdy, B. M. C.

    2015-12-15

    Purpose: Radiation treatments have become increasingly more complex with the development of volumetric modulated arc therapy (VMAT) and the use of stereotactic body radiation therapy (SBRT). SBRT involves the delivery of substantially larger doses over fewer fractions than conventional therapy. SBRT–VMAT treatments will strongly benefit from in vivo patient dose verification, as any errors in delivery can be more detrimental to the radiobiology of the patient as compared to conventional therapy. Electronic portal imaging devices (EPIDs) are available on most commercial linear accelerators (Linacs) and their documented use for dosimetry makes them valuable tools for patient dose verification. In this work, the authors customize and validate a physics-based model which utilizes on-treatment EPID images to reconstruct the 3D dose delivered to the patient during SBRT–VMAT delivery. Methods: The SBRT Linac head, including jaws, multileaf collimators, and flattening filter, were modeled using Monte Carlo methods and verified with measured data. The simulation provides energy spectrum data that are used by their “forward” model to then accurately predict fluence generated by a SBRT beam at a plane above the patient. This fluence is then transported through the patient and then the dose to the phosphor layer in the EPID is calculated. Their “inverse” model back-projects the EPID measured focal fluence to a plane upstream of the patient and recombines it with the extra-focal fluence predicted by the forward model. This estimate of total delivered fluence is then forward projected onto the patient’s density matrix and a collapsed cone convolution algorithm calculates the dose delivered to the patient. The model was tested by reconstructing the dose for two prostate, three lung, and two spine SBRT–VMAT treatment fractions delivered to an anthropomorphic phantom. It was further validated against actual patient data for a lung and spine SBRT–VMAT plan. The

  7. Numerical system utilising a Monte Carlo calculation method for accurate dose assessment in radiation accidents.

    PubMed

    Takahashi, F; Endo, A

    2007-01-01

    A system utilising radiation transport codes has been developed to derive accurate dose distributions in a human body for radiological accidents. A suitable model is quite essential for a numerical analysis. Therefore, two tools were developed to setup a 'problem-dependent' input file, defining a radiation source and an exposed person to simulate the radiation transport in an accident with the Monte Carlo calculation codes-MCNP and MCNPX. Necessary resources are defined by a dialogue method with a generally used personal computer for both the tools. The tools prepare human body and source models described in the input file format of the employed Monte Carlo codes. The tools were validated for dose assessment in comparison with a past criticality accident and a hypothesized exposure. PMID:17510203

  8. A hybrid approach for rapid, accurate, and direct kilovoltage radiation dose calculations in CT voxel space

    SciTech Connect

    Kouznetsov, Alexei; Tambasco, Mauro

    2011-03-15

    Purpose: To develop and validate a fast and accurate method that uses computed tomography (CT) voxel data to estimate absorbed radiation dose at a point of interest (POI) or series of POIs from a kilovoltage (kV) imaging procedure. Methods: The authors developed an approach that computes absorbed radiation dose at a POI by numerically evaluating the linear Boltzmann transport equation (LBTE) using a combination of deterministic and Monte Carlo (MC) techniques. This hybrid approach accounts for material heterogeneity with a level of accuracy comparable to the general MC algorithms. Also, the dose at a POI is computed within seconds using the Intel Core i7 CPU 920 2.67 GHz quad core architecture, and the calculations are performed using CT voxel data, making it flexible and feasible for clinical applications. To validate the method, the authors constructed and acquired a CT scan of a heterogeneous block phantom consisting of a succession of slab densities: Tissue (1.29 cm), bone (2.42 cm), lung (4.84 cm), bone (1.37 cm), and tissue (4.84 cm). Using the hybrid transport method, the authors computed the absorbed doses at a set of points along the central axis and x direction of the phantom for an isotropic 125 kVp photon spectral point source located along the central axis 92.7 cm above the phantom surface. The accuracy of the results was compared to those computed with MCNP, which was cross-validated with EGSnrc, and served as the benchmark for validation. Results: The error in the depth dose ranged from -1.45% to +1.39% with a mean and standard deviation of -0.12% and 0.66%, respectively. The error in the x profile ranged from -1.3% to +0.9%, with standard deviations of -0.3% and 0.5%, respectively. The number of photons required to achieve these results was 1x10{sup 6}. Conclusions: The voxel-based hybrid method evaluates the LBTE rapidly and accurately to estimate the absorbed x-ray dose at any POI or series of POIs from a kV imaging procedure.

  9. Tumor cell survival dependence on helical tomotherapy, continuous arc and segmented dose delivery

    NASA Astrophysics Data System (ADS)

    Yang, Wensha; Wang, Li; Larner, James; Read, Paul; Benedict, Stan; Sheng, Ke

    2009-11-01

    The temporal pattern of radiation delivery has been shown to influence the tumor cell survival fractions for the same radiation dose. To study the effect more specifically for state of the art rotational radiation delivery modalities, 2 Gy of radiation dose was delivered to H460 lung carcinoma, PC3 prostate cancer cells and MCF-7 breast tumor cells by helical tomotherapy (HT), seven-field LINAC (7F), and continuous dose delivery (CDD) over 2 min that simulates volumetric rotational arc therapy. Cell survival was measured by the clonogenic assay. The number of viable H460 cell colonies was 23.2 ± 14.4% and 27.7 ± 15.6% lower when irradiated by CDD compared with HT and 7F, respectively, and the corresponding values were 36.8 ± 18.9% and 35.3 ± 18.9% lower for MCF7 cells (p < 0.01). The survival of PC3 was also lower when irradiated by CDD than by HT or 7F but the difference was not as significant (p = 0.06 and 0.04, respectively). The higher survival fraction from HT delivery was unexpected because 90% of the 2 Gy was delivered in less than 1 min at a significantly higher dose rate than the other two delivery techniques. The results suggest that continuous dose delivery at a constant dose rate results in superior in vitro tumor cell killing compared with prolonged, segmented or variable dose rate delivery.

  10. NOTE: Monte Carlo dose calculation of segmental IMRT delivery to a moving phantom using dynamic MLC and gating log files

    NASA Astrophysics Data System (ADS)

    Oliver, Mike; Staruch, Robert; Gladwish, Adam; Craig, Jeff; Chen, Jeff; Wong, Eugene

    2008-05-01

    Respiratory gating is emerging as a tool to limit the effect of motion for liver and lung tumors. In order to study the impact of target motion and gated intensity modulated radiation therapy (IMRT) delivery, a computer program was developed to simulate segmental IMRT delivery to a moving phantom. Two distinct plans were delivered to a rigid-motion phantom with a film insert in place under four conditions: static, sinusoidal motion, gated sinusoidal motion with a duty cycle of 25% and gated sinusoidal motion with duty cycle of 50% under motion conditions of a typical patient (A = 1 cm, T = 4 s). The MLC controller log files and gating log files were retained to perform a retrospective Monte Carlo dose calculation of the plans. Comparison of the 2D planar dose distributions between simulation and measurement demonstrated that our technique had at least 94% of the points passing gamma criteria of 3% for dose difference and 3 mm as the distance to agreement. This note demonstrates that the use of dynamic multi-leaf collimator and respiratory monitoring system log files together with a fast Monte Carlo dose calculation algorithm is an accurate and efficient way to study the dosimetric effect of motion for gated or non-gated IMRT delivery on a rigidly-moving body.

  11. Wind-tunnel tests and modeling indicate that aerial dispersant delivery operations are highly accurate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The United States Department of Agriculture’s high-speed wind tunnel facility in College Station, Texas, USA was used to determine droplet size distributions generated by dispersant delivery nozzles at wind speeds comparable to those used in aerial dispersant application. A laser particle size anal...

  12. Deformable Dose Reconstruction to Optimize the Planning and Delivery of Liver Cancer Radiotherapy

    NASA Astrophysics Data System (ADS)

    Velec, Michael

    The precise delivery of radiation to liver cancer patients results in improved control with higher tumor doses and minimized normal tissues doses. A margin of normal tissue around the tumor requires irradiation however to account for treatment delivery uncertainties. Daily image-guidance allows targeting of the liver, a surrogate for the tumor, to reduce geometric errors. However poor direct tumor visualization, anatomical deformation and breathing motion introduce uncertainties between the planned dose, calculated on a single pre-treatment computed tomography image, and the dose that is delivered. A novel deformable image registration algorithm based on tissue biomechanics was applied to previous liver cancer patients to track targets and surrounding organs during radiotherapy. Modeling these daily anatomic variations permitted dose accumulation, thereby improving calculations of the delivered doses. The accuracy of the algorithm to track dose was validated using imaging from a deformable, 3-dimensional dosimeter able to optically track absorbed dose. Reconstructing the delivered dose revealed that 70% of patients had substantial deviations from the initial planned dose. An alternative image-guidance technique using respiratory-correlated imaging was simulated, which reduced both the residual tumor targeting errors and the magnitude of the delivered dose deviations. A planning and delivery strategy for liver radiotherapy was then developed that minimizes the impact of breathing motion, and applied a margin to account for the impact of liver deformation during treatment. This margin is 38% smaller on average than the margin used clinically, and permitted an average dose-escalation to liver tumors of 9% for the same risk of toxicity. Simulating the delivered dose with deformable dose reconstruction demonstrated the plans with smaller margins were robust as 90% of patients' tumors received the intended dose. This strategy can be readily implemented with widely

  13. The development and verification of a highly accurate collision prediction model for automated noncoplanar plan delivery

    SciTech Connect

    Yu, Victoria Y.; Tran, Angelia; Nguyen, Dan; Cao, Minsong; Ruan, Dan; Low, Daniel A.; Sheng, Ke

    2015-11-15

    Purpose: Significant dosimetric benefits had been previously demonstrated in highly noncoplanar treatment plans. In this study, the authors developed and verified an individualized collision model for the purpose of delivering highly noncoplanar radiotherapy and tested the feasibility of total delivery automation with Varian TrueBeam developer mode. Methods: A hand-held 3D scanner was used to capture the surfaces of an anthropomorphic phantom and a human subject, which were positioned with a computer-aided design model of a TrueBeam machine to create a detailed virtual geometrical collision model. The collision model included gantry, collimator, and couch motion degrees of freedom. The accuracy of the 3D scanner was validated by scanning a rigid cubical phantom with known dimensions. The collision model was then validated by generating 300 linear accelerator orientations corresponding to 300 gantry-to-couch and gantry-to-phantom distances, and comparing the corresponding distance measurements to their corresponding models. The linear accelerator orientations reflected uniformly sampled noncoplanar beam angles to the head, lung, and prostate. The distance discrepancies between measurements on the physical and virtual systems were used to estimate treatment-site-specific safety buffer distances with 0.1%, 0.01%, and 0.001% probability of collision between the gantry and couch or phantom. Plans containing 20 noncoplanar beams to the brain, lung, and prostate optimized via an in-house noncoplanar radiotherapy platform were converted into XML script for automated delivery and the entire delivery was recorded and timed to demonstrate the feasibility of automated delivery. Results: The 3D scanner measured the dimension of the 14 cm cubic phantom within 0.5 mm. The maximal absolute discrepancy between machine and model measurements for gantry-to-couch and gantry-to-phantom was 0.95 and 2.97 cm, respectively. The reduced accuracy of gantry-to-phantom measurements was

  14. Human Growth Hormone Delivery with a Microneedle Transdermal System: Preclinical Formulation, Stability, Delivery and PK of Therapeutically Relevant Doses

    PubMed Central

    Ameri, Mahmoud; Kadkhodayan, Miryam; Nguyen, Joe; Bravo, Joseph A.; Su, Rebeca; Chan, Kenneth; Samiee, Ahmad; Daddona, Peter E.

    2014-01-01

    This study evaluated the feasibility of coating formulated recombinant human growth hormone (rhGH) on a titanium microneedle transdermal delivery system, Zosano Pharma (ZP)-hGH, and assessed preclinical patch delivery performance. Formulation rheology and surface activity were assessed by viscometry and contact angle measurement. rhGH liquid formulation was coated onto titanium microneedles by dip-coating and drying. The stability of coated rhGH was determined by size exclusion chromatography-high performance liquid chromatography (SEC-HPLC). Preclinical delivery and pharmacokinetic studies were conducted in female hairless guinea pigs (HGP) using rhGH coated microneedle patches at 0.5 and 1 mg doses and compared to Norditropin® a commercially approved rhGH subcutaneous injection. Studies demonstrated successful rhGH formulation development and coating on microneedle arrays. The ZP-hGH patches remained stable at 40 °C for six months with no significant change in % aggregates. Pharmacokinetic studies showed that the rhGH-coated microneedle patches, delivered with high efficiency and the doses delivered indicated linearity with average Tmax of 30 min. The absolute bioavailability of the microneedle rhGH patches was similar to subcutaneous Norditropin® injections. These results suggest that ZP-transdermal microneedle patch delivery of rhGH is feasible and may offer an effective and patient-friendly alternative to currently marketed rhGH injectables. PMID:24838219

  15. A comprehensive analysis of the IMRT dose delivery process using statistical process control (SPC)

    SciTech Connect

    Gerard, Karine; Grandhaye, Jean-Pierre; Marchesi, Vincent; Kafrouni, Hanna; Husson, Francois; Aletti, Pierre

    2009-04-15

    The aim of this study is to introduce tools to improve the security of each IMRT patient treatment by determining action levels for the dose delivery process. To achieve this, the patient-specific quality control results performed with an ionization chamber--and which characterize the dose delivery process--have been retrospectively analyzed using a method borrowed from industry: Statistical process control (SPC). The latter consisted in fulfilling four principal well-structured steps. The authors first quantified the short term variability of ionization chamber measurements regarding the clinical tolerances used in the cancer center ({+-}4% of deviation between the calculated and measured doses) by calculating a control process capability (C{sub pc}) index. The C{sub pc} index was found superior to 4, which implies that the observed variability of the dose delivery process is not biased by the short term variability of the measurement. Then, the authors demonstrated using a normality test that the quality control results could be approximated by a normal distribution with two parameters (mean and standard deviation). Finally, the authors used two complementary tools--control charts and performance indices--to thoroughly analyze the IMRT dose delivery process. Control charts aim at monitoring the process over time using statistical control limits to distinguish random (natural) variations from significant changes in the process, whereas performance indices aim at quantifying the ability of the process to produce data that are within the clinical tolerances, at a precise moment. The authors retrospectively showed that the analysis of three selected control charts (individual value, moving-range, and EWMA control charts) allowed efficient drift detection of the dose delivery process for prostate and head-and-neck treatments before the quality controls were outside the clinical tolerances. Therefore, when analyzed in real time, during quality controls, they should

  16. A comprehensive analysis of the IMRT dose delivery process using statistical process control (SPC).

    PubMed

    Gérard, Karine; Grandhaye, Jean-Pierre; Marchesi, Vincent; Kafrouni, Hanna; Husson, François; Aletti, Pierre

    2009-04-01

    The aim of this study is to introduce tools to improve the security of each IMRT patient treatment by determining action levels for the dose delivery process. To achieve this, the patient-specific quality control results performed with an ionization chamber--and which characterize the dose delivery process--have been retrospectively analyzed using a method borrowed from industry: Statistical process control (SPC). The latter consisted in fulfilling four principal well-structured steps. The authors first quantified the short-term variability of ionization chamber measurements regarding the clinical tolerances used in the cancer center (+/- 4% of deviation between the calculated and measured doses) by calculating a control process capability (C(pc)) index. The C(pc) index was found superior to 4, which implies that the observed variability of the dose delivery process is not biased by the short-term variability of the measurement. Then, the authors demonstrated using a normality test that the quality control results could be approximated by a normal distribution with two parameters (mean and standard deviation). Finally, the authors used two complementary tools--control charts and performance indices--to thoroughly analyze the IMRT dose delivery process. Control charts aim at monitoring the process over time using statistical control limits to distinguish random (natural) variations from significant changes in the process, whereas performance indices aim at quantifying the ability of the process to produce data that are within the clinical tolerances, at a precise moment. The authors retrospectively showed that the analysis of three selected control charts (individual value, moving-range, and EWMA control charts) allowed efficient drift detection of the dose delivery process for prostate and head-and-neck treatments before the quality controls were outside the clinical tolerances. Therefore, when analyzed in real time, during quality controls, they should improve the

  17. Dose-volume delivery guided proton therapy using beam on-line PET system

    SciTech Connect

    Nishio, Teiji; Ogino, Takashi; Nomura, Kazuhiro; Uchida, Hiroshi

    2006-11-15

    Proton therapy is one form of radiotherapy in which the irradiation can be concentrated on a tumor using a scanned or modulated Bragg peak. Therefore, it is very important to evaluate the proton-irradiated volume accurately. The proton-irradiated volume can be confirmed by detection of pair annihilation gamma rays from positron emitter nuclei generated by the target nuclear fragment reaction of irradiated proton nuclei and nuclei in the irradiation target using a positron emission tomography (PET) apparatus, and dose-volume delivery guided proton therapy (DGPT) can thereby be achieved using PET images. In the proton treatment room, a beam ON-LINE PET system (BOLPs) was constructed so that a PET apparatus of the planar-type with a high spatial resolution of about 2 mm was mounted with the field of view covering the isocenter of the beam irradiation system. The position and intensity of activity were measured using the BOLPs immediately after the proton irradiation of a gelatinous water target containing {sup 16}O nuclei at different proton irradiation energy levels. The change of the activity-distribution range against the change of the physical range was observed within 2 mm. The experiments of proton irradiation to a rabbit and the imaging of the activity were performed. In addition, the proton beam energy used to irradiate the rabbit was changed. When the beam condition was changed, the difference between the two images acquired from the measurement of the BOLPs was confirmed to clearly identify the proton-irradiated volume.

  18. Hyperbaric spinal anesthesia with ropivacaine coadministered with sufentanil for cesarean delivery: a dose-response study

    PubMed Central

    Zheng, Dongyue; Wu, Guowei; Qin, Peishun; Ji, Bin; Ye, Lisha; Shi, Tong; Huang, Huang; Jin, Lexiao

    2015-01-01

    Adjuvant sufentanil could achieve effective spinal anesthesia with low dose of hyperbaric ropivacaine for cesarean delivery. Two previous studies had calculated the 50% effective dose (ED50) of intrathecal ropivacaine coadministered with sufentanil for cesarean delivery. However, the 95% effective dose (ED95) of intrathecal hyperbaric ropivacaine coadministered with sufentanil for cesarean delivery remains uncertain. This study determined the ED95 of intrathecal hyperbaric ropivacaine coadministered with sufentanil for cesarean delivery. 80 ASA physical status I or II parturients undergoing elective cesarean delivery were enrolled in this prospective, randomized, double-blind investigation. A combined spinal and epidural anesthesia was performed at the L3-L4 interspace. Patients received a dose of spinal ropivacaine coadministered with sufentanil 5 μg diluted to 3.0 ml with normal saline and 0.5 ml of 10% dextrose: 7.5 mg (n = 20), 9.0 mg (n = 20), 10.5 mg (n = 20), or 12 mg (n = 20). An effective dose was defined as a dose that provided bilateral sensory block to T7 within 10 min after intrathecal drug administration and required no epidural top-up for surgery to be completed. The ED50 and ED95 values for successful anesthesia were determined using a logistic regression model. The ED50 (95% confidence interval [CI]) for successful anesthesia was 8.4 (4.0-9.8) mg and the ED95 (95% CI) was 11.4 (9.7-13.9) mg. The results show that the ED95 of intrathecal hyperbaric ropivacaine coadministered with sufentanil 5 μg for cesarean delivery was 11.4 mg. The addition of sufentanil could significantly reduce the dosage of ropivacaine. PMID:26131159

  19. SU-E-T-475: An Accurate Linear Model of Tomotherapy MLC-Detector System for Patient Specific Delivery QA

    SciTech Connect

    Chen, Y; Mo, X; Chen, M; Olivera, G; Parnell, D; Key, S; Lu, W; Reeher, M; Galmarini, D

    2014-06-01

    Purpose: An accurate leaf fluence model can be used in applications such as patient specific delivery QA and in-vivo dosimetry for TomoTherapy systems. It is known that the total fluence is not a linear combination of individual leaf fluence due to leakage-transmission, tongue-and-groove, and source occlusion effect. Here we propose a method to model the nonlinear effects as linear terms thus making the MLC-detector system a linear system. Methods: A leaf pattern basis (LPB) consisting of no-leaf-open, single-leaf-open, double-leaf-open and triple-leaf-open patterns are chosen to represent linear and major nonlinear effects of leaf fluence as a linear system. An arbitrary leaf pattern can be expressed as (or decomposed to) a linear combination of the LPB either pulse by pulse or weighted by dwelling time. The exit detector responses to the LPB are obtained by processing returned detector signals resulting from the predefined leaf patterns for each jaw setting. Through forward transformation, detector signal can be predicted given a delivery plan. An equivalent leaf open time (LOT) sinogram containing output variation information can also be inversely calculated from the measured detector signals. Twelve patient plans were delivered in air. The equivalent LOT sinograms were compared with their planned sinograms. Results: The whole calibration process was done in 20 minutes. For two randomly generated leaf patterns, 98.5% of the active channels showed differences within 0.5% of the local maximum between the predicted and measured signals. Averaged over the twelve plans, 90% of LOT errors were within +/−10 ms. The LOT systematic error increases and shows an oscillating pattern when LOT is shorter than 50 ms. Conclusion: The LPB method models the MLC-detector response accurately, which improves patient specific delivery QA and in-vivo dosimetry for TomoTherapy systems. It is sensitive enough to detect systematic LOT errors as small as 10 ms.

  20. Mathematical model accurately predicts protein release from an affinity-based delivery system.

    PubMed

    Vulic, Katarina; Pakulska, Malgosia M; Sonthalia, Rohit; Ramachandran, Arun; Shoichet, Molly S

    2015-01-10

    Affinity-based controlled release modulates the delivery of protein or small molecule therapeutics through transient dissociation/association. To understand which parameters can be used to tune release, we used a mathematical model based on simple binding kinetics. A comprehensive asymptotic analysis revealed three characteristic regimes for therapeutic release from affinity-based systems. These regimes can be controlled by diffusion or unbinding kinetics, and can exhibit release over either a single stage or two stages. This analysis fundamentally changes the way we think of controlling release from affinity-based systems and thereby explains some of the discrepancies in the literature on which parameters influence affinity-based release. The rate of protein release from affinity-based systems is determined by the balance of diffusion of the therapeutic agent through the hydrogel and the dissociation kinetics of the affinity pair. Equations for tuning protein release rate by altering the strength (KD) of the affinity interaction, the concentration of binding ligand in the system, the rate of dissociation (koff) of the complex, and the hydrogel size and geometry, are provided. We validated our model by collapsing the model simulations and the experimental data from a recently described affinity release system, to a single master curve. Importantly, this mathematical analysis can be applied to any single species affinity-based system to determine the parameters required for a desired release profile. PMID:25449806

  1. Dose calculation for hypofractionated volumetric-modulated arc therapy: approximating continuous arc delivery and tongue-and-groove modeling*

    PubMed Central

    Yang, Jie; Tang, Grace; Zhang, Pengpeng; Hunt, Margie; Lim, Seng B.; LoSasso, Thomas; Mageras, Gig

    2016-01-01

    Hypofractionated treatments generally increase the complexity of a treatment plan due to the more stringent constraints of normal tissues and target coverage. As a result, treatment plans contain more modulated MLC motions that may require extra efforts for accurate dose calculation. This study explores methods to minimize the differences between in-house dose calculation and actual delivery of hypofractionated volumetric-modulated arc therapy (VMAT), by focusing on arc approximation and tongue-and-groove (TG) modeling. For dose calculation, the continuous delivery arc is typically approximated by a series of static beams with an angular spacing of 2°. This causes significant error when there is large MLC movement from one beam to the next. While increasing the number of beams will minimize the dose error, calculation time will increase significantly. We propose a solution by inserting two additional apertures at each of the beam angle for dose calculation. These additional apertures were interpolated at two-thirds’ degree before and after each beam. Effectively, there were a total of three MLC apertures at each beam angle, and the weighted average fluence from the three apertures was used for calculation. Because the number of beams was kept the same, calculation time was only increased by about 6%–8%. For a lung plan, areas of high local dose differences (> 4%) between film measurement and calculation with one aperture were significantly reduced in calculation with three apertures. Ion chamber measurement also showed similar results, where improvements were seen with calculations using additional apertures. Dose calculation accuracy was further improved for TG modeling by developing a sampling method for beam fluence matrix. Single element point sampling for fluence transmitted through MLC was used for our fluence matrix with 1 mm resolution. For Varian HDMLC, grid alignment can cause fluence sampling error. To correct this, transmission volume averaging was

  2. Dose calculation for hypofractionated volumetric-modulated arc therapy: approximating continuous arc delivery and tongue-and-groove modeling.

    PubMed

    Yang, Jie; Tang, Grace; Zhang, Pengpeng; Hunt, Margie; Lim, Seng B; LoSasso, Thomas; Mageras, Gig

    2016-01-01

     Hypofractionated treatments generally increase the complexity of a treatment plan due to the more stringent constraints of normal tissues and target coverage. As a result, treatment plans contain more modulated MLC motions that may require extra efforts for accurate dose calculation. This study explores methods to minimize the differences between in-house dose calculation and actual delivery of hypofractionated volumetric-modulated arc therapy (VMAT), by focusing on arc approximation and tongue-and-groove (TG) modeling. For dose calculation, the continuous delivery arc is typically approximated by a series of static beams with an angular spacing of 2°. This causes significant error when there is large MLC movement from one beam to the next. While increasing the number of beams will minimize the dose error, calculation time will increase significantly. We propose a solution by inserting two additional apertures at each of the beam angle for dose calculation. These additional apertures were interpolated at two-thirds' degree before and after each beam. Effectively, there were a total of three MLC apertures at each beam angle, and the weighted average fluence from the three apertures was used for calculation. Because the number of beams was kept the same, calculation time was only increased by about 6%-8%. For a lung plan, areas of high local dose differences (> 4%) between film measurement and calculation with one aperture were significantly reduced in calculation with three apertures. Ion chamber measure-ment also showed similar results, where improvements were seen with calculations using additional apertures. Dose calculation accuracy was further improved for TG modeling by developing a sampling method for beam fluence matrix. Single ele-ment point sampling for fluence transmitted through MLC was used for our fluence matrix with 1 mm resolution. For Varian HDMLC, grid alignment can cause fluence sampling error. To correct this, transmission volume averaging was

  3. Dosimetric verification of IMAT delivery with a conventional EPID system and a commercial portal dose image prediction tool

    SciTech Connect

    Iori, Mauro; Cagni, Elisabetta; Paiusco, Marta; Munro, Peter; Nahum, Alan E.

    2010-01-15

    Purpose: The electronic portal imaging device (EPID) is a system for checking the patient setup; as a result of its integration with the linear accelerator and software customized for dosimetry, it is increasingly used for verification of the delivery of fixed-field intensity-modulated radiation therapy (IMRT). In order to extend such an approach to intensity-modulated arc therapy (IMAT), the combined use of an EPID system and a portal dose image prediction (PDIP) tool has been investigated. Methods: The dosimetric behavior of an EPID system, mechanically reinforced to maintain its positional stability during the accelerator gantry rotation, has been studied to assess its ability to measure portal dose distributions for IMAT treatment beams. In addition, the PDIP tool of a commercial treatment planning system, commonly used for static IMRT dosimetry, has been validated for simulating the PDIs of IMAT treatment fields. The method has been applied to the delivery verification of 23 treatment fields that were measured in their dual mode of IMRT and IMAT modalities. Results: The EPID system has proved to be appropriate for measuring the PDIs of IMAT fields; additionally the PDIP tool was able to simulate these accurately. The results are quite similar to those obtained for static IMRT treatment verification, although it was necessary to investigate the dependence of the EPID signal and of the accelerator monitor chamber response on variable dose rate. Conclusions: Our initial tests indicate that the EPID system, together with the PDIP tool, is a suitable device for the verification of IMAT plan delivery; however, additional tests are necessary to confirm these results.

  4. Investigation of pulsed low dose rate radiotherapy using dynamic arc delivery techniques

    NASA Astrophysics Data System (ADS)

    Ma, C.-M.; Lin, M. H.; Dai, X. F.; Koren, Sion; Klayton, T.; Wang, L.; Li, J. S.; Chen, L.; Price, R. A.

    2012-07-01

    There has been no consensus standard of care to treat recurrent cancer patients who have previously been irradiated. Pulsed low dose rate (PLDR) external beam radiotherapy has the potential to reduce normal tissue toxicities while still providing significant tumor control for recurrent cancers. This work investigates the dosimetry feasibility of PLDR treatment using dynamic arc delivery techniques. Five treatment sites were investigated in this study including breast, pancreas, prostate, head and neck, and lung. Dynamic arc plans were generated using the Varian Eclipse system and the RapidArc delivery technique with 6 and 10 MV photon beams. Each RapidArc plan consisted of two full arcs and the plan was delivered five times to achieve a daily dose of 200 cGy. The dosimetry requirement was to deliver approximately 20 cGy/arc with a 3 min interval to achieve an effective dose rate of 6.7 cGy min-1. Monte Carlo simulations were performed to calculate the actual dose delivered to the planning target volume (PTV) per arc taking into account beam attenuation/scattering and intensity modulation. The maximum, minimum and mean doses to the PTV were analyzed together with the dose volume histograms and isodose distributions. The dose delivery for the five plans was validated using solid water phantoms inserted with an ionization chamber and film, and a cylindrical detector array. Two intensity-modulated arcs were used to efficiently deliver the PLDR plans that provided conformal dose distributions for treating complex recurrent cancers. For the five treatment sites, the mean PTV dose ranged from 18.9 to 22.6 cGy/arc. For breast, the minimum and maximum PTV dose was 8.3 and 35.2 cGy/arc, respectively. The PTV dose varied between 12.9 and 27.5 cGy/arc for pancreas, 12.6 and 28.3 cGy/arc for prostate, 12.1 and 30.4 cGy/arc for H&N, and 16.2 and 27.6 cGy/arc for lung. Advanced radiation therapy can provide superior target coverage and normal tissue sparing for PLDR

  5. Radiochromic film based transit dosimetry for verification of dose delivery with intensity modulated radiotherapy

    SciTech Connect

    Chung, Kwangzoo; Lee, Kiho; Shin, Dongho; Kyung Lim, Young; Byeong Lee, Se; Yoon, Myonggeun; Son, Jaeman; Yong Park, Sung

    2013-02-15

    Purpose: To evaluate the transit dose based patient specific quality assurance (QA) of intensity modulated radiation therapy (IMRT) for verification of the accuracy of dose delivered to the patient. Methods: Five IMRT plans were selected and utilized to irradiate a homogeneous plastic water phantom and an inhomogeneous anthropomorphic phantom. The transit dose distribution was measured with radiochromic film and was compared with the computed dose map on the same plane using a gamma index with a 3% dose and a 3 mm distance-to-dose agreement tolerance limit. Results: While the average gamma index for comparisons of dose distributions was less than one for 98.9% of all pixels from the transit dose with the homogeneous phantom, the passing rate was reduced to 95.0% for the transit dose with the inhomogeneous phantom. Transit doses due to a 5 mm setup error may cause up to a 50% failure rate of the gamma index. Conclusions: Transit dose based IMRT QA may be superior to the traditional QA method since the former can show whether the inhomogeneity correction algorithm from TPS is accurate. In addition, transit dose based IMRT QA can be used to verify the accuracy of the dose delivered to the patient during treatment by revealing significant increases in the failure rate of the gamma index resulting from errors in patient positioning during treatment.

  6. New approach based on tetrahedral-mesh geometry for accurate 4D Monte Carlo patient-dose calculation.

    PubMed

    Han, Min Cheol; Yeom, Yeon Soo; Kim, Chan Hyeong; Kim, Seonghoon; Sohn, Jason W

    2015-02-21

    In the present study, to achieve accurate 4D Monte Carlo dose calculation in radiation therapy, we devised a new approach that combines (1) modeling of the patient body using tetrahedral-mesh geometry based on the patient's 4D CT data, (2) continuous movement/deformation of the tetrahedral patient model by interpolation of deformation vector fields acquired through deformable image registration, and (3) direct transportation of radiation particles during the movement and deformation of the tetrahedral patient model. The results of our feasibility study show that it is certainly possible to construct 4D patient models (= phantoms) with sufficient accuracy using the tetrahedral-mesh geometry and to directly transport radiation particles during continuous movement and deformation of the tetrahedral patient model. This new approach not only produces more accurate dose distribution in the patient but also replaces the current practice of using multiple 3D voxel phantoms and combining multiple dose distributions after Monte Carlo simulations. For routine clinical application of our new approach, the use of fast automatic segmentation algorithms is a must. In order to achieve, simultaneously, both dose accuracy and computation speed, the number of tetrahedrons for the lungs should be optimized. Although the current computation speed of our new 4D Monte Carlo simulation approach is slow (i.e. ~40 times slower than that of the conventional dose accumulation approach), this problem is resolvable by developing, in Geant4, a dedicated navigation class optimized for particle transportation in tetrahedral-mesh geometry. PMID:25615567

  7. SU-F-BRF-13: Investigating the Feasibility of Accurate Dose Measurement in a Deforming Radiochromic Dosimeter

    SciTech Connect

    Juang, T; Adamovics, J; Oldham, M

    2014-06-15

    Purpose: Presage-Def, a deformable radiochromic 3D dosimeter, has been previously shown to have potential for validating deformable image registration algorithms. This work extends this effort to investigate the feasibility of using Presage-Def to validate dose-accumulation algorithms in deforming structures. Methods: Two cylindrical Presage-Def dosimeters (8cm diameter, 4.5cm length) were irradiated in a water-bath with a simple 4-field box treatment. Isocentric dose was 20Gy. One dosimeter served as control (no deformation) while the other was laterally compressed during irradiation by 21%. Both dosimeters were imaged before and after irradiation with a fast (∼10 minutes for 1mm isotropic resolution), broad beam, high resolution optical-CT scanner. Measured dose distributions were compared to corresponding distributions calculated by a commissioned Eclipse planning system. Accuracy in the control was evaluated with 3D gamma (3%/3mm). The dose distribution calculated for the compressed dosimeter in the irradiation geometry cannot be directly compared via profiles or 3D gamma to the measured distribution, which deforms with release from compression. Thus, accuracy under deformation was determined by comparing integral dose within the high dose region of the deformed dosimeter distribution versus calculated dose. Dose profiles were used to study temporal stability of measured dose distributions. Results: Good dose agreement was demonstrated in the control with a 3D gamma passing rate of 96.6%. For the dosimeter irradiated under compression, the measured integral dose in the high dose region (518.0Gy*cm3) was within 6% of the Eclipse-calculated integral dose (549.4Gy*cm3). Elevated signal was noted on the dosimeter edge in the direction of compression. Change in dosimeter signal over 1.5 hours was ≤2.7%, and the relative dose distribution remained stable over this period of time. Conclusion: Presage-Def is promising as a 3D dosimeter capable of accurately

  8. The dose delivery effect of the different Beam ON interval in FFF SBRT: TrueBEAM

    NASA Astrophysics Data System (ADS)

    Tawonwong, T.; Suriyapee, S.; Oonsiri, S.; Sanghangthum, T.; Oonsiri, P.

    2016-03-01

    The purpose of this study is to determine the dose delivery effect of the different Beam ON interval in Flattening Filter Free Stereotactic Body Radiation Therapy (FFF-SBRT). The three 10MV-FFF SBRT plans (2 half rotating Rapid Arc, 9 to10 Gray/Fraction) were selected and irradiated in three different intervals (100%, 50% and 25%) using the RPM gating system. The plan verification was performed by the ArcCHECK for gamma analysis and the ionization chamber for point dose measurement. The dose delivery time of each interval were observed. For gamma analysis (2%&2mm criteria), the average percent pass of all plans for 100%, 50% and 25% intervals were 86.1±3.3%, 86.0±3.0% and 86.1±3.3%, respectively. For point dose measurement, the average ratios of each interval to the treatment planning were 1.012±0.015, 1.011±0.014 and 1.011±0.013 for 100%, 50% and 25% interval, respectively. The average dose delivery time was increasing from 74.3±5.0 second for 100% interval to 154.3±12.6 and 347.9±20.3 second for 50% and 25% interval, respectively. The same quality of the dose delivery from different Beam ON intervals in FFF-SBRT by TrueBEAM was illustrated. While the 100% interval represents the breath-hold treatment technique, the differences for the free-breathing using RPM gating system can be treated confidently.

  9. Significantly reduced radiation dose to operators during percutaneous vertebroplasty using a new cement delivery device

    PubMed Central

    2014-01-01

    Background Percutaneous vertebroplasy (PVP) might lead to significant radiation exposure to patients, operators, and operating room personnel. Therefore, radiaton exposure is a concern. The aim of this study was to present a remote control cement delivery device and study whether it can reduce dose exposue to operators. Methods After meticulous preoperative preparation, a series of 40 osteoporosis patients were treated with unilateral approach PVP using the new cement delivery divice. We compared levels of fluoroscopic exposure to operator standing on different places during operation. group A: operator stood about 4 meters away from X-ray tube behind the lead sheet. group B: operator stood adjacent to patient as using conventional manual cement delivery device. Results During whole operation process, radiation dose to the operator (group A) was 0.10 ± 0.03 (0.07-0.15) μSv, group B was 12.09 ± 4.67 (10–20) μSv. a difference that was found to be statistically significant (P < 0.001) between group A and group B. Conclusion New cement delivery device plus meticulous preoperative preparation can significantly decrease radiation dose to operators. PMID:25084860

  10. ACCURATE ACCUMULATION OF DOSE FOR IMPROVED UNDERSTANDING OF RADIATION EFFECTS IN NORMAL TISSUE

    PubMed Central

    Jaffray, David A.; Lindsay, Patricia E.; Brock, Kristy K.; Deasy, Joseph O.; Tomé, W. A.

    2013-01-01

    The actual distribution of radiation dose accumulated in normal tissues over the complete course of radiation therapy is, in general, poorly quantified. Differences in the patient anatomy between planning and treatment can occur gradually (e.g., tumor regression, resolution of edema) or relatively rapidly (e.g., bladder filling, breathing motion) and these undermine the accuracy of the planned dose distribution. Current efforts to maximize the therapeutic ratio require models that relate the true accumulated dose to clinical outcome. The needed accuracy can only be achieved through the development of robust methods that track the accumulation of dose within the various tissues in the body. Specific needs include the development of segmentation methods, tissue-mapping algorithms, uncertainty estimation, optimal schedules for image-based monitoring, and the development of informatics tools to support subsequent analysis. These developments will not only improve radiation outcomes modeling but will address the technical demands of the adaptive radiotherapy paradigm. The next 5 years need to see academia and industry bring these tools into the hands of the clinician and the clinical scientist. PMID:20171508

  11. Accurate Accumulation of Dose for Improved Understanding of Radiation Effects in Normal Tissue

    SciTech Connect

    Jaffray, David A.; Lindsay, Patricia E.; Brock, Kristy K.; Deasy, Joseph O.; Tome, W.A.

    2010-03-01

    The actual distribution of radiation dose accumulated in normal tissues over the complete course of radiation therapy is, in general, poorly quantified. Differences in the patient anatomy between planning and treatment can occur gradually (e.g., tumor regression, resolution of edema) or relatively rapidly (e.g., bladder filling, breathing motion) and these undermine the accuracy of the planned dose distribution. Current efforts to maximize the therapeutic ratio require models that relate the true accumulated dose to clinical outcome. The needed accuracy can only be achieved through the development of robust methods that track the accumulation of dose within the various tissues in the body. Specific needs include the development of segmentation methods, tissue-mapping algorithms, uncertainty estimation, optimal schedules for image-based monitoring, and the development of informatics tools to support subsequent analysis. These developments will not only improve radiation outcomes modeling but will address the technical demands of the adaptive radiotherapy paradigm. The next 5 years need to see academia and industry bring these tools into the hands of the clinician and the clinical scientist.

  12. Accurate Dosing of Antiretrovirals at Home Using a Foilized, Polyethylene Pouch to Prevent the Transmission of HIV From Mother to Child

    PubMed Central

    Choy, Alexa; Ortiz, Mercedes; Malkin, Robert

    2015-01-01

    Abstract Mother-to-child HIV transmission rates remain elevated in countries with high home birth rates. This risk can be dramatically reduced if infants receive antiretroviral (ARV) medication within 24 hours after birth. However, many barriers prevent access to these medications immediately after delivery, for example, there is currently no suitable mechanism to preserve predosed ARVs in the home during the months before birth. In response to this, students of the Duke University developed the Pratt pouch, a foilized polyethylene packet designed to preserve predosed ARVs. This cross-sectional study presents the data from the first clinical trials of the Pratt pouch in Guayaquil, Ecuador. Fourteen HIV-positive mothers and nurses were observed using the pouch to deliver a dose of ARVs to an infant. Weight measurements, time, and notes on spillage were taken at each observation period. Successful usage was quantitatively assessed through the calculation of dosing accuracy based on the volume of liquid medication emptied from the pouch. Additionally, mothers were surveyed after a month of using the device at home to assess their perception of the accuracy, acceptability, and ease of use of the pouch. Used pouches were collected for physical analysis of tearing. Observed users delivered accurate doses (M = 101.1%, standard deviation = 8.2%) in an average time of 2.6 minutes. A total of 2869 used pouches were recovered. No seal failures or failed attempts at opening/delivering the pouches were observed or detected. Forty-three mothers were surveyed. All mothers (100%) reported that they were able to follow their physician's treatment plan, all pouches were received in good condition and the pictorial sheets provided clear instructions. We conclude that the Pratt pouch is a highly accurate and easy-to-use device for delivering liquid oral ARVs to infants and is appropriate for prepackaging ARVs for home use. PMID:26107673

  13. Accurate dose assessment system for an exposed person utilising radiation transport calculation codes in emergency response to a radiological accident.

    PubMed

    Takahashi, F; Shigemori, Y; Seki, A

    2009-01-01

    A system has been developed to assess radiation dose distribution inside the body of exposed persons in a radiological accident by utilising radiation transport calculation codes-MCNP and MCNPX. The system consists mainly of two parts, pre-processor and post-processor of the radiation transport calculation. Programs for the pre-processor are used to set up a 'problem-dependent' input file, which defines the accident condition and dosimetric quantities to be estimated. The program developed for the post-processor part can effectively indicate dose information based upon the output file of the code. All of the programs in the dosimetry system can be executed with a generally used personal computer and accurately give the dose profile to an exposed person in a radiological accident without complicated procedures. An experiment using a physical phantom was carried out to verify the availability of the dosimetry system with the developed programs in a gamma ray irradiation field. PMID:19181661

  14. Systemic Delivery of Atropine Sulfate by the MicroDose Dry-Powder Inhaler

    PubMed Central

    Venkataramanan, R.; Hoffman, R.M.; George, M.P.; Petrov, A.; Richards, T.; Zhang, S.; Choi, J.; Gao, Y.Y.; Oakum, C.D.; Cook, R.O.; Donahoe, M.

    2013-01-01

    Abstract Background Inhaled atropine is being developed as a systemic and pulmonary treatment for the extended recovery period after chemical weapons exposure. We performed a pharmacokinetics study comparing inhaled atropine delivery using the MicroDose Therapeutx Dry Powder Inhaler (DPIA) with intramuscular (IM) atropine delivery via auto-injector (AUTO). Methods The MicroDose DPIA utilizes a novel piezoelectric system to aerosolize drug and excipient from a foil dosing blister. Subjects inhaled a 1.95-mg atropine sulfate dose from the dry powder inhaler on one study day [5 doses×0.4 mg per dose (nominal) delivered over 12 min] and received a 2-mg IM injection via the AtroPen® auto-injector on another. Pharmacokinetics, pharmacodynamic response, and safety were studied for 12 hr. Results A total of 17 subjects were enrolled. All subjects completed IM dosing. One subject did not perform inhaled delivery due to a skin reaction from the IM dose. Pharmacokinetic results were as follows: area under the curve concentration, DPIA=20.1±5.8, AUTO=23.7±4.9 ng hr/mL (means±SD); maximum concentration reached, DPIA=7.7±3.5, AUTO=11.0±3.8 ng/mL; time to reach maximum concentration, DPIA=0.25±0.47, AUTO=0.19±0.23 hr. Pharmacodynamic results were as follows: maximum increase in heart rate, DPIA=18±12, AUTO=23±13 beats/min; average change in 1-sec forced expiratory volume at 30 min, DPIA=0.16±0.22 L, AUTO=0.11±0.29 L. The relative bioavailability for DPIA was 87% (based on output dose). Two subjects demonstrated allergic responses: one to the first dose (AUTO), which was mild and transient, and one to the second dose (DPIA), which was moderate in severity, required treatment with oral and intravenous (IV) diphenhydramine and IV steroids, and lasted more than 7 days. Conclusions Dry powder inhalation is a highly bioavailable route for attaining rapid and consistent systemic concentrations of atropine. PMID:22691110

  15. In vitro study of cell survival following dynamic MLC intensity-modulated radiation therapy dose delivery

    SciTech Connect

    Moiseenko, Vitali; Duzenli, Cheryl; Durand, Ralph E.

    2007-04-15

    The possibility of reduced cell kill following intensity-modulated radiation therapy (IMRT) compared to conventional radiation therapy has been debated in the literature. This potential reduction in cell kill relates to prolonged treatment times typical of IMRT dose delivery and consequently increased repair of sublethal lesions. While there is some theoretical support to this reduction in cell kill published in the literature, direct experimental evidence specific to IMRT dose delivery patterns is lacking. In this study we present cell survival data for three cell lines: Chinese hamster V79 fibroblasts, human cervical carcinoma, SiHa and colon adenocarcinoma, WiDr. Cell survival was obtained for 2.1 Gy delivered as acute dose with parallel-opposed pair (POP), irradiation time 75 s, which served as a reference; regular seven-field IMRT, irradiation time 5 min; and IMRT with a break for multiple leaf collimator (MLC) re-initialization after three fields were delivered, irradiation time 10 min. An actual seven-field dynamic MLC IMRT plan for a head and neck patient was used. The IMRT plan was generated for a Varian EX or iX linear accelerator with 120 leaf Millenium MLC. Survival data were also collected for doses 1x, 2x, 3x, 4x, and 5x 2.1 Gy to establish parameters of the linear-quadratic equation describing survival following acute dose delivery. Cells were irradiated inside an acrylic cylindrical phantom specifically designed for this study. Doses from both IMRT and POP were validated using ion chamber measurements. A reproducible increase in cell survival was observed following IMRT dose delivery. This increase varied from small for V79, with a surviving fraction of 0.8326 following POP vs 0.8420 following uninterrupted IMRT, to very pronounced for SiHa, with a surviving fraction of 0.3903 following POP vs 0.5330 for uninterrupted IMRT. When compared to IMRT or IMRT with a break for MLC initialization, cell survival following acute dose delivery was

  16. Dose comparison of ultrasonic transdermal insulin delivery to subcutaneous insulin injection

    NASA Astrophysics Data System (ADS)

    Park, Eun-Joo; Dodds, Jeff; Barrie Smith, Nadine

    2010-03-01

    Prior studies have demonstrated the effectiveness of noninvasive transdermal insulin delivery using a cymbal transducer array. In this study the physiologic response to ultrasound mediated transdermal insulin delivery is compared to that of subcutaneously administered insulin. Anesthetized rats (350-550 g) were divided into four groups of four animals; one group representing ultrasound mediated insulin delivery and three representing subcutaneously administered insulin (0.15, 0.20, and 0.25 U/kg). The cymbal array was operated for 60 minutes at 20 kHz with 100 mW/cm2 spatial-peak temporal-peak intensity and a 20% duty cycle. The blood glucose level was determined at the beginning of the experiment and, following insulin administration, every 15 minutes for 90 minutes for both the ultrasound and injection groups. The change in blood glucose from baseline was compared between groups. When administered by subcutaneous injection at insulin doses of 0.15 and 0.20 U/kg, there was little change in the blood glucose levels over the 90 minute experiment. Following subcutaneous administration of insulin at a dose of 0.25 U/kg, blood glucose decreased by 190±96 mg/dl (mean±SD) at 90 minutes. The change in blood glucose following ultrasound mediated insulin delivery was -262±40 mg/dl at 90 minutes. As expected, the magnitude of change in blood glucose between the three injection groups was dependant on the dose of insulin administered. The change in blood glucose in the ultrasound group was greater than that observed in the injection groups suggesting that a higher effective dose of insulin was delivered.

  17. Pretreatment verification of dose calculation and delivery by means of measurements with PLEXITOM™ phantom

    PubMed Central

    Wołowiec, Paweł; Kukołowicz, Paweł; Lis, Krzysztof

    2013-01-01

    Aim To validate a pretreatment verification method of dose calculation and dose delivery based on measurements with Metaplex PTW phantom. Background The dose-response relationships for local tumor control and radiosensitive tissue complications are strong. It is widely accepted that an accuracy of dose delivery of about 3.5% (one standard deviation) is required in modern radiotherapy. This goal is difficult to achieve. This paper describes our experience with the control of dose delivery and calculations at the ICRU reference point. Materials and methods The calculations of dose at the ICRU reference point performed with the treatment planning system CMS XiO were checked by measurements carried out in the PLEXITOM™ phantom. All measurements were performed with the ion chamber positioned in the phantom, at the central axis of the beam, at depth equivalent to the radiological depth (at gantry zero position). The source-to-phantom surface distance was always set to keep the source-to-detector distance equal to the reference point depth defined in the ICRU Report 50 (generally, 100 cm). The dose was measured according to IAEA TRS 398 report for measurements in solid phantoms. The measurement results were corrected with the actual accelerator's output factor and for the non-full scatter conditions. Measurements were made for 111 patients and 327 fields. Results The average differences between measurements and calculations were 0.03% (SD = 1.4%), 0.3% (SD = 1.0%), 0.1% (SD = 1.1%), 0.6% (SD = 1.8%), 0.3% (SD = 1.5%) for all measurements, for total dose, for pelvis, thorax and H&N patients, respectively. Only in 15 cases (4.6%), the difference between the measured and the calculated dose was greater than 3%. For these fields, a detailed analysis was undertaken. Conclusion The verification method provides an instantaneous verification of dose calculations before the beginning of a patient's treatment. It allows to detect differences smaller than 3.5%. PMID

  18. Delivery of formoterol from a novel multi-dose inhaler Airmax.

    PubMed

    Zeng, X M; Jones, S; O'Leary, D; Phelan, M; Colledge, J

    2002-06-01

    Using a proprietary technology known as the X-ACT system--Active-metering, Cyclone-separator Technology, a novel multi-dose inhaler (Airmax) was developed to provide accurate and consistent dosing and a high-fine particle fraction ofthe drug. Formoterol, present as a blend with lactose monohydrate was delivered from Airmax to obtain a nominal formoterol dose of 6 or 12 microg. The devices were tested using a five-stage liquid impinger and a unit dose sampling apparatus, operated under conditions specified in European Pharmacopoeia (2000). Fine-particle dose (FPD) was defined as the dose of the aerosolized drug particles with an aerodynamic diameter < 5 microm and fine particle fraction (FPF) was the ratio of FPD to the total recovered dose. Dose per actuation was found to be 97.0+/-11.5% label claim (LC) or 5.8+/-0.7 microg (n = 140), and 100+/-9.4% LC or 12+/-1.1 microg (n=440), for the 6 and 12 microg strengths, respectively. The mass median aerodynamic diameter was 2.4+/-0.1 microm (n = 14), the geometric standard deviation 2.1+/-0.1 (n = 14), and FPF 44.4+/-24% (n= 14) for both strengths. Thus, the combination of active metering and cyclone separator produces highly consistent doses of formoterol that have a large respirable fraction. PMID:12117038

  19. Optimization of monoclonal antibody delivery via the lymphatics: the dose dependence

    SciTech Connect

    Steller, M.A.; Parker, R.J.; Covell, D.G.; Holton, O.D. 3d.; Keenan, A.M.; Sieber, S.M.; Weinstein, J.N.

    1986-04-01

    After interstitial injection in mice, antibody molecules enter local lymphatic vessels, flow with the lymph to regional lymph nodes, and bind to target antigens there. Compared with i.v. administration, delivery via the lymphatics provides a more efficient means for localizing antibody in lymph nodes. An IgG2a (36-7-5) directed against the murine class I major histocompatibility antigen H-2Kk has proved useful for studying the pharmacology of lymphatic delivery. At very low doses, most of the antibody remains at the injection site in Kk-positive animals. As the dose is progressively increased, most effective labeling occurs first in nodes proximal to the injection site and then in the next group of nodes along the lymphatic chain. At higher doses, antibody overflows the lymphatic system and enters the blood-stream via the thoracic duct and other lymphatic-venous connections. Once in the blood, antibody is rapidly cleared, apparently by binding to Kk-bearing cells. These findings indicate that the single-pass distribution of monoclonal antibodies in the lymphatics can be strongly dose dependent, a principle which may be of clinical significance in the improvement of immunolymphoscintigraphic imaging, especially with antibodies directed against normal and malignant lymphoid cells. Monoclonal antibodies directed against normal cell types in the lymph node may be useful for assessing the integrity of lymphatic chains by immunolymphoscintigraphy or, more speculatively, for altering the status of regional immune function. The results presented here indicate that a low or intermediate antibody dose may optimize the signal:noise ratio for imaging. In Kk-negative animals, the percentage of dose taken up in the major organs was essentially independent of the dose administered; there was no evidence for saturable sites of nonspecific binding.

  20. Small field dose delivery evaluations using cone beam optical computed tomography-based polymer gel dosimetry

    PubMed Central

    Olding, Timothy; Holmes, Oliver; DeJean, Paul; McAuley, Kim B.; Nkongchu, Ken; Santyr, Giles; Schreiner, L. John

    2011-01-01

    This paper explores the combination of cone beam optical computed tomography with an N-isopropylacrylamide (NIPAM)-based polymer gel dosimeter for three-dimensional dose imaging of small field deliveries. Initial investigations indicate that cone beam optical imaging of polymer gels is complicated by scattered stray light perturbation. This can lead to significant dosimetry failures in comparison to dose readout by magnetic resonance imaging (MRI). For example, only 60% of the voxels from an optical CT dose readout of a 1 l dosimeter passed a two-dimensional Low's gamma test (at a 3%, 3 mm criteria, relative to a treatment plan for a well-characterized pencil beam delivery). When the same dosimeter was probed by MRI, a 93% pass rate was observed. The optical dose measurement was improved after modifications to the dosimeter preparation, matching its performance with the imaging capabilities of the scanner. With the new dosimeter preparation, 99.7% of the optical CT voxels passed a Low's gamma test at the 3%, 3 mm criteria and 92.7% at a 2%, 2 mm criteria. The fitted interjar dose responses of a small sample set of modified dosimeters prepared (a) from the same gel batch and (b) from different gel batches prepared on the same day were found to be in agreement to within 3.6% and 3.8%, respectively, over the full dose range. Without drawing any statistical conclusions, this experiment gives a preliminary indication that intrabatch or interbatch NIPAM dosimeters prepared on the same day should be suitable for dose sensitivity calibration. PMID:21430853

  1. Evaluation of a head-repositioner and Z-plate system for improved accuracy of dose delivery.

    PubMed

    Charney, Sarah C; Lutz, Wendell R; Klein, Mary K; Jones, Pamela D

    2009-01-01

    Radiation therapy requires accurate dose delivery to targets often identifiable only on computed tomography (CT) images. Translation between the isocenter localized on CT and laser setup for radiation treatment, and interfractional head repositioning are frequent sources of positioning error. The objective was to design a simple, accurate apparatus to eliminate these sources of error. System accuracy was confirmed with phantom and in vivo measurements. A head repositioner that fixates the maxilla via dental mold with fiducial marker Z-plates attached was fabricated to facilitate the connection between the isocenter on CT and laser treatment setup. A phantom study targeting steel balls randomly located within the head repositioner was performed. The center of each ball was marked on a transverse CT slice on which six points of the Z-plate were also visible. Based on the relative position of the six Z-plate points and the ball center, the laser setup position on each Z-plate and a top plate was calculated. Based on these setup marks, orthogonal port films, directed toward each target, were evaluated for accuracy without regard to visual setup. A similar procedure was followed to confirm accuracy of in vivo treatment setups in four dogs using implanted gold seeds. Sequential port films of three dogs were made to confirm interfractional accuracy. Phantom and in vivo measurements confirmed accuracy of 2 mm between isocenter on CT and the center of the treatment dose distribution. Port films confirmed similar accuracy for interfractional treatments. The system reliably connects CT target localization to accurate initial and interfractional radiation treatment setup. PMID:19507401

  2. A microfluidic reciprocating intracochlear drug delivery system with reservoir and active dose control

    PubMed Central

    Kim, Ernest S.; Gustenhoven, Erich; Mescher, Mark J.; Pararas, Erin E. Leary; Smith, Kim A.; Spencer, Abigail J.; Tandon, Vishal; Borenstein, Jeffrey T.; Fiering, Jason

    2014-01-01

    Reciprocating microfluidic drug delivery, as compared to steady or pulsed infusion, has unique features which may be advantageous in many therapeutic applications. We have previously described a device, designed for wearable use in small animal models, which periodically infuses then withdraws a sub-microliter volume of drug solution to and from the endogenous fluid of the inner ear. This delivery approach results in zero net volume of liquid transfer while enabling mass transport of compounds to the cochlea by means of diffusion and mixing. We report here on an advanced wearable delivery system aimed at further miniaturization and complex dose protocols. Enhancements to the system include the incorporation of a planar micropump to generate reciprocating flow and a novel drug reservoir which maintains zero net volume delivery and permits programmable modulation of the drug concentration in the infused bolus. The reciprocating pump is fabricated from laminated polymer films and employs a miniature electromagnetic actuator to meet the size and weight requirements of a head-mounted in vivo guinea pig testing system. The reservoir comprises a long microchannel in series with a micropump, connected in parallel with the reciprocating flow network. We characterized in vitro the response and repeatability of the planar pump and compared the results with a lumped element simulation. We also characterized the performance of the reservoir, including repeatability of dosing and range of dose modulation. Acute in vivo experiments were performed in which the reciprocating pump was used to deliver a test compound to the cochlea of anesthetized guinea pigs to evaluate short-term safety and efficacy of the system. These advances are key steps toward realization of an implantable device for long-term therapeutic applications in humans. PMID:24302432

  3. Cobalt-60 tomotherapy: Clinical treatment planning and phantom dose delivery studies

    SciTech Connect

    Dhanesar, Sandeep; Darko, Johnson; Joshi, Chandra P.; Kerr, Andrew; John Schreiner, L.

    2013-08-15

    Purpose: Investigations have shown that a Cobalt-60 (Co-60) radioactive source has the potential to play a role in intensity modulated radiation therapy (IMRT). In this paper, Co-60 tomotherapy's conformal dose delivery potential is evaluated by delivering conformal dose plans on a cylindrical homogeneous phantom containing clinical structures similar to those found in a typical head and neck (H and N) cancer. Also, the clinical potential of Co-60 tomotherapy is investigated by generating 2D clinical treatment plans for H and N and prostate anatomical regions. These plans are compared with the 6 MV based treatment plans for modalities such as linear accelerator-based tomotherapy and broad beam IMRT, and 15 MV based 3D conformal radiation therapy (3DCRT).Methods: For experimental validation studies, clinical and nonclinical conformal dose patterns were delivered on circular, homogeneous phantoms containing GafChromic film. For clinical planning study, dose calculations were performed with the EGSnrc Monte Carlo program, where a Theratronics 780C Co-60 unit and a 6 MV linear accelerator were modeled with a MIMiC binary multileaf collimator. An inhouse inverse treatment planning system was used to optimize tomotherapy plans using the same optimization parameters for both Co-60 and 6 MV beams. The IMRT and 3DCRT plans for the clinical cases were generated entirely in the Eclipse treatment planning system based on inhouse IMRT and 3DCRT site specific protocols.Results: The doses delivered to the homogeneous phantoms agreed with the calculations, indicating that it is possible to deliver highly conformal doses with the Co-60 unit. The dose distributions for Co-60 tomotherapy clinical plans for both clinical cases were similar to those obtained with 6 MV based tomotherapy and IMRT, and much more conformal compared to 3DCRT plans. The dose area histograms showed that the Co-60 plans achieve the dose objectives for the targets and organs at risk.Conclusions: These results

  4. The role of Cobalt-60 source in Intensity Modulated Radiation Therapy: From modeling finite sources to treatment planning and conformal dose delivery

    NASA Astrophysics Data System (ADS)

    Dhanesar, Sandeep Kaur

    Cobalt-60 (Co-60) units played an integral role in radiation therapy from the mid-1950s to the 1970s. Although they continue to be used to treat cancer in some parts of the world, their role has been significantly reduced due to the invention of medical linear accelerators. A number of groups have indicated a strong potential for Co-60 units in modern radiation therapy. The Medical Physics group at the Cancer Center of the Southeastern Ontario and Queen's University has shown the feasibility of Intensity Modulated Radiation Therapy (IMRT) via simple conformal treatment planning and dose delivery using a Co-60 unit. In this thesis, initial Co-60 tomotherapy planning investigations on simple uniform phantoms are extended to actual clinical cases based on patient CT data. The planning is based on radiation dose data from a clinical Co-60 unit fitted with a multileaf collimator (MLC) and modeled in the EGSnrc Monte Carlo system. An in house treatment planning program is used to calculate IMRT dose distributions. Conformal delivery in a single slice on a uniform phantom based on sequentially delivered pencil beams is verified by Gafchromic film. Volumetric dose distributions for Co-60 serial tomotherapy are then generated for typical clinical sites that had been treated at our clinic by conventional 6MV IMRT using Varian Eclipse treatment plans. The Co-60 treatment plans are compared with the clinical IMRT plans using conventional matrices such as dose volume histograms (DVH). Dose delivery based on simultaneously opened MLC leaves is also explored and a novel MLC segmentation method is proposed. In order to increase efficiency of dose calculations, a novel convolution based fluence model for treatment planning is also proposed. The ion chamber measurements showed that the Monte Carlo modeling of the beam data under the MIMiC MLC is accurate. The film measurements from the uniform phantom irradiations confirm that IMRT plans from our in-house treatment planning system

  5. Is Heparin Effective for the Controlled Delivery of High-Dose Bone Morphogenetic Protein-2?

    PubMed

    Kim, Ri Youn; Lee, Beomseok; Park, Si-Nae; Ko, Jae-Hyung; Kim, In Sook; Hwang, Soon Jung

    2016-05-01

    Sustained release of bone morphogenetic protein (BMP)-2 by heparin-contained biomaterials is advantageous for bone tissue regeneration using low-dose BMP-2. However, its effect with high-dose BMP-2 is still unclear and should be clarified considering the clinical use of a high dose of BMP-2 in spine and oral surgery. This study aimed to evaluate the efficacy of a heparin-conjugated collagen sponge (HCS) with high-dose BMP-2 delivery by investigating in vivo initial osteogenic regulation and bone healing over 12 weeks in comparison with that of an absorbable collagen sponge (ACS). The in vitro BMP-2 release profile in the HCS exhibited a lower burst followed by a sustained release of BMP-2, whereas that of the ACS showed an initial burst phase only. As a result of a lower burst, the HCS-BMP group showed higher expression of bone-forming/resorbing markers and enhanced activation of osteoclasts than the ACS-BMP group within the scaffold of defect after 7 days, which is presumed to be because of retention of relatively higher amounts of BMP-2. However, the surrounding calvariae were less resorbed in the HCS-BMP group, compared with the aggressive resorptive response in the ACS-BMP group. Microcomputed tomography and histology revealed that HCS-BMP guided more effective bone regeneration of central defect over time inducing minor ossification at the defect exterior, whereas ACS-BMP exhibited excessive ossification at the defect exterior. These results showed that HCS-mediated BMP-2 delivery at a high dose has advantages over ACS, including less early resorption of surrounding bone tissue and higher efficacy in compact bone regeneration over a longer period, highlighting a clinical feasibility of this technology. PMID:27098389

  6. Has the use of computers in radiation therapy improved the accuracy in radiation dose delivery?

    NASA Astrophysics Data System (ADS)

    Van Dyk, J.; Battista, J.

    2014-03-01

    Purpose: It is well recognized that computer technology has had a major impact on the practice of radiation oncology. This paper addresses the question as to how these computer advances have specifically impacted the accuracy of radiation dose delivery to the patient. Methods: A review was undertaken of all the key steps in the radiation treatment process ranging from machine calibration to patient treatment verification and irradiation. Using a semi-quantitative scale, each stage in the process was analysed from the point of view of gains in treatment accuracy. Results: Our critical review indicated that computerization related to digital medical imaging (ranging from target volume localization, to treatment planning, to image-guided treatment) has had the most significant impact on the accuracy of radiation treatment. Conversely, the premature adoption of intensity-modulated radiation therapy has actually degraded the accuracy of dose delivery compared to 3-D conformal radiation therapy. While computational power has improved dose calibration accuracy through Monte Carlo simulations of dosimeter response parameters, the overall impact in terms of percent improvement is relatively small compared to the improvements accrued from 3-D/4-D imaging. Conclusions: As a result of computer applications, we are better able to see and track the internal anatomy of the patient before, during and after treatment. This has yielded the most significant enhancement to the knowledge of "in vivo" dose distributions in the patient. Furthermore, a much richer set of 3-D/4-D co-registered dose-image data is thus becoming available for retrospective analysis of radiobiological and clinical responses.

  7. Wireless programmable electrochemical drug delivery micropump with fully integrated electrochemical dosing sensors.

    PubMed

    Sheybani, Roya; Cobo, Angelica; Meng, Ellis

    2015-08-01

    We present a fully integrated implantable electrolysis-based micropump with incorporated EI dosing sensors. Wireless powering and data telemetry (through amplitude and frequency modulation) were utilized to achieve variable flow control and a bi-directional data link with the sensors. Wireless infusion rate control (0.14-1.04 μL/min) and dose sensing (bolus resolution of 0.55-2 μL) were each calibrated separately with the final circuit architecture and then simultaneous wireless flow control and dose sensing were demonstrated. Recombination detection using the dosing system, as well as, effects of coil separation distance and misalignment in wireless power and data transfer were studied. A custom-made normally closed spring-loaded ball check valve was designed and incorporated at the reservoir outlet to prevent backflow of fluids as a result of the reverse pressure gradient caused by recombination of electrolysis gases. Successful delivery, infusion rate control, and dose sensing were achieved in simulated brain tissue. PMID:26149696

  8. Dose and Chemical Modification Considerations for Continuous Cyclic AMP Analog Delivery to the Injured CNS

    PubMed Central

    Fouad, Karim; Ghosh, Mousumi; Vavrek, Romana; Tse, Arthur D.

    2009-01-01

    Abstract In this investigation, two cell-permeable synthetic analogs of cAMP, dibutyryl-cAMP (db-cAMP) and 8-bromo-cAMP, which are widely used to elevate intracellular cAMP levels under experimental conditions, were investigated for their ability to dose-dependently improve histological and functional outcomes following continuous delivery in two models of incomplete spinal cord injury (SCI). The cAMP analogs were delivered via osmotic minipumps at 1–250 mM through an indwelling cortical cannula or by intrathecal infusion for up to 4 weeks after either a T8 unilateral over-hemisection or a C2-3 dorsolateral quadrant lesion, respectively. In both SCI models, continuous db-cAMP delivery was associated with histopathological changes that included sporadic micro-hemorrhage formation and cavitation, enhanced macrophage infiltration and tissue damage at regions beyond the immediate application site; no deleterious or beneficial effect of agent delivery was observed at the spinal injury site. Furthermore, these changes were accompanied by pronounced behavioral deficits that included an absence of progressive locomotor recovery, increased extensor tone, paralysis, and sensory abnormalities. These deleterious effects were not observed in saline-treated animals, in animals in which the db-cAMP dose did not exceed 1 mM, or in those animals that received a high dose (250 mM) of the alternative cAMP analog, 8-bromo-cAMP. These results demonstrate that, for continuous intraparenchymal or intrathecal administration of cAMP analogs for the study of biological or therapeutic effects within the central nervous system (CNS), consideration of the effective concentration applied as well as the potential toxicity of chemical moieties on the parent molecule and/or their activity needs to be taken into account. PMID:19397425

  9. The efficacy and safety of low dose epidural butorphanol on postoperative analgesia following cesarean delivery.

    PubMed

    Pokharel, K; Rahman, T R; Singh, S N; Bhattarai, B; Basnet, N; Khaniya, S

    2008-01-01

    Butorphanol is considered an effective and safe analgesic after cesarean delivery but is associated with profound dose-dependent sedation. Somnolence may cause hindrance in early mother-baby interaction. This study was designed to assess the analgesic efficacy and to monitor side-effects of low doses (0.5 mg and 0.75 mg) of epidural butorphanol with bupivacaine compared to bupivacaine alone in parturients following cesarean delivery. One hundred and twenty parturients (American Society of Anesthesiologists physical status 1 and 2) undergoing cesarean delivery were allocated into three groups: group 1 received epidural 0.125% bupivacaine while group 2 and 3 received an additional 0.5 mg and 0.75 mg butorphanol respectively. A combined spinal, epidural technique was used. Spinal anaesthesia was used for surgery. The epidural route was used for postoperative analgesia with the study drug. Onset, duration and quality of analgesia, lowest visual analogue scales (VAS) score, and side effects were noted. The onset and duration of analgesia in group 2 (4.1+/-2.6 min and 202.4+/-62.8 min) and group 3 (4.0+/-2.5 min and 192.3+/-69.1 min) were significantly different (P<0.01) from group 1 (6.6+/-2.7 min and 145.7+/-89.6 min). The quality of analgesia in terms of time to first independent movement and satisfactory VAS were statistically better (P<0.01) in group 2 (3.9+/-0.3 hour and 8.1+/-0.1 mm) and group 3 (3.8+/-0.4 hour and 8.1+/-0.9 mm) than in group 1 (5.2+/-0.4 hour and 6.3+/-1.3 mm). The incidence of sedation was 5% in all the three groups. A lower dose of epidural butorphanol with bupivacaine produces a significantly earlier onset, longer duration and better quality of analgesia than bupivacaine does. PMID:18709032

  10. Poster — Thur Eve — 33: The Influence of a Modeled Treatment Couch on Dose Distributions During IMRT and RapidArc Treatment Delivery

    SciTech Connect

    Aldosary, Ghada; Nobah, Ahmad; Al-Zorkani, Faisal; Moftah, Belal; Devic, Slobodan

    2014-08-15

    Treatment couches have been known to perturb dose delivery in patients. This effect is most pronounced in techniques such as IMRT and RapidArc. Although modern treatment planning systems (TPS) include data for a “default” treatment couch, actual couches are not manufactured identically. Thus, variations in their Hounsfield Unit (HU) values may exist. This study demonstrates a practical and simple method of acquiring reliable HU data for any treatment couch. We also investigate the effects of both the default and modeled treatment couches on absorbed dose. Experimental verifications show that by neglecting to incorporate the treatment couch in the TPS, dose differences of up to 9.5% and 7.3% were present for 4 MV and 10 MV photon beams, respectively. Furthermore, a clinical study based on a cohort of 20 RapidArc and IMRT (brain, pelvis and abdominal) cases is performed. 2D dose distributions show that without the couch in the planning phase, differences ≤ 4.6% and 5.9% for RapidArc and IMRT cases are present for the same cases that the default couch was added to. Additionally, in comparison to the default couch, employing the modeled couch in the calculation process influences dose distributions by ≤ 2.7% and 8% for RapidArc and IMRT cases, respectively. This result was found to be site specific; where an accurate couch proves to be preferable for IMRT brain plans. As such, adding the couch during dose calculation decreases dose calculation errors, and a precisely modeled treatment couch offers higher dose delivery accuracy for brain treatment using IMRT.

  11. A non-rigid point matching method with local topology preservation for accurate bladder dose summation in high dose rate cervical brachytherapy

    NASA Astrophysics Data System (ADS)

    Chen, Haibin; Zhong, Zichun; Liao, Yuliang; Pompoš, Arnold; Hrycushko, Brian; Albuquerque, Kevin; Zhen, Xin; Zhou, Linghong; Gu, Xuejun

    2016-02-01

    GEC-ESTRO guidelines for high dose rate cervical brachytherapy advocate the reporting of the D2cc (the minimum dose received by the maximally exposed 2cc volume) to organs at risk. Due to large interfractional organ motion, reporting of accurate cumulative D2cc over a multifractional course is a non-trivial task requiring deformable image registration and deformable dose summation. To efficiently and accurately describe the point-to-point correspondence of the bladder wall over all treatment fractions while preserving local topologies, we propose a novel graphic processing unit (GPU)-based non-rigid point matching algorithm. This is achieved by introducing local anatomic information into the iterative update of correspondence matrix computation in the ‘thin plate splines-robust point matching’ (TPS-RPM) scheme. The performance of the GPU-based TPS-RPM with local topology preservation algorithm (TPS-RPM-LTP) was evaluated using four numerically simulated synthetic bladders having known deformations, a custom-made porcine bladder phantom embedded with twenty one fiducial markers, and 29 fractional computed tomography (CT) images from seven cervical cancer patients. Results show that TPS-RPM-LTP achieved excellent geometric accuracy with landmark residual distance error (RDE) of 0.7  ±  0.3 mm for the numerical synthetic data with different scales of bladder deformation and structure complexity, and 3.7  ±  1.8 mm and 1.6  ±  0.8 mm for the porcine bladder phantom with large and small deformation, respectively. The RDE accuracy of the urethral orifice landmarks in patient bladders was 3.7  ±  2.1 mm. When compared to the original TPS-RPM, the TPS-RPM-LTP improved landmark matching by reducing landmark RDE by 50  ±  19%, 37  ±  11% and 28  ±  11% for the synthetic, porcine phantom and the patient bladders, respectively. This was achieved with a computational time of less than 15 s in all cases

  12. A non-rigid point matching method with local topology preservation for accurate bladder dose summation in high dose rate cervical brachytherapy.

    PubMed

    Chen, Haibin; Zhong, Zichun; Liao, Yuliang; Pompoš, Arnold; Hrycushko, Brian; Albuquerque, Kevin; Zhen, Xin; Zhou, Linghong; Gu, Xuejun

    2016-02-01

    GEC-ESTRO guidelines for high dose rate cervical brachytherapy advocate the reporting of the D2cc (the minimum dose received by the maximally exposed 2cc volume) to organs at risk. Due to large interfractional organ motion, reporting of accurate cumulative D2cc over a multifractional course is a non-trivial task requiring deformable image registration and deformable dose summation. To efficiently and accurately describe the point-to-point correspondence of the bladder wall over all treatment fractions while preserving local topologies, we propose a novel graphic processing unit (GPU)-based non-rigid point matching algorithm. This is achieved by introducing local anatomic information into the iterative update of correspondence matrix computation in the 'thin plate splines-robust point matching' (TPS-RPM) scheme. The performance of the GPU-based TPS-RPM with local topology preservation algorithm (TPS-RPM-LTP) was evaluated using four numerically simulated synthetic bladders having known deformations, a custom-made porcine bladder phantom embedded with twenty one fiducial markers, and 29 fractional computed tomography (CT) images from seven cervical cancer patients. Results show that TPS-RPM-LTP achieved excellent geometric accuracy with landmark residual distance error (RDE) of 0.7  ±  0.3 mm for the numerical synthetic data with different scales of bladder deformation and structure complexity, and 3.7  ±  1.8 mm and 1.6  ±  0.8 mm for the porcine bladder phantom with large and small deformation, respectively. The RDE accuracy of the urethral orifice landmarks in patient bladders was 3.7  ±  2.1 mm. When compared to the original TPS-RPM, the TPS-RPM-LTP improved landmark matching by reducing landmark RDE by 50  ±  19%, 37  ±  11% and 28  ±  11% for the synthetic, porcine phantom and the patient bladders, respectively. This was achieved with a computational time of less than 15 s in all cases

  13. Measurement of neutron ambient dose equivalent in carbon-ion radiotherapy with an active scanned delivery system.

    PubMed

    Yonai, S; Furukawa, T; Inaniwa, T

    2014-10-01

    In ion beam radiotherapy, secondary neutrons contribute to an undesired dose outside the target volume, and consequently the increase of secondary cancer risk is a growing concern. In this study, neutron ambient dose equivalents in carbon-ion radiotherapy (CIRT) with an active beam delivery system were measured with a rem meter, WENDI-II, at National Institute of Radiological Sciences. When the same irradiation target was assumed, the measured neutron dose with an active beam was at most ∼15 % of that with a passive beam. This percentage became smaller as larger distances from the iso-centre. Also, when using an active beam delivery system, the neutron dose per treatment dose in CIRT was comparable with that in proton radiotherapy. Finally, it was experimentally demonstrated that the use of an active scanned beam in CIRT can greatly reduce the secondary neutron dose. PMID:24126486

  14. Treatment planning and delivery of shell dose distribution for precision irradiation

    NASA Astrophysics Data System (ADS)

    Matinfar, Mohammad; Iyer, Santosh; Ford, Eric; Wong, John; Kazanzides, Peter

    2010-02-01

    The motivation for shell dose irradiation is to deliver a high therapeutic dose to the surrounding supplying blood-vessels of a lesion. Our approach's main utility is in enabling laboratory experiments to test the much disputed hypothesis about tumor vascular damage. That is, at high doses, tumor control is driven by damage to the tumor vascular supply and not the damage to the tumor cells themselves. There is new evidence that bone marrow derived cells can reconstitute tumor blood vessels in mice after irradiation. Shell dosimetry is also of interest to study the effect of radiation on neurogenic stem cells that reside in small niche surface of the mouse ventricles, a generalized form of shell. The type of surface that we are considering as a shell is a sphere which is created by intersection of cylinders. The results are then extended to create the contours of different organ shapes. Specifically, we present a routine to identify the 3-D structure of a mouse brain, project it into 2-D contours and convert the contours into trajectories that can be executed by our platform. We use the Small Animal Radiation Research Platform (SARRP) to demonstrate the dose delivery procedure. The SARRP is a portable system for precision irradiation with beam sizes down to 0.5 mm and optimally planned radiation with on-board cone-beam CT guidance.

  15. A comparative study of folate receptor-targeted doxorubicin delivery systems: dosing regimens and therapeutic index.

    PubMed

    Scomparin, Anna; Salmaso, Stefano; Eldar-Boock, Anat; Ben-Shushan, Dikla; Ferber, Shiran; Tiram, Galia; Shmeeda, Hilary; Landa-Rouben, Natalie; Leor, Jonathan; Caliceti, Paolo; Gabizon, Alberto; Satchi-Fainaro, Ronit

    2015-06-28

    Ligand-receptor mediated targeting may affect differently the performance of supramolecular drug carriers depending on the nature of the nanocarrier. In this study, we compare the selectivity, safety and activity of doxorubicin (Dox) entrapped in liposomes versus Dox conjugated to polymeric nanocarriers in the presence or absence of a folic acid (FA)-targeting ligand to cancer cells that overexpress the folate receptor (FR). Two pullulan (Pull)-based conjugates of Dox were synthesized, (FA-PEG)-Pull-(Cyst-Dox) and (NH2-PEG)-Pull-(Cyst-Dox). The other delivery systems are Dox loaded PEGylated liposomes (PLD, Doxil®) and the FR-targeted version (PLD-FA) obtained by ligand post-insertion into the commercial formulation. Both receptor-targeted drug delivery systems (DDS) were shown to interact in vitro specifically with cells via the folate ligand. Treatment of FR-overexpressing human cervical carcinoma KB tumor-bearing mice with three-weekly injections resulted in slightly enhanced anticancer activity of PLD-FA compared to PLD and no activity for both pullulan-based conjugates. When the DDS were administered intravenously every other day, the folated-Pull conjugate and the non-folated-Pull conjugate displayed similar and low antitumor activity as free Dox. At this dosing regimen, the liposome-based formulations displayed enhanced antitumor activity with an advantage to the non-folated liposome. However, both liposomal formulations suffered from toxicity that was reversible following treatment discontinuation. Using a daily dosing schedule, with higher cumulative dose, the folated-Pull conjugate strongly inhibited tumor growth while free Dox was toxic at this regimen. For polymeric constructs, increasing dose intensity and cumulative dose strongly affects the therapeutic index and reveals a major therapeutic advantage for the FR-targeted formulation. All DDS were able to abrogate doxorubicin-induced cardiotoxicity. This study constitutes the first side

  16. Detection of IMRT delivery errors based on a simple constancy check of transit dose by using an EPID

    NASA Astrophysics Data System (ADS)

    Baek, Tae Seong; Chung, Eun Ji; Son, Jaeman; Yoon, Myonggeun

    2015-11-01

    Beam delivery errors during intensity modulated radiotherapy (IMRT) were detected based on a simple constancy check of the transit dose by using an electronic portal imaging device (EPID). Twenty-one IMRT plans were selected from various treatment sites, and the transit doses during treatment were measured by using an EPID. Transit doses were measured 11 times for each course of treatment, and the constancy check was based on gamma index (3%/3 mm) comparisons between a reference dose map (the first measured transit dose) and test dose maps (the following ten measured dose maps). In a simulation using an anthropomorphic phantom, the average passing rate of the tested transit dose was 100% for three representative treatment sites (head & neck, chest, and pelvis), indicating that IMRT was highly constant for normal beam delivery. The average passing rate of the transit dose for 1224 IMRT fields from 21 actual patients was 97.6% ± 2.5%, with the lower rate possibly being due to inaccuracies of patient positioning or anatomic changes. An EPIDbased simple constancy check may provide information about IMRT beam delivery errors during treatment.

  17. Exploring trade-offs between VMAT dose quality and delivery efficiency using a network optimization approach

    NASA Astrophysics Data System (ADS)

    Salari, Ehsan; Wala, Jeremiah; Craft, David

    2012-09-01

    To formulate and solve the fluence-map merging procedure of the recently-published VMAT treatment-plan optimization method, called vmerge, as a bi-criteria optimization problem. Using an exact merging method rather than the previously-used heuristic, we are able to better characterize the trade-off between the delivery efficiency and dose quality. vmerge begins with a solution of the fluence-map optimization problem with 180 equi-spaced beams that yields the ‘ideal’ dose distribution. Neighboring fluence maps are then successively merged, meaning that they are added together and delivered as a single map. The merging process improves the delivery efficiency at the expense of deviating from the initial high-quality dose distribution. We replace the original merging heuristic by considering the merging problem as a discrete bi-criteria optimization problem with the objectives of maximizing the treatment efficiency and minimizing the deviation from the ideal dose. We formulate this using a network-flow model that represents the merging problem. Since the problem is discrete and thus non-convex, we employ a customized box algorithm to characterize the Pareto frontier. The Pareto frontier is then used as a benchmark to evaluate the performance of the standard vmerge algorithm as well as two other similar heuristics. We test the exact and heuristic merging approaches on a pancreas and a prostate cancer case. For both cases, the shape of the Pareto frontier suggests that starting from a high-quality plan, we can obtain efficient VMAT plans through merging neighboring fluence maps without substantially deviating from the initial dose distribution. The trade-off curves obtained by the various heuristics are contrasted and shown to all be equally capable of initial plan simplifications, but to deviate in quality for more drastic efficiency improvements. This work presents a network optimization approach to the merging problem. Contrasting the trade-off curves of the

  18. In-phantom dose verification of prostate IMRT and VMAT deliveries using plastic scintillation detectors

    PubMed Central

    Klein, David; Briere, Tina Marie; Kudchadker, Rajat; Archambault, Louis; Beaulieu, Luc; Lee, Andrew; Beddar, Sam

    2012-01-01

    patient treatment by providing accurate in vivo dose reports during treatment and verify in real-time whether treatments are being delivered according to the prescribed plan. PMID:23180976

  19. Evaluation of fluence-based dose delivery incorporating the spatial variation of dosimetric leaf gap (DLG).

    PubMed

    Kumaraswamy, Lalith K; Xu, Zhengzheng; Bailey, Daniel W; Schmitt, Jonathan D; Podgorsak, Matthew B

    2016-01-01

    The Eclipse treatment planning system uses a single dosimetric leaf gap (DLG) value to retract all multileaf collimator leaf positions during dose calculation to model the rounded leaf ends. This study evaluates the dosimetric impact of the 2D variation of DLG on clinical treatment plans based on their degree of fluence modulation. In-house software was developed to retrospectively apply the 2D variation of DLG to 61 clinically treated VMAT plans, as well as to several test plans. The level of modulation of the VMAT cases were determined by calculating their modulation complexity score (MCS). Dose measurements were done using the MapCHECK device at a depth of 5.0 cm for plans with and without the 2D DLG correction. Measurements were compared against predicted dose planes from the TPS using absolute 3%/3 mm and 2%/2 mm gamma criteria for test plans and for VMAT cases, respectively. The gamma pass rate for the 2 mm, 4 mm, and 6 mm sweep test plans increased by 23.2%, 28.7%, and 26.0%, respectively, when the measurements were corrected with 2D variation of DLG. The clinical anal VMAT cases, which had very high MLC modulation, showed the most improvement. The majority of the improvement occurred for doses created by the 1.0 cm width leaves for both the test plans and the VMAT cases. The gamma pass rates for the highly modulated head and neck (H&N) cases, moderately modulated prostate and esophageal cases, and minimally modulated brain cases improved only slightly when corrected with 2D variation of DLG. This is because these cases did not employ the 1.0 cm width leaves for dose calculation and delivery. These data suggest that, at the very least, the TPS plans with highly modulated fluences created by the 1.0 cm fields require 2D DLG correction. Incorporating the 2D variation of DLG for the highly modulated clinical treatment plans improves their planar dose gamma pass rates, especially for fields employing the outer 1.0 cm width MLC leaves. This is because there are

  20. SU-E-T-335: Transit Dosimetry for Verification of Dose Delivery Using Electronic Portal Imaging Device (EPID)

    SciTech Connect

    Baek, T; Chung, E; Lee, S; Yoon, M

    2014-06-01

    Purpose: To evaluate the effectiveness of transit dose, measured with an electronic portal imaging device (EPID), in verifying actual dose delivery to patients. Methods: Plans of 5 patients with lung cancer, who received IMRT treatment, were examined using homogeneous solid water phantom and inhomogeneous anthropomorphic phantom. To simulate error in patient positioning, the anthropomorphic phantom was displaced from 5 mm to 10 mm in the inferior to superior (IS), superior to inferior (SI), left to right (LR), and right to left (RL) directions. The transit dose distribution was measured with EPID and was compared to the planed dose using gamma index. Results: Although the average passing rate based on gamma index (GI) with a 3% dose and a 3 mm distance-to-dose agreement tolerance limit was 94.34 % for the transit dose with homogeneous phantom, it was reduced to 84.63 % for the transit dose with inhomogeneous anthropomorphic phantom. The Result also shows that the setup error of 5mm (10mm) in IS, SI, LR and SI direction can Result in the decrease in values of GI passing rates by 1.3% (3.0%), 2.2% (4.3%), 5.9% (10.9%), and 8.9% (16.3%), respectively. Conclusion: Our feasibility study suggests that the transit dose-based quality assurance may provide information regarding accuracy of dose delivery as well as patient positioning.

  1. Application of in vitro transmucosal permeability, dose number, and maximum absorbable dose for biopharmaceutics assessment during early drug development for intraoral delivery.

    PubMed

    Yang, Zhen; Sotthivirat, Sutthilug; Wu, Yunhui; Lalloo, Anita; Nissley, Becky; Manser, Kimberly; Li, Hankun

    2016-04-30

    Intraoral (IO) administration is a unique route that takes advantage of transmucosal absorption in the oral cavity to deliver a drug substance locally or systemically. IO delivery can also enhance or enable oral administration, providing a better therapeutic benefit/safety risk profile for patient compliance. However, there are relatively few systematic biopharmaceutics assessments for IO delivery to date. Therefore, the goals of this study were to i) identify the most relevant in vitro permeability models as alternatives to porcine oral tissues (gold standard) for predicting human IO absorption and ii) establish guidelines for biopharmaceutics assessment during early drug development for IO delivery. Porcine kidney LLC-PK1 cells provided the strongest correlation of transmucosal permeability with porcine oral tissues followed by human Caco-2 cells. Furthermore, cultured human buccal tissues predicted high/low permeability classification and correlated well with porcine oral tissues, which are used for predicting clinical IO absorption. In the meantime, we introduced maximum absorbable dose and dose number in the oral cavity for IO delivery assessment as well as a decision tree to provide guidance for biopharmaceutics assessment during early drug development for IO delivery. PMID:26906458

  2. Microfabricated reciprocating micropump for intracochlear drug delivery with integrated drug/fluid storage and electronically controlled dosing.

    PubMed

    Tandon, Vishal; Kang, Woo Seok; Robbins, Tremaan A; Spencer, Abigail J; Kim, Ernest S; McKenna, Michael J; Kujawa, Sharon G; Fiering, Jason; Pararas, Erin E L; Mescher, Mark J; Sewell, William F; Borenstein, Jeffrey T

    2016-03-01

    The anatomical and pharmacological inaccessibility of the inner ear is a major challenge in drug-based treatment of auditory disorders. This also makes pharmacokinetic characterization of new drugs with systemic delivery challenging, because efficacy is coupled with how efficiently a drug can reach its target. Direct delivery of drugs to cochlear fluids bypasses pharmacokinetic barriers and helps to minimize systemic toxicity, but anatomical barriers make administration of multiple doses difficult without an automated delivery system. Such a system may be required for hair-cell regeneration treatments, which will likely require timed delivery of several drugs. To address these challenges, we have developed a micropump for controlled, automated inner-ear drug delivery with the ultimate goal of producing a long-term implantable/wearable delivery system. The current pump is designed to be used with a head mount for guinea pigs in preclinical drug characterization experiments. In this system, we have addressed several microfluidic challenges, including maintaining controlled delivery at safe, low flow rates and delivering drug without increasing the volume of fluid in the cochlea. By integrating a drug reservoir and all fluidic components into the microfluidic structure of the pump, we have made the drug delivery system robust compared to previous systems that utilized separate, tubing-connected components. In this study, we characterized the pump's unique infuse-withdraw and on-demand dosing capabilities on the bench and in guinea pig animal models. For the animal experiments, we used DNQX, a glutamate receptor antagonist, as a physiological indicator of drug delivery. DNQX suppresses compound action potentials (CAPs), so we were able to infer the distribution and spreading of the DNQX over time by measuring the changes in CAPs in response to stimuli at several characteristic frequencies. PMID:26778829

  3. Color-Coded Prefilled Medication Syringes Decrease Time to Delivery and Dosing Error in Simulated Emergency Department Pediatric Resuscitations

    PubMed Central

    Moreira, Maria E.; Hernandez, Caleb; Stevens, Allen D.; Jones, Seth; Sande, Margaret; Blumen, Jason R.; Hopkins, Emily; Bakes, Katherine; Haukoos, Jason S.

    2016-01-01

    Study objective The Institute of Medicine has called on the US health care system to identify and reduce medical errors. Unfortunately, medication dosing errors remain commonplace and may result in potentially life-threatening outcomes, particularly for pediatric patients when dosing requires weight-based calculations. Novel medication delivery systems that may reduce dosing errors resonate with national health care priorities. Our goal was to evaluate novel, prefilled medication syringes labeled with color-coded volumes corresponding to the weight-based dosing of the Broselow Tape, compared with conventional medication administration, in simulated pediatric emergency department (ED) resuscitation scenarios. Methods We performed a prospective, block-randomized, crossover study in which 10 emergency physician and nurse teams managed 2 simulated pediatric arrest scenarios in situ, using either prefilled, color-coded syringes (intervention) or conventional drug administration methods (control). The ED resuscitation room and the intravenous medication port were video recorded during the simulations. Data were extracted from video review by blinded, independent reviewers. Results Median time to delivery of all doses for the conventional and color-coded delivery groups was 47 seconds (95% confidence interval [CI] 40 to 53 seconds) and 19 seconds (95% CI 18 to 20 seconds), respectively (difference=27 seconds; 95% CI 21 to 33 seconds). With the conventional method, 118 doses were administered, with 20 critical dosing errors (17%); with the color-coded method, 123 doses were administered, with 0 critical dosing errors (difference=17%; 95% CI 4% to 30%). Conclusion A novel color-coded, prefilled syringe decreased time to medication administration and significantly reduced critical dosing errors by emergency physician and nurse teams during simulated pediatric ED resuscitations. PMID:25701295

  4. Impact of small MU/segment and dose rate on delivery accuracy of volumetric-modulated arc therapy (VMAT).

    PubMed

    Huang, Long; Zhuang, Tingliang; Mastroianni, Anthony; Djemil, Toufik; Cui, Taoran; Xia, Ping

    2016-01-01

    Volumetric-modulated arc therapy (VMAT) plans may require more control points (or segments) than some of fixed-beam IMRT plans that are created with a limited number of segments. Increasing number of control points in a VMAT plan for a given prescription dose could create a large portion of the total number of segments with small number monitor units (MUs) per segment. The purpose of this study is to investigate the impact of the small number MU/segment on the delivery accuracy of VMAT delivered with various dose rates. Ten patient datasets were planned for hippocampus sparing for whole brain irradiation. For each dataset, two VMAT plans were created with maximum dose rates of 600 MU/min (the maximum field size of 21 × 40 cm2) and 1000 MU/min (the maximum field size of 15 × 15 cm2) for a daily dose of 3 Gy. Without reoptimization, the daily dose of these plans was purposely reduced to 1.5 Gy and 1.0 Gy while keeping the same total dose. Using the two dose rates and three different daily doses, six VMAT plans for each dataset were delivered to a physical phantom to investigate how the changes of dose rate and daily doses impact on delivery accuracy. Using the gamma index, we directly compared the delivered planar dose profiles with the reduced daily doses (1.5 Gy and 1.0 Gy) to the delivered planar dose at 3 Gy daily dose, delivered at dose rate of 600 MU/min and 1000 MU/min, respectively. The average numbers of segments with MU/segment ≤ 1 were 35 ± 8, 87 ± 6 for VMAT-600 1.5 Gy, VMAT-600 1 Gy plans, and 30 ± 7 and 42 ± 6 for VMAT-1000 1.5 Gy and VMAT-1000 1 Gy plans, respectively. When delivered at 600 MU/min dose rate, the average gamma index passing rates (1%/1 mm criteria) of comparing delivered 1.5 Gy VMAT planar dose profiles to 3.0 Gy VMAT delivered planar dose profiles was 98.28% ± 1.66%, and the average gamma index passing rate of comparing delivered 1.0 Gy VMAT planar dose to 3.0 Gy VMAT delivered planar dose was 83.75% ± 4.86%. If using 2%/2mm

  5. Use of dose-dependent absorption into target tissues to more accurately predict cancer risk at low oral doses of hexavalent chromium.

    PubMed

    Haney, J

    2015-02-01

    The mouse dose at the lowest water concentration used in the National Toxicology Program hexavalent chromium (CrVI) drinking water study (NTP, 2008) is about 74,500 times higher than the approximate human dose corresponding to the 35-city geometric mean reported in EWG (2010) and over 1000 times higher than that based on the highest reported tap water concentration. With experimental and environmental doses differing greatly, it is a regulatory challenge to extrapolate high-dose results to environmental doses orders of magnitude lower in a meaningful and toxicologically predictive manner. This seems particularly true for the low-dose extrapolation of results for oral CrVI-induced carcinogenesis since dose-dependent differences in the dose fraction absorbed by mouse target tissues are apparent (Kirman et al., 2012). These data can be used for a straightforward adjustment of the USEPA (2010) draft oral slope factor (SFo) to be more predictive of risk at environmentally-relevant doses. More specifically, the evaluation of observed and modeled differences in the fraction of dose absorbed by target tissues at the point-of-departure for the draft SFo calculation versus lower doses suggests that the draft SFo be divided by a dose-specific adjustment factor of at least an order of magnitude to be less over-predictive of risk at more environmentally-relevant doses. PMID:25445295

  6. SU-E-T-107: Development of a GPU-Based Dose Delivery System for Adaptive Pencil Beam Scanning

    SciTech Connect

    Giordanengo, S; Russo, G; Marchetto, F; Attili, A; Monaco, V; Varasteh, M; Pella, A

    2014-06-01

    Purpose: A description of a GPU-based dose delivery system (G-DDS) to integrate a fast forward planning implementing in real-time the prescribed sequence of pencil beams. The system, which is under development, is designed to evaluate the dose distribution deviations due to range variations and interplay effects affecting mobile tumors treatments. Methods: The Dose Delivery System (DDS) in use at the Italian Centro Nazionale di Adroterapia Oncologica (CNAO), is the starting point for the presented system. A fast and partial forward planning (FP) tool has been developed to evaluate in few seconds the delivered dose distributions using the DDS data (on-line measurements of spot properties, i.e. number of particles and positions). The computation is performed during the intervals between synchrotron spills and, made available at the end of each spill. In the interval between two spills, the G-DDS will evaluate the delivered dose distributions taking into account the real-time target positions measured by a tracking system. The sequence of prescribed pencil beams for the following spill will be adapted taking into account the variations with respect to the original plan due to the target motion. In order to speed up the computation required to modify pencil beams distribution (up to 400 times has been reached), the Graphics Processing Units (GPUs) and advanced Field Programmable Gate Arrays (FPGAs) are used. Results: An existing offline forward planning is going to be optimized for the CUDA architecture: the gain in time will be presented. The preliminary performances of the developed GPU-based FP algorithms will be shown. Conclusion: A prototype of a GPU-based dose delivery system is under development and will be presented. The system workflow will be illustrated together with the approach adopted to integrate the three main systems, i.e. CNAO dose delivery system, fast forward planning, and tumor tracking system.

  7. An accurate derivation of the air dose-rate and the deposition concentration distribution by aerial monitoring in a low level contaminated area

    NASA Astrophysics Data System (ADS)

    Nishizawa, Yukiyasu; Sugita, Takeshi; Sanada, Yukihisa; Torii, Tatsuo

    2015-04-01

    Since 2011, MEXT (Ministry of Education, Culture, Sports, Science and Technology, Japan) have been conducting aerial monitoring to investigate the distribution of radioactive cesium dispersed into the atmosphere after the accident at the Fukushima Dai-ichi Nuclear Power Plant (FDNPP), Tokyo Electric Power Company. Distribution maps of the air dose-rate at 1 m above the ground and the radioactive cesium deposition concentration on the ground are prepared using spectrum obtained by aerial monitoring. The radioactive cesium deposition is derived from its dose rate, which is calculated by excluding the dose rate of the background radiation due to natural radionuclides from the air dose-rate at 1 m above the ground. The first step of the current method of calculating the dose rate due to natural radionuclides is calculate the ratio of the total count rate of areas where no radioactive cesium is detected and the count rate of regions with energy levels of 1,400 keV or higher (BG-Index). Next, calculate the air dose rate of radioactive cesium by multiplying the BG-Index and the integrated count rate of 1,400 keV or higher for the area where the radioactive cesium is distributed. In high dose-rate areas, however, the count rate of the 1,365-keV peak of Cs-134, though small, is included in the integrated count rate of 1,400 keV or higher, which could cause an overestimation of the air dose rate of natural radionuclides. We developed a method for accurately evaluating the distribution maps of natural air dose-rate by excluding the effect of radioactive cesium, even in contaminated areas, and obtained the accurate air dose-rate map attributed the radioactive cesium deposition on the ground. Furthermore, the natural dose-rate distribution throughout Japan has been obtained by this method.

  8. Influence of robust optimization in intensity-modulated proton therapy with different dose delivery techniques

    SciTech Connect

    Liu Wei; Li Yupeng; Li Xiaoqiang; Cao Wenhua; Zhang Xiaodong

    2012-06-15

    Purpose: The distal edge tracking (DET) technique in intensity-modulated proton therapy (IMPT) allows for high energy efficiency, fast and simple delivery, and simple inverse treatment planning; however, it is highly sensitive to uncertainties. In this study, the authors explored the application of DET in IMPT (IMPT-DET) and conducted robust optimization of IMPT-DET to see if the planning technique's sensitivity to uncertainties was reduced. They also compared conventional and robust optimization of IMPT-DET with three-dimensional IMPT (IMPT-3D) to gain understanding about how plan robustness is achieved. Methods: They compared the robustness of IMPT-DET and IMPT-3D plans to uncertainties by analyzing plans created for a typical prostate cancer case and a base of skull (BOS) cancer case (using data for patients who had undergone proton therapy at our institution). Spots with the highest and second highest energy layers were chosen so that the Bragg peak would be at the distal edge of the targets in IMPT-DET using 36 equally spaced angle beams; in IMPT-3D, 3 beams with angles chosen by a beam angle optimization algorithm were planned. Dose contributions for a number of range and setup uncertainties were calculated, and a worst-case robust optimization was performed. A robust quantification technique was used to evaluate the plans' sensitivity to uncertainties. Results: With no uncertainties considered, the DET is less robust to uncertainties than is the 3D method but offers better normal tissue protection. With robust optimization to account for range and setup uncertainties, robust optimization can improve the robustness of IMPT plans to uncertainties; however, our findings show the extent of improvement varies. Conclusions: IMPT's sensitivity to uncertainties can be improved by using robust optimization. They found two possible mechanisms that made improvements possible: (1) a localized single-field uniform dose distribution (LSFUD) mechanism, in which the

  9. Influence of robust optimization in intensity-modulated proton therapy with different dose delivery techniques

    PubMed Central

    Liu, Wei; Li, Yupeng; Li, Xiaoqiang; Cao, Wenhua; Zhang, Xiaodong

    2012-01-01

    Purpose: The distal edge tracking (DET) technique in intensity-modulated proton therapy (IMPT) allows for high energy efficiency, fast and simple delivery, and simple inverse treatment planning; however, it is highly sensitive to uncertainties. In this study, the authors explored the application of DET in IMPT (IMPT-DET) and conducted robust optimization of IMPT-DET to see if the planning technique’s sensitivity to uncertainties was reduced. They also compared conventional and robust optimization of IMPT-DET with three-dimensional IMPT (IMPT-3D) to gain understanding about how plan robustness is achieved. Methods: They compared the robustness of IMPT-DET and IMPT-3D plans to uncertainties by analyzing plans created for a typical prostate cancer case and a base of skull (BOS) cancer case (using data for patients who had undergone proton therapy at our institution). Spots with the highest and second highest energy layers were chosen so that the Bragg peak would be at the distal edge of the targets in IMPT-DET using 36 equally spaced angle beams; in IMPT-3D, 3 beams with angles chosen by a beam angle optimization algorithm were planned. Dose contributions for a number of range and setup uncertainties were calculated, and a worst-case robust optimization was performed. A robust quantification technique was used to evaluate the plans’ sensitivity to uncertainties. Results: With no uncertainties considered, the DET is less robust to uncertainties than is the 3D method but offers better normal tissue protection. With robust optimization to account for range and setup uncertainties, robust optimization can improve the robustness of IMPT plans to uncertainties; however, our findings show the extent of improvement varies. Conclusions: IMPT’s sensitivity to uncertainties can be improved by using robust optimization. They found two possible mechanisms that made improvements possible: (1) a localized single-field uniform dose distribution (LSFUD) mechanism, in which the

  10. Spatial Variation of Dosimetric Leaf Gap and Its Impact on Absolute Dose Delivery in Radiation Therapy

    NASA Astrophysics Data System (ADS)

    Kumaraswamy, Lalith

    During dose calculation, the Eclipse Treatment Planning system (TPS) retracts the MLC leaf positions by half of the dosimetric leaf gap (DLG) value (measured at central axis) for all leaf positions in a dynamic MLC plan to accurately model the rounded leaf ends. The aim of this study is to map the variation of DLG along the travel path of each MLC leaf pair and quantify how this variation impacts delivered dose. 6 MV DLG values were measured for all MLC leaf pairs in increments of 1.0 cm (from the line intersecting the CAX and perpendicular to MLC motion) to 13.0 cm off axis distance at depth of dose maximum. The measurements were performed on two Varian LINACs, both employing the Millennium 120-leaf MLC. The measurements were performed at several locations in the beam with both a Sun Nuclear MapCHECK device and a PTW pinpoint ion chamber. The measured DLGs for the middle 40 MLC leaf pairs (each 0.5 cm width) at positions along a line through the CAX and perpendicular to MLC leaf travel direction were very similar, varying maximally by only 0.2 mm. The outer 20 MLC leaf pairs (each 1.0 cm width) have much lower DLG values, about 0.3 to 0.5 mm lower than the central MLC leaf pair, at their respective central line position. Overall, the mean and the maximum variation between the 0.5 cm width leaves and the 1.0 cm width leaf pairs is 0.32 mm and 0.65 mm, respectively. The spatial variation in DLG is caused by the variation of intraleaf transmission through MLC leaves. Fluences centered on the CAX would not be affected since DLG does not vary; but any fluences residing significantly off-axis with narrow sweeping leaves may exhibit significant dose differences. This is due to the fact that there are differences in DLG between the true DLG exhibited by the 1.0 cm width outer leaves and the constant DLG value utilized by the TPS for dose calculation. Since there are large differences in DLG between the 0.5 cm width leaf pairs and 1.0 cm width leaf pairs, there is a need

  11. Optimizing human in vivo dosing and delivery of β-alanine supplements for muscle carnosine synthesis.

    PubMed

    Stellingwerff, Trent; Decombaz, Jacques; Harris, Roger C; Boesch, Chris

    2012-07-01

    Interest into the effects of carnosine on cellular metabolism is rapidly expanding. The first study to demonstrate in humans that chronic β-alanine (BA) supplementation (~3-6 g BA/day for ~4 weeks) can result in significantly augmented muscle carnosine concentrations (>50%) was only recently published. BA supplementation is potentially poised for application beyond the niche exercise and performance-enhancement field and into other more clinical populations. When examining all BA supplementation studies that directly measure muscle carnosine (n=8), there is a significant linear correlation between total grams of BA consumed (of daily intake ranges of 1.6-6.4 g BA/day) versus both the relative and absolute increases in muscle carnosine. Supporting this, a recent dose-response study demonstrated a large linear dependency (R2=0.921) based on the total grams of BA consumed over 8 weeks. The pre-supplementation baseline carnosine or individual subjects' body weight (from 65 to 90 kg) does not appear to impact on subsequent carnosine synthesis from BA consumption. Once muscle carnosine is augmented, the washout is very slow (~2%/week). Recently, a slow-release BA tablet supplement has been developed showing a smaller peak plasma BA concentration and delayed time to peak, with no difference in the area under the curve compared to pure BA in solution. Further, this slow-release profile resulted in a reduced urinary BA loss and improved retention, while at the same time, eliciting minimal paraesthesia symptoms. However, our complete understanding of optimizing in vivo delivery and dosing of BA is still in its infancy. Thus, this review will clarify our current knowledge of BA supplementation to augment muscle carnosine as well as highlight future research questions on the regulatory points of control for muscle carnosine synthesis. PMID:22358258

  12. TH-C-BRD-07: Minimizing Dose Uncertainty for Spot Scanning Beam Proton Therapy of Moving Tumor with Optimization of Delivery Sequence

    SciTech Connect

    Li, H; Zhang, X; Zhu, X; Li, Y

    2014-06-15

    Purpose: Intensity modulated proton therapy (IMPT) has been shown to be able to reduce dose to normal tissue compared to intensity modulated photon radio-therapy (IMRT), and has been implemented for selected lung cancer patients. However, respiratory motion-induced dose uncertainty remain one of the major concerns for the radiotherapy of lung cancer, and the utility of IMPT for lung patients was limited because of the proton dose uncertainty induced by motion. Strategies such as repainting and tumor tracking have been proposed and studied but repainting could result in unacceptable long delivery time and tracking is not yet clinically available. We propose a novel delivery strategy for spot scanning proton beam therapy. Method: The effective number of delivery (END) for each spot position in a treatment plan was calculated based on the parameters of the delivery system, including time required for each spot, spot size and energy. The dose uncertainty was then calculated with an analytical formula. The spot delivery sequence was optimized to maximize END and minimize the dose uncertainty. 2D Measurements with a detector array on a 1D moving platform were performed to validate the calculated results. Results: 143 2D measurements on a moving platform were performed for different delivery sequences of a single layer uniform pattern. The measured dose uncertainty is a strong function of the delivery sequence, the worst delivery sequence results in dose error up to 70% while the optimized delivery sequence results in dose error of <5%. END vs. measured dose uncertainty follows the analytical formula. Conclusion: With optimized delivery sequence, it is feasible to minimize the dose uncertainty due to motion in spot scanning proton therapy.

  13. Spatial variation of dosimetric leaf gap and its impact on dose delivery

    SciTech Connect

    Kumaraswamy, Lalith K.; Schmitt, Jonathan D.; Bailey, Daniel W.; Xu, Zheng Zheng; Podgorsak, Matthew B.

    2014-11-01

    Purpose: During dose calculation, the Eclipse treatment planning system (TPS) retracts the multileaf collimator (MLC) leaf positions by half of the dosimetric leaf gap (DLG) value (measured at central axis) for all leaf positions in a dynamic MLC plan to accurately model the rounded leaf ends. The aim of this study is to map the variation of DLG along the travel path of each MLC leaf pair and quantify how this variation impacts delivered dose. Methods: 6 MV DLG values were measured for all MLC leaf pairs in increments of 1.0 cm (from the line intersecting the CAX and perpendicular to MLC motion) to 13.0 cm off axis distance at dmax. The measurements were performed on two Varian linear accelerators, both employing the Millennium 120-leaf MLCs. The measurements were performed at several locations in the beam with both a Sun Nuclear MapCHECK device and a PTW pinpoint ion chamber. Results: The measured DLGs for the middle 40 MLC leaf pairs (each 0.5 cm width) at positions along a line through the CAX and perpendicular to MLC leaf travel direction were very similar, varying maximally by only 0.2 mm. The outer 20 MLC leaf pairs (each 1.0 cm width) have much lower DLG values, about 0.3–0.5 mm lower than the central MLC leaf pair, at their respective central line position. Overall, the mean and the maximum variation between the 0.5 cm width leaves and the 1.0 cm width leaf pairs are 0.32 and 0.65 mm, respectively. Conclusions: The spatial variation in DLG is caused by the variation of intraleaf transmission through MLC leaves. Fluences centered on the CAX would not be affected since DLG does not vary; but any fluences residing significantly off axis with narrow sweeping leaves may exhibit significant dose differences. This is due to the fact that there are differences in DLG between the true DLG exhibited by the 1.0 cm width outer leaves and the constant DLG value utilized by the TPS for dose calculation. Since there are large differences in DLG between the 0.5 cm width

  14. Design and physicochemical characterisation of novel dissolving polymeric microneedle arrays for transdermal delivery of high dose, low molecular weight drugs

    PubMed Central

    McCrudden, Maelíosa T.C.; Alkilani, Ahlam Zaid; McCrudden, Cian M.; McAlister, Emma; McCarthy, Helen O.; Woolfson, A. David; Donnelly, Ryan F.

    2014-01-01

    We describe formulation and evaluation of novel dissolving polymeric microneedle (MN) arrays for the facilitated delivery of low molecular weight, high dose drugs. Ibuprofen sodium was used as the model here and was successfully formulated at approximately 50% w/w in the dry state using the copolymer poly(methylvinylether/maleic acid). These MNs were robust and effectively penetrated skin in vitro, dissolving rapidly to deliver the incorporated drug. The delivery of 1.5 mg ibuprofen sodium, the theoretical mass of ibuprofen sodium contained within the dry MN alone, was vastly exceeded, indicating extensive delivery of the drug loaded into the baseplates. Indeed in in vitro transdermal delivery studies, approximately 33 mg (90%) of the drug initially loaded into the arrays was delivered over 24 h. Iontophoresis produced no meaningful increase in delivery. Biocompatibility studies and in vivo rat skin tolerance experiments raised no concerns. The blood plasma ibuprofen sodium concentrations achieved in rats (263 μg ml− 1 at the 24 h time point) were approximately 20 times greater than the human therapeutic plasma level. By simplistic extrapolation of average weights from rats to humans, a MN patch design of no greater than 10 cm2 could cautiously be estimated to deliver therapeutically-relevant concentrations of ibuprofen sodium in humans. This work, therefore, represents a significant progression in exploitation of MN for successful transdermal delivery of a much wider range of drugs. PMID:24556420

  15. Adaptive Liver Stereotactic Body Radiation Therapy: Automated Daily Plan Reoptimization Prevents Dose Delivery Degradation Caused by Anatomy Deformations

    SciTech Connect

    Leinders, Suzanne M.; Breedveld, Sebastiaan; Méndez Romero, Alejandra; Schaart, Dennis; Seppenwoolde, Yvette; Heijmen, Ben J.M.

    2013-12-01

    Purpose: To investigate how dose distributions for liver stereotactic body radiation therapy (SBRT) can be improved by using automated, daily plan reoptimization to account for anatomy deformations, compared with setup corrections only. Methods and Materials: For 12 tumors, 3 strategies for dose delivery were simulated. In the first strategy, computed tomography scans made before each treatment fraction were used only for patient repositioning before dose delivery for correction of detected tumor setup errors. In adaptive second and third strategies, in addition to the isocenter shift, intensity modulated radiation therapy beam profiles were reoptimized or both intensity profiles and beam orientations were reoptimized, respectively. All optimizations were performed with a recently published algorithm for automated, multicriteria optimization of both beam profiles and beam angles. Results: In 6 of 12 cases, violations of organs at risk (ie, heart, stomach, kidney) constraints of 1 to 6 Gy in single fractions occurred in cases of tumor repositioning only. By using the adaptive strategies, these could be avoided (<1 Gy). For 1 case, this needed adaptation by slightly underdosing the planning target volume. For 2 cases with restricted tumor dose in the planning phase to avoid organ-at-risk constraint violations, fraction doses could be increased by 1 and 2 Gy because of more favorable anatomy. Daily reoptimization of both beam profiles and beam angles (third strategy) performed slightly better than reoptimization of profiles only, but the latter required only a few minutes of computation time, whereas full reoptimization took several hours. Conclusions: This simulation study demonstrated that replanning based on daily acquired computed tomography scans can improve liver stereotactic body radiation therapy dose delivery.

  16. Cosuspensions of microcrystals and engineered microparticles for uniform and efficient delivery of respiratory therapeutics from pressurized metered dose inhalers.

    PubMed

    Vehring, Reinhard; Lechuga-Ballesteros, David; Joshi, Vidya; Noga, Brian; Dwivedi, Sarvajna K

    2012-10-23

    Engineered porous phospholipid microparticles with aerodynamic diameters in the respirable range of 1-2 μm were cosuspended in 1,1,1,2-tetrafluoroethane, a propellant, with microcrystals of glycopyrrolate, formoterol fumarate dihydrate, or Mometasone furoate-three drugs with different solubilities in the propellant, and different physical, chemical, and pharmacological attributes. The drug microcrystals were added individually, in pairs, or all three together to prepare different cosuspensions, contained in a pressurized metered dose inhaler (pMDI). The drug microcrystals irreversibly associated with the porous particles, and the resultant cosuspensions possessed greatly improved suspension stability compared with suspensions of drug microcrystals alone. In general, all cosuspensions showed efficient dose delivery of the drugs, with fine particle fractions of more than 60% for a wide range of doses, including those as low as 300 ng per inhaler actuation. In the cosuspension pMDIs, comparable fine particle fractions were delivered for all tested drugs, whether or not they were emitted from an inhaler containing one, two, or three drugs. We demonstrate that the cosuspension approach solves at least three long-standing problems in the clinical development of pMDI-based products: (1) dose and drug dependent delivery efficiency, (2) inability to formulate dose strengths below 1 μg to fully explore drug efficacy and safety, and (3) combination suspensions delivering a different fine particle fraction than individual drug suspensions. PMID:22985189

  17. Calibrating the High Density Magnetic Port within Tissue Expanders to Achieve more Accurate Dose Calculations for Postmastectomy Patients with Immediate Breast Reconstruction

    NASA Astrophysics Data System (ADS)

    Jones, Jasmine; Zhang, Rui; Heins, David; Castle, Katherine

    In postmastectomy radiotherapy, an increasing number of patients have tissue expanders inserted subpectorally when receiving immediate breast reconstruction. These tissue expanders are composed of silicone and are inflated with saline through an internal metallic port; this serves the purpose of stretching the muscle and skin tissue over time, in order to house a permanent implant. The issue with administering radiation therapy in the presence of a tissue expander is that the port's magnetic core can potentially perturb the dose delivered to the Planning Target Volume, causing significant artifacts in CT images. Several studies have explored this problem, and suggest that density corrections must be accounted for in treatment planning. However, very few studies accurately calibrated commercial TP systems for the high density material used in the port, and no studies employed fusion imaging to yield a more accurate contour of the port in treatment planning. We compared depth dose values in the water phantom between measurement and TPS calculations, and we were able to overcome some of the inhomogeneities presented by the image artifact by fusing the KVCT and MVCT images of the tissue expander together, resulting in a more precise comparison of dose calculations at discrete locations. We expect this method to be pivotal in the quantification of dose distribution in the PTV. Research funded by the LS-AMP Award.

  18. WE-E-18A-03: How Accurately Can the Peak Skin Dose in Fluoroscopy Be Determined Using Indirect Dose Metrics?

    SciTech Connect

    Jones, A; Pasciak, A

    2014-06-15

    Purpose: Skin dosimetry is important for fluoroscopically-guided interventions, as peak skin doses (PSD) that Result in skin reactions can be reached during these procedures. The purpose of this study was to assess the accuracy of different indirect dose estimates and to determine if PSD can be calculated within ±50% for embolization procedures. Methods: PSD were measured directly using radiochromic film for 41 consecutive embolization procedures. Indirect dose metrics from procedures were collected, including reference air kerma (RAK). Four different estimates of PSD were calculated and compared along with RAK to the measured PSD. The indirect estimates included a standard method, use of detailed information from the RDSR, and two simplified calculation methods. Indirect dosimetry was compared with direct measurements, including an analysis of uncertainty associated with film dosimetry. Factors affecting the accuracy of the indirect estimates were examined. Results: PSD calculated with the standard calculation method were within ±50% for all 41 procedures. This was also true for a simplified method using a single source-to-patient distance (SPD) for all calculations. RAK was within ±50% for all but one procedure. Cases for which RAK or calculated PSD exhibited large differences from the measured PSD were analyzed, and two causative factors were identified: ‘extreme’ SPD and large contributions to RAK from rotational angiography or runs acquired at large gantry angles. When calculated uncertainty limits [−12.8%, 10%] were applied to directly measured PSD, most indirect PSD estimates remained within ±50% of the measured PSD. Conclusions: Using indirect dose metrics, PSD can be determined within ±50% for embolization procedures, and usually to within ±35%. RAK can be used without modification to set notification limits and substantial radiation dose levels. These results can be extended to similar procedures, including vascular and interventional oncology

  19. Novel lung IMRT planning algorithms with nonuniform dose delivery strategy to account for respiratory motion.

    PubMed

    Li, Xiang; Zhang, Pengpeng; Mah, Dennis; Gewanter, Richard; Kutcher, Gerald

    2006-09-01

    To effectively deliver radiation dose to lung tumors, respiratory motion has to be considered in treatment planning. In this paper we first present a new lung IMRT planning algorithm, referred as the dose shaping (DS) method, that shapes the dose distribution according to the probability distribution of the tumor over the breathing cycle to account for respiratory motion. In IMRT planning a dose-based convolution method was generally adopted to compensate for random organ motion by performing 4-D dose calculations using a tumor motion probability density function. We modified the CON-DOSE method to a dose volume histogram based convolution method (CON-DVH) that allows nonuniform dose distribution to account for respiratory motion. We implemented the two new planning algorithms on an in-house IMRT planning system that uses the Eclipse (Varian, Palo Alto, CA) planning workstation as the dose calculation engine. The new algorithms were compared with (1) the conventional margin extension approach in which margin is generated based on the extreme positions of the tumor, (2) the dose-based convolution method, and (3) gating with 3 mm residual motion. Dose volume histogram, tumor control probability, normal tissue complication probability, and mean lung dose were calculated and used to evaluate the relative performance of these approaches at the end-exhale phase of the respiratory cycle. We recruited six patients in our treatment planning study. The study demonstrated that the two new methods could significantly reduce the ipsilateral normal lung dose and outperformed the margin extension method and the dose-based convolution method. Compared with the gated approach that has the best performance in the low dose region, the two methods we proposed have similar potential to escalate tumor dose, but could be more efficient because dose is delivered continuously. PMID:17022235

  20. A multi-head intradermal electroporation device allows for tailored and increased dose DNA vaccine delivery to the skin.

    PubMed

    McCoy, Jay R; Mendoza, Janess M; Spik, Kristin W; Badger, Catherine; Gomez, Alan F; Schmaljohn, Connie S; Sardesai, Niranjan Y; Broderick, Kate E

    2015-01-01

    The identification of an effective and tolerable delivery method is a necessity for the success of DNA vaccines in the clinic. This article describes the development and validation of a multi-headed intradermal electroporation device which would be applicable for delivering multiple DNA vaccine plasmids simultaneously but spatially separated. Reporter gene plasmids expressing green and red fluorescent proteins were used to demonstrate the impact of spatial separation on DNA delivery to increase the number of transfected cells and avoid interference through visible expression patterns. To investigate the impact of plasmid interference on immunogenicity, a disease target was investigated where issues with multi-valent vaccines had been previously described. DNA-based Hantaan and Puumala virus vaccines were delivered separately or as a combination and the effect of multi-valence was determined by appropriate assays. While a negative impact was observed for both antigenic vaccines when delivered together, these effects were mitigated when the vaccine was delivered using the multi-head device. We also demonstrate how the multi-head device facilitates higher dose delivery to the skin resulting in improved immune responses. This new multi-head platform device is an efficient, tolerable and non-invasive method to deliver multiple plasmid DNA constructs simultaneously allowing the tailoring of delivery sites for combination vaccines. Additionally, this device would allow the delivery of multi-plasmid vaccine formulations without risk of impacted immune responses through interference. Such a low-cost, easy to use device platform for the delivery of multi-agent DNA vaccines would have direct applications by the military and healthcare sectors for mass vaccination purposes. PMID:25839221

  1. A multi-head intradermal electroporation device allows for tailored and increased dose DNA vaccine delivery to the skin.

    PubMed

    McCoy, Jay R; Mendoza, Janess M; Spik, Kristin W; Badger, Catherine; Gomez, Alan F; Schmaljohn, Connie S; Sardesai, Niranjan Y; Broderick, Kate E

    2014-01-01

    The identification of an effective and tolerable delivery method is a necessity for the success of DNA vaccines in the clinic. This manuscript describes the development and validation of a multi-headed intradermal electroporation device which would be applicable for delivering multiple DNA vaccine plasmids simultaneously but spatially separated. Reporter gene plasmids expressing green and red fluorescent proteins were used to demonstrate the impact of spatial separation on DNA delivery to increase the number of transfected cells and avoid interference through visible expression patterns. To investigate the impact of plasmid interference on immunogenicity, a disease target was investigated where issues with multi-valent vaccines had been previously described. DNA-based Hantaan and Puumala virus vaccines were delivered separately or as a combination and the effect of multi-valence was determined by appropriate assays. While a negative impact was observed for both antigenic vaccines when delivered together, these effects were mitigated when the vaccine was delivered using the multi-head device. We also demonstrate how the multi-head device facilitates higher dose delivery to the skin resulting in improved immune responses. This new multi-head platform device is an efficient, tolerable and non-invasive method to deliver multiple plasmid DNA constructs simultaneously allowing the tailoring of delivery sites for combination vaccines. Additionally, this device would allow the delivery of multi-plasmid vaccine formulations without risk of impacted immune responses through interference. Such a low-cost, easy to use device platform for the delivery of multi-agent DNA vaccines would have direct applications by the military and healthcare sectors for mass vaccination purposes. PMID:25483486

  2. A multi-head intradermal electroporation device allows for tailored and increased dose DNA vaccine delivery to the skin

    PubMed Central

    McCoy, Jay R; Mendoza, Janess M; Spik, Kristin W; Badger, Catherine; Gomez, Alan F; Schmaljohn, Connie S; Sardesai, Niranjan Y; Broderick, Kate E

    2015-01-01

    The identification of an effective and tolerable delivery method is a necessity for the success of DNA vaccines in the clinic. This article describes the development and validation of a multi-headed intradermal electroporation device which would be applicable for delivering multiple DNA vaccine plasmids simultaneously but spatially separated. Reporter gene plasmids expressing green and red fluorescent proteins were used to demonstrate the impact of spatial separation on DNA delivery to increase the number of transfected cells and avoid interference through visible expression patterns. To investigate the impact of plasmid interference on immunogenicity, a disease target was investigated where issues with multi-valent vaccines had been previously described. DNA-based Hantaan and Puumala virus vaccines were delivered separately or as a combination and the effect of multi-valence was determined by appropriate assays. While a negative impact was observed for both antigenic vaccines when delivered together, these effects were mitigated when the vaccine was delivered using the multi-head device. We also demonstrate how the multi-head device facilitates higher dose delivery to the skin resulting in improved immune responses. This new multi-head platform device is an efficient, tolerable and non-invasive method to deliver multiple plasmid DNA constructs simultaneously allowing the tailoring of delivery sites for combination vaccines. Additionally, this device would allow the delivery of multi-plasmid vaccine formulations without risk of impacted immune responses through interference. Such a low-cost, easy to use device platform for the delivery of multi-agent DNA vaccines would have direct applications by the military and healthcare sectors for mass vaccination purposes. PMID:25839221

  3. Determination of dosimetric leaf gap using amorphous silicon electronic portal imaging device and its influence on intensity modulated radiotherapy dose delivery

    PubMed Central

    Balasingh, S. Timothy Peace; Singh, I. Rabi Raja; Rafic, K. Mohamathu; Babu, S. Ebenezer Suman; Ravindran, B. Paul

    2015-01-01

    As complex treatment techniques such as intensity modulated radiotherapy (IMRT) entail the modeling of rounded leaf-end transmission in the treatment planning system, it is important to accurately determine the dosimetric leaf gap (DLG) value for a precise calculation of dose. The advancements in the application of the electronic portal imaging device (EPID) in quality assurance (QA) and dosimetry have facilitated the determination of DLG in this study. The DLG measurements were performed using both the ionization chamber (DLGion) and EPID (DLGEPID) for sweeping gap fields of different widths. The DLGion values were found to be 1.133 mm and 1.120 mm for perpendicular and parallel orientations of the 0.125 cm3 ionization chamber, while the corresponding DLGEPID values were 0.843 mm and 0.819 mm, respectively. It was found that the DLG was independent of volume and orientation of the ionization chamber, depth, source to surface distance (SSD), and the rate of dose delivery. Since the patient-specific QA tests showed comparable results between the IMRT plans based on the DLGEPID and DLGion, it is concluded that the EPID can be a suitable alternative in the determination of DLG. PMID:26500398

  4. Delivery

    PubMed Central

    Miller, Thomas A

    2013-01-01

    Enthusiasm greeted the development of synthetic organic insecticides in the mid-twentieth century, only to see this give way to dismay and eventually scepticism and outright opposition by some. Regardless of how anyone feels about this issue, insecticides and other pesticides have become indispensable, which creates something of a dilemma. Possibly as a result of the shift in public attitude towards insecticides, genetic engineering of microbes was first met with scepticism and caution among scientists. Later, the development of genetically modified crop plants was met with an attitude that hardened into both acceptance and hard-core resistance. Transgenic insects, which came along at the dawn of the twenty-first century, encountered an entrenched opposition. Those of us responsible for studying the protection of crops have been affected more or less by these protagonist and antagonistic positions, and the experiences have often left one thoughtfully mystified as decisions are made by non-participants. Most of the issues boil down to concerns over delivery mechanisms. © 2013 Society of Chemical Industry PMID:23852646

  5. Use of a hand-held, metered-dose aerosol delivery device to administer pirbuterol acetate to horses with 'heaves'.

    PubMed

    Derksen, F J; Olszewski, M; Robinson, N E; Berney, C; Lloyd, J W; Hakala, J; Matson, C; Ruth, D

    1996-07-01

    Aerosol administration of bronchodilators to horses is recommended for treatment of certain airway diseases such as 'heaves'. We have developed a novel, hand-held, metered-dose inhaler and we sought to determine the bronchodilator efficacy of the beta 2 adrenoceptor agonist pirbuterol delivered by this device to horses affected with 'heaves'. To induce airway obstruction, 6 heaves-susceptible horses were stabled, bedded on straw and fed hay. When the maximum change in pleural pressure during tidal breathing (delta Pplmax) was greater than 20 cmH2O on 2 consecutive days, pulmonary function was measured before and 5, 10 and 30 min, as well as 1, 2, 3, 4, 5, 6 and 7 h after administration of aerosol pirbuterol. Pirbuterol was administered using a metered canister and the hand-held delivery device that was inserted into the left nostril. Either vehicle or pirbuterol acetate (400, 600, 800, 1200 or 1600 micrograms) was administered to each horse. Relief of airway obstruction indicated by changes in pulmonary function was observed within 5 min after administration of both vehicle and pirbuterol. Significant decreases in delta Pplmax and pulmonary resistance (RL) and an increase in dynamic compliance (Cdyn) persisted for the 7 h duration of the experiment. Comparison of the effect of vehicle and pirbuterol at each time period showed that pirbuterol decreased RL and delta Pplmax significantly for up to 1 h. The optimal dose was determined to be 600 micrograms. Immediate response to treatment, magnitude of drug effect and lack of side effects indicated that aerosol pirbuterol is an effective and safe bronchodilator in horses with 'heaves'. The hand-held, metered-dose aerosol delivery device was very convenient and extremely effective and is, therefore, recommended for delivery of therapeutic aerosols to horses. PMID:8818596

  6. The impacts of dental filling materials on RapidArc treatment planning and dose delivery: Challenges and solution

    SciTech Connect

    Mail, Noor; Al-Ghamdi, S.; Saoudi, A.; Albarakati, Y.; Ahmad Khan, M.; Saeedi, F.; Safadi, N.

    2013-08-15

    Purpose: The presence of high-density material in the oral cavity creates dose perturbation in both downstream and upstream directions at the surfaces of dental filling materials (DFM). In this study, the authors have investigated the effect of DFM on head and neck RapidArc treatment plans and delivery. Solutions are proposed to address (1) the issue of downstream dose perturbation, which might cause target under dosage, and (2) to reduce the upstream dose from DFM which may be the primary source of mucositis. In addition, an investigation of the clinical role of a custom-made plastic dental mold/gutter (PDM) in sparing the oral mucosa and tongue reaction is outlined.Methods: The influence of the dental filling artifacts on dose distribution was investigated using a geometrically well-defined head and neck intensity modulated radiation therapy (IMRT) verification phantom (PTW, Freiberg, Germany) with DFM inserts called amalgam, which contained 50% mercury, 25% silver, 14% tin, 8% copper, and 3% other trace metals. Three RapidArc plans were generated in the Varian Eclipse System to treat the oral cavity using the same computer tomography (CT) dataset, including (1) a raw CT image, (2) a streaking artifacts region, which was replaced with a mask of 10 HU, and (3) a 2 cm-thick 6000 HU virtual filter [a volume created in treatment planning system to compensate for beam attenuation, where the thickness of this virtual filter is based on the measured percent depth dose (PDD) data and Eclipse calculation]. The dose delivery for the three plans was verified using Gafchromic-EBT2 film measurements. The custom-made PDM technique to reduce backscatter dose was clinically tested on four head and neck cancer patients (T3, N1, M0) with DFM, two patients with PDM and the other two patients without PDM. The thickness calculation of the PDM toward the mucosa and tongue was purely based on the measured upstream dose. Patients’ with oral mucosal reaction was clinically examined

  7. Effects of ramp-up of inspired airflow on in vitro aerosol dose delivery performance for certain dry powder inhalers.

    PubMed

    Ung, Keith T; Chan, Hak-Kim

    2016-03-10

    This study investigated the effect of airflow ramp-up on the dose delivery performance of seven dry powder inhalers, covering a broad range of powder formulations and powder dispersion mechanisms. In vitro performance tests were performed at a target pressure drop of 4kPa, using two inspiratory flow ramp-up conditions, representing slow and fast ramp-up of airflow, respectively. The fluidization of bulk powder and aerosol clearance from the inhaler was assessed by laser photometer evaluation of aerosol emission kinetics and measurement of the delivered dose (DD). The quality of aerosol dispersion (i.e. de-agglomeration) and associated lung targeting performance was assessed by measuring the total lung dose (TLD) using the Alberta idealized mouth-throat model. The ratio of DD and TLD under slow/fast ramp conditions was used as a metric to rank-order flow ramp effects. Test results show that the delivered dose is relatively unaffected by flow ramp (DD ratio ~1 for all dry powder inhalers). In contrast, the total lung dose showed significantly more variation as a function of flow ramp and inhaler type. Engineered (spray dried) powder formulations were associated with relatively high TLD (>50% of nominal dose) compared to lactose blend and agglomerate based formulations, which had a lower TLD (7-40% of nominal dose), indicative of less efficient targeting of the lung. The TLD for the Tobi Podhaler was the least influenced by flow ramp (TLD ratio ~1), while the TLD for the Asmanex Twisthaler was the most sensitive to flow ramp (TLD ratio ≪1). The relatively high sensitivity of the Asmanex Twisthaler to flow ramp is attributed to rapid aerosol clearance (from the inhaler) combined with a strong effect of flow-rate on particle de-agglomeration and resulting size distribution. PMID:26780380

  8. Motion as a perturbation: Measurement-guided dose estimates to moving patient voxels during modulated arc deliveries

    SciTech Connect

    Feygelman, Vladimir; Zhang, Geoffrey; Hunt, Dylan; Opp, Daniel; Stambaugh, Cassandra; Wolf, Theresa K.; Nelms, Benjamin E.

    2013-02-15

    MLC sequences. For all phantoms and plans, time-resolved (10 Hz) ion chamber dose was collected. In addition, coronal (XY) films were exposed in the cube phantom to a VMAT beam with two different starting phases, and compared to the reconstructed motion-perturbed dose planes. Results: For the X or Y motions with the moving strip and geometrical phantoms, the maximum difference between perturbation-reconstructed and ion chamber doses did not exceed 1.9%, and the average for any motion pattern/starting phase did not exceed 1.3%. For the VMAT plans on the cubic and thoracic phantoms, one point exhibited a 3.5% error, while the remaining five were all within 1.1%. Across all the measurements (N = 22), the average disagreement was 0.5 {+-} 1.3% (1 SD). The films exhibited {gamma}(3%/3 mm) passing rates {>=}90%. Conclusions: The dose to an arbitrary moving voxel in a patient can be estimated with acceptable accuracy for a VMAT delivery, by performing a single QA measurement with a cylindrical phantom and applying two consecutive perturbations to the TPS-calculated patient dose. The first one accounts for the differences between the planned and delivered static doses, while the second one corrects for the motion.

  9. Direct absorbed dose to water determination based on water calorimetry in scanning proton beam delivery

    SciTech Connect

    Sarfehnia, A.; Clasie, B.; Chung, E.; Lu, H. M.; Flanz, J.; Cascio, E.; Engelsman, M.; Paganetti, H.; Seuntjens, J.

    2010-07-15

    Purpose: The aim of this manuscript is to describe the direct measurement of absolute absorbed dose to water in a scanned proton radiotherapy beam using a water calorimeter primary standard. Methods: The McGill water calorimeter, which has been validated in photon and electron beams as well as in HDR {sup 192}Ir brachytherapy, was used to measure the absorbed dose to water in double scattering and scanning proton irradiations. The measurements were made at the Massachusetts General Hospital proton radiotherapy facility. The correction factors in water calorimetry were numerically calculated and various parameters affecting their magnitude and uncertainty were studied. The absorbed dose to water was compared to that obtained using an Exradin T1 Chamber based on the IAEA TRS-398 protocol. Results: The overall 1-sigma uncertainty on absorbed dose to water amounts to 0.4% and 0.6% in scattered and scanned proton water calorimetry, respectively. This compares to an overall uncertainty of 1.9% for currently accepted IAEA TRS-398 reference absorbed dose measurement protocol. The absorbed dose from water calorimetry agrees with the results from TRS-398 well to within 1-sigma uncertainty. Conclusions: This work demonstrates that a primary absorbed dose standard based on water calorimetry is feasible in scattered and scanned proton beams.

  10. SU-D-16A-02: A Novel Methodology for Accurate, Semi-Automated Delineation of Oral Mucosa for Radiation Therapy Dose-Response Studies

    SciTech Connect

    Dean, J; Welsh, L; Gulliford, S; Harrington, K; Nutting, C

    2014-06-01

    Purpose: The significant morbidity caused by radiation-induced acute oral mucositis means that studies aiming to elucidate dose-response relationships in this tissue are a high priority. However, there is currently no standardized method for delineating the mucosal structures within the oral cavity. This report describes the development of a methodology to delineate the oral mucosa accurately on CT scans in a semi-automated manner. Methods: An oral mucosa atlas for automated segmentation was constructed using the RayStation Atlas-Based Segmentation (ABS) module. A radiation oncologist manually delineated the full surface of the oral mucosa on a planning CT scan of a patient receiving radiotherapy (RT) to the head and neck region. A 3mm fixed annulus was added to incorporate the mucosal wall thickness. This structure was saved as an atlas template. ABS followed by model-based segmentation was performed on four further patients sequentially, adding each patient to the atlas. Manual editing of the automatically segmented structure was performed. A dose comparison between these contours and previously used oral cavity volume contours was performed. Results: The new approach was successful in delineating the mucosa, as assessed by an experienced radiation oncologist, when applied to a new series of patients receiving head and neck RT. Reductions in the mean doses obtained when using the new delineation approach, compared with the previously used technique, were demonstrated for all patients (median: 36.0%, range: 25.6% – 39.6%) and were of a magnitude that might be expected to be clinically significant. Differences in the maximum dose that might reasonably be expected to be clinically significant were observed for two patients. Conclusion: The method developed provides a means of obtaining the dose distribution delivered to the oral mucosa more accurately than has previously been achieved. This will enable the acquisition of high quality dosimetric data for use in

  11. Use of a realistic breathing lung phantom to evaluate dose delivery errors

    SciTech Connect

    Court, Laurence E.; Seco, Joao; Lu Xingqi; Ebe, Kazuyu; Mayo, Charles; Ionascu, Dan; Winey, Brian; Giakoumakis, Nikos; Aristophanous, Michalis; Berbeco, Ross; Rottman, Joerg; Bogdanov, Madeleine; Schofield, Deborah; Lingos, Tania

    2010-11-15

    Purpose: To compare the effect of respiration-induced motion on delivered dose (the interplay effect) for different treatment techniques under realistic clinical conditions. Methods: A flexible resin tumor model was created using rapid prototyping techniques based on a computed tomography (CT) image of an actual tumor. Twenty micro-MOSFETs were inserted into the tumor model and the tumor model was inserted into an anthropomorphic breathing phantom. Phantom motion was programed using the motion trajectory of an actual patient. A four-dimensional CT image was obtained and several treatment plans were created using different treatment techniques and planning systems: Conformal (Eclipse), step-and-shoot intensity-modulated radiation therapy (IMRT) (Pinnacle), step-and-shoot IMRT (XiO), dynamic IMRT (Eclipse), complex dynamic IMRT (Eclipse), hybrid IMRT [60% conformal, 40% dynamic IMRT (Eclipse)], volume-modulated arc therapy (VMAT) [single-arc (Eclipse)], VMAT [double-arc (Eclipse)], and complex VMAT (Eclipse). The complex plans were created by artificially pushing the optimizer to give complex multileaf collimator sequences. Each IMRT field was irradiated five times and each VMAT field was irradiated ten times, with each irradiation starting at a random point in the respiratory cycle. The effect of fractionation was calculated by randomly summing the measured doses. The maximum deviation for each measurement point per fraction and the probability that 95% of the model tumor had dose deviations less than 2% and 5% were calculated as a function of the number of fractions. Tumor control probabilities for each treatment plan were calculated and compared. Results: After five fractions, measured dose deviations were less than 2% for more than 95% of measurement points within the tumor model for all plans, except the complex dynamic IMRT, step-and-shoot IMRT (XiO), complex VMAT, and single-arc VMAT plans. Reducing the dose rate of the complex IMRT plans from 600 to 200 MU

  12. Efficacy of prophylactic intravenous ondansetron on the prevention of hypotension during cesarean delivery: a dose-dependent study

    PubMed Central

    Wang, Meng; Zhuo, Lang; Wang, Qun; Shen, Ming-Kun; Yu, Yan-Yun; Yu, Jun-Jing; Wang, Zhi-Ping

    2014-01-01

    Objective: This study was to determine the optimal dosage of ondansetron for preventing maternal hypotension during cesarean delivery. Methods: One hundred and fifty parturient women scheduled for elective cesarean section were randomly assigned to five groups (n=30). Five minutes prior to spinal anesthesia, women were injected with 5 ml of physiological saline (S), 2 mg (O2), 4 mg (O4), 6 mg (O6), or 8 mg (O8) of ondansetron in saline, respectively. Maternal blood pressure and heart rate were measured at 2-min intervals for 30 min. The serum parameters in umbilical cord blood were analyzed after delivery. Results: Compared with group S, the incidence of maternal hypotension was significantly lower in groups O4 and O6 (P < 0.05). The umbilical venous pH was significantly higher in group O4 (P < 0.05); while the partial pressure of carbon dioxide (Pco2) was significantly lower in groups O4, O6, and O8 (P < 0.05); and the bicarbonate (Hco3 -) and base excess in extracellular fluid (BEecf) were significantly lower in groups O6 and O8 (P < 0.05). Moreover, minimal changes of systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure were observed in group O4 (P < 0.05). Conclusion: The optimal dose of ondansetron preloading was 4 mg during cesarean delivery. PMID:25664023

  13. Targeted delivery of low-dose dexamethasone using PCL-PEG micelles for effective treatment of rheumatoid arthritis.

    PubMed

    Wang, Qin; Jiang, Jiayu; Chen, Wenfei; Jiang, Hao; Zhang, Zhirong; Sun, Xun

    2016-05-28

    Glucocorticoid (GC) is the cornerstone therapy of rheumatoid arthritis, but high doses are associated with serious adverse effects. In an effort to improve the efficacy of low-dose GC therapy, we developed a micelle system for targeted delivery to inflamed joints and validated the approach in a rat model of arthritis. Micelles loaded with dexamethasone (Dex) self-assembled from the amphipathic poly (ethylene glycol)-block-poly (ε-caprolactone) (PCL-PEG) polymer via film dispersion, and they were injected intravenously at a dose of only 0.8mg/kg into rats with adjuvant-induced arthritis. The micelles persisted for a relatively long time in the circulation, and they accumulated preferentially in inflamed joints. Micelle-delivered Dex potently reduced joint swelling, bone erosion, and inflammatory cytokine expression in both joint tissue and serum. PCL-PEG micelles caused only moderate adverse effects on body weight, lymphocyte count and blood glucose concentration, and they weakly activated the host complement system. These results suggest that encapsulating Dex in PCL-PEG micelles may allow for safe and effective low-dose GC therapy targeting inflammatory disorders. PMID:27057749

  14. Intensity-modulated radiation therapy for pancreatic and prostate cancer using pulsed low–dose rate delivery techniques

    SciTech Connect

    Li, Jie; Lang, Jinyi; Wang, Pei; Kang, Shengwei; Lin, Mu-han; Chen, Xiaoming; Chen, Fu; Guo, Ming; Chen, Lili; Ma, Chang-Ming Charlie

    2014-01-01

    Reirradiation of patients who were previously treated with radiotherapy is vastly challenging. Pulsed low–dose rate (PLDR) external beam radiotherapy has the potential to reduce normal tissue toxicities while providing significant tumor control for recurrent cancers. This work investigates treatment planning techniques for intensity-modulated radiation therapy (IMRT)-based PLDR treatment of various sites, including cases with pancreatic and prostate cancer. A total of 20 patients with clinical recurrence were selected for this study, including 10 cases with pancreatic cancer and 10 with prostate cancer. Large variations in the target volume were included to test the ability of IMRT using the existing treatment planning system and optimization algorithm to deliver uniform doses in individual gantry angles/fields for PLDR treatments. Treatment plans were generated with 10 gantry angles using the step-and-shoot IMRT delivery technique, which can be delivered in 3-minute intervals to achieve an effective low dose rate of 6.7 cGy/min. Instead of dose constraints on critical structures, ring structures were mainly used in PLDR-IMRT optimization. In this study, the PLDR-IMRT plans were compared with the PLDR-3-dimensional conformal radiation therapy (3DCRT) plans and the PLDR-RapidArc plans. For the 10 cases with pancreatic cancer that were investigated, the mean planning target volume (PTV) dose for each gantry angle in the PLDR-IMRT plans ranged from 17.6 to 22.4 cGy. The maximum doses ranged between 22.9 and 34.8 cGy. The minimum doses ranged from 8.2 to 17.5 cGy. For the 10 cases with prostate cancer that were investigated, the mean PTV doses for individual gantry angles ranged from 18.8 to 22.6 cGy. The maximum doses per gantry angle were between 24.0 and 34.7 cGy. The minimum doses per gantry angle ranged from 4.4 to 17.4 cGy. A significant reduction in the organ at risk (OAR) dose was observed with the PLDR-IMRT plan when compared with that using the PLDR-3DCRT

  15. Clinical usefulness of the management and delivery of radiation dose-distribution images using the Internet.

    PubMed

    Nakagawa, K; Onogi, Y; Aoki, Y; Kozuka, T; Ohtomo, K

    1998-01-01

    Dose distribution images in radiation therapy play important roles in the management of cancer patients. To date, hard copies of these images have been stored for referral by radiation oncologists as needed. In most cases, these images are not available to medical personnel outside the radiation oncology department. We have developed a means to access these dose distribution images from the hospital via the World-Wide Web (WWW). A screen snapshot of a dose distribution image on the CRT of a treatment planning unit is copied to the WWW server and converted to a GIF (graphic interchange format) image. Similarly, we can register dose volume histograms and digitally reconstructed radiographs (DRR) on the WWW. Medical personnel can view these images through the WWW browser from anywhere in the hospital. As a result, radiation oncologists are given detailed information on target definition in treatment planning by expert physicians. The system also helps co-medical personnel in understanding dose distribution and predicting radiation injury. At the same time, it actualizes an electronic archive of dose distribution images, which is a database for quick and reliable review, evaluation, and comparison of treatment plans. This technique also fosters closer relationships among radiation oncologists, physicians, and co-medical personnel. PMID:9814423

  16. [Management and delivery of radiation dose distribution images using the Internet].

    PubMed

    Onogi, Y; Nakagawa, K; Aoki, Y; Kozuka, T; Toyoda, T; Sasaki, Y

    1998-01-01

    Dose distribution images play important roles in the management of cancer patients. To date hard copies of these images have been stored and referred to by radiation oncologists as needed. In most cases, these images were not available to medical personnel outside the radiation oncology department. We have developed a mechanism in the hospital to access these dose distribution images via WWW (World Wide Web). A screen snapshot of a dose distribution image on the CRT of a treatment planning machine is copied to the WWW server and converted to a GIF image. Similarly, we can register dose volume histograms and digitally reconstructed radiographs on the WWW. Medical personnel throughout the hospital can access the images through the WWW browser. As a result, radiation oncologists are given detailed information on target definition in treatment planning by expert physicians. The system also helps co-medical staff in understanding dose distributions and predicting radiation injuries. At the same time, it actualizes an electronic archive of dose distribution images, which is a database for quick and reliable review, evaluation and comparison of treatment plans. This technique also furthers a close relationship among radiation oncologists, physicians, and co-medical personnel. PMID:9493431

  17. TBI lung dose comparisons using bilateral and anteroposterior delivery techniques and tissue density corrections.

    PubMed

    Bailey, Daniel W; Wang, Iris Z; Lakeman, Tara; Hales, Lee D; Singh, Anurag K; Podgorsak, Matthew B

    2015-01-01

    This study compares lung dose distributions for two common techniques of total body photon irradiation (TBI) at extended source-to-surface distance calculated with, and without, tissue density correction (TDC). Lung dose correction factors as a function of lateral thorax separation are approximated for bilateral opposed TBI (supine), similar to those published for anteroposterior-posteroanterior (AP-PA) techniques in AAPM Report 17 (i.e., Task Group 29). 3D treatment plans were created retrospectively for 24 patients treated with bilateral TBI, and for whom CT data had been acquired from the head to the lower leg. These plans included bilateral opposed and AP-PA techniques- each with and without - TDC, using source-to-axis distance of 377 cm and largest possible field size. On average, bilateral TBI requires 40% more monitor units than AP-PA TBI due to increased separation (26% more for 23 MV). Calculation of midline thorax dose without TDC leads to dose underestimation of 17% on average (standard deviation, 4%) for bilateral 6 MV TBI, and 11% on average (standard deviation, 3%) for 23 MV. Lung dose correction factors (CF) are calculated as the ratio of midlung dose (with TDC) to midline thorax dose (without TDC). Bilateral CF generally increases with patient separation, though with high variability due to individual uniqueness of anatomy. Bilateral CF are 5% (standard deviation, 4%) higher than the same corrections calculated for AP-PA TBI in the 6 MV case, and 4% higher (standard deviation, 2%) for 23 MV. The maximum lung dose is much higher with bilateral TBI (up to 40% higher than prescribed, depending on patient anatomy) due to the absence of arm tissue blocking the anterior chest. Dose calculations for bilateral TBI without TDC are incorrect by up to 24% in the thorax for 6 MV and up to 16% for 23 MV. Bilateral lung CF may be calculated as 1.05 times the values published in Table 6 of AAPM Report 17, though a larger patient pool is necessary to better

  18. Leakage-Penumbra effect in intensity modulated radiation therapy step-and-shoot dose delivery

    PubMed Central

    Grigorov, Grigor N; Chow, James CL

    2016-01-01

    AIM: To study the leakage-penumbra (LP) effect with a proposed correction method for the step-and-shoot intensity modulated radiation therapy (IMRT). METHODS: Leakage-penumbra dose profiles from 10 randomly selected prostate IMRT plans were studied. The IMRT plans were delivered by a Varian 21 EX linear accelerator equipped with a 120-leaf multileaf collimator (MLC). For each treatment plan created by the Pinnacle3 treatment planning system, a 3-dimensional LP dose distribution generated by 5 coplanar photon beams, starting from 0o with equal separation of 72o, was investigated. For each photon beam used in the step-and-shoot IMRT plans, the first beam segment was set to have the largest area in the MLC leaf-sequencing, and was equal to the planning target volume (PTV). The overshoot effect (OSE) and the segment positional errors were measured using a solid water phantom with Kodak (TL and X-OMAT V) radiographic films. Film dosimetric analysis and calibration were carried out using a film scanner (Vidar VXR-16). The LP dose profiles were determined by eliminating the OSE and segment positional errors with specific individual irradiations. RESULTS: A non-uniformly distributed leaf LP dose ranging from 3% to 5% of the beam dose was measured in clinical IMRT beams. An overdose at the gap between neighboring segments, represented as dose peaks of up to 10% of the total BP, was measured. The LP effect increased the dose to the PTV and surrounding critical tissues. In addition, the effect depends on the number of beams and segments for each beam. Segment positional error was less than the maximum tolerance of 1 mm under a dose rate of 600 monitor units per minute in the treatment plans. The OSE varying with the dose rate was observed in all photon beams, and the effect increased from 1 to 1.3 Gy per treatment of the rectal intersection. As the dosimetric impacts from the LP effect and OSE may increase the rectal post-radiation effects, a correction of LP was proposed and

  19. Experimental study on the application of a compressed-sensing (CS) algorithm to dental cone-beam CT (CBCT) for accurate, low-dose image reconstruction

    NASA Astrophysics Data System (ADS)

    Oh, Jieun; Cho, Hyosung; Je, Uikyu; Lee, Minsik; Kim, Hyojeong; Hong, Daeki; Park, Yeonok; Lee, Seonhwa; Cho, Heemoon; Choi, Sungil; Koo, Yangseo

    2013-03-01

    In practical applications of three-dimensional (3D) tomographic imaging, there are often challenges for image reconstruction from insufficient data. In computed tomography (CT); for example, image reconstruction from few views would enable fast scanning with reduced doses to the patient. In this study, we investigated and implemented an efficient reconstruction method based on a compressed-sensing (CS) algorithm, which exploits the sparseness of the gradient image with substantially high accuracy, for accurate, low-dose dental cone-beam CT (CBCT) reconstruction. We applied the algorithm to a commercially-available dental CBCT system (Expert7™, Vatech Co., Korea) and performed experimental works to demonstrate the algorithm for image reconstruction in insufficient sampling problems. We successfully reconstructed CBCT images from several undersampled data and evaluated the reconstruction quality in terms of the universal-quality index (UQI). Experimental demonstrations of the CS-based reconstruction algorithm appear to show that it can be applied to current dental CBCT systems for reducing imaging doses and improving the image quality.

  20. Development of a dose-controlled multiculture cell exposure chamber for efficient delivery of airborne and engineered nanoparticles

    NASA Astrophysics Data System (ADS)

    Asimakopoulou, Akrivi; Daskalos, Emmanouil; Lewinski, Nastassja; Riediker, Michael; Papaioannou, Eleni; Konstandopoulos, Athanasios G.

    2013-04-01

    In order to study the various health influencing parameters related to engineered nanoparticles as well as to soot emitted by Diesel engines, there is an urgent need for appropriate sampling devices and methods for cell exposure studies that simulate the respiratory system and facilitate associated biological and toxicological tests. The objective of the present work was the further advancement of a Multiculture Exposure Chamber (MEC) into a dose-controlled system for efficient delivery of nanoparticles to cells. It was validated with various types of nanoparticles (Diesel engine soot aggregates, engineered nanoparticles for various applications) and with state-of-the-art nanoparticle measurement instrumentation to assess the local deposition of nanoparticles on the cell cultures. The dose of nanoparticles to which cell cultures are being exposed was evaluated in the normal operation of the in vitro cell culture exposure chamber based on measurements of the size specific nanoparticle collection efficiency of a cell free device. The average efficiency in delivering nanoparticles in the MEC was approximately 82%. The nanoparticle deposition was demonstrated by Transmission Electron Microscopy (TEM). Analysis and design of the MEC employs Computational Fluid Dynamics (CFD) and true to geometry representations of nanoparticles with the aim to assess the uniformity of nanoparticle deposition among the culture wells. Final testing of the dose-controlled cell exposure system was performed by exposing A549 lung cell cultures to fluorescently labeled nanoparticles. Delivery of aerosolized nanoparticles was demonstrated by visualization of the nanoparticle fluorescence in the cell cultures following exposure. Also monitored was the potential of the aerosolized nanoparticles to generate reactive oxygen species (ROS) (e.g. free radicals and peroxides generation), thus expressing the oxidative stress of the cells which can cause extensive cellular damage or damage on DNA.

  1. Delivery characteristics and patients’ handling of two single-dose dry-powder inhalers used in COPD

    PubMed Central

    Chapman, Kenneth R; Fogarty, Charles M; Peckitt, Clare; Lassen, Cheryl; Jadayel, Dalal; Dederichs, Juergen; Dalvi, Mukul; Kramer, Benjamin

    2011-01-01

    For optimal efficacy, an inhaler should deliver doses consistently and be easy for patients to use with minimal instruction. The delivery characteristics, patients’ correct use, and preference of two single-dose dry powder inhalers (Breezhaler and HandiHaler) were evaluated in two complementary studies. The first study examined aerodynamic particle size distribution, using inhalation profiles of seven patients with moderate to very severe chronic obstructive pulmonary disease (COPD). The second was an open-label, two-period, 7-day crossover study, evaluating use of the inhalers with placebo capsules by 82 patients with mild to severe COPD. Patients’ correct use of the inhalers was assessed after reading written instructions on Day 1, and after training and 7 days of daily use. Patients’ preference was assessed after completion of both study periods. Patient inhalation profiles showed average peak inspiratory flows of 72 L/minute through Breezhaler and 36 L/minute through HandiHaler. For Breezhaler and HandiHaler, fine particle fractions were 27% and 10%, respectively. In the second study, correct use of Breezhaler and HandiHaler was achieved by >77% of patients for any step after 7 days; 61% of patients showed an overall preference for Breezhaler and 31% for HandiHaler (P = 0.01). Breezhaler is a low-resistance inhaler suitable for use by patients with a range of disease severities. Most patients used both inhalers correctly after 7 days, but more patients showed an overall preference for the Breezhaler compared with the HandiHaler. These are important factors for optimum dose delivery and successful COPD management. PMID:21760722

  2. The effect of flattening filter free delivery on endothelial dose enhancement with gold nanoparticles

    SciTech Connect

    Detappe, Alexandre; Tsiamas, Panagiotis; Ngwa, Wilfred; Zygmanski, Piotr; Makrigiorgos, Mike; Berbeco, Ross

    2013-03-15

    Purpose: The aim of this study is to quantify and to compare the dose enhancement factor from gold nanoparticles (AuNP) to tumor endothelial cells for different concentrations of AuNP, and clinical MV beam configurations. Methods: Tumor endothelial cells are modeled as slabs measuring 10 Multiplication-Sign 10 Multiplication-Sign 2 {mu}m. A spherical AuNP is simulated on the surface of the endothelial cell, within the blood vessel. 6 MV photon beams with and without the flattening filter are investigated for different field sizes, depths in material and beam modulation. The incident photon energy spectra for each configuration is generated using EGSnrc. The dose enhancement in the tumor endothelial cell is found using an analytical calculation. The endothelial dose enhancement factor is defined to be the ratio of the dose deposited with and without AuNPs. Results: It is found that clinical beam parameters may be chosen to maximize the effect of gold nanoparticles during radiotherapy. This effect is further amplified {approx}20% by the removal of the flattening filter. Modulation of the clinical beam with the multileaf collimator tends to decrease the proportion of low energy photons, therefore providing less enhancement than the corresponding open field. Conclusions: The results of this work predict a dose enhancement to tumor blood vessel endothelial cells using conventional therapeutic (MV) x-rays and quantify the relative change in enhancement with treatment depth and field size.

  3. Cumulative dose on fractional delivery of tomotherapy to periodically moving organ: A phantom QA suggestion

    SciTech Connect

    Shin, Eunhyuk; Han, Youngyih; Park, Hee-Chul; Sung Kim, Jin; Hwan Ahn, Sung; Suk Shin, Jung; Gyu Ju, Sang; Ho Choi, Doo; Lee, Jaiki

    2013-01-01

    This study was conducted to evaluate the cumulative dosimetric error that occurs in both target and surrounding normal tissues when treating a moving target in multifractional treatment with tomotherapy. An experiment was devised to measure cumulative error in multifractional treatments delivered to a horseshoe-shaped clinical target volume (CTV) surrounding a cylinder shape of organ at risk (OAR). Treatments differed in jaw size (1.05 vs 2.5 cm), pitch (0.287 vs 0.660), and modulation factor (1.5 vs 2.5), and tumor motion characteristics differing in amplitude (1 to 3 cm), period (3 to 5 second), and regularity (sinusoidal vs irregular) were tested. Treatment plans were delivered to a moving phantom up to 5-times exposure. Dose distribution on central coronal plane from 1 to 5 times exposure was measured with GAFCHROMIC EBT film. Dose differences occurring across 1 to 5 times exposure of treatment and between treatment plans were evaluated by analyzing measurements of gamma index, gamma index histogram, histogram changes, and dose at the center of the OAR. The experiment showed dose distortion due to organ motion increased between multiexposure 1 to 3 times but plateaued and remained constant after 3-times exposure. In addition, although larger motion amplitude and a longer period of motion both increased dosimetric error, the dose at the OAR was more significantly affected by motion amplitude rather than motion period. Irregularity of motion did not contribute significantly to dosimetric error when compared with other motion parameters. Restriction of organ motion to have small amplitude and short motion period together with larger jaw size and small modulation factor (with small pitch) is effective in reducing dosimetric error. Pretreatment measurements for 3-times exposure of treatment to a moving phantom with patient-specific tumor motion would provide a good estimation of the delivered dose distribution.

  4. SU-F-BRF-09: A Non-Rigid Point Matching Method for Accurate Bladder Dose Summation in Cervical Cancer HDR Brachytherapy

    SciTech Connect

    Chen, H; Zhen, X; Zhou, L; Zhong, Z; Pompos, A; Yan, H; Jiang, S; Gu, X

    2014-06-15

    Purpose: To propose and validate a deformable point matching scheme for surface deformation to facilitate accurate bladder dose summation for fractionated HDR cervical cancer treatment. Method: A deformable point matching scheme based on the thin plate spline robust point matching (TPSRPM) algorithm is proposed for bladder surface registration. The surface of bladders segmented from fractional CT images is extracted and discretized with triangular surface mesh. Deformation between the two bladder surfaces are obtained by matching the two meshes' vertices via the TPS-RPM algorithm, and the deformation vector fields (DVFs) characteristic of this deformation is estimated by B-spline approximation. Numerically, the algorithm is quantitatively compared with the Demons algorithm using five clinical cervical cancer cases by several metrics: vertex-to-vertex distance (VVD), Hausdorff distance (HD), percent error (PE), and conformity index (CI). Experimentally, the algorithm is validated on a balloon phantom with 12 surface fiducial markers. The balloon is inflated with different amount of water, and the displacement of fiducial markers is benchmarked as ground truth to study TPS-RPM calculated DVFs' accuracy. Results: In numerical evaluation, the mean VVD is 3.7(±2.0) mm after Demons, and 1.3(±0.9) mm after TPS-RPM. The mean HD is 14.4 mm after Demons, and 5.3mm after TPS-RPM. The mean PE is 101.7% after Demons and decreases to 18.7% after TPS-RPM. The mean CI is 0.63 after Demons, and increases to 0.90 after TPS-RPM. In the phantom study, the mean Euclidean distance of the fiducials is 7.4±3.0mm and 4.2±1.8mm after Demons and TPS-RPM, respectively. Conclusions: The bladder wall deformation is more accurate using the feature-based TPS-RPM algorithm than the intensity-based Demons algorithm, indicating that TPS-RPM has the potential for accurate bladder dose deformation and dose summation for multi-fractional cervical HDR brachytherapy. This work is supported in part by

  5. The Dose-response of Intrathecal Ropivacaine Co-administered with Sufentanil for Cesarean Delivery under Combined Spinal-epidural Anesthesia in Patients with Scarred Uterus

    PubMed Central

    Xiao, Fei; Xu, Wen-Ping; Zhang, Yin-Fa; Liu, Lin; Liu, Xia; Wang, Li-Zhong

    2015-01-01

    Background: Spinal anesthesia is considered as a reasonable anesthetic option in lower abdominal and lower limb surgery. This study was to determine the dose-response of intrathecal ropivacaine in patients with scarred uterus undergoing cesarean delivery under combined spinal-epidural anesthesia. Methods: Seventy-five patients with scarred uterus undergoing elective cesarean delivery under combined spinal-epidural anesthesia were enrolled in this randomized, double-blinded, dose-ranging study. Patients received 6, 8, 10, 12, or 14 mg intrathecal hyperbaric ropivacaine with 5 μg sufentanil. Successful spinal anesthesia was defined as a T4 sensory level achieved with no need for epidural supplementation. The 50% effective dose (ED50) and 95% effective dose (ED95) were calculated with a logistic regression model. Results: ED50 and ED95 of intrathecal hyperbaric ropivacaine for patients with scarred uterus undergoing cesarean delivery under combined spinal-epidural anesthesia (CSEA) were 8.28 mg (95% confidence interval [CI]: 2.28–9.83 mg) and 12.24 mg (95% CI: 10.53–21.88 mg), respectively. Conclusion: When a CSEA technique is to use in patients with scarred uterus for an elective cesarean delivery, the ED50 and ED95 of intrathecal hyperbaric ropivacaine along with 5 μg sufentanil were 8.28 mg and 12.24 mg, respectively. In addition, this local anesthetic is unsuitable for emergent cesarean delivery, but it has advantages for ambulatory patients. PMID:26415793

  6. SU-E-T-303: Spot Scanning Dose Delivery with Rapid Cycling Proton Beams From RCMS

    SciTech Connect

    Cheng, C; Liu, H; Lee, S

    2014-06-01

    Purpose: A rapid cycling proton beam has several distinct characteristics superior to a slow extraction synchrotron: The beam energy and energy spread, beam intensity and spot size can be varied spot by spot. The feasibility of using a spot scanning beam from a rapidc-ycling-medical-synchrotron (RCMS) at 10 Hz repetition frequency is investigated in this study for its application in proton therapy. Methods: The versatility of the beam is illustrated by two examples in water phantoms: (1) a cylindrical PTV irradiated by a single field and (2) a spherical PTV irradiated by two parallel opposed fields. A uniform dose distribution is to be delivered to the volumes. Geant4 Monte Carlo code is used to validate the dose distributions in each example. Results: Transverse algorithms are developed to produce uniform distributions in each transverseplane in the two examples with a cylindrical and a spherical PTV respectively. Longitudinally, different proton energies are used in successive transverse planes toproduce the SOBP required to cover the PTVs. In general, uniformity of dosedistribution within 3% is obtained for the cylinder and 3.5% for the sphere. The transversealgorithms requires only few hundred beam spots for each plane The algorithms may beapplied to larger volumes by increasing the intensity spot by spot for the same deliverytime of the same dose. The treatment time can be shorter than 1 minute for any fieldconfiguration and tumor shape. Conclusion: The unique beam characteristics of a spot scanning beam from a RCMS at 10 Hz repetitionfrequency are used to design transverse and longitudinal algorithms to produce uniformdistribution for any arbitrary shape and size of targets. The proposed spot scanning beam ismore versatile than existing spot scanning beams in proton therapy with better beamcontrol and lower neutron dose. This work is supported in part by grants from the US Department of Energy under contract; DE-FG02-12ER41800 and the National Science

  7. Compressed-sensing (CS)-based digital breast tomosynthesis (DBT) reconstruction for low-dose, accurate 3D breast X-ray imaging

    NASA Astrophysics Data System (ADS)

    Park, Yeonok; Cho, Hyosung; Je, Uikyu; Hong, Daeki; Lee, Minsik; Park, Chulkyu; Cho, Heemoon; Choi, Sungil; Koo, Yangseo

    2014-08-01

    In practical applications of three-dimensional (3D) tomographic techniques, such as digital breast tomosynthesis (DBT), computed tomography (CT), etc., there are often challenges for accurate image reconstruction from incomplete data. In DBT, in particular, the limited-angle and few-view projection data are theoretically insufficient for exact reconstruction; thus, the use of common filtered-backprojection (FBP) algorithms leads to severe image artifacts, such as the loss of the average image value and edge sharpening. One possible approach to alleviate these artifacts may employ iterative statistical methods because they potentially yield reconstructed images that are in better accordance with the measured projection data. In this work, as another promising approach, we investigated potential applications to low-dose, accurate DBT imaging with a state-of-the-art reconstruction scheme based on compressed-sensing (CS) theory. We implemented an efficient CS-based DBT algorithm and performed systematic simulation works to investigate the imaging characteristics. We successfully obtained DBT images of substantially very high accuracy by using the algorithm and expect it to be applicable to developing the next-generation 3D breast X-ray imaging system.

  8. Feasibility study for application of the compressed-sensing framework to interior computed tomography (ICT) for low-dose, high-accurate dental x-ray imaging

    NASA Astrophysics Data System (ADS)

    Je, U. K.; Cho, H. M.; Cho, H. S.; Park, Y. O.; Park, C. K.; Lim, H. W.; Kim, K. S.; Kim, G. A.; Park, S. Y.; Woo, T. H.; Choi, S. I.

    2016-02-01

    In this paper, we propose a new/next-generation type of CT examinations, the so-called Interior Computed Tomography (ICT), which may presumably lead to dose reduction to the patient outside the target region-of-interest (ROI), in dental x-ray imaging. Here an x-ray beam from each projection position covers only a relatively small ROI containing a target of diagnosis from the examined structure, leading to imaging benefits such as decreasing scatters and system cost as well as reducing imaging dose. We considered the compressed-sensing (CS) framework, rather than common filtered-backprojection (FBP)-based algorithms, for more accurate ICT reconstruction. We implemented a CS-based ICT algorithm and performed a systematic simulation to investigate the imaging characteristics. Simulation conditions of two ROI ratios of 0.28 and 0.14 between the target and the whole phantom sizes and four projection numbers of 360, 180, 90, and 45 were tested. We successfully reconstructed ICT images of substantially high image quality by using the CS framework even with few-view projection data, still preserving sharp edges in the images.

  9. IMRT planning and delivery incorporating daily dose from mega-voltage cone-beam computed tomography imaging

    SciTech Connect

    Miften, Moyed; Gayou, Olivier; Reitz, Bodo; Fuhrer, Russell; Leicher, Brian; Parda, David S.

    2007-10-15

    The technology of online mega-voltage cone-beam (CB) computed tomography (MV-CBCT) imaging is currently used in many institutions to generate a 3D anatomical dataset of a patient in treatment position. It utilizes an accelerator therapy beam, delivered with 200 deg. gantry rotation, and captured by an electronic portal imager to account for organ motion and setup variations. Although the patient dose exposure from a single volumetric MV-CBCT imaging procedure is comparable to that from standard double-exposure orthogonal portal images, daily image localization procedures can result in a significant dose increase to healthy tissue. A technique to incorporate the daily dose, from a MV-CBCT imaging procedure, in the IMRT treatment planning optimization process was developed. A composite IMRT plan incorporating the total dose from the CB was optimized with the objective of ensuring uniform target coverage while sparing the surrounding normal tissue. One head and neck cancer patient and four prostate cancer patients were planned and treated using this technique. Dosimetric results from the prostate IMRT plans optimized with or without CB showed similar target coverage and comparable sparing of bladder and rectum volumes. Average mean doses were higher by 1.6{+-}1.0 Gy for the bladder and comparable for the rectum (-0.3{+-}1.4 Gy). In addition, an average mean dose increase of 1.9{+-}0.8 Gy in the femoral heads and 1.7{+-}0.6 Gy in irradiated tissue was observed. However, the V{sub 65} and V{sub 70} values for bladder and rectum were lower by 2.3{+-}1.5% and 2.4{+-}2.1% indicating better volume sparing at high doses with the optimized plans incorporating CB. For the head and neck case, identical target coverage was achieved, while a comparable sparing of the brain stem, optic chiasm, and optic nerves was observed. The technique of optimized planning incorporating doses from daily online MV-CBCT procedures provides an alternative method for imaging IMRT patients. It

  10. Drug delivery systems.

    PubMed

    Robinson, D H; Mauger, J W

    1991-10-01

    New and emerging drug delivery systems for traditional drugs and the products of biotechnology are discussed, and the role of the pharmacist in ensuring the appropriate use of these systems is outlined. Advantages of advanced drug delivery systems over traditional systems are the ability to deliver a drug more selectively to a specific site; easier, more accurate, less frequent dosing; decreased variability in systemic drug concentrations; absorption that is more consistent with the site and mechanism of action; and reductions in toxic metabolites. Four basic strategies govern the mechanisms of advanced drug delivery: physical, chemical, biological, and mechanical. Oral drug delivery systems use natural and synthetic polymers to deliver the product to a specific region in the gastrointestinal tract in a timely manner that minimizes adverse effects and increases drug efficacy. Innovations in injectable and implantable delivery systems include emulsions, particulate delivery systems, micromolecular products and macromolecular drug adducts, and enzymatic-controlled delivery. Options for noninvasive drug delivery include the transdermal, respiratory, intranasal, ophthalmic, lymphatic, rectal, intravaginal, and intrauterine routes as well as topical application. Rapid growth is projected in the drug delivery systems market worldwide in the next five years. Genetic engineering has mandated the development of new strategies to deliver biotechnologically derived protein and peptide drugs and chemoimmunoconjugates. The role of the pharmacist in the era of advanced drug delivery systems will be broad based, including administering drugs, compounding, calculating dosages based on pharmacokinetic and pharmacodynamic monitoring, counseling, and research. The advent of advanced drug delivery systems offers pharmacists a new opportunity to assume an active role in patient care. PMID:1772110

  11. Er:YAG laser pulse for small-dose splashback-free microjet transdermal drug delivery.

    PubMed

    Park, Mi-ae; Jang, Hun-jae; Sirotkin, Fedir V; Yoh, Jack J

    2012-09-15

    The microjet injector system accelerates drugs and delivers them without a needle, which is shown to overcome the weaknesses of existing jet injectors. A significant increase in the delivered dose of drugs is reported with multiple pulses of laser beam at lower laser energy than was previously used in a Nd:YAG system. The new injection scheme uses the beam wavelength best absorbable by water at a longer pulse mode for elongated microjet penetration into a skin target. A 2.9 μm Er:YAG laser at 250 μs pulse duration is used for fluorescent staining of guinea pig skin and for injection controllability study. Hydrodynamic theory confirms the nozzle exit jet velocity obtained by the present microjet system. PMID:23041895

  12. Dose-dependent attenuation of intravenous nalbuphine on epidural morphine-induced pruritus and analgesia after cesarean delivery.

    PubMed

    Chen, Mao-Kai; Chau, Siu-Wah; Shen, Ya-Chun; Sun, Yu-Ning; Tseng, Kuang-Yi; Long, Chen-Yu; Feng, Yu-Tung; Cheng, Kuang-I

    2014-05-01

    Epidural morphine in patient-controlled analgesia regimens controls postoperative pain well but easily induces pruritus and other epidural morphine-related side effects. With 90 pregnant American Society of Anesthesiologists physical status II females scheduled for elective cesarean delivery, the present study was designed to evaluate the efficacy and safety profile of patient-controlled antipruritus (PCP) use of intravenous nalbuphine-based regimens for attenuation of postoperative pruritus and related side effects in combination with epidural morphine patient-controlled analgesia with regard to the quality of postoperative pain management. Patients were randomly assigned to two nalbuphine groups (5 μg/kg/hour, Group N5 or 10 μg/kg/hour, Group N10) and bolus dose of 1.6 μg/kg for PCP or the control (normal saline) group. Comparable visual analog scale scores for rest pain at each measured time interval among the three groups demonstrated that adequate pain relief was offered; however, the cumulative dose of nalbuphine administered to the patients in Group N10 attenuated the analgesic effect of epidural morphine in moving pain at POh24 only. Fewer episodes and milder severity of pruritus were observed in patients in Groups N5 and N10 at all postoperative time intervals. Epidural morphine provided good postoperative pain relief but with incommodious side effects. In addition, intravenous nalbuphine not only attenuated the incidence of pruritus but also decreased total morphine consumption. In conclusion, intravenous administration of low-dose nalbuphine (5 μg/kg/hour) for PCP maintained analgesia produced by epidural morphine and offered low pruritus incidence. PMID:24751388

  13. A Broad Range of Dose Optima Achieve High-level, Long-term Gene Expression After Hydrodynamic Delivery of Sleeping Beauty Transposons Using Hyperactive SB100x Transposase.

    PubMed

    Podetz-Pedersen, Kelly M; Olson, Erik R; Somia, Nikunj V; Russell, Stephen J; McIvor, R Scott

    2016-01-01

    The Sleeping Beauty (SB) transposon system has been shown to enable long-term gene expression by integrating new sequences into host cell chromosomes. We found that the recently reported SB100x hyperactive transposase conferred a surprisingly high level of long-term expression after hydrodynamic delivery of luciferase-encoding reporter transposons in the mouse. We conducted dose-ranging studies to determine the effect of varying the amount of SB100x transposase-encoding plasmid (pCMV-SB100x) at a set dose of luciferase transposon and of varying the amount of transposon-encoding DNA at a set dose of pCMV-SB100x in hydrodynamically injected mice. Animals were immunosuppressed using cyclophosphamide in order to prevent an antiluciferase immune response. At a set dose of transposon DNA (25 µg), we observed a broad range of pCMV-SB100x doses (0.1-2.5 µg) conferring optimal levels of long-term expression (>10(11) photons/second/cm(2)). At a fixed dose of 0.5 μg of pCMV-SB100x, maximal long-term luciferase expression (>10(10) photons/second/cm(2)) was achieved at a transposon dose of 5-125 μg. We also found that in the linear range of transposon doses (100 ng), co-delivering the CMV-SB100x sequence on the same plasmid was less effective in achieving long-term expression than delivery on separate plasmids. These results show marked flexibility in the doses of SB transposon plus pCMV-SB100x that achieve maximal SB-mediated gene transfer efficiency and long-term gene expression after hydrodynamic DNA delivery to mouse liver. PMID:26784638

  14. A Phase I Trial of Preoperative Partial Breast Radiotherapy: Patient Selection, Target Delineation, and Dose Delivery

    PubMed Central

    Blitzblau, Rachel C.; Arya, Ritu; Yoo, Sua; Baker, Jay A.; Chang, Zheng; Palta, Manisha; Duffy, Eileen; Horton, Janet K.

    2015-01-01

    Purpose Diffusion of accelerated partial breast irradiation (APBI) into clinical practice is limited by the need for specialized equipment and training. The accessible external beam technique yields unacceptable complication rates, likely due to large post-operative target volumes. We designed a phase I trial evaluating preoperative radiotherapy to the intact tumor utilizing widely available technology. Methods Patients received 15, 18, or 21Gy in a single fraction to the breast tumor plus margin. Magnetic resonance imaging (MRI) was used in conjunction with standard computed tomography (CT)-based planning to identify contrast enhancing tumor. Skin markers and an intra-tumor biopsy marker were utilized for verification during treatment. Results MRI imaging was critical for target delineation as not all breast tumors were reliably identified on CT scan. Breast shape differences were consistently seen between CT and MRI but did not impede image registration or tumor identification. Target volumes were markedly smaller than historical post-operative volumes and normal tissue constraints were easily met. A biopsy marker within the breast proved sufficient for set up localization. Conclusions This single fraction linear-accelerator based ABPI approach can be easily incorporated at most treatment centers. In vivo targeting may improve accuracy and can reduce the dose to normal tissues. PMID:25834942

  15. Sci—Thur AM: YIS - 06: An EPID-based 3D patient dose verification method for SBRT-VMAT delivery

    SciTech Connect

    McCowan, P.; Uytven, E van; Beek, T van; McCurdy, B

    2014-08-15

    Purpose: Stereotactic body radiation therapy (SBRT) delivered via volumetric modulated arc therapy (VMAT) can strongly benefit from an in vivo patient dose verification due to the large doses per fraction. Electronic portal imaging devices (EPIDs) can be utilized as a patient dose dosimeter. In this work we present a physics-based model which utilizes on-treatment EPID images to reconstruct the dose delivered to an anthropomorphic phantom during SBRT-VMAT delivery. Methods: An SBRT linac beam was modeled using Monte Carlo methods and verified with measured data. Our dose reconstruction model back-projects EPID measured focal fluence upstream of the patient and adds a predicted extra-focal fluence component. This fluence is forward projected onto the patient's density matrix and convolved with dose kernels to calculate dose. The model was validated for two prostate, three lung, and two spine SBRT-VMAT treatments. Results were compared to the treatment planning system's calculation. Results: 2%/2 mm chi comparison calculations gave pass rates for the whole volume, infield, and high dose region respectively, and no lower than: 98%, 95%, 99% for the prostate plans, 99%, 92%, 85% for the lung plans, and 91%, 85%, 81% for the spine plans. A 3%/3mm calculation gave pass rates no lower than 99%, 94%, and 90% for all dose regions for the prostate, lung, and spine respectively. Conclusions: We have developed a physics-based model which calculates delivered dose to phantom (or patient) for SBRT-VMAT delivery using on treatment EPID images. The accuracy of the results has allowed us to test this model clinically.

  16. Color-coded prefilled medication syringes decrease time to delivery and dosing errors in simulated prehospital pediatric resuscitations: A randomized crossover trial☆, ☆

    PubMed Central

    Stevens, Allen D.; Hernandez, Caleb; Jones, Seth; Moreira, Maria E.; Blumen, Jason R.; Hopkins, Emily; Sande, Margaret; Bakes, Katherine; Haukoos, Jason S.

    2016-01-01

    Background Medication dosing errors remain commonplace and may result in potentially life-threatening outcomes, particularly for pediatric patients where dosing often requires weight-based calculations. Novel medication delivery systems that may reduce dosing errors resonate with national healthcare priorities. Our goal was to evaluate novel, prefilled medication syringes labeled with color-coded volumes corresponding to the weight-based dosing of the Broselow Tape, compared to conventional medication administration, in simulated prehospital pediatric resuscitation scenarios. Methods We performed a prospective, block-randomized, cross-over study, where 10 full-time paramedics each managed two simulated pediatric arrests in situ using either prefilled, color-coded-syringes (intervention) or their own medication kits stocked with conventional ampoules (control). Each paramedic was paired with two emergency medical technicians to provide ventilations and compressions as directed. The ambulance patient compartment and the intravenous medication port were video recorded. Data were extracted from video review by blinded, independent reviewers. Results Median time to delivery of all doses for the intervention and control groups was 34 (95% CI: 28–39) seconds and 42 (95% CI: 36–51) seconds, respectively (difference = 9 [95% CI: 4–14] seconds). Using the conventional method, 62 doses were administered with 24 (39%) critical dosing errors; using the prefilled, color-coded syringe method, 59 doses were administered with 0 (0%) critical dosing errors (difference = 39%, 95% CI: 13–61%). Conclusions A novel color-coded, prefilled syringe decreased time to medication administration and significantly reduced critical dosing errors by paramedics during simulated prehospital pediatric resuscitations. PMID:26247145

  17. SU-E-T-586: Optimal Determination of Tolerance Level for Radiation Dose Delivery Verification in An in Vivo Dosimetry System

    SciTech Connect

    Chen, Y; Souri, S; Gill, G; Rea, A; Kuruvilla, A; Riegel, A; Cao, Y; Jamshidi, A

    2015-06-15

    Purpose: To statistically determine the optimal tolerance level in the verification of delivery dose compared to the planned dose in an in vivo dosimetry system in radiotherapy. Methods: The LANDAUER MicroSTARii dosimetry system with screened nanoDots (optically stimulated luminescence dosimeters) was used for in vivo dose measurements. Ideally, the measured dose should match with the planned dose and falls within a normal distribution. Any deviation from the normal distribution may be redeemed as a mismatch, therefore a potential sign of the dose misadministration. Randomly mis-positioned nanoDots can yield a continuum background distribution. A percentage difference of the measured dose to its corresponding planned dose (ΔD) can be used to analyze combined data sets for different patients. A model of a Gaussian plus a flat function was used to fit the ΔD distribution. Results: Total 434 nanoDot measurements for breast cancer patients were collected across a period of three months. The fit yields a Gaussian mean of 2.9% and a standard deviation (SD) of 5.3%. The observed shift of the mean from zero is attributed to the machine output bias and calibration of the dosimetry system. A pass interval of −2SD to +2SD was applied and a mismatch background was estimated to be 4.8%. With such a tolerance level, one can expect that 99.99% of patients should pass the verification and at most 0.011% might have a potential dose misadministration that may not be detected after 3 times of repeated measurements. After implementation, a number of new start breast cancer patients were monitored and the measured pass rate is consistent with the model prediction. Conclusion: It is feasible to implement an optimal tolerance level in order to maintain a low limit of potential dose misadministration while still to keep a relatively high pass rate in radiotherapy delivery verification.

  18. Compensating for the impact of non-stationary spherical air cavities on IMRT dose delivery in transverse magnetic fields

    NASA Astrophysics Data System (ADS)

    Bol, G. H.; Lagendijk, J. J. W.; Raaymakers, B. W.

    2015-01-01

    With the development of the 1.5 T MRI linear accelerator and the clinical introduction of the 0.35 T ViewRay™ system, delivering intensity-modulated radiotherapy (IMRT) in a transverse magnetic field becomes increasingly important. When delivering dose in the presence of a transverse magnetic field, one of the most prominent phenomena occurs around air cavities: the electron return effect (ERE). For stationary, spherical air cavities which are centrally located in the phantom, the ERE can be compensated by using opposing beams configurations in combination with IMRT. In this paper we investigate the effects of non-stationary spherical air cavities, centrally located within the target in a phantom containing no organs at risk, on IMRT dose delivery in 0.35 T and 1.5 T transverse magnetic fields by using Monte Carlo simulations. We show that IMRT can be used for compensating ERE around those air cavities, except for intrafraction appearing or disappearing air cavities. For these cases, gating or plan re-optimization should be used. We also analyzed the option of using IMRT plans optimized at 0 T to be delivered in the presence of 0.35 T and 1.5 T magnetic field. When delivering dose at 0.35 T, IMRT plans optimized at 0 T and 0.35 T perform equally well regarding ERE compensation. Within a 1.5 T environment, the 1.5 T optimized plans perform slightly better for the static and random intra- and interfraction air cavity movement cases than the 0 T optimized plans. For non-stationary spherical air cavities with a baseline shift (intra- and interfraction) the 0 T optimized plans perform better. These observations show the intrinsic ERE compensation by equidistant and opposing beam configurations for spherical air cavities within the target area. IMRT gives some additional compensation, but only in case of correct positioning of the air cavity according to the IMRT compensation. For intrafraction appearing or disappearing air cavities this correct positioning is absent

  19. Impact of dose rate on accuracy of intensity modulated radiation therapy plan delivery using the pretreatment portal dosimetry quality assurance and setting up the workflow at hospital levels

    PubMed Central

    Kaviarasu, Karunakaran; Raj, N. Arunai Nambi; Murthy, K. Krishna; Babu, A. Ananda Giri; Prasad, Bhaskar Laxman Durga

    2015-01-01

    The aim of this study was to examine the impact of dose rate on accuracy of intensity modulated radiation therapy (IMRT) plan delivery by comparing the gamma agreement between the calculated and measured portal doses by pretreatment quality assurance (QA) using electronic portal imaging device dosimetry and creating a workflow for the pretreatment IMRT QA at hospital levels. As the improvement in gamma agreement leads to increase in the quality of IMRT treatment delivery, gamma evaluation was carried out for the calculated and the measured portal images for the criteria of 3% dose difference and 3 mm distance-to-agreement (DTA). Three gamma parameters: Maximum gamma, average gamma, and percentage of the field area with a gamma value>1.0 were analyzed. Three gamma index parameters were evaluated for 40 IMRT plans (315 IMRT fields) which were calculated for 400 monitor units (MU)/min dose rate and maximum multileaf collimator (MLC) speed of 2.5 cm/s. Gamma parameters for all 315 fields are within acceptable limits set at our center. Further, to improve the gamma results, we set an action level for this study using the mean and standard deviation (SD) values from the 315 fields studied. Forty out of 315 IMRT fields showed low gamma agreement (gamma parameters>2 SD as per action level of the study). The parameters were recalculated and reanalyzed for the dose rates of 300, 400 and 500 MU/min. Lowering the dose rate helped in getting an enhanced gamma agreement between the calculated and measured portal doses of complicated fields. This may be attributed to the less complex motion of MLC over time and the MU of the field/segment. An IMRT QA work flow was prepared which will help in improving the quality of IMRT delivery. PMID:26865759

  20. Ex vivo studies for the passive transdermal delivery of low-dose naltrexone from a cream; detection of naltrexone and its active metabolite, 6β-naltrexol, using a novel LC Q-ToF MS assay.

    PubMed

    Dodou, Kalliopi; Armstrong, Andrew; Kelly, Ivan; Wilkinson, Simon; Carr, Kevin; Shattock, Paul; Whiteley, Paul

    2015-01-01

    Naltrexone (NTX) is a long-acting opiate antagonist. Low-dose naltrexone (LDN) therapy has shown promising results in the treatment of several autoimmune disorders. Our aim was to formulate NTX into a cream for the delivery of LDN and develop an analytical technique for the quantification of NTX and its active metabolite 6-β-naltrexol (NTXol) during transdermal diffusion cell permeation studies. A 1% w/w NTX cream was formulated and drug permeation was examined over 24 h using static Franz diffusion cells mounted with pig skin. A Liquid Chromatography Quadrupole-Time of Flight Mass Spectrometry (LC-MS Q-ToF) method was developed for the detection of NTX and NTXol in the receptor solution, skin membrane and residual cream on the donor chamber after completion of the diffusion studies. The cream formulation exhibited steady state release of NTX over 24 h after an initial lag time of 2.74 h. The bioconversion of NTX to NTXol in the skin membrane was 1.1%. It was concluded that the cream may be an effective formulation for the sustained transdermal delivery of LDN. The novel LC Q-ToF MS method allowed the accurate measurement of NTX and NTXol levels across the diffusion cell assemblies and the quantification of NTX metabolism in the skin. PMID:24785567

  1. TH-C-12A-07: Implementation of a Pulsed Low Dose Date Radiotherapy (PLRT) Protocol for Recurrent Cancers Using Advanced Beam Delivery

    SciTech Connect

    Ma, C; Lin, M; Chen, L; Price, R; Li, J; Kang, S; Wang, P; Lang, J

    2014-06-15

    Purpose: Recent in vitro and in vivo experimental findings provided strong evidence that pulsed low-dose-rate radiotherapy (PLDR) produced equivalent tumor control as conventional radiotherapy with significantly reduced normal tissue toxicities. This work aimed to implement a PLDR clinical protocol for the management of recurrent cancers utilizing IMRT and VMAT. Methods: Our PLDR protocol requires that the daily 2Gy dose be delivered in 0.2Gy×10 pulses with a 3min interval between the pulses. To take advantage of low-dose hyper-radiosensitivity the mean dose to the target is set at 0.2Gy and the maximum dose is limited to 0.4Gy per pulse. Practical planning strategies were developed for IMRT and VMAT: (1) set 10 ports for IMRT and 10 arcs for VMAT with each angle/arc as a pulse; (2) set the mean dose (0.2Gy) and maximum dose (0.4Gy) to the target per pulse as hard constraints (no constraints to OARs); (3) select optimal port/arc angles to avoid OARs; and (4) use reference structures in or around target/OARs to reduce maximum dose to the target/OARs. IMRT, VMAT and 3DCRT plans were generated for 60 H and N, breast, lung, pancreas and prostate patients and compared. Results: All PLDR treatment plans using IMRT and VMAT met the dosimetry requirements of the PLDR protocol (mean target dose: 0.20Gy±0.01Gy; maximum target dose < 0.4Gy). In comparison with 3DCRT, IMRT and VMAT exhibited improved target dose conformity and OAR dose sparing. A single arc can minimize the difference in the target dose due to multi-angle incidence although the delivery time is longer than 3DCRT and IMRT. Conclusion: IMRT and VMAT are better modalities for PLDR treatment of recurrent cancers with superior target dose conformity and critical structure sparing. The planning strategies/guidelines developed in this work are practical for IMRT/VMAT treatment planning to meet the dosimetry requirements of the PLDR protocol.

  2. Titrating Optimal Dose of Osmotic-Controlled Release Oral Delivery (OROS)-Methylphenidate and Its Efficacy and Safety in Korean Children with ADHD: A Multisite Open Labeled Study

    PubMed Central

    Song, Dong-Ho; Choi, Soul; Joung, Yoo Sook; Ha, Eun Hye; Kim, Boong-Nyun; Shin, Yee-Jin; Shin, Dongwon; Yoo, Hee Jeong

    2012-01-01

    Objective This study was aimed to determine effectiveness and tolerability of Osmotic-controlled Release Oral delivery (OROS) methylphenidate (MPH) and its optimal dose administered openly over a period of up to 12 weeks in drug naïve Korean children with ADHD. Methods Subjects (n=143), ages 6 to 18-years, with a clinical diagnosis of any subtype of ADHD were recruited from 7 medical centers in Korea. An individualized dose of OROS-MPH was determined for each subject depending on the response criteria. The subjects were assessed with several symptom rating scales in week 1, 3, 6, 9 and 12. Results 77 of 116 subjects (66.4%) achieved the criteria for response and the average of optimal daily dose for response was to 30.05±12.52 mg per day (0.90±0.31 mg/kg/d) at the end of the study. Optimal dose was not significantly different between ADHD subtypes, whereas, significant higher dose was needed in older aged groups than younger groups. The average of optimal daily dose for response for the subjects aged above 12 years old was 46.38±15.52 per day (0.81±0.28 mg/kg/d) compared to younger groups (p<0.01). No serious adverse effects were reported and the dose did not have a significant effect on adverse effects. Conclusion Optimal mean dose of OROS-MPH was significantly different by age groups. Higher dose was needed in older aged groups than younger groups. Effectiveness and tolerability of OROS-MPH in symptoms of ADHD is sustained for up to 12 weeks. PMID:22993525

  3. SU-E-J-100: The Combination of Deformable Image Registration and Regions-Of-Interest Mapping Technique to Accomplish Accurate Dose Calculation On Cone Beam Computed Tomography for Esophageal Cancer

    SciTech Connect

    Huang, B-T; Lu, J-Y

    2015-06-15

    Purpose: We introduce a new method combined with the deformable image registration (DIR) and regions-of-interest mapping (ROIM) technique to accurately calculate dose on daily CBCT for esophageal cancer. Methods: Patients suffered from esophageal cancer were enrolled in the study. Prescription was set to 66 Gy/30 F and 54 Gy/30 F to the primary tumor (PTV66) and subclinical disease (PTV54) . Planning CT (pCT) were segmented into 8 substructures in terms of their differences in physical density, such as gross target volume (GTV), venae cava superior (SVC), aorta, heart, spinal cord, lung, muscle and bones. The pCT and its substructures were transferred to the MIM software to readout their mean HU values. Afterwards, a deformable planning CT to daily KV-CBCT image registration method was then utilized to acquire a new structure set on CBCT. The newly generated structures on CBCT were then transferred back to the treatment planning system (TPS) and its HU information were overridden manually with mean HU values obtained from pCT. Finally, the treatment plan was projected onto the CBCT images with the same beam arrangements and monitor units (MUs) to accomplish dose calculation. Planning target volume (PTV) and organs at risk (OARs) from both of the pCT and CBCT were compared to evaluate the dose calculation accuracy. Results: It was found that the dose distribution in the CBCT showed little differences compared to the pCT, regardless of whether PTV or OARs were concerned. Specifically, dose variation in GTV, PTV54, PTV66, SVC, lung and heart were within 0.1%. The maximum dose variation was presented in the spinal cord, which was up to 2.7% dose difference. Conclusion: The proposed method combined with DIR and ROIM technique to accurately calculate dose distribution on CBCT for esophageal cancer is feasible.

  4. Measurements of the neutron dose equivalent for various radiation qualities, treatment machines and delivery techniques in radiation therapy.

    PubMed

    Hälg, R A; Besserer, J; Boschung, M; Mayer, S; Lomax, A J; Schneider, U

    2014-05-21

    In radiation therapy, high energy photon and proton beams cause the production of secondary neutrons. This leads to an unwanted dose contribution, which can be considerable for tissues outside of the target volume regarding the long term health of cancer patients. Due to the high biological effectiveness of neutrons in regards to cancer induction, small neutron doses can be important. This study quantified the neutron doses for different radiation therapy modalities. Most of the reports in the literature used neutron dose measurements free in air or on the surface of phantoms to estimate the amount of neutron dose to the patient. In this study, dose measurements were performed in terms of neutron dose equivalent inside an anthropomorphic phantom. The neutron dose equivalent was determined using track etch detectors as a function of the distance to the isocenter, as well as for radiation sensitive organs. The dose distributions were compared with respect to treatment techniques (3D-conformal, volumetric modulated arc therapy and intensity-modulated radiation therapy for photons; spot scanning and passive scattering for protons), therapy machines (Varian, Elekta and Siemens linear accelerators) and radiation quality (photons and protons). The neutron dose equivalent varied between 0.002 and 3 mSv per treatment gray over all measurements. Only small differences were found when comparing treatment techniques, but substantial differences were observed between the linear accelerator models. The neutron dose equivalent for proton therapy was higher than for photons in general and in particular for double-scattered protons. The overall neutron dose equivalent measured in this study was an order of magnitude lower than the stray dose of a treatment using 6 MV photons, suggesting that the contribution of the secondary neutron dose equivalent to the integral dose of a radiotherapy patient is small. PMID:24778349

  5. Measurements of the neutron dose equivalent for various radiation qualities, treatment machines and delivery techniques in radiation therapy

    NASA Astrophysics Data System (ADS)

    Hälg, R. A.; Besserer, J.; Boschung, M.; Mayer, S.; Lomax, A. J.; Schneider, U.

    2014-05-01

    In radiation therapy, high energy photon and proton beams cause the production of secondary neutrons. This leads to an unwanted dose contribution, which can be considerable for tissues outside of the target volume regarding the long term health of cancer patients. Due to the high biological effectiveness of neutrons in regards to cancer induction, small neutron doses can be important. This study quantified the neutron doses for different radiation therapy modalities. Most of the reports in the literature used neutron dose measurements free in air or on the surface of phantoms to estimate the amount of neutron dose to the patient. In this study, dose measurements were performed in terms of neutron dose equivalent inside an anthropomorphic phantom. The neutron dose equivalent was determined using track etch detectors as a function of the distance to the isocenter, as well as for radiation sensitive organs. The dose distributions were compared with respect to treatment techniques (3D-conformal, volumetric modulated arc therapy and intensity-modulated radiation therapy for photons; spot scanning and passive scattering for protons), therapy machines (Varian, Elekta and Siemens linear accelerators) and radiation quality (photons and protons). The neutron dose equivalent varied between 0.002 and 3 mSv per treatment gray over all measurements. Only small differences were found when comparing treatment techniques, but substantial differences were observed between the linear accelerator models. The neutron dose equivalent for proton therapy was higher than for photons in general and in particular for double-scattered protons. The overall neutron dose equivalent measured in this study was an order of magnitude lower than the stray dose of a treatment using 6 MV photons, suggesting that the contribution of the secondary neutron dose equivalent to the integral dose of a radiotherapy patient is small.

  6. Local Delivery of High-Dose Chondroitinase ABC in the Sub-Acute Stage Promotes Axonal Outgrowth and Functional Recovery after Complete Spinal Cord Transection

    PubMed Central

    Cheng, Chu-Hsun; Lin, Chi-Te; Lee, Meng-Jen; Tsai, May-Jywan; Huang, Wen-Hung; Huang, Ming-Chao; Lin, Yi-Lo; Chen, Ching-Jung

    2015-01-01

    Chondroitin sulfate proteoglycans (CSPGs) are glial scar-associated molecules considered axonal regeneration inhibitors and can be digested by chondroitinase ABC (ChABC) to promote axonal regeneration after spinal cord injury (SCI). We previously demonstrated that intrathecal delivery of low-dose ChABC (1 U) in the acute stage of SCI promoted axonal regrowth and functional recovery. In this study, high-dose ChABC (50 U) introduced via intrathecal delivery induced subarachnoid hemorrhage and death within 48 h. However, most SCI patients are treated in the sub-acute or chronic stages, when the dense glial scar has formed and is minimally digested by intrathecal delivery of ChABC at the injury site. The present study investigated whether intraparenchymal delivery of ChABC in the sub-acute stage of complete spinal cord transection would promote axonal outgrowth and improve functional recovery. We observed no functional recovery following the low-dose ChABC (1 U or 5 U) treatments. Furthermore, animals treated with high-dose ChABC (50 U or 100 U) showed decreased CSPGs levels. The extent and area of the lesion were also dramatically decreased after ChABC treatment. The outgrowth of the regenerating axons was significantly increased, and some partially crossed the lesion site in the ChABC-treated groups. In addition, retrograde Fluoro-Gold (FG) labeling showed that the outgrowing axons could cross the lesion site and reach several brain stem nuclei involved in sensory and motor functions. The Basso, Beattie and Bresnahan (BBB) open field locomotor scores revealed that the ChABC treatment significantly improved functional recovery compared to the control group at eight weeks after treatment. Our study demonstrates that high-dose ChABC treatment in the sub-acute stage of SCI effectively improves glial scar digestion by reducing the lesion size and increasing axonal regrowth to the related functional nuclei, which promotes locomotor recovery. Thus, our results will aid in

  7. NOTE: How accurate is a CT-based dose calculation on a pencil beam TPS for a patient with a metallic prosthesis?

    NASA Astrophysics Data System (ADS)

    Roberts, Ralph

    2001-09-01

    The accuracy of a CT-based dose calculation on a treatment planning system (TPS) for a radiotherapy patient with a metallic prosthesis has not previously been reported. In this study, the accuracy of the CT-based inhomogeneity correction on a pencil beam TPS (Helax TMS) was determined in a phantom containing a metallic prosthesis. A steel prosthesis phantom and a titanium prosthesis phantom were investigated. The phantoms were CT-scanned and dose plans produced on the TPS, using the CT images to provide density information for the inhomogeneity corrections. Verification measurements were performed on a linear accelerator for 6 and 15 MV x-rays. Measured dose profiles at three different depths were compared to the calculations of the TPS. For the titanium prosthesis and for 6 MV x-rays, the TPS overestimated the beam attenuation by approximately 20% at 15 and 20 cm depths in the phantom. This is due to a limitation in the density allocation of this TPS: any Hounsfield number (HN) above a certain threshold is allocated the density of steel. For the steel prosthesis, the TPS performed the correct mapping of HN to mass density. The dose calculation was within 6% for 6 MV x-rays at 15 and 20 cm depths. However, the accuracy of dose calculation varied with beam energy and depth, with large errors in the region close to the prosthesis. The TPS overestimated the dose by 11% for 6 MV and 15% for 15 MV x-rays at 11 cm depth, 2.5 cm beyond the steel prosthesis. These results highlight the limitations in the density allocation of this TPS and demonstrate shortcomings in the pencil beam dose calculation.

  8. Design of a Dissolving Microneedle Platform for Transdermal Delivery of a Fixed-Dose Combination of Cardiovascular Drugs.

    PubMed

    Quinn, Helen L; Bonham, Louise; Hughes, Carmel M; Donnelly, Ryan F

    2015-10-01

    Microneedles (MNs) are a minimally invasive drug delivery platform, designed to enhance transdermal drug delivery by breaching the stratum corneum. For the first time, this study describes the simultaneous delivery of a combination of three drugs using a dissolving polymeric MN system. In the present study, aspirin, lisinopril dihydrate, and atorvastatin calcium trihydrate were used as exemplar cardiovascular drugs and formulated into MN arrays using two biocompatible polymers, poly(vinylpyrrollidone) and poly(methylvinylether/maleic acid). Following fabrication, dissolution, mechanical testing, and determination of drug recovery from the MN arrays, in vitro drug delivery studies were undertaken, followed by HPLC analysis. All three drugs were successfully delivered in vitro across neonatal porcine skin, with similar permeation profiles achieved from both polymer formulations. An average of 126.3 ± 18.1 μg of atorvastatin calcium trihydrate was delivered, notably lower than the 687.9 ± 101.3 μg of lisinopril and 3924 ± 1011 μg of aspirin, because of the hydrophobic nature of the atorvastatin molecule and hence poor dissolution from the array. Polymer deposition into the skin may be an issue with repeat application of such a MN array, hence future work will consider more appropriate MN systems for continuous use, alongside tailoring delivery to less hydrophilic compounds. PMID:26149914

  9. Sustained platelet-sparing effect of weekly low dose paclitaxel allows effective, tolerable delivery of extended dose dense weekly carboplatin in platinum resistant/refractory epithelial ovarian cancer

    PubMed Central

    2011-01-01

    Background Platinum agents have shown demonstrable activity in the treatment of patients with platinum resistant, recurrent ovarian cancer when delivered in a "dose-dense" fashion. However, the development of thrombocytopenia limits the weekly administration of carboplatin to no greater than AUC 2. Paclitaxel has a well-described platelet sparing effect however its use to explicitly provide thromboprotection in the context of dose dense carboplatin has not been explored. Methods We treated seven patients with platinum resistant ovarian cancer who had previously received paclitaxel or who had developed significant peripheral neuropathy precluding the use of further full dose weekly paclitaxel. Results We were able to deliver carboplatin AUC 3 and paclitaxel 20 mg/m2 with no thrombocytopenia or worsening of neuropathic side-effects, and with good activity. Conclusions We conclude that this regimen may be feasible and active, and could be formally developed as a "platinum-focussed dose-dense scaffold" into which targeted therapies that reverse platinum resistance can be incorporated, and merits further evaluation. PMID:21745358

  10. Multileaf Collimator Tracking Improves Dose Delivery for Prostate Cancer Radiation Therapy: Results of the First Clinical Trial

    SciTech Connect

    Colvill, Emma; Booth, Jeremy T.; O'Brien, Ricky T.; Eade, Thomas N.; Kneebone, Andrew B.; Poulsen, Per R.; Keall, Paul J.

    2015-08-01

    Purpose: To test the hypothesis that multileaf collimator (MLC) tracking improves the consistency between the planned and delivered dose compared with the dose without MLC tracking, in the setting of a prostate cancer volumetric modulated arc therapy trial. Methods and Materials: Multileaf collimator tracking was implemented for 15 patients in a prostate cancer radiation therapy trial; in total, 513 treatment fractions were delivered. During each treatment fraction, the prostate trajectory and treatment MLC positions were collected. These data were used as input for dose reconstruction (multiple isocenter shift method) to calculate the treated dose (with MLC tracking) and the dose that would have been delivered had MLC tracking not been applied (without MLC tracking). The percentage difference from planned for target and normal tissue dose-volume points were calculated. The hypothesis was tested for each dose-volume value via analysis of variance using the F test. Results: Of the 513 fractions delivered, 475 (93%) were suitable for analysis. The mean difference and standard deviation between the planned and treated MLC tracking doses and the planned and without-MLC tracking doses for all 475 fractions were, respectively, PTV D{sub 99%} −0.8% ± 1.1% versus −2.1% ± 2.7%; CTV D{sub 99%} −0.6% ± 0.8% versus −0.6% ± 1.1%; rectum V{sub 65%} 1.6% ± 7.9% versus −1.2% ± 18%; and bladder V{sub 65%} 0.5% ± 4.4% versus −0.0% ± 9.2% (P<.001 for all dose-volume results). Conclusion: This study shows that MLC tracking improves the consistency between the planned and delivered doses compared with the modeled doses without MLC tracking. The implications of this finding are potentially improved patient outcomes, as well as more reliable dose-volume data for radiobiological parameter determination.

  11. High-Precision Radiosurgical Dose Delivery by Interlaced Microbeam Arrays of High-Flux Low-Energy Synchrotron X-Rays

    PubMed Central

    Serduc, Raphaël; Bräuer-Krisch, Elke; Siegbahn, Erik A.; Bouchet, Audrey; Pouyatos, Benoit; Carron, Romain; Pannetier, Nicolas; Renaud, Luc; Berruyer, Gilles; Nemoz, Christian; Brochard, Thierry; Rémy, Chantal; Barbier, Emmanuel L.; Bravin, Alberto; Le Duc, Géraldine; Depaulis, Antoine; Estève, François; Laissue, Jean A.

    2010-01-01

    Microbeam Radiation Therapy (MRT) is a preclinical form of radiosurgery dedicated to brain tumor treatment. It uses micrometer-wide synchrotron-generated X-ray beams on the basis of spatial beam fractionation. Due to the radioresistance of normal brain vasculature to MRT, a continuous blood supply can be maintained which would in part explain the surprising tolerance of normal tissues to very high radiation doses (hundreds of Gy). Based on this well described normal tissue sparing effect of microplanar beams, we developed a new irradiation geometry which allows the delivery of a high uniform dose deposition at a given brain target whereas surrounding normal tissues are irradiated by well tolerated parallel microbeams only. Normal rat brains were exposed to 4 focally interlaced arrays of 10 microplanar beams (52 µm wide, spaced 200 µm on-center, 50 to 350 keV in energy range), targeted from 4 different ports, with a peak entrance dose of 200Gy each, to deliver an homogenous dose to a target volume of 7 mm3 in the caudate nucleus. Magnetic resonance imaging follow-up of rats showed a highly localized increase in blood vessel permeability, starting 1 week after irradiation. Contrast agent diffusion was confined to the target volume and was still observed 1 month after irradiation, along with histopathological changes, including damaged blood vessels. No changes in vessel permeability were detected in the normal brain tissue surrounding the target. The interlacing radiation-induced reduction of spontaneous seizures of epileptic rats illustrated the potential pre-clinical applications of this new irradiation geometry. Finally, Monte Carlo simulations performed on a human-sized head phantom suggested that synchrotron photons can be used for human radiosurgical applications. Our data show that interlaced microbeam irradiation allows a high homogeneous dose deposition in a brain target and leads to a confined tissue necrosis while sparing surrounding tissues. The use of

  12. A comparison of intensity modulated x-ray therapy to intensity modulated proton therapy for the delivery of non-uniform dose distributions

    NASA Astrophysics Data System (ADS)

    Flynn, Ryan

    2007-12-01

    The distribution of biological characteristics such as clonogen density, proliferation, and hypoxia throughout tumors is generally non-uniform, therefore it follows that the optimal dose prescriptions should also be non-uniform and tumor-specific. Advances in intensity modulated x-ray therapy (IMXT) technology have made the delivery of custom-made non-uniform dose distributions possible in practice. Intensity modulated proton therapy (IMPT) has the potential to deliver non-uniform dose distributions as well, while significantly reducing normal tissue and organ at risk dose relative to IMXT. In this work, a specialized treatment planning system was developed for the purpose of optimizing and comparing biologically based IMXT and IMPT plans. The IMXT systems of step-and-shoot (IMXT-SAS) and helical tomotherapy (IMXT-HT) and the IMPT systems of intensity modulated spot scanning (IMPT-SS) and distal gradient tracking (IMPT-DGT), were simulated. A thorough phantom study was conducted in which several subvolumes, which were contained within a base tumor region, were boosted or avoided with IMXT and IMPT. Different boosting situations were simulated by varying the size, proximity, and the doses prescribed to the subvolumes, and the size of the phantom. IMXT and IMPT were also compared for a whole brain radiation therapy (WBRT) case, in which a brain metastasis was simultaneously boosted and the hippocampus was avoided. Finally, IMXT and IMPT dose distributions were compared for the case of non-uniform dose prescription in a head and neck cancer patient that was based on PET imaging with the Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone (Cu-ATSM) hypoxia marker. The non-uniform dose distributions within the tumor region were comparable for IMXT and IMPT. IMPT, however, was capable of delivering the same non-uniform dose distributions within a tumor using a 180° arc as for a full 360° rotation, which resulted in the reduction of normal tissue integral dose by a factor of

  13. The development of new devices for accurate radiation dose measurement: A guarded liquid ionization chamber and an electron sealed water calorimeter

    NASA Astrophysics Data System (ADS)

    Stewart, Kristin J.

    In this work we developed two new devices that aim to improve the accuracy of relative and reference dosimetry for radiation therapy: a guarded liquid ionization chamber (GLIC) and an electron sealed water (ESW) calorimeter. With the GLIC we aimed to develop a perturbation-free energy-independent detector with high spatial resolution for relative dosimetry. We achieved sufficient stability for short-term measurements using the GLIC-03, which has a sensitive volume of approximately 2 mm3. We evaluated ion recombination in pulsed photon beams using a theoretical model and also determined a new empirical method to correct for relative differences in general recombination which could be used in cases where the theoretical model was not applicable. The energy dependence of the GLIC-03 was 1.1% between 6 and 18 MV photon beams. Measurements in the build-up region of an 18 MV beam indicated that this detector produces minimal perturbation to the radiation field and confirmed the validity of the empirical recombination correction. The ESW calorimeter was designed to directly measure absorbed dose to water in clinical electron beams. We obtained reproducible measurements for 6 to 20 MeV beams. We determined corrections for perturbations to the radiation field caused by the glass calorimeter vessel and for conductive heat transfer due to the dose gradient and non-water materials. The overall uncertainty on the ESW calorimeter dose was 0.5% for the 9 to 20 MeV beams and 1.0% for 6 MeV, showing for the first time that the development of a water-calorimeter-based standard for electron beams over a wide range of energies is feasible. Comparison between measurements with the ESW calorimeter and the NRC photon beam standard calorimeter in a 6 MeV beam revealed a discrepancy of 0.7+/-0.2% which is still under investigation. Absorbed-dose beam quality conversion factors in electron beams were measured using the ESW calorimeter for the Exradin A12 and PTW Roos ionization chambers

  14. Zero-order delivery of a highly soluble, low dose drug alfuzosin hydrochloride via gastro-retentive system.

    PubMed

    Liu, Quan; Fassihi, Reza

    2008-02-01

    A composite gastro-retentive matrix for zero-order delivery of highly soluble drug alfuzosin hydrochloride (10mg) has been designed and characterized. Two systems containing polyethylene oxide (PEO), hydroxypropylmethylcellulose (HPMC), sodium bicarbonate, citric acid and polyvinyl pyrrolidone were dry blended and compressed into triple layer and bi-layer composite matrices. Dissolution studies using the USP 27 paddle method at 100 and 50rpm in pH 2.0 and 6.8 were performed using UV spectroscopy at 244nm, with automatic sampling over a 24h period using a marketed product as a reference to calculate the "f(2)" factor. Textural characteristics of each layer, the composite matrix as a whole, and floatation potential were determined under conditions similar to dissolution. Percent matrix swelling and erosion along with digital images were also obtained. Both systems proved to be effective in providing prolonged floatation, zero-order release, and complete disentanglement and erosion based on the analysis of data with "f(2)" of 68 and 71 for PEO and HPMC based systems, respectively. The kinetics of drug release, swelling and erosion, and dynamics of textural changes during dissolution for the designed composite systems offer a novel approach for developing gastro-retentive drug delivery system that has potential to enhance bioavailability and site-specific delivery to the proximal small intestine. PMID:17850997

  15. Dosimetric investigation of high dose rate, gated IMRT

    SciTech Connect

    Lin, Teh; Chen Yan; Hossain, Murshed; Li, Jinsheng; Ma, C.-M.

    2008-11-15

    Increasing the dose rate offers time saving for IMRT delivery but the dosimetric accuracy is a concern, especially in the case of treating a moving target. The objective of this work is to determine the effect of dose rate associated with organ motion and gated treatment using step-and-shoot IMRT delivery. Both measurements and analytical simulation on clinical plans are performed to study the dosimetric differences between high dose rate and low dose rate gated IMRT step-and-shoot delivery. Various sites of IMRT plans for liver, lung, pancreas, and breast cancers were delivered to a custom-made motorized phantom, which simulated sinusoidal movement. Repeated measurements were taken for gated and nongated delivery with different gating settings and three dose rates, 100, 500, and 1000 MU/min using ion chambers and extended dose range films. For the study of the residual motion effect for individual segment dose and composite dose of IMRT plans, our measurements with 30%-60% phase gating and without gating for various dose rates were compared. A small but clinically acceptable difference in delivered dose was observed between 1000, 500, and 100 MU/min at 30%-60% phase gating. A simulation is presented, which can be used for predicting dose profiles for patient cases in the presence of motion and gating to confirm that IMRT step-and-shoot delivery with gating for 1000 MU/min are not much different from 500 MU/min. Based on the authors sample plan analyses, our preliminary results suggest that using 1000 MU/Min dose rate is dosimetrically accurate and efficient for IMRT treatment delivery with gating. Nonetheless, for the concern of patient care and safety, a patient specific QA should be performed as usual for IMRT plans for high dose rate deliveries.

  16. Articulating feedstock delivery device

    DOEpatents

    Jordan, Kevin

    2013-11-05

    A fully articulable feedstock delivery device that is designed to operate at pressure and temperature extremes. The device incorporates an articulating ball assembly which allows for more accurate delivery of the feedstock to a target location. The device is suitable for a variety of applications including, but not limited to, delivery of feedstock to a high-pressure reaction chamber or process zone.

  17. Slow and continuous delivery of a low dose of nimodipine improves survival and electrocardiogram parameters in rescue therapy of mice with experimental cerebral malaria

    PubMed Central

    2013-01-01

    Background Human cerebral malaria (HCM) is a life-threatening complication caused by Plasmodium falciparum infection that continues to be a major global health problem despite optimal anti-malarial treatment. In the experimental model of cerebral malaria (ECM) by Plasmodium berghei ANKA, bolus administration of nimodipine at high doses together with artemether, increases survival of mice with ECM. However, the dose and administration route used is associated with cardiovascular side effects such as hypotension and bradycardia in humans and mice, which could preclude its potential use as adjunctive treatment in HCM. Methods In the present study, alternative delivery systems for nimodipine during late-stage ECM in association with artesunate were searched to define optimal protocols to achieve maximum efficacy in increasing survival in rescue therapy while causing the least cardiac side effects. The baseline electrocardiogram (ECG) and arterial pressure characteristics of uninfected control animals and of mice with ECM and its response upon rescue treatment with artesunate associated or not with nimodipine is also analysed. Results Nimodipine, given at 0.5 mg/kg/day via a slow and continuous delivery system by osmotic pumps, increases survival of mice with ECM when used as adjunctive treatment to artesunate. Mice with ECM showed hypotension and ECG changes, including bradycardia and increases in PR, QRS, QTc and ST interval duration. ECM mice also show increased QTc dispersion, heart rate variability (HRV), RMSSD, low frequency (LF) and high frequency (HF) bands of the power spectrum. Both sympathetic and parasympathetic inputs to the heart were increased, but there was a predominance of sympathetic tone as demonstrated by an increased LF/HF ratio. Nimodipine potentiated bradycardia when given by bolus injection, but not when via osmotic pumps. In addition, nimodipine shortened PR duration and improved HRV, RMSSD, LF and HF powers in mice with ECM. In addition

  18. Low-dose combined spinal-epidural anesthesia for cesarean delivery: a comparison of three plain local anesthetics.

    PubMed

    Coppejans, H C; Vercauteren, M P

    2006-01-01

    The new local anesthetics have been poorly studied for intrathecal use during Cesarean section surely in low doses and in combination with an opioid substance. The purpose of the present study was to compare bupivacaine and the newer local anesthetics in equipotent doses. During the induction of combined spinal-epidural anesthesia, 91 elective Cesarean section patients were randomly assigned to receive a spinal injection of either 10 mg ropivacaine or 6.6 mg bupivacaine or levobupivacaine both combined with sufentanil 3.3 microg. After securing the epidural catheter patients were turned to the supine position respecting a 15 degrees left lateral tilt. The three local anesthetics were compared with respect to sensory and motor block, the need for epidural supplementation, the severity of hypotension and neonatal outcome. More patients in bupivacaine had a Bromage-3 motor block at incision. The ropivacaine group required additional local anesthetics by the epidural route in 23% of the cases versus 10% in the bupivacaine group and 9% with levobupivacaine. This caused the interval between the spinal injection and the end of surgery to be longer in the ropivacaine group. Hemodynamic values were comparable between the three groups although a trend towards better systolic blood pressures and a lower incidence of severe hypotension were noticed in favor of levobupivacaine. Apgar scores and umbilical pH values did not differ. When performing a low-dose combined spinal-epidural technique for Cesarean section, the present study confirms that the new local anesthetics can be used successfully, induce less motor block but that ropivacaine requires at least a 50% larger dose than bupivacaine or levobupivacaine. PMID:16617756

  19. Simple methods to reduce patient dose in a Varian cone beam CT system for delivery verification in pelvic radiotherapy.

    PubMed

    Roxby, P; Kron, T; Foroudi, F; Haworth, A; Fox, C; Mullen, A; Cramb, J

    2009-10-01

    Cone-beam computed tomography (CBCT) is a three-dimensional imaging modality that has recently become available on linear accelerators for radiotherapy patient position verification. It was the aim of the present study to implement simple strategies for reduction of the dose delivered in a commercial CBCT system. The dose delivered in a CBCT procedure (Varian, half-fan acquisition, 650 projections, 125 kVp) was assessed using a cylindrical Perspex phantom (diameter, 32 cm) with a calibrated Farmer type ionisation chamber. A copper filter (thickness, 0.15 mm) was introduced increasing the half value layer of the beam from 5.5 mm Al to 8 mm Al. Image quality and noise were assessed using an image quality phantom (CatPhan) while the exposure settings per projection were varied from 25 ms/80 mA to 2 ms/2 mA per projection. Using the copper filter reduced the dose to the phantom from approximately 45 mGy to 30 mGy at standard settings (centre/periphery weighting 1/3 to 2/3). Multiple CBCT images were acquired for six patients with pelvic malignancies to compare CBCTs with and without a copper filter. Although the reconstructed image is somewhat noisier with the filter, it features similar contrast in the centre of the patient and was often preferred by the radiation oncologist because of greater image uniformity. The X-ray shutters were adjusted to the minimum size required to obtain the desired image volume for a given patient diameter. The simple methods described here reduce the effective dose to patients undergoing daily CBCT and are easy to implement, and initial evidence suggests that they do not affect the ability to identify soft tissue for the purpose of treatment verification. PMID:19289401

  20. Local delivery of antitumor necrosis factor-α through conjugation to hyaluronic acid: dosing strategies and early healing effects in a rat burn model.

    PubMed

    Friedrich, Emily E; Azofiefa, Andrea; Fisch, Evan; Washburn, Newell R

    2015-01-01

    The objective of this study was to measure dose-response effects of topical delivery of inhibitors of tumor necrosis factor-α (TNF-α) through conjugation to hyaluronic acid in a rat burn model to determine effects on inflammatory responses, burn progression, and early stages of healing. Monoclonal antibodies against TNF-α were conjugated to hyaluronic acid and applied topically in a rat partial-thickness burn model. Metrics of inflammatory responses and tissue necrosis were measured as well as the quantitative analysis of collagen composition and organization. The minimum effective conjugated antibody dose was found to be 100 μg with three applications 48 hours apart. Nonviable tissue thicknesses decreased with increasing dose and dose frequency. Free antibody retarded macrophage infiltration in the periphery but not at the surface, while the conjugated antibody was able to hinder macrophage infiltration at both the periphery and the surface. Quantification of collagen I and III staining ratios at days 4, 7, and 14 and quantitative image analysis of collagen organization at day 14 demonstrated differences between saline and conjugate treatment. This correlated with increases in re-epithelialization observed in conjugate-treated sites. Reductions in inflammatory markers and secondary tissue necrosis under treatment with the conjugates were understood in terms of differences in antibody transport compared to nonconjugated antibody. Differences in collagen composition and organization at Day 14 suggested that the reductions in inflammatory responses altered early healing responses. These results indicate anti-TNF-α conjugated to hyaluronic acid can be an effective treatment for reducing secondary necrosis and improving healing outcomes in burns. PMID:25526179

  1. The Technique, Resources and Costs of Stereotactic Body Radiotherapy of Prostate Cancer: A Comparison of Dose Regimens and Delivery Systems.

    PubMed

    Sharieff, Waseem; Greenspoon, Jeffrey N; Dayes, Ian; Chow, Tom; Wright, James; Lukka, Himu

    2016-02-01

    Robotic system has been used for stereotactic body radiotherapy (SBRT) of prostate cancer. Arc-based and fixed-gantry systems are used for hypofractionated regimens (10-20 ractions) and the standard regimen (39 fractions); they may also be used to deliver SBRT. Studies are currently underway to compare efficacy and safety of these systems and regimens. Thus, we describe the technique and required resources for the provision of robotic SBRT in relation to the standard regimen and other systems to guide investment decisions. Using administrative data of resource volumes and unit prices, we computed the cost per patient, cost per cure and cost per quality adjusted life year (QALY) of four regimens (5, 12, 20 and 39 fractions) and three delivery systems (robotic, arc-based and fixed-gantry) from a payer's perspective. We performed sensitivity analyses to examine the effects of daily hours of operation and in-room treatment delivery times on cost per patient. In addition, we estimated the budget impact when a robotic system is preferred over an arc-based or fixed-gantry system. Costs of SBRT were $6333/patient (robotic), $4368/patient (arc-based) and $4443/patient (fixed-gantry). When daily hours of operation were varied, the cost of robotic SBRT varied from $9324/patient (2 hours daily) to $5250/patient (10 hours daily). This was comparable to the costs of 39 fraction standard regimen which were $5935/patient (arc-based) and $7992/ patient (fixed-gantry). In settings of moderate to high patient volume, robotic SBRT is cost effective compared to the standard regimen. If SBRT can be delivered with equivalent efficacy and safety, the arc-based system would be the most cost effective system. PMID:24750007

  2. α-Tocopherol in breast milk of women with preterm delivery after a single postpartum oral dose of vitamin E.

    PubMed

    Pires Medeiros, Jeane Franco; Ribeiro, Karla Danielly da Silva; Lima, Mayara Santa Rosa; das Neves, Renata Alexandra Moreira; Lima, Amanda Cibely Pinheiro; Dantas, Raquel Costa Silva; da Silva, Alyne Batista; Dimenstein, Roberto

    2016-04-01

    We evaluated the effect of maternal vitamin E supplementation on the α-tocopherol concentrations of colostrum, transitional milk and mature milk of women who had given birth prematurely. This longitudinal randomised-controlled trial divided eighty-nine women into two groups: a control group and a supplemented group. Blood and breast milk were collected from all the participants after delivery. Next, each woman in the supplemented group received 400 IU of RRR-α-tocopheryl acetate. Further breast milk samples were collected 24 h after the first collection, as well as 7 and 30 d after delivery. α-Tocopherol concentrations were determined by HPLC. The baseline α-tocopherol concentrations in the maternal serum of the two groups were similar: 1159·8 (sd 292·4) μg/dl (27·0 (SD 6·8) μmol/l) for the control group and 1128·3 (sd 407·2) μg/dl (26·2 (SD 9·5) μmol/l) for the supplemented group. None of the women was vitamin E deficient. Breast milk α-tocopherol concentrations increased by 60 % 24 h after supplementation in the intervention group and did not increase at all in the control group. α-Tocopherol concentration of the transitional milk in the supplemented group was 35 % higher compared with the control group. α-Tocopherol concentrations of the mature milk in both groups were similar. Maternal supplementation with 400 IU of RRR-α-tocopherol increased the vitamin E concentrations of the colostrum and transitional milk, but not of the mature milk. This study presents relevant information for the design of strategies to prevent and combat vitamin E deficiency in the risk group of preterm infants. PMID:26931347

  3. Ocular delivery of macromolecules

    PubMed Central

    Kim, Yoo-Chun; Chiang, Bryce; Wu, Xianggen; Prausnitz, Mark R.

    2014-01-01

    Biopharmaceuticals are making increasing impact on medicine, including treatment of indications in the eye. Macromolecular drugs are typically given by physician-administered invasive delivery methods, because non--invasive ocular delivery methods, such as eye drops, and systemic delivery, have low bioavailability and/or poor ocular targeting. There is a need to improve delivery of biopharmaceuticals to enable less-invasive delivery routes, less-frequent dosing through controlled-release drug delivery and improved drug targeting within the eye to increase efficacy and reduce side effects. This review discusses the barriers to drug delivery via various ophthalmic routes of administration in the context of macromolecule delivery and discusses efforts to develop controlled-release systems for delivery of biopharmaceuticals to the eye. The growing number of macromolecular therapies in the eye needs improved drug delivery methods that increase drug efficacy, safety and patient compliance. PMID:24998941

  4. Development of a novel ArcCHECK{sup Trade-Mark-Sign} insert for routine quality assurance of VMAT delivery including dose calculation with inhomogeneities

    SciTech Connect

    Fakir, H.; Gaede, S.; Mulligan, M.; Chen, J. Z.

    2012-07-15

    Purpose: To design a versatile, nonhomogeneous insert for the dose verification phantom ArcCHECK{sup Trade-Mark-Sign} (Sun Nuclear Corp., FL) and to demonstrate its usefulness for the verification of dose distributions in inhomogeneous media. As an example, we demonstrate it can be used clinically for routine quality assurance of two volumetric modulated arc therapy (VMAT) systems for lung stereotactic body radiation therapy (SBRT): SmartArc{sup Registered-Sign} (Pinnacle{sup 3}, Philips Radiation Oncology Systems, Fitchburg, WI) and RapidArc{sup Registered-Sign} (Eclipse{sup Trade-Mark-Sign }, Varian Medical Systems, Palo Alto, CA). Methods: The cylindrical detector array ArcCHECK{sup Trade-Mark-Sign} has a retractable homogeneous acrylic insert. In this work, we designed and manufactured a customized heterogeneous insert with densities that simulate soft tissue, lung, bone, and air. The insert offers several possible heterogeneity configurations and multiple locations for point dose measurements. SmartArc{sup Registered-Sign} and RapidArc{sup Registered-Sign} plans for lung SBRT were generated and copied to ArcCHECK{sup Trade-Mark-Sign} for each inhomogeneity configuration. Dose delivery was done on a Varian 2100 ix linac. The evaluation of dose distributions was based on gamma analysis of the diode measurements and point doses measurements at different positions near the inhomogeneities. Results: The insert was successfully manufactured and tested with different measurements of VMAT plans. Dose distributions measured with the homogeneous insert showed gamma passing rates similar to our clinical results ({approx}99%) for both treatment-planning systems. Using nonhomogeneous inserts decreased the passing rates by up to 3.6% in the examples studied. Overall, SmartArc{sup Registered-Sign} plans showed better gamma passing rates for nonhomogeneous measurements. The discrepancy between calculated and measured point doses was increased up to 6.5% for the nonhomogeneous

  5. Feasibility of low-dose single-view 3D fiducial tracking concurrent with external beam delivery

    SciTech Connect

    Speidel, Michael A.; Wilfley, Brian P.; Hsu, Annie; Hristov, Dimitre

    2012-04-15

    Purpose: In external-beam radiation therapy, existing on-board x-ray imaging chains orthogonal to the delivery beam cannot recover 3D target trajectories from a single view in real-time. This limits their utility for real-time motion management concurrent with beam delivery. To address this limitation, the authors propose a novel concept for on-board imaging based on the inverse-geometry Scanning-Beam Digital X-ray (SBDX) system and evaluate its feasibility for single-view 3D intradelivery fiducial tracking. Methods: A chest phantom comprising a posterior wall, a central lung volume, and an anterior wall was constructed. Two fiducials were placed along the mediastinal ridge between the lung cavities: a 1.5 mm diameter steel sphere superiorly and a gold cylinder (2.6 mm length x 0.9 mm diameter) inferiorly. The phantom was placed on a linear motion stage that moved sinusoidally. Fiducial motion was along the source-detector (z) axis of the SBDX system with {+-}10 mm amplitude and a programmed period of either 3.5 s or 5 s. The SBDX system was operated at 15 frames per second, 100 kVp, providing good apparent conspicuity of the fiducials. With the stage moving, detector data were acquired and subsequently reconstructed into 15 planes with a 12 mm plane-to-plane spacing using digital tomosynthesis. A tracking algorithm was applied to the image planes for each temporal frame to determine the position of each fiducial in (x,y,z)-space versus time. A 3D time-sinusoidal motion model was fit to the measured 3D coordinates and root mean square (RMS) deviations about the fitted trajectory were calculated. Results: Tracked motion was sinusoidal and primarily along the source-detector (z) axis. The RMS deviation of the tracked z-coordinate ranged from 0.53 to 0.71 mm. The motion amplitude derived from the model fit agreed with the programmed amplitude to within 0.28 mm for the steel sphere and within -0.77 mm for the gold seed. The model fit periods agreed with the programmed

  6. SU-E-T-426: Dose Delivery Accuracy in Breast Field Junction for Free Breath and Deep Inspiration Breath Hold Techniques

    SciTech Connect

    Epstein, D; Shekel, E; Levin, D

    2014-06-01

    Purpose: The purpose of this work was to verify the accuracy of the dose distribution along the field junction in a half beam irradiation technique for breast cancer patients receiving radiation to the breast or chest wall (CW) and the supraclavicular LN region for both free breathing and deep inspiration breath hold (DIBH) technique. Methods: We performed in vivo measurements for nine breast cancer patients receiving radiation to the breast/CW and to the supraclavicular LN region. Six patients were treated to the left breast/CW using DIBH technique and three patients were treated to the right breast/CW in free breath. We used five microMOSFET dosimeters: three located along the field junction, one located 1 cm above the junction and the fifth microMOSFET located 1 cm below the junction. We performed consecutive measurements over several days for each patient and compared the measurements to the TPS calculation (Eclipse, Varian™). Results: The calculated and measured doses along the junction were 0.97±0.08 Gy and 1.02±0.14 Gy, respectively. Above the junction calculated and measured doses were 0.91±0.08 Gy and 0.98±0.09 Gy respectively, and below the junction calculated and measured doses were 1.70±0.15 Gy and 1.61±0.09 Gy, respectively. All differences were not statistically significant. When comparing calculated and measured doses for DIBH patients only, there was still no statistically significant difference between values for all dosimeter locations. Analysis was done using the Mann-Whitney Rank-Sum Test. Conclusion: We found excellent correlation between calculated doses from the TPS and measured skin doses at the junction of several half beam fields. Even for the DIBH technique, where there is more potential for variance due to depth of breath, there is no over or underdose along the field junction. This correlation validates the TPS, as well an accurate, reproducible patient setup.

  7. In Vitro Determination of Respimat® Dose Delivery in Children: An Evaluation Based on Inhalation Flow Profiles and Mouth–Throat Models

    PubMed Central

    Bickmann, Deborah; Kamin, Wolfgang; Sharma, Ashish; Moroni-Zentgraf, Petra; Zielen, Stefan

    2016-01-01

    Abstract Background: Aerosol therapy in young children can be difficult. A realistic model based on handling studies and in vitro investigations can complement clinical deposition studies and be used to enable dose-to-the-lung (DTL) predictions. Methods: Predictions on dose delivery to the lung were based on (1) representative inhalation flow profiles from children enrolled in a Respimat® handling study, (2) in vitro measurement of the fine-particle DTL using mouth–throat models derived from nuclear magnetic resonance/computed tomography (NMR/CT) scans of children, and (3) a mathematical model to predict the tiotropium DTL. Accuracy of the prediction was confirmed using pharmacokinetic (PK) data from children with cystic fibrosis enrolled in a phase 3 clinical trial of tiotropium Respimat with valved holding chamber (VHC). Results: Representative inhalation flow profiles for each age group were obtained from 56 children who successfully inhaled a volume >0.15 L from the Respimat with VHC. Average dimensions of the mouth–throat region for 38 children aged 1–<2 years, 2–<3 years, 3–<4 years, and 4–<5 years were determined from NMR/CT scans. The DTL from the Respimat plus VHC were determined by in vitro measurement and were 5.1±1.1%, 15.6%±1.4%, 17.9%±1.5%, and 37.1%±1.8% of the delivered dose for child models 0–<2 years, 2–<3 years, 3–<4 years, and 4–<5 years, respectively. This provides a possible explanation for the age dependence of clinical PK data obtained from the phase 3 tiotropium trial. Calculated in vitro DTL per body mass (μg/kg [±SD]) were 0.031±0.014, 0.066±0.031, 0.058±0.024, and 0.059±0.029, respectively, compared to 0.046 in adults. Therefore, efficacy of the treatment was not negatively impacted in spite of the seemingly low percentages of the DTL. Conclusions: We conclude that the combination of real-life inhalation profiles with respective mouth–throat models and in vitro determination of delivered DTL is a good

  8. Randomised, double-blind controlled trial by dose reduction of implanted intrathecal morphine delivery in chronic non-cancer pain

    PubMed Central

    Raphael, Jon H; Duarte, Rui V; Southall, Jane L; Nightingale, Peter; Kitas, George D

    2013-01-01

    Objective This study aimed to investigate the efficacy of intrathecal morphine in the long term by hypothesising that a reduction of the intrathecal opioid dose following long-term administration would increase the level of pain intensity. Design Randomised, double-blind, controlled, parallel group trial. Setting Department of Pain Management, Russells Hall Hospital, Dudley, UK. Participants 24 patients with non-cancer pain implanted with morphine reservoirs were assessed for eligibility. Interventions Participants were randomly allocated to one of two parallel groups in which one of the groups had no change in morphine dose and the other group had a small reduction (20%) in dosage every week during a 10-week follow-up. Outcome Primary outcomes were visual analogue scale (VAS) pain score change and withdrawal from the study due to lack of efficacy. Results 9 of the patients assessed for eligibility declined to participate in the study. 15 patients were randomised to control (n=5) or intervention (n=10) and included in an intention-to-treat analysis. Owing to worsening of pain, seven patients withdrew from the study prematurely. None knew prior to withdrawal which arm of the study they were in, but all turned out to be in the dose-reduction arm. The calculation of dropout rates between groups indicated a significant statistical difference (p=0.026) and recruitment was ceased. The VAS change between baseline and the last observation was smaller in the control group (median, Mdn=11) than in the intervention group (Mdn=30.5), although not statistically significant, Z=−1.839, p=0.070; r=−0.47. Within groups, VAS was significantly lower at baseline (Mdn=49.5) than at the last observation (Mdn=77.5) for the reduction group, Z=−2.805, p=0.002; r=−0.627 but not for the control group (p=0.188). Conclusions This double-blind randomised controlled trial of chronic intrathecal morphine administration suggests the effectiveness of this therapy for the management of

  9. Transdermal drug delivery

    PubMed Central

    Prausnitz, Mark R.; Langer, Robert

    2009-01-01

    Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, non-cavitational ultrasound and iontophoresis have also resulted in clinical products; the ability of iontophoresis to control delivery rates in real time provides added functionality. Third-generation delivery systems target their effects to skin’s barrier layer of stratum corneum using microneedles, thermal ablation, microdermabrasion, electroporation and cavitational ultrasound. Microneedles and thermal ablation are currently progressing through clinical trials for delivery of macromolecules and vaccines, such as insulin, parathyroid hormone and influenza vaccine. Using these novel second- and third-generation enhancement strategies, transdermal delivery is poised to significantly increase impact on medicine. PMID:18997767

  10. SU-E-J-269: Assessing the Precision of Dose Delivery in CBCT-Guided Stereotactic Body Radiation Therapy for Lung and Soft Tissue Metastatic Lesions

    SciTech Connect

    Parsai, S; Dalhart, A; Chen, C; Parsai, E; Pearson, D; Sperling, N; Reddy, K

    2014-06-01

    Purpose: Ensuring reproducibility of target localization is critical to accurate stereotactic body radiation treatment (SBRT) for lung and soft tissue metastatic lesions. To characterize interfraction variability in set-up and evaluate PTV margins utilized for SBRT, daily CBCTs were used to calculate delivered target and OAR doses compared to those expected from planning. Methods: CBCT images obtained prior to each fraction of SBRT for a lung and thyroid metastatic lesion were evaluated. The target CTV/ITV and OARs on each of 8 CBCT data sets were contoured. Using MIM fusion software and Pinnacle{sup 3} RTP system, delivered dose distribution was reconstructed on each CBCT, utilizing translational shifts performed prior to treatment. Actual delivered vs. expected doses received by target CTV/ITV and adjacent critical structures were compared to characterize accuracy of pre-treatment translational shifts and PTV margins. Results: The planned CTV/ITV D95% and V100% were 4595cGy and 91.47% for the lung lesion, and 3010cGy and 96.34% for the thyroid lesion. Based on CBCT analysis, actual mean D95% and V100% for lung ITV were 4542±344.4cGy and 91.54±3.45%; actual mean D95% and V100% for thyroid metastasis CTV were 3005±25.98cGy and 95.20±2.522%. For the lung lesion, ipsilateral lung V20, heart V32 (cc) and spinal cord (.03 cc) max were 110.15cc, 3.33cc, and 1680cGy vs. 110.27±14.79cc, 6.74±3.76cc, and 1711±46.56cGy for planned vs. delivered doses, respectively. For the thyroid metastatic lesion, esophagus V18, trachea (.03 cc) max, and spinal cord (.03 cc) max were 0.35cc, 2555cGy, and 850cGy vs. 0.16±0.13cc, 2147±367cGy, and 838±45cGy for planned vs. delivered treatments, respectively. Conclusion: Minimal variability in SBRT target lesion dose delivered based on pre-treatment CBCT-based translational shifts suggests tighter PTV margins may be considered to further decrease dose to surrounding critical structures. Guidelines for optimal target alignment during

  11. Surface delivery of tunable doses of BMP-2 from an adaptable polymeric scaffold induces volumetric bone regeneration.

    PubMed

    Bouyer, Michael; Guillot, Raphael; Lavaud, Jonathan; Plettinx, Cedric; Olivier, Cécile; Curry, Véronique; Boutonnat, Jean; Coll, Jean-Luc; Peyrin, Françoise; Josserand, Véronique; Bettega, Georges; Picart, Catherine

    2016-10-01

    The rapid and effective bone regeneration of large non-healing defects remains challenging. Bioactive proteins, such as bone morphogenetic protein (BMP)-2, are proved their osteoinductivity, but their clinical use is currently limited to collagen as biomaterial. Being able to deliver BMP-2 from any other biomaterial would broaden its clinical use. This work presents a novel means for repairing a critical size volumetric bone femoral defect in the rat by combining a osteoinductive surface coating (2D) to a polymeric scaffold (3D hollow tube) made of commercially-available PLGA. Using a polyelectrolyte film as BMP-2 carrier, we tune the amount of BMP-2 loaded in and released from the polyelectrolyte film coating over a large extent by controlling the film crosslinking level and initial concentration of BMP-2 in solution. Using microcomputed tomography and quantitative analysis of the regenerated bone growth kinetics, we show that the amount of newly formed bone and kinetics can be modulated: an effective and fast repair was obtained in 1-2 weeks in the best conditions, including complete defect bridging, formation of vascularized and mineralized bone tissue. Histological staining and high-resolution computed tomography revealed the presence of bone regeneration inside and around the tube with spatially distinct organization for trabecular-like and cortical bones. The amount of cortical bone and its thickness increased with the BMP-2 dose. In view of the recent developments in additive manufacturing techniques, this surface-coating technology may be applied in combination with various types of polymeric or metallic scaffolds to offer new perspectives of bone regeneration in personalized medicine. PMID:27454063

  12. Acyclic Cucurbit[n]uril-Type Molecular Container Enables Systemic Delivery of Effective Doses of Albendazole for Treatment of SK-OV-3 Xenograft Tumors.

    PubMed

    Hettiarachchi, Gaya; Samanta, Soumen K; Falcinelli, Shane; Zhang, Ben; Moncelet, Damien; Isaacs, Lyle; Briken, Volker

    2016-03-01

    Approximately, 40-70% of active pharmaceutical ingredients (API) are severely limited by their extremely poor aqueous solubility, and consequently, there is a high demand for excipients that can be used to formulate clinically relevant doses of these drug candidates. Here, proof-of-concept studies demonstrate the potential of our recently discovered acyclic cucurbit[n]uril-type molecular container Motor1 (M1) as a solubilizing agent for insoluble drugs. M1 did not induce significant rates of mutations in various Salmonella typhimurium test strains during the Ames test, suggesting low genotoxicity. M1 also has low risk of causing cardiac toxicity in humans since it did not inhibit the human Ether-à-go-go-Related Gene channel as tested on transfected CHO cell lines via patch clamp analysis. Albendazole (ABZ) is a widely used antihelminthic agent but that has also shown promising efficacy against cancerous cells in vitro. However, due to its low aqueous solubility (2.7 μM) and poor pharmacokinetics, ABZ is clinically limited as an anticancer agent. Here we investigated the potential of M1 as a solubilizing excipient for ABZ formulation. A pharmacokinetic study indicated that ABZ escapes the peritoneal cavity resulting in 78% absolute bioavailability, while its active intermediate metabolite, albendazole sulfoxide, achieved 43% absolute bioavailability. The daily dosing of 681 mg/kg M1 complexed with 3.2 mg/kg of ABZ for 14 days did not result in significant weight loss or pathology in Swiss Webster mice. In vivo efficacy studies using this M1·ABZ inclusion complex showed significant decreases in tumor growth rates and increases in survival of mice bearing SK-OV-3 xenograft tumors. In conclusion, we provide substantial new evidence demonstrating that M1 is a safe and efficient excipient that enables in vivo parenteral delivery of poorly water-soluble APIs. PMID:26756920

  13. Formulation and in Vitro Evaluation of Self-microemulsifying Drug Delivery System Containing Fixed-Dose Combination of Atorvastatin and Ezetimibe.

    PubMed

    Hwang, Kyu-Mok; Park, Shin-Ae; Kim, Ju-Young; Park, Chun-Woong; Rhee, Yun-Seok; Park, Eun-Seok

    2015-01-01

    This paper focuses on the development and physicochemical characterization of a self-microemulsifying drug delivery system (SMEDDS) containing a fixed-dose combination of atorvastatin (ATR) and ezetimibe (EZT). The solubility of both drugs was determined in excipient screening studies. Ternary-phase diagrams were drawn for 27 systems composed of different surfactants, cosurfactants, and oils at different surfactant-to-cosurfactant (S/CoS) ratios, and the system exhibiting the largest percentage area of the self-microemulsifying region was selected. The optimum oil ratio in the SMEDDS was selected by evaluating the mean droplet size of the resultant microemulsions. The underlying mechanism of the lower ATR loading capacity compared with EZT was elucidated by measurement of the zeta potential and UV absorption analysis. The results implied that ATR was located exclusively in the surfactant-cosurfactant layer, whereas EZT was located both in the microemulsion core and the surfactant-cosurfactant layer. In vitro dissolution studies showed that the SMEDDS had higher initial dissolution rates for both drugs when compared with marketed products. More importantly, EZT had a significantly increased dissolution profile in distilled water and pH 4.0 acetate buffer, implying enhanced bioavailability. PMID:26027466

  14. Independent dose calculations for commissioning, quality assurance and dose reconstruction of PBS proton therapy

    NASA Astrophysics Data System (ADS)

    Meier, G.; Besson, R.; Nanz, A.; Safai, S.; Lomax, A. J.

    2015-04-01

    Pencil beam scanning proton therapy allows the delivery of highly conformal dose distributions by delivering several thousand pencil beams. These beams have to be individually optimised and accurately delivered requiring a significant quality assurance workload. In this work we describe a toolkit for independent dose calculations developed at Paul Scherrer Institut which allows for dose reconstructions at several points in the treatment workflow. Quality assurance based on reconstructed dose distributions was shown to be favourable to pencil beam by pencil beam comparisons for the detection of delivery uncertainties and estimation of their effects. Furthermore the dose reconstructions were shown to have a sensitivity of the order of or higher than the measurements currently employed in the clinical verification procedures. The design of the independent dose calculation tool allows for a high modifiability of the dose calculation parameters (e.g. depth dose profiles, angular spatial distributions) allowing for a safe environment outside of the clinical treatment planning system for investigating the effect of such parameters on the resulting dose distributions and thus distinguishing between different contributions to measured dose deviations. The presented system could potentially reduce the amount of patient-specific quality assurance measurements which currently constitute a bottleneck in the clinical workflow.

  15. Importance of novel drug delivery systems in herbal medicines.

    PubMed

    Devi, V Kusum; Jain, Nimisha; Valli, Kusum S

    2010-01-01

    Novel drug delivery system is a novel approach to drug delivery that addresses the limitations of the traditional drug delivery systems. Our country has a vast knowledge base of Ayurveda whose potential is only being realized in the recent years. However, the drug delivery system used for administering the herbal medicine to the patient is traditional and out-of-date, resulting in reduced efficacy of the drug. If the novel drug delivery technology is applied in herbal medicine, it may help in increasing the efficacy and reducing the side effects of various herbal compounds and herbs. This is the basic idea behind incorporating novel method of drug delivery in herbal medicines. Thus it is important to integrate novel drug delivery system and Indian Ayurvedic medicines to combat more serious diseases. For a long time herbal medicines were not considered for development as novel formulations owing to lack of scientific justification and processing difficulties, such as standardization, extraction and identification of individual drug components in complex polyherbal systems. However, modern phytopharmaceutical research can solve the scientific needs (such as determination of pharmacokinetics, mechanism of action, site of action, accurate dose required etc.) of herbal medicines to be incorporated in novel drug delivery system, such as nanoparticles, microemulsions, matrix systems, solid dispersions, liposomes, solid lipid nanoparticles and so on. This article summarizes various drug delivery technologies, which can be used for herbal actives together with some examples. PMID:22228938

  16. Rectal cancer delivery of radiotherapy in adequate time and with adequate dose is influenced by treatment center, treatment schedule, and gender and is prognostic parameter for local control: Results of study CAO/ARO/AIO-94

    SciTech Connect

    Fietkau, Rainer . E-mail: rainer.fietkau@med.uni-rostock.de; Roedel, Claus; Hohenberger, Werner; Raab, Rudolf; Hess, Clemens; Liersch, Torsten; Becker, Heinz; Wittekind, Christian; Hutter, Matthias; Hager, Eva; Karstens, Johann; Ewald, Hermann; Christen, Norbert; Jagoditsch, Michael; Martus, Peter; Sauer, Rolf

    2007-03-15

    Purpose: The impact of the delivery of radiotherapy (RT) on treatment results in rectal cancer patients is unknown. Methods and Materials: The data from 788 patients with rectal cancer treated within the German CAO/AIO/ARO-94 phase III trial were analyzed concerning the impact of the delivery of RT (adequate RT: minimal radiation RT dose delivered, 4300 cGy for neoadjuvant RT or 4700 cGy for adjuvant RT; completion of RT in <44 days for neoadjuvant RT or <49 days for adjuvant RT) in different centers on the locoregional recurrence rate (LRR) and disease-free survival (DFS) at 5 years. The LRR, DFS, and delivery of RT were analyzed as endpoints in multivariate analysis. Results: A significant difference was found between the centers and the delivery of RT. The overall delivery of RT was a prognostic factor for the LRR (no RT, 29.6% {+-} 7.8%; inadequate RT, 21.2% {+-} 5.6%; adequate RT, 6.8% {+-} 1.4%; p = 0.0001) and DFS (no RT, 55.1% {+-} 9.1%; inadequate RT, 57.4% {+-} 6.3%; adequate RT, 69.1% {+-} 2.3%; p = 0.02). Postoperatively, delivery of RT was a prognostic factor for LRR on multivariate analysis (together with pathologic stage) but not for DFS (independent parameters, pathologic stage and age). Preoperatively, on multivariate analysis, pathologic stage, but not delivery of RT, was an independent prognostic parameter for LRR and DFS (together with adequate chemotherapy). On multivariate analysis, the treatment center, treatment schedule (neoadjuvant vs. adjuvant RT), and gender were prognostic parameters for adequate RT. Conclusion: Delivery of RT should be regarded as a prognostic factor for LRR in rectal cancer and is influenced by the treatment center, treatment schedule, and patient gender.

  17. PRELIMINARY COMMUNICATION: Abutment region dosimetry for sequential arc IMRT delivery

    NASA Astrophysics Data System (ADS)

    Low, Daniel A.; Mutic, Sasa

    1997-07-01

    Arc-based intensity modulated radiation therapy (IMRT) planning and delivery is available as a commercial product (Nomos Corp.). The dose distribution is delivered to 1.68 cm thick regions, and the patient moved in a precise manner between treatments. Assuming accurate patient positioning, the abutment region dose distribution near the gantry isocentre is delivered with no undesired dose heterogeneities. However, for regions far from the isocentre, the dose distribution may exhibit high- or low-dose regions due to uncompensated beam divergence for arc treatments of less than gantry angle length. A study has been initiated to characterize abutment region dose distribution heterogeneities for sequential arc IMRT delivery. Five dose distributions were optimized, each using 8 cm diameter target volumes at different distances from the isocentre, and the arc delivery limited to symmetric about the vertical axis. The target lengths were sufficient to require a treatment consisting of five couch positions, yielding four abutment regions. The dose within the abutment regions was measured using film and analysed as a function of off-axis position along both the vertical and horizontal directions. Little dependence on the dose heterogeneity was seen along the horizontal axis passing through the isocentre. However, the abutment regions along the vertical axis contained 15% low and 7% high doses at 7 cm above and below the isocentre respectively. This dose heterogeneity is not predicted by the current clinical release of the treatment planning software due to limitations of the dose calculation algorithm. The intensity of dose heterogeneity is considered sufficient to warrant further study.

  18. Safety and Efficacy of High Dose AAV9 Encoding SERCA2a Delivered by Molecular Cardiac Surgery with Recirculating Delivery (MCARD) in Ovine Ischemic Cardiomyopathy

    PubMed Central

    Katz, Michael G.; Fargnoli, Anthony S.; Williams, Richard D.; Steuerwald, Nury M.; Isidro, Alice; Ivanina, Anna V.; Sokolova, Inna M.; Bridges, Charles R.

    2014-01-01

    Objective Therapeutic safety and efficacy are the basic prerequisites for clinical gene therapy. Herein we investigate the effect of high dose MCARD-mediated AAV9/SERCA2a gene delivery on clinical parameters, oxidative stress, humoral and cellular immune response, and cardiac remodeling. Methods Ischemic cardiomyopathy was generated in a sheep model. Then animals were assigned to one of two groups: control (n=10), and study (MCARD, n=6). The control had no intervention while the study group received 1014 gc of AAV9.SERCA2a 4 weeks post-infarction. Results Our ischemic model produced reliable infarcts leading to heart failure. The baseline ejection fraction (EF) in the MCARD group was 57.6±1.6 vs. 61.2±1.9 in the control group, (p>0.05). Twelve weeks post-infarction, the MCARD group had superior LV function compared to control: stroke volume index (46.6±1.8 vs. 35.8±2.5 mL/m2, p<0.05), EF (46.2±1.9 vs. 38.7±2.5%, p<0.05); and LV end systolic and end diastolic dimensions [41.3±1.7 vs. 48.2±1.4 mm; 51.2±1.5 vs. 57.6±1.7 mm], p<0.05. Markers of oxidative stress were significantly reduced in the infarct zone in the MCARD group. There was no positive T cell mediated immune response in the MCARD group at any time point. Myocyte hypertrophy was also significantly attenuated in the MCARD group compared to control. Conclusions Cardiac overexpression of the SERCA2a gene via MCARD is a safe therapeutic intervention. It significantly improves LV function, decreases markers of oxidative stress, abrogates myocyte hypertrophy, arrests remodeling and does not induce a T cell mediated immune response. PMID:25037619

  19. Delivery validation of an automated modulated electron radiotherapy plan

    SciTech Connect

    Connell, T. Papaconstadopoulos, P.; Alexander, A.; Serban, M.; Devic, S.; Seuntjens, J.

    2014-06-15

    Purpose: Modulated electron radiation therapy (MERT) represents an active area of interest that offers the potential to improve healthy tissue sparing in treatment of certain cancer cases. Challenges remain however in accurate beamlet dose calculation, plan optimization, collimation method, and delivery accuracy. In this work, the authors investigate the accuracy and efficiency of an end-to-end MERT plan and automated delivery method. Methods: Treatment planning was initiated on a previously treated whole breast irradiation case including an electron boost. All dose calculations were performed using Monte Carlo methods and beam weights were determined using a research-based treatment planning system capable of inverse optimization. The plan was delivered to radiochromic film placed in a water equivalent phantom for verification, using an automated motorized tertiary collimator. Results: The automated delivery, which covered four electron energies, 196 subfields, and 6183 total MU was completed in 25.8 min, including 6.2 min of beam-on time. The remainder of the delivery time was spent on collimator leaf motion and the automated interfacing with the accelerator in service mode. Comparison of the planned and delivered film dose gave 3%/3mm gamma pass rates of 62.1%, 99.8%, 97.8%, 98.3%, and 98.7% for the 9, 12, 16, and 20 MeV, and combined energy deliveries, respectively. Delivery was also performed with a MapCHECK device and resulted in 3%/3  mm gamma pass rates of 88.8%, 86.1%, 89.4%, and 94.8% for the 9, 12, 16, and 20 MeV energies, respectively. Conclusions: Results of the authors’ study showed that an accurate delivery utilizing an add-on tertiary electron collimator is possible using Monte Carlo calculated plans and inverse optimization, which brings MERT closer to becoming a viable option for physicians in treating superficial malignancies.

  20. Sci—Thur PM: Planning and Delivery — 03: Automated delivery and quality assurance of a modulated electron radiation therapy plan

    SciTech Connect

    Connell, T; Papaconstadopoulos, P; Alexander, A; Serban, M; Devic, S; Seuntjens, J

    2014-08-15

    Modulated electron radiation therapy (MERT) offers the potential to improve healthy tissue sparing through increased dose conformity. Challenges remain, however, in accurate beamlet dose calculation, plan optimization, collimation method and delivery accuracy. In this work, we investigate the accuracy and efficiency of an end-to-end MERT plan and automated-delivery workflow for the electron boost portion of a previously treated whole breast irradiation case. Dose calculations were performed using Monte Carlo methods and beam weights were determined using a research-based treatment planning system capable of inverse optimization. The plan was delivered to radiochromic film placed in a water equivalent phantom for verification, using an automated motorized tertiary collimator. The automated delivery, which covered 4 electron energies, 196 subfields and 6183 total MU was completed in 25.8 minutes, including 6.2 minutes of beam-on time with the remainder of the delivery time spent on collimator leaf motion and the automated interfacing with the accelerator in service mode. The delivery time could be reduced by 5.3 minutes with minor electron collimator modifications and the beam-on time could be reduced by and estimated factor of 2–3 through redesign of the scattering foils. Comparison of the planned and delivered film dose gave 3%/3 mm gamma pass rates of 62.1, 99.8, 97.8, 98.3, and 98.7 percent for the 9, 12, 16, 20 MeV, and combined energy deliveries respectively. Good results were also seen in the delivery verification performed with a MapCHECK 2 device. The results showed that accurate and efficient MERT delivery is possible with current technologies.

  1. MEMS: Enabled Drug Delivery Systems.

    PubMed

    Cobo, Angelica; Sheybani, Roya; Meng, Ellis

    2015-05-01

    Drug delivery systems play a crucial role in the treatment and management of medical conditions. Microelectromechanical systems (MEMS) technologies have allowed the development of advanced miniaturized devices for medical and biological applications. This Review presents the use of MEMS technologies to produce drug delivery devices detailing the delivery mechanisms, device formats employed, and various biomedical applications. The integration of dosing control systems, examples of commercially available microtechnology-enabled drug delivery devices, remaining challenges, and future outlook are also discussed. PMID:25703045

  2. Total Body Irradiation, Toward Optimal Individual Delivery: Dose Evaluation With Metal Oxide Field Effect Transistors, Thermoluminescence Detectors, and a Treatment Planning System

    SciTech Connect

    Bloemen-van Gurp, Esther J. Mijnheer, Ben J.; Verschueren, Tom A.M.; Lambin, Philippe

    2007-11-15

    Purpose: To predict the three-dimensional dose distribution of our total body irradiation technique, using a commercial treatment planning system (TPS). In vivo dosimetry, using metal oxide field effect transistors (MOSFETs) and thermoluminescence detectors (TLDs), was used to verify the calculated dose distributions. Methods and Materials: A total body computed tomography scan was performed and loaded into our TPS, and a three-dimensional-dose distribution was generated. In vivo dosimetry was performed at five locations on the patient. Entrance and exit dose values were converted to midline doses using conversion factors, previously determined with phantom measurements. The TPS-predicted dose values were compared with the MOSFET and TLD in vivo dose values. Results: The MOSFET and TLD dose values agreed within 3.0% and the MOSFET and TPS data within 0.5%. The convolution algorithm of the TPS, which is routinely applied in the clinic, overestimated the dose in the lung region. Using a superposition algorithm reduced the calculated lung dose by approximately 3%. The dose inhomogeneity, as predicted by the TPS, can be reduced using a simple intensity-modulated radiotherapy technique. Conclusions: The use of a TPS to calculate the dose distributions in individual patients during total body irradiation is strongly recommended. Using a TPS gives good insight of the over- and underdosage in a patient and the influence of patient positioning on dose homogeneity. MOSFETs are suitable for in vivo dosimetry purposes during total body irradiation, when using appropriate conversion factors. The MOSFET, TLD, and TPS results agreed within acceptable margins.

  3. Experimental evaluation of actual delivered dose using mega-voltage cone-beam CT and direct point dose measurement

    SciTech Connect

    Matsubara, Kana; Kohno, Ryosuke; Nishioka, Shie; Shibuya, Toshiyuki; Ariji, Takaki; Akimoto, Tetsuo; Saitoh, Hidetoshi

    2013-07-01

    Radiation therapy in patients is planned by using computed tomography (CT) images acquired before start of the treatment course. Here, tumor shrinkage or weight loss or both, which are common during the treatment course for patients with head-and-neck (H and N) cancer, causes unexpected differences from the plan, as well as dose uncertainty with the daily positional error of patients. For accurate clinical evaluation, it is essential to identify these anatomical changes and daily positional errors, as well as consequent dosimetric changes. To evaluate the actual delivered dose, the authors proposed direct dose measurement and dose calculation with mega-voltage cone-beam CT (MVCBCT). The purpose of the present study was to experimentally evaluate dose calculation by MVCBCT. Furthermore, actual delivered dose was evaluated directly with accurate phantom setup. Because MVCBCT has CT-number variation, even when the analyzed object has a uniform density, a specific and simple CT-number correction method was developed and applied for the H and N site of a RANDO phantom. Dose distributions were calculated with the corrected MVCBCT images of a cylindrical polymethyl methacrylate phantom. Treatment processes from planning to beam delivery were performed for the H and N site of the RANDO phantom. The image-guided radiation therapy procedure was utilized for the phantom setup to improve measurement reliability. The calculated dose in the RANDO phantom was compared to the measured dose obtained by metal-oxide-semiconductor field-effect transistor detectors. In the polymethyl methacrylate phantom, the calculated and measured doses agreed within about +3%. In the RANDO phantom, the dose difference was less than +5%. The calculated dose based on simulation-CT agreed with the measured dose within±3%, even in the region with a high dose gradient. The actual delivered dose was successfully determined by dose calculation with MVCBCT, and the point dose measurement with the image

  4. Benchmark Dose Modeling

    EPA Science Inventory

    Finite doses are employed in experimental toxicology studies. Under the traditional methodology, the point of departure (POD) value for low dose extrapolation is identified as one of these doses. Dose spacing necessarily precludes a more accurate description of the POD value. ...

  5. Relationship of glucose values to sliding scale insulin (correctional insulin) dose delivery and meal time in acute care patients with diabetes mellitus.

    PubMed

    Trotter, Barbara; Conaway, Mark R; Burns, Suzanne M

    2013-01-01

    Findings of this study suggest the traditional sliding scale insulin (SSI) method does not improve target glucose values among adult medical inpatients. Timing of blood glucose (BC) measurement does affect the required SSI dose. BC measurement and insulin dose administration should be accomplished immediately prior to mealtime. PMID:23802496

  6. Dose reconstruction for intensity-modulated radiation therapy using a non-iterative method and portal dose image

    NASA Astrophysics Data System (ADS)

    Yeo, Inhwan Jason; Jung, Jae Won; Chew, Meng; Kim, Jong Oh; Wang, Brian; Di Biase, Steven; Zhu, Yunping; Lee, Dohyung

    2009-09-01

    A straightforward and accurate method was developed to verify the delivery of intensity-modulated radiation therapy (IMRT) and to reconstruct the dose in a patient. The method is based on a computational algorithm that linearly describes the physical relationship between beamlets and dose-scoring voxels in a patient and the dose image from an electronic portal imaging device (EPID). The relationship is expressed in the form of dose response functions (responses) that are quantified using Monte Carlo (MC) particle transport techniques. From the dose information measured by the EPID the received patient dose is reconstructed by inversely solving the algorithm. The unique and novel non-iterative feature of this algorithm sets it apart from many existing dose reconstruction methods in the literature. This study presents the algorithm in detail and validates it experimentally for open and IMRT fields. Responses were first calculated for each beamlet of the selected fields by MC simulation. In-phantom and exit film dosimetry were performed on a flat phantom. Using the calculated responses and the algorithm, the exit film dose was used to inversely reconstruct the in-phantom dose, which was then compared with the measured in-phantom dose. The dose comparison in the phantom for all irradiated fields showed a pass rate of higher than 90% dose points given the criteria of dose difference of 3% and distance to agreement of 3 mm.

  7. Impact of conventional fractionated RT to pelvic lymph nodes and dose-escalated hypofractionated RT to prostate gland using IMRT treatment delivery in high-risk prostate cancer

    NASA Astrophysics Data System (ADS)

    Pervez, Nadeem

    Prostate cancer is the most common cancer among Canadian men. The standard treatment in high-risk category is radical radiation, with androgen suppression treatment (AST). Significant disease progression is reported despite this approach. Radiation dose escalation has been shown to improve disease-free survival; however, it results in higher toxicities. Hypofractionated radiation schedules (larger dose each fraction in shorter overall treatment time) are expected to deliver higher biological doses. A hypofractionated scheme was used in this study to escalate radiation doses with AST. Treatment was well tolerated acutely. Early results of self-administered quality of life reported by patients shows a decrease in QOL which is comparable to other treatment schedules. Significant positional variation of the prostate was observed during treatment. Therefore, we suggest daily target verification to avoid a target miss. Initial late effects are reasonable and early treatment outcomes are promising. Longer follow-up is required for full outcomes assessments.

  8. Animal Models of Depression and Drug Delivery with Food as an Effective Dosing Method: Evidences from Studies with Celecoxib and Dicholine Succinate

    PubMed Central

    Costa-Nunes, João P.; Cline, Brandon H.; Araújo-Correia, Margarida; Valença, Andreia; Markova, Natalyia; Dolgov, Oleg; Kubatiev, Aslan; Yeritsyan, Naira; Steinbusch, Harry W. M.

    2015-01-01

    Multiple models of human neuropsychiatric pathologies have been generated during the last decades which frequently use chronic dosing. Unfortunately, some drug administration methods may result in undesirable effects creating analysis confounds hampering model validity and preclinical assay outcomes. Here, automated analysis of floating behaviour, a sign of a depressive-like state, revealed that mice, subjected to a three-week intraperitoneal injection regimen, had increased floating. In order to probe an alternative dosing design that would preclude this effect, we studied the efficacy of a low dose of the antidepressant imipramine (7 mg/kg/day) delivered via food pellets. Antidepressant action for this treatment was found while no other behavioural effects were observed. We further investigated the potential efficacy of chronic dosing via food pellets by testing the antidepressant activity of new drug candidates, celecoxib (30 mg/kg/day) and dicholine succinate (50 mg/kg/day), against standard antidepressants, imipramine (7 mg/kg/day) and citalopram (15 mg/kg/day), utilizing the forced swim and tail suspension tests. Antidepressant effects of these compounds were found in both assays. Thus, chronic dosing via food pellets is efficacious in small rodents, even with a low drug dose design, and can prevail against potential confounds in translational research within depression models applicable to adverse chronic invasive pharmacotherapies. PMID:26064929

  9. Animal Models of Depression and Drug Delivery with Food as an Effective Dosing Method: Evidences from Studies with Celecoxib and Dicholine Succinate.

    PubMed

    Costa-Nunes, João P; Cline, Brandon H; Araújo-Correia, Margarida; Valença, Andreia; Markova, Natalyia; Dolgov, Oleg; Kubatiev, Aslan; Yeritsyan, Naira; Steinbusch, Harry W M; Strekalova, Tatyana

    2015-01-01

    Multiple models of human neuropsychiatric pathologies have been generated during the last decades which frequently use chronic dosing. Unfortunately, some drug administration methods may result in undesirable effects creating analysis confounds hampering model validity and preclinical assay outcomes. Here, automated analysis of floating behaviour, a sign of a depressive-like state, revealed that mice, subjected to a three-week intraperitoneal injection regimen, had increased floating. In order to probe an alternative dosing design that would preclude this effect, we studied the efficacy of a low dose of the antidepressant imipramine (7 mg/kg/day) delivered via food pellets. Antidepressant action for this treatment was found while no other behavioural effects were observed. We further investigated the potential efficacy of chronic dosing via food pellets by testing the antidepressant activity of new drug candidates, celecoxib (30 mg/kg/day) and dicholine succinate (50 mg/kg/day), against standard antidepressants, imipramine (7 mg/kg/day) and citalopram (15 mg/kg/day), utilizing the forced swim and tail suspension tests. Antidepressant effects of these compounds were found in both assays. Thus, chronic dosing via food pellets is efficacious in small rodents, even with a low drug dose design, and can prevail against potential confounds in translational research within depression models applicable to adverse chronic invasive pharmacotherapies. PMID:26064929

  10. Online image-guided intensity-modulated radiotherapy for prostate cancer: How much improvement can we expect? A theoretical assessment of clinical benefits and potential dose escalation by improving precision and accuracy of radiation delivery

    SciTech Connect

    Ghilezan, Michel; Yan Di . E-mail: dyan@beaumont.edu; Liang Jian; Jaffray, David; Wong, John; Martinez, Alvaro

    2004-12-01

    Purpose: To quantify the theoretical benefit, in terms of improvement in precision and accuracy of treatment delivery and in dose increase, of using online image-guided intensity-modulated radiotherapy (IG-IMRT) performed with onboard cone-beam computed tomography (CT), in an ideal setting of no intrafraction motion/deformation, in the treatment of prostate cancer. Methods and materials: Twenty-two prostate cancer patients treated with conventional radiotherapy underwent multiple serial CT scans (median 18 scans per patient) during their treatment. We assumed that these data sets were equivalent to image sets obtainable by an onboard cone-beam CT. Each patient treatment was simulated with conventional IMRT and online IG-IMRT separately. The conventional IMRT plan was generated on the basis of pretreatment CT, with a clinical target volume to planning target volume (CTV-to-PTV) margin of 1 cm, and the online IG-IMRT plan was created before each treatment fraction on the basis of the CT scan of the day, without CTV-to-PTV margin. The inverse planning process was similar for both conventional IMRT and online IG-IMRT. Treatment dose for each organ of interest was quantified, including patient daily setup error and internal organ motion/deformation. We used generalized equivalent uniform dose (EUD) to compare the two approaches. The generalized EUD (percentage) of each organ of interest was scaled relative to the prescription dose at treatment isocenter for evaluation and comparison. On the basis of bladder wall and rectal wall EUD, a dose-escalation coefficient was calculated, representing the potential increment of the treatment dose achievable with online IG-IMRT as compared with conventional IMRT. Results: With respect to radiosensitive tumor, the average EUD for the target (prostate plus seminal vesicles) was 96.8% for conventional IMRT and 98.9% for online IG-IMRT, with standard deviations (SDs) of 5.6% and 0.7%, respectively (p < 0.0001). The average EUDs of

  11. Application of monodirectional Janus patch to oromucosal delivery system.

    PubMed

    You, Jae Bem; Choi, Ah Young; Baek, Jieung; Oh, Myung Seok; Im, Sung Gap; Lee, Kyung Eun; Gwak, Hye Sun

    2015-10-28

    Drug delivery through mucosae has received huge research attention owing to its advantageous characteristics such as accurate dose control and the avoidance of premature metabolism of vulnerable drugs by oral administration. However, body fluid in mucosae may dissolve the drug, releasing it to unwanted directions. Here, a Janus drug delivery patch with monodirectional diffusion property is devised to deliver drugs efficiently and to overcome the issue of unwanted drug release. A polyester fabric is coated with a hydrophobic polymer, poly(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10-heptadecafluorodecyl methacrylate), via initiated chemical vapor deposition. Subsequently, hydrophilicity is rendered selectively on one surface by base-catalyzed hydrolysis to obtain a Janus substrate with both hydrophobic and hydrophilic surfaces. The hydrophilic surface of the Janus substrate is further coated with resveratrol-loaded hydrogel to produce a Janus drug delivery patch. The fabricated patch efficiently blocks fluid penetration from one side to the other in mucous environment. Delivery of resveratrol through hairless mouse skin and reconstructed human mucosae using Janus patch shows higher permeation flux compared to bare control patch. The Janus drug delivery patch shown in this study can be a useful tool for efficient transmucosal delivery of various kinds of drugs. PMID:26346613

  12. SU-C-BRB-06: Utilizing 3D Scanner and Printer for Dummy Eye-Shield: Artifact-Free CT Images of Tungsten Eye-Shield for Accurate Dose Calculation

    SciTech Connect

    Park, J; Lee, J; Kim, H; Kim, I; Ye, S

    2015-06-15

    Purpose: To evaluate the effect of a tungsten eye-shield on the dose distribution of a patient. Methods: A 3D scanner was used to extract the dimension and shape of a tungsten eye-shield in the STL format. Scanned data was transferred into a 3D printer. A dummy eye shield was then produced using bio-resin (3D systems, VisiJet M3 Proplast). For a patient with mucinous carcinoma, the planning CT was obtained with the dummy eye-shield placed on the patient’s right eye. Field shaping of 6 MeV was performed using a patient-specific cerrobend block on the 15 x 15 cm{sup 2} applicator. The gantry angle was 330° to cover the planning target volume near by the lens. EGS4/BEAMnrc was commissioned from our measurement data from a Varian 21EX. For the CT-based dose calculation using EGS4/DOSXYZnrc, the CT images were converted to a phantom file through the ctcreate program. The phantom file had the same resolution as the planning CT images. By assigning the CT numbers of the dummy eye-shield region to 17000, the real dose distributions below the tungsten eye-shield were calculated in EGS4/DOSXYZnrc. In the TPS, the CT number of the dummy eye-shield region was assigned to the maximum allowable CT number (3000). Results: As compared to the maximum dose, the MC dose on the right lens or below the eye shield area was less than 2%, while the corresponding RTP calculated dose was an unrealistic value of approximately 50%. Conclusion: Utilizing a 3D scanner and a 3D printer, a dummy eye-shield for electron treatment can be easily produced. The artifact-free CT images were successfully incorporated into the CT-based Monte Carlo simulations. The developed method was useful in predicting the realistic dose distributions around the lens blocked with the tungsten shield.

  13. Therapeutic potential of targeted multifunctional nanocomplex co-delivery of siRNA and low-dose doxorubicin in breast cancer.

    PubMed

    Dong, Dawen; Gao, Wei; Liu, Yujie; Qi, Xian-Rong

    2015-04-10

    Malignant tumors remain a major health burden throughout the world, and effective therapeutic strategies are urgently needed. Combining gene therapy with chemotherapeutics in a single delivery system is more effective than co-treatment of cancer with individual delivery systems carrying either gene or drug. In this study, a multifunctional folate-decorated and pH-responsive PHD/PPF/siVEGF nanocomplex is developed via a self-assembly process utilizing ternary pre-functionalized polymers with vascular endothelial growth factor targeted siRNA. Antitumor effects of the combination therapy are evaluated in both in vitro and in vivo orthotopic xenograft models of breast cancer with systemic administration. The improved therapeutic response was supported by the observation of over 70% and 55% down-regulation of VEGF mRNA expressed in vitro and in vivo, effective antiproliferation and inhibition of tumor spheroids in vitro, significant decrease in tumor microvessel density in vivo, dramatic increase in life span of mice with a tumor xenograft and a decrease in toxicity in vivo. In addition, the current studies demonstrated the potential of combination of antiangiogenic therapy of siVEGF and killing off tumor cells of DOX, with the incorporation of tumor microenvironment sensitivity and target modified into a single nanoparticulate formulation for profound therapeutic effect. PMID:25592040

  14. Low–dose RUTF protocol and improved service delivery lead to good programme outcomes in the treatment of uncomplicated SAM: a programme report from Myanmar

    PubMed Central

    James, Philip T; Van den Briel, Natalie; Rozet, Aurélie; Israël, Anne-Dominique; Fenn, Bridget; Navarro-Colorado, Carlos

    2015-01-01

    The treatment of uncomplicated severe acute malnutrition (SAM) requires substantial amounts of ready-to-use therapeutic food (RUTF). In 2009, Action Contre la Faim anticipated a shortfall of RUTF for their nutrition programme in Myanmar. A low-dose RUTF protocol to treat children with uncomplicated SAM was adopted. In this protocol, RUTF was dosed according to beneficiary's body weight, until the child reached a Weight-for-Height z-score of ≥−3 and mid-upper arm circumference ≥110 mm. From this point, the child received a fixed quantity of RUTF per day, independent of body weight until discharge. Specific measures were implemented as part of this low-dose RUTF protocol in order to improve service quality and beneficiary support. We analysed individual records of 3083 children treated from July 2009 to January 2010. Up to 90.2% of children recovered, 2.0% defaulted and 0.9% were classified as non-responders. No deaths were recorded. Among children who recovered, median [IQR] length of stay and weight gain were 42 days [28; 56] and 4.0 g kg–1 day–1 [3.0; 5.7], respectively. Multivariable logistic regression showed that children older than 48 months had higher odds of non-response to treatment than younger children (adjusted odds ratio: 3.51, 95% CI: 1.67–7.42). Our results indicate that a low-dose RUTF protocol, combined with specific measures to ensure good service quality and beneficiary support, was successful in treating uncomplicated SAM in this setting. This programmatic experience should be validated by randomised studies aiming to test, quantify and attribute the effect of the protocol adaptation and programme improvements presented here. PMID:25850698

  15. Low-dose RUTF protocol and improved service delivery lead to good programme outcomes in the treatment of uncomplicated SAM: a programme report from Myanmar.

    PubMed

    James, Philip T; Van den Briel, Natalie; Rozet, Aurélie; Israël, Anne-Dominique; Fenn, Bridget; Navarro-Colorado, Carlos

    2015-10-01

    The treatment of uncomplicated severe acute malnutrition (SAM) requires substantial amounts of ready-to-use therapeutic food (RUTF). In 2009, Action Contre la Faim anticipated a shortfall of RUTF for their nutrition programme in Myanmar. A low-dose RUTF protocol to treat children with uncomplicated SAM was adopted. In this protocol, RUTF was dosed according to beneficiary's body weight, until the child reached a Weight-for-Height z-score of ≥-3 and mid-upper arm circumference ≥110 mm. From this point, the child received a fixed quantity of RUTF per day, independent of body weight until discharge. Specific measures were implemented as part of this low-dose RUTF protocol in order to improve service quality and beneficiary support. We analysed individual records of 3083 children treated from July 2009 to January 2010. Up to 90.2% of children recovered, 2.0% defaulted and 0.9% were classified as non-responders. No deaths were recorded. Among children who recovered, median [IQR] length of stay and weight gain were 42 days [28; 56] and 4.0 g kg(-1) day(-1) [3.0; 5.7], respectively. Multivariable logistic regression showed that children older than 48 months had higher odds of non-response to treatment than younger children (adjusted odds ratio: 3.51, 95% CI: 1.67-7.42). Our results indicate that a low-dose RUTF protocol, combined with specific measures to ensure good service quality and beneficiary support, was successful in treating uncomplicated SAM in this setting. This programmatic experience should be validated by randomised studies aiming to test, quantify and attribute the effect of the protocol adaptation and programme improvements presented here. PMID:25850698

  16. Dose Imaging Detectors for Radiotherapy Based on Gas Electron Multipliers

    PubMed Central

    Klyachko, A.V.; Friesel, D.L.; Kline, C.; Liechty, J.; Nichiporov, D.F.; Solberg, K.A.

    2010-01-01

    New techniques in charged particle therapy and widespread use of modern dynamic beam delivery systems demand new beam monitoring devices as well as accurate 2D dosimetry systems to verify the delivered dose distribution. We are developing dose imaging detectors based on gas electron multipliers (GEM) with the goal of improving dose measurement linearity, position and timing resolution, and to ultimately allow pre-treatment verification of dose distributions and dose delivery monitoring employing scanning beam technology. A prototype 10×10 cm2 double-GEM detector has been tested in the 205 MeV proton beam using electronic and optical readout modes. Preliminary results with electronic cross-strip readout demonstrate fast response and single-pixel (4 mm) position resolution. In optical readout mode, the line spread function of the detector was found to have σ=0.7 mm. In both readout modes, the detector response was linear up to dose rates of 50 Gy/min, with adequate representation of the Bragg peak in depth-dose profile measurements. PMID:21528010

  17. Dose profile measurements during respiratory-gated lung stereotactic radiotherapy: A phantom study

    NASA Astrophysics Data System (ADS)

    Jong, W. L.; Wong, J. H. D.; Ng, K. H.; Ung, N. M.

    2016-03-01

    During stereotactic body radiotherapy, high radiation dose (∼60 Gy) is delivered to the tumour in small fractionation regime. In this study, the dosimetric characteristics were studied using radiochromic film during respiratory-gated and non-gated lung stereotactic body radiotherapy (SBRT). Specifically, the effect of respiratory cycle and amplitude, as well as gating window on the dosimetry were studied. In this study, the dose profiles along the irradiated area were measured. The dose profiles for respiratory-gated radiation delivery with different respiratory or tumour motion amplitudes, gating windows and respiratory time per cycle were in agreement with static radiation delivery. The respiratory gating system was able to deliver the radiation dose accurately (±1.05 mm) in the longitudinal direction. Although the treatment time for respiratory-gated SBRT was prolonged, this approach can potentially reduce the margin for internal tumour volume without compromising the tumour coverage. In addition, the normal tissue sparing effect can be improved.

  18. How much does it cost to get a dose of vaccine to the service delivery location? Empirical evidence from Vietnam's Expanded Program on Immunization.

    PubMed

    Mvundura, Mercy; Kien, Vu Duy; Nga, Nguyen Tuyet; Robertson, Joanie; Cuong, Nguyen Van; Tung, Ho Thanh; Hong, Duong Thi; Levin, Carol

    2014-02-01

    Few studies document the costs of operating vaccine supply chains, but decision-makers need this information to inform cost projections for investments to accommodate new vaccine introduction. This paper presents empirical estimates of vaccine supply chain costs for Vietnam's Expanded Program on Immunization (EPI) for routine vaccines at each level of the supply chain, before and after the introduction of the pentavalent vaccine. We used micro-costing methods to collect resource-use data associated with storage and transportation of vaccines and immunization supplies at the national store, the four regional stores, and a sample of provinces, districts, and commune health centers. We collected stock ledger data on the total number of doses of vaccines handled by each facility during the assessment year. Total supply chain costs were estimated at approximately US$65,000 at the national store and an average of US$39,000 per region, US$5800 per province, US$2200 per district, and US$300 per commune health center. Across all levels, cold chain equipment capital costs and labor were the largest drivers of costs. The cost per dose delivered was estimated at US$0.19 before the introduction of pentavalent and US$0.24 cents after introduction. At commune health centers, supply chain costs were 104% of the value of vaccines before introduction of pentavalent vaccine and 24% after introduction, mainly due to the higher price per dose of the pentavalent vaccine. The aggregated costs at the last tier of the health system can be substantial because of the large number of facilities. Even in countries with high-functioning systems, empirical evidence on current costs from all levels of the system can help estimate resource requirements for expanding and strengthening resources to meet future immunization program needs. Other low- and middle-income countries can benefit from similar studies, in view of new vaccine introductions that will put strains on existing systems. PMID

  19. Curtailing patient-specific IMRT QA procedures from 2D dose error distribution.

    PubMed

    Kurosu, Keita; Sumida, Iori; Mizuno, Hirokazu; Otani, Yuki; Oda, Michio; Isohashi, Fumiaki; Seo, Yuji; Suzuki, Osamu; Ogawa, Kazuhiko

    2016-06-01

    A patient-specific quality assurance (QA) test is conducted to verify the accuracy of dose delivery. It generally consists of three verification processes: the absolute point dose difference, the planar dose differences at each gantry angle, and the planar dose differences by 3D composite irradiation. However, this imposes a substantial workload on medical physicists. The objective of this study was to determine whether our novel method that predicts the 3D delivered dose allows certain patient-specific IMRT QAs to be curtailed. The object was IMRT QA for the pelvic region with regard to point dose and composite planar dose differences. We compared measured doses, doses calculated in the treatment planning system, and doses predicted by in-house software. The 3D predicted dose was reconstructed from the per-field measurement by incorporating the relative dose error distribution into the original dose grid of each beam. All point dose differences between the measured and the calculated dose were within ±3%, whereas 93.3% of them between the predicted and the calculated dose were within ±3%. As for planar dose differences, the gamma passing rates between the calculated and the predicted dose were higher than those between the calculated and the measured dose. Comparison and statistical analysis revealed a correlation between the predicted and the measured dose with regard to both point dose and planar dose differences. We concluded that the prediction-based approach is an accurate substitute for the conventional measurement-based approach in IMRT QA for the pelvic region. Our novel approach will help medical physicists save time on IMRT QA. PMID:26661854

  20. Curtailing patient-specific IMRT QA procedures from 2D dose error distribution

    PubMed Central

    Kurosu, Keita; Sumida, Iori; Mizuno, Hirokazu; Otani, Yuki; Oda, Michio; Isohashi, Fumiaki; Seo, Yuji; Suzuki, Osamu; Ogawa, Kazuhiko

    2016-01-01

    A patient-specific quality assurance (QA) test is conducted to verify the accuracy of dose delivery. It generally consists of three verification processes: the absolute point dose difference, the planar dose differences at each gantry angle, and the planar dose differences by 3D composite irradiation. However, this imposes a substantial workload on medical physicists. The objective of this study was to determine whether our novel method that predicts the 3D delivered dose allows certain patient-specific IMRT QAs to be curtailed. The object was IMRT QA for the pelvic region with regard to point dose and composite planar dose differences. We compared measured doses, doses calculated in the treatment planning system, and doses predicted by in-house software. The 3D predicted dose was reconstructed from the per-field measurement by incorporating the relative dose error distribution into the original dose grid of each beam. All point dose differences between the measured and the calculated dose were within ±3%, whereas 93.3% of them between the predicted and the calculated dose were within ±3%. As for planar dose differences, the gamma passing rates between the calculated and the predicted dose were higher than those between the calculated and the measured dose. Comparison and statistical analysis revealed a correlation between the predicted and the measured dose with regard to both point dose and planar dose differences. We concluded that the prediction-based approach is an accurate substitute for the conventional measurement-based approach in IMRT QA for the pelvic region. Our novel approach will help medical physicists save time on IMRT QA. PMID:26661854

  1. Nanomedicine in pulmonary delivery

    PubMed Central

    Mansour, Heidi M; Rhee, Yun-Seok; Wu, Xiao

    2009-01-01

    The lung is an attractive target for drug delivery due to noninvasive administration via inhalation aerosols, avoidance of first-pass metabolism, direct delivery to the site of action for the treatment of respiratory diseases, and the availability of a huge surface area for local drug action and systemic absorption of drug. Colloidal carriers (ie, nanocarrier systems) in pulmonary drug delivery offer many advantages such as the potential to achieve relatively uniform distribution of drug dose among the alveoli, achievement of improved solubility of the drug from its own aqueous solubility, a sustained drug release which consequently reduces dosing frequency, improves patient compliance, decreases incidence of side effects, and the potential of drug internalization by cells. This review focuses on the current status and explores the potential of colloidal carriers (ie, nanocarrier systems) in pulmonary drug delivery with special attention to their pharmaceutical aspects. Manufacturing processes, in vitro/in vivo evaluation methods, and regulatory/toxicity issues of nanomedicines in pulmonary delivery are also discussed. PMID:20054434

  2. Optimising the manufacture, formulation, and dose of antiretroviral drugs for more cost-efficient delivery in resource-limited settings: a consensus statement.

    PubMed

    Crawford, Keith W; Ripin, David H Brown; Levin, Andrew D; Campbell, Jennifer R; Flexner, Charles

    2012-07-01

    It is expected that funding limitations for worldwide HIV treatment and prevention in resource-limited settings will continue, and, because the need for treatment scale-up is urgent, the emphasis on value for money has become an increasing priority. The Conference on Antiretroviral Drug Optimization--a collaborative project between the Clinton Health Access Initiative, the Johns Hopkins University School of Medicine, and the Bill & Melinda Gates Foundation--brought together process chemists, clinical pharmacologists, pharmaceutical scientists, physicians, pharmacists, and regulatory specialists to explore strategies for the reduction of antiretroviral drug costs. The antiretroviral drugs discussed were prioritised for consideration on the basis of their market impact, and the objectives of the conference were framed as discussion questions generated to guide scientific assessment of potential strategies. These strategies included modifications to the synthesis of the active pharmaceutical ingredient (API) and use of cheaper sources of raw materials in synthesis of these ingredients. Innovations in product formulation could improve bioavailability thus needing less API. For several antiretroviral drugs, studies show efficacy is maintained at doses below the approved dose (eg, efavirenz, lopinavir plus ritonavir, atazanavir, and darunavir). Optimising pharmacoenhancement and extending shelf life are additional strategies. The conference highlighted a range of interventions; optimum cost savings could be achieved through combining approaches. PMID:22742638

  3. Grading More Accurately

    ERIC Educational Resources Information Center

    Rom, Mark Carl

    2011-01-01

    Grades matter. College grading systems, however, are often ad hoc and prone to mistakes. This essay focuses on one factor that contributes to high-quality grading systems: grading accuracy (or "efficiency"). I proceed in several steps. First, I discuss the elements of "efficient" (i.e., accurate) grading. Next, I present analytical results…

  4. Direct dose mapping versus energy/mass transfer mapping for 4D dose accumulation: fundamental differences and dosimetric consequences

    NASA Astrophysics Data System (ADS)

    Li, Haisen S.; Zhong, Hualiang; Kim, Jinkoo; Glide-Hurst, Carri; Gulam, Misbah; Nurushev, Teamour S.; Chetty, Indrin J.

    2014-01-01

    The direct dose mapping (DDM) and energy/mass transfer (EMT) mapping are two essential algorithms for accumulating the dose from different anatomic phases to the reference phase when there is organ motion or tumor/tissue deformation during the delivery of radiation therapy. DDM is based on interpolation of the dose values from one dose grid to another and thus lacks rigor in defining the dose when there are multiple dose values mapped to one dose voxel in the reference phase due to tissue/tumor deformation. On the other hand, EMT counts the total energy and mass transferred to each voxel in the reference phase and calculates the dose by dividing the energy by mass. Therefore it is based on fundamentally sound physics principles. In this study, we implemented the two algorithms and integrated them within the Eclipse treatment planning system. We then compared the clinical dosimetric difference between the two algorithms for ten lung cancer patients receiving stereotactic radiosurgery treatment, by accumulating the delivered dose to the end-of-exhale (EE) phase. Specifically, the respiratory period was divided into ten phases and the dose to each phase was calculated and mapped to the EE phase and then accumulated. The displacement vector field generated by Demons-based registration of the source and reference images was used to transfer the dose and energy. The DDM and EMT algorithms produced noticeably different cumulative dose in the regions with sharp mass density variations and/or high dose gradients. For the planning target volume (PTV) and internal target volume (ITV) minimum dose, the difference was up to 11% and 4% respectively. This suggests that DDM might not be adequate for obtaining an accurate dose distribution of the cumulative plan, instead, EMT should be considered.

  5. Polymers for Drug Delivery Systems

    PubMed Central

    Liechty, William B.; Kryscio, David R.; Slaughter, Brandon V.; Peppas, Nicholas A.

    2012-01-01

    Polymers have played an integral role in the advancement of drug delivery technology by providing controlled release of therapeutic agents in constant doses over long periods, cyclic dosage, and tunable release of both hydrophilic and hydrophobic drugs. From early beginnings using off-the-shelf materials, the field has grown tremendously, driven in part by the innovations of chemical engineers. Modern advances in drug delivery are now predicated upon the rational design of polymers tailored for specific cargo and engineered to exert distinct biological functions. In this review, we highlight the fundamental drug delivery systems and their mathematical foundations and discuss the physiological barriers to drug delivery. We review the origins and applications of stimuli-responsive polymer systems and polymer therapeutics such as polymer-protein and polymer-drug conjugates. The latest developments in polymers capable of molecular recognition or directing intracellular delivery are surveyed to illustrate areas of research advancing the frontiers of drug delivery. PMID:22432577

  6. Accurate monotone cubic interpolation

    NASA Technical Reports Server (NTRS)

    Huynh, Hung T.

    1991-01-01

    Monotone piecewise cubic interpolants are simple and effective. They are generally third-order accurate, except near strict local extrema where accuracy degenerates to second-order due to the monotonicity constraint. Algorithms for piecewise cubic interpolants, which preserve monotonicity as well as uniform third and fourth-order accuracy are presented. The gain of accuracy is obtained by relaxing the monotonicity constraint in a geometric framework in which the median function plays a crucial role.

  7. Accurate Finite Difference Algorithms

    NASA Technical Reports Server (NTRS)

    Goodrich, John W.

    1996-01-01

    Two families of finite difference algorithms for computational aeroacoustics are presented and compared. All of the algorithms are single step explicit methods, they have the same order of accuracy in both space and time, with examples up to eleventh order, and they have multidimensional extensions. One of the algorithm families has spectral like high resolution. Propagation with high order and high resolution algorithms can produce accurate results after O(10(exp 6)) periods of propagation with eight grid points per wavelength.

  8. Feasibility study of volumetric modulated arc therapy with constant dose rate for endometrial cancer

    SciTech Connect

    Yang, Ruijie; Wang, Junjie; Xu, Feng; Li, Hua; Zhang, Xile

    2013-10-01

    To investigate the feasibility, efficiency, and delivery accuracy of volumetric modulated arc therapy with constant dose rate (VMAT-CDR) for whole-pelvic radiotherapy (WPRT) of endometrial cancer. The nine-field intensity-modulated radiotherapy (IMRT), VMAT with variable dose-rate (VMAT-VDR), and VMAT-CDR plans were created for 9 patients with endometrial cancer undergoing WPRT. The dose distribution of planning target volume (PTV), organs at risk (OARs), and normal tissue (NT) were compared. The monitor units (MUs) and treatment delivery time were also evaluated. For each VMAT-CDR plan, a dry run was performed to assess the dosimetric accuracy with MatriXX from IBA. Compared with IMRT, the VMAT-CDR plans delivered a slightly greater V{sub 20} of the bowel, bladder, pelvis bone, and NT, but significantly decreased the dose to the high-dose region of the rectum and pelvis bone. The MUs decreased from 1105 with IMRT to 628 with VMAT-CDR. The delivery time also decreased from 9.5 to 3.2 minutes. The average gamma pass rate was 95.6% at the 3%/3 mm criteria with MatriXX pretreatment verification for 9 patients. VMAT-CDR can achieve comparable plan quality with significant shorter delivery time and smaller number of MUs compared with IMRT for patients with endometrial cancer undergoing WPRT. It can be accurately delivered and be an alternative to IMRT on the linear accelerator without VDR capability.

  9. Feasibility study of volumetric modulated arc therapy with constant dose rate for endometrial cancer.

    PubMed

    Yang, Ruijie; Wang, Junjie; Xu, Feng; Li, Hua; Zhang, Xile

    2013-01-01

    To investigate the feasibility, efficiency, and delivery accuracy of volumetric modulated arc therapy with constant dose rate (VMAT-CDR) for whole-pelvic radiotherapy (WPRT) of endometrial cancer. The nine-field intensity-modulated radiotherapy (IMRT), VMAT with variable dose-rate (VMAT-VDR), and VMAT-CDR plans were created for 9 patients with endometrial cancer undergoing WPRT. The dose distribution of planning target volume (PTV), organs at risk (OARs), and normal tissue (NT) were compared. The monitor units (MUs) and treatment delivery time were also evaluated. For each VMAT-CDR plan, a dry run was performed to assess the dosimetric accuracy with MatriXX from IBA. Compared with IMRT, the VMAT-CDR plans delivered a slightly greater V20 of the bowel, bladder, pelvis bone, and NT, but significantly decreased the dose to the high-dose region of the rectum and pelvis bone. The MUs decreased from 1105 with IMRT to 628 with VMAT-CDR. The delivery time also decreased from 9.5 to 3.2 minutes. The average gamma pass rate was 95.6% at the 3%/3mm criteria with MatriXX pretreatment verification for 9 patients. VMAT-CDR can achieve comparable plan quality with significant shorter delivery time and smaller number of MUs compared with IMRT for patients with endometrial cancer undergoing WPRT. It can be accurately delivered and be an alternative to IMRT on the linear accelerator without VDR capability. PMID:23669454

  10. Accurate measurement of time

    NASA Astrophysics Data System (ADS)

    Itano, Wayne M.; Ramsey, Norman F.

    1993-07-01

    The paper discusses current methods for accurate measurements of time by conventional atomic clocks, with particular attention given to the principles of operation of atomic-beam frequency standards, atomic hydrogen masers, and atomic fountain and to the potential use of strings of trapped mercury ions as a time device more stable than conventional atomic clocks. The areas of application of the ultraprecise and ultrastable time-measuring devices that tax the capacity of modern atomic clocks include radio astronomy and tests of relativity. The paper also discusses practical applications of ultraprecise clocks, such as navigation of space vehicles and pinpointing the exact position of ships and other objects on earth using the GPS.

  11. Radiation delivery system and method

    DOEpatents

    Sorensen, Scott A.; Robison, Thomas W.; Taylor, Craig M. V.

    2002-01-01

    A radiation delivery system and method are described. The system includes a treatment configuration such as a stent, balloon catheter, wire, ribbon, or the like, a portion of which is covered with a gold layer. Chemisorbed to the gold layer is a radiation-emitting self-assembled monolayer or a radiation-emitting polymer. The radiation delivery system is compatible with medical catheter-based technologies to provide a therapeutic dose of radiation to a lesion following an angioplasty procedure.

  12. Accurate quantum chemical calculations

    NASA Technical Reports Server (NTRS)

    Bauschlicher, Charles W., Jr.; Langhoff, Stephen R.; Taylor, Peter R.

    1989-01-01

    An important goal of quantum chemical calculations is to provide an understanding of chemical bonding and molecular electronic structure. A second goal, the prediction of energy differences to chemical accuracy, has been much harder to attain. First, the computational resources required to achieve such accuracy are very large, and second, it is not straightforward to demonstrate that an apparently accurate result, in terms of agreement with experiment, does not result from a cancellation of errors. Recent advances in electronic structure methodology, coupled with the power of vector supercomputers, have made it possible to solve a number of electronic structure problems exactly using the full configuration interaction (FCI) method within a subspace of the complete Hilbert space. These exact results can be used to benchmark approximate techniques that are applicable to a wider range of chemical and physical problems. The methodology of many-electron quantum chemistry is reviewed. Methods are considered in detail for performing FCI calculations. The application of FCI methods to several three-electron problems in molecular physics are discussed. A number of benchmark applications of FCI wave functions are described. Atomic basis sets and the development of improved methods for handling very large basis sets are discussed: these are then applied to a number of chemical and spectroscopic problems; to transition metals; and to problems involving potential energy surfaces. Although the experiences described give considerable grounds for optimism about the general ability to perform accurate calculations, there are several problems that have proved less tractable, at least with current computer resources, and these and possible solutions are discussed.

  13. Computing Proton Dose to Irregularly Moving Targets

    PubMed Central

    Phillips, Justin; Gueorguiev, Gueorgui; Shackleford, James A.; Grassberger, Clemens; Dowdell, Stephen; Paganetti, Harald; Sharp, Gregory C.

    2014-01-01

    Purpose While four-dimensional computed tomography (4DCT) and deformable registration can be used to assess the dose delivered to regularly moving targets, there are few methods available for irregularly moving targets. 4DCT captures an idealized waveform, but human respiration during treatment is characterized by gradual baseline shifts and other deviations from a periodic signal. This paper describes a method for computing the dose delivered to irregularly moving targets based on 1D or 3D waveforms captured at the time of delivery. Methods The procedure uses CT or 4DCT images for dose calculation, and 1D or 3D respiratory waveforms of the target position at time of delivery. Dose volumes are converted from their Cartesian geometry into a beam-specific radiological depth space, parameterized in 2D by the beam aperture, and longitudinally by the radiological depth. In this new frame of reference, the proton doses are translated according to the motion found in the 1D or 3D trajectory. These translated dose volumes are weighted and summed, then transformed back into Cartesian space, yielding an estimate of the dose that includes the effect of the measured breathing motion. The method was validated using a synthetic lung phantom and a single representative patient CT. Simulated 4DCT was generated for the phantom with 2 cm peak-to-peak motion. Results A passively-scattered proton treatment plan was generated using 6 mm and 5 mm smearing for the phantom and patient plans, respectively. The method was tested without motion, and with two simulated breathing signals: a 2 cm amplitude sinusoid, and a 2 cm amplitude sinusoid with 3 cm linear drift in the phantom. The tumor positions were equally weighted for the patient calculation. Motion-corrected dose was computed based on the mid-ventilation CT image in the phantom and the peak exhale position in the patient. Gamma evaluation was 97.8% without motion, 95.7% for 2 cm sinusoidal motion, and 95.7% with 3 cm drift in the

  14. Computing proton dose to irregularly moving targets

    NASA Astrophysics Data System (ADS)

    Phillips, Justin; Gueorguiev, Gueorgui; Shackleford, James A.; Grassberger, Clemens; Dowdell, Stephen; Paganetti, Harald; Sharp, Gregory C.

    2014-08-01

    Purpose: While four-dimensional computed tomography (4DCT) and deformable registration can be used to assess the dose delivered to regularly moving targets, there are few methods available for irregularly moving targets. 4DCT captures an idealized waveform, but human respiration during treatment is characterized by gradual baseline shifts and other deviations from a periodic signal. This paper describes a method for computing the dose delivered to irregularly moving targets based on 1D or 3D waveforms captured at the time of delivery. Methods: The procedure uses CT or 4DCT images for dose calculation, and 1D or 3D respiratory waveforms of the target position at time of delivery. Dose volumes are converted from their Cartesian geometry into a beam-specific radiological depth space, parameterized in 2D by the beam aperture, and longitudinally by the radiological depth. In this new frame of reference, the proton doses are translated according to the motion found in the 1D or 3D trajectory. These translated dose volumes are weighted and summed, then transformed back into Cartesian space, yielding an estimate of the dose that includes the effect of the measured breathing motion. The method was validated using a synthetic lung phantom and a single representative patient CT. Simulated 4DCT was generated for the phantom with 2 cm peak-to-peak motion. Results: A passively-scattered proton treatment plan was generated using 6 mm and 5 mm smearing for the phantom and patient plans, respectively. The method was tested without motion, and with two simulated breathing signals: a 2 cm amplitude sinusoid, and a 2 cm amplitude sinusoid with 3 cm linear drift in the phantom. The tumor positions were equally weighted for the patient calculation. Motion-corrected dose was computed based on the mid-ventilation CT image in the phantom and the peak exhale position in the patient. Gamma evaluation was 97.8% without motion, 95.7% for 2 cm sinusoidal motion, 95.7% with 3 cm drift in the

  15. VMAT linear accelerator commissioning and quality assurance: dose control and gantry speed tests.

    PubMed

    Barnes, Michael P; Rowshanfarzad, Pejman; Greer, Peter B

    2016-01-01

    In VMAT treatment delivery the ability of the linear accelerator (linac) to accurately control dose versus gantry angle is critical to delivering the plan correctly. A new VMAT test delivery was developed to specifically test the dose versus gantry angle with the full range of allowed gantry speeds and dose rates. The gantry-mounted IBA MatriXX with attached inclinometer was used in movie mode to measure the instantaneous relative dose versus gantry angle during the plan every 0.54 s. The results were compared to the expected relative dose at each gantry angle calculated from the plan. The same dataset was also used to compare the instantaneous gan-try speeds throughout the delivery compared to the expected gantry speeds from the plan. Measurements performed across four linacs generally show agreement between measurement and plan to within 1.5% in the constant dose rate regions and dose rate modulation within 0.1 s of the plan. Instantaneous gantry speed was measured to be within 0.11°/s of the plan (1 SD). An error in one linac was detected in that the nominal gantry speed was incorrectly calibrated. This test provides a practical method to quality-assure critical aspects of VMAT delivery including dose versus gantry angle and gantry speed control. The method can be performed with any detector that can acquire time-resolved dosimetric information that can be synchronized with a measurement of gantry angle. The test fulfils several of the aims of the recent Netherlands Commission on Radiation Dosimetry (NCS) Report 24, which provides recommendations for comprehensive VMAT quality assurance. PMID:27167282

  16. An algorithm to calculate a collapsed arc dose matrix in volumetric modulated arc therapy

    SciTech Connect

    Arumugam, Sankar; Xing Aitang; Jameson, Michael; Holloway, Lois

    2013-07-15

    Purpose: The delivery of volumetric modulated arc therapy (VMAT) is more complex than other conformal radiotherapy techniques. In this work, the authors present the feasibility of performing routine verification of VMAT delivery using a dose matrix measured by a gantry mounted 2D ion chamber array and corresponding dose matrix calculated by an inhouse developed algorithm.Methods: Pinnacle, v9.0, treatment planning system (TPS) was used in this study to generate VMAT plans for a 6 MV photon beam from an Elekta-Synergy linear accelerator. An algorithm was developed and implemented with inhouse computer code to calculate the dose matrix resulting from a VMAT arc in a plane perpendicular to the beam at isocenter. The algorithm was validated using measurement of standard patterns and clinical VMAT plans with a 2D ion chamber array. The clinical VMAT plans were also validated using ArcCHECK measurements. The measured and calculated dose matrices were compared using gamma ({gamma}) analysis with 3%/3 mm criteria and {gamma} tolerance of 1.Results: The dose matrix comparison of standard patterns has shown excellent agreement with the mean {gamma} pass rate 97.7 ({sigma}= 0.4)%. The validation of clinical VMAT plans using the dose matrix predicted by the algorithm and the corresponding measured dose matrices also showed good agreement with the mean {gamma} pass rate of 97.6 ({sigma}= 1.6)%. The validation of clinical VMAT plans using ArcCHECK measurements showed a mean pass rate of 95.6 ({sigma}= 1.8)%.Conclusions: The developed algorithm was shown to accurately predict the dose matrix, in a plane perpendicular to the beam, by considering all possible leaf trajectories in a VMAT delivery. This enables the verification of VMAT delivery using a 2D array detector mounted on a treatment head.

  17. Delivery confirmation of bolus electron conformal therapy combined with intensity modulated x-ray therapy

    SciTech Connect

    Kavanaugh, James A.; Hogstrom, Kenneth R.; Fontenot, Jonas P.; Henkelmann, Gregory; Chu, Connel; Carver, Robert A.

    2013-02-15

    .62%, respectively, for the bolus ECT plans and 89.2% and 95.1%, respectively, for the mixed beam plans. For all regions, pass rates for the parotid and CW plans were 98.8% and 97.3%, respectively, for the bolus ECT plans and 97.5% and 95.9%, respectively, for the mixed beam plans. For the IMXT component of the mixed beam plans, pass rates for the parotid and CW plans were 93.7% and 95.8%. Conclusions: Bolus ECT and mixed beam therapy dose delivery to the phantom were more accurate than IMXT delivery, adding confidence to the use of planning, fabrication, and delivery for bolus ECT tools either alone or as part of mixed beam therapy. The methodology reported in this work could serve as a basis for future standardization of the commissioning of bolus ECT or mixed beam therapy. When applying this technology to patients, it is recommended that an electron dose algorithm more accurate than the pencil beam algorithm, e.g., a Monte Carlo algorithm or analytical transport such as the pencil beam redefinition algorithm, be used for planning to ensure the desired accuracy.

  18. Verification of dose distribution for volumetric modulated arc therapy total marrow irradiation in a humanlike phantom

    SciTech Connect

    Surucu, Murat; Yeginer, Mete; Kavak, Gulbin O.; Fan, John; Radosevich, James A.; Aydogan, Bulent

    2012-01-15

    Purpose: Volumetric modulated arc therapy (VMAT) treatment planning studies have been reported to provide good target coverage and organs at risk (OARs) sparing in total marrow irradiation (TMI). A comprehensive dosimetric study simulating the clinical situation as close as possible is a norm in radiotherapy before a technique can be used to treat a patient. Without such a study, it would be difficult to make a reliable and safe clinical transition especially with a technique as complicated as VMAT-TMI. To this end, the dosimetric feasibility of VMAT-TMI technique in terms of treatment planning, delivery efficiency, and the most importantly three dimensional dose distribution accuracy was investigated in this study. The VMAT-TMI dose distribution inside a humanlike Rando phantom was measured and compared to the dose calculated using RapidArc especially in the field junctions and the inhomogeneous tissues including the lungs, which is the dose-limiting organ in TMI. Methods: Three subplans with a total of nine arcs were used to treat the planning target volume (PTV), which was determined as all the bones plus the 3 mm margin. Thermoluminescent detectors (TLDs) were placed at 39 positions throughout the phantom. The measured TLD doses were compared to the calculated plan doses. Planar dose for each arc was verified using mapcheck. Results: TLD readings demonstrated accurate dose delivery, with a median dose difference of 0.5% (range: -4.3% and 6.6%) from the calculated dose in the junctions and in the inhomogeneous medium including the lungs. Conclusions: The results from this study suggest that RapidArc VMAT technique is dosimetrically accurate, safe, and efficient in delivering TMI within clinically acceptable time frame.

  19. NovoPen Echo(®) insulin delivery device.

    PubMed

    Hyllested-Winge, Jacob; Sparre, Thomas; Pedersen, Line Kynemund

    2016-01-01

    The introduction of insulin pen devices has provided easier, well-tolerated, and more convenient treatment regimens for patients with diabetes mellitus. When compared with vial and syringe regimens, insulin pens offer a greater clinical efficacy, improved quality of life, and increased dosing accuracy, particularly at low doses. The portable and discreet nature of pen devices reduces the burden on the patient, facilitates adherence, and subsequently contributes to the improvement in glycemic control. NovoPen Echo(®) is one of the latest members of the NovoPen(®) family that has been specifically designed for the pediatric population and is the first to combine half-unit increment (=0.5 U of insulin) dosing with a simple memory function. The half-unit increment dosing amendments and accurate injection of 0.5 U of insulin are particularly beneficial for children (and insulin-sensitive adults/elders), who often require small insulin doses. The memory function can be used to record the time and amount of the last dose, reducing the fear of double dosing or missing a dose. The memory function also provides parents with extra confidence and security that their child is taking insulin at the correct doses and times. NovoPen Echo is a lightweight, durable insulin delivery pen; it is available in two different colors, which may help to distinguish between different types of insulin, providing more confidence for both users and caregivers. Studies have demonstrated a high level of patient satisfaction, with 80% of users preferring NovoPen Echo to other pediatric insulin pens. PMID:26793007

  20. NovoPen Echo® insulin delivery device

    PubMed Central

    Hyllested-Winge, Jacob; Sparre, Thomas; Pedersen, Line Kynemund

    2016-01-01

    The introduction of insulin pen devices has provided easier, well-tolerated, and more convenient treatment regimens for patients with diabetes mellitus. When compared with vial and syringe regimens, insulin pens offer a greater clinical efficacy, improved quality of life, and increased dosing accuracy, particularly at low doses. The portable and discreet nature of pen devices reduces the burden on the patient, facilitates adherence, and subsequently contributes to the improvement in glycemic control. NovoPen Echo® is one of the latest members of the NovoPen® family that has been specifically designed for the pediatric population and is the first to combine half-unit increment (=0.5 U of insulin) dosing with a simple memory function. The half-unit increment dosing amendments and accurate injection of 0.5 U of insulin are particularly beneficial for children (and insulin-sensitive adults/elders), who often require small insulin doses. The memory function can be used to record the time and amount of the last dose, reducing the fear of double dosing or missing a dose. The memory function also provides parents with extra confidence and security that their child is taking insulin at the correct doses and times. NovoPen Echo is a lightweight, durable insulin delivery pen; it is available in two different colors, which may help to distinguish between different types of insulin, providing more confidence for both users and caregivers. Studies have demonstrated a high level of patient satisfaction, with 80% of users preferring NovoPen Echo to other pediatric insulin pens. PMID:26793007

  1. A Monte Carlo tool for evaluating VMAT and DIMRT treatment deliveries including planar detectors

    NASA Astrophysics Data System (ADS)

    Asuni, G.; van Beek, T. A.; Venkataraman, S.; Popescu, I. A.; McCurdy, B. M. C.

    2013-06-01

    , we defined an acceptable pass rate of >90% of percentage pixels with γ <1. We found that over 90% of control points in the plans passed this criterion. In general, our results indicate that the simulation tool is suitable for accurately calculating both patient/phantom doses and planar doses for VMAT dose delivery. The tool will be valuable to check performance and advance the development of in vivo planar detectors for use in measurement-based VMAT dose verification. In addition, the tool can be useful as an independent research tool for VMAT commissioning of the TPS and delivery system.

  2. Real-time motion-adaptive delivery (MAD) using binary MLC: I. Static beam (topotherapy) delivery

    NASA Astrophysics Data System (ADS)

    Lu, Weiguo

    2008-11-01

    Intra-fraction target motion hits the fundamental basis of IMRT where precise target positions are assumed. Real-time motion compensation is necessary to ensure that the same dose is delivered as planned. Strategies for conventional IMRT delivery for moving targets by dynamic multi-leaf collimators (MLC) tracking are well published. Binary MLC-based IMRT, such as TomoTherapy®, requires synchronized motion of MLC, the couch and the gantry, which suggests a unique motion management strategy. Thanks to its ultra-fast leaf response and fast projection rate, real-time motion compensation for binary MLC-based IMRT is feasible. Topotherapy is a new IMRT delivery technique, which can be implemented in commercial helical TomoTherapy® machines using only fixed gantry positions. In this paper, we present a novel approach for TopoTherapy delivery that adjusts for moving targets without additional hardware and control requirement. This technique uses the planned leaf sequence but rearranges the projection and leaf indices. It does not involve time-consuming operations, such as reoptimization. Unlike gating or breath-hold-based methods, this technique can achieve nearly a 100% duty cycle with little breath control. Unlike dynamic MLC-based tracking methods, this technique requires neither the whole target motion trajectory nor the velocity of target motion. Instead, it only requires instantaneous target positions, which greatly simplifies the system implementation. Extensive simulations, including the worst-case scenarios, validated the presented technique to be applicable to relatively regular or mild irregular respirations. The delivered dose conforms well to the target, and significant margin reduction can be achieved provided that accurate, real-time tumor localization is available.

  3. Improving Delivery Accuracy of Stereotactic Body Radiotherapy to a Moving Tumor Using Simplified Volumetric Modulated Arc Therapy

    PubMed Central

    Ko, Young Eun; Cho, Byungchul; Kim, Su Ssan; Song, Si Yeol; Choi, Eun Kyung; Ahn, Seung Do; Yi, Byongyong

    2016-01-01

    Purpose To develop a simplified volumetric modulated arc therapy (VMAT) technique for more accurate dose delivery in thoracic stereotactic body radiation therapy (SBRT). Methods and Materials For each of the 22 lung SBRT cases treated with respiratory-gated VMAT, a dose rate modulated arc therapy (DrMAT) plan was retrospectively generated. A dynamic conformal arc therapy plan with 33 adjoining coplanar arcs was designed and their beam weights were optimized by an inverse planning process. All sub-arc beams were converted into a series of control points with varying MLC segment and dose rates and merged into an arc beam for a DrMAT plan. The plan quality of original VMAT and DrMAT was compared in terms of target coverage, compactness of dose distribution, and dose sparing of organs at risk. To assess the delivery accuracy, the VMAT and DrMAT plans were delivered to a motion phantom programmed with the corresponding patients’ respiratory signal; results were compared using film dosimetry with gamma analysis. Results The plan quality of DrMAT was equivalent to that of VMAT in terms of target coverage, dose compactness, and dose sparing for the normal lung. In dose sparing for other critical organs, DrMAT was less effective than VMAT for the spinal cord, heart, and esophagus while being well within the limits specified by the Radiation Therapy Oncology Group. Delivery accuracy of DrMAT to a moving target was similar to that of VMAT using a gamma criterion of 2%/2mm but was significantly better using a 2%/1mm criterion, implying the superiority of DrMAT over VMAT in SBRT for thoracic/abdominal tumors with respiratory movement. Conclusion We developed a DrMAT technique for SBRT that produces plans of a quality similar to that achieved with VMAT but with better delivery accuracy. This technique is well-suited for small tumors with motion uncertainty. PMID:27333199

  4. Four-dimensional dose distributions of step-and-shoot IMRT delivered with real-time tumor tracking for patients with irregular breathing: Constant dose rate vs dose rate regulation

    SciTech Connect

    Yang Xiaocheng; Han-Oh, Sarah; Gui Minzhi; Niu Ying; Yu, Cedric X.; Yi Byongyong

    2012-09-15

    slower than the planning day. In contrast, DRRT method showed less than 1% reduction in target dose and no noticeable change in OAR dose under the same breathing period irregularities. When {+-}20% variation of target motion amplitude was present as breathing irregularity, the two delivery methods show compatible plan quality if the dose distribution of CDRT delivery is renormalized. Conclusions: Delivery of 4D-IMRT treatment plans, stemmed from 3D step-and-shoot IMRT and preprogrammed using SAM algorithm, is simulated for two dynamic MLC-based real-time tumor tracking strategies: with and without dose-rate regulation. Comparison of cumulative dose distribution indicates that the preprogrammed 4D plan is more accurately and efficiently conformed using the DRRT strategy, as it compensates the interplay between patient breathing irregularity and tracking delivery without compromising the segment-weight modulation.

  5. Insights into direct nose to brain delivery: current status and future perspective.

    PubMed

    Mittal, Deepti; Ali, Asgar; Md, Shadab; Baboota, Sanjula; Sahni, Jasjeet K; Ali, Javed

    2014-03-01

    Now a day's intranasal (i.n) drug delivery is emerging as a reliable method to bypass the blood-brain barrier (BBB) and deliver a wide range of therapeutic agents including both small and large molecules, growth factors, viral vectors and even stem cells to the brain and has shown therapeutic effects in both animals and humans. This route involves the olfactory or trigeminal nerve systems which initiate in the brain and terminate in the nasal cavity at the olfactory neuroepithelium or respiratory epithelium. They are the only externally exposed portions of the central nervous system (CNS) and therefore represent the most direct method of noninvasive entry into the brain. This approach has been primarily used to explore therapeutic avenues for neurological diseases. The potential for treatment possibilities with olfactory transfer of drugs will increase as more effective formulations and delivery devices are developed. Recently, the apomorphine hydrochloride dry powders have been developed for i.n. delivery (Apomorphine nasal, Lyonase technology, Britannia Pharmaceuticals, Surrey, UK). The results of clinical trial Phase III suggested that the prepared formulation had clinical effect equivalent to subcutaneously administered apomorphine. In coming years, intranasal delivery of drugs will demand more complex and automated delivery devices to ensure accurate and repeatable dosing. Thus, new efforts are needed to make this noninvasive route of delivery more efficient and popular, and it is also predicted that in future a range of intranasal products will be used in diagnosis as well as treatment of CNS diseases. This review will embark the existing evidence of nose-to-brain transport. It also provides insights into the most relevant pre-clinical studies of direct nose-brain delivery and delivery devices which will provide relative success of intranasal delivery system. We have, herein, outlined the relevant aspects of CNS drugs given intranasally to direct the brain in

  6. Dose-calculation algorithms in the context of inhomogeneity corrections for high energy photon beams

    SciTech Connect

    Papanikolaou, Niko; Stathakis, Sotirios

    2009-10-15

    Radiation therapy has witnessed a plethora of innovations and developments in the past 15 years. Since the introduction of computed tomography for treatment planning there has been a steady introduction of new methods to refine treatment delivery. Imaging continues to be an integral part of the planning, but also the delivery, of modern radiotherapy. However, all the efforts of image guided radiotherapy, intensity-modulated planning and delivery, adaptive radiotherapy, and everything else that we pride ourselves in having in the armamentarium can fall short, unless there is an accurate dose-calculation algorithm. The agreement between the calculated and delivered doses is of great significance in radiation therapy since the accuracy of the absorbed dose as prescribed determines the clinical outcome. Dose-calculation algorithms have evolved greatly over the years in an effort to be more inclusive of the effects that govern the true radiation transport through the human body. In this Vision 20/20 paper, we look back to see how it all started and where things are now in terms of dose algorithms for photon beams and the inclusion of tissue heterogeneities. Convolution-superposition algorithms have dominated the treatment planning industry for the past few years. Monte Carlo techniques have an inherent accuracy that is superior to any other algorithm and as such will continue to be the gold standard, along with measurements, and maybe one day will be the algorithm of choice for all particle treatment planning in radiation therapy.

  7. Electronic compensation technique to deliver a total body dose

    NASA Astrophysics Data System (ADS)

    Lakeman, Tara E.

    Purpose: Total body irradiation (TBI) uses large parallel-opposed radiation fields to suppress the patient's immune system and eradicate the residual cancer cells in preparation of recipient for bone marrow transplant. The manual placement of lead compensators has been conventionally used to compensate for the varying thickness throughout the body in large-field TBI. The goal of this study is to pursue utilizing the modern electronic compensation technique to more accurately and efficiently deliver dose to patients in need of TBI. Method: Treatment plans utilizing the electronic compensation to deliver a total body dose were created retrospectively for patients for whom CT data had been previously acquired. Each treatment plan includes two pair of parallel opposed fields. One pair of large fields is used to encompass the majority of the patient's anatomy. The other pair are very small open fields focused only on the thin bottom portion of the patient's anatomy, which requires much less radiation than the rest of the body to reach 100% of the prescribed dose. A desirable fluence pattern was manually painted within each of the larger fields for each patient to provide a more uniform distribution. Results: Dose-volume histograms (DVH) were calculated for evaluating the electronic compensation technique. In the electronically compensated plans, the maximum body doses calculated from the DVH were reduced from the conventionally-compensated plans by an average of 15%, indicating a more uniform dose. The mean body doses calculated from the electronically compensated DVH remained comparable to that of the conventionally-compensated plans, indicating an accurate delivery of the prescription dose using electronic compensation. All calculated monitor units were within clinically acceptable limits. Conclusion: Electronic compensation technique for TBI will not increase the beam on time beyond clinically acceptable limits while it can substantially reduce the compensator setup

  8. Two-dimensional inverse planning and delivery with a preclinical image guided microirradiator

    SciTech Connect

    Stewart, James M. P.; Lindsay, Patricia E.; Jaffray, David A.

    2013-10-15

    Purpose: Recent advances in preclinical radiotherapy systems have provided the foundation for scaling many of the elements of clinical radiation therapy practice to the dimensions and energy demanded in small animal studies. Such systems support the technical capabilities to accurately deliver highly complex dose distributions, but methods to optimize and deliver such distributions remain in their infancy. This study developed an optimization method based on empirically measured two-dimensional dose kernel measurements to deliver arbitrary planar dose distributions on a recently developed small animal radiotherapy platform.Methods: A two-dimensional dose kernel was measured with repeated radiochromic film measurements for the circular 1 mm diameter fixed collimator of the small animal radiotherapy system at 1 cm depth in a solid water phantom. This kernel was utilized in a sequential quadratic programming optimization framework to determine optimal beam positions and weights to deliver an arbitrary desired dose distribution. The positions and weights were then translated to a set of stage motions to automatically deliver the optimized dose distribution. End-to-end efficacy of the framework was quantified through five repeated deliveries of two dosimetric challenges: (1) a 5 mm radius bullseye distribution, and (2) a “sock” distribution contained within a 9 × 13 mm bounding box incorporating rectangular, semicircular, and exponentially decaying geometric constructs and a rectangular linear dose gradient region. These two challenges were designed to gauge targeting, geometric, and dosimetric fidelity.Results: Optimization of the bullseye and sock distributions required 2.1 and 5.9 min and utilized 50 and 77 individual beams for delivery, respectively. Automated delivery of the resulting optimized distributions, validated using radiochromic film measurements, revealed an average targeting accuracy of 0.32 mm, and a dosimetric delivery error along four line

  9. Bioresponsive matrices in drug delivery

    PubMed Central

    2010-01-01

    For years, the field of drug delivery has focused on (1) controlling the release of a therapeutic and (2) targeting the therapeutic to a specific cell type. These research endeavors have concentrated mainly on the development of new degradable polymers and molecule-labeled drug delivery vehicles. Recent interest in biomaterials that respond to their environment have opened new methods to trigger the release of drugs and localize the therapeutic within a particular site. These novel biomaterials, usually termed "smart" or "intelligent", are able to deliver a therapeutic agent based on either environmental cues or a remote stimulus. Stimuli-responsive materials could potentially elicit a therapeutically effective dose without adverse side effects. Polymers responding to different stimuli, such as pH, light, temperature, ultrasound, magnetism, or biomolecules have been investigated as potential drug delivery vehicles. This review describes the most recent advances in "smart" drug delivery systems that respond to one or multiple stimuli. PMID:21114841

  10. Neutron dose equivalent meter

    DOEpatents

    Olsher, Richard H.; Hsu, Hsiao-Hua; Casson, William H.; Vasilik, Dennis G.; Kleck, Jeffrey H.; Beverding, Anthony

    1996-01-01

    A neutron dose equivalent detector for measuring neutron dose capable of accurately responding to neutron energies according to published fluence to dose curves. The neutron dose equivalent meter has an inner sphere of polyethylene, with a middle shell overlying the inner sphere, the middle shell comprising RTV.RTM. silicone (organosiloxane) loaded with boron. An outer shell overlies the middle shell and comprises polyethylene loaded with tungsten. The neutron dose equivalent meter defines a channel through the outer shell, the middle shell, and the inner sphere for accepting a neutron counter tube. The outer shell is loaded with tungsten to provide neutron generation, increasing the neutron dose equivalent meter's response sensitivity above 8 MeV.

  11. Teflon cylindrical phantom for delivery quality assurance of stereotactic body radiotherapy (SBRT).

    PubMed

    Lack, Danielle W; Kakakhel, Ali; Starin, Ross; Snyder, Michael

    2014-01-01

    At our institution the standard delivery quality assurance (DQA) procedure for tomotherapy plans is accomplished with a water equivalent phantom, EDR2 film, and ion chamber point-dose measurements. Most plans deliver at most 5 Gy to the dose plane; however, recently a stereotactic body radiotherapy (SBRT) protocol has produced plans delivering upwards of 12 Gy to the film plane. EDR2 film saturates at a dose of ~ 7 Gy, requiring a modification of our DQA procedure for SBRT plans. To reduce the dose to the film plane and accommodate a possible move to SBRT using Varian RapidArc, a Teflon phantom has been constructed and tested. Our Teflon phantom is cylindrical in shape and of a similar design to the standard phantom. The phantom was MVCT scanned on the TomoTherapy system with images imported into the TomoTherapy and Varian Eclipse planning systems. Phantom images were smoothed to reduce artifacts for treatment planning purposes. Verification SBRT plans were delivered with film and point-dose benchmarked against the standard procedure. Verification tolerance criteria were 3% dose difference for chamber measurements and a gamma pass rate > 90% for film (criteria: 3 mm DTA, 3% dose difference, 10% threshold). The phantom sufficiently reduced dose to the film plane for DQA of SBRT plans. Both planning systems calculated accurate point doses in phantom, with the largest differences being 2.4% and 4.4% for TomoTherapy and Rapid Arc plans. Measured dose distributions correlated well with planning system calculations (γ < 1 for > 95%). These results were comparable to the standard phantom. The Teflon phantom appears to be a potential option for SBRT DQA. Preliminary data show that the planning systems are capable of calculating point doses in the Teflon, and the dose to the film plane is reduced sufficiently to allow for a direct measured DQA without the need for dose rescaling. PMID:24423855

  12. Consideration of the radiation dose delivered away from the treatment field to patients in radiotherapy

    PubMed Central

    Taylor, Michael L.; Kron, Tomas

    2011-01-01

    Radiation delivery to cancer patients for radiotherapy is invariably accompanied by unwanted radiation to other parts of the patient’s body. Traditionally, considerable effort has been made to calculate and measure the radiation dose to the target as well as to nearby critical structures. Only recently has attention been focused also on the relatively low doses that exist far from the primary radiation beams. In several clinical scenarios, such doses have been associated with cardiac toxicity as well as an increased risk of secondary cancer induction. Out-of-field dose is a result of leakage and scatter and generally difficult to predict accurately. The present review aims to present existing data, from measurements and calculations, and discuss its implications for radiotherapy. PMID:21731221

  13. Monte Carlo dose calculation in dental amalgam phantom

    PubMed Central

    Aziz, Mohd. Zahri Abdul; Yusoff, A. L.; Osman, N. D.; Abdullah, R.; Rabaie, N. A.; Salikin, M. S.

    2015-01-01

    It has become a great challenge in the modern radiation treatment to ensure the accuracy of treatment delivery in electron beam therapy. Tissue inhomogeneity has become one of the factors for accurate dose calculation, and this requires complex algorithm calculation like Monte Carlo (MC). On the other hand, computed tomography (CT) images used in treatment planning system need to be trustful as they are the input in radiotherapy treatment. However, with the presence of metal amalgam in treatment volume, the CT images input showed prominent streak artefact, thus, contributed sources of error. Hence, metal amalgam phantom often creates streak artifacts, which cause an error in the dose calculation. Thus, a streak artifact reduction technique was applied to correct the images, and as a result, better images were observed in terms of structure delineation and density assigning. Furthermore, the amalgam density data were corrected to provide amalgam voxel with accurate density value. As for the errors of dose uncertainties due to metal amalgam, they were reduced from 46% to as low as 2% at d80 (depth of the 80% dose beyond Zmax) using the presented strategies. Considering the number of vital and radiosensitive organs in the head and the neck regions, this correction strategy is suggested in reducing calculation uncertainties through MC calculation. PMID:26500401

  14. Monte Carlo dose calculation in dental amalgam phantom.

    PubMed

    Aziz, Mohd Zahri Abdul; Yusoff, A L; Osman, N D; Abdullah, R; Rabaie, N A; Salikin, M S

    2015-01-01

    It has become a great challenge in the modern radiation treatment to ensure the accuracy of treatment delivery in electron beam therapy. Tissue inhomogeneity has become one of the factors for accurate dose calculation, and this requires complex algorithm calculation like Monte Carlo (MC). On the other hand, computed tomography (CT) images used in treatment planning system need to be trustful as they are the input in radiotherapy treatment. However, with the presence of metal amalgam in treatment volume, the CT images input showed prominent streak artefact, thus, contributed sources of error. Hence, metal amalgam phantom often creates streak artifacts, which cause an error in the dose calculation. Thus, a streak artifact reduction technique was applied to correct the images, and as a result, better images were observed in terms of structure delineation and density assigning. Furthermore, the amalgam density data were corrected to provide amalgam voxel with accurate density value. As for the errors of dose uncertainties due to metal amalgam, they were reduced from 46% to as low as 2% at d80 (depth of the 80% dose beyond Zmax) using the presented strategies. Considering the number of vital and radiosensitive organs in the head and the neck regions, this correction strategy is suggested in reducing calculation uncertainties through MC calculation. PMID:26500401

  15. MO-G-BRE-04: Automatic Verification of Daily Treatment Deliveries and Generation of Daily Treatment Reports for a MR Image-Guided Treatment Machine

    SciTech Connect

    Yang, D; Li, X; Li, H; Wooten, H; Green, O; Rodriguez, V; Mutic, S

    2014-06-15

    Purpose: Two aims of this work were to develop a method to automatically verify treatment delivery accuracy immediately after patient treatment and to develop a comprehensive daily treatment report to provide all required information for daily MR-IGRT review. Methods: After systematically analyzing the requirements for treatment delivery verification and understanding the available information from a novel MR-IGRT treatment machine, we designed a method to use 1) treatment plan files, 2) delivery log files, and 3) dosimetric calibration information to verify the accuracy and completeness of daily treatment deliveries. The method verifies the correctness of delivered treatment plans and beams, beam segments, and for each segment, the beam-on time and MLC leaf positions. Composite primary fluence maps are calculated from the MLC leaf positions and the beam-on time. Error statistics are calculated on the fluence difference maps between the plan and the delivery. We also designed the daily treatment delivery report by including all required information for MR-IGRT and physics weekly review - the plan and treatment fraction information, dose verification information, daily patient setup screen captures, and the treatment delivery verification results. Results: The parameters in the log files (e.g. MLC positions) were independently verified and deemed accurate and trustable. A computer program was developed to implement the automatic delivery verification and daily report generation. The program was tested and clinically commissioned with sufficient IMRT and 3D treatment delivery data. The final version has been integrated into a commercial MR-IGRT treatment delivery system. Conclusion: A method was developed to automatically verify MR-IGRT treatment deliveries and generate daily treatment reports. Already in clinical use since December 2013, the system is able to facilitate delivery error detection, and expedite physician daily IGRT review and physicist weekly chart

  16. Investigation of Advanced Dose Verification Techniques for External Beam Radiation Treatment

    NASA Astrophysics Data System (ADS)

    Asuni, Ganiyu Adeniyi

    Intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) have been introduced in radiation therapy to achieve highly conformal dose distributions around the tumour while minimizing dose to surrounding normal tissues. These techniques have increased the need for comprehensive quality assurance tests, to verify that customized patient treatment plans are accurately delivered during treatment. in vivo dose verification, performed during treatment delivery, confirms that the actual dose delivered is the same as the prescribed dose, helping to reduce treatment delivery errors. in vivo measurements may be accomplished using entrance or exit detectors. The objective of this project is to investigate a novel entrance detector designed for in vivo dose verification. This thesis is separated into three main investigations, focusing on a prototype entrance transmission detector (TRD) developed by IBA Dosimetry, Germany. First contaminant electrons generated by the TRD in a 6 MV photon beam were investigated using Monte Carlo (MC) simulation. This study demonstrates that modification of the contaminant electron model in the treatment planning system is required for accurate patient dose calculation in buildup regions when using the device. Second, the ability of the TRD to accurately measure dose from IMRT and VMAT was investigated by characterising the spatial resolution of the device. This was accomplished by measuring the point spread function with further validation provided by MC simulation. Comparisons of measured and calculated doses show that the spatial resolution of the TRD allows for measurement of clinical IMRT fields within acceptable tolerance. Finally, a new general research tool was developed to perform MC simulations for VMAT and IMRT treatments, simultaneously tracking dose deposition in both the patient CT geometry and an arbitrary planar detector system, generalized to handle either entrance or exit orientations. It was

  17. Patient dose and image quality from mega-voltage cone beam computed tomography imaging

    SciTech Connect

    Gayou, Olivier; Parda, David S.; Johnson, Mark; Miften, Moyed

    2007-02-15

    The evolution of ever more conformal radiation delivery techniques makes the subject of accurate localization of increasing importance in radiotherapy. Several systems can be utilized including kilo-voltage and mega-voltage cone-beam computed tomography (MV-CBCT), CT on rail or helical tomography. One of the attractive aspects of mega-voltage cone-beam CT is that it uses the therapy beam along with an electronic portal imaging device to image the patient prior to the delivery of treatment. However, the use of a photon beam energy in the mega-voltage range for volumetric imaging degrades the image quality and increases the patient radiation dose. To optimize image quality and patient dose in MV-CBCT imaging procedures, a series of dose measurements in cylindrical and anthropomorphic phantoms using an ionization chamber, radiographic films, and thermoluminescent dosimeters was performed. Furthermore, the dependence of the contrast to noise ratio and spatial resolution of the image upon the dose delivered for a 20-cm-diam cylindrical phantom was evaluated. Depending on the anatomical site and patient thickness, we found that the minimum dose deposited in the irradiated volume was 5-9 cGy and the maximum dose was between 9 and 17 cGy for our clinical MV-CBCT imaging protocols. Results also demonstrated that for high contrast areas such as bony anatomy, low doses are sufficient for image registration and visualization of the three-dimensional boundaries between soft tissue and bony structures. However, as the difference in tissue density decreased, the dose required to identify soft tissue boundaries increased. Finally, the dose delivered by MV-CBCT was simulated using a treatment planning system (TPS), thereby allowing the incorporation of MV-CBCT dose in the treatment planning process. The TPS-calculated doses agreed well with measurements for a wide range of imaging protocols.

  18. Intrathecal Drug Delivery (ITDD) systems for cancer pain

    PubMed Central

    Bhatia, Gaurav; Lau, Mary E; Koury, Katharine M; Gulur, Padma

    2014-01-01

    Intrathecal drug delivery is an effective pain management option for patients with chronic and cancer pain. The delivery of drugs into the intrathecal space provides superior analgesia with smaller doses of analgesics to minimize side effects while significantly improving quality of life. This article aims to provide a general overview of the use of intrathecal drug delivery to manage pain, dosing recommendations, potential risks and complications, and growing trends in the field. PMID:24555051

  19. Physically facilitating drug-delivery systems

    PubMed Central

    Rodriguez-Devora, Jorge I; Ambure, Sunny; Shi, Zhi-Dong; Yuan, Yuyu; Sun, Wei; Xu, Tao

    2012-01-01

    Facilitated/modulated drug-delivery systems have emerged as a possible solution for delivery of drugs of interest to pre-allocated sites at predetermined doses for predefined periods of time. Over the past decade, the use of different physical methods and mechanisms to mediate drug release and delivery has grown significantly. This emerging area of research has important implications for development of new therapeutic drugs for efficient treatments. This review aims to introduce and describe different modalities of physically facilitating drug-delivery systems that are currently in use for cancer and other diseases therapy. In particular, delivery methods based on ultrasound, electrical, magnetic and photo modulations are highlighted. Current uses and areas of improvement for these different physically facilitating drug-delivery systems are discussed. Furthermore, the main advantages and drawbacks of these technologies reviewed are compared. The review ends with a speculative viewpoint of how research is expected to evolve in the upcoming years. PMID:22485192

  20. SU-E-J-89: Motion Effects On Organ Dose in Respiratory Gated Stereotactic Body Radiation Therapy

    SciTech Connect

    Wang, T; Zhu, L; Khan, M; Landry, J; Rajpara, R; Hawk, N

    2014-06-01

    Purpose: Existing reports on gated radiation therapy focus mainly on optimizing dose delivery to the target structure. This work investigates the motion effects on radiation dose delivered to organs at risk (OAR) in respiratory gated stereotactic body radiation therapy (SBRT). A new algorithmic tool of dose analysis is developed to evaluate the optimality of gating phase for dose sparing on OARs while ensuring adequate target coverage. Methods: Eight patients with pancreatic cancer were treated on a phase I prospective study employing 4DCT-based SBRT. For each patient, 4DCT scans are acquired and sorted into 10 respiratory phases (inhale-exhale- inhale). Treatment planning is performed on the average CT image. The average CT is spatially registered to other phases. The resultant displacement field is then applied on the plan dose map to estimate the actual dose map for each phase. Dose values of each voxel are fitted to a sinusoidal function. Fitting parameters of dose variation, mean delivered dose and optimal gating phase for each voxel over respiration cycle are mapped on the dose volume. Results: The sinusoidal function accurately models the dose change during respiratory motion (mean fitting error 4.6%). In the eight patients, mean dose variation is 3.3 Gy on OARs with maximum of 13.7 Gy. Two patients have about 100cm{sup 3} volumes covered by more than 5 Gy deviation. The mean delivered dose maps are similar to plan dose with slight deformation. The optimal gating phase highly varies across the patient, with phase 5 or 6 on about 60% of the volume, and phase 0 on most of the rest. Conclusion: A new algorithmic tool is developed to conveniently quantify dose deviation on OARs from plan dose during the respiratory cycle. The proposed software facilitates the treatment planning process by providing the optimal respiratory gating phase for dose sparing on each OAR.

  1. NNLOPS accurate associated HW production

    NASA Astrophysics Data System (ADS)

    Astill, William; Bizon, Wojciech; Re, Emanuele; Zanderighi, Giulia

    2016-06-01

    We present a next-to-next-to-leading order accurate description of associated HW production consistently matched to a parton shower. The method is based on reweighting events obtained with the HW plus one jet NLO accurate calculation implemented in POWHEG, extended with the MiNLO procedure, to reproduce NNLO accurate Born distributions. Since the Born kinematics is more complex than the cases treated before, we use a parametrization of the Collins-Soper angles to reduce the number of variables required for the reweighting. We present phenomenological results at 13 TeV, with cuts suggested by the Higgs Cross section Working Group.

  2. Nanoparticle-based cancer treatment: can delivered dose and biological dose be reliably modeled and quantified?

    NASA Astrophysics Data System (ADS)

    Hoopes, P. Jack; Petryk, Alicia A.; Giustini, Andrew J.; Stigliano, Robert V.; D'Angelo, Robert N.; Tate, Jennifer A.; Cassim, Shiraz M.; Foreman, Allan; Bischof, John C.; Pearce, John A.; Ryan, Thomas

    2011-03-01

    the target cells/tissue, and an effective and matching alternating magnetic field (AMF) for optimal and safe excitation of the nanoparticles. Our initial studies have shown that appropriately delivered and targeted nanoparticles are capable of achieving effective tumor cytotoxicity at measured thermal doses significantly less than the understood thermal dose values necessary to achieve equivalent treatment effects using conventional heat delivery techniques. Therefore conventional CEM based thermal dose - tissues effect relationships will not hold for mNPH. The goal of this effort is to provide a platform for determining the biological and physical parameters that will be necessary for accurately planning and performing safe and effective mNPH, creating a new, viable primary or adjuvant cancer therapy.

  3. Dose specification for radiation therapy: dose to water or dose to medium?

    PubMed

    Ma, C-M; Li, Jinsheng

    2011-05-21

    The Monte Carlo method enables accurate dose calculation for radiation therapy treatment planning and has been implemented in some commercial treatment planning systems. Unlike conventional dose calculation algorithms that provide patient dose information in terms of dose to water with variable electron density, the Monte Carlo method calculates the energy deposition in different media and expresses dose to a medium. This paper discusses the differences in dose calculated using water with different electron densities and that calculated for different biological media and the clinical issues on dose specification including dose prescription and plan evaluation using dose to water and dose to medium. We will demonstrate that conventional photon dose calculation algorithms compute doses similar to those simulated by Monte Carlo using water with different electron densities, which are close (<4% differences) to doses to media but significantly different (up to 11%) from doses to water converted from doses to media following American Association of Physicists in Medicine (AAPM) Task Group 105 recommendations. Our results suggest that for consistency with previous radiation therapy experience Monte Carlo photon algorithms report dose to medium for radiotherapy dose prescription, treatment plan evaluation and treatment outcome analysis. PMID:21508447

  4. Establishment and validation of a method for multi-dose irradiation of cells in 96-well microplates

    SciTech Connect

    Abatzoglou, Ioannis; Zois, Christos E.; Pouliliou, Stamatia

    2013-02-15

    Highlights: ► We established a method for multi-dose irradiation of cell cultures within a 96-well plate. ► Equations to adjust to preferable dose levels are produced and provided. ► Up to eight different dose levels can be tested in one microplate. ► This method results in fast and reliable estimation of radiation dose–response curves. -- Abstract: Microplates are useful tools in chemistry, biotechnology and molecular biology. In radiobiology research, these can be also applied to assess the effect of a certain radiation dose delivered to the whole microplate, to test radio-sensitivity, radio-sensitization or radio-protection. Whether different radiation doses can be accurately applied to a single 96-well plate to further facilitate and accelerated research by one hand and spare funds on the other, is a question dealt in the current paper. Following repeated ion-chamber, TLD and radiotherapy planning dosimetry we established a method for multi-dose irradiation of cell cultures within a 96-well plate, which allows an accurate delivery of desired doses in sequential columns of the microplate. Up to eight different dose levels can be tested in one microplate. This method results in fast and reliable estimation of radiation dose–response curves.

  5. How to accurately bypass damage

    PubMed Central

    Broyde, Suse; Patel, Dinshaw J.

    2016-01-01

    Ultraviolet radiation can cause cancer through DNA damage — specifically, by linking adjacent thymine bases. Crystal structures show how the enzyme DNA polymerase η accurately bypasses such lesions, offering protection. PMID:20577203

  6. Development of insulin delivery systems.

    PubMed

    Siddiqui, N I; Siddiqui, Ni; Rahman, S; Nessa, A

    2008-01-01

    Delivery system of insulin is vital for its acceptance and adherence to therapy for achieving the glycemic targets. Enormous developments have occurred in the delivery system of insulin during the last twenty years and each improvement was aimed at two common goals: patients convenience and better glycemic control. Till to date, the various insulin delivery systems are: syringes/vials, injection aids, jet injectors, transmucosal delivery, transdermal delivery, external insulin infusion pump, implantable insulin pumps, insulin pens and insulin inhalers. Syringe/vial is the oldest and conventional method, still widely used and relatively cheaper. Modern plastic syringes are disposable, light weight with microfine needle for patients convenience and comfort. Oral route could be the most acceptable and viable, if the barriers can be overcome and under extensive trial. Insulin pen device is an important milestone in the delivery system of insulin as it is convenient, discrete, painless, attractive, portable with flexible life style and improved quality of life. More than 80% of European diabetic patients are using insulin pen. Future digital pen will have better memory option, blood glucose monitoring system, insulin dose calculator etc. Insulin infusion pump is a good option for the children, busy patients with flexible lifestyle and those who want to avoid multiple daily injections. Pulmonary route of insulin delivery is a promising, effective, non-invasive and acceptable alternative method. Exubera, the world first insulin inhaler was approved by FDA in 28 January 2006. But due to certain limitations, it has been withdrawn from the market in October 2007. The main concern of inhaled insulin are: long term pulmonary safety issues, cost effectiveness and user friendly device. In future, more acceptable and cost effective insulin inhaler will be introduced. Newer avenues are under extensive trial for better future insulin delivery systems. PMID:18285745

  7. Accurate Evaluation of Quantum Integrals

    NASA Technical Reports Server (NTRS)

    Galant, David C.; Goorvitch, D.

    1994-01-01

    Combining an appropriate finite difference method with Richardson's extrapolation results in a simple, highly accurate numerical method for solving a Schr\\"{o}dinger's equation. Important results are that error estimates are provided, and that one can extrapolate expectation values rather than the wavefunctions to obtain highly accurate expectation values. We discuss the eigenvalues, the error growth in repeated Richardson's extrapolation, and show that the expectation values calculated on a crude mesh can be extrapolated to obtain expectation values of high accuracy.

  8. TH-A-9A-10: Prostate SBRT Delivery with Flattening-Filter-Free Mode: Benefit and Accuracy

    SciTech Connect

    Li, T; Yuan, L; Sheng, Y; Wu, Q

    2014-06-15

    Purpose: Flattening-filter-free (FFF) beam mode offered on TrueBeam™ linac enables delivering IMRT at 2400 MU/min dose rate. This study investigates the benefit and delivery accuracy of using high dose rate in the context of prostate SBRT. Methods: 8 prostate SBRT patients were retrospectively studied. In 5 cases treated with 600-MU/min dose rate, continuous prostate motion data acquired during radiation-beam-on was used to analyze motion range. In addition, the initial 1/3 of prostate motion trajectories during each radiation-beam-on was separated to simulate motion range if 2400-MU/min were used. To analyze delivery accuracy in FFF mode, MLC trajectory log files from an additional 3 cases treated at 2400-MU/min were acquired. These log files record MLC expected and actual positions every 20ms, and therefore can be used to reveal delivery accuracy. Results: (1) Benefit. On average treatment at 600-MU/min takes 30s per beam; whereas 2400-MU/min requires only 11s. When shortening delivery time to ~1/3, the prostate motion range was significantly smaller (p<0.001). Largest motion reduction occurred in Sup-Inf direction, from [−3.3mm, 2.1mm] to [−1.7mm, 1.7mm], followed by reduction from [−2.1mm, 2.4mm] to [−1.0mm, 2.4mm] in Ant-Pos direction. No change observed in LR direction [−0.8mm, 0.6mm]. The combined motion amplitude (vector norm) confirms that average motion and ranges are significantly smaller when beam-on was limited to the 1st 1/3 of actual delivery time. (2) Accuracy. Trajectory log file analysis showed excellent delivery accuracy with at 2400 MU/min. Most leaf deviations during beam-on were within 0.07mm (99-percentile). Maximum leaf-opening deviations during each beam-on were all under 0.1mm for all leaves. Dose-rate was maintained at 2400-MU/min during beam-on without dipping. Conclusion: Delivery prostate SBRT with 2400 MU/min is both beneficial and accurate. High dose rates significantly reduced both treatment time and intra-beam prostate

  9. Positron Emission Tomography Image-Guided Drug Delivery: Current Status and Future Perspectives

    PubMed Central

    2015-01-01

    Positron emission tomography (PET) is an important modality in the field of molecular imaging, which is gradually impacting patient care by providing safe, fast, and reliable techniques that help to alter the course of patient care by revealing invasive, de facto procedures to be unnecessary or rendering them obsolete. Also, PET provides a key connection between the molecular mechanisms involved in the pathophysiology of disease and the according targeted therapies. Recently, PET imaging is also gaining ground in the field of drug delivery. Current drug delivery research is focused on developing novel drug delivery systems with emphasis on precise targeting, accurate dose delivery, and minimal toxicity in order to achieve maximum therapeutic efficacy. At the intersection between PET imaging and controlled drug delivery, interest has grown in combining both these paradigms into clinically effective formulations. PET image-guided drug delivery has great potential to revolutionize patient care by in vivo assessment of drug biodistribution and accumulation at the target site and real-time monitoring of the therapeutic outcome. The expected end point of this approach is to provide fundamental support for the optimization of innovative diagnostic and therapeutic strategies that could contribute to emerging concepts in the field of “personalized medicine”. This review focuses on the recent developments in PET image-guided drug delivery and discusses intriguing opportunities for future development. The preclinical data reported to date are quite promising, and it is evident that such strategies in cancer management hold promise for clinically translatable advances that can positively impact the overall diagnostic and therapeutic processes and result in enhanced quality of life for cancer patients. PMID:24865108

  10. Using In-Service and Coaching to Increase Teachers' Accurate Use of Research-Based Strategies

    ERIC Educational Resources Information Center

    Kretlow, Allison G.; Cooke, Nancy L.; Wood, Charles L.

    2012-01-01

    Increasing the accurate use of research-based practices in classrooms is a critical issue. Professional development is one of the most practical ways to provide practicing teachers with training related to research-based practices. This study examined the effects of in-service plus follow-up coaching on first grade teachers' accurate delivery of…

  11. How flatbed scanners upset accurate film dosimetry.

    PubMed

    van Battum, L J; Huizenga, H; Verdaasdonk, R M; Heukelom, S

    2016-01-21

    Film is an excellent dosimeter for verification of dose distributions due to its high spatial resolution. Irradiated film can be digitized with low-cost, transmission, flatbed scanners. However, a disadvantage is their lateral scan effect (LSE): a scanner readout change over its lateral scan axis. Although anisotropic light scattering was presented as the origin of the LSE, this paper presents an alternative cause. Hereto, LSE for two flatbed scanners (Epson 1680 Expression Pro and Epson 10000XL), and Gafchromic film (EBT, EBT2, EBT3) was investigated, focused on three effects: cross talk, optical path length and polarization. Cross talk was examined using triangular sheets of various optical densities. The optical path length effect was studied using absorptive and reflective neutral density filters with well-defined optical characteristics (OD range 0.2-2.0). Linear polarizer sheets were used to investigate light polarization on the CCD signal in absence and presence of (un)irradiated Gafchromic film. Film dose values ranged between 0.2 to 9 Gy, i.e. an optical density range between 0.25 to 1.1. Measurements were performed in the scanner's transmission mode, with red-green-blue channels. LSE was found to depend on scanner construction and film type. Its magnitude depends on dose: for 9 Gy increasing up to 14% at maximum lateral position. Cross talk was only significant in high contrast regions, up to 2% for very small fields. The optical path length effect introduced by film on the scanner causes 3% for pixels in the extreme lateral position. Light polarization due to film and the scanner's optical mirror system is the main contributor, different in magnitude for the red, green and blue channel. We concluded that any Gafchromic EBT type film scanned with a flatbed scanner will face these optical effects. Accurate dosimetry requires correction of LSE, therefore, determination of the LSE per color channel and dose delivered to the film. PMID:26689962

  12. How flatbed scanners upset accurate film dosimetry

    NASA Astrophysics Data System (ADS)

    van Battum, L. J.; Huizenga, H.; Verdaasdonk, R. M.; Heukelom, S.

    2016-01-01

    Film is an excellent dosimeter for verification of dose distributions due to its high spatial resolution. Irradiated film can be digitized with low-cost, transmission, flatbed scanners. However, a disadvantage is their lateral scan effect (LSE): a scanner readout change over its lateral scan axis. Although anisotropic light scattering was presented as the origin of the LSE, this paper presents an alternative cause. Hereto, LSE for two flatbed scanners (Epson 1680 Expression Pro and Epson 10000XL), and Gafchromic film (EBT, EBT2, EBT3) was investigated, focused on three effects: cross talk, optical path length and polarization. Cross talk was examined using triangular sheets of various optical densities. The optical path length effect was studied using absorptive and reflective neutral density filters with well-defined optical characteristics (OD range 0.2-2.0). Linear polarizer sheets were used to investigate light polarization on the CCD signal in absence and presence of (un)irradiated Gafchromic film. Film dose values ranged between 0.2 to 9 Gy, i.e. an optical density range between 0.25 to 1.1. Measurements were performed in the scanner’s transmission mode, with red-green-blue channels. LSE was found to depend on scanner construction and film type. Its magnitude depends on dose: for 9 Gy increasing up to 14% at maximum lateral position. Cross talk was only significant in high contrast regions, up to 2% for very small fields. The optical path length effect introduced by film on the scanner causes 3% for pixels in the extreme lateral position. Light polarization due to film and the scanner’s optical mirror system is the main contributor, different in magnitude for the red, green and blue channel. We concluded that any Gafchromic EBT type film scanned with a flatbed scanner will face these optical effects. Accurate dosimetry requires correction of LSE, therefore, determination of the LSE per color channel and dose delivered to the film.

  13. Cerebellar medulloblastoma: the importance of posterior fossa dose to survival and patterns of failure

    SciTech Connect

    Silverman, C.L.; Simpson, J.R.

    1982-11-01

    Fifty patients with biopsy-proven cerebellar medulloblastoma were retrospectively analyzed for prognostic factors, survival and patterns of failure. Five- and ten-year actuarial survivals for the entire group were 51% and 42%. Survival and local control were significantly better for the 21 patients who received doses greater than 5000 rad to the posterior fossa (85% and 80% respectively) than for the remaining patients (38% and 38%, respectively). Significant prognostic factors included achievement of local control in the posterior fossa (p = .0001) and dose to the posterior fossa (p = .0005). Sex, age, duration of symptoms, extent of surgery and initial T-stage of disease were not significant. Posterior fossa was the predominant site of failure (71% of failures), but 10% of patients failed in the cerebrum and 12% outside the CNS. This experience confirms that survival rates of 70-80% are achievable with current treatment policies but accurate and consistent dose delivery to the posterior fossa is essential.

  14. Cerebellar medulloblastoma: the importance of posterior fossa dose to survival and patterns of failure

    SciTech Connect

    Silverman, C.L.; Simpson, J.R.

    1982-11-01

    Fifty patients with biopsy-proven cerebellar medulloblastoma were retrospectively analyzed for prognostic factors, survival and patterns of failure. Five- and ten-year actuarial survivals for the entire group were 51% and 42%. Survival and local control were significantly better for the 21 patients who received doses greater that 5000 rad to the posterior fossa (85% and 80% respectively) than for the remaining patients (38% and 38%, respectively). Significant prognostic factors included achievement of local control in the posterior fossa (p = .0001) and dose to the posterior fossa (p = .0005). Sex, age, duration of symptoms, extent of surgery and initial T-stage of disease were not significant. Posterior fossa was the predominant site of failure (71% of failures), but 10% of patients failed in the cerebrum and 12% outside the CNS. This experience confirms that survival rates of 70-80% are achievable with current treatment policies but accurate and consistent dose delivery to the posterior fossa is essential.

  15. Imaging dose in breast radiotherapy: does breast size affect the dose to the organs at risk and the risk of secondary cancer to the contralateral breast?

    SciTech Connect

    Batumalai, Vikneswary; Quinn, Alexandra; Jameson, Michael; Delaney, Geoff; Holloway, Lois

    2015-03-15

    Correct target positioning is crucial for accurate dose delivery in breast radiotherapy resulting in utilisation of daily imaging. However, the radiation dose from daily imaging is associated with increased probability of secondary induced cancer. The aim of this study was to quantify doses associated with three imaging modalities and investigate the correlation of dose and varying breast size in breast radiotherapy. Planning computed tomography (CT) data sets of 30 breast cancer patients were utilised to simulate the dose received by various organs from a megavoltage computed tomography (MV-CT), megavoltage electronic portal image (MV-EPI) and megavoltage cone-beam computed tomography (MV-CBCT). The mean dose to organs adjacent to the target volume (contralateral breast, lungs, spinal cord and heart) were analysed. Pearson correlation analysis was performed to determine the relationship between imaging dose and primary breast volume and the lifetime attributable risk (LAR) of induced secondary cancer was calculated for the contralateral breast. The highest contralateral breast mean dose was from the MV-CBCT (1.79 Gy), followed by MV-EPI (0.22 Gy) and MV-CT (0.11 Gy). A similar trend was found for all organs at risk (OAR) analysed. The primary breast volume inversely correlated with the contralateral breast dose for all three imaging modalities. As the primary breast volume increases, the likelihood of a patient developing a radiation-induced secondary cancer to the contralateral breast decreases. MV-CBCT showed a stronger relationship between breast size and LAR of developing a radiation-induced contralateral breast cancer in comparison with the MV-CT and MV-EPI. For breast patients, imaging dose to OAR depends on imaging modality and treated breast size. When considering the use of imaging during breast radiotherapy, the patient's breast size and contralateral breast dose should be taken into account.

  16. A method of dose reconstruction for moving targets compatible with dynamic treatments

    PubMed Central

    Poulsen, Per Rugaard; Schmidt, Mai Lykkegaard; Keall, Paul; Worm, Esben Schjødt; Fledelius, Walther; Hoffmann, Lone

    2012-01-01

    Purpose: To develop a method that allows a commercial treatment planning system (TPS) to perform accurate dose reconstruction for rigidly moving targets and to validate the method in phantom measurements for a range of treatments including intensity modulated radiation therapy (IMRT), volumetric arc therapy (VMAT), and dynamic multileaf collimator (DMLC) tracking. Methods: An in-house computer program was developed to manipulate Dicom treatment plans exported from a TPS (Eclipse, Varian Medical Systems) such that target motion during treatment delivery was incorporated into the plans. For each treatment, a motion including plan was generated by dividing the intratreatment target motion into 1 mm position bins and construct sub-beams that represented the parts of the treatment that were delivered, while the target was located within each position bin. For each sub-beam, the target shift was modeled by a corresponding isocenter shift. The motion incorporating Dicom plans were reimported into the TPS, where dose calculation resulted in motion including target dose distributions. For experimental validation of the dose reconstruction a thorax phantom with a moveable lung equivalent rod with a tumor insert of solid water was first CT scanned. The tumor insert was delineated as a gross tumor volume (GTV), and a planning target volume (PTV) was formed by adding margins. A conformal plan, two IMRT plans (step-and-shoot and sliding windows), and a VMAT plan were generated giving minimum target doses of 95% (GTV) and 67% (PTV) of the prescription dose (3 Gy). Two conformal fields with MLC leaves perpendicular and parallel to the tumor motion, respectively, were generated for DMLC tracking. All treatment plans were delivered to the thorax phantom without tumor motion and with a sinusoidal tumor motion. The two conformal fields were delivered with and without portal image guided DMLC tracking based on an embedded gold marker. The target dose distribution was measured with a

  17. Investigating the accuracy of microstereotactic-body-radiotherapy utilizing anatomically accurate 3D printed rodent-morphic dosimeters

    SciTech Connect

    Bache, Steven T.; Juang, Titania; Belley, Matthew D.; Koontz, Bridget F.; Yoshizumi, Terry T.; Kirsch, David G.; Oldham, Mark; Adamovics, John

    2015-02-15

    Purpose: Sophisticated small animal irradiators, incorporating cone-beam-CT image-guidance, have recently been developed which enable exploration of the efficacy of advanced radiation treatments in the preclinical setting. Microstereotactic-body-radiation-therapy (microSBRT) is one technique of interest, utilizing field sizes in the range of 1–15 mm. Verification of the accuracy of microSBRT treatment delivery is challenging due to the lack of available methods to comprehensively measure dose distributions in representative phantoms with sufficiently high spatial resolution and in 3 dimensions (3D). This work introduces a potential solution in the form of anatomically accurate rodent-morphic 3D dosimeters compatible with ultrahigh resolution (0.3 mm{sup 3}) optical computed tomography (optical-CT) dose read-out. Methods: Rodent-morphic dosimeters were produced by 3D-printing molds of rodent anatomy directly from contours defined on x-ray CT data sets of rats and mice, and using these molds to create tissue-equivalent radiochromic 3D dosimeters from Presage. Anatomically accurate spines were incorporated into some dosimeters, by first 3D printing the spine mold, then forming a high-Z bone equivalent spine insert. This spine insert was then set inside the tissue equivalent body mold. The high-Z spinal insert enabled representative cone-beam CT IGRT targeting. On irradiation, a linear radiochromic change in optical-density occurs in the dosimeter, which is proportional to absorbed dose, and was read out using optical-CT in high-resolution (0.5 mm isotropic voxels). Optical-CT data were converted to absolute dose in two ways: (i) using a calibration curve derived from other Presage dosimeters from the same batch, and (ii) by independent measurement of calibrated dose at a point using a novel detector comprised of a yttrium oxide based nanocrystalline scintillator, with a submillimeter active length. A microSBRT spinal treatment was delivered consisting of a 180

  18. Investigating the accuracy of microstereotactic-body-radiotherapy utilizing anatomically accurate 3D printed rodent-morphic dosimeters

    PubMed Central

    Bache, Steven T.; Juang, Titania; Belley, Matthew D.; Koontz, Bridget F.; Adamovics, John; Yoshizumi, Terry T.; Kirsch, David G.; Oldham, Mark

    2015-01-01

    Purpose: Sophisticated small animal irradiators, incorporating cone-beam-CT image-guidance, have recently been developed which enable exploration of the efficacy of advanced radiation treatments in the preclinical setting. Microstereotactic-body-radiation-therapy (microSBRT) is one technique of interest, utilizing field sizes in the range of 1–15 mm. Verification of the accuracy of microSBRT treatment delivery is challenging due to the lack of available methods to comprehensively measure dose distributions in representative phantoms with sufficiently high spatial resolution and in 3 dimensions (3D). This work introduces a potential solution in the form of anatomically accurate rodent-morphic 3D dosimeters compatible with ultrahigh resolution (0.3 mm3) optical computed tomography (optical-CT) dose read-out. Methods: Rodent-morphic dosimeters were produced by 3D-printing molds of rodent anatomy directly from contours defined on x-ray CT data sets of rats and mice, and using these molds to create tissue-equivalent radiochromic 3D dosimeters from Presage. Anatomically accurate spines were incorporated into some dosimeters, by first 3D printing the spine mold, then forming a high-Z bone equivalent spine insert. This spine insert was then set inside the tissue equivalent body mold. The high-Z spinal insert enabled representative cone-beam CT IGRT targeting. On irradiation, a linear radiochromic change in optical-density occurs in the dosimeter, which is proportional to absorbed dose, and was read out using optical-CT in high-resolution (0.5 mm isotropic voxels). Optical-CT data were converted to absolute dose in two ways: (i) using a calibration curve derived from other Presage dosimeters from the same batch, and (ii) by independent measurement of calibrated dose at a point using a novel detector comprised of a yttrium oxide based nanocrystalline scintillator, with a submillimeter active length. A microSBRT spinal treatment was delivered consisting of a 180

  19. Real time sensor for therapeutic radiation delivery

    DOEpatents

    Bliss, Mary; Craig, Richard A.; Reeder, Paul L.

    1998-01-01

    The invention is a real time sensor for therapeutic radiation. A probe is placed in or near the patient that senses in real time the dose at the location of the probe. The strength of the dose is determined by either an insertion or an exit probe. The location is determined by a series of vertical and horizontal sensing elements that gives the operator a real time read out dose location relative to placement of the patient. The increased accuracy prevents serious tissue damage to the patient by preventing overdose or delivery of a dose to a wrong location within the body.

  20. Real time sensor for therapeutic radiation delivery

    DOEpatents

    Bliss, M.; Craig, R.A.; Reeder, P.L.

    1998-01-06

    The invention is a real time sensor for therapeutic radiation. A probe is placed in or near the patient that senses in real time the dose at the location of the probe. The strength of the dose is determined by either an insertion or an exit probe. The location is determined by a series of vertical and horizontal sensing elements that gives the operator a real time read out dose location relative to placement of the patient. The increased accuracy prevents serious tissue damage to the patient by preventing overdose or delivery of a dose to a wrong location within the body. 14 figs.

  1. Helical tomotherapy superficial dose measurements

    SciTech Connect

    Ramsey, Chester R.; Seibert, Rebecca M.; Robison, Benjamin; Mitchell, Martha

    2007-08-15

    Helical tomotherapy is a treatment technique that is delivered from a 6 MV fan beam that traces a helical path while the couch moves linearly into the bore. In order to increase the treatment delivery dose rate, helical tomotherapy systems do not have a flattening filter. As such, the dose distributions near the surface of the patient may be considerably different from other forms of intensity-modulated delivery. The purpose of this study was to measure the dose distributions near the surface for helical tomotherapy plans with a varying separation between the target volume and the surface of an anthropomorphic phantom. A hypothetical planning target volume (PTV) was defined on an anthropomorphic head phantom to simulate a 2.0 Gy per fraction IMRT parotid-sparing head and neck treatment of the upper neck nodes. A total of six target volumes were created with 0, 1, 2, 3, 4, and 5 mm of separation between the surface of the phantom and the outer edge of the PTV. Superficial doses were measured for each of the treatment deliveries using film placed in the head phantom and thermoluminescent dosimeters (TLDs) placed on the phantom's surface underneath an immobilization mask. In the 0 mm test case where the PTV extends to the phantom surface, the mean TLD dose was 1.73{+-}0.10 Gy (or 86.6{+-}5.1% of the prescribed dose). The measured superficial dose decreases to 1.23{+-}0.10 Gy (61.5{+-}5.1% of the prescribed dose) for a PTV-surface separation of 5 mm. The doses measured by the TLDs indicated that the tomotherapy treatment planning system overestimates superficial doses by 8.9{+-}3.2%. The radiographic film dose for the 0 mm test case was 1.73{+-}0.07 Gy, as compared to the calculated dose of 1.78{+-}0.05 Gy. Given the results of the TLD and film measurements, the superficial calculated doses are overestimated between 3% and 13%. Without the use of bolus, tumor volumes that extend to the surface may be underdosed. As such, it is recommended that bolus be added for these

  2. Improving radiotherapy planning, delivery accuracy, and normal tissue sparing using cutting edge technologies

    PubMed Central

    Glide-Hurst, Carri K.

    2014-01-01

    In the United States, more than half of all new invasive cancers diagnosed are non-small cell lung cancer, with a significant number of these cases presenting at locally advanced stages, resulting in about one-third of all cancer deaths. While the advent of stereotactic ablative radiation therapy (SABR, also known as stereotactic body radiotherapy, or SBRT) for early-staged patients has improved local tumor control to >90%, survival results for locally advanced stage lung cancer remain grim. Significant challenges exist in lung cancer radiation therapy including tumor motion, accurate dose calculation in low density media, limiting dose to nearby organs at risk, and changing anatomy over the treatment course. However, many recent technological advancements have been introduced that can meet these challenges, including four-dimensional computed tomography (4DCT) and volumetric cone-beam computed tomography (CBCT) to enable more accurate target definition and precise tumor localization during radiation, respectively. In addition, advances in dose calculation algorithms have allowed for more accurate dosimetry in heterogeneous media, and intensity modulated and arc delivery techniques can help spare organs at risk. New delivery approaches, such as tumor tracking and gating, offer additional potential for further reducing target margins. Image-guided adaptive radiation therapy (IGART) introduces the potential for individualized plan adaptation based on imaging feedback, including bulky residual disease, tumor progression, and physiological changes that occur during the treatment course. This review provides an overview of the current state of the art technology for lung cancer volume definition, treatment planning, localization, and treatment plan adaptation. PMID:24688775

  3. Actual Dose Variation of Parotid Glands and Spinal Cord for Nasopharyngeal Cancer Patients During Radiotherapy

    SciTech Connect

    Han Chunhui Chen Yijen; Liu An; Schultheiss, Timothy E.; Wong, Jeffrey Y.C.

    2008-03-15

    Purpose: For intensity-modulated radiotherapy of nasopharyngeal cancer, accurate dose delivery is crucial to the success of treatment. This study aimed to evaluate the significance of daily image-guided patient setup corrections and to quantify the parotid gland volume and dose variations for nasopharyngeal cancer patients using helical tomotherapy megavoltage computed tomography (CT). Methods and Materials: Five nasopharyngeal cancer patients who underwent helical tomotherapy were selected retrospectively. Each patient had received 70 Gy in 35 fractions. Daily megavoltage CT scans were registered with the planning CT images to correct the patient setup errors. Contours of the spinal cord and parotid glands were drawn on the megavoltage CT images at fixed treatment intervals. The actual doses delivered to the critical structures were calculated using the helical tomotherapy Planned Adaptive application. Results: The maximal dose to the spinal cord showed a significant increase and greater variation without daily setup corrections. The significant decrease in the parotid gland volume led to a greater median dose in the later phase of treatment. The average parotid gland volume had decreased from 20.5 to 13.2 cm{sup 3} by the end of treatment. On average, the median dose to the parotid glands was 83 cGy and 145 cGy for the first and the last treatment fractions, respectively. Conclusions: Daily image-guided setup corrections can eliminate significant dose variations to critical structures. Constant monitoring of patient anatomic changes and selective replanning should be used during radiotherapy to avoid critical structure complications.

  4. Multiple anatomy optimization of accumulated dose

    SciTech Connect

    Watkins, W. Tyler Siebers, Jeffrey V.; Moore, Joseph A.; Gordon, James; Hugo, Geoffrey D.

    2014-11-01

    Purpose: To investigate the potential advantages of multiple anatomy optimization (MAO) for lung cancer radiation therapy compared to the internal target volume (ITV) approach. Methods: MAO aims to optimize a single fluence to be delivered under free-breathing conditions such that the accumulated dose meets the plan objectives, where accumulated dose is defined as the sum of deformably mapped doses computed on each phase of a single four dimensional computed tomography (4DCT) dataset. Phantom and patient simulation studies were carried out to investigate potential advantages of MAO compared to ITV planning. Through simulated delivery of the ITV- and MAO-plans, target dose variations were also investigated. Results: By optimizing the accumulated dose, MAO shows the potential to ensure dose to the moving target meets plan objectives while simultaneously reducing dose to organs at risk (OARs) compared with ITV planning. While consistently superior to the ITV approach, MAO resulted in equivalent OAR dosimetry at planning objective dose levels to within 2% volume in 14/30 plans and to within 3% volume in 19/30 plans for each lung V20, esophagus V25, and heart V30. Despite large variations in per-fraction respiratory phase weights in simulated deliveries at high dose rates (e.g., treating 4/10 phases during single fraction beams) the cumulative clinical target volume (CTV) dose after 30 fractions and per-fraction dose were constant independent of planning technique. In one case considered, however, per-phase CTV dose varied from 74% to 117% of prescription implying the level of ITV-dose heterogeneity may not be appropriate with conventional, free-breathing delivery. Conclusions: MAO incorporates 4DCT information in an optimized dose distribution and can achieve a superior plan in terms of accumulated dose to the moving target and OAR sparing compared to ITV-plans. An appropriate level of dose heterogeneity in MAO plans must be further investigated.

  5. Multiple anatomy optimization of accumulated dose

    PubMed Central

    Watkins, W. Tyler; Moore, Joseph A.; Gordon, James; Hugo, Geoffrey D.; Siebers, Jeffrey V.

    2014-01-01

    Purpose: To investigate the potential advantages of multiple anatomy optimization (MAO) for lung cancer radiation therapy compared to the internal target volume (ITV) approach. Methods: MAO aims to optimize a single fluence to be delivered under free-breathing conditions such that the accumulated dose meets the plan objectives, where accumulated dose is defined as the sum of deformably mapped doses computed on each phase of a single four dimensional computed tomography (4DCT) dataset. Phantom and patient simulation studies were carried out to investigate potential advantages of MAO compared to ITV planning. Through simulated delivery of the ITV- and MAO-plans, target dose variations were also investigated. Results: By optimizing the accumulated dose, MAO shows the potential to ensure dose to the moving target meets plan objectives while simultaneously reducing dose to organs at risk (OARs) compared with ITV planning. While consistently superior to the ITV approach, MAO resulted in equivalent OAR dosimetry at planning objective dose levels to within 2% volume in 14/30 plans and to within 3% volume in 19/30 plans for each lung V20, esophagus V25, and heart V30. Despite large variations in per-fraction respiratory phase weights in simulated deliveries at high dose rates (e.g., treating 4/10 phases during single fraction beams) the cumulative clinical target volume (CTV) dose after 30 fractions and per-fraction dose were constant independent of planning technique. In one case considered, however, per-phase CTV dose varied from 74% to 117% of prescription implying the level of ITV-dose heterogeneity may not be appropriate with conventional, free-breathing delivery. Conclusions: MAO incorporates 4DCT information in an optimized dose distribution and can achieve a superior plan in terms of accumulated dose to the moving target and OAR sparing compared to ITV-plans. An appropriate level of dose heterogeneity in MAO plans must be further investigated. PMID:25370619

  6. The effect of low dose fentanyl as a premedication before induction of general anesthesia on the neonatal apgar score in cesarean section delivery: randomized, double-blind controlled trial

    PubMed Central

    Karbasy, Seyyed Hasan; Derakhshan, Pooya

    2016-01-01

    Background: The administration of opioids before induction of general anesthesia can be considered as a problem in cesarean section. The aim of this study was to compare the effects of intravenous Fentanyl as a premedication before induction of general anesthesia versus placebo on maternal hemodynamic parameters and on the first and fifth minutes Apgar score in the neonates in elective cesarean delivery. Methods: This double- blinded, randomized, clinical trial study was conducted in 2014-2015 at Vali-e-Asr hospital, Birjand, Iran. Ninety full term pregnant women undergoing elective cesarean section delivery under general anesthesia were selected. The participants were randomly classified into two groups: The Fentanyl group and the placebo. Iintravenous Fentanyl 1μg/kg was administrated three minutes before anesthesia induction for the Fentanyl group, and 2 milliliter normal saline was administered for the placebo group. Maternal mean arterial pressure, heart rate before the start of anesthesia induction and thirty seconds after intubation were measured. Also, the first and fifth minutes Apgar scores of the neonates were evaluated and recorded by a blinded anesthesiologist. The clinical trial registration number was IRCT2015010320112N3. Results: Maternal mean arterial pressure was significantly lower in the Fentanyl group than the placebo group after intubation. Heart rate was significantly higher in the placebo group before the start of anesthesia induction and after intubation compared to the Fentanyl group. The first and fifth minutes’ Apgar scores of the neonates were not statistically different between the two groups. Conclusion: Administration of 1μg/Kg intravenous Fentanyl before the induction of anesthesia for cesarean section delivery decreases maternal hemodynamic changes after intubation. In addition, it does not have any effect on Apgar scores of the neonate in the 1st and 5th minutes after birth. PMID:27493905

  7. Evaluating and improving patient-specific QA for IMRT delivery

    NASA Astrophysics Data System (ADS)

    Yan, Guanghua

    2009-12-01

    Modern radiation therapy techniques such as intensity-modulated radiation therapy (IMRT) and newly-emerging volumetric modulated arc therapy (VMAT) aim to deliver highly conformal radiation dose to the target volume while sparing nearby critical organs as much as possible with the complex motion of multi-leaf collimator (MLC) leaves. Pre-treatment patient specific quality assurance (QA) has become an essential part of IMRT in making sure the delivered dose distributions agree with the planned ones. This dissertation evaluates the performance of current patient-specific QA process and proposes solutions to improve its sensitivity, accuracy and efficiency. In step and shoot IMRT, the study on the sensitivity of patient-specific QA to minor MLC errors reveals tighter criterion such as 2%/2mm must be employed to detect systematic MLC positioning errors of 2 mm. However, such criterion results in low average passing rate which leads to excessive false alarms, mainly due to inadequate treatment planning system (TPS) beam modeling on beam penumbra. An analytical deconvolution approach is proposed to recover true photon beam profiles to obtain a true beam model which significantly improves agreement between calculated and measured dose distributions. Thus a tighter criterion could be employed to enhance the sensitivity of patient-specific QA to minor errors in the delivery system. Measurement based patient-specific IMRT QA is a time-consuming process. A fast and accurate independent planar dose calculation algorithm is proposed to replace measurement based QA. The algorithm analytically models photons coming out from the accelerator and computes dose distribution from first principles. Accuracy of the algorithm is validated against 2D diode array measurements. The algorithm is found to be fast and accurate enough to replace time consuming measurement based QA. Patient-specific QA for VMAT differs significantly from step and shoot IMRT due to the increased use of dynamic

  8. Surfactant Delivery into the Lung

    NASA Astrophysics Data System (ADS)

    Grotberg, James; Filoche, Marcel

    2014-11-01

    We have developed a multiscale, compartmentalized model of surfactant and liquid delivery into the lung. Assuming liquid plug propagation, the airway compartment accounts for the plug's volume deposition (coating) on the airway wall, while the bifurcation compartment accounts for plug splitting from the parent airway to the two daughter airways. Generally the split is unequal due to gravity and geometry effects. Both the deposition ratio RD (deposition volume/airway volume), and the splitting ratio, RS, of the daughters volumes are solved independently from one another. Then they are used in a 3D airway network geometry to achieve the distribution of delivery into the lung. The airway geometry is selected for neonatal as well as adult applications, and can be advanced from symmetric, to stochastically asymmetric, to personalized. RD depends primarily on the capillary number, Ca, while RS depends on Ca, the Reynolds number, Re, the Bond number, Bo, the dose volume, VD, and the branch angles. The model predicts the distribution of coating on the airway walls and the remaining plug volume delivered to the alveolar region at the end of the tree. Using this model, we are able to simulate and test various delivery protocols, in order to optimize delivery and improve the respiratory function.

  9. The dose response relation for rat spinal cord paralysis analyzed in terms of the effective size of the functional subunit

    NASA Astrophysics Data System (ADS)

    Adamus-Górka, Magdalena; Mavroidis, Panayiotis; Brahme, Anders; Lind, Bengt K.

    2008-11-01

    Radiobiological models for estimating normal tissue complication probability (NTCP) are increasingly used in order to quantify or optimize the clinical outcome of radiation therapy. A good NTCP model should fulfill at least the following two requirements: (a) it should predict the sigmoid shape of the corresponding dose-response curve and (b) it should accurately describe the probability of a specified response for arbitrary non-uniform dose delivery for a given endpoint as accurately as possible, i.e. predict the volume dependence. In recent studies of the volume effect of a rat spinal cord after irradiation with narrow and broad proton beams the authors claim that none of the existing NTCP models is able to describe their results. Published experimental data have been used here to try to quantify the change in the effective dose (D50) causing 50% response for different field sizes. The present study was initiated to describe the induction of white matter necrosis in a rat spinal cord after irradiation with narrow proton beams in terms of the mean dose to the effective volume of the functional subunit (FSU). The physically delivered dose distribution was convolved with a function describing the effective size or, more accurately, the sensitivity distribution of the FSU to obtain the effective mean dose deposited in it. This procedure allows the determination of the mean D50 value of the FSUs of a certain size which is of interest for example if the cell nucleus of the oligodendrocyte is the sensitive target. Using the least-squares method to compare the effective doses for different sizes of the functional subunits with the experimental data the best fit was obtained with a length of about 9 mm. For the non-uniform dose distributions an effective FSU length of 8 mm gave the optimal fit with the probit dose-response model. The method could also be used to interpret the so-called bath and shower experiments where the heterogeneous dose delivery was used in the

  10. SU-E-T-421: Feasibility Study of Volumetric Modulated Arc Therapy with Constant Dose Rate for Endometrial Cancer

    SciTech Connect

    Yang, R; Wang, J

    2014-06-01

    Purpose: To investigate the feasibility, efficiency, and delivery accuracy of volumetric modulated arc therapy with constant dose rate (VMAT-CDR) for whole-pelvic radiotherapy (WPRT) of endometrial cancer. Methods: The nine-Field intensity-modulated radiotherapy (IMRT), VMAT with variable dose-rate (VMAT-VDR), and VMAT-CDR plans were created for 9 patients with endometrial cancer undergoing WPRT. The dose distribution of planning target volume (PTV), organs at risk (OARs), and normal tissue (NT) were compared. The monitor units (MUs) and treatment delivery time were also evaluated. For each VMAT-CDR plan, a dry Run was performed to assess the dosimetric accuracy with MatriXX from IBA. Results: Compared with IMRT, the VMAT-CDR plans delivered a slightly greater V20 of the bowel, bladder, pelvis bone, and NT, but significantly decreased the dose to the high-dose region of the rectum and pelvis bone. The MUs Decreased from 1105 with IMRT to 628 with VMAT-CDR. The delivery time also decreased from 9.5 to 3.2 minutes. The average gamma pass rate was 95.6% at the 3%/3 mm criteria with MatriXX pretreatment verification for 9 patients. Conclusion: VMAT-CDR can achieve comparable plan quality with significant shorter delivery time and smaller number of MUs compared with IMRT for patients with endometrial cancer undergoing WPRT. It can be accurately delivered and be an alternative to IMRT on the linear accelerator without VDR capability. This work is supported by the grant project, National Natural; Science Foundation of China (No. 81071237)

  11. Imaging doses in radiation therapy from kilovoltage cone-beam computed tomography

    NASA Astrophysics Data System (ADS)

    Hyer, Daniel Ellis

    Advances in radiation treatment delivery, such as intensity modulated radiation therapy (IMRT), have made it possible to deliver large doses of radiation with a high degree of conformity. While highly conformal treatments offers the advantage of sparing surrounding normal tissue, this benefit can only be realized if the patient is accurately positioned during each treatment fraction. The need to accurately position the patient has led to the development and use of gantry mounted kilovoltage cone-beam computed tomography (kV-CBCT) systems. These systems are used to acquire high resolution volumetric images of the patient which are then digitally registered with the planning CT dataset to confirm alignment of the patient on the treatment table. While kV-CBCT is a very useful tool for aligning the patient prior to treatment, daily use in a high fraction therapy regimen results in a substantial radiation dose. In order to quantify the radiation dose associated with CBCT imaging, an anthropomorphic phantom representing a 50th percentile adult male and a fiber-optic coupled (FOC) dosimetry system were both constructed as part of this dissertation. These tools were then used to directly measure organ doses incurred during clinical protocols for the head, chest, and pelvis. For completeness, the dose delivered from both the X-ray Volumetric Imager (XVI, Elekta Oncology Systems, Crawley, UK) and the On-Board Imager (OBI, Varian Medical Systems, Palo Alto, CA) were investigated. While this study provided a direct measure of organ doses for estimating risk to the patient, a practical method for estimating organ doses that could be performed with phantoms and dosimeters currently available at most clinics was also desired. To accomplish this goal, a 100 mm pencil ion chamber was used to measure the "cone beam dose index" (CBDI) inside standard CT dose index (CTDI) acrylic phantoms. A weighted CBDI (CBDIw), similar to the weighted CT dose index (CTDIw), was then calculated to

  12. Image reconstruction of optical computed tomography by using the algebraic reconstruction technique for dose readouts of polymer gel dosimeters.

    PubMed

    Shih, Cheng-Ting; Chang, Yuan-Jen; Hsu, Jui-Ting; Chuang, Keh-Shih; Chang, Shu-Jun; Wu, Jay

    2015-12-01

    Optical computed tomography (optical CT) has been proven to be a useful tool for dose readouts of polymer gel dosimeters. In this study, the algebraic reconstruction technique (ART) for image reconstruction of gel dosimeters was used to improve the image quality of optical CT. Cylindrical phantoms filled with N-isopropyl-acrylamide polymer gels were irradiated using a medical linear accelerator. A circular dose distribution and a hexagonal dose distribution were produced by applying the VMAT technique and the six-field dose delivery, respectively. The phantoms were scanned using optical CT, and the images were reconstructed using the filtered back-projection (FBP) algorithm and the ART. For the circular dose distribution, the ART successfully reduced the ring artifacts and noise in the reconstructed image. For the hexagonal dose distribution, the ART reduced the hot spots at the entrances of the beams and increased the dose uniformity in the central region. Within 50% isodose line, the gamma pass rates for the 2 mm/3% criteria for the ART and FBP were 99.2% and 88.1%, respectively. The ART could be used for the reconstruction of optical CT images to improve image quality and provide accurate dose conversion for polymer gel dosimeters. PMID:26165178

  13. Predict amine solution properties accurately

    SciTech Connect

    Cheng, S.; Meisen, A.; Chakma, A.

    1996-02-01

    Improved process design begins with using accurate physical property data. Especially in the preliminary design stage, physical property data such as density viscosity, thermal conductivity and specific heat can affect the overall performance of absorbers, heat exchangers, reboilers and pump. These properties can also influence temperature profiles in heat transfer equipment and thus control or affect the rate of amine breakdown. Aqueous-amine solution physical property data are available in graphical form. However, it is not convenient to use with computer-based calculations. Developed equations allow improved correlations of derived physical property estimates with published data. Expressions are given which can be used to estimate physical properties of methyldiethanolamine (MDEA), monoethanolamine (MEA) and diglycolamine (DGA) solutions.

  14. Accurate thickness measurement of graphene

    NASA Astrophysics Data System (ADS)

    Shearer, Cameron J.; Slattery, Ashley D.; Stapleton, Andrew J.; Shapter, Joseph G.; Gibson, Christopher T.

    2016-03-01

    Graphene has emerged as a material with a vast variety of applications. The electronic, optical and mechanical properties of graphene are strongly influenced by the number of layers present in a sample. As a result, the dimensional characterization of graphene films is crucial, especially with the continued development of new synthesis methods and applications. A number of techniques exist to determine the thickness of graphene films including optical contrast, Raman scattering and scanning probe microscopy techniques. Atomic force microscopy (AFM), in particular, is used extensively since it provides three-dimensional images that enable the measurement of the lateral dimensions of graphene films as well as the thickness, and by extension the number of layers present. However, in the literature AFM has proven to be inaccurate with a wide range of measured values for single layer graphene thickness reported (between 0.4 and 1.7 nm). This discrepancy has been attributed to tip-surface interactions, image feedback settings and surface chemistry. In this work, we use standard and carbon nanotube modified AFM probes and a relatively new AFM imaging mode known as PeakForce tapping mode to establish a protocol that will allow users to accurately determine the thickness of graphene films. In particular, the error in measuring the first layer is reduced from 0.1-1.3 nm to 0.1-0.3 nm. Furthermore, in the process we establish that the graphene-substrate adsorbate layer and imaging force, in particular the pressure the tip exerts on the surface, are crucial components in the accurate measurement of graphene using AFM. These findings can be applied to other 2D materials.

  15. Helical tomotherapy with dynamic running-start-stop delivery compared to conventional tomotherapy delivery

    SciTech Connect

    Rong, Yi; Chen, Yu; Lu, Weiguo; Shang, Lu; Zuo, Li; Chen, Quan

    2014-05-15

    Purpose: Despite superior target dose uniformity, helical tomotherapy{sup ®} (HT) may involve a trade-off between longitudinal dose conformity and beam-on time (BOT), due to the limitation of only three available jaw sizes with the conventional HT (1.0, 2.5, and 5.0 cm). The recently introduced dynamic running-start-stop (RSS) delivery allows smaller jaw opening at the superior and inferior ends of the target when a sharp penumbra is needed. This study compared the dosimetric performance of RSS delivery with the fixed jaw HT delivery. Methods: Twenty patient cases were selected and deidentified prior to treatment planning, including 16 common clinical cases (brain, head and neck (HN), lung, and prostate) and four special cases of whole brain with hippocampus avoidance (WBHA) that require a high degree of dose modulation. HT plans were generated for common clinical cases using the fixed 2.5 cm jaw width (HT2.5) and WBHA cases using 1.0 cm (HT1.0). The jaw widths for RSS were preset with a larger size (RSS5.0 vs HT2.5 and RSS2.5 vs HT1.0). Both delivery techniques were planned based on identical contours, prescriptions, and planning objectives. Dose indices for targets and critical organs were compared using dose-volume histograms, BOT, and monitor units. Results: The average BOT was reduced from 4.8 min with HT2.5 to 2.5 min with RSS5.0. Target dose homogeneity with RSS5.0 was shown comparable to HT2.5 for common clinical sites. Superior normal tissue sparing was observed in RSS5.0 for optic nerves and optic chiasm in brain and HN cases. RSS5.0 demonstrated improved dose sparing for cord and esophagus in lung cases, as well as penile bulb in prostate cases. The mean body dose was comparable for both techniques. For the WBHA cases, the target homogeneity was significantly degraded in RSS2.5 without distinct dose sparing for hippocampus, compared to HT1.0. Conclusions: Compared to the fixed jaw HT delivery, RSS combined with a larger jaw width provides faster

  16. Ultrasound mediated nanoparticle drug delivery

    NASA Astrophysics Data System (ADS)

    Mullin, Lee B.

    Ultrasound is not only a powerful diagnostic tool, but also a promising therapeutic technology that can be used to improve localized drug delivery. Microbubble contrast agents are micron sized encapsulated gas filled bubbles that are administered intravenously. Originally developed to enhance ultrasound images, microbubbles are highly echogenic due to the gas core that provides a detectable impedance difference from the surrounding medium. The core also allows for controlled response of the microbubbles to ultrasound pulses. Microbubbles can be pushed using acoustic radiation force and ruptured using high pressures. Destruction of microbubbles can increase permeability at the cellular and vascular level, which can be advantageous for drug delivery. Advances in drug delivery methods have been seen with the introduction of nanoparticles, nanometer sized objects often carrying a drug payload. In chemotherapy, nanoparticles can deliver drugs to tumors while limiting systemic exposure due to abnormalities in tumor vasculature such large gaps between endothelial cells that allow nanoparticles to enter into the interstitial space; this is referred to as the enhanced permeability and retention (EPR) effect. However, this effect may be overestimated in many tumors. Additionally, only a small percentage of the injected dose accumulates in the tumor, which most the nanoparticles accumulating in the liver and spleen. It is hypothesized that combining the acoustic activity of an ultrasound contrast agent with the high payload and extravasation ability of a nanoparticle, localized delivery to the tumor with reduced systemic toxicity can be achieved. This method can be accomplished by either loading nanoparticles onto the shell of the microbubble or through a coadministration method of both nanoparticles and microbubbles. The work presented in this dissertation utilizes novel and commercial nanoparticle formulations, combined with microbubbles and a variety of ultrasound systems

  17. Accurate ab Initio Spin Densities

    PubMed Central

    2012-01-01

    We present an approach for the calculation of spin density distributions for molecules that require very large active spaces for a qualitatively correct description of their electronic structure. Our approach is based on the density-matrix renormalization group (DMRG) algorithm to calculate the spin density matrix elements as a basic quantity for the spatially resolved spin density distribution. The spin density matrix elements are directly determined from the second-quantized elementary operators optimized by the DMRG algorithm. As an analytic convergence criterion for the spin density distribution, we employ our recently developed sampling-reconstruction scheme [J. Chem. Phys.2011, 134, 224101] to build an accurate complete-active-space configuration-interaction (CASCI) wave function from the optimized matrix product states. The spin density matrix elements can then also be determined as an expectation value employing the reconstructed wave function expansion. Furthermore, the explicit reconstruction of a CASCI-type wave function provides insight into chemically interesting features of the molecule under study such as the distribution of α and β electrons in terms of Slater determinants, CI coefficients, and natural orbitals. The methodology is applied to an iron nitrosyl complex which we have identified as a challenging system for standard approaches [J. Chem. Theory Comput.2011, 7, 2740]. PMID:22707921

  18. Intratumoral delivery of low doses of anti-CD40 mAb combined with monophosphoryl lipid A induces local and systemic antitumor effects in immunocompetent and T cell-deficient mice

    PubMed Central

    Van De Voort, Tyler J.; Felder, Mildred A. R.; Yang, Richard K.; Sondel, Paul M.; Rakhmilevich, Alexander L.

    2012-01-01

    In this study, an agonistic anti-CD40 monoclonal antibody was combined with monophosphoryl lipid A (MPL), a nontoxic derivative of LPS and agonist of toll-like receptor 4, to assess the immunomodulatory and antitumor synergy between the two agents in mice. Anti-CD40 was capable of priming macrophages to subsequent ex vivo activation by MPL in immunocompetent and T cell-depleted mice. Intraperitoneal injections of anti-CD40+MPL induced additive to synergistic suppression of poorly immunogenic B16-F10 melanoma growing subcutaneously in syngeneic mice. When anti-CD40+MPL were injected directly into the subcutaneous tumor, the combination treatment was more effective, even with a 25-fold reduction in dose. Low-dose intratumoral treatment also slowed the growth of a secondary tumor growing simultaneously at a distant, untreated site. Antitumor effects were also induced in immunodeficient SCID mice and in T cell-depleted C57BL/6 mice. Taken together, our results show that the antitumor effects of anti-CD40 are enhanced by subsequent treatment with MPL, even in T cell-deficient hosts. These preclinical data suggest that an anti-CD40+MPL combined regimen is appropriate for clinical testing in human patients, including cancer patients that may be immunosuppressed from prior chemotherapy. PMID:23211623

  19. SU-E-T-373: A Motorized Stage for Fast and Accurate QA of Machine Isocenter

    SciTech Connect

    Moore, J; Velarde, E; Wong, J

    2014-06-01

    Purpose: Precision delivery of radiation dose relies on accurate knowledge of the machine isocenter under a variety of machine motions. This is typically determined by performing a Winston-Lutz test consisting of imaging a known object at multiple gantry/collimator/table angles and ensuring that the maximum offset is within specified tolerance. The first step in the Winston-Lutz test is careful placement of a ball bearing at the machine isocenter as determined by repeated imaging and shifting until accurate placement has been determined. Conventionally this is performed by adjusting a stage manually using vernier scales which carry the limitation that each adjustment must be done inside the treatment room with the risks of inaccurate adjustment of the scale and physical bumping of the table. It is proposed to use a motorized system controlled outside of the room to improve the required time and accuracy of these tests. Methods: The three dimensional vernier scales are replaced by three motors with accuracy of 1 micron and a range of 25.4mm connected via USB to a computer in the control room. Software is designed which automatically detects the motors and assigns them to proper axes and allows for small shifts to be entered and performed. Input values match calculated offsets in magnitude and sign to reduce conversion errors. Speed of setup, number of iterations to setup, and accuracy of final placement are assessed. Results: Automatic BB placement required 2.25 iterations and 13 minutes on average while manual placement required 3.76 iterations and 37.5 minutes. The average final XYZ offsets is 0.02cm, 0.01cm, 0.04cm for automatic setup and 0.04cm, 0.02cm, 0.04cm for manual setup. Conclusion: Automatic placement decreased time and repeat iterations for setup while improving placement accuracy. Automatic placement greatly reduces the time required to perform QA.

  20. Importance of dose intensity in neuro-oncology clinical trials: summary report of the Sixth Annual Meeting of the Blood-Brain Barrier Disruption Consortium.

    PubMed

    Doolittle, N D; Anderson, C P; Bleyer, W A; Cairncross, J G; Cloughesy, T; Eck, S L; Guastadisegni, P; Hall, W A; Muldoon, L L; Patel, S J; Peereboom, D; Siegal, T; Neuwelt, E A

    2001-01-01

    Therapeutic options for the treatment of malignant brain tumors have been limited, in part, because of the presence of the blood-brain barrier. For this reason, the Sixth Annual Meeting of the Blood-Brain Barrier Disruption Consortium, the focus of which was the "Importance of Dose Intensity in Neuro-Oncology Clinical Trials," was convened in April 2000, at Government Camp, Mount Hood, Oregon. This meeting, which was supported by the National Cancer Institute, the National Institute of Neurological Disorders and Stroke, and the National Institute of Deafness and Other Communication Disorders, brought together clinicians and basic scientists from across the U.S. to discuss the role of dose intensity and enhanced chemotherapy delivery in the treatment of malignant brain tumors and to design multicenter clinical trials. Optimizing chemotherapy delivery to the CNS is crucial, particularly in view of recent progress identifying certain brain tumors as chemosensitive. The discovery that specific constellations of genetic alterations can predict which tumors are chemoresponsive, and can therefore more accurately predict prognosis, has important implications for delivery of intensive, effective chemotherapy regimens with acceptable toxicities. This report summarizes the discussions, future directions, and key questions regarding dose-intensive treatment of primary CNS lymphoma, CNS relapse of systemic non-Hodgkin's lymphoma, anaplastic oligodendroglioma, high-grade glioma, and metastatic cancer of the brain. The promising role of cytoenhancers and chemoprotectants as part of dose-intensive regimens for chemosensitive brain tumors and development of improved gene therapies for malignant gliomas are discussed. PMID:11305417

  1. Year in Review 2014: Aerosol Delivery Devices.

    PubMed

    Myers, Timothy R

    2015-08-01

    After centuries of discoveries and technological growth, aerosol therapy remains a cornerstone of care in the management of both acute and chronic respiratory conditions. Aerosol therapy embraces the concept that medicine is both an art and a science, where an explicit understanding of the science of aerosol therapy, the nuances of the different delivery devices, and the ability to provide accurate and reliable education to patients become increasingly important. The purpose of this article is to review recent literature regarding aerosol delivery devices in a style that readers of Respiratory Care may use as a key topic resource. PMID:26038596

  2. Mucoadhesive vaginal drug delivery systems.

    PubMed

    Acartürk, Füsun

    2009-11-01

    Vaginal delivery is an important route of drug administration for both local and systemic diseases. The vaginal route has some advantages due to its large surface area, rich blood supply, avoidance of the first-pass effect, relatively high permeability to many drugs and self-insertion. The traditional commercial preparations, such as creams, foams, gels, irrigations and tablets, are known to reside in the vaginal cavity for a relatively short period of time owing to the self-cleaning action of the vaginal tract, and often require multiple daily doses to ensure the desired therapeutic effect. The vaginal route appears to be highly appropriate for bioadhesive drug delivery systems in order to retain drugs for treating largely local conditions, or for use in contraception. In particular, protection against sexually-transmitted diseases is critical. To prolong the residence time in the vaginal cavity, bioadhesive therapeutic systems have been developed in the form of semi-solid and solid dosage forms. The most commonly used mucoadhesive polymers that are capable of forming hydrogels are synthetic polyacrylates, polycarbophil, chitosan, cellulose derivatives (hydroxyethycellulose, hydroxy-propylcellulose and hydroxypropylmethylcellulose), hyaluronic acid derivatives, pectin, tragacanth, carrageenan and sodium alginate. The present article is a comprehensive review of the patents related to mucoadhesive vaginal drug delivery systems. PMID:19925443

  3. Dose computation in conformal radiation therapy including geometric uncertainties: Methods and clinical implications

    NASA Astrophysics Data System (ADS)

    Rosu, Mihaela

    The aim of any radiotherapy is to tailor the tumoricidal radiation dose to the target volume and to deliver as little radiation dose as possible to all other normal tissues. However, the motion and deformation induced in human tissue by ventilatory motion is a major issue, as standard practice usually uses only one computed tomography (CT) scan (and hence one instance of the patient's anatomy) for treatment planning. The interfraction movement that occurs due to physiological processes over time scales shorter than the delivery of one treatment fraction leads to differences between the planned and delivered dose distributions. Due to the influence of these differences on tumors and normal tissues, the tumor control probabilities and normal tissue complication probabilities are likely to be impacted upon in the face of organ motion. In this thesis we apply several methods to compute dose distributions that include the effects of the treatment geometric uncertainties by using the time-varying anatomical information as an alternative to the conventional Planning Target Volume (PTV) approach. The proposed methods depend on the model used to describe the patient's anatomy. The dose and fluence convolution approaches for rigid organ motion are discussed first, with application to liver tumors and the rigid component of the lung tumor movements. For non-rigid behavior a dose reconstruction method that allows the accumulation of the dose to the deforming anatomy is introduced, and applied for lung tumor treatments. Furthermore, we apply the cumulative dose approach to investigate how much information regarding the deforming patient anatomy is needed at the time of treatment planning for tumors located in thorax. The results are evaluated from a clinical perspective. All dose calculations are performed using a Monte Carlo based algorithm to ensure more realistic and more accurate handling of tissue heterogeneities---of particular importance in lung cancer treatment planning.

  4. A convolution-superposition dose calculation engine for GPUs

    SciTech Connect

    Hissoiny, Sami; Ozell, Benoit; Despres, Philippe

    2010-03-15

    Purpose: Graphic processing units (GPUs) are increasingly used for scientific applications, where their parallel architecture and unprecedented computing power density can be exploited to accelerate calculations. In this paper, a new GPU implementation of a convolution/superposition (CS) algorithm is presented. Methods: This new GPU implementation has been designed from the ground-up to use the graphics card's strengths and to avoid its weaknesses. The CS GPU algorithm takes into account beam hardening, off-axis softening, kernel tilting, and relies heavily on raytracing through patient imaging data. Implementation details are reported as well as a multi-GPU solution. Results: An overall single-GPU acceleration factor of 908x was achieved when compared to a nonoptimized version of the CS algorithm implemented in PlanUNC in single threaded central processing unit (CPU) mode, resulting in approximatively 2.8 s per beam for a 3D dose computation on a 0.4 cm grid. A comparison to an established commercial system leads to an acceleration factor of approximately 29x or 0.58 versus 16.6 s per beam in single threaded mode. An acceleration factor of 46x has been obtained for the total energy released per mass (TERMA) calculation and a 943x acceleration factor for the CS calculation compared to PlanUNC. Dose distributions also have been obtained for a simple water-lung phantom to verify that the implementation gives accurate results. Conclusions: These results suggest that GPUs are an attractive solution for radiation therapy applications and that careful design, taking the GPU architecture into account, is critical in obtaining significant acceleration factors. These results potentially can have a significant impact on complex dose delivery techniques requiring intensive dose calculations such as intensity-modulated radiation therapy (IMRT) and arc therapy. They also are relevant for adaptive radiation therapy where dose results must be obtained rapidly.

  5. VMAT QA: Measurement-guided 4D dose reconstruction on a patient

    SciTech Connect

    Nelms, Benjamin E.; Opp, Daniel; Robinson, Joshua; Wolf, Theresa K.; Zhang, Geoffrey; Moros, Eduardo; Feygelman, Vladimir

    2012-07-15

    global fluence change. Results: Across four TG-119 plans, the average PTV point dose difference in the cube between 3DVH and ion chamber is 0.1 {+-} 1.0%. Average film vs TPS {gamma}-analysis passing rates are 83.0%, 91.1%, and 98.4% for 1%/2 mm, 2%/2 mm, and 3%/3 mm threshold combinations, respectively, while average film vs 3DVH {gamma}-analysis passing rates are 88.6%, 96.1%, and 99.5% for the same respective criteria. 4D MGDR was also sufficiently accurate. First, for 99.5% voxels in each case, the doses from 3D and 4D MGDR at the end of delivery agree within 0.5%local dose-error/1 mm distance. Moreover, all failing voxels are confined to the edge of the cylindrical reconstruction volume. Second, dose vs time curves track between the ion chamber and 4D MGDR within 1%. Finally, 4D MGDR dose changes linearly with the accelerator output: the difference between cumulative ion chamber and MGDR dose changed by no more than 1% (randomly) with the output variation range of 10%. Conclusions: Even for a well-commissioned TPS, comparison metrics show better agreement on average to MGDR than to TPS on the arbitrary-shaped measurable 'patient.' The method requires no more accelerator time than standard QA, while producing more clinically relevant information. Validation in a heterogeneous thoracic phantom is under way, as is the ultimate application of 4D MGDR to virtual motion studies.

  6. Renal-dose dopamine: from hypothesis to paradigm to dogma to myth and, finally, superstition?

    PubMed

    Jones, Daryl; Bellomo, Rinaldo

    2005-01-01

    Acute renal failure (ARF) is common in the critically ill and is associated with a high mortality rate. Its pathogenesis is not understood. Because animal models use ischemia to induce experimental ARF, there is the widespread belief that lack of blood flow is responsible for ARF. Low-dose dopamine (LDD) has been shown to increase renal blood flow in animal and in human volunteers. Thus, it has been administered to humans for almost 3 decades in the belief that it would lead to renal arterial vasodilation and increase renal blood flow (RBF). However, the etiology of ARF in critical illness is likely multifactorial, and the contribution of hypovolemia and reduced renal perfusion is unknown. Furthermore, interindividual variation in the pharmacokinetics of dopamine typically results in poor correlation between blood levels and administered dose, making accurate and reliable delivery of LDD difficult. Finally, dopamine is a proximal tubular diuretic that increases Na(+) delivery to tubular cells, thus increasing their oxygen demands. Accordingly, even if LDD were able to preferentially increase RBF, there is no guarantee that it would restore renal parenchymal oxygen homeostasis. More important, 2 meta-analyses and a large double-blind, prospective, multiple-center, randomized controlled trial have failed to demonstrate that dopamine protects the kidney in critically ill patients with ARF. Currently, there is insufficient evidence to support the use of renal-dose dopamine in the intensive care unit. PMID:16061903

  7. A slow release calcium delivery system for the study of reparative dentine formation.

    PubMed

    Hunter, A R; Kirk, E E; Robinson, D H; Kardos, T B

    1998-06-01

    Several liquid, semi-solid and solid delivery systems were formulated and tested to devise a method of reproducibly administering accurate micro-doses of calcium into a 700 microns diameter cavity in a rat maxillary incisor tooth, in the absence of hydroxyl ions. Development of this delivery system was necessary to facilitate studies of the mechanisms of pulpal repair and odontoblast differentiation. The principal requirements for the delivery system were that it should be easily administered into a small pulp exposure in the rat incisor and that a greater than 1000-fold range in calcium ion concentrations could be incorporated and delivered for a period of 2-3 days, preferably in an acidic environment to minimize the effect of non-specific nucleation under alkaline conditions. Poly- (ethylene) glycol microspheres were found to be an ideal vehicle. Under the in vitro dissolution conditions used, complete release of all calcium salts occurred within 12-15 hours, except for the very water-insoluble calcium stearate. It was anticipated that the release of calcium ions would be significantly more prolonged in vivo because of the physical constraints of the prepared cavity as well as the restricted access to fluid flow. PMID:9863419

  8. Ultrasound-Mediated Transdermal Protein Delivery

    NASA Astrophysics Data System (ADS)

    Mitragotri, Samir; Blankschtein, Daniel; Langer, Robert

    1995-08-01

    Transdermal drug delivery offers a potential method of drug administration. However, its application has been limited to a few low molecular weight compounds because of the extremely low permeability of human skin. Low-frequency ultrasound was shown to increase the permeability of human skin to many drugs, including high molecular weight proteins, by several orders of magnitude, thus making transdermal administration of these molecules potentially feasible. It was possible to deliver and control therapeutic doses of proteins such as insulin, interferon γ, and erythropoeitin across human skin. Low-frequency ultrasound is thus a potential noninvasive substitute for traditional methods of drug delivery, such as injections.

  9. Therapeutic potential of CERE-110 (AAV2-NGF): Targeted, stable, and sustained NGF delivery and trophic activity on rodent basal forebrain cholinergic neurons

    PubMed Central

    Bishop, Kathie M.; Hofer, Eva K.; Mehta, Arpesh; Ramirez, Anthony; Sun, Liangwu; Tuszynski, Mark; Bartus, Raymond T.

    2009-01-01

    Treatment of degenerating basal forebrain cholinergic neurons with nerve growth factor (NGF) in Alzheimer’s disease has long been contemplated, but an effective and safe delivery method has been lacking. Towards achieving this goal, we are currently developing CERE-110, an adeno-associated virus-based gene delivery vector that encodes for human NGF, for stereotactic surgical delivery to the human nucleus basalis of Meynert. Results indicate that NGF transgene delivery to the targeted brain region via CERE-110 is reliable and accurate, that NGF transgene distribution can be controlled by altering CERE-110 dose, and that it is possible to achieve restricted NGF expression limited to but covering the target brain region. Results from animals examined at longer time periods of 3, 6, 9 and 12 months after CERE-110 delivery indicate that NGF transgene expression is stable and sustained at all time points, with no loss or build-up of protein over the long-term. In addition, results from a series of experiments indicate that CERE-110 is neuroprotective and neurorestorative to basal forebrain cholinergic neurons in the rat fimbria-fornix lesion and aged rat models, and has bioactive effects on young rat basal forebrain cholinergic neurons. These findings, as well as those from several additional non-clinical experiments conducted in both rats and monkeys, led to the initiation of a Phase I clinical study to evaluate the safety and efficacy of CERE-110 in Alzheimer’s disease subjects, which is currently ongoing. PMID:18439998

  10. Intracochlear Drug Delivery Systems

    PubMed Central

    Borenstein, Jeffrey T.

    2011-01-01

    Introduction Advances in molecular biology and in the basic understanding of the mechanisms associated with sensorineural hearing loss and other diseases of the inner ear, are paving the way towards new approaches for treatments for millions of patients. However, the cochlea is a particularly challenging target for drug therapy, and new technologies will be required to provide safe and efficacious delivery of these compounds. Emerging delivery systems based on microfluidic technologies are showing promise as a means for direct intracochlear delivery. Ultimately, these systems may serve as a means for extended delivery of regenerative compounds to restore hearing in patients suffering from a host of auditory diseases. Areas covered in this review Recent progress in the development of drug delivery systems capable of direct intracochlear delivery is reviewed, including passive systems such as osmotic pumps, active microfluidic devices, and systems combined with currently available devices such as cochlear implants. The aim of this article is to provide a concise review of intracochlear drug delivery systems currently under development, and ultimately capable of being combined with emerging therapeutic compounds for the treatment of inner ear diseases. Expert Opinion Safe and efficacious treatment of auditory diseases will require the development of microscale delivery devices, capable of extended operation and direct application to the inner ear. These advances will require miniaturization and integration of multiple functions, including drug storage, delivery, power management and sensing, ultimately enabling closed-loop control and timed-sequence delivery devices for treatment of these diseases. PMID:21615213

  11. 38 CFR 4.46 - Accurate measurement.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Accurate measurement. 4... RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.46 Accurate measurement. Accurate measurement of the length of stumps, excursion of joints, dimensions and location of scars with respect...

  12. 38 CFR 4.46 - Accurate measurement.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Accurate measurement. 4... RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.46 Accurate measurement. Accurate measurement of the length of stumps, excursion of joints, dimensions and location of scars with respect...

  13. 38 CFR 4.46 - Accurate measurement.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Accurate measurement. 4... RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.46 Accurate measurement. Accurate measurement of the length of stumps, excursion of joints, dimensions and location of scars with respect...

  14. 38 CFR 4.46 - Accurate measurement.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Accurate measurement. 4... RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.46 Accurate measurement. Accurate measurement of the length of stumps, excursion of joints, dimensions and location of scars with respect...

  15. 38 CFR 4.46 - Accurate measurement.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Accurate measurement. 4... RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.46 Accurate measurement. Accurate measurement of the length of stumps, excursion of joints, dimensions and location of scars with respect...

  16. The FLUKA Code: An Accurate Simulation Tool for Particle Therapy

    PubMed Central

    Battistoni, Giuseppe; Bauer, Julia; Boehlen, Till T.; Cerutti, Francesco; Chin, Mary P. W.; Dos Santos Augusto, Ricardo; Ferrari, Alfredo; Ortega, Pablo G.; Kozłowska, Wioletta; Magro, Giuseppe; Mairani, Andrea; Parodi, Katia; Sala, Paola R.; Schoofs, Philippe; Tessonnier, Thomas; Vlachoudis, Vasilis

    2016-01-01

    Monte Carlo (MC) codes are increasingly spreading in the hadrontherapy community due to their detailed description of radiation transport and interaction with matter. The suitability of a MC code for application to hadrontherapy demands accurate and reliable physical models capable of handling all components of the expected radiation field. This becomes extremely important for correctly performing not only physical but also biologically based dose calculations, especially in cases where ions heavier than protons are involved. In addition, accurate prediction of emerging secondary radiation is of utmost importance in innovative areas of research aiming at in vivo treatment verification. This contribution will address the recent developments of the FLUKA MC code and its practical applications in this field. Refinements of the FLUKA nuclear models in the therapeutic energy interval lead to an improved description of the mixed radiation field as shown in the presented benchmarks against experimental data with both 4He and 12C ion beams. Accurate description of ionization energy losses and of particle scattering and interactions lead to the excellent agreement of calculated depth–dose profiles with those measured at leading European hadron therapy centers, both with proton and ion beams. In order to support the application of FLUKA in hospital-based environments, Flair, the FLUKA graphical interface, has been enhanced with the capability of translating CT DICOM images into voxel-based computational phantoms in a fast and well-structured way. The interface is capable of importing also radiotherapy treatment data described in DICOM RT standard. In addition, the interface is equipped with an intuitive PET scanner geometry generator and automatic recording of coincidence events. Clinically, similar cases will be presented both in terms of absorbed dose and biological dose calculations describing the various available features. PMID:27242956

  17. The FLUKA Code: An Accurate Simulation Tool for Particle Therapy.

    PubMed

    Battistoni, Giuseppe; Bauer, Julia; Boehlen, Till T; Cerutti, Francesco; Chin, Mary P W; Dos Santos Augusto, Ricardo; Ferrari, Alfredo; Ortega, Pablo G; Kozłowska, Wioletta; Magro, Giuseppe; Mairani, Andrea; Parodi, Katia; Sala, Paola R; Schoofs, Philippe; Tessonnier, Thomas; Vlachoudis, Vasilis

    2016-01-01

    Monte Carlo (MC) codes are increasingly spreading in the hadrontherapy community due to their detailed description of radiation transport and interaction with matter. The suitability of a MC code for application to hadrontherapy demands accurate and reliable physical models capable of handling all components of the expected radiation field. This becomes extremely important for correctly performing not only physical but also biologically based dose calculations, especially in cases where ions heavier than protons are involved. In addition, accurate prediction of emerging secondary radiation is of utmost importance in innovative areas of research aiming at in vivo treatment verification. This contribution will address the recent developments of the FLUKA MC code and its practical applications in this field. Refinements of the FLUKA nuclear models in the therapeutic energy interval lead to an improved description of the mixed radiation field as shown in the presented benchmarks against experimental data with both (4)He and (12)C ion beams. Accurate description of ionization energy losses and of particle scattering and interactions lead to the excellent agreement of calculated depth-dose profiles with those measured at leading European hadron therapy centers, both with proton and ion beams. In order to support the application of FLUKA in hospital-based environments, Flair, the FLUKA graphical interface, has been enhanced with the capability of translating CT DICOM images into voxel-based computational phantoms in a fast and well-structured way. The interface is capable of importing also radiotherapy treatment data described in DICOM RT standard. In addition, the interface is equipped with an intuitive PET scanner geometry generator and automatic recording of coincidence events. Clinically, similar cases will be presented both in terms of absorbed dose and biological dose calculations describing the various available features. PMID:27242956

  18. A novel phantom model for mouse tumor dose assessment under MV beams.

    PubMed

    Gossman, Michael S; Das, Indra J; Sharma, Subhash C; Lopez, Jeffrey P; Howard, Candace M; Claudio, Pier

    2011-12-01

    In order to determine a mouse's dose accurately and prior to engaging in live mouse radiobiological research, a tissue-equivalent tumor-bearing phantom mouse was constructed and bored to accommodate detectors. Comparisons were made among four different types of radiation detectors, each inserted into the mouse phantom for radiation measurement under a 6 MV linear accelerator beam. Dose detection response from a diode, thermoluminescent dosimeters, and metal-oxide semiconductor field-effect transistors were used and compared to that of a reference pinpoint ionization chamber. A computerized treatment planning system was also directly compared to the chamber. Each detector system demonstrated results similar to the dose computed by the treatment planning system, although some differences were noted. The average disagreement from an accelerator calibrated output dose prescription in the range of 200-400 cGy was -0.4% ± 0.5 σ for the diode, -2.4% ± 2.6 σ for the TLD, -2.9% ± 5.0 σ for the MOSFET, and +1.3% ± 1.4 σ for the treatment planning system. This phantom mouse design is unique, simple, reproducible, and therefore recommended as a standard approach to dosimetry for radiobiological mouse studies by means of any of the detectors used in this study. The authors fully advocate for treatment planning modeling when possible prior to linac-based dose delivery. PMID:22048493

  19. Radiobiological advantages of an immediate interstitial boost dose in conservative treatment of breast cancer

    SciTech Connect

    Krishnan, E.C.; Krishnan, L.; Cytaki, E.P.; Woolf, C.D.; Henry, M.M.; Lin, F.; Jewell, W.R. )

    1990-02-01

    Minimum surgery with irradiation is emerging as one of the main modalities of therapy for operable early breast cancer. Between June 1982 and June 1986, 110 breasts with Tis, T1 to T3 lesions have been treated at our institution with lumpectomy and interstitial irradiation to the tumor bed with Iridium-192 perioperatively followed by external beam irradiation. There have been two local recurrences at or near the vicinity of the primary, at a median follow-up of 60 months. To analyze the parameters that might have contributed to the local control, we have examined the treatment volumes, prescribed dose to the tumor bed, dose at the core of the tumor bed, and dose to the surrounding normal tissue. Immediate interstitial implant has the radiobiological advantage of delivering continuous low dose irradiation, immediately upon removal of gross tumor to residual foci. Implantation of the afterloading catheters intraoperatively facilitates accurate dose delivery and avoidance of geographical misses. By precise treatment of any residual foci, immediately upon removal of the gross mass, perioperative interstitial irradiation improves local control and by facilitating less radical surgical excision, leads to better cosmetic results.

  20. Commissioning of the discrete spot scanning proton beam delivery system at University of Texas M.D. Anderson Cancer Center, Proton Therapy Center, Houston

    SciTech Connect

    Gillin, Michael T.; Sahoo, Narayan; Bues, Martin; Ciangaru, George; Sawakuchi, Gabriel; Poenisch, Falk; Arjomandy, Bijan; Martin, Craig; Titt, Uwe; Suzuki, Kazumichi; Smith, Alfred R.; Zhu, X. Ronald

    2010-01-15

    Purpose: To describe a summary of the clinical commissioning of the discrete spot scanning proton beam at the Proton Therapy Center, Houston (PTC-H). Methods: Discrete spot scanning system is composed of a delivery system (Hitachi ProBeat), an electronic medical record (Mosaiq V 1.5), and a treatment planning system (TPS) (Eclipse V 8.1). Discrete proton pencil beams (spots) are used to deposit dose spot by spot and layer by layer for the proton distal ranges spanning from 4.0 to 30.6 g/cm{sup 2} and over a maximum scan area at the isocenter of 30x30 cm{sup 2}. An arbitrarily chosen reference calibration condition has been selected to define the monitor units (MUs). Using radiochromic film and ion chambers, the authors have measured spot positions, the spot sizes in air, depth dose curves, and profiles for proton beams with various energies in water, and studied the linearity of the dose monitors. In addition to dosimetric measurements and TPS modeling, significant efforts were spent in testing information flow and recovery of the delivery system from treatment interruptions. Results: The main dose monitors have been adjusted such that a specific amount of charge is collected in the monitor chamber corresponding to a single MU, following the IAEA TRS 398 protocol under a specific reference condition. The dose monitor calibration method is based on the absolute dose per MU, which is equivalent to the absolute dose per particle, the approach used by other scanning beam institutions. The full width at half maximum for the spot size in air varies from approximately 1.2 cm for 221.8 MeV to 3.4 cm for 72.5 MeV. The measured versus requested 90% depth dose in water agrees to within 1 mm over ranges of 4.0-30.6 cm. The beam delivery interlocks perform as expected, guarantying the safe and accurate delivery of the planned dose. Conclusions: The dosimetric parameters of the discrete spot scanning proton beam have been measured as part of the clinical commissioning program

  1. Assessing dose rate distributions in VMAT plans

    NASA Astrophysics Data System (ADS)

    Mackeprang, P.-H.; Volken, W.; Terribilini, D.; Frauchiger, D.; Zaugg, K.; Aebersold, D. M.; Fix, M. K.; Manser, P.

    2016-04-01

    Dose rate is an essential factor in radiobiology. As modern radiotherapy delivery techniques such as volumetric modulated arc therapy (VMAT) introduce dynamic modulation of the dose rate, it is important to assess the changes in dose rate. Both the rate of monitor units per minute (MU rate) and collimation are varied over the course of a fraction, leading to different dose rates in every voxel of the calculation volume at any point in time during dose delivery. Given the radiotherapy plan and machine specific limitations, a VMAT treatment plan can be split into arc sectors between Digital Imaging and Communications in Medicine control points (CPs) of constant and known MU rate. By calculating dose distributions in each of these arc sectors independently and multiplying them with the MU rate, the dose rate in every single voxel at every time point during the fraction can be calculated. Independently calculated and then summed dose distributions per arc sector were compared to the whole arc dose calculation for validation. Dose measurements and video analysis were performed to validate the calculated datasets. A clinical head and neck, cranial and liver case were analyzed using the tool developed. Measurement validation of synthetic test cases showed linac agreement to precalculated arc sector times within  ±0.4 s and doses  ±0.1 MU (one standard deviation). Two methods for the visualization of dose rate datasets were developed: the first method plots a two-dimensional (2D) histogram of the number of voxels receiving a given dose rate over the course of the arc treatment delivery. In similarity to treatment planning system display of dose, the second method displays the dose rate as color wash on top of the corresponding computed tomography image, allowing the user to scroll through the variation over time. Examining clinical cases showed dose rates spread over a continuous spectrum, with mean dose rates hardly exceeding 100 cGy min-1 for conventional

  2. Transdermal delivery of contraceptives.

    PubMed

    Friend, D R

    1990-01-01

    Contraceptive agents are administered to the body through a variety of routes. Research has recently been directed at examining the transdermal route for systemic delivery of contraceptive agents, including estrogens and progestins. The transdermal route has several potential advantages over the other routes of administration: (1) improved compliance, (2) once-weekly administration, (3) delivery is easily terminated, and (4) some side effects can be alleviated based on more constant delivery rates. This article reviews the permeability of skin toward contraceptive steroids and how skin permeability is evaluated. The metabolism of contraceptive steroids is also considered. Transdermal delivery systems used to deliver contraceptives are presented, followed by a detailed discussion of several delivery systems for specific contraceptive agents such as levonorgestrel and estradiol. The potential problem of skin irritation is presented as it relates to transdermal contraceptive delivery systems, all of which will be worn chronically. PMID:2272099

  3. Antibiotic delivery by nanobioceramics.

    PubMed

    Kumar, Ts Sampath; Madhumathi, K

    2016-08-01

    The role of nanotechnology has evinced remarkable interest in the field of drug delivery. Bioceramics are inorganic biomaterials which are frequently used as bone substitutes. They have been explored in drug delivery as carriers for antibiotics, anti-osteoporotic drugs and anticancer drugs. Bioceramic nanoparticles are excellent alternatives to polymers due to their bioactivity, pH and temperature stability, multifunctionality, biocompatibility and tunable biodegradability. The use of bioceramics for local drug delivery in the field of orthopedics offer an efficient, safe mode of drug delivery directly to the surgical site thereby overcoming the limitations of systemic drug delivery. This review focuses on the development and applications of various nanobioceramics employed as drug delivery systems for the treatment of bone infections. PMID:27444496

  4. Dose homogeneity specification for reference dosimetry of nonstandard fields

    SciTech Connect

    Chung, Eunah; Soisson, Emilie; Seuntjens, Jan

    2012-01-15

    Purpose: To investigate the sensitivity of the plan-class specific correction factor to dose distributions in composite nonstandard field dosimetry. Methods: A cylindrical water-filled PMMA phantom was constructed at the center of which reference absorbed dose could be measured. Ten different TomoTherapy-based IMRT fields were created on the CT images of the phantom. The dose distribution for each IMRT field was estimated at the position of a radiation detector or ionization chamber. The dose in each IMRT field normalized to that in a reference 10 x 10 cm{sup 2} field was measured using a PTW micro liquid ion chamber. Based on the new dosimetry formalism, a plan-class specific correction factor k{sub Q{sub p{sub c{sub s{sub r,Q}{sup f{sub p}{sub c}{sub s}{sub r},f{sub r}{sub e}{sub f}}}}}} for each field was measured for two Farmer-type chambers, Exradin A12 and NE2571, as well as for a smaller Exradin A1SL chamber. The dependence of the measured correction factor on parameters characterizing dose distribution was analyzed. Results: Uncertainty on the plan-class specific correction factor measurement was in the range of 0.3%-0.5% and 0.3%-0.8% for the Farmer-type chambers and the Exradin A1SL, respectively. When the heterogeneity of the central region of the target volume was less than 5%, the correction factor did not differ from unity by more than 0.7% for the three air-filled ionization chambers. For more heterogeneous dose deliveries, the correction factor differed from unity by up to 2.4% for the Farmer-type chambers. For the Exradin A1SL, the correction factor was closer to unity due to the reduced effect of dose gradients, while it was highly variable in different IMRT fields because of a more significant impact of positioning uncertainties on the response of this chamber. Conclusions: The authors have shown that a plan-class specific correction factor can be specified as a function of plan evaluation parameters especially for Farmer-type chambers. This work

  5. Achieving target voriconazole concentrations more accurately in children and adolescents.

    PubMed

    Neely, Michael; Margol, Ashley; Fu, Xiaowei; van Guilder, Michael; Bayard, David; Schumitzky, Alan; Orbach, Regina; Liu, Siyu; Louie, Stan; Hope, William

    2015-01-01

    Despite the documented benefit of voriconazole therapeutic drug monitoring, nonlinear pharmacokinetics make the timing of steady-state trough sampling and appropriate dose adjustments unpredictable by conventional methods. We developed a nonparametric population model with data from 141 previously richly sampled children and adults. We then used it in our multiple-model Bayesian adaptive control algorithm to predict measured concentrations and doses in a separate cohort of 33 pediatric patients aged 8 months to 17 years who were receiving voriconazole and enrolled in a pharmacokinetic study. Using all available samples to estimate the individual Bayesian posterior parameter values, the median percent prediction bias relative to a measured target trough concentration in the patients was 1.1% (interquartile range, -17.1 to 10%). Compared to the actual dose that resulted in the target concentration, the percent bias of the predicted dose was -0.7% (interquartile range, -7 to 20%). Using only trough concentrations to generate the Bayesian posterior parameter values, the target bias was 6.4% (interquartile range, -1.4 to 14.7%; P = 0.16 versus the full posterior parameter value) and the dose bias was -6.7% (interquartile range, -18.7 to 2.4%; P = 0.15). Use of a sample collected at an optimal time of 4 h after a dose, in addition to the trough concentration, resulted in a nonsignificantly improved target bias of 3.8% (interquartile range, -13.1 to 18%; P = 0.32) and a dose bias of -3.5% (interquartile range, -18 to 14%; P = 0.33). With the nonparametric population model and trough concentrations, our control algorithm can accurately manage voriconazole therapy in children independently of steady-state conditions, and it is generalizable to any drug with a nonparametric pharmacokinetic model. (This study has been registered at ClinicalTrials.gov under registration no. NCT01976078.). PMID:25779580

  6. Achieving Target Voriconazole Concentrations More Accurately in Children and Adolescents

    PubMed Central

    Margol, Ashley; Fu, Xiaowei; van Guilder, Michael; Bayard, David; Schumitzky, Alan; Orbach, Regina; Liu, Siyu; Louie, Stan; Hope, William

    2015-01-01

    Despite the documented benefit of voriconazole therapeutic drug monitoring, nonlinear pharmacokinetics make the timing of steady-state trough sampling and appropriate dose adjustments unpredictable by conventional methods. We developed a nonparametric population model with data from 141 previously richly sampled children and adults. We then used it in our multiple-model Bayesian adaptive control algorithm to predict measured concentrations and doses in a separate cohort of 33 pediatric patients aged 8 months to 17 years who were receiving voriconazole and enrolled in a pharmacokinetic study. Using all available samples to estimate the individual Bayesian posterior parameter values, the median percent prediction bias relative to a measured target trough concentration in the patients was 1.1% (interquartile range, −17.1 to 10%). Compared to the actual dose that resulted in the target concentration, the percent bias of the predicted dose was −0.7% (interquartile range, −7 to 20%). Using only trough concentrations to generate the Bayesian posterior parameter values, the target bias was 6.4% (interquartile range, −1.4 to 14.7%; P = 0.16 versus the full posterior parameter value) and the dose bias was −6.7% (interquartile range, −18.7 to 2.4%; P = 0.15). Use of a sample collected at an optimal time of 4 h after a dose, in addition to the trough concentration, resulted in a nonsignificantly improved target bias of 3.8% (interquartile range, −13.1 to 18%; P = 0.32) and a dose bias of −3.5% (interquartile range, −18 to 14%; P = 0.33). With the nonparametric population model and trough concentrations, our control algorithm can accurately manage voriconazole therapy in children independently of steady-state conditions, and it is generalizable to any drug with a nonparametric pharmacokinetic model. (This study has been registered at ClinicalTrials.gov under registration no. NCT01976078.) PMID:25779580

  7. Current perspectives on intrathecal drug delivery

    PubMed Central

    Bottros, Michael M; Christo, Paul J

    2014-01-01

    Advances in intrathecal analgesia and intrathecal drug delivery systems have allowed for a range of medications to be used in the control of pain and spasticity. This technique allows for reduced medication doses that can decrease the side effects typically associated with oral or parenteral drug delivery. Recent expert panel consensus guidelines have provided care paths in the treatment of nociceptive, neuropathic, and mixed pain syndromes. While the data for pain relief, adverse effect reduction, and cost-effectiveness with cancer pain control are compelling, the evidence is less clear for noncancer pain, other than spasticity. Physicians should be aware of mechanical, pharmacological, surgical, and patient-specific complications, including possible granuloma formation. Newer intrathecal drug delivery systems may allow for better safety and quality of life outcomes. PMID:25395870

  8. Transdermal delivery of heparin: Physical enhancement techniques.

    PubMed

    Ita, Kevin

    2015-12-30

    Thromboembolic complications are the most common preventable cause of mortality and morbidity in trauma patients. Thrombosis is also the common cause of ischemic heart disease (acute coronary syndrome), stroke, and venous thromboembolism. Heparin, as a potent anticoagulant, has been used in clinical practice for more than five decades and remains the major medicine for the prevention and treatment of venous thromboembolism. However it binds to the endothelium and has a high affinity for plasma proteins resulting in a short half-life and unpredictable bioavailability. Transdermal drug delivery can address the problems of short half-life and unpredictable bioavailability. Other advantages of transdermal drug delivery include convenience, improved patient compliance, prompt termination of dosing and avoidance of the first-pass effect. This review focuses on different approaches used for transdermal delivery of heparin. PMID:26611668

  9. Transdermal delivery: product and patent update.

    PubMed

    Gupta, Himanshu; Babu, R J

    2013-12-01

    Transdermal drug delivery is an attractive alternative to the oral and parenteral drug delivery. Drugs which are prone to first-pass metabolism can be delivered easily in small doses with sustained blood levels through this method. An update to available products along with a review of clinical trials and patents are discussed in this study. In this review, we have compiled 16 drugs, i.e. Buprenorphine, Clonidine, Estradiol, Fentanyl, Granisetron, Lidocaine, Methylphenidate, Nicotine, Nitroglycerin, Oxybutynin, Rivastigmine, Rotigotine, Scopolamine, Selegiline, Testosterone, Influenza virus vaccine (Microneedle) and covering about 22 marketed products on the transdermal system. We present instrumental information on them along with the compilation of current clinical trials on transdermal systems. We summarize the contents of patents granted in last 5 years under different pharmacological categories. This article serves, accordingly as a source of available information focused on transdermal drug delivery research. PMID:24025130

  10. Barriers to drug delivery in solid tumors

    PubMed Central

    Sriraman, Shravan Kumar; Aryasomayajula, Bhawani; Torchilin, Vladimir P

    2014-01-01

    Over the last decade, significant progress has been made in the field of drug delivery. The advent of engineered nanoparticles has allowed us to circumvent the initial limitations to drug delivery such as pharmacokinetics and solubility. However, in spite of significant advances to tumor targeting, an effective treatment strategy for malignant tumors still remains elusive. Tumors possess distinct physiological features which allow them to resist traditional treatment approaches. This combined with the complexity of the biological system presents significant hurdles to the site-specific delivery of therapeutic drugs. One of the key features of engineered nanoparticles is that these can be tailored to execute specific functions. With this review, we hope to provide the reader with a clear understanding and knowledge of biological barriers and the methods to exploit these characteristics to design multifunctional nanocarriers, effect useful dosing regimens and subsequently improve therapeutic outcomes in the clinic. PMID:25068098

  11. A machine learning approach to the accurate prediction of multi-leaf collimator positional errors

    NASA Astrophysics Data System (ADS)

    Carlson, Joel N. K.; Park, Jong Min; Park, So-Yeon; In Park, Jong; Choi, Yunseok; Ye, Sung-Joon

    2016-03-01

    Discrepancies between planned and delivered movements of multi-leaf collimators (MLCs) are an important source of errors in dose distributions during radiotherapy. In this work we used machine learning techniques to train models to predict these discrepancies, assessed the accuracy of the model predictions, and examined the impact these errors have on quality assurance (QA) procedures and dosimetry. Predictive leaf motion parameters for the models were calculated from the plan files, such as leaf position and velocity, whether the leaf was moving towards or away from the isocenter of the MLC, and many others. Differences in positions between synchronized DICOM-RT planning files and DynaLog files reported during QA delivery were used as a target response for training of the models. The final model is capable of predicting MLC positions during delivery to a high degree of accuracy. For moving MLC leaves, predicted positions were shown to be significantly closer to delivered positions than were planned positions. By incorporating predicted positions into dose calculations in the TPS, increases were shown in gamma passing rates against measured dose distributions recorded during QA delivery. For instance, head and neck plans with 1%/2 mm gamma criteria had an average increase in passing rate of 4.17% (SD  =  1.54%). This indicates that the inclusion of predictions during dose calculation leads to a more realistic representation of plan delivery. To assess impact on the patient, dose volumetric histograms (DVH) using delivered positions were calculated for comparison with planned and predicted DVHs. In all cases, predicted dose volumetric parameters were in closer agreement to the delivered parameters than were the planned parameters, particularly for organs at risk on the periphery of the treatment area. By incorporating the predicted positions into the TPS, the treatment planner is given a more realistic view of the dose distribution as it will truly be

  12. A machine learning approach to the accurate prediction of multi-leaf collimator positional errors.

    PubMed

    Carlson, Joel N K; Park, Jong Min; Park, So-Yeon; Park, Jong In; Choi, Yunseok; Ye, Sung-Joon

    2016-03-21

    Discrepancies between planned and delivered movements of multi-leaf collimators (MLCs) are an important source of errors in dose distributions during radiotherapy. In this work we used machine learning techniques to train models to predict these discrepancies, assessed the accuracy of the model predictions, and examined the impact these errors have on quality assurance (QA) procedures and dosimetry. Predictive leaf motion parameters for the models were calculated from the plan files, such as leaf position and velocity, whether the leaf was moving towards or away from the isocenter of the MLC, and many others. Differences in positions between synchronized DICOM-RT planning files and DynaLog files reported during QA delivery were used as a target response for training of the models. The final model is capable of predicting MLC positions during delivery to a high degree of accuracy. For moving MLC leaves, predicted positions were shown to be significantly closer to delivered positions than were planned positions. By incorporating predicted positions into dose calculations in the TPS, increases were shown in gamma passing rates against measured dose distributions recorded during QA delivery. For instance, head and neck plans with 1%/2 mm gamma criteria had an average increase in passing rate of 4.17% (SD  =  1.54%). This indicates that the inclusion of predictions during dose calculation leads to a more realistic representation of plan delivery. To assess impact on the patient, dose volumetric histograms (DVH) using delivered positions were calculated for comparison with planned and predicted DVHs. In all cases, predicted dose volumetric parameters were in closer agreement to the delivered parameters than were the planned parameters, particularly for organs at risk on the periphery of the treatment area. By incorporating the predicted positions into the TPS, the treatment planner is given a more realistic view of the dose distribution as it will truly be

  13. Design of Drug Delivery Methods for the Brain and Central Nervous System

    NASA Astrophysics Data System (ADS)

    Lueshen, Eric

    Due to the impermeability of the blood-brain barrier (BBB) to macromolecules delivered systemically, drug delivery to the brain and central nervous system (CNS) is quite difficult and has become an area of intense research. Techniques such as convection-enhanced intraparenchymal delivery and intrathecal magnetic drug targeting offer a means of circumventing the blood-brain barrier for targeted delivery of therapeutics. This dissertation focuses on three aspects of drug delivery: pharmacokinetics, convection-enhanced delivery, and intrathecal magnetic drug targeting. Classical pharmacokinetics mainly uses black-box curve fitting techniques without biochemical or biological basis. This dissertation advances the state-of-the-art of pharmacokinetics and pharmacodynamics by incorporating first principles and biochemical/biotransport mechanisms in the prediction of drug fate in vivo. A whole body physiologically-based pharmacokinetics (PBPK) modeling framework is engineered which creates multiscale mathematical models for entire organisms composed of organs, tissues, and a detailed vasculature network to predict drug bioaccumulation and to rigorously determine kinetic parameters. These models can be specialized to account for species, weight, gender, age, and pathology. Systematic individual therapy design using the proposed mechanistic PBPK modeling framework is also a possibility. Biochemical, anatomical, and physiological scaling laws are also developed to accurately project drug kinetics in humans from small animal experiments. Our promising results demonstrate that the whole-body mechanistic PBPK modeling approach not only elucidates drug mechanisms from a biochemical standpoint, but offers better scaling precision. Better models can substantially accelerate the introduction of drug leads to clinical trials and eventually to the market by offering more understanding of the drug mechanisms, aiding in therapy design, and serving as an accurate dosing tool. Convection

  14. Pathophysiological and disease constraints on aerosol delivery

    SciTech Connect

    Gerrity, T.R.

    1989-01-01

    The dose of inhaled particles to the respiratory tract depends upon many factors. These factors include the size of the particles, the pattern of breathing (flow and tidal volume), the physical properties of the articles (hygroscopic or non-hygroscopic), anatomy of the respiratory tract, and the pathophysiologic status of the respiratory tract. In addition to these factors, which are primarily related to the deposition of particles, the rate of particle clearance from the respiratory tract also influences the dose of particles. The paper is a review of the various factors influencing dose of inhaled particles to the respiratory tract. The emphasis of the paper is on therapeutic aerosol particles, though the principals discussed also apply to toxic particles as well. An important area of consideration is the influence of disease on the delivery of particle dose. From the point of view of toxic particles this is important when considering potential susceptible populations.

  15. Improving Dose Determination Accuracy in Nonstandard Fields of the Varian TrueBeam Accelerator

    NASA Astrophysics Data System (ADS)

    Hyun, Megan A.

    In recent years, the use of flattening-filter-free (FFF) linear accelerators in radiation-based cancer therapy has gained popularity, especially for hypofractionated treatments (high doses of radiation given in few sessions). However, significant challenges to accurate radiation dose determination remain. If physicists cannot accurately determine radiation dose in a clinical setting, cancer patients treated with these new machines will not receive safe, accurate and effective treatment. In this study, an extensive characterization of two commonly used clinical radiation detectors (ionization chambers and diodes) and several potential reference detectors (thermoluminescent dosimeters, plastic scintillation detectors, and alanine pellets) has been performed to investigate their use in these challenging, nonstandard fields. From this characterization, reference detectors were identified for multiple beam sizes, and correction factors were determined to improve dosimetric accuracy for ionization chambers and diodes. A validated computational (Monte Carlo) model of the TrueBeam(TM) accelerator, including FFF beam modes, was also used to calculate these correction factors, which compared favorably to measured results. Small-field corrections of up to 18 % were shown to be necessary for clinical detectors such as microionization chambers. Because the impact of these large effects on treatment delivery is not well known, a treatment planning study was completed using actual hypofractionated brain, spine, and lung treatments that were delivered at the UW Carbone Cancer Center. This study demonstrated that improperly applying these detector correction factors can have a substantial impact on patient treatments. This thesis work has taken important steps toward improving the accuracy of FFF dosimetry through rigorous experimentally and Monte-Carlo-determined correction factors, the validation of an important published protocol (TG-51) for use with FFF reference fields, and a

  16. Monte Carlo calculations and measurements of absorbed dose per monitor unit for the treatment of uveal melanoma with proton therapy

    PubMed Central

    Koch, Nicholas; Newhauser, Wayne D; Titt, Uwe; Gombos, Dan; Coombes, Kevin; Starkschall, George

    2014-01-01

    The treatment of uveal melanoma with proton radiotherapy has provided excellent clinical outcomes. However, contemporary treatment planning systems use simplistic dose algorithms that limit the accuracy of relative dose distributions. Further, absolute predictions of absorbed dose per monitor unit are not yet available in these systems. The purpose of this study was to determine if Monte Carlo methods could predict dose per monitor unit (D/MU) value at the center of a proton spread-out Bragg peak (SOBP) to within 1% on measured values for a variety of treatment fields relevant to ocular proton therapy. The MCNPX Monte Carlo transport code, in combination with realistic models for the ocular beam delivery apparatus and a water phantom, was used to calculate dose distributions and D/MU values, which were verified by the measurements. Measured proton beam data included central-axis depth dose profiles, relative cross-field profiles and absolute D/MU measurements under several combinations of beam penetration ranges and range-modulation widths. The Monte Carlo method predicted D/MU values that agreed with measurement to within 1% and dose profiles that agreed with measurement to within 3% of peak dose or within 0.5 mm distance-to-agreement. Lastly, a demonstration of the clinical utility of this technique included calculations of dose distributions and D/MU values in a realistic model of the human eye. It is possible to predict D/MU values accurately for clinical relevant range-modulated proton beams for ocular therapy using the Monte Carlo method. It is thus feasible to use the Monte Carlo method as a routine absolute dose algorithm for ocular proton therapy. PMID:18367789

  17. Ultraviolet radiation cataract: dose dependence

    NASA Astrophysics Data System (ADS)

    Soderberg, Per G.; Loefgren, Stefan

    1994-07-01

    Current safety limits for cataract development after acute exposure to ultraviolet radiation (UVR) are based on experiments analyzing experimental data with a quantal, effect-no effect, dose-response model. The present study showed that intensity of forward light scattering is better described with a continuous dose-response model. It was found that 3, 30 and 300 kJ/m2UVR300nm induces increased light scattering within 6 h. For all three doses the intensity of forward light scattering was constant after 6 h. The intensity of forward light scattering was proportional to the log dose of UVR300nm. There was a slight increase of the intensity of forward light scattering on the contralateral side in animals that received 300 kJ/m2. Altogether 72 Sprague-Dawley male rats were included. Half of the rats were exposed in vivo on one side to UVR300nm. The other half was kept as a control group, receiving the same treatment as exposed rats but without delivery of UVR300nm to the eye. Subgroups of the rats received either of the three doses. Rats were sacrificed at varying intervals after the exposure. The lenses were extracted and the forward light scattering was estimated. It is concluded that intensity of forward light scattering in the lens after exposure to UVR300nm should be described with a continuous dose-reponse model.

  18. Advanced drug delivery approaches against periodontitis.

    PubMed

    Joshi, Deeksha; Garg, Tarun; Goyal, Amit K; Rath, Goutam

    2016-01-01

    Periodontitis is an inflammatory disease of gums involving the degeneration of periodontal ligaments, creation of periodontal pocket and resorption of alveolar bone, resulting in the disruption of the support structure of teeth. According to WHO, 10-15% of the global population suffers from severe periodontitis. The disease results from the growth of a diverse microflora (especially anaerobes) in the pockets and release of toxins, enzymes and stimulation of body's immune response. Various local or systemic approaches were used for an effective treatment of periodontitis. Currently, controlled local drug delivery approach is more favorable as compared to systemic approach because it mainly focuses on improving the therapeutic outcomes by achieving factors like site-specific delivery, low dose requirement, bypass of first-pass metabolism, reduction in gastrointestinal side effects and decrease in dosing frequency. Overall it provides a safe and effective mode of treatment, which enhances patient compliance. Complete eradication of the organisms from the sites was not achieved by using various surgical and mechanical treatments. So a number of polymer-based delivery systems like fibers, films, chips, strips, microparticles, nanoparticles and nanofibers made from a variety of natural and synthetic materials have been successfully tested to deliver a variety of drugs. These systems are biocompatible and biodegradable, completely fill the pockets, and have strong retention on the target site due to excellent mucoadhesion properties. The review summarizes various available and recently developing targeted delivery devices for the treatment of periodontitis. PMID:25005586

  19. Systemic delivery of artemether by dissolving microneedles.

    PubMed

    Qiu, Yuqin; Li, Chun; Zhang, Suohui; Yang, Guozhong; He, Meilin; Gao, Yunhua

    2016-07-11

    Dissolving microneedles (DMNs) based transdermal delivery is an attractive drug delivery approach with minimal invasion. However, it is still challenging to load poorly water-soluble drugs in DMNs for systemic delivery. The aim of the study was to develop DMNs loaded with artemether (ARM) as a model drug, to enable efficient drug penetration through skin for systemic absorption and distribution. The micro-conduits created by microneedles were imaged by confocal laser scanning microscopy (CLSM), and the insertion depth was suggested to be about 270μm. The maximum amount of ARM delivered into skin was 72.67±2.69% of the initial dose loaded on DMNs preparation. Pharmacokinetics study in rats indicated a dose-dependent profile of plasma ARM concentrations, after ARM-loaded DMNs treatment. In contrast to intramuscular injection, DMNs application resulted in lower peak plasma levels, but higher plasma ARM concentration at 8h after administration. There were no significant difference in area under the curve and bioavailability between DMNs group and intramuscular group (P>0.05). Pharmacodynamics studies performed in collagen-induced arthritis (CIA) rats showed that ARM-loaded DMNs could reverse paw edema, similar to ARM intramuscular injection. In conclusion, developed DMNs provided a potential minimally invasive route for systemic delivery of poorly water-soluble drugs. PMID:27150946

  20. Targeted Lung Delivery of Nasally Administered Aerosols

    PubMed Central

    Tian, Geng; Hindle, Michael; Longest, P. Worth

    2014-01-01

    Using the nasal route to deliver pharmaceutical aerosols to the lungs has a number of advantages including co-administration during non-invasive ventilation. The objective of this study was to evaluate the growth and deposition characteristics of nasally administered aerosol throughout the conducting airways based on delivery with streamlined interfaces implementing two forms of controlled condensational growth technology. Characteristic conducting airways were considered including a nose-mouth-throat (NMT) geometry, complete upper tracheobronchial (TB) model through the third bifurcation (B3), and stochastic individual path (SIP) model to the terminal bronchioles (B15). Previously developed streamlined nasal cannula interfaces were used for the delivery of submicrometer particles using either enhanced condensational growth (ECG) or excipient enhanced growth (EEG) techniques. Computational fluid dynamics (CFD) simulations predicted aerosol transport, growth and deposition for a control (4.7 μm) and three submicrometer condensational aerosols with budesonide as a model insoluble drug. Depositional losses with condensational aerosols in the cannula and NMT were less than 5% of the initial dose, which represents an order-of-magnitude reduction compared to the control. The condensational growth techniques increased the TB dose by a factor of 1.1–2.6x, delivered at least 70% of the dose to the alveolar region, and produced final aerosol sizes ≥2.5 μm. Compared to multiple commercial orally inhaled products, the nose-to-lung delivery approach increased dose to the biologically important lower TB region by factors as large as 35x. In conclusion, nose-to-lung delivery with streamlined nasal cannulas and condensational aerosols was highly efficient and targeted deposition to the lower TB and alveolar regions. PMID:24932058

  1. Delivery system for molten salt oxidation of solid waste

    DOEpatents

    Brummond, William A.; Squire, Dwight V.; Robinson, Jeffrey A.; House, Palmer A.

    2002-01-01

    The present invention is a delivery system for safety injecting solid waste particles, including mixed wastes, into a molten salt bath for destruction by the process of molten salt oxidation. The delivery system includes a feeder system and an injector that allow the solid waste stream to be accurately metered, evenly dispersed in the oxidant gas, and maintained at a temperature below incineration temperature while entering the molten salt reactor.

  2. Ocular drug delivery.

    PubMed

    Gaudana, Ripal; Ananthula, Hari Krishna; Parenky, Ashwin; Mitra, Ashim K

    2010-09-01

    Ocular drug delivery has been a major challenge to pharmacologists and drug delivery scientists due to its unique anatomy and physiology. Static barriers (different layers of cornea, sclera, and retina including blood aqueous and blood-retinal barriers), dynamic barriers (choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution), and efflux pumps in conjunction pose a significant challenge for delivery of a drug alone or in a dosage form, especially to the posterior segment. Identification of influx transporters on various ocular tissues and designing a transporter-targeted delivery of a parent drug has gathered momentum in recent years. Parallelly, colloidal dosage forms such as nanoparticles, nanomicelles, liposomes, and microemulsions have been widely explored to overcome various static and dynamic barriers. Novel drug delivery strategies such as bioadhesive gels and fibrin sealant-based approaches were developed to sustain drug levels at the target site. Designing noninvasive sustained drug delivery systems and exploring the feasibility of topical application to deliver drugs to the posterior segment may drastically improve drug delivery in the years to come. Current developments in the field of ophthalmic drug delivery promise a significant improvement in overcoming the challenges posed by various anterior and posterior segment diseases. PMID:20437123

  3. Octavius 4D characterization for flattened and flattening filter free rotational deliveries

    SciTech Connect

    McGarry, Conor K.; Hounsell, Alan R.; O’Connell, Barry F.; Grattan, Mark W. D.; Agnew, Christina E.; Irvine, Denise M.

    2013-09-15

    Purpose: In this study the Octavius detector 729 ionization chamber (IC) array with the Octavius 4D phantom was characterized for flattening filter (FF) and flattening filter free (FFF) static and rotational beams. The device was assessed for verification with FF and FFF RapidArc treatment plans.Methods: The response of the detectors to field size, dose linearity, and dose rate were assessed for 6 MV FF beams and also 6 and 10 MV FFF beams. Dosimetric and mechanical accuracy of the detector array within the Octavius 4D rotational phantom was evaluated against measurements made using semiflex and pinpoint ionization chambers, and radiochromic film. Verification FF and FFF RapidArc plans were assessed using a gamma function with 3%/3 mm tolerances and 2%/2 mm tolerances and further analysis of these plans was undertaken using film and a second detector array with higher spatial resolution.Results: A warm-up dose of >6 Gy was required for detector stability. Dose-rate measurements were stable across a range from 0.26 to 15 Gy/min and dose response was linear, although the device overestimated small doses compared with pinpoint ionization chamber measurements. Output factors agreed with ionization chamber measurements to within 0.6% for square fields of side between 3 and 25 cm and within 1.2% for 2 × 2 cm{sup 2} fields. The Octavius 4D phantom was found to be consistent with measurements made with radiochromic film, where the gantry angle was found to be within 0.4° of that expected during rotational deliveries. RapidArc FF and FFF beams were found to have an accuracy of >97.9% and >90% of pixels passing 3%/3 mm and 2%/2 mm, respectively. Detector spatial resolution was observed to be a factor in determining the accurate delivery of each plan, particularly at steep dose gradients. This was confirmed using data from a second detector array with higher spatial resolution and with radiochromic film.Conclusions: The Octavius 4D phantom with associated Octavius detector

  4. Analytic IMRT dose calculations utilizing Monte Carlo to predict MLC fluence modulation

    PubMed Central

    Mihaylov, I. B.; Lerma, F. A.; Wu, Y.; Siebers, J. V.

    2007-01-01

    A hybrid dose-computation method is designed which accurately accounts for multileaf collimator (MLC)-induced intensity modulation in intensity modulated radiation therapy (IMRT) dose calculations. The method employs Monte Carlo (MC) modeling to determine the fluence modulation caused by the delivery of dynamic or multisegmental (step-and-shoot) MLC fields, and a conventional dose-computation algorithm to estimate the delivered dose to a phantom or a patient. Thus, it determines the IMRT fluence prediction accuracy achievable by analytic methods in the limit that the analytic method includes all details of the MLC leaf transport and scatter. The hybrid method is validated and benchmarked by comparison with in-phantom film dose measurements, as well as dose calculations from two in-house, and two commercial treatment planning system analytic fluence estimation methods. All computation methods utilize the same dose algorithm to calculate dose to a phantom, varying only in the estimation of the MLC modulation of the incident photon energy fluence. Gamma analysis, with respect to measured two-dimensional (2D) dose planes, is used to benchmark each algorithm’s performance. The analyzed fields include static and dynamic test patterns, as well as fields from ten DMLC IMRT treatment plans (79 fields) and five SMLC treatment plans (29 fields). The test fields (fully closed MLC, picket fence, sliding windows of different size, and leaf-tip profiles) cover the extremes of MLC usage during IMRT, while the patient fields represent realistic clinical conditions. Of the methods tested, the hybrid method most accurately reproduces measurements. For the hybrid method, 79 of 79 DMLC field calculations have γ ≤1 (3% /3 mm) for more than 95% of the points (per field) while for SMLC fields, 27 of 29 pass the same criteria. The analytic energy fluence estimation methods show inferior pass rates, with 76 of 79 DMLC and 24 of 29 SMLC fields having more than 95% of the test points

  5. Optical delivery and monitoring of photodynamic therapy of prostate cancer

    NASA Astrophysics Data System (ADS)

    Weersink, Robert A.; Bogaards, Arjun; Gertner, Mark; Davidson, Sean; Zhang, Kai; Netchev, George; Giewercer, David J.; Trachtenberg, John; Wilson, Brian C.

    2004-10-01

    Photodynamic therapy of recurrent prostate cancer is currently undergoing Phase II clinical trials with the vascular targeting drug TOOKAD. Proper PDT dosage requires sound estimates of the light fluence and drug concentration throughout the organ. The treatment requires multiple diffusing light delivery fibers placed in position according to a light dose treatment plan under ultrasound guidance. Fluence rate is monitored by multiple sensor fibers placed throughout the organ and in sensitive organs near the prostate. The combination of multiple light delivery and fluence sensor fibers is used to estimate the optical properties of the tissue and to provide a general fluence map throughout the organ. This fluence map is then used to estimate extent of photodynamic dose. Optical spectroscopy is used to monitor drug pharmacokinetics in the organ and blood hemodynamics within the organ. Further development of these delivery and monitoring techniques will permit full online monitoring of the treatment that will enable real-time patient-specific delivery of photodynamic therapy.

  6. Evaluation of Aerosol Delivery of Nanosuspension for Pre-clinical Pulmonary Drug Delivery

    NASA Astrophysics Data System (ADS)

    Chiang, Po-Chang; Alsup, Jason W.; Lai, Yurong; Hu, Yiding; Heyde, Bruce R.; Tung, David

    2009-03-01

    Asthma and chronic obstructive pulmonary disease (COPD) are pulmonary diseases that are characterized by inflammatory cell infiltration, cytokine production, and airway hyper-reactivity. Most of the effector cells responsible for these pathologies reside in the lungs. One of the most direct ways to deliver drugs to the target cells is via the trachea. In a pre-clinical setting, this can be achieved via intratracheal (IT), intranasal (IN), or aerosol delivery in the desired animal model. In this study, we pioneered the aerosol delivery of a nanosuspension formulation in a rodent model. The efficiency of different dosing techniques and formulations to target the lungs were compared, and fluticasone was used as the model compound. For the aerosol particle size determination, a ten-stage cascade impactor was used. The mass median aerodynamic diameter (MMAD) was calculated based on the percent cumulative accumulation at each stage. Formulations with different particle size of fluticasone were made for evaluation. The compatibility of regular fluticasone suspension and nanosuspension for aerosol delivery was also investigated. The in vivo studies were conducted on mice with optimized setting. It was found that the aerosol delivery of fluticasone with nanosuspension was as efficient as intranasal (IN) dosing, and was able to achieve dose dependent lung deposition.

  7. Elective Delivery Before 39 Weeks

    MedlinePlus

    ... Delivery, and Postpartum Care Elective Delivery Before 39 Weeks • What is a “medically indicated” delivery? • What is ... the baby grow and develop during the last weeks of pregnancy? • What are the risks for babies ...

  8. Transdermal Delivery of Nisoldipine: Refinement of Vehicles.

    PubMed

    El Maghraby, Gamal M; Ahmed, Amal A; Osman, Mohamed A

    2015-01-01

    Nisoldipine is used for the treatment of hypertension and angina pectoris. However, it has very low bioavailabil-ty, which is attributed to extensive pre-systemic metabolism. In addition, nisol-ipine is highly potent (used at a low dose). Taking into consideration the fact that transdermal delivery avoids the pre-systemic metabolism and is only suit-ble for potent drugs, nisoldipine can be considered as an excellent candidate for transdermal delivery. Accordingly, the purpose of this study was to optimize nisoldipine transdermal delivery. That was achieved initially by investigating the effect of vehicles on skin penetration. The tested vehicles were ranked with respect to transdermal flux of nisoldipine as isopropyl myristate > oleic acid > propylene glycol > water > polyethylene glycol 400. A combination of oleic acid with propylene glycol was synergistic with a ratio of 1:2 w/w being the best. These results were taken further to develop microemulsion systems using either oleic acid or isopropyl myristate as the oil phase. Both cases employed polyoxy-thylene sorbitan monooleate as a surfactant with propylene glycol being uti-ized as a cosurfactant in the case of oleic acid and ethanol in the case of isopropyl myristate. The developed microemulsions produced significant enhancement in nisoldipine transdermal delivery with the flux being even greater than that obtained from the corresponding pure vehicles. This achieve-ent was recorded in optimum microemulsion formulations which contained a cosurfactant. The study provided stepwise optimization of a vehicle for trans-ermal delivery of nisoldipine. PMID:26685495

  9. Methods of Drug Delivery in Neurotrauma.

    PubMed

    Deng-Bryant, Ying; Readnower, Ryan; Leung, Lai Yee; Tortella, Frank; Shear, Deborah

    2016-01-01

    The central nervous system (CNS) is protected by blood-brain barrier (BBB) and blood-cerebrospinal-fluid (CSF) barrier that limit toxic agents and most molecules from penetrating the brain and spinal cord. However, these barriers also prevent most pharmaceuticals from entering into the CNS. Drug delivery to the CNS following neurotrauma is complicated. Although studies have shown BBB permeability increases in various TBI models, it remains as the key mitigating factor for delivering drugs into the CNS. The commonly used methods for drug delivery in preclinical neurotrauma studies include intraperitoneal, subcutaneous, intravenous, and intracerebroventricular delivery. It should be noted that for a drug to be successfully translated into the clinic, it needs to be administered preclinically as it would be anticipated to be administered to patients. And this likely leads to better dose selection of the drug, as well as recognition of any possible side effects, prior to transition into a clinical trial. Additionally, novel approach that is noninvasive and yet circumvents BBB, such as drug delivery through nerve pathways innervating the nasal passages, needs to be investigated in animal models, as it may provide a viable drug delivery method for patients who sustain mild CNS injury or require chronic treatments. Therefore, the focus of this chapter is to present rationales and methods for delivering drugs by IV infusion via the jugular vein, and intranasally in preclinical studies. PMID:27604714

  10. In vivo TLD dose measurements in catheter-based high-dose-rate brachytherapy.

    PubMed

    Adlienė, Diana; Jakštas, Karolis; Urbonavičius, Benas Gabrielis

    2015-07-01

    Routine in vivo dosimetry is well established in external beam radiotherapy; however, it is restricted mainly to detection of gross errors in high-dose-rate (HDR) brachytherapy due to complicated measurements in the field of steep dose gradients in the vicinity of radioactive source and high uncertainties. The results of in vivo dose measurements using TLD 100 mini rods and TLD 'pin worms' in catheter-based HDR brachytherapy are provided in this paper alongside with their comparison with corresponding dose values obtained using calculation algorithm of the treatment planning system. Possibility to perform independent verification of treatment delivery in HDR brachytherapy using TLDs is discussed. PMID:25809111

  11. Available evidence on re-irradiation with stereotactic ablative radiotherapy following high-dose previous thoracic radiotherapy for lung malignancies.

    PubMed

    De Bari, Berardino; Filippi, Andrea Riccardo; Mazzola, Rosario; Bonomo, Pierluigi; Trovò, Marco; Livi, Lorenzo; Alongi, Filippo

    2015-06-01

    Patients affected with intra-thoracic recurrences of primary or secondary lung malignancies after a first course of definitive radiotherapy have limited therapeutic options, and they are often treated with a palliative intent. Re-irradiation with stereotactic ablative radiotherapy (SABR) represents an appealing approach, due to the optimized dose distribution that allows for high-dose delivery with better sparing of organs at risk. This strategy has the goal of long-term control and even cure. Aim of this review is to report and discuss published data on re-irradiation with SABR in terms of efficacy and toxicity. Results indicate that thoracic re-irradiation may offer satisfactory disease control, however the data on outcome and toxicity are derived from low quality retrospective studies, and results should be cautiously interpreted. As SABR may be associated with serious toxicity, attention should be paid for an accurate patients' selection. PMID:25913714

  12. Nanocarriers for Nitric Oxide Delivery

    PubMed Central

    Saraiva, Juliana; Marotta-Oliveira, Samantha S.; Cicillini, Simone Aparecida; Eloy, Josimar de Oliveira; Marchetti, Juliana Maldonado

    2011-01-01

    Nitric oxide (NO) is a promising pharmaceutical agent that has vasodilative, antibacterial, and tumoricidal effects. To study the complex and wide-ranging roles of NO and to facilitate its therapeutic use, a great number of synthetic compounds (e.g., nitrosothiols, nitrosohydroxyamines, N-diazeniumdiolates, and nitrosyl metal complexes) have been developed to chemically stabilize and release NO in a controlled manner. Although NO is currently being exploited in many biomedical applications, its use is limited by several factors, including a short half-life, instability during storage, and potential toxicity. Additionally, efficient methods of both localized and systemic in vivo delivery and dose control are needed. One strategy for addressing these limitations and thus increasing the utility of NO donors is based on nanotechnology. PMID:21869934

  13. SU-E-J-17: Intra-Fractional Prostate Movement Correction During Treatment Delivery Period for Prostate Cancer Using the Intra-Fractional Orthogonal KV-MV Image Pairs

    SciTech Connect

    Zhang, J; Azawi, S; Cho-Lim, J; Wei, R; Williams, R; Frank, E

    2015-06-15

    Purpose: To evaluate the intra-fractional prostate movement range during the beam delivery and implement new IGRT method to correct the prostate movement during the hypofractionated prostate treatment delivery. Methods: To evaluate the prostate internal motion range during the beam delivery, 11 conventional treatments were utilized. Two-arc RapidArc plans were used for the treatment delivery. Orthogonal KV imaging is performed in the middle of the treatment to correct intra-fractional prostate movement. However, it takes gantry-mounted on-board imaging system relative long time to finish the orthogonal KV imaging because of gantry rotation. To avoid gantry movement and accelerate the IGRT processing time, orthogonal KV-MV image pair is tested using the OBI daily QA Cube phantom. Results: The average prostate movement between two orthogonal KV image pairs was 0.38cm (0.20cm ∼ 0.85cm). And the interval time between them was 6.71 min (4.64min ∼ 9.22 min). 2-arc beam delivery time is within 3 minutes for conventional RapidArc treatment delivery. Hypofractionated treatment or SBRT need 4 partial arc and possible non-coplanar technology, which need much longer beam delivery time. Therefore prostate movement might be larger. New orthogonal KV-MV image pair is a new method to correct the prostate movement in the middle of the beam delivery if real time tracking method is not available. Orthogonal KV-MV image pair doesn’t need gantry rotation. Images were acquired quickly which minimized possible new prostate movement. Therefore orthogonal KV-MV image pair is feasible for IGRT. Conclusion: Hypofractionated prostate treatment with less PTV margin always needs longer beam delivery time. Therefore prostate movement correction during the treatment delivery is critical. Orthogonal KV-MV imaging pair is efficient and accurate to correct the prostate movement during treatment beam delivery. Due to limited fraction number and high dose per fraction, the MV imaging dose is

  14. Characterization of exposure and dose of man made vitreous fiber in experimental studies.

    PubMed Central

    Hamilton, R D; Miiller, W C; Christensen, D R; Anderson, R; Hesterberg, T W

    1994-01-01

    The use of fibrous test materials in in vivo experiments introduces a number of significant problems not associated with nonfibrous particulates. The key to all aspects of the experiment is the accurate characterization of the test material in terms of fiber length, diameter, particulate content, and chemistry. All data related to fiber properties must be collected in a statistically sound manner to eliminate potential bias. Procedures similar to those outlined by the National Institute of Occupational Safety and Health (NIOSH) or the World Health Organization (WHO) must be the basis of any fiber characterization. The test material to which the animal is exposed must be processed to maximize the amount of respirable fiber and to minimize particulate content. The complex relationship among the characteristics of the test material, the properties of the delivery system, and the actual dose that reaches the target tissue in the lung makes verification of dose essential. In the case of man-made vitreous fibers (MMVF), dose verification through recovery of fiber from exposed animals is a complex task. The potential for high fiber solubility makes many of the conventional techniques for tissue preservation and digestion inappropriate. Processes based on the minimum use of aggressive chemicals, such as cold storage and low temperature ashing, are potentially useful for a wide range of inorganic fibers. Any processes used to assess fiber exposure and dose must be carefully validated to establish that the chemical and physical characteristics of the fibers have not been changed and that the dose to the target tissue is completely and accurately described. PMID:7882912

  15. Delivery efficiency of an Elekta linac under gated operation.

    PubMed

    Cui, Guoqiang; Housley, David J; Chen, Fan; Mehta, Vivek K; Shepard, David M

    2014-01-01

    In this study, we have characterized the efficiency of an Elekta linac in the delivery of gated radiotherapy. We have explored techniques to reduce the beam-on delay and to improve the delivery efficiency, and have investigated the impact of frequent beam interruptions on the dosimetric accuracy of gated deliveries. A newly available gating interface was installed on an Elekta Synergy. Gating signals were generated using a surface mapping system in conjunction with a respiratory motion phantom. A series of gated deliveries were performed using volumetric modulated arc therapy (VMAT) treatment plans previously generated for lung cancer patients treated with stereotactic body radiotherapy. Baseline values were determined for the delivery times. The machine was then tuned in an effort to minimize beam-on delays and improve delivery efficiency. After that process was completed, the dosimetric accuracy of the gated deliveries was evaluated by comparing the measured and the planned coronal dose distributions using gamma index analyses. Comparison of the gated and the non-gated deliveries were also performed. The results demonstrated that, with the optimal machine settings, the average beam-on delay was reduced to less than 0.22 s. High dosimetric accuracy was demonstrated with gamma index passing rates no lower than 99.0% for all tests (3%/3 mm criteria). Consequently, Elekta linacs can provide a practical solution for gated VMAT treatments with high dosimetric accuracy and only a moderate increase in the overall delivery time. PMID:25207561

  16. Implantable microchip: the futuristic controlled drug delivery system.

    PubMed

    Sutradhar, Kumar Bishwajit; Sumi, Chandra Datta

    2016-01-01

    There is no doubt that controlled and pulsatile drug delivery system is an important challenge in medicine over the conventional drug delivery system in case of therapeutic efficacy. However, the conventional drug delivery systems often offer a limited by their inability to drug delivery which consists of systemic toxicity, narrow therapeutic window, complex dosing schedule for long term treatment etc. Therefore, there has been a search for the drug delivery system that exhibit broad enhancing activity for more drugs with less complication. More recently, some elegant study has noted that, a new type of micro-electrochemical system or MEMS-based drug delivery systems called microchip has been improved to overcome the problems related to conventional drug delivery. Moreover, micro-fabrication technology has enabled to develop the implantable controlled released microchip devices with improved drug administration and patient compliance. In this article, we have presented an overview of the investigations on the feasibility and application of microchip as an advanced drug delivery system. Commercial manufacturing materials and methods, related other research works and current advancement of the microchips for controlled drug delivery have also been summarized. PMID:24758139

  17. Reservoir design and dose availability with long-term metered dose inhaler corticosteroid use.

    PubMed

    Rau, J L; Zhu, Y

    1998-01-01

    The effect of reservoir design and long-term use with inhaled metered dose inhaler (MDI) corticosteroids on aerosol dose availability was examined. Beclomethasone dipropionate (Vanceril) was delivered by MDI with three brands of available reservoir devices: the AeroChamber, the OptiHaler, and the Aerosol Cloud Enhancer (ACE). An in vitro lung model simulated inspiration. Long-term use was simulated by exhausting five MDI canisters of beclomethasone through each sample of reservoir tested. Each canister exhausted through a reservoir represented approximately 1 month of use with one drug. Total inhaled dose was collected at the reservoir mouthpiece and measured using a spectrophotometric assay. Dose delivery was measured before simulated use and after each MDI canister was exhausted through the reservoir. Three samples of each brand were tested with cleaning and three samples were tested without cleaning. With cleaning, the AeroChamber, OptiHaler, and ACE delivered significantly different average doses of 16.6, 10.3, and 8.7 micrograms per MDI actuation, respectively, (P = 0.0017) over time of use. Changes in dose delivery over time of use were not significant (P = 0.2011). Without cleaning, the same three brands averaged 21.1, 9.7, and 7.8 micrograms per MDI actuation, respectively, (P = 0.0019), and changes in dose delivery over time were not significant (P = 0.3265). Reservoir design can affect the delivery of an inhaled corticosteroid, although the delivery over 4 to 5 months remained stable. PMID:10177218

  18. Pre-treatment radiotherapy dose verification using Monte Carlo doselet modulation in a spherical phantom

    NASA Astrophysics Data System (ADS)

    Townson, Reid W.; Zavgorodni, Sergei

    2014-04-01

    Due to the increasing complexity of radiotherapy delivery, accurate dose verification has become an essential part of the clinical treatment process. The purpose of this work was to develop a pre-treatment verification technique capable of quickly reconstructing 3D dose distributions from both coplanar and non-coplanar treatments. For each treatment field, electronic portal images were taken in non-transmission mode (with no patient in the beam) allowing the derivation of the delivered fluence maps. The dose reconstruction was then performed in a spherical water phantom by modulating and summing the Monte Carlo (MC) doselets, defined on a spherical co-ordinate system, and pre-calculated from azimuthally symmetric fluence above the jaws. The technique, called the spherical doselet modulation (SDM) method, essentially eliminates the statistical uncertainty of the MC dose calculations by exploiting the azimuthal symmetry in both a patient-independent phase-space and in a virtual spherical water phantom. For example, this symmetry allowed the number of doselets necessary for dose reconstruction to be reduced by a factor of ˜250. In this work, only 51 radially binned doselets were used (each generated from all particles in a given annulus of the phase-space, azimuthally redistributed into a small cylindrical sector). The SDM method mitigates the most computationally intensive part of this type of dose reconstruction--reading, weighting and summing dose matrices. The accuracy of the system was tested against MC calculations as well as our previously reported phase-space modulation method, using a series of open field and IMRT cases. The mean chi- and gamma-test 3%/3 mm success rates of the SDM method were 98.6% and 99.5%, respectively, when compared to full MC simulation. The total calculation time was 96 s per treatment field on a single processor core.

  19. Monte Carlo dose mapping on deforming anatomy

    NASA Astrophysics Data System (ADS)

    Zhong, Hualiang; Siebers, Jeffrey V.

    2009-10-01

    This paper proposes a Monte Carlo-based energy and mass congruent mapping (EMCM) method to calculate the dose on deforming anatomy. Different from dose interpolation methods, EMCM separately maps each voxel's deposited energy and mass from a source image to a reference image with a displacement vector field (DVF) generated by deformable image registration (DIR). EMCM was compared with other dose mapping methods: energy-based dose interpolation (EBDI) and trilinear dose interpolation (TDI). These methods were implemented in EGSnrc/DOSXYZnrc, validated using a numerical deformable phantom and compared for clinical CT images. On the numerical phantom with an analytically invertible deformation map, EMCM mapped the dose exactly the same as its analytic solution, while EBDI and TDI had average dose errors of 2.5% and 6.0%. For a lung patient's IMRT treatment plan, EBDI and TDI differed from EMCM by 1.96% and 7.3% in the lung patient's entire dose region, respectively. As a 4D Monte Carlo dose calculation technique, EMCM is accurate and its speed is comparable to 3D Monte Carlo simulation. This method may serve as a valuable tool for accurate dose accumulation as well as for 4D dosimetry QA.

  20. Reservoir-Based Drug Delivery Systems Utilizing Microtechnology

    PubMed Central

    Stevenson, Cynthia L.; Santini, John T.; Langer, Robert

    2012-01-01

    This review covers reservoir-based drug delivery systems that incorporate microtechnology, with an emphasis on oral, dermal, and implantable systems. Key features of each technology are highlighted such as working principles, fabrication methods, dimensional constraints, and performance criteria. Reservoir-based systems include a subset of microfabricated drug delivery systems and provide unique advantages. Reservoirs, whether external to the body or implanted, provide a well-controlled environment for a drug formulation, allowing increased drug stability and prolonged delivery times. Reservoir systems have the flexibility to accommodate various delivery schemes, including zero order, pulsatile, and on demand dosing, as opposed to a standard sustained release profile. Furthermore, the development of reservoir-based systems for targeted delivery for difficult to treat applications (e.g., ocular) has resulted in potential platforms for patient therapy. PMID:22465783

  1. Reformulation of a clinical-dose system for carbon-ion radiotherapy treatment planning at the National Institute of Radiological Sciences, Japan

    NASA Astrophysics Data System (ADS)

    Inaniwa, Taku; Kanematsu, Nobuyuki; Matsufuji, Naruhiro; Kanai, Tatsuaki; Shirai, Toshiyuki; Noda, Koji; Tsuji, Hiroshi; Kamada, Tadashi; Tsujii, Hirohiko

    2015-04-01

    At the National Institute of Radiological Sciences (NIRS), more than 8,000 patients have been treated for various tumors with carbon-ion (C-ion) radiotherapy in the past 20 years based on a radiobiologically defined clinical-dose system. Through clinical experience, including extensive dose escalation studies, optimum dose-fractionation protocols have been established for respective tumors, which may be considered as the standards in C-ion radiotherapy. Although the therapeutic appropriateness of the clinical-dose system has been widely demonstrated by clinical results, the system incorporates several oversimplifications such as dose-independent relative biological effectiveness (RBE), empirical nuclear fragmentation model, and use of dose-averaged linear energy transfer to represent the spectrum of particles. We took the opportunity to update the clinical-dose system at the time we started clinical treatment with pencil beam scanning, a new beam delivery method, in 2011. The requirements for the updated system were to correct the oversimplifications made in the original system, while harmonizing with the original system to maintain the established dose-fractionation protocols. In the updated system, the radiation quality of the therapeutic C-ion beam was derived with Monte Carlo simulations, and its biological effectiveness was predicted with a theoretical model. We selected the most used C-ion beam with αr = 0.764 Gy-1 and β = 0.0615 Gy-2 as reference radiation for RBE. The C-equivalent biological dose distribution is designed to allow the prescribed survival of tumor cells of the human salivary gland (HSG) in entire spread-out Bragg peak (SOBP) region, with consideration to the dose dependence of the RBE. This C-equivalent biological dose distribution is scaled to a clinical dose distribution to harmonize with our clinical experiences with C-ion radiotherapy. Treatment plans were made with the original and the updated clinical-dose systems, and both

  2. Sci—Sat AM: Stereo — 01: 3D Pre-treatment Dose Verification for Stereotactic Body Radiation Therapy Patients

    SciTech Connect

    Asuni, G; Beek, T van; Van Utyven, E; McCowan, P; McCurdy, B.M.C.

    2014-08-15

    Radical treatment techniques such as stereotactic body radiation therapy (SBRT) are becoming popular and they involve delivery of large doses in fewer fractions. Due to this feature of SBRT, a high-resolution, pre-treatment dose verification method that makes use of a 3D patient representation would be appropriate. Such a technique will provide additional information about dose delivered to the target volume(s) and organs-at-risk (OARs) in the patient volume compared to 2D verification methods. In this work, we investigate an electronic portal imaging device (EPID) based pre-treatment QA method which provides an accurate reconstruction of the 3D-dose distribution in the patient model. Customized patient plans are delivered ‘in air’ and the portal images are collected using the EPID in cine mode. The images are then analysed to determine an estimate of the incident energy fluence. This is then passed to a collapsed-cone convolution dose algorithm which reconstructs a 3D patient dose estimate on the CT imaging dataset. To date, the method has been applied to 5 SBRT patient plans. Reconstructed doses were compared to those calculated by the TPS. Reconstructed mean doses were mostly within 3% of those in the TPS. DVHs of target volumes and OARs compared well. The Chi pass rates using 3%/3mm in the high dose region are greater than 97% in all cases. These initial results demonstrate clinical feasibility and utility of a robust, efficient, effective and convenient pre-treatment QA method using EPID. Research sponsored in part by Varian Medical Systems.

  3. A dosimetric phantom study of dose accuracy and build-up effects using IMRT and RapidArc in stereotactic irradiation of lung tumours

    PubMed Central

    2012-01-01

    Background and purpose Stereotactic lung radiotherapy (SLRT) has emerged as a curative treatment for medically inoperable patients with early-stage non-small cell lung cancer (NSCLC) and the use of intensity-modulated radiotherapy (IMRT) and volumetric modulated arc treatments (VMAT) have been proposed as the best practical approaches for the delivery of SLRT. However, a large number of narrow field shapes are needed in the dose delivery of intensity-modulated techniques and the probability of underdosing the tumour periphery increases as the effective field size is decreased. The purpose of this study was to evaluate small lung tumour doses irradiated by intensity-modulated techniques to understand the risk for dose calculation errors in precision radiotherapy such as SLRT. Materials and methods The study was executed with two heterogeneous phantoms with targets of Ø1.5 and Ø4.0 cm. Dose distributions in the simulated tumours delivered by small sliding window apertures (SWAs), IMRT and RapidArc treatment plans were measured with radiochromic film. Calculation algorithms of pencil beam convolution (PBC) and anisotropic analytic algorithm (AAA) were used to calculate the corresponding dose distributions. Results Peripheral doses of the tumours were decreased as SWA decreased, which was not modelled by the calculation algorithms. The smallest SWA studied was 2 mm, which reduced the 90% isodose line width by 4.2 mm with the Ø4.0 cm tumour as compared to open field irradiation. PBC was not able to predict the dose accurately as the gamma evaluation failed to meet the criteria of ±3%/±1 mm on average in 61% of the defined volume with the smaller tumour. With AAA the corresponding value was 16%. The dosimetric inaccuracy of AAA was within ±3% with the optimized treatment plans of IMRT and RapidArc. The exception was the clinical RapidArc plan with dose overestimation of 4%. Conclusions Overall, the peripheral doses of the simulated lung tumours were

  4. Optimization of temporal dose modulation: Comparison of theory and experiment

    SciTech Connect

    Bewes, J. M.; Suchowerska, N.; Cartwright, L.; Ebert, M. A.; McKenzie, D. R.

    2012-06-15

    Purpose: To compare theoretical predictions and experimental measurements of cell survival after exposure to two different temporally modulated radiation dose patterns that deliver the same dose in the same overall time. Methods: The authors derived an analytic expression for the dose protraction factor G in the Lea-Catcheside formalism for cell survival for 'triangle' and 'V' temporal modulation of dose. These temporal dose patterns were used in experimental clonogenic studies of a melanoma cell line (MM576) and a nonsmall-cell lung cancer line (NCI-H460) that have different alpha, beta, and repair parameters. The overall treatment time and total dose were kept constant. Results: The analytic expressions for G for the two temporal modulations are presented as a function of a single variable, the product of the exposure time, and the repair constant, enabling G to be evaluated for any exposure time and for any cell line. G for the triangle delivery pattern is always the larger. For the MM576 cell line, following a large dose of 6 Gy, a larger survival fraction was found for the V delivery pattern. No difference in survival was observed for lower doses or for the NCI-H460 cell line at any dose. These results are predicted by our theory, using published values of alpha, beta, and repair time within the limits of experimental uncertainty. Conclusions: The study provides evidence to confirm that cell lines having large beta values exhibit a response that is sensitive to the pattern of dose delivery when the delivery time is comparable with the repair time. It is recommended that the dose delivery pattern be considered in hypofractionated treatments.

  5. Dose audit failures and dose augmentation

    NASA Astrophysics Data System (ADS)

    Herring, C.

    1999-01-01

    Standards EN 552 and ISO 11137, covering radiation sterilization, are technically equivalent in their requirements for the selection of the sterilization dose. Dose Setting Methods 1 and 2 described in Annex B of ISO 11137 can be used to meet these requirements for the selection of the sterilization dose. Both dose setting methods require a dose audit every 3 months to determine the continued validity of the sterilization dose. This paper addresses the subject of dose audit failures and investigations into their cause. It also presents a method to augment the sterilization dose when the number of audit positives exceeds the limits imposed by ISO 11137.

  6. Nebulized Live-Attenuated Influenza Vaccine Provides Protection in Ferrets at a Reduced Dose

    PubMed Central

    Smith, Jennifer Humberd; Papania, Mark; Knaus, Darin; Brooks, Paula; Haas, Debra L.; Mair, Raydel; Barry, James; Tompkins, S. Mark; Tripp, Ralph A.

    2011-01-01

    Live-attenuated influenza vaccine (LAIV) is delivered to vaccine recipients using a nasal spray syringe. LAIV delivered by this method is immunogenic at current doses; however, improvements in nasal delivery might allow for significant dose reduction. We investigated LAIV vaccination in ferrets using a high efficiency nebulizer designed for nasal delivery. LAIV nasal aerosol elicited high levels of serum neutralizing antibodies and protected ferrets from homologous virus challenge at conventional (107 TCID50) and significantly reduced (103 TCID50) doses. Aerosol LAIV also provided a significant level of subtype-specific cross protection. These results demonstrate the dose-sparing potential of nebulizer-based nasal aerosol LAIV delivery. PMID:22075083

  7. A silicon strip detector dose magnifying glass for IMRT dosimetry

    SciTech Connect

    Wong, J. H. D.; Carolan, M.; Lerch, M. L. F.; Petasecca, M.; Khanna, S.; Perevertaylo, V. L.; Metcalfe, P.; Rosenfeld, A. B.

    2010-02-15

    Purpose: Intensity modulated radiation therapy (IMRT) allows the delivery of escalated radiation dose to tumor while sparing adjacent critical organs. In doing so, IMRT plans tend to incorporate steep dose gradients at interfaces between the target and the organs at risk. Current quality assurance (QA) verification tools such as 2D diode arrays, are limited by their spatial resolution and conventional films are nonreal time. In this article, the authors describe a novel silicon strip detector (CMRP DMG) of high spatial resolution (200 {mu}m) suitable for measuring the high dose gradients in an IMRT delivery. Methods: A full characterization of the detector was performed, including dose per pulse effect, percent depth dose comparison with Farmer ion chamber measurements, stem effect, dose linearity, uniformity, energy response, angular response, and penumbra measurements. They also present the application of the CMRP DMG in the dosimetric verification of a clinical IMRT plan. Results: The detector response changed by 23% for a 390-fold change in the dose per pulse. A correction function is derived to correct for this effect. The strip detector depth dose curve agrees with the Farmer ion chamber within 0.8%. The stem effect was negligible (0.2%). The dose linearity was excellent for the dose range of 3-300 cGy. A uniformity correction method is described to correct for variations in the individual detector pixel responses. The detector showed an over-response relative to tissue dose at lower photon energies with the maximum dose response at 75 kVp nominal photon energy. Penumbra studies using a Varian Clinac 21EX at 1.5 and 10.0 cm depths were measured to be 2.77 and 3.94 mm for the secondary collimators, 3.52 and 5.60 mm for the multileaf collimator rounded leaf ends, respectively. Point doses measured with the strip detector were compared to doses measured with EBT film and doses predicted by the Philips Pinnacle treatment planning system. The differences were 1

  8. Project Delivery Methods.

    ERIC Educational Resources Information Center

    Dolan, Thomas G.

    2003-01-01

    Describes project delivery methods that are replacing the traditional Design/Bid/Build linear approach to the management, design, and construction of new facilities. These variations can enhance construction management and teamwork. (SLD)

  9. Delivery by Cesarean Section

    MedlinePlus

    ... Español Text Size Email Print Share Delivery by Cesarean Section Page Content Article Body More than one mother in three gives birth by Cesarean section in the United States (it is also called ...

  10. Assisted Vaginal Delivery

    MedlinePlus

    ... having a repeat assisted vaginal delivery in a future pregnancy? If you have had one assisted vaginal ... a vacuum device. Vacuum Device: A metal or plastic cup that is applied to the fetus’ head ...

  11. Posterior Segment Drug Delivery Devices: Current and Novel Therapies in Development.

    PubMed

    Bansal, Pooja; Garg, Satpal; Sharma, Yograj; Venkatesh, Pradeep

    2016-04-01

    Ocular drug delivery by conventional routes of administration does not maintain therapeutic drug concentrations in the target tissues for a long duration because of various anatomical and physiological barriers. Treatment of diseases of the posterior segment of the eye requires novel drug delivery systems that can overcome these barriers for efficacious delivery, provide controlled release for the treatment of chronic diseases, and increase patient's and doctor's convenience to reduce the dosing frequency and associated side effects. Thereby, an increasing number of sustained-release drug delivery devices using different mechanisms have been developed. This article discusses various current and future sustained-release drug delivery systems for the posterior segment disorders. PMID:26811883

  12. Nanotransporters for drug delivery.

    PubMed

    Lühmann, Tessa; Meinel, Lorenz

    2016-06-01

    Soluble nanotransporters for drugs can be profiled for targeted delivery particularly to maximize the efficacy of highly potent drugs while minimizing off target effects. This article outlines on the use of biological carrier molecules with a focus on albumin, various drug linkers for site specific release of the drug payload from the nanotransporter and strategies to combine these in various ways to meet different drug delivery demands particularly the optimization of the payload per nanotransporter. PMID:26773302

  13. [Transdermal Delivery of NSAIDs].

    PubMed

    Nakajima, Takehisa; Makino, Kimiko

    2015-11-01

    Skin has been studied as administration site of drug for its systemic effects, since systemic therapeutic agents can be delivered for long time with a controlled ratio, escaping from the first pass effect by liver by the transdermal delivery, which can decrease the dosage form. The low permeability of drug molecules through stratum corneum has been the limiting factor for developing transdermal delivery system of therapeutic agents. To enhance the permeability of drug molecules, many studies have been reported. PMID:26689064

  14. Investigation of simple IMRT delivery techniques for non-small cell lung cancer patients with respiratory motion using 4DCT.

    PubMed

    Reitz, Bodo; Parda, David S; Colonias, Athanasios; Lee, Vincent; Miften, Moyed

    2009-01-01

    Techniques for generating simplified IMRT treatment plans for treating non-small cell lung cancer (NSCLC) patients with respiratory motion were investigated. To estimate and account for respiratory motion, 4-dimensional computed tomography (4DCT) datasets from 5 patients were used to design 5-field 6-MV ungated step-and-shoot intensity modulated radiotherapy (IMRT) plans delivering a dose of 66 Gy to the planning target volume (PTV). For each patient, 2 plans were generated using the mean intensity and the maximum intensity of 10 CT datasets from different breathing phases. The plans also utilized different margins around the clinical target volume/internal target volume (CTV/ITV) to account for tumor motion. To reduce the treatment time and ensure accurate dose delivery to moving targets, the number of intensity levels was minimized while maintaining dose coverage to PTV and minimizing dose to organs at risk (OARs). Dose-volume histograms (DVHs), dosimetric metrics, and outcome probabilities were evaluated for all plans. Plans using the averaged CT image dataset were inferior, requiring larger margins around the PTV, with a maximum of 1.5 cm, to ensure coverage of the tumor, and therefore increased the dose to OARs located in proximity of the tumor. The plans based on superimposed CT image datasets achieved full coverage of the tumor, while allowing tight margins around the PTV and minimizing the dose to OARs. A small number of intensity-levels (3 to 5), resulting in IMRT plans with a total of 13 to 30 segments, were sufficient for homogeneous PTV coverage, without affecting the sparing of OARs. In conclusion, a technique involving treatment planning with the superimposed CT scans of all respiratory phases, and the application of IMRT with only a small number of segments was feasible despite significant tumor motion; however, greater patient numbers are needed to support the statistical significance of the results presented in this work. PMID:19410146

  15. Neutron/gamma dose characterization for use with TLD

    SciTech Connect

    Kee, J.C.; Magee, L.; Hefley, T.

    1991-01-01

    The work described in this paper was performed in preparation for establishing a thermoluminescent dosimetry (TLD) system for workers exposed to spontaneous fission neutrons from mixed plutonium isotopes, {sup 232}Th, and depleted uranium at the US Department of Energy (DOE) Pantex facility. The method proposed uses a neutron-insensitive thermoluminescent dosimeter to measure the gamma dose and apply a neutron dose/gamma dose ratio to calculate the neutron dose equivalent. This approach, while requiring multibadge dosimetry for each individual, provides a more accurate neutron dose calculation than was previously in use and reduces the maximum missed dose and falsely reported dose.

  16. Vectors for airway gene delivery.

    PubMed

    Davis, Pamela B; Cooper, Mark J

    2007-01-01

    Delivery of genes to the airway epithelium for therapeutic purposes seemed easy at first, because the epithelial cells interface with the environment and are therefore accessible. However, problems encountered were more substantial than were originally expected. Nonviral systems may be preferred for long-term gene expression, for they can be dosed repeatedly. Two nonviral gene transfer systems have been in clinical trials, lipid-mediated gene transfer and DNA nanoparticles. Both have sufficient efficiency to be candidates for correction of the cystic fibrosis defect, and both can be dosed repeatedly. However, lipid-mediated gene transfer in the first generation provokes significant inflammatory toxicity, which may be engineered out by adjustments of the lipids, the plasmid CpG content, or both. Both lipid-mediated gene transfer and DNA nanoparticles in the first generation have short duration of expression, but reengineering of the plasmid DNA to contain mostly eukaryotic sequences may address this problem. Considerable advances in the understanding of the cellular uptake and expression of these agents and in their practical utility have occurred in the last few years; these advances are reviewed here. PMID:17408235

  17. Volumetric Modulated Arc Therapy for Spine Radiosurgery: Superior Treatment Planning and Delivery Compared to Static Beam Intensity Modulated Radiotherapy

    PubMed Central

    Zach, Leor; Tsvang, Lev; Alezra, Dror; Ben Ayun, Maoz

    2016-01-01

    Purpose. Spine stereotactic radiosurgery (SRS) delivers an accurate and efficient high radiation dose to vertebral metastases in 1–5 fractions. We aimed to compare volumetric modulated arc therapy (VMAT) to static beam intensity modulated radiotherapy (IMRT) for spine SRS. Methods and Materials. Ten spine lesions of previously treated SRS patients were planned retrospectively using both IMRT and VMAT with a prescribed dose of 16 Gy to 100% of the planning target volume (PTV). The plans were compared for conformity, homogeneity, treatment delivery time, and safety (spinal cord dose). Results. All evaluated parameters favored the VMAT plan over the IMRT plans. Dmin in the IMRT was significantly lower than in the VMAT plan (7.65 Gy/10.88 Gy, p < 0.001), the Dice Similarity Coefficient (DSC) was found to be significantly better for the VMAT plans compared to the IMRT plans (0.77/0.58, resp., p  value < 0.01), and an almost 50% reduction in the net treatment time was calculated for the VMAT compared to the IMRT plans (6.73 min/12.96 min, p < 0.001). Conclusions. In our report, VMAT provides better conformity, homogeneity, and safety profile. The shorter treatment time is a major advantage and not only provides convenience to the painful patient but also contributes to the precision of this high dose radiation therapy. PMID:26885513

  18. MODIFICATION AND CHARACTERIZATION OF DRY MATERIAL FEEDER FOR DELIVERY OF RED AND VIOLET DYE MIXTURES

    EPA Science Inventory

    Uniform delivery of dry material for stable concentrations of aerosols in inhalation exposure chambers is essential in inhalation experiments. his paper characterizes an AccuRate dry material feeder with modifications, for different helix sizes, actuation rates, nozzle types and ...

  19. Imaging method for monitoring delivery of high dose rate brachytherapy

    DOEpatents

    Weisenberger, Andrew G; Majewski, Stanislaw

    2012-10-23

    A method for in-situ monitoring both the balloon/cavity and the radioactive source in brachytherapy treatment utilizing using at least one pair of miniature gamma cameras to acquire separate images of: 1) the radioactive source as it is moved in the tumor volume during brachytherapy; and 2) a relatively low intensity radiation source produced by either an injected radiopharmaceutical rendering cancerous tissue visible or from a radioactive solution filling a balloon surgically implanted into the cavity formed by the surgical resection of a tumor.

  20. Mill profiler machines soft materials accurately

    NASA Technical Reports Server (NTRS)

    Rauschl, J. A.

    1966-01-01

    Mill profiler machines bevels, slots, and grooves in soft materials, such as styrofoam phenolic-filled cores, to any desired thickness. A single operator can accurately control cutting depths in contour or straight line work.

  1. Remote balance weighs accurately amid high radiation

    NASA Technical Reports Server (NTRS)

    Eggenberger, D. N.; Shuck, A. B.

    1969-01-01

    Commercial beam-type balance, modified and outfitted with electronic controls and digital readout, can be remotely controlled for use in high radiation environments. This allows accurate weighing of breeder-reactor fuel pieces when they are radioactively hot.

  2. Understanding the Code: keeping accurate records.

    PubMed

    Griffith, Richard

    2015-10-01

    In his continuing series looking at the legal and professional implications of the Nursing and Midwifery Council's revised Code of Conduct, Richard Griffith discusses the elements of accurate record keeping under Standard 10 of the Code. This article considers the importance of accurate record keeping for the safety of patients and protection of district nurses. The legal implications of records are explained along with how district nurses should write records to ensure these legal requirements are met. PMID:26418404

  3. Synthetic Tumor Networks for Screening Drug Delivery Systems

    PubMed Central

    Prabhakarpandian, Balabhaskar; Shen, Ming-Che; Nichols, Joseph B.; Garson, Charles J.; Mills, Ivy R.; Matar, Majed M.; Fewell, Jason G.; Pant, Kapil

    2015-01-01

    Tumor drug delivery is a complex phenomenon affected by several elements in addition to drug or delivery vehicle’s physico-chemical properties. A key factor is tumor microvasculature with complex effects including convective transport, high interstitial pressure and enhanced vascular permeability due to the presence of “leaky vessels”. Current in vitro models of the tumor microenvironment for evaluating drug delivery are oversimplified and, as a result, show poor correlation with in vivo performance. In this study, we report on the development of a novel microfluidic platform that models the tumor microenvironment more accurately, with physiologically and morphologically realistic microvasculature including endothelial cell lined leaky capillary vessels along with 3D solid tumors. Endothelial cells and 3D spheroids of cervical tumor cells were co-cultured in the networks. Drug vehicle screening was demonstrated using GFP gene delivery by different formulations of nanopolymers. The synthetic tumor network was successful in predicting in vivo delivery efficiencies of the drug vehicles. The developed assay will have critical applications both in basic research, where it can be used to develop next generation delivery vehicles, and in drug discovery where it can be used to study drug transport and delivery efficacy in realistic tumor microenvironment, thereby enabling drug compound and/or delivery vehicle screening. PMID:25599856

  4. Synthetic tumor networks for screening drug delivery systems.

    PubMed

    Prabhakarpandian, Balabhaskar; Shen, Ming-Che; Nichols, Joseph B; Garson, Charles J; Mills, Ivy R; Matar, Majed M; Fewell, Jason G; Pant, Kapil

    2015-03-10

    Tumor drug delivery is a complex phenomenon affected by several elements in addition to drug or delivery vehicle's physico-chemical properties. A key factor is tumor microvasculature with complex effects including convective transport, high interstitial pressure and enhanced vascular permeability due to the presence of "leaky vessels". Current in vitro models of the tumor microenvironment for evaluating drug delivery are oversimplified and, as a result, show poor correlation with in vivo performance. In this study, we report on the development of a novel microfluidic platform that models the tumor microenvironment more accurately, with physiologically and morphologically realistic microvasculature including endothelial cell lined leaky capillary vessels along with 3D solid tumors. Endothelial cells and 3D spheroids of cervical tumor cells were co-cultured in the networks. Drug vehicle screening was demonstrated using GFP gene delivery by different formulations of nanopolymers. The synthetic tumor network was successful in predicting in vivo delivery efficiencies of the drug vehicles. The developed assay will have critical applications both in basic research, where it can be used to develop next generation delivery vehicles, and in drug discovery where it can be used to study drug transport and delivery efficacy in realistic tumor microenvironment, thereby enabling drug compound and/or delivery vehicle screening. PMID:25599856

  5. Technical basis for dose reconstruction

    SciTech Connect

    Anspaugh, L.R.

    1996-12-31

    The purpose of this paper is to consider two general topics: Technical considerations of why dose-reconstruction studies should or should not be performed and methods of dose reconstruction. The first topic is of general and growing interest as the number of dose-reconstruction studies increases, and one asks the question whether it is necessary to perform a dose reconstruction for virtually every site at which, for example, the Department of Energy (DOE) has operated a nuclear-related facility. And there is the broader question of how one might logically draw the line at performing or not performing dose-reconstruction (radiological and chemical) studies for virtually every industrial complex in the entire country. The second question is also of general interest. There is no single correct way to perform a dose-reconstruction study, and it is important not to follow blindly a single method to the point that cheaper, faster, more accurate, and more transparent methods might not be developed and applied. 90 refs., 4 tabs.

  6. Technical basis for dose reconstruction

    SciTech Connect

    Anspaugh, L.R.

    1996-01-31

    The purpose of this paper is to consider two general topics: technical considerations of why dose-reconstruction studies should or should not be performed and methods of dose reconstruction. The first topic is of general and growing interest as the number of dose-reconstruction studies increases, and one asks the question whether it is necessary to perform a dose reconstruction for virtually every site at which, for example, the Department of Energy (DOE) has operated a nuclear-related facility. And there is the broader question of how one might logically draw the line at performing or not performing dose-reconstruction (radiological and chemical) studies for virtually every industrial complex in the entire country. The second question is also of general interest. There is no single correct way to perform a dose-reconstruction study, and it is important not to follow blindly a single method to the point that cheaper, faster, more accurate, and more transparent methods might not be developed and applied.

  7. Confectionery-based dose forms.

    PubMed

    Tangso, Kristian J; Ho, Quy Phuong; Boyd, Ben J

    2015-01-01

    Conventional dosage forms such as tablets, capsules and syrups are prescribed in the normal course of practice. However, concerns about patient preferences and market demands have given rise to the exploration of novel unconventional dosage forms. Among these, confectionery-based dose forms have strong potential to overcome compliance problems. This report will review the availability of these unconventional dose forms used in treating the oral cavity and for systemic drug delivery, with a focus on medicated chewing gums, medicated lollipops, and oral bioadhesive devices. The aim is to stimulate increased interest in the opportunities for innovative new products that are available to formulators in this field, particularly for atypical patient populations. PMID:25146440

  8. Robotic Delivery of Complex Radiation Volumes for Small Animal Research

    PubMed Central

    Matinfar, Mohammad; Iordachita, Iulian; Wong, John; Kazanzides, Peter

    2011-01-01

    The Small Animal Radiation Research Platform (SARRP) is a novel and complete system capable of delivering multidirectional (focal), kilo-voltage radiation fields to targets in small animals under robotic control using cone-beam CT (CBCT) image guidance. The capability of the SARRP to deliver highly focused beams to multiple animal models provides new research opportunities that more realistically bridge laboratory research and clinical translation. This paper describes the design and operation of the SARRP for precise radiation delivery. Different delivery procedures are presented which enable the system to radiate through a series of points, representative of a complex shape. A particularly interesting case is shell dose irradiation, where the goal is to deliver a high dose of radiation to the shape surface, with minimal dose to the shape interior. The ability to deliver a dose shell allows mechanistic research of how a tumor interacts with its microenvironment to sustain its growth and lead to its resistance or recurrence. PMID:21643448

  9. Peripheral doses from pediatric IMRT

    SciTech Connect

    Klein, Eric E.; Maserang, Beth; Wood, Roy; Mansur, David

    2006-07-15

    Peripheral dose (PD) data exist for conventional fields ({>=}10 cm) and intensity-modulated radiotherapy (IMRT) delivery to standard adult-sized phantoms. Pediatric peripheral dose reports are limited to conventional therapy and are model based. Our goal was to ascertain whether data acquired from full phantom studies and/or pediatric models, with IMRT treatment times, could predict Organ at Risk (OAR) dose for pediatric IMRT. As monitor units (MUs) are greater for IMRT, it is expected IMRT PD will be higher; potentially compounded by decreased patient size (absorption). Baseline slab phantom peripheral dose measurements were conducted for very small field sizes (from 2 to 10 cm). Data were collected at distances ranging from 5 to 72 cm away from the field edges. Collimation was either with the collimating jaws or the multileaf collimator (MLC) oriented either perpendicular or along the peripheral dose measurement plane. For the clinical tests, five patients with intracranial or base of skull lesions were chosen. IMRT and conventional three-dimensional (3D) plans for the same patient/target/dose (180 cGy), were optimized without limitation to the number of fields or wedge use. Six MV, 120-leaf MLC Varian axial beams were used. A phantom mimicking a 3-year-old was configured per Center for Disease Control data. Micro (0.125 cc) and cylindrical (0.6 cc) ionization chambers were appropriated for the thyroid, breast, ovaries, and testes. The PD was recorded by electrometers set to the 10{sup -10} scale. Each system set was uniquely calibrated. For the slab phantom studies, close peripheral points were found to have a higher dose for low energy and larger field size and when MLC was not deployed. For points more distant from the field edge, the PD was higher for high-energy beams. MLC orientation was found to be inconsequential for the small fields tested. The thyroid dose was lower for IMRT delivery than that predicted for conventional (ratio of IMRT/cnventional ranged

  10. Characterization of differences in calculated and actual measured skin doses to canine limbs during stereotactic radiosurgery using Gafchromic film

    SciTech Connect

    Walters, Jerri; Ryan, Stewart; Harmon, Joseph F.

    2012-07-01

    Accurate calculation of absorbed dose to the skin, especially the superficial and radiosensitive basal cell layer, is difficult for many reasons including, but not limited to, the build-up effect of megavoltage photons, tangential beam effects, mixed energy scatter from support devices, and dose interpolation caused by a finite resolution calculation matrix. Stereotactic body radiotherapy (SBRT) has been developed as an alternative limb salvage treatment option at Colorado State University Veterinary Teaching Hospital for dogs with extremity bone tumors. Optimal dose delivery to the tumor during SBRT treatment can be limited by uncertainty in skin dose calculation. The aim of this study was to characterize the difference between measured and calculated radiation dose by the Varian Eclipse (Varian Medical Systems, Palo Alto, CA) AAA treatment planning algorithm (for 1-mm, 2-mm, and 5-mm calculation voxel dimensions) as a function of distance from the skin surface. The study used Gafchromic EBT film (International Specialty Products, Wayne, NJ), FilmQA analysis software, a limb phantom constructed from plastic water Trade-Mark-Sign (fluke Biomedical, Everett, WA) and a canine cadaver forelimb. The limb phantom was exposed to 6-MV treatments consisting of a single-beam, a pair of parallel opposed beams, and a 7-beam coplanar treatment plan. The canine forelimb was exposed to the 7-beam coplanar plan. Radiation dose to the forelimb skin at the surface and at depths of 1.65 mm and 1.35 mm below the skin surface were also measured with the Gafchromic film. The calculation algorithm estimated the dose well at depths beyond buildup for all calculation voxel sizes. The calculation algorithm underestimated the dose in portions of the buildup region of tissue for all comparisons, with the most significant differences observed in the 5-mm calculation voxel and the least difference in the 1-mm voxel. Results indicate a significant difference between measured and calculated data

  11. Evaluation of Rectal Dose During High-Dose-Rate Intracavitary Brachytherapy for Cervical Carcinoma

    SciTech Connect

    Sha, Rajib Lochan; Reddy, Palreddy Yadagiri; Rao, Ramakrishna; Muralidhar, Kanaparthy R.; Kudchadker, Rajat J.

    2011-01-01

    High-dose-rate intracavitary brachytherapy (HDR-ICBT) for carcinoma of the uterine cervix often results in high doses being delivered to surrounding organs at risk (OARs) such as the rectum and bladder. Therefore, it is important to accurately determine and closely monitor the dose delivered to these OARs. In this study, we measured the dose delivered to the rectum by intracavitary applications and compared this measured dose to the International Commission on Radiation Units and Measurements rectal reference point dose calculated by the treatment planning system (TPS). To measure the dose, we inserted a miniature (0.1 cm{sup 3}) ionization chamber into the rectum of 86 patients undergoing radiation therapy for cervical carcinoma. The response of the miniature chamber modified by 3 thin lead marker rings for identification purposes during imaging was also characterized. The difference between the TPS-calculated maximum dose and the measured dose was <5% in 52 patients, 5-10% in 26 patients, and 10-14% in 8 patients. The TPS-calculated maximum dose was typically higher than the measured dose. Our study indicates that it is possible to measure the rectal dose for cervical carcinoma patients undergoing HDR-ICBT. We also conclude that the dose delivered to the rectum can be reasonably predicted by the TPS-calculated dose.

  12. Low Dose Suppression of Neoplastic Transformation in Vitro

    SciTech Connect

    John Leslie Redpath

    2012-05-01

    This grant was to study the low dose suppression of neoplastic transformation in vitro and the shape of the dose-response curve at low doses and dose-rates of ionizing radiation. Previous findings had indicated a suppression of transformation at dose <10cGy of low-LET radiation when delivered at high dose-rate. The present study indicates that such suppression extends out to doses in excess of 100cGy when the dose (from I-125 photons) is delivered at dose-rates as low as 0.2 mGy/min and out to in excess of {approx}25cGy the highest dose studied at the very low dose-rate of 0.5 mGy/day. We also examined dose-rate effects for high energy protons (which are a low-LET radiation) and suppression was evident below {approx}10cGy for high dose-rate delivery and at least out to 50cGy for low dose-rate (20cGy/h) delivery. Finally, we also examined the effect of low doses of 1 GeV/n iron ions (a high-LET radiation) delivered at high dose-rate on transformation at low doses and found a suppression below {approx}10cGy that could be attributable to an adaptive response in bystander cells induced by the associated low-LET delta rays. These results have implications for cancer risk assessment at low doses.

  13. Trans-ungual iontophoretic delivery of terbinafine.

    PubMed

    Nair, Anroop B; Vaka, Siva Ram K; Sammeta, Srinivasa M; Kim, Hyun D; Friden, Phillip M; Chakraborty, Bireswar; Murthy, S Narasimha

    2009-05-01

    Successful treatment of deep-seated nail infections remains elusive as the delivery of efficacious levels of antifungal drug to the site of action is very difficult. The aim of the present study was to attain rapid trans-ungual delivery of an antifungal agent, terbinafine, via the topical route using iontophoresis. Initial studies revealed that application of current (0.5 mA/cm(2)) could significantly enhance the trans-ungual delivery of terbinafine. An increase in the applied current or duration of current application enhanced the trans-ungual delivery of terbinafine. Permeation of terbinafine through the nail and drug load in the nail correlated well with the applied electrical dose. Release of drug from nails loaded using iontophoresis followed a two-phase release profile. Light microscopy studies substantiated the capability of iontophoresis to drive a charged molecule across the nail plate. The results of these studies indicate that iontophoresis could be developed as a potential technique for onychomycosis therapy. PMID:18781625

  14. Inhaled nano- and microparticles for drug delivery

    PubMed Central

    El-Sherbiny, Ibrahim M.; El-Baz, Nancy M.; Yacoub, Magdi H.

    2015-01-01

    The 21st century has seen a paradigm shift to inhaled therapy, for both systemic and local drug delivery, due to the lung's favourable properties of a large surface area and high permeability. Pulmonary drug delivery possesses many advantages, including non-invasive route of administration, low metabolic activity, control environment for systemic absorption and avoids first bypass metabolism. However, because the lung is one of the major ports of entry, it has multiple clearance mechanisms, which prevent foreign particles from entering the body. Although these clearance mechanisms maintain the sterility of the lung, clearance mechanisms can also act as barriers to the therapeutic effectiveness of inhaled drugs. This effectiveness is also influenced by the deposition site and delivered dose. Particulate-based drug delivery systems have emerged as an innovative and promising alternative to conventional inhaled drugs to circumvent pulmonary clearance mechanisms and provide enhanced therapeutic efficiency and controlled drug release. The principle of multiple pulmonary clearance mechanisms is reviewed, including mucociliary, alveolar macrophages, absorptive, and metabolic degradation. This review also discusses the current approaches and formulations developed to achieve optimal pulmonary drug delivery systems. PMID:26779496

  15. A novel time dependent gamma evaluation function for dynamic 2D and 3D dose distributions.

    PubMed

    Podesta, Mark; Persoon, Lucas C G G; Verhaegen, Frank

    2014-10-21

    Modern external beam radiotherapy requires detailed verification and quality assurance so that confidence can be placed on both the delivery of a single treatment fraction and on the consistency of delivery throughout the treatment course. To verify dose distributions, a comparison between prediction and measurement must be made. Comparisons between two dose distributions are commonly performed using a Gamma evaluation which is a calculation of two quantities on a pixel by pixel basis; the dose difference, and the distance to agreement. By providing acceptance criteria (e.g. 3%, 3 mm), the function will find the most appropriate match within its two degrees of freedom. For complex dynamic treatments such as IMRT or VMAT it is important to verify the dose delivery in a time dependent manner and so a gamma evaluation that includes a degree of freedom in the time domain via a third parameter, time to agreement, is presented here. A C++ (mex) based gamma function was created that could be run on either CPU and GPU computing platforms that would allow a degree of freedom in the time domain. Simple test cases were created in both 2D and 3D comprising of simple geometrical shapes with well-defined boundaries varying over time. Changes of varying magnitude in either space or time were introduced and repeated gamma analyses were performed varying the criteria. A clinical VMAT case was also included, artificial air bubbles of varying size were introduced to a patient geometry, along with shifts of varying magnitude in treatment time. For all test cases where errors in distance, dose or time were introduced, the time dependent gamma evaluation could accurately highlight the errors.The time dependent gamma function presented here allows time to be included as a degree of freedom in gamma evaluations. The function allows for 2D and 3D data sets which are varying over time to be compared using appropriate criteria without penalising minor offsets of subsequent radiation fields

  16. Telerobotic system concept for real-time soft-tissue imaging during radiotherapy beam delivery

    SciTech Connect

    Schlosser, Jeffrey; Salisbury, Kenneth; Hristov, Dimitre

    2010-12-15

    Purpose: The curative potential of external beam radiation therapy is critically dependent on having the ability to accurately aim radiation beams at intended targets while avoiding surrounding healthy tissues. However, existing technologies are incapable of real-time, volumetric, soft-tissue imaging during radiation beam delivery, when accurate target tracking is most critical. The authors address this challenge in the development and evaluation of a novel, minimally interfering, telerobotic ultrasound (U.S.) imaging system that can be integrated with existing medical linear accelerators (LINACs) for therapy guidance. Methods: A customized human-safe robotic manipulator was designed and built to control the pressure and pitch of an abdominal U.S. transducer while avoiding LINAC gantry collisions. A haptic device was integrated to remotely control the robotic manipulator motion and U.S. image acquisition outside the LINAC room. The ability of the system to continuously maintain high quality prostate images was evaluated in volunteers over extended time periods. Treatment feasibility was assessed by comparing a clinically deployed prostate treatment plan to an alternative plan in which beam directions were restricted to sectors that did not interfere with the transabdominal U.S. transducer. To demonstrate imaging capability concurrent with delivery, robot performance and U.S. target tracking in a phantom were tested with a 15 MV radiation beam active. Results: Remote image acquisition and maintenance of image quality with the haptic interface was successfully demonstrated over 10 min periods in representative treatment setups of volunteers. Furthermore, the robot's ability to maintain a constant probe force and desired pitch angle was unaffected by the LINAC beam. For a representative prostate patient, the dose-volume histogram (DVH) for a plan with restricted sectors remained virtually identical to the DVH of a clinically deployed plan. With reduced margins, as

  17. Practical applications of internal dose calculations

    SciTech Connect

    Carbaugh, E.H.

    1994-06-01

    Accurate estimates of intake magnitude and internal dose are the goal for any assessment of an actual intake of radioactivity. When only one datum is available on which to base estimates, the choices for internal dose assessment become straight-forward: apply the appropriate retention or excretion function, calculate the intake, and calculate the dose. The difficulty comes when multiple data and different types of data become available. Then practical decisions must be made on how to interpret conflicting data, or how to adjust the assumptions and techniques underlying internal dose assessments to give results consistent with the data. This article describes nine types of adjustments which can be incorporated into calculations of intake and internal dose, and then offers several practical insights to dealing with some real-world internal dose puzzles.

  18. Mouse model for efficacy testing of antituberculosis agents via intrapulmonary delivery.

    PubMed

    Gonzalez-Juarrero, Mercedes; Woolhiser, Lisa K; Brooks, Elizabeth; DeGroote, Mary Ann; Lenaerts, Anne J

    2012-07-01

    Here we describe an experimental murine model that allows for aerosolized antituberculosis drug efficacy testing. Intrapulmonary aerosol delivery of isoniazid, capreomycin, and amikacin to mice with pulmonary infection of Mycobacterium tuberculosis demonstrated efficacy in reducing pulmonary bacterial loads similar to that seen by standard drug delivery methods, even when lower concentrations of drugs and fewer doses were used in the aerosolized drug regimens. Interestingly, intrapulmonary delivery of isoniazid also reduced the bacterial load in the spleen. PMID:22547626

  19. Megavoltage cone beam computed tomography: Commissioning and evaluation of patient dose

    PubMed Central

    Abou-elenein, Hassan S.; Attalla, Ehab M.; Ammar, H.; Eldesoky, Ismail; Farouk, Mohamed; Zaghloul, Mohamed S.

    2011-01-01

    The improvement in conformal radiotherapy techniques enables us to achieve steep dose gradients around the target which allows the delivery of higher doses to a tumor volume while maintaining the sparing of surrounding normal tissue. One of the reasons for this improvement was the implementation of intensity-modulated radio therapy (IMRT) by using linear accelerators fitted with multi-leaf collimator (MLC), Tomo therapy and Rapid arc. In this situation, verification of patient set-up and evaluation of internal organ motion just prior to radiation delivery become important. To this end, several volumetric image-guided techniques have been developed for patient localization, such as Siemens OPTIVUE/MVCB and MVision megavoltage cone beam CT (MV-CBCT) system. Quality assurance for MV-CBCT is important to insure that the performance of the Electronic portal image device (EPID) and MV-CBCT is suitable for the required treatment accuracy. In this work, the commissioning and clinical implementation of the OPTIVUE/MVCB system was presented. The geometry and gain calibration procedures for the system were described. The image quality characteristics of the OPTIVUE/MVCB system were measured and assessed qualitatively and quantitatively, including the image noise and uniformity, low-contrast resolution, and spatial resolution. The image reconstruction and registration software were evaluated. Dose at isocenter from CBCT and the EPID were evaluated using ionization chamber and thermo-luminescent dosimeters; then compared with that calculated by the treatment planning system (TPS- XiO 4.4). The results showed that there are no offsets greater than 1 mm in the flat panel alignment in the lateral and longitudinal direction over 18 months of the study. The image quality tests showed that the image noise and uniformity were within the acceptable range, and that a 2 cm large object with 1% electron density contrast can be detected with the OPTIVUE/MVCB system with 5 monitor units (MU

  20. A study of IMRT planning parameters on planning efficiency, delivery efficiency, and plan quality

    SciTech Connect

    Mittauer, Kathryn; Lu Bo; Yan Guanghua; Kahler, Darren; Amdur, Robert; Liu Chihray; Gopal, Arun

    2013-06-15

    Purpose: To improve planning and delivery efficiency of head and neck IMRT without compromising planning quality through the evaluation of inverse planning parameters.Methods: Eleven head and neck patients with pre-existing IMRT treatment plans were selected for this retrospective study. The Pinnacle treatment planning system (TPS) was used to compute new treatment plans for each patient by varying the individual or the combined parameters of dose/fluence grid resolution, minimum MU per segment, and minimum segment area. Forty-five plans per patient were generated with the following variations: 4 dose/fluence grid resolution plans, 12 minimum segment area plans, 9 minimum MU plans, and 20 combined minimum segment area/minimum MU plans. Each plan was evaluated and compared to others based on dose volume histograms (DVHs) (i.e., plan quality), planning time, and delivery time. To evaluate delivery efficiency, a model was developed that estimated the delivery time of a treatment plan, and validated through measurements on an Elekta Synergy linear accelerator. Results: The uncertainty (i.e., variation) of the dose-volume index due to dose calculation grid variation was as high as 8.2% (5.5 Gy in absolute dose) for planning target volumes (PTVs) and 13.3% (2.1 Gy in absolute dose) for planning at risk volumes (PRVs). Comparison results of dose distributions indicated that smaller volumes were more susceptible to uncertainties. The grid resolution of a 4 mm dose grid with a 2 mm fluence grid was recommended, since it can reduce the final dose calculation time by 63% compared to the accepted standard (2 mm dose grid with a 2 mm fluence grid resolution) while maintaining a similar level of dose-volume index variation. Threshold values that maintained adequate plan quality (DVH results of the PTVs and PRVs remained satisfied for their dose objectives) were 5 cm{sup 2} for minimum segment area and 5 MU for minimum MU. As the minimum MU parameter was increased, the number of

  1. Transcutaneous antigen delivery system

    PubMed Central

    Lee, Mi-Young; Shin, Meong-Cheol; Yang, Victor C.

    2013-01-01

    Transcutaneous immunization refers to the topical application of antigens onto the epidermis. Transcutaneous immunization targeting the Langerhans cells of the skin has received much attention due to its safe, needle-free, and noninvasive antigen delivery. The skin has important immunological functions with unique roles for antigen-presenting cells such as epidermal Langerhans cells and dermal dendritic cells. In recent years, novel vaccine delivery strategies have continually been developed; however, transcutaneous immunization has not yet been fully exploited due to the penetration barrier represented by the stratum corneum, which inhibits the transport of antigens and adjuvants. Herein we review recent achievements in transcutaneous immunization, focusing on the various strategies for the enhancement of antigen delivery and vaccination efficacy. [BMB Reports 2013; 46(1): 17-24] PMID:23351379

  2. Metrology for drug delivery.

    PubMed

    Lucas, Peter; Klein, Stephan

    2015-08-01

    In various recently published studies, it is argued that there are underestimated risks with infusion technology, i.e., adverse incidents believed to be caused by inadequate administration of the drugs. This is particularly the case for applications involving very low-flow rates, i.e., <1 ml/h and applications involving drug delivery by means of multiple pumps. The risks in infusing are caused by a lack of awareness, incompletely understood properties of the complete drug delivery system and a lack of a proper metrological infrastructure for low-flow rates. Technical challenges such as these were the reason a European research project "Metrology for Drug Delivery" was started in 2011. In this special issue of Biomedical Engineering, the results of that project are discussed. PMID:25879307

  3. Fast Monte Carlo Electron-Photon Transport Method and Application in Accurate Radiotherapy

    NASA Astrophysics Data System (ADS)

    Hao, Lijuan; Sun, Guangyao; Zheng, Huaqing; Song, Jing; Chen, Zhenping; Li, Gui

    2014-06-01

    Monte Carlo (MC) method is the most accurate computational method for dose calculation, but its wide application on clinical accurate radiotherapy is hindered due to its poor speed of converging and long computation time. In the MC dose calculation research, the main task is to speed up computation while high precision is maintained. The purpose of this paper is to enhance the calculation speed of MC method for electron-photon transport with high precision and ultimately to reduce the accurate radiotherapy dose calculation time based on normal computer to the level of several hours, which meets the requirement of clinical dose verification. Based on the existing Super Monte Carlo Simulation Program (SuperMC), developed by FDS Team, a fast MC method for electron-photon coupled transport was presented with focus on two aspects: firstly, through simplifying and optimizing the physical model of the electron-photon transport, the calculation speed was increased with slightly reduction of calculation accuracy; secondly, using a variety of MC calculation acceleration methods, for example, taking use of obtained information in previous calculations to avoid repeat simulation of particles with identical history; applying proper variance reduction techniques to accelerate MC method convergence rate, etc. The fast MC method was tested by a lot of simple physical models and clinical cases included nasopharyngeal carcinoma, peripheral lung tumor, cervical carcinoma, etc. The result shows that the fast MC method for electron-photon transport was fast enough to meet the requirement of clinical accurate radiotherapy dose verification. Later, the method will be applied to the Accurate/Advanced Radiation Therapy System ARTS as a MC dose verification module.

  4. Nanofibers based antibacterial drug design, delivery and applications.

    PubMed

    Ulubayram, Kezban; Calamak, Semih; Shahbazi, Reza; Eroglu, Ipek

    2015-01-01

    Infections caused by microorganisms like bacteria, fungi, etc. are the main obstacle in healing processes. Conventional antibacterial administration routes can be listed as oral, intravenous/intramuscular, topical and inhalation. These kinds of drug administrations are faced with critical vital issues such as; more rapid delivery of the drug than intended which can result in bacterial resistance, dose related systemic toxicity, tissue irritation and finally delayed healing process that need to be tackled. Recently, studies have been focused on new drug delivery systems, overcoming resistance and toxicological problems and finally localizing the molecules at the site of action in a proper dose. In this regard, many nanotechnological approaches such as nanoparticulate therapeutic systems have been developed to address accompanying problems mentioned above. Among them, drug loaded electrospun nanofibers propose main advantages like controlled drug delivery, high drug loading capacity, high encapsulation efficiency, simultaneous delivery of multiple drugs, ease of production and cost effectiveness for pharmaceutical and biomedical applications. Therefore, some particular attention has been devoted to the design of electrospun nanofibers as promising antibacterial drug carrier systems. A variety of antibacterials e.g., biocides, antibiotics, quaternary ammonium salts, triclosan, metallic nanoparticles (silver, titanium dioxide, and zinc oxide) and antibacterial polymers (chitosan, polyethyleneimine, etc.) have been impregnated by various techniques into nanofibers that exhibit strong antibacterial activity in standard assays. This review highlights the design and delivery of antibacterial drug loaded nanofibers with particular focus on their function in the fields of drug delivery, wound healing, tissue engineering, cosmetics and other biomedical applications. PMID:25732666

  5. Midline Dose Verification with Diode In Vivo Dosimetry for External Photon Therapy of Head and Neck and Pelvis Cancers During Initial Large-Field Treatments

    SciTech Connect

    Tung, Chuan-Jong; Yu, Pei-Chieh; Chiu, Min-Chi; Yeh, Chi-Yuan; Lee, Chung-Chi; Chao, Tsi-Chian

    2010-01-01

    During radiotherapy treatments, quality assurance/control is essential, particularly dose delivery to patients. This study was designed to verify midline doses with diode in vivo dosimetry. Dosimetry was studied for 6-MV bilateral fields in head and neck cancer treatments and 10-MV bilateral and anteroposterior/posteroanterior (AP/PA) fields in pelvic cancer treatments. Calibrations with corrections of diodes were performed using plastic water phantoms; 190 and 100 portals were studied for head and neck and pelvis treatments, respectively. Calculations of midline doses were made using the midline transmission, arithmetic mean, and geometric mean algorithms. These midline doses were compared with the treatment planning system target doses for lateral or AP (PA) portals and paired opposed portals. For head and neck treatments, all 3 algorithms were satisfactory, although the geometric mean algorithm was less accurate and more uncertain. For pelvis treatments, the arithmetic mean algorithm seemed unacceptable, whereas the other algorithms were satisfactory. The random error was reduced by using averaged midline doses of paired opposed portals because the asymmetric effect was averaged out. Considering the simplicity of in vivo dosimetry, the arithmetic mean and geometric mean algorithm should be adopted for head/neck and pelvis treatments, respectively.

  6. Nanocarriers for delivery of platinum anticancer drugs☆

    PubMed Central

    Oberoi, Hardeep S.; Nukolova, Natalia V.; Kabanov, Alexander V.; Bronich, Tatiana K.

    2014-01-01

    Platinum based anticancer drugs have revolutionized cancer chemotherapy, and continue to be in widespread clinical use especially for management of tumors of the ovary, testes, and the head and neck. However, several dose limiting toxicities associated with platinum drug use, partial anti-tumor response in most patients, development of drug resistance, tumor relapse, and many other challenges have severely limited the patient quality of life. These limitations have motivated an extensive research effort towards development of new strategies for improving platinum therapy. Nanocarrier-based delivery of platinum compounds is one such area of intense research effort beginning to provide encouraging preclinical and clinical results and may allow the development of the next generation of platinum chemotherapy. This review highlights current understanding on the pharmacology and limitations of platinum compounds in clinical use, and provides a comprehensive analysis of various platinum–polymer complexes, micelles, dendrimers, liposomes and other nanoparticles currently under investigation for delivery of platinum drugs. PMID:24113520

  7. A highly accurate interatomic potential for argon

    NASA Astrophysics Data System (ADS)

    Aziz, Ronald A.

    1993-09-01

    A modified potential based on the individually damped model of Douketis, Scoles, Marchetti, Zen, and Thakkar [J. Chem. Phys. 76, 3057 (1982)] is presented which fits, within experimental error, the accurate ultraviolet (UV) vibration-rotation spectrum of argon determined by UV laser absorption spectroscopy by Herman, LaRocque, and Stoicheff [J. Chem. Phys. 89, 4535 (1988)]. Other literature potentials fail to do so. The potential also is shown to predict a large number of other properties and is probably the most accurate characterization of the argon interaction constructed to date.

  8. Controlled Delivery of Zoledronate Improved Bone Formation Locally In Vivo

    PubMed Central

    Peng, Jiang; Lu, Qiang; Wang, Yu; Wang, Aiyuan; Guo, Quanyi; Gao, Xupeng; Xu, Wenjing; Lu, Shibi

    2014-01-01

    Bisphosphonates (BPs) have been widely used in clinical treatment of bone diseases with increased bone resorption because of their strong affinity for bone and their inhibition of bone resorption. Recently, there has been growing interest in their improvement of bone formation. However, the effect of local controlled delivery of BPs is unclear. We used polylactide acid-glycolic acid copolymer (PLGA) as a drug carrier to deliver various doses of the bisphosphonate zoledronate (Zol) into the distal femur of 8-week-old Sprague-Dawley rats. After 6 weeks, samples were harvested and analyzed by micro-CT and histology. The average bone mineral density and mineralized bone volume fraction were higher with medium- and high-dose PLGA-Zol (30 and 300 µg Zol, respectively) than control and low-dose Zol (3 µg PLGA-Zol; p<0.05). Local controlled delivery of Zol decreased the numbers of osteoclast and increased the numbers of osteoblast. Moreover, local controlled delivery of medium- and high-dose Zol accelerated the expression of bone-formation markers. PLGA used as a drug carrier for controlled delivery of Zol may promote local bone formation. PMID:24618585

  9. Pharmacokinetics of Prophylactic Cefazolin in Parturients Undergoing Cesarean Delivery

    PubMed Central

    Elkomy, Mohammed H.; Sultan, Pervez; Epshtein, Ekaterina; Galinkin, Jeffery L.; Carvalho, Brendan

    2014-01-01

    The objectives of this work were (i) to characterize the pharmacokinetics of cefazolin in pregnant women undergoing elective cesarean delivery and in their neonates; (ii) to assess cefazolin transplacental transmission; (iii) to evaluate the dosing and timing of preoperative, prophylactic administration of cefazolin to pregnant women; and (iv) to investigate the impact of maternal dosing on therapeutic duration and exposure in newborns. Twenty women received 1 g of cefazolin preoperatively. Plasma concentrations of total cefazolin were analyzed from maternal blood samples taken before, during, and after delivery; umbilical cord blood samples obtained at delivery; and neonatal blood samples collected 24 h after birth. The distribution volume of cefazolin was 9.44 liters/h. The values for pre- and postdelivery clearance were 7.18 and 4.12 liters/h, respectively. Computer simulations revealed that the probability of maintaining free cefazolin concentrations in plasma above 8 mg/liter during scheduled caesarean surgery was <50% in the cord blood when cefazolin was administered in doses of <2 g or when it was administered <1 h before delivery. Therapeutic concentrations of cefazolin persisted in neonates >5 h after birth. Cefazolin clearance increases during pregnancy, and larger doses are recommended for surgical prophylaxis in pregnant women to obtain the same antibacterial effect as in nonpregnant patients. Cefazolin has a longer half-life in neonates than in adults. Maternal administration of up to 2 g of cefazolin is effective and produces exposure within clinically approved limits in neonates. PMID:24733461

  10. Validation of a method for in vivo 3D dose reconstruction for IMRT and VMAT treatments using on-treatment EPID images and a model-based forward-calculation algorithm

    SciTech Connect

    Van Uytven, Eric Van Beek, Timothy; McCowan, Peter M.; Chytyk-Praznik, Krista; Greer, Peter B.; McCurdy, Boyd M. C.

    2015-12-15

    Purpose: Radiation treatments are trending toward delivering higher doses per fraction under stereotactic radiosurgery and hypofractionated treatment regimens. There is a need for accurate 3D in vivo patient dose verification using electronic portal imaging device (EPID) measurements. This work presents a model-based technique to compute full three-dimensional patient dose reconstructed from on-treatment EPID portal images (i.e., transmission images). Methods: EPID dose is converted to incident fluence entering the patient using a series of steps which include converting measured EPID dose to fluence at the detector plane and then back-projecting the primary source component of the EPID fluence upstream of the patient. Incident fluence is then recombined with predicted extra-focal fluence and used to calculate 3D patient dose via a collapsed-cone convolution method. This method is implemented in an iterative manner, although in practice it provides accurate results in a single iteration. The robustness of the dose reconstruction technique is demonstrated with several simple slab phantom and nine anthropomorphic phantom cases. Prostate, head and neck, and lung treatments are all included as well as a range of delivery techniques including VMAT and dynamic intensity modulated radiation therapy (IMRT). Results: Results indicate that the patient dose reconstruction algorithm compares well with treatment planning system computed doses for controlled test situations. For simple phantom and square field tests, agreement was excellent with a 2%/2 mm 3D chi pass rate ≥98.9%. On anthropomorphic phantoms, the 2%/2 mm 3D chi pass rates ranged from 79.9% to 99.9% in the planning target volume (PTV) region and 96.5% to 100% in the low dose region (>20% of prescription, excluding PTV and skin build-up region). Conclusions: An algorithm to reconstruct delivered patient 3D doses from EPID exit dosimetry measurements was presented. The method was applied to phantom and patient

  11. Fast and accurate sensitivity analysis of IMPT treatment plans using Polynomial Chaos Expansion

    NASA Astrophysics Data System (ADS)

    Perkó, Zoltán; van der Voort, Sebastian R.; van de Water, Steven; Hartman, Charlotte M. H.; Hoogeman, Mischa; Lathouwers, Danny

    2016-06-01

    The highly conformal planned dose distribution achievable in intensity modulated proton therapy (IMPT) can severely be compromised by uncertainties in patient setup and proton range. While several robust optimization approaches have been presented to address this issue, appropriate methods to accurately estimate the robustness of treatment plans are still lacking. To fill this gap we present Polynomial Chaos Expansion (PCE) techniques which are easily applicable and create a meta-model of the dose engine by approximating the dose in every voxel with multidimensional polynomials. This Polynomial Chaos (PC) model can be built in an automated fashion relatively cheaply and subsequently it can be used to perform comprehensive robustness analysis. We adapted PC to provide among others the expected dose, the dose variance, accurate probability distribution of dose-volume histogram (DVH) metrics (e.g. minimum tumor or maximum organ dose), exact bandwidths of DVHs, and to separate the effects of random and systematic errors. We present the outcome of our verification experiments based on 6 head-and-neck (HN) patients, and exemplify the usefulness of PCE by comparing a robust and a non-robust treatment plan for a selected HN case. The results suggest that PCE is highly valuable for both research and clinical applications.

  12. Fast and accurate sensitivity analysis of IMPT treatment plans using Polynomial Chaos Expansion.

    PubMed

    Perkó, Zoltán; van der Voort, Sebastian R; van de Water, Steven; Hartman, Charlotte M H; Hoogeman, Mischa; Lathouwers, Danny

    2016-06-21

    The highly conformal planned dose distribution achievable in intensity modulated proton therapy (IMPT) can severely be compromised by uncertainties in patient setup and proton range. While several robust optimization approaches have been presented to address this issue, appropriate methods to accurately estimate the robustness of treatment plans are still lacking. To fill this gap we present Polynomial Chaos Expansion (PCE) techniques which are easily applicable and create a meta-model of the dose engine by approximating the dose in every voxel with multidimensional polynomials. This Polynomial Chaos (PC) model can be built in an automated fashion relatively cheaply and subsequently it can be used to perform comprehensive robustness analysis. We adapted PC to provide among others the expected dose, the dose variance, accurate probability distribution of dose-volume histogram (DVH) metrics (e.g. minimum tumor or maximum organ dose), exact bandwidths of DVHs, and to separate the effects of random and systematic errors. We present the outcome of our verification experiments based on 6 head-and-neck (HN) patients, and exemplify the usefulness of PCE by comparing a robust and a non-robust treatment plan for a selected HN case. The results suggest that PCE is highly valuable for both research and clinical applications. PMID:27227661

  13. Systems and Components Fuel Delivery System, Water Delivery System, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Systems and Components - Fuel Delivery System, Water Delivery System, Derrick Crane System, and Crane System Details - Marshall Space Flight Center, F-1 Engine Static Test Stand, On Route 565 between Huntsville and Decatur, Huntsville, Madison County, AL

  14. Accurate pointing of tungsten welding electrodes

    NASA Technical Reports Server (NTRS)

    Ziegelmeier, P.

    1971-01-01

    Thoriated-tungsten is pointed accurately and quickly by using sodium nitrite. Point produced is smooth and no effort is necessary to hold the tungsten rod concentric. The chemically produced point can be used several times longer than ground points. This method reduces time and cost of preparing tungsten electrodes.

  15. Advances in the applications of polyhydroxyalkanoate nanoparticles for novel drug delivery system.

    PubMed

    Shrivastav, Anupama; Kim, Hae-Yeong; Kim, Young-Rok

    2013-01-01

    Drug delivery technology is emerging as an interdisciplinary science aimed at improving human health. The controlled delivery of pharmacologically active agents to the specific site of action at the therapeutically optimal rate and dose regimen has been a major goal in designing drug delivery systems. Over the past few decades, there has been considerable interest in developing biodegradable drug carriers as effective drug delivery systems. Polymeric materials from natural sources play an important role in controlled release of drug at a particular site. Polyhydroxyalkanoates, due to their origin from natural sources, are given attention as candidates for drug delivery materials. Biodegradable and biocompatible polyhydroxyalkanoates are linear polyesters produced by microorganisms under unbalanced growth conditions, which have emerged as potential polymers for use as biomedical materials for drug delivery due to their unique physiochemical and mechanical properties. This review summarizes many of the key findings in the applications of polyhydroxyalkanoates and polyhydroxyalkanoate nanoparticles for drug delivery system. PMID:23984383

  16. Advances in the Applications of Polyhydroxyalkanoate Nanoparticles for Novel Drug Delivery System

    PubMed Central

    Shrivastav, Anupama; Kim, Hae-Yeong; Kim, Young-Rok

    2013-01-01

    Drug delivery technology is emerging as an interdisciplinary science aimed at improving human health. The controlled delivery of pharmacologically active agents to the specific site of action at the therapeutically optimal rate and dose regimen has been a major goal in designing drug delivery systems. Over the past few decades, there has been considerable interest in developing biodegradable drug carriers as effective drug delivery systems. Polymeric materials from natural sources play an important role in controlled release of drug at a particular site. Polyhydroxyalkanoates, due to their origin from natural sources, are given attention as candidates for drug delivery materials. Biodegradable and biocompatible polyhydroxyalkanoates are linear polyesters produced by microorganisms under unbalanced growth conditions, which have emerged as potential polymers for use as biomedical materials for drug delivery due to their unique physiochemical and mechanical properties. This review summarizes many of the key findings in the applications of polyhydroxyalkanoates and polyhydroxyalkanoate nanoparticles for drug delivery system. PMID:23984383

  17. Optimization, delivery and evaluation of intensity modulated arc therapy

    NASA Astrophysics Data System (ADS)

    Oliver, Michael R.

    Intensity modulated arc therapy (IMAT) is a radiation therapy technique whereby the shape of the cone beam of radiation changes as it rotates around the patient. This is in contrast to other more commonly delivered forms of advanced radiation therapy, Intensity Modulated Radiation Therapy (IMRT) or helical tomotherapy. IMRT is a radiation technique where a patient is treated with a cone beam of radiation from a number of fixed beam directions, where the shapes and weights of the radiation beams are varied and tomotherapy is treated with a fan beam of radiation that follows a helical trajectory. In this thesis two aspects of IMAT were investigated: optimization of treatment plans and delivery of plans in conjunction with and without respiratory motion management. Optimization of IMAT deliveries consisted of two studies. In the first study, an algorithm that uses dosimetric ray tracing to set multi-leaf collimator (MLC) positions then directly optimizes the MLC positions to create IMAT treatment plans with only beam shape variations was developed and tested in three phantom studies and a clinical case. The second study investigated variable angular dose rate deliveries to a concave target and assessed the optimization strategy including arc initialization strategy, angular sampling and delivery efficiency. IMAT delivery with and without respiratory gated radiation delivery was studied with dose measurement using radiographic film in a motion phantom. In addition, simulations based on delivered log files were used to confirm that motion management for IMAT is effective and within dosimetric tolerances. As a pilot test, plans from IMRT and tomotherapy for partial breast irradiation were first studied, comparing them to conventional treatments. An IMAT plan was generated for one patient, demonstrating feasibility and was compared with IMRT and tomotherapy. This thesis has introduced a new IMAT optimization algorithm with and without variable angular dose rate, applied

  18. Vaccinia virus as a vaccine delivery system for marsupial wildlife.

    PubMed

    Cross, Martin L; Fleming, Stephen B; Cowan, Phil E; Scobie, Susie; Whelan, Ellena; Prada, Diana; Mercer, Andrew A; Duckworth, Janine A

    2011-06-20

    Vaccines based on recombinant poxviruses have proved successful in controlling diseases such as rabies and plague in wild eutherian mammals. They have also been trialled experimentally as delivery agents for fertility-control vaccines in rodents and foxes. In some countries, marsupial mammals represent a wildlife disease reservoir or a threat to conservation values but, as yet there has been no bespoke study of efficacy or immunogenicity of a poxvirus-based vaccine delivery system in a marsupial. Here, we report a study of the potential for vaccination using vaccinia virus in the Australian brushtail possum Trichosurus vulpecula, an introduced pest species in New Zealand. Parent-strain vaccinia virus (Lister) infected 8/8 possums following delivery of virus to the oral cavity and outer nares surfaces (oronasal immunisation), and persisted in the mucosal epithelium around the palatine tonsils for up to 2 weeks post-exposure. A recombinant vaccinia virus construct (VV399, which expresses the Eg95 antigen of the hydatid disease parasite Echinococcus granulosus) was shown to infect 10/15 possums after a single-dose oronasal delivery and to also persist. Both parent vaccinia virus and the VV399 construct virus induced peripheral blood lymphocyte reactivity against viral antigens in possums, first apparent at 4 weeks post-exposure and still detectable at 4 months post-exposure. Serum antibody reactivity to Eg95 was recorded in 7/8 possums which received a single dose of the VV399 construct and 7/7 animals which received triple-dose delivery, with titre end-points in the latter case exceeding 1/4000 dilution. This study demonstrates that vaccinia virus will readily infect possums via a delivery means used to deploy wildlife vaccines, and in doing is capable of generating immune reactivity against viral and heterologous antigens. This highlights the future potential of recombinant vaccinia virus as a vaccine delivery system in marsupial wildlife. PMID:21570435

  19. Microencapsulation: A promising technique for controlled drug delivery

    PubMed Central

    Singh, M.N.; Hemant, K.S.Y.; Ram, M.; Shivakumar, H.G.

    2010-01-01

    Microparticles offer various significant advantages as drug delivery systems, including: (i) an effective protection of the encapsulated active agent against (e.g. enzymatic) degradation, (ii) the possibility to accurately control the release rate of the incorporated drug over periods of hours to months, (iii) an easy administration (compared to alternative parenteral controlled release dosage forms, such as macro-sized implants), and (iv) Desired, pre-programmed drug release profiles can be provided which match the therapeutic needs of the patient. This article gives an overview on the general aspects and recent advances in drug-loaded microparticles to improve the efficiency of various medical treatments. An appropriately designed controlled release drug delivery system can be a foot ahead towards solving problems concerning to the targeting of drug to a specific organ or tissue, and controlling the rate of drug delivery to the target site. The development of oral controlled release systems has been a challenge to formulation scientist due to their inability to restrain and localize the system at targeted areas of gastrointestinal tract. Microparticulate drug delivery systems are an interesting and promising option when developing an oral controlled release system. The objective of this paper is to take a closer look at microparticles as drug delivery devices for increasing efficiency of drug delivery, improving the release profile and drug targeting. In order to appreciate the application possibilities of microcapsules in drug delivery, some fundamental aspects are briefly reviewed. PMID:21589795

  20. Targeted Delivery Systems for Molecular Therapy in Skeletal Disorders

    PubMed Central

    Dang, Lei; Liu, Jin; Li, Fangfei; Wang, Luyao; Li, Defang; Guo, Baosheng; He, Xiaojuan; Jiang, Feng; Liang, Chao; Liu, Biao; Badshah, Shaikh Atik; He, Bing; Lu, Jun; Lu, Cheng; Lu, Aiping; Zhang, Ge

    2016-01-01

    Abnormalities in the integral components of bone, including bone matrix, bone mineral and bone cells, give rise to complex disturbances of skeletal development, growth and homeostasis. Non-specific drug delivery using high-dose systemic administration may decrease therapeutic efficacy of drugs and increase the risk of toxic effects in non-skeletal tissues, which remain clinical challenges in the treatment of skeletal disorders. Thus, targeted delivery systems are urgently needed to achieve higher drug delivery efficiency, improve therapeutic efficacy in the targeted cells/tissues, and minimize toxicities in non-targeted cells/tissues. In this review, we summarize recent progress in the application of different targeting moieties and nanoparticles for targeted drug delivery in skeletal disorders, and also discuss the advantages, challenges and perspectives in their clinical translation. PMID:27011176

  1. Evaluation of absorbed dose in Gadolinium neutron capture therapy

    NASA Astrophysics Data System (ADS)

    Abdullaeva, Gayane; Djuraeva, Gulnara; Kim, Andrey; Koblik, Yuriy; Kulabdullaev, Gairatulla; Rakhmonov, Turdimukhammad; Saytjanov, Shavkat

    2015-02-01

    Gadolinium neutron capture therapy (GdNCT) is used for treatment of radioresistant malignant tumors. The absorbed dose in GdNCT can be divided into four primary dose components: thermal neutron, fast neutron, photon and natural gadolinium doses. The most significant is the dose created by natural gadolinium. The amount of gadolinium at the irradiated region is changeable and depends on the gadolinium delivery agent and on the structure of the location where the agent is injected. To de- fine the time dependence of the gadolinium concentration ρ(t) in the irradiated region the pharmacokinetics of gadolinium delivery agent (Magnevist) was studied at intratumoral injection in mice and intramuscular injection in rats. A polynomial approximation was applied to the experimental data and the influence of ρ(t) on the relative change of the absorbed dose of gadolinium was studied.

  2. Dose characterization in the near-source region for two high dose rate brachytherapy sources.

    PubMed

    Wang, Ruqing; Li, X Allen

    2002-08-01

    High dose rate (HDR) 192Ir sources are currently used in intravascular brachytherapy (IVB) for the peripheral arterial system. This poses a demand on evaluating accurate dose parameters in the near-source region for such sources. The purpose of this work is to calculate the dose parameters for the old VariSource HDR 192Ir source and the new microSelectron HDR 192Ir source, using Monte Carlo electron and photon transport simulation. The two-dimensional (2D) dose rate distributions and the air kerma strengths for the two HDR sources were calculated by EGSnrc and EGS4 Monte Carlo codes. Based on these data, the dose parameters proposed in the AAPM TG-60 protocol were derived. The dose rate constants obtained are 13.119+/-0.028 cGy h(-1) U(-1) for the old VariSource source, and 22.751+/-0.031 cGy h(-1) U(-1) for the new microSelectron source at the reference point (r0 = 2 mm, theta = pi/2). The 2D dose rate distributions, the radial dose functions, and the anisotropy functions presented for the two sources cover radial distances ranging from 0.5 to 10 mm. In the near-source region on the transverse plane, the dose effects of the charged particle nonequilibrium and the beta-particle dose contribution were studied. It is found that at radial distances ranging from 0.5 to 2 mm, these effects increase the calculated dose rates by up to 29% for the old VariSource source, and by up to 12% for the new microSelectron source, which, in turn, change values of the radial dose function and the anisotropy function. The present dose parameters, which account for the charged particle nonequilibrium and the beta particle contribution, may be used for accurate IVB dose calculation. PMID:12201413

  3. Vaccine delivery using nanoparticles

    PubMed Central

    Gregory, Anthony E.; Titball, Richard; Williamson, Diane

    2013-01-01

    Vaccination has had a major impact on the control of infectious diseases. However, there are still many infectious diseases for which the development of an effective vaccine has been elusive. In many cases the failure to devise vaccines is a consequence of the inability of vaccine candidates to evoke appropriate immune responses. This is especially true where cellular immunity is required for protective immunity and this problem is compounded by the move toward devising sub-unit vaccines. Over the past decade nanoscale size (<1000 nm) materials such as virus-like particles, liposomes, ISCOMs, polymeric, and non-degradable nanospheres have received attention as potential delivery vehicles for vaccine antigens which can both stabilize vaccine antigens and act as adjuvants. Importantly, some of these nanoparticles (NPs) are able to enter antigen-presenting cells by different pathways, thereby modulating the immune response to the antigen. This may be critical for the induction of protective Th1-type immune responses to intracellular pathogens. Their properties also make them suitable for the delivery of antigens at mucosal surfaces and for intradermal administration. In this review we compare the utilities of different NP systems for the delivery of sub-unit vaccines and evaluate the potential of these delivery systems for the development of new vaccines against a range of pathogens. PMID:23532930

  4. Technological Delivery Systems.

    ERIC Educational Resources Information Center

    Kennedy, Don; And Others

    A section on technological delivery systems, presented as part of the second Australian National Workshop on Distance Education (Perth, 1983), contains four papers on using technological resources to provide educational services to persons in isolated locations. The first paper, by Don Kennedy, covers the use of satellite broadcasting of course…

  5. Fluid delivery control system

    SciTech Connect

    Hoff, Brian D.; Johnson, Kris William; Algrain, Marcelo C.; Akasam, Sivaprasad

    2006-06-06

    A method of controlling the delivery of fluid to an engine includes receiving a fuel flow rate signal. An electric pump is arranged to deliver fluid to the engine. The speed of the electric pump is controlled based on the fuel flow rate signal.

  6. Document Delivery Update.

    ERIC Educational Resources Information Center

    Nelson, Nancy Melin

    1992-01-01

    Presents highlights of research that used industrywide surveys, focus groups, personal interviews, and industry-published data to explore the future of electronic information delivery in libraries. Topics discussed include CD-ROMs; prices; full-text products; magnetic tape leasing; engineering and technical literature; connections between online…

  7. Chitosan Microspheres in Novel Drug Delivery Systems

    PubMed Central

    Mitra, Analava; Dey, Baishakhi

    2011-01-01

    The main aim in the drug therapy of any disease is to attain the desired therapeutic concentration of the drug in plasma or at the site of action and maintain it for the entire duration of treatment. A drug on being used in conventional dosage forms leads to unavoidable fluctuations in the drug concentration leading to under medication or overmedication and increased frequency of dose administration as well as poor patient compliance. To minimize drug degradation and loss, to prevent harmful side effects and to increase drug bioavailability various drug delivery and drug targeting systems are currently under development. Handling the treatment of severe disease conditions has necessitated the development of innovative ideas to modify drug delivery techniques. Drug targeting means delivery of the drug-loaded system to the site of interest. Drug carrier systems include polymers, micelles, microcapsules, liposomes and lipoproteins to name some. Different polymer carriers exert different effects on drug delivery. Synthetic polymers are usually non-biocompatible, non-biodegradable and expensive. Natural polymers such as chitin and chitosan are devoid of such problems. Chitosan comes from the deacetylation of chitin, a natural biopolymer originating from crustacean shells. Chitosan is a biocompatible, biodegradable, and nontoxic natural polymer with excellent film-forming ability. Being of cationic character, chitosan is able to react with polyanions giving rise to polyelectrolyte complexes. Hence chitosan has become a promising natural polymer for the preparation of microspheres/nanospheres and microcapsules. The techniques employed to microencapsulate with chitosan include ionotropic gelation, spray drying, emulsion phase separation, simple and complex coacervation. This review focuses on the preparation, characterization of chitosan microspheres and their role in novel drug delivery systems. PMID:22707817

  8. MO-G-BRE-01: A Real-Time Virtual Delivery System for Photon Radiotherapy Delivery Monitoring

    SciTech Connect

    Shi, F; Gu, X; Jiang, S; Jia, X; Graves, Y

    2014-06-15

    Purpose: Treatment delivery monitoring is important for radiotherapy, which enables catching dosimetric error at the earliest possible opportunity. This project develops a virtual delivery system to monitor the dose delivery process of photon radiotherapy in real-time using GPU-based Monte Carlo (MC) method. Methods: The simulation process consists of 3 parallel CPU threads. A thread T1 is responsible for communication with a linac, which acquires a set of linac status parameters, e.g. gantry angles, MLC configurations, and beam MUs every 20 ms. Since linac vendors currently do not offer interface to acquire data in real time, we mimic this process by fetching information from a linac dynalog file at the set frequency. Instantaneous beam fluence map (FM) is calculated. A FM buffer is also created in T1 and the instantaneous FM is accumulated to it. This process continues, until a ready signal is received from thread T2 on which an inhouse developed MC dose engine executes on GPU. At that moment, the accumulated FM is transferred to T2 for dose calculations, and the FM buffer in T1 is cleared. Once the calculation finishes, the resulting 3D dose distribution is directed to thread T3, which displays it in three orthogonal planes overlaid on the CT image for treatment monitoring. This process continues to monitor the 3D dose distribution in real-time. Results: An IMRT and a VMAT cases used in our patient-specific QA are studied. Maximum dose differences between our system and treatment planning system are 0.98% and 1.58% for the two cases, respectively. The average time per MC calculation is 0.1sec with <2% relative uncertainty. The update frequency of ∼10Hz is considered as real time. Conclusion: By embedding a GPU-based MC code in a novel data/work flow, it is possible to achieve real-time MC dose calculations to monitor delivery process.

  9. Comparison of Elekta VMAT with helical tomotherapy and fixed field IMRT: Plan quality, delivery efficiency and accuracy

    SciTech Connect

    Rao Min; Yang Wensha; Chen Fan; Sheng Ke; Ye Jinsong; Mehta, Vivek; Shepard, David; Cao Daliang

    2010-03-15

    Purpose: Helical tomotherapy (HT) and volumetric modulated arc therapy (VMAT) are arc-based approaches to IMRT delivery. The objective of this study is to compare VMAT to both HT and fixed field IMRT in terms of plan quality, delivery efficiency, and accuracy. Methods: Eighteen cases including six prostate, six head-and-neck, and six lung cases were selected for this study. IMRT plans were developed using direct machine parameter optimization in the Pinnacle{sup 3} treatment planning system. HT plans were developed using a Hi-Art II planning station. VMAT plans were generated using both the Pinnacle{sup 3} SmartArc IMRT module and a home-grown arc sequencing algorithm. VMAT and HT plans were delivered using Elekta's PreciseBeam VMAT linac control system (Elekta AB, Stockholm, Sweden) and a TomoTherapy Hi-Art II system (TomoTherapy Inc., Madison, WI), respectively. Treatment plan quality assurance (QA) for VMAT was performed using the IBA MatriXX system while an ion chamber and films were used for HT plan QA. Results: The results demonstrate that both VMAT and HT are capable of providing more uniform target doses and improved normal tissue sparing as compared with fixed field IMRT. In terms of delivery efficiency, VMAT plan deliveries on average took 2.2 min for prostate and lung cases and 4.6 min for head-and-neck cases. These values increased to 4.7 and 7.0 min for HT plans. Conclusions: Both VMAT and HT plans can be delivered accurately based on their own QA standards. Overall, VMAT was able to provide approximately a 40% reduction in treatment time while maintaining comparable plan quality to that of HT.

  10. The consequence of day-to-day stochastic dose deviation from the planned dose in fractionated radiation therapy.

    PubMed

    Paul, Subhadip; Roy, Prasun Kumar

    2016-02-01

    Radiation therapy is one of the important treatment procedures of cancer. The day-to-day delivered dose to the tissue in radiation therapy often deviates from the planned fixed dose per fraction. This day-to-day variation of radiation dose is stochastic. Here, we have developed the mathematical formulation to represent the day-to-day stochastic dose variation effect in radiation therapy. Our analysis shows that that the fixed dose delivery approximation under-estimates the biological effective dose, even if the average delivered dose per fraction is equal to the planned dose per fraction. The magnitude of the under-estimation effect relies upon the day-to-day stochastic dose variation level, the dose fraction size and the values of the radiobiological parameters of the tissue. We have further explored the application of our mathematical formulation for adaptive dose calculation. Our analysis implies that, compared to the premise of the Linear Quadratic Linear (LQL) framework, the Linear Quadratic framework based analytical formulation under-estimates the required dose per fraction necessary to produce the same biological effective dose as originally planned. Our study provides analytical formulation to calculate iso-effect in adaptive radiation therapy considering day-to-day stochastic dose deviation from planned dose and also indicates the potential utility of LQL framework in this context. PMID:26776265

  11. Nanotopography applications in drug delivery.

    PubMed

    Walsh, Laura A; Allen, Jessica L; Desai, Tejal A

    2015-01-01

    Refinement of micro- and nanofabrication in the semiconductor field has led to innovations in biomedical technologies. Nanotopography, in particular, shows great potential in facilitating drug delivery. The flexibility of fabrication techniques has created a diverse array of topographies that have been developed for drug delivery applications. Nanowires and nanostraws deliver drug cytosolically for in vitro and ex vivo applications. In vivo drug delivery is limited by the barrier function of the epithelium. Nanowires on microspheres increase adhesion and residence time for oral drug delivery, while also increasing permeability of the epithelium. Low aspect ratio nanocolumns increase paracellular permeability, and in conjunction with microneedles increase transdermal drug delivery of biologics in vivo. In summary, nanotopography is a versatile tool for drug delivery. It can deliver directly to cells or be used for in vivo delivery across epithelial barriers. This editorial highlights the application of nanotopography in the field of drug delivery. PMID:26512871

  12. Pulmonary drug delivery. Part II: The role of inhalant delivery devices and drug formulations in therapeutic effectiveness of aerosolized medications

    PubMed Central

    Labiris, N R; Dolovich, M B

    2003-01-01

    Research in the area of pulmonary drug delivery has gathered momentum in the last several years, with increased interest in using the lung as a means of delivering drugs systemically. Advances in device technology have led to the development of more efficient delivery systems capable of delivering larger doses and finer particles into the lung. As more efficient pulmonary delivery devices and sophisticated formulations become available, physicians and health professionals will have a choice of a wide variety of device and formulation combinations that will target specific cells or regions of the lung, avoid the lung's clearance mechanisms and be retained within the lung for longer periods. It is now recognized that it is not enough just to have inhalation therapy available for prescribing; physicians and other healthcare providers need a basic understanding of aerosol science, inhaled formulations, delivery devices, and bioequivalence of products to prescribe these therapies optimally. PMID:14616419

  13. Feedback about More Accurate versus Less Accurate Trials: Differential Effects on Self-Confidence and Activation

    ERIC Educational Resources Information Center

    Badami, Rokhsareh; VaezMousavi, Mohammad; Wulf, Gabriele; Namazizadeh, Mahdi

    2012-01-01

    One purpose of the present study was to examine whether self-confidence or anxiety would be differentially affected by feedback from more accurate rather than less accurate trials. The second purpose was to determine whether arousal variations (activation) would predict performance. On Day 1, participants performed a golf putting task under one of…

  14. Feedback about more accurate versus less accurate trials: differential effects on self-confidence and activation.

    PubMed

    Badami, Rokhsareh; VaezMousavi, Mohammad; Wulf, Gabriele; Namazizadeh, Mahdi

    2012-06-01

    One purpose of the present study was to examine whether self-confidence or anxiety would be differentially affected byfeedback from more accurate rather than less accurate trials. The second purpose was to determine whether arousal variations (activation) would predict performance. On day 1, participants performed a golf putting task under one of two conditions: one group received feedback on the most accurate trials, whereas another group received feedback on the least accurate trials. On day 2, participants completed an anxiety questionnaire and performed a retention test. Shin conductance level, as a measure of arousal, was determined. The results indicated that feedback about more accurate trials resulted in more effective learning as well as increased self-confidence. Also, activation was a predictor of performance. PMID:22808705

  15. Polyelectrolyte Complex for Heparin Binding Domain Osteogenic Growth Factor Delivery.

    PubMed

    Wing Moon Lam, Raymond; Abbah, Sunny Akogwu; Ming, Wang; Naidu, Mathanapriya; Ng, Felly; Tao, Hu; Goh Cho Hong, James; Ting, Kang; Hee Kit, Wong

    2016-01-01

    During reconstructive bone surgeries, supraphysiological amounts of growth factors are empirically loaded onto scaffolds to promote successful bone fusion. Large doses of highly potent biological agents are required due to growth factor instability as a result of rapid enzymatic degradation as well as carrier inefficiencies in localizing sufficient amounts of growth factor at implant sites. Hence, strategies that prolong the stability of growth factors such as BMP-2/NELL-1, and control their release could actually lower their efficacious dose and thus reduce the need for larger doses during future bone regeneration surgeries. This in turn will reduce side effects and growth factor costs. Self-assembled PECs have been fabricated to provide better control of BMP-2/NELL-1 delivery via heparin binding and further potentiate growth factor bioactivity by enhancing in vivo stability. Here we illustrate the simplicity of PEC fabrication which aids in the delivery of a variety of growth factors during reconstructive bone surgeries. PMID:27585207

  16. Dose perturbations due to contrast medium and air in MammoSite registered treatment: An experimental and Monte Carlo study

    SciTech Connect

    Cheng, C.-W.; Mitra, R.; Allen Li, X.; Das, Indra J.

    2005-07-15

    . Monte Carlo simulation suggests that the interface effect (enhanced dose near surface) is primarily due to Compton electrons of short range (<0.5 mm). For more accurate dosimetry in MammoSite delivery, the dose perturbation due to the presence of a radio-opaque contrast medium and air bubbles should be considered in a brachytherapy planning system.

  17. PECTIN IN CONTROLLED DRUG DELIVERY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Controlled drug delivery remains a research focus for public health to enhance patient compliance, drug efficiency and to reduce the side effects of drugs. Pectin, an edible plant polysaccharide, has shown potential for the construction of drug delivery systems for site-specific drug delivery. Sev...

  18. Continuing Professional Education Delivery Systems.

    ERIC Educational Resources Information Center

    Weeks, James P.

    This investigation of delivery systems for continuing professional education provides an overview of current operational delivery systems in continuing professional education, drawing on experience as found in the literature. Learning theories and conclusions are woven into the descriptive text. Delivery systems profiled in the paper include the…

  19. Characterizing a proton beam scanning system for Monte Carlo dose calculation in patients

    NASA Astrophysics Data System (ADS)

    Grassberger, C.; Lomax, Anthony; Paganetti, H.

    2015-01-01

    The presented work has two goals. First, to demonstrate the feasibility of accurately characterizing a proton radiation field at treatment head exit for Monte Carlo dose calculation of active scanning patient treatments. Second, to show that this characterization can be done based on measured depth dose curves and spot size alone, without consideration of the exact treatment head delivery system. This is demonstrated through calibration of a Monte Carlo code to the specific beam lines of two institutions, Massachusetts General Hospital (MGH) and Paul Scherrer Institute (PSI). Comparison of simulations modeling the full treatment head at MGH to ones employing a parameterized phase space of protons at treatment head exit reveals the adequacy of the method for patient simulations. The secondary particle production in the treatment head is typically below 0.2% of primary fluence, except for low-energy electrons (<0.6 MeV for 230 MeV protons), whose contribution to skin dose is negligible. However, there is significant difference between the two methods in the low-dose penumbra, making full treatment head simulations necessary to study out-of-field effects such as secondary cancer induction. To calibrate the Monte Carlo code to measurements in a water phantom, we use an analytical Bragg peak model to extract the range-dependent energy spread at the two institutions, as this quantity is usually not available through measurements. Comparison of the measured with the simulated depth dose curves demonstrates agreement within 0.5 mm over the entire energy range. Subsequently, we simulate three patient treatments with varying anatomical complexity (liver, head and neck and lung) to give an example how this approach can be employed to investigate site-specific discrepancies between treatment planning system and Monte Carlo simulations.

  20. The retina dose-area histogram: a metric for quantitatively comparing rival eye plaque treatment options

    PubMed Central

    2013-01-01

    Purpose Episcleral plaques have a history of over a half century in the delivery of radiation therapy to intraocular tumors such as choroidal melanoma. Although the tumor control rate is high, vision-impairing complications subsequent to treatment remain an issue. Notable, late complications are radiation retinopathy and maculopathy. The obvious way to reduce the risk of radiation damage to the retina is to conform the prescribed isodose surface to the tumor base and to reduce the dose delivered to the surrounding healthy retina, especially the macula. Using a fusion of fundus photography, ultrasound and CT images, tumor size, shape and location within the eye can be accurately simulated as part of the radiation planning process. In this work an adaptation of the dose-volume histogram (DVH), the retina dose-area histogram (RDAH) is introduced as a metric to help compare rival plaque designs and conformal treatment planning options with the goal of reducing radiation retinopathy. Material and methods The RDAH is calculated by transforming a digitized fundus-photo collage of the tumor into a rasterized polar map of the retinal surface known as a retinal diagram (RD). The perimeter of the tumor base is digitized on the RD and its area computed. Area and radiation dose are calculated for every pixel in the RD. Results The areal resolution of the RDAH is a function of the pixel resolution of the raster image used to display the RD and the number of polygon edges used to digitize the perimeter of the tumor base. A practical demonstration is presented. Conclusions The RDAH provides a quantitative metric by which episcleral plaque treatment plan options may be evaluated and compared in order to confirm adequate dosimetric coverage of the tumor and margin, and to help minimize dose to the macula and retina. PMID:23634152

  1. Characterizing a proton beam scanning system for Monte Carlo dose calculation in patients.

    PubMed

    Grassberger, C; Lomax, Anthony; Paganetti, H

    2015-01-21

    The presented work has two goals. First, to demonstrate the feasibility of accurately characterizing a proton radiation field at treatment head exit for Monte Carlo dose calculation of active scanning patient treatments. Second, to show that this characterization can be done based on measured depth dose curves and spot size alone, without consideration of the exact treatment head delivery system. This is demonstrated through calibration of a Monte Carlo code to the specific beam lines of two institutions, Massachusetts General Hospital (MGH) and Paul Scherrer Institute (PSI). Comparison of simulations modeling the full treatment head at MGH to ones employing a parameterized phase space of protons at treatment head exit reveals the adequacy of the method for patient simulations. The secondary particle production in the treatment head is typically below 0.2% of primary fluence, except for low-energy electrons (<0.6 MeV for 230 MeV protons), whose contribution to skin dose is negligible. However, there is significant difference between the two methods in the low-dose penumbra, making full treatment head simulations necessary to study out-of-field effects such as secondary cancer induction. To calibrate the Monte Carlo code to measurements in a water phantom, we use an analytical Bragg peak model to extract the range-dependent energy spread at the two institutions, as this quantity is usually not available through measurements. Comparison of the measured with the simulated depth dose curves demonstrates agreement within 0.5 mm over the entire energy range. Subsequently, we simulate three patient treatments with varying anatomical complexity (liver, head and neck and lung) to give an example how this approach can be employed to investigate site-specific discrepancies between treatment planning system and Monte Carlo simulations. PMID:25549079

  2. Steroids: Pharmacology, Complications, and Practice Delivery Issues

    PubMed Central

    Ericson-Neilsen, William; Kaye, Alan David

    2014-01-01

    Background Since their identification nearly 80 years ago, steroids have played a prominent role in the treatment of many disease states. Many of the clinical roles of steroids are related to their potent antiinflammatory and immune-modulating properties. Methods This review summarizes the basic pharmacology, complications, and practice delivery issues regarding steroids. Results Clinically relevant side effects of steroids are common and problematic. Side effects can occur at a wide range of doses and vary depending on the route of administration. The full spectrum of side effects can be present even in patients taking low doses. Conclusions Practitioners must be aware that these drugs might exacerbate a preexisting condition or present a new medical condition. Knowledge of the clinical implications of prescribing these agents is critical. PMID:24940130

  3. New model accurately predicts reformate composition

    SciTech Connect

    Ancheyta-Juarez, J.; Aguilar-Rodriguez, E. )

    1994-01-31

    Although naphtha reforming is a well-known process, the evolution of catalyst formulation, as well as new trends in gasoline specifications, have led to rapid evolution of the process, including: reactor design, regeneration mode, and operating conditions. Mathematical modeling of the reforming process is an increasingly important tool. It is fundamental to the proper design of new reactors and revamp of existing ones. Modeling can be used to optimize operating conditions, analyze the effects of process variables, and enhance unit performance. Instituto Mexicano del Petroleo has developed a model of the catalytic reforming process that accurately predicts reformate composition at the higher-severity conditions at which new reformers are being designed. The new AA model is more accurate than previous proposals because it takes into account the effects of temperature and pressure on the rate constants of each chemical reaction.

  4. Accurate colorimetric feedback for RGB LED clusters

    NASA Astrophysics Data System (ADS)

    Man, Kwong; Ashdown, Ian

    2006-08-01

    We present an empirical model of LED emission spectra that is applicable to both InGaN and AlInGaP high-flux LEDs, and which accurately predicts their relative spectral power distributions over a wide range of LED junction temperatures. We further demonstrate with laboratory measurements that changes in LED spectral power distribution with temperature can be accurately predicted with first- or second-order equations. This provides the basis for a real-time colorimetric feedback system for RGB LED clusters that can maintain the chromaticity of white light at constant intensity to within +/-0.003 Δuv over a range of 45 degrees Celsius, and to within 0.01 Δuv when dimmed over an intensity range of 10:1.

  5. Accurate mask model for advanced nodes

    NASA Astrophysics Data System (ADS)

    Zine El Abidine, Nacer; Sundermann, Frank; Yesilada, Emek; Ndiaye, El Hadji Omar; Mishra, Kushlendra; Paninjath, Sankaranarayanan; Bork, Ingo; Buck, Peter; Toublan, Olivier; Schanen, Isabelle

    2014-07-01

    Standard OPC models consist of a physical optical model and an empirical resist model. The resist model compensates the optical model imprecision on top of modeling resist development. The optical model imprecision may result from mask topography effects and real mask information including mask ebeam writing and mask process contributions. For advanced technology nodes, significant progress has been made to model mask topography to improve optical model accuracy. However, mask information is difficult to decorrelate from standard OPC model. Our goal is to establish an accurate mask model through a dedicated calibration exercise. In this paper, we present a flow to calibrate an accurate mask enabling its implementation. The study covers the different effects that should be embedded in the mask model as well as the experiment required to model them.

  6. Accurate guitar tuning by cochlear implant musicians.

    PubMed

    Lu, Thomas; Huang, Juan; Zeng, Fan-Gang

    2014-01-01

    Modern cochlear implant (CI) users understand speech but find difficulty in music appreciation due to poor pitch perception. Still, some deaf musicians continue to perform with their CI. Here we show unexpected results that CI musicians can reliably tune a guitar by CI alone and, under controlled conditions, match simultaneously presented tones to <0.5 Hz. One subject had normal contralateral hearing and produced more accurate tuning with CI than his normal ear. To understand these counterintuitive findings, we presented tones sequentially and found that tuning error was larger at ∼ 30 Hz for both subjects. A third subject, a non-musician CI user with normal contralateral hearing, showed similar trends in performance between CI and normal hearing ears but with less precision. This difference, along with electric analysis, showed that accurate tuning was achieved by listening to beats rather than discriminating pitch, effectively turning a spectral task into a temporal discrimination task. PMID:24651081

  7. Two highly accurate methods for pitch calibration

    NASA Astrophysics Data System (ADS)

    Kniel, K.; Härtig, F.; Osawa, S.; Sato, O.

    2009-11-01

    Among profiles, helix and tooth thickness pitch is one of the most important parameters of an involute gear measurement evaluation. In principle, coordinate measuring machines (CMM) and CNC-controlled gear measuring machines as a variant of a CMM are suited for these kinds of gear measurements. Now the Japan National Institute of Advanced Industrial Science and Technology (NMIJ/AIST) and the German national metrology institute the Physikalisch-Technische Bundesanstalt (PTB) have each developed independently highly accurate pitch calibration methods applicable to CMM or gear measuring machines. Both calibration methods are based on the so-called closure technique which allows the separation of the systematic errors of the measurement device and the errors of the gear. For the verification of both calibration methods, NMIJ/AIST and PTB performed measurements on a specially designed pitch artifact. The comparison of the results shows that both methods can be used for highly accurate calibrations of pitch standards.

  8. Accurate modeling of parallel scientific computations

    NASA Technical Reports Server (NTRS)

    Nicol, David M.; Townsend, James C.

    1988-01-01

    Scientific codes are usually parallelized by partitioning a grid among processors. To achieve top performance it is necessary to partition the grid so as to balance workload and minimize communication/synchronization costs. This problem is particularly acute when the grid is irregular, changes over the course of the computation, and is not known until load time. Critical mapping and remapping decisions rest on the ability to accurately predict performance, given a description of a grid and its partition. This paper discusses one approach to this problem, and illustrates its use on a one-dimensional fluids code. The models constructed are shown to be accurate, and are used to find optimal remapping schedules.

  9. Accurate Guitar Tuning by Cochlear Implant Musicians

    PubMed Central

    Lu, Thomas; Huang, Juan; Zeng, Fan-Gang

    2014-01-01

    Modern cochlear implant (CI) users understand speech but find difficulty in music appreciation due to poor pitch perception. Still, some deaf musicians continue to perform with their CI. Here we show unexpected results that CI musicians can reliably tune a guitar by CI alone and, under controlled conditions, match simultaneously presented tones to <0.5 Hz. One subject had normal contralateral hearing and produced more accurate tuning with CI than his normal ear. To understand these counterintuitive findings, we presented tones sequentially and found that tuning error was larger at ∼30 Hz for both subjects. A third subject, a non-musician CI user with normal contralateral hearing, showed similar trends in performance between CI and normal hearing ears but with less precision. This difference, along with electric analysis, showed that accurate tuning was achieved by listening to beats rather than discriminating pitch, effectively turning a spectral task into a temporal discrimination task. PMID:24651081

  10. Nanosuspensions as advanced printing ink for accurate dosing of poorly soluble drugs in personalized medicines.

    PubMed

    Pardeike, Jana; Strohmeier, Daniela M; Schrödl, Nina; Voura, Christine; Gruber, Michael; Khinast, Johannes G; Zimmer, Andreas

    2011-11-25

    Folic acid was used as a model drug to demonstrate the advantages of formulating poorly soluble drugs as nanosuspensions and their use in an inkjet-type printing technique to produce personalized medicines. 10% folic acid nanosuspensions stabilized with Tween 20, a stabilizer showing the best wetting potential for folic acid, were prepared via high pressure homogenization. The particle size of the folic acid nanosuspension was well below 5 μm being a prerequisite for inkjet type printing technique. A good reproducibility of the particle size of folic acid nanosuspension prepared via high pressure homogenization was found. As indicated by the zeta potential the formulation showed a good storage stability. High pressure homogenization had no influence on the crystalline state of folic acid. An increase in the saturation solubility by 53.7% was found reducing the particle size from the micrometer range to the nanometer range. The dissolution velocity of the folic acid nanosuspension was significantly enhanced compared to a folic acid suspension, i.e. after 5 min 78.6% of the folic acid was dissolved from the nanosuspension and only 6.2% from the suspension. Moreover, the printing of 10% folic acid nanosuspension could be successfully demonstrated. PMID:21889582

  11. Protease-mediated drug delivery

    NASA Astrophysics Data System (ADS)

    Dickson, Eva F.; Goyan, Rebecca L.; Kennedy, James C.; Mackay, M.; Mendes, M. A. K.; Pottier, Roy H.

    2003-12-01

    Drugs used in disease treatment can cause damage to both malignant and normal tissue. This toxicity limits the maximum therapeutic dose. Drug targeting is of high interest to increase the therapeutic efficacy of the drug without increasing systemic toxicity. Certain tissue abnormalities, disease processes, cancers, and infections are characterized by high levels of activity of specific extracellular and/or intracellular proteases. Abnormally high activity levels of specific proteases are present at sites of physical or chemical trauma, blood clots, malignant tumors, rheumatoid arthritis, inflammatory bowel disease, gingival disease, glomerulonerphritis, and acute pancreatitis. Abnormal protease activity is suspected in development of liver thrombosis, pulmonary emphysema, atherosclerosis, and muscular dystrophy. Inactiviating disease-associated proteases by the administration of appropriate protease inhibitors has had limited success. Instead, one could use such proteases to target drugs to treat the condition. Protease mediated drug delivery offers such a possibility. Solubilizing groups are attached to insoluble drugs via a polypeptide chain which is specifically cleavable by certian proteases. When the solubilized drug enounters the protease, the solubilizing moieties are cleaved, and the drug precipitates at the disease location. Thus, a smaller systemic dosage could result in a therapeutic drug concentration at the treatment site with less systemic toxicity.

  12. An accurate registration technique for distorted images

    NASA Technical Reports Server (NTRS)

    Delapena, Michele; Shaw, Richard A.; Linde, Peter; Dravins, Dainis

    1990-01-01

    Accurate registration of International Ultraviolet Explorer (IUE) images is crucial because the variability of the geometrical distortions that are introduced by the SEC-Vidicon cameras ensures that raw science images are never perfectly aligned with the Intensity Transfer Functions (ITFs) (i.e., graded floodlamp exposures that are used to linearize and normalize the camera response). A technique for precisely registering IUE images which uses a cross correlation of the fixed pattern that exists in all raw IUE images is described.

  13. Accurate maser positions for MALT-45

    NASA Astrophysics Data System (ADS)

    Jordan, Christopher; Bains, Indra; Voronkov, Maxim; Lo, Nadia; Jones, Paul; Muller, Erik; Cunningham, Maria; Burton, Michael; Brooks, Kate; Green, James; Fuller, Gary; Barnes, Peter; Ellingsen, Simon; Urquhart, James; Morgan, Larry; Rowell, Gavin; Walsh, Andrew; Loenen, Edo; Baan, Willem; Hill, Tracey; Purcell, Cormac; Breen, Shari; Peretto, Nicolas; Jackson, James; Lowe, Vicki; Longmore, Steven

    2013-10-01

    MALT-45 is an untargeted survey, mapping the Galactic plane in CS (1-0), Class I methanol masers, SiO masers and thermal emission, and high frequency continuum emission. After obtaining images from the survey, a number of masers were detected, but without accurate positions. This project seeks to resolve each maser and its environment, with the ultimate goal of placing the Class I methanol maser into a timeline of high mass star formation.

  14. Effect of dosimeter type for commissioning small photon beams on calculated dose distribution in stereotactic radiosurgery

    SciTech Connect

    García-Garduño, O. A. E-mail: amanda.garcia.g@gmail.com; Rodríguez-Ponce, M.; Gamboa-deBuen, I.; Rodríguez-Villafuerte, M.; Galván de la Cruz, O. O.; and others

    2014-09-15

    . Finally, the dose volume histogram results were independent of the size of the calculation grid used. Conclusions: The results of this study showed that all of the studied detectors produced similar commissioned data sets for the TPS dose calculations. However, this result only validated the dose distribution calculation in the TPS and could not be used to assess the dose delivery to the target in which the TFS data were used to calculate the monitor units (the TFS data were not used in the TPS dose distribution calculation). Therefore, this study could not be used to determine the most accurate detector commissioning data set; however, all of the detectors exhibited superior performance for the relative dosimetry of small photon beams.

  15. Peptide and protein delivery using new drug delivery systems.

    PubMed

    Jain, Ashish; Jain, Aviral; Gulbake, Arvind; Shilpi, Satish; Hurkat, Pooja; Jain, Sanjay K

    2013-01-01

    Pharmaceutical and biotechnological research sorts protein drug delivery systems by importance based on their various therapeutic applications. The effective and potent action of the proteins/peptides makes them the drugs of choice for the treatment of numerous diseases. Major research issues in protein delivery include the stabilization of proteins in delivery devices and the design of appropriate target-specific protein carriers. Many efforts have been made for effective delivery of proteins/peptidal drugs through various routes of administrations for successful therapeutic effects. Nanoparticles made of biodegradable polymers such as poly lactic acid, polycaprolactone, poly(lactic-co-glycolic acid), the poly(fumaric-co-sebacic) anhydride chitosan, and modified chitosan, as well as solid lipids, have shown great potential in the delivery of proteins/peptidal drugs. Moreover, scientists also have used liposomes, PEGylated liposomes, niosomes, and aquasomes, among others, for peptidal drug delivery. They also have developed hydrogels and transdermal drug delivery systems for peptidal drug delivery. A receptor-mediated delivery system is another attractive strategy to overcome the limitation in drug absorption that enables the transcytosis of the protein across the epithelial barrier. Modification such as PEGnology is applied to various proteins and peptides of the desired protein and peptides also increases the circulating life, solubility and stability, pharmacokinetic properties, and antigenicity of protein. This review focuses on various approaches for effective protein/peptidal drug delivery, with special emphasis on insulin delivery. PMID:23662604

  16. Accurate phase-shift velocimetry in rock.

    PubMed

    Shukla, Matsyendra Nath; Vallatos, Antoine; Phoenix, Vernon R; Holmes, William M

    2016-06-01

    Spatially resolved Pulsed Field Gradient (PFG) velocimetry techniques can provide precious information concerning flow through opaque systems, including rocks. This velocimetry data is used to enhance flow models in a wide range of systems, from oil behaviour in reservoir rocks to contaminant transport in aquifers. Phase-shift velocimetry is the fastest way to produce velocity maps but critical issues have been reported when studying flow through rocks and porous media, leading to inaccurate results. Combining PFG measurements for flow through Bentheimer sandstone with simulations, we demonstrate that asymmetries in the molecular displacement distributions within each voxel are the main source of phase-shift velocimetry errors. We show that when flow-related average molecular displacements are negligible compared to self-diffusion ones, symmetric displacement distributions can be obtained while phase measurement noise is minimised. We elaborate a complete method for the production of accurate phase-shift velocimetry maps in rocks and low porosity media and demonstrate its validity for a range of flow rates. This development of accurate phase-shift velocimetry now enables more rapid and accurate velocity analysis, potentially helping to inform both industrial applications and theoretical models. PMID:27111139

  17. Accurate Molecular Polarizabilities Based on Continuum Electrostatics

    PubMed Central

    Truchon, Jean-François; Nicholls, Anthony; Iftimie, Radu I.; Roux, Benoît; Bayly, Christopher I.

    2013-01-01

    A novel approach for representing the intramolecular polarizability as a continuum dielectric is introduced to account for molecular electronic polarization. It is shown, using a finite-difference solution to the Poisson equation, that the Electronic Polarization from Internal Continuum (EPIC) model yields accurate gas-phase molecular polarizability tensors for a test set of 98 challenging molecules composed of heteroaromatics, alkanes and diatomics. The electronic polarization originates from a high intramolecular dielectric that produces polarizabilities consistent with B3LYP/aug-cc-pVTZ and experimental values when surrounded by vacuum dielectric. In contrast to other approaches to model electronic polarization, this simple model avoids the polarizability catastrophe and accurately calculates molecular anisotropy with the use of very few fitted parameters and without resorting to auxiliary sites or anisotropic atomic centers. On average, the unsigned error in the average polarizability and anisotropy compared to B3LYP are 2% and 5%, respectively. The correlation between the polarizability components from B3LYP and this approach lead to a R2 of 0.990 and a slope of 0.999. Even the F2 anisotropy, shown to be a difficult case for existing polarizability models, can be reproduced within 2% error. In addition to providing new parameters for a rapid method directly applicable to the calculation of polarizabilities, this work extends the widely used Poisson equation to areas where accurate molecular polarizabilities matter. PMID:23646034

  18. Accurate phase-shift velocimetry in rock

    NASA Astrophysics Data System (ADS)

    Shukla, Matsyendra Nath; Vallatos, Antoine; Phoenix, Vernon R.; Holmes, William M.

    2016-06-01

    Spatially resolved Pulsed Field Gradient (PFG) velocimetry techniques can provide precious information concerning flow through opaque systems, including rocks. This velocimetry data is used to enhance flow models in a wide range of systems, from oil behaviour in reservoir rocks to contaminant transport in aquifers. Phase-shift velocimetry is the fastest way to produce velocity maps but critical issues have been reported when studying flow through rocks and porous media, leading to inaccurate results. Combining PFG measurements for flow through Bentheimer sandstone with simulations, we demonstrate that asymmetries in the molecular displacement distributions within each voxel are the main source of phase-shift velocimetry errors. We show that when flow-related average molecular displacements are negligible compared to self-diffusion ones, symmetric displacement distributions can be obtained while phase measurement noise is minimised. We elaborate a complete method for the production of accurate phase-shift velocimetry maps in rocks and low porosity media and demonstrate its validity for a range of flow rates. This development of accurate phase-shift velocimetry now enables more rapid and accurate velocity analysis, potentially helping to inform both industrial applications and theoretical models.

  19. The KFM, A Homemade Yet Accurate and Dependable Fallout Meter

    SciTech Connect

    Kearny, C.H.

    2001-11-20

    The KFM is a homemade fallout meter that can be made using only materials, tools, and skills found in millions of American homes. It is an accurate and dependable electroscope-capacitor. The KFM, in conjunction with its attached table and a watch, is designed for use as a rate meter. Its attached table relates observed differences in the separations of its two leaves (before and after exposures at the listed time intervals) to the dose rates during exposures of these time intervals. In this manner dose rates from 30 mR/hr up to 43 R/hr can be determined with an accuracy of {+-}25%. A KFM can be charged with any one of the three expedient electrostatic charging devices described. Due to the use of anhydrite (made by heating gypsum from wallboard) inside a KFM and the expedient ''dry-bucket'' in which it can be charged when the air is very humid, this instrument always can be charged and used to obtain accurate measurements of gamma radiation no matter how high the relative humidity. The heart of this report is the step-by-step illustrated instructions for making and using a KFM. These instructions have been improved after each successive field test. The majority of the untrained test families, adequately motivated by cash bonuses offered for success and guided only by these written instructions, have succeeded in making and using a KFM. NOTE: ''The KFM, A Homemade Yet Accurate and Dependable Fallout Meter'', was published by Oak Ridge National Laboratory report in1979. Some of the materials originally suggested for suspending the leaves of the Kearny Fallout Meter (KFM) are no longer available. Because of changes in the manufacturing process, other materials (e.g., sewing thread, unwaxed dental floss) may not have the insulating capability to work properly. Oak Ridge National Laboratory has not tested any of the suggestions provided in the preface of the report, but they have been used by other groups. When using these instructions, the builder can verify the

  20. A comparison of entrance skin dose delivered by clinical angiographic c-arms using the real-time dosimeter: the MOSkin.

    PubMed

    Thorpe, Nathan Kenneth; Cutajar, Dean; Lian, Cheryl; Pitney, Mark; Friedman, Daniel; Perevertaylo, Vladimir; Rosenfeld, Anatoly

    2016-06-01

    Coronary angiography is a procedure used in the diagnosis and intervention of coronary heart disease. The procedure is often considered one of the highest dose diagnostic procedures in clinical use. Despite this, there is minimal use of dosimeters within angiographic catheterisation laboratories due to challenges resulting from their implementation. The aim of this study was to compare entrance dose delivery across locally commissioned c-arms to assess the need for real-time dosimetry solutions during angiographic procedures. The secondary aim of this study was to establish a calibration method for the MOSkin dosimeter that accurately produces entrance dose values from the clinically sampled beam qualities and energies. The MOSkin is a real-time dosimeter used to measure the skin dose delivered by external radiation beams. The suitability of the MOSkin for measurements in the angiographic catheterisation laboratory was assessed. Measurements were performed using a 30 × 30 × 30 cm(3) PMMA phantom positioned at the rotational isocenter of the c-arm gantry. The MOSkin calibration factor was established through comparison of the MOSkin response to EBT2 film response. Irradiation of the dosimeters was performed using several clinical beam qualities ranging in energy from 70 to 105 kVp. A total of four different interventional c-arm machines were surveyed and compared using the MOSkin dosimeter. The phantom was irradiated from a normal angle of incidence using clinically relevant protocols, field sizes and source to image detector distance values. The MOSkin was observed to be radiotranslucent to the c-arm beam in all clinical environments. The MOSkin response was reproducible to within 2 % of the average value across repeated measurements for each beam setting. There were large variations in entrance dose delivery to the phantom between the different c-arm machines with the highest observed cine-acquisition entrance dose rate measuring 326 % higher than the